complications—hypoglycemia 2115-pub 2118-pub ... - diabetes€¦ · acute and chronic...

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A541 For author disclosure information, see page A696. Acute and Chronic Complications PUBLISHED ONLY ADA-Supported Research COMPLICATIONS—HYPOGLYCEMIA COMPLICATIONS—HYPOGLYCEMIA 2115-PUB Glucose Excursions and Insulin Delivery Rates in the Field Predict In-Hospital Measured Glucagon Counterregulation in Adults with Type 1 Diabetes LEON S. FARHY, STEPHEN PATEK, SUE BROWN, EDWARD ORTIZ, MARC D. BRETON, BORIS P. KOVATCHEV, Charlottesville , VA Background: In type 1 diabetes (T1DM) the glucagon counterregulation (GCR) becomes defective as the disease progresses and is a key obstacle to safe use of insulin therapy. Knowledge of the state of GCR level could pro- vide information to improve the effectiveness and safety of the control of glycemia or can be used as a marker for disease progression. We propose a methodology for estimating GCR in T1DM patients from Continuous Glucose Monitor (CGM) and insulin pump field data. Methods: Fifty-five T1DM patients, age 41±12.2 years, duration of diabe- tes 24.1±11.0 years, HbA1c of 7.7±1.2%, had a month of CGM and insulin pump data collected in a field study. Twenty-five completed a follow-up inpa- tient study to evaluate their GCR caused by meal overbolusing and estimated by the fold change in glucagon after vs. before hypoglycemia (70 mg/dl). The field data were used to compute a net carbohydrate signal, Net Effect (NE), accounting for data variability not explained by a model of glucose metabo- lism. The NE prior to a low BG event in the field was correlated with inpa- tient GCR. Results: In the field, the NE in the 90 min intervals preceding a low BG events (70 mg/dl) was negative and significantly lower than the individual mean NE (p<0.0001). Moreover, the field NE thirty min before a BG event of < 50 mg/dl was highly correlated with inpatient measured GCR when accounting for age, duration of diabetes, and HbA1c (r=0.728; p<0.0001). As expected, the magnitude of the inpatient GCR was marginal: fold increase of 1.17±0.042. Conclusion: In T1DM patients, low BG events are preceded by a measur- able change of a net carbohydrate signal computed from CGM and insulin field data which can be used for identifying periods of higher hypoglycemia risk. In addition, GCR can be inferred from this net signal, which suggests a role for GCR in glucose regulation and a possibility to develop a procedure to track the progression of GCR impairment from field data only. Supported By: DP3 DK106907, RO1 DK 51562, RO1 DK 085623 2116-PUB WITHDRAWN 2117-PUB Hypoglycemia Incidence and Awareness among Insulin-Treated Patients with Diabetes: The HAT Study in Brazil RODRIGO N. LAMOUNIER, MARIANA N. ERMETICE, FABIANO GRICIUNAS, SIL- MARA A.O. LEITE, Belo Horizonte , Brazil , São Paulo , Brazil , Curitiba , Brazil Hypoglycemia affects patient safety and glycemic control during insulin treatment of both type 1 diabetes mellitus (T1) and type 2 (T2). The Hypo- glycemia Assessment Tool (HAT) study in Brazil aimed to determine the pro- portion of patients experiencing hypoglycemic events and to characterize patient awareness and fear about hypoglycemia, among insulin-treated patients with both T1 and T2. This was a non-interventional, multicenter study, with a 6-month retrospective and a 4-week prospective evaluation of hypoglycemic events. Patients completed a questionnaire each at baseline and at the end of the study and also a Patient Diary. The answers “occasion- ally” and “never” to the question “Do you have symptoms when you have a low sugar level?” denoted impaired hypoglycemia awareness. Fear was reported on a 10-point scale, from “not afraid at all” to “absolutely terri- fied.” From 679 included patients, 321 were T1 and 293 T2, with a mean age of 35.0 ± 13.1 and 61.6 ± 10 years, respectively. 41 and 44% were male, with mean diabetes duration of 16.7 and 16.9 years in T1 and T2 respec- tively. Time of insulin use was 11.8 ± 9.9 and 7.9 ± 6.2 years. 91.7% T1 and 61.8% T2 patients had at least one hypoglycemic event during the observa- tion period. In the same period, 54.0% T1 and 27.4% T2 patients had noctur- nal hypoglycemia, severe events occurred in 20.0% and 10.3% respectively. At baseline, 21.4% T1 and 34.3% T2 had impaired awareness. The mean score of hypoglycemia fear was 5.9 ± 3.1 in T1 and 5.4 ± 3.9 in T2. The most common reactions to hypoglycemia were to increase blood glucose monitor- ing (58.0%) and calorie intake (60.3%), and reduce (30.8%) or skip (16.1%) insulin doses. Estimated rates of hypoglycemia were high, in both T1 and T2 patients. Patient reactions to hypoglycemia, such as reduction in insulin and increase in calorie intake, can affect diabetes management. These findings may support clinicians in tailoring diabetes education and insulin treatment for Brazilian diabetic patients. Supported By: Novo Nordisk A/S 2118-PUB Frequency of Hypoglycemia during Driving in Patients with Dia- betes Treated with Insulin and Oral Antidiabetics: Evaluation of a Graveling Questionnaire Survey LENKA SYC ˇ OVA-KRIVAN ˇ OVA, MAREK BRABEC, VIERA DONIC ˇ OVA, DARIO RAHE- LIC, DENISA JANICKOVA ZDARSKA, DANIEL VÍCH, YOU JEE YOUNG, JAN POLAK, MILAN KVAPIL, JAN BROŽ, Prague , Czech Republic , Kosice , Slovakia , Zagreb , Croa- tia Hypoglycemia as a common side-effect of insulin therapy can impair driv- ing performance with potential fatal consequences. Data describing the frequency of hypoglycemic episodes during driving in the group of patients with type 1 diabetes mellitus (DM) are available, while similar data concern- ing those with type 2 DM on combination therapy of insulin and oral antidi- abetic drugs (OADs) are missing. Our study aimed at obtaining relevant data describing the situation in type 2 DM patients. 196 patients with type 2 DM on combination therapy with insulin and OADs (159 men, 38 women, mean age 62±10.6, mean duration of disease 14.2 ± 8.7 years) from 4 outpatient diabetes clinics filled out the adapted Graveling´s questionnaire with 67 questions about important aspects of driv- ing and hypoglycemia. At least one mild hypoglycemia during driving per year was reported by 7 patients (11.63%) treated with multiple daily insulin injection (MDI), by 5 patients (11.63%) with basal insulin (BI) and by 3 patients (10.71%) treated with mixed insulin (MI). At least one severe hypoglycemia per year was reported by 15 patients (11, 90%) in MDI group, by 6 (13.95%) in BI and by 4 (14, 28%) in MI group. Severe hypoglycemia during driving per year was reported by 4 patients (3, 20%) in MDI and by 1 (2, 30%) in BI group. We did not find significant differences in hypoglycemia frequency between patient subgroups with different OADs. Hypoglycemia during driving was reported by a substantial number of patients of all type of treatment. Frequency of severe hypoglycemia per year was surprisingly high especially in the group of patients with mixed insulin twice daily and basal insulin only. Both these facts should bring more atten- tion to education of type 2 diabetics subject to all types of insulin treatment. 2119-PUB Frequency of Patients with Impaired Hypoglycemia Awareness among Drivers with Type 1 Diabetes: Evaluation of a Graveling Questionnaire Survey LENKA SYC ˇ OVA-KRIVAN ˇ OVA, MAREK BRABEC, VIERA DONIC ˇ OVA, DANIEL VÍCH, DARIO RAHELIC, DOVILE SIMONAVICIUTE, EDITA KREVENAITE, JAN POLAK, MILAN KVAPIL, JAN BROŽ, Prague , Czech Republic , Kosice , Slovakia , Zagreb , Croa- tia , Kaunas , Lithuania Hypoglycemia is a common side-effect of insulin therapy which - among other problems - can impair driving performance of patients with diabetes mellitus. Data describing the frequency of episodes of mild and severe hypo- glycemia during driving in type 1 diabetic patients are relatively sufficient. Data on the number of patients with impaired hypoglycemia awareness in the same group are, however, missing. Data obtained from 328 type 1 diabetic patients (mean age 39 ± 14.7 years; 221 men, 107 women; mean diabetes duration 15.7 ± 11.3) from 4 out- patient units who answered the adapted Graveling´s questionnaire with 67 questions about important aspects of diabetes and the topic of driving were analyzed. Seven point Gold score which was part of the questionnaire was employed to evaluate impaired hypoglycemia awareness (points 4-7 indicate impaired hypoglycemia awareness). 50 patients with impaired hypoglycemia awareness (15.2% of the total number) with 9 patients at point 7 of the scale and 10 patients at point 6 (5.26%) were identified. There was no significant difference observed in the two groups of patients (with and without impaired hypoglycemia aware- ness) as to the frequency of glycemia measurement before driving (0.20%, resp. 0.23% of patients measure their glycemia before every single drive, 1.43% resp. 1.31% before every second one). There is a substantial number of patients with impaired hypoglycemia awareness among drivers with type 1 diabetes. Preventing hypoglycemia while driving is in a majority of cases insufficient. This should be taken into consideration and emphasized during the education process.

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Page 1: COMPLICATIONS—HYPOGLYCEMIA 2115-PUB 2118-PUB ... - Diabetes€¦ · Acute and Chronic Complications PUBLISHED ONLY ADA-Supported Research COMPLICATIONS—HYPOGLYCEMIA COMPLICATIONS—HYPOGLYCEMIA

A541

For author disclosure information, see page A696.

CATEGORY

Acu

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ADA-Supported Research

COMPLICATIONS—HYPOGLYCEMIA

COMPLICATIONS—HYPOGLYCEMIA

2115-PUBGlucose Excursions and Insulin Delivery Rates in the Field Predict In-Hospital Measured Glucagon Counterregulation in Adults with Type 1 DiabetesLEON S. FARHY, STEPHEN PATEK, SUE BROWN, EDWARD ORTIZ, MARC D. BRETON, BORIS P. KOVATCHEV, Charlottesville, VA

Background: In type 1 diabetes (T1DM) the glucagon counterregulation (GCR) becomes defective as the disease progresses and is a key obstacle to safe use of insulin therapy. Knowledge of the state of GCR level could pro-vide information to improve the effectiveness and safety of the control of glycemia or can be used as a marker for disease progression. We propose a methodology for estimating GCR in T1DM patients from Continuous Glucose Monitor (CGM) and insulin pump fi eld data.

Methods: Fifty-fi ve T1DM patients, age 41±12.2 years, duration of diabe-tes 24.1±11.0 years, HbA1c of 7.7±1.2%, had a month of CGM and insulin pump data collected in a fi eld study. Twenty-fi ve completed a follow-up inpa-tient study to evaluate their GCR caused by meal overbolusing and estimated by the fold change in glucagon after vs. before hypoglycemia (70 mg/dl). The fi eld data were used to compute a net carbohydrate signal, Net Effect (NE), accounting for data variability not explained by a model of glucose metabo-lism. The NE prior to a low BG event in the fi eld was correlated with inpa-tient GCR.

Results: In the fi eld, the NE in the 90 min intervals preceding a low BG events (70 mg/dl) was negative and signifi cantly lower than the individual mean NE (p<0.0001). Moreover, the fi eld NE thirty min before a BG event of < 50 mg/dl was highly correlated with inpatient measured GCR when accounting for age, duration of diabetes, and HbA1c (r=0.728; p<0.0001). As expected, the magnitude of the inpatient GCR was marginal: fold increase of 1.17±0.042.

Conclusion: In T1DM patients, low BG events are preceded by a measur-able change of a net carbohydrate signal computed from CGM and insulin fi eld data which can be used for identifying periods of higher hypoglycemia risk. In addition, GCR can be inferred from this net signal, which suggests a role for GCR in glucose regulation and a possibility to develop a procedure to track the progression of GCR impairment from fi eld data only.

Supported By: DP3 DK106907, RO1 DK 51562, RO1 DK 085623

2116-PUBWITHDRAWN

2117-PUBHypoglycemia Incidence and Awareness among Insulin-Treated Patients with Diabetes: The HAT Study in BrazilRODRIGO N. LAMOUNIER, MARIANA N. ERMETICE, FABIANO GRICIUNAS, SIL-MARA A.O. LEITE, Belo Horizonte, Brazil, São Paulo, Brazil, Curitiba, Brazil

Hypoglycemia affects patient safety and glycemic control during insulin treatment of both type 1 diabetes mellitus (T1) and type 2 (T2). The Hypo-glycemia Assessment Tool (HAT) study in Brazil aimed to determine the pro-portion of patients experiencing hypoglycemic events and to characterize patient awareness and fear about hypoglycemia, among insulin-treated patients with both T1 and T2. This was a non-interventional, multicenter study, with a 6-month retrospective and a 4-week prospective evaluation of hypoglycemic events. Patients completed a questionnaire each at baseline and at the end of the study and also a Patient Diary. The answers “occasion-ally” and “never” to the question “Do you have symptoms when you have a low sugar level?” denoted impaired hypoglycemia awareness. Fear was reported on a 10-point scale, from “not afraid at all” to “absolutely terri-fi ed.” From 679 included patients, 321 were T1 and 293 T2, with a mean age of 35.0 ± 13.1 and 61.6 ± 10 years, respectively. 41 and 44% were male, with mean diabetes duration of 16.7 and 16.9 years in T1 and T2 respec-tively. Time of insulin use was 11.8 ± 9.9 and 7.9 ± 6.2 years. 91.7% T1 and 61.8% T2 patients had at least one hypoglycemic event during the observa-tion period. In the same period, 54.0% T1 and 27.4% T2 patients had noctur-nal hypoglycemia, severe events occurred in 20.0% and 10.3% respectively. At baseline, 21.4% T1 and 34.3% T2 had impaired awareness. The mean score of hypoglycemia fear was 5.9 ± 3.1 in T1 and 5.4 ± 3.9 in T2. The most common reactions to hypoglycemia were to increase blood glucose monitor-ing (58.0%) and calorie intake (60.3%), and reduce (30.8%) or skip (16.1%) insulin doses. Estimated rates of hypoglycemia were high, in both T1 and T2 patients. Patient reactions to hypoglycemia, such as reduction in insulin and

increase in calorie intake, can affect diabetes management. These fi ndings may support clinicians in tailoring diabetes education and insulin treatment for Brazilian diabetic patients.

Supported By: Novo Nordisk A/S

2118-PUBFrequency of Hypoglycemia during Driving in Patients with Dia-betes Treated with Insulin and Oral Antidiabetics: Evaluation of a Graveling Questionnaire SurveyLENKA SYCOVA-KRIVANOVA, MAREK BRABEC, VIERA DONICOVA, DARIO RAHE-LIC, DENISA JANICKOVA ZDARSKA, DANIEL VÍCH, YOU JEE YOUNG, JAN POLAK, MILAN KVAPIL, JAN BROŽ, Prague, Czech Republic, Kosice, Slovakia, Zagreb, Croa-tia

Hypoglycemia as a common side-effect of insulin therapy can impair driv-ing performance with potential fatal consequences. Data describing the frequency of hypoglycemic episodes during driving in the group of patients with type 1 diabetes mellitus (DM) are available, while similar data concern-ing those with type 2 DM on combination therapy of insulin and oral antidi-abetic drugs (OADs) are missing. Our study aimed at obtaining relevant data describing the situation in type 2 DM patients.

196 patients with type 2 DM on combination therapy with insulin and OADs (159 men, 38 women, mean age 62±10.6, mean duration of disease 14.2 ± 8.7 years) from 4 outpatient diabetes clinics fi lled out the adapted Graveling´s questionnaire with 67 questions about important aspects of driv-ing and hypoglycemia.

At least one mild hypoglycemia during driving per year was reported by 7 patients (11.63%) treated with multiple daily insulin injection (MDI), by 5 patients (11.63%) with basal insulin (BI) and by 3 patients (10.71%) treated with mixed insulin (MI). At least one severe hypoglycemia per year was reported by 15 patients (11, 90%) in MDI group, by 6 (13.95%) in BI and by 4 (14, 28%) in MI group. Severe hypoglycemia during driving per year was reported by 4 patients (3, 20%) in MDI and by 1 (2, 30%) in BI group. We did not fi nd signifi cant differences in hypoglycemia frequency between patient subgroups with different OADs.

Hypoglycemia during driving was reported by a substantial number of patients of all type of treatment. Frequency of severe hypoglycemia per year was surprisingly high especially in the group of patients with mixed insulin twice daily and basal insulin only. Both these facts should bring more atten-tion to education of type 2 diabetics subject to all types of insulin treatment.

2119-PUBFrequency of Patients with Impaired Hypoglycemia Awareness among Drivers with Type 1 Diabetes: Evaluation of a Graveling Questionnaire SurveyLENKA SYCOVA-KRIVANOVA, MAREK BRABEC, VIERA DONICOVA, DANIEL VÍCH, DARIO RAHELIC, DOVILE SIMONAVICIUTE, EDITA KREVENAITE, JAN POLAK, MILAN KVAPIL, JAN BROŽ, Prague, Czech Republic, Kosice, Slovakia, Zagreb, Croa-tia, Kaunas, Lithuania

Hypoglycemia is a common side-effect of insulin therapy which - among other problems - can impair driving performance of patients with diabetes mellitus. Data describing the frequency of episodes of mild and severe hypo-glycemia during driving in type 1 diabetic patients are relatively suffi cient. Data on the number of patients with impaired hypoglycemia awareness in the same group are, however, missing.

Data obtained from 328 type 1 diabetic patients (mean age 39 ± 14.7 years; 221 men, 107 women; mean diabetes duration 15.7 ± 11.3) from 4 out-patient units who answered the adapted Graveling´s questionnaire with 67 questions about important aspects of diabetes and the topic of driving were analyzed. Seven point Gold score which was part of the questionnaire was employed to evaluate impaired hypoglycemia awareness (points 4-7 indicate impaired hypoglycemia awareness).

50 patients with impaired hypoglycemia awareness (15.2% of the total number) with 9 patients at point 7 of the scale and 10 patients at point 6 (5.26%) were identifi ed. There was no signifi cant difference observed in the two groups of patients (with and without impaired hypoglycemia aware-ness) as to the frequency of glycemia measurement before driving (0.20%, resp. 0.23% of patients measure their glycemia before every single drive, 1.43% resp. 1.31% before every second one).

There is a substantial number of patients with impaired hypoglycemia awareness among drivers with type 1 diabetes. Preventing hypoglycemia while driving is in a majority of cases insuffi cient. This should be taken into consideration and emphasized during the education process.

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For author disclosure information, see page A696.

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2120-PUBImpact of OADs on Hypoglycemia Frequency during Titration with Insulin Glargine 100 units/mL (Gla-100) in Type 2 Diabetes (T2D) DAVID R. OWENS, WOLFGANG LANDGRAF, BRIAN M. FRIER, MEI ZHANG, MAYA VINCENT, GEREMIA B. BOLLI, Swansea, United Kingdom, Frankfurt, Germany, Edin-burgh, United Kingdom, King of Prussia, PA, Paris, France, Perugia, Italy

This post-hoc subject-level analysis examined standardized data from 16 RCTs (FPG target 100 mg/dL, ≥ 24 weeks duration) adding Gla-100 to OADs in people with T2D. The impact of Metformin (MET), sulfonylurea (SU), or MET + SU on overall hypoglycemia frequency (confi rmed PG < 70 mg/dL or assistance required) stratifi ed according to 0, 1−3, 4−6, or > 6 events during insulin dose titration from weeks 0−8 was assessed; effi cacy and insulin dose change at week 24 were also examined.

Data from 3,153 people receiving either MET (n = 623), SU (n = 906), or MET + SU (n = 1,624) in combination with Gla-100 for 24 weeks were ana-lyzed. The concomitant OAD to which Gla-100 is added has a differential effect on HbA1c reduction. MET-treated subjects had the shortest diabe-tes duration and highest baseline BMI; the longest diabetes duration and lowest BMI were seen in the SU-only treated group (Table). In all OAD sub-groups the majority experienced 3 hypoglycemic events during titration. The frequency of hypoglycemia was inversely related to the baseline BMI in all but the MET + SU-treated group with > 6 events. The adjusted insulin dose change from baseline was lowest in those with more hypoglycemic events, irrespective of OAD treatment.

In people with T2D, OADs co-administered with basal insulin therapy infl uence effi cacy outcomes and overall hypoglycemia risk during the early period of insulin dose titration.

Table. Patient Characteristics Stratifi ed by Frequency of Hypoglycemic Events and Concomitant OAD During Gla-100 Titration.Parameter Glargine

+ OAD subgroup

Frequency of Hypoglycemic Events (PG < 70 mg/dL) During Titration (Week 0-8)

0 1−3 4−6 > 6Number of people, N (%) MET

MET + SUSU

535 (85.9) 1047 (64.5) 683 (75.4)

75 (12.0) 421 (25.9) 168 (18.5)

6 (1.0) 100 (6.2) 35 (3.9)

7 (1.1) 56 (3.4) 20 (2.2)

Duration of diabetes, years METMET + SUSU

6.9 (5.3) 9.2 (6.0) 9.5 (6.6)

9.1 (6.9) 9.8 (6.3) 9.6 (6.8)

11.4 (8.8) 10.0 (6.4) 10.2 ( 6.6)

11.5 (6.9) 10.6 (8.4) 8.0 (5.2)

Baseline BMI, kg/m2 METMET + SUSU

31.8 ( 5.7) 31.4 (5.0) 29.6 (5.2)

29.3 (4.9) 30.4 (4.8) 27.7 (4.6)

27.6 (5.0) 28.7 (4.4) 27.0 (3.9)

26.0 (4.4) 29.7 (4.5) 25.9 (4.1)

Baseline FPG, mg/dL METMET + SUSU

187 (55) 192 (51) 202 (57)

177 (53) 180 (48) 206 (58)

152 (28) 176 (63) 222 (66)

177 (49) 163 (41) 242 (59)

Baseline HbA1c, % METMET + SUSU

8.8 (1.1) 8.7 (1.0) 9.0 (1.1)

8.4 (1.0) 8.4 (0.9) 9.0 (1.0)

8.5 (0.8) 8.4 (0.9) 9.1 (1.1)

9.0 (1.0) 8.2 (0.8) 9.3 (0.7)

Adjusted HbA1c change from baseline to Week 24, % (SE)

METMET + SUSU

−1.7 (0.06) −1.4 (0.03) −1.5 (0.06)

−1.9 (0.11) −1.6 (0.04) −1.7 ( 0.10)

−1.5 (0.37) −1.6 (0.08) −1.8 (0.19)

−1.4 (0.34) −1.7 (0.10) −2.3 (0.24)

Adjusted insulin dose change from baseline to Week 24, U/kg (SE)

METMET + SUSU

0.3 (0.02) 0.3 (0.01) 0.3 (0.01)

0.2 (0.03) 0.2 (0.01) 0.2 (0.02)

0.2 (0.10) 0.2 (0.02) 0.1 (0.03)

0.1 (0.10) 0.1 (0.03) 0.0 (0.04)

Data presented represent mean (SD) unless otherwise specifi ed. Adjusted means of HbA1c and insulin dose (U/kg) at endpoint, and change to endpoint come from an analysis of covariance model including age, duration of diabe-tes, BMI, FPG, insulin dose and, HbA1c at baseline as covariates, and sex, hypoglycemia group and study as the fi xed factors. SD, standard deviation. SE, standard error.

Supported By: Sanofi

2121-PUBTwo Antagonistic Metabolic Defects that Make Glycemic Manage-ment a ChallengeJORGE VIVAR AGUIRRE, ANUPAM OHRI, New Brunswick, NJ

Reports of diabetes mellitus (DM) in glycogen storage disease type Ia (GSD Ia) are very rare. The pathogenesis and management in these patients remains unclear. Here we present a rare case of DM in GSD Ia. 34 years old female diagnosed with GSD Ia at 6 months of age after hypoglycemic seizures. Her diagnosis was confi rmed by liver biopsy at age 3. Patient was initially treated with frequent feeding until age 9 when she started on corn-starch. Over time she developed multiple complications of GSD-Ia includ-ing: hepatic adenomas, nephrolithiasis, proteinuria, hyperuricemia, gout and osteopenia. In 2014 blood work showed a fasting blood glucose (BG) of 311

mg/dL with an HbA1c 11.5%. At that time she was taking cornstarch 5 table-spoons daily and her BMI was 41.6 kg/m2. A 5-day continuous glucose moni-toring (CGM) report showed that 64% of the time her BG were >140 mg/dL. No hypoglycemic episodes were identifi ed. Patient was advised to follow therapeutic lifestyle changes (TLC), cornstarch was decreased to 3 table-spoons and a low dose SGLT2 inhibitor was started. Despite a maximized dose of SGLT2 inhibitor glycemic control remained suboptimal and an alpha glucosidase inhibitor (AGI) was added. After 2 years of diet control, SGLT2 inhibitor and AGI she was able to lose >20 pounds and her HbA1c improved to 6.5%. Patients with GSD-Ia experience recurrent episodes of severe hypo-glycemia. Our patient developed the opposite metabolic derangement, overt DM. Review of literature describes only one previously reported case of con-comitant DM and GSD Ia. Management is this patient is not clearly defi ned and it should be individualized in a case to case basis. Regardless of the treatment patients with GSD Ia should be frequently monitor for hypoglyce-mia and worsening lactic acidosis. With the improved life expectancy seen in patients with GSD-Ia, long term complications become the major cause of morbidity and mortality. Physicians should be aware of DM as a potential late complication in patients with GSD-1a.

2122-PUBIn-Patient Hypoglycemia and National Service Framework for Dia-betes in the United KingdomRANJNA GARG, EVA PATEL, Waltham Cross, United Kingdom, London, United King-dom

Introduction: National Service Framework (NSF) for diabetes, standard-7 and 8 focus on management of diabetic emergencies and diabetes manage-ment during hospital admissions. We looked at the management of hypogly-cemia episode (HE) in admitted patients.

Aims: To identify 1. Prevalence of hypoglycaemia in admitted patients. 2. Dia betes team input following episode. 3. Impact on length of hospital stay (LOS).

Methods: HE were identifi ed from centrally recorded point of care testing data. Trust hypoglycaemia protocol was used as audit standards. We also looked at patient demographic and LOS.

Results: 1458 capillary blood glucose (CBG) tests performed over a two-weeks period, HE=148 hypoglycemic episodes CBG<4mmol/l in 54 patients (mean age 69.3±15.3 years). Location: 65.8% Medical ward, 6.8% Surgical, 7.4% in emergency department. Mean CBG was 3.38±0.44 mmol/l. 35-patients had single HE (SHE) and 19 patients had recurrent HE (RHE). RHE predic-tors included low baseline CBG (mean for SHE=3.5mmol/l, RHE=2.9mmol/l, p=0.012). RHE was not associated with age, nil by mouth status, baseline renal function and co-morbidities including baseline renal function, stroke/ischaemic heart disease/hypercholesterolaemia. RHE was associated with longer LOS (18.2±15 vs. 9.4±10.5 days, p=0.016), 21% were on insulin and 81% on oral agents. Only 21% were reviewed by a doctor following HE, 12.5% were reviewed by a diabetic team. Immediate treatment changes following HE were made only in 13.4% of the patients leading to RHE.

Conclusion: In-patients HE is managed inappropriately, results in longer LOS with lack of input by specialist diabetes team to improve care as rec-ommended by NSF. Acute diabetic complication require improved care in in-hospital settings and room for improvement exists based on NSF recom-mendations.

Recommendation: All patients with hypoglycaemia should be seen by the diabetes team to reduce recurrence of further/severe hypoglycemia and reduce length of stay in hospital.

2123-PUBIs HbA1c an Equally Reliable Indicator of Low Blood Glucose in Type 1 and Type 2 Diabetes?ANNA BORKOWSKA, ELEKTRA SZYMANSKA-GARBACZ, JERZY LOBA, LESZEK CZUPRYNIAK, Lodz, Poland, Warsaw, Poland

Low HbA1c levels - as opposite to high ones - are being usually associated with increased risk of hypoglycaemia in all persons with diabetes. We evalu-ated the relationship between low blood glucose (BG) and HbA1c in well and poorly controlled type 1 (DM1) and type 2 diabetes (DM2). The subjects were patients with DM1 and DM2 with HbA1c~7% (i.e., 6-8%) and HbA1c~10% (i.e., 9-12%): DM1 7% (n=29); DM1 10% (n=30); DM2 7% (n=28); and DM2 10% (n=35). Their mean age, duration of diabetes, BMI and HbA1c were 42±13, 41±14, 62±11, 64±8 years; 14±11, 13±7, 11±6, 16±8 years; 23.1±3.2, 26.1±4.0, 30.7±5.3, 33.0±5.1 kg/m2; 7.1±0.6, 10.1±0.9, 7.2±0.6, 9.6±0.8%, respectively. Each subject underwent blinded continuous glucose monitor-ing (CGMS; iPro2, Medtronic) for 5.8±0.8 days. Minimum BG values from eight periods of the day were analysed in relationship to HbA1c. In patients

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Table 1. Patient Characteristics and Health-related Quality of Life Outcomes by Hypoglycemia Severity among Patients with T2DM Using Basal Insulin.

2125-PUBAsymptomatic Hypoglycemia in Hospitalized Patients with Diabe-tes: Prevalence, Risk Factors, and OutcomesPATRICIA C. GOMEZ, ISABEL ANZOLA, M. AGUSTINA URRUTIA, MAYA FAYF-MAN, PRIYATHAMA VELLANKI, FRANCISCO PASQUEL, SONYA HAW, LIMIN PENG, GUILLERMO E. UMPIERREZ, Atlanta, GA, Decatur, GA

The frequency of hypoglycemic symptoms in hospitalized patients with diabetes is not known. Accordingly, this prospective study determined the frequency of symptomatic and asymptomatic hypoglycemia (<70 mg/dl) in general medicine and surgery patients with diabetes. Following hospital protocol, patients underwent point-of-care glucose testing before meals and at bedtime. Patients with hypoglycemia were identifi ed by electronic medical record and were interviewed by the research team for symptoms of hypoglycemia. The study included 134 subjects with mean age 55.4±12.6 yrs, 47% were female, and mean BMI 29.6±8.5 kg/m2 admitted to 2 uni-versity-affi liated hospitals between 4/2015 and 12/2015. Patients were treated with basal insulin (27%), basal bolus (38%), sliding scale insulin (14%), oral agents ± insulin (10%), or no antidiabetic regimen (10%). A total of 69 patients (51.4%) were asymptomatic and 65 (48.5%) had ≥1 symptom of hypoglycemia. Symptoms were more common in women than men (58.7% vs. 39.4%, p=0.03) and in patients with higher admission HbA1c (9.3±2.9% vs. 7.7±2.3%, p<0.001). Adrenergic symptoms including sweating (66%), anx-iety (48%), tremors (51%) and palpitations (22%) were more common than neuroglycopenic fi ndings such as confusion (49%), blurred vision (35%) and slurred speech (22%). BMI, duration of diabetes, treatment on admission, medicine vs. surgery service, use of beta-blockers, length of hospital stay or mortality did not differ between symptomatic and asymptomatic patients. Risk factors for hypoglycemia were poor oral intake/nausea (43%), eGFR <60 ml/min (52%) and heart failure (10%). In summary, more than half of hypoglycemic events were asymptomatic in hospitalized patients with dia-betes. Women and patients with poor glycemic control were more likely to experience symptomatic hypoglycemia. Clinical vigilance and glucose moni-toring are needed to prevent complications of hypoglycemia in hospitalized patients with diabetes.

2126-PUBWITHDRAWN

2127-PUBDevelopment and Validation of a Hypoglycemia Risk Score Tool (HYPOSCORE) for People with Type 2 Diabetes Commencing InsulinBRUNO LINETZKY, BRIAN M. FRIER, BRADLEY H. CURTIS, RAN DUAN, JESUS REVIRIEGO, JUAN JOSE GAGLIARDINO, Buenos Aires, Argentina, Edinburgh, United Kingdom, Indianapolis, IN, Madrid, Spain, La Plata, Argentina

No tool is available to predict hypoglycemia risk before commencing insulin. Aim: To develop a risk score (HYPOSCORE) to identify patients at high

risk of hypoglycemia. Data were used from Eli Lilly clinical trials of insu-lin naïve patients who were commenced on insulin (n=409 with a valida-tion dataset n=418). To develop the HYPOSCORE a Cox regression model was fi tted on the development dataset by estimating relative hazard ratios with covariates including race, age, diabetes duration, BMI, baseline HbA1c, GFR and blood glucose variability. The subgroup cut off “R1” (hypoglycemia rate 1.6 times/month) and the corresponding risk score cut off “R2” were chosen to maximize a weighted summation of sensitivity and specifi city of the HYPOSCORE with “High Risk” being defi ned as a positive outcome. The HYPOSCORE was applied to the validation dataset to evaluate performance.

with HbA1c~7% minimum BG levels since after breakfast until after dinner were signifi cantly lower in DM1 than DM2 (Figure 1a). Interestingly, mini-mum postprandial BG levels in DM1 10% were not statistically signifi cant different from the respective minimum BG values in DM2 7% (Figure 1b). We suggest that low values of HbA1c as an indicator of low blood glucose are not equally reliable in DM1 and DM2. High HbA1c levels in DM1 do not exclude the occurrence of low BG levels, particularly in the prandial period.Figure. Mean Minimum CGMS BG Values during Eight Day Periods in Well Controlled DM1 and DM2 Patients (Figure 1a) and Well Controlled DM2 and Poorly Controlled DM1 Patients (Figure 1b).

Supported By: Medical University of Lodz

2124-PUBThe Association of Hypoglycemia Severity and Health Related Qual-ity of Life among Patients with Type 2 Diabetes Mellitus Using Basal InsulinHONGWEI WANG, LULU LEE, LIYUE TONG, SHALOO GUPTA, RONALD PREBLICK, LUIGI F. MENEGHINI, Bridgewater, NJ, New York, NY, Dallas, TX

This study was to assess if health-related quality of life (HRQoL) differed by severity of hypoglycemia (HYPO) among patients with T2DM on basal insulin (±oral antidiabetic, rapid/premixed insulin). Data were obtained from the 2011-2013 National Health and Wellness Survey, an annual Internet-based survey demographically representative of the U.S. adult population. Eligible patients were categorized as having no HYPO (n=938; 38.7%), non-severe HYPO (n=1335; 55.1%), or severe HYPO (n=150; 6.2%) in the preced-ing 3 months. HRQoL was assessed with the Physical Component Summary (PCS), Mental Component Summary (MCS), and SF-6D health utility scores derived from the SF-36v2. Multivariable models were used to compare dif-ferences in HRQoL by HYPO severity. Regardless of HYPO severity, one-third of patients reported experiencing nocturnal HYPO. A higher percentage of non-severe and severe HYPO were seen in patients on a basal plus rapid/pre-mix insulin regimen. Among eligible patients, those with severe HYPO were associated with worsening outcomes on MCS, PCS, and health utili-ties vs. those with non-severe or no HYPO, with MCS (>3 points) and health utilities (>0.041 points) exceeding minimally important difference thresholds (Table 1). Findings imply that reducing severe to non-severe or no HYPO could potentially lead to clinically meaningful improvements in HRQoL.

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tices. Regional variation suggests that shared decision making approaches to setting A1c goals be tailored.Figure. Rates of Overtreatment (OT) and Undertreatment (UT) Measures, %.

Supported By: U.S. Department of Veterans Affairs

2130-PUBWITHDRAWN

2131-PUBUse of Continuous Glucose Monitoring to Prevent Hypoglycemia in the HospitalEILEEN FAULDS, SHEILA MAPES, LINDSEY KARNES, KATHLEEN M. DUNGAN, KATHLEEN WYNE, Columbus, OH

Severe hypoglycemia in the hospital is considered a medical emergency requiring increased resource utilization and typically causing an increase in the hospital length of stay. We describe a patient with type 1 diabetes man-aged with an insulin pump and Renal Failure treated with hemodialysis who was having severe hypoglycemia at least 1-2 times weekly while hospitalized for treatment of osteomyelitis. Despite multiple adjustments to the settings of her insulin pump and multiple changes of the site of the Continuous Glu-cose Monitor (CGM) device that was associated with the pump over the fi rst 6 weeks of the hospitalization the severe hypoglycemic events, requiring Code Blue alert for Rapid Response Team assistance, persisted. A different, inde-pendent, CGM was then placed in an attempt to obtain 24 hour monitoring of her glucose with alerts set for when her glucose decreased below 80 and/or if it dropped by more than 3 mg/dL/minute. These alerts were transmitted to the diabetes team by her mobile phone allowing close monitoring by the inpa-tient team. Upon placement of the new CGM the Code Blue alerts stopped completely for the next 12 weeks with critical lows resuming within one week after the patient stopped using the CGM after having inadvertently misplaced the transmitter at the time of sensor site change. The transmitter was found and the sensor reinserted; once again there was resolution of the severe hypo-glycemic events. Although it is unusual for a patient to have such a prolonged (6 month) hospitalization, we were given an opportunity to test the value of

C statistic and chi-square test were used to measure its discrimination and calibration properties. HYPOSCORE sensitivity has a reasonable capacity to identify insulin naïve patients at high risk of hypoglycemia. However, lack of consistency of the fi ndings in the validation data limits its generalizability. Further work to refi ne this tool is required using larger real world datasets.

Table. Performance of the HYPOSCORE.Score Development Data Validation Data

Sensitivity 76.4% 93.9%Specifi city 71.0% 20.2%AUC 0.7831 0.6434Chi-Square Test 2.77 (p=0.10) 290.7 (p<0.001C-Statistic 0.7831 (p<0.0001) 0.6434 (p<0.0001)

Supported By: Eli Lilly and Company

2128-PUBPhysician Knowledge about Hypoglycemia Predicts Better T2DM Treatment DecisionsXINGYUE HUANG, SIMON J. FISHER, SILVIO E. INZUCCHI, RAVI SHANKAR, EDWARD A. WITT, Lebanon, NJ, Salt Lake City, UT, New Haven, CT, Rahway, NJ, Princeton, NJ

Hypoglycemia (hypo) is considered a rate-limiting step in the management of T2DM, especially when insulin therapy is used. Appropriate clinical deci-sions for patients experiencing or at risk for hypo events may substantially improve the quality of care delivered. There is little research, however, on how physicians’ medical knowledge concerning hypo might affect treatment decisions. We sought to assess physicians’ hypo knowledge and its relation-ship to treatment decisions in standardized T2DM patient vignettes. A total of 1,003 physicians completed our on-line study (752 PCPs, 251 endocrinolo-gists [endos)]: male 76%, >age 44 years 81%, and mean years in practice 19.9. On average, the number of T2DM patients being treated by PCPs and endos in a typical month was 122.4±68.4 and 201.0±105.3 (p<.001), respec-tively. Endos had a greater % of their patients taking insulin, SGLT2-i‘s and GLP-1 RAs. The reported % of patients experiencing hypo in the preceding month was 9% for PCPs and 19% for endos, with both indicating 15% of these as being severe. Endos’ hypo knowledge score on a 9 fact-based question test trended slightly higher than PCPs (69.9±20.2% vs. 67.2±19.8%; p=.063). After multivariable adjustment for a variety of demographic and practice variables, however, being an endo (vs. a PCP) was positively associated with better hypo knowledge (β=0.148, p<.001). Moreover, hypo knowledge was the only variable to be signifi cantly associated with both more appropriate treatment decision-making in the patient vignettes (β= .199, p<.001) as well as the correct rationale for those treatment decisions (β=.209, p<.001). In conclusion, making and understanding optimal treatment decisions involving T2DM patients experiencing or at risk for hypo is associated with physician specialty and physician’s medical knowledge about hypo. Increasing physi-cians’ understanding of hypo may therefore be a desirable goal to improve the clinical care of patients with T2DM.

Supported By: Merck & Co., Inc.

2129-PUBTrends in Glycemic Over- and Undertreatment of Vulnerable Veter-ans Administration Patients, 2009-2013DAVID C. ARON, CHIN-LIN TSENG, ORYSYA SOROKA, LEONARD POGACH, Cleve-land, OH, East Orange, NJ

The <7% HEDIS measure for patients 18-75 years implemented in 2007 was withdrawn in 2008. We evaluated trends in over (OT) and under (UT) treatment from 2009 to 2013 in vulnerable patients. This was a serial cross-sectional design of patients on insulin/sulfonylurea at high risk for hypoglyce-mia: ≥75 years old, or cognitive impairment/dementia, or a serum creatinine ≥2.0 mg/dL. Annual rates of OT (A1c <6.0%, <6.5%, <7%) and UT (A1c>9%) were derived using a patient’s last A1c value in a year for 138 VA facilities grouped into 5 geographic regions. There were 205,857 and 171,875 patients at high risk for hypoglycemia in 2009 and 2013. Nationally, there were down-ward trends (p<0.001): 50.2% in 2009 to 40.3% in 2013 (A1c <7%), 28.9% to 22.2% (<6.5%), and 11.3% to 9.1% (<6%), representing 19.7%, 23.2%, and 19.5% relative decreases. Rates of UT rose 45% from 7.1% to 10.3% during the same time. Rates differed across regions (p<0.05) but regional trends were similar (p>0.10). Generally, South and West had higher rates (e.g., A1c <7%: 51.7%/42.3% and 51.4%/43.3% in 2009/2013) than North East (47.9%/37.4%). Decreased but persistently high OT rates, including A1c <6% rates comparable to A1c >9% rates, indicates the diffi culty in develop-ing strategies for de-implementation of harmful, but ingrained, clinical prac-

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years with normal systolic and diastolic cardiac function. We collected demographic, clinical and laboratory data and performed echocardiographic evaluation to each participant. Fasting plasma was drawn for BNP, sST2 and hs-CRP measurements. This procedure was repeated every 12 months for a 48-month time period. On Metformin therapy was the 91.7% while 27.1 on SU, 8.3% on DPP-4 inhibitors, 8.3% on glinides and 4.2% on insulin therapy. Among the anti-hypertensives, 18.8% was on ACE-inhibitors, 16.7% ARB’s, 4.2% HCT and 4.2% b-blockers. At the end of the study 28 subjects had LVDD. Univariate analysis showed that the presence of LVDD was related with: BMI [odds ratio (OR): 1.14, 95% confi dence interval (CI): 0.99-1.29, p=0.05], therapy with ARB’s (OR: 0.17, 95% CI: 0.03-1.01, p=0.05), hs-CRP (OR: 1.29, 95% CI: 1.04-1.59, p=0.02), HDL-C (OR: 0.95, 95% CI: 0.91-0.99, p=0.03), fasting triglycerides (OR: 1.02, 95% CI: 1.00-1.04, p=0.003) and Left Ventricular Myocardial Index (LVMI) (OR: 1.05, 95% CI: 1.00-1.08, p=0.03). No correlation was observed for BNP and sST2. Regression analysis revealed that the new onset of LVDD was positively correlated with hs-CRP levels (OR: 1.12, 95% CI: 1.08-1.51, p=0.02) and fasting triglycerides (OR: 1.07, 95% CI: 1.01-1.14, p=0.02) and negatively with the therapy with ARB’s (OR: 0.14, 95% CI: 0.05-0.43, p=0.05). Higher hs-CRP levels and fasting triglycerides may predict the new onset of LVDD - the echocardiographic depiction of diabetic cardiomyopathy - in type 2 diabetes patients with normal cardiac function, while therapy with ARB’s may play a protective role in this 4-year prospective study.

2134-PUBEffects of Continuous Positive Airway Pressure on Blood Pressure and Arterial Stiffness in Diabetic Patients with Hypertension and Sleep Apnea SyndromeTAKEHIKO WAGO, SHUNICHI TANAKA, Yokohama, Japan

Obstructive sleep apnea syndrome (OSAS) is caused by the obstruction of the upper airway and is considered as a complexed metabolic disorders characterized with tachycardia, hypertension, dyslipidemia and hyperglyce-mia. The possible complications of ischemic heart diseases such as angina or myocardial infarction have been reported. We investigated the effects of continuous positive airway pressure (CPAP) therapy in hypertensive OSAS patients (n=37, BMI: 28.1±1.3, AHI 20 by polysomnography (PSG)) with type 2 diabetes.

All patients with uncontrolled hypertension (SBP 140mmHg or DBP 90mmHg) were recruited from the outpatient clinic for diabetes in Minatomi-rai clinic and screened for OSAS by pulse-oximeter and diagnosed by PSG.

All pharmaceutical treatments as well as dietary or exercise therapy were not changed throughout the observation periods. Heart rate (HR: 83±2.1 bpm) and blood pressure (BP: 154±2.4/94±2.4 mmHg) were measured on sitting position after 15 minutes rest on bed. Ankle Brachial Index (ABI: 1.07±0.24), Pulse Wave Velocity (PWV: 1645±61 cm/sec) and Intima Media Thickness (IMT: 0.83±0.04 mm) were measured and blood samples (HbA1c: 6.9±0.3%, PG: 159±16 mg/dl, LDL-C: 124±6.7) were obtained every 3 months.

After 12 months CPAP treatment, HbA1c (6.3±0.3%, p<0.005), PG (125±12 mg/dl, p<0.05) and BMI (24.7±1.3, p<0.01) were signifi cantly improved. Both systolic and diastolic BP (128±2.3/76±1.2 mmHg, both p<0.001), HR (73±1.5 bpm, p<0.05), PWV (1506±51 cm/sec, p<0.05), IMT (0.80±0.04 mm) and LDL-C (103±6.1 mg/dl, p<0.005) were also decreased signifi cantly. The improve-ments observed in this study suggested the amelioration of the status of the arteriosclerosis.

CPAP therapy may improve the control of hyperglycemia, hypertension, and dyslipidemia and thus reduce cardiovascular risks in type 2 diabetes.

2135-PUBHigh Visceral Fat with Low Subcutaneous Fat Accumulation as a Determinant of Atherosclerosis in Patients with Type 2 DiabetesRYOTARO BOUCHI, TAKATO TAKEUCHI, NORIHIKO OHARA, YUJIRO NAKANO, MASANORI MURAKAMI, MASAHIRO ASAKAWA, YURIKO SASAHARA, MIT-SUYUKI NUMASAWA, ISAO MINAMI, HAJIME IZUMIYAMA, KOSHI HASHIM-OTO, TAKANOBU YOSHIMOTO, YOSHIHIRO OGAWA, Tokyo, Japan

Little is known regarding the association between high visceral fat with low subcutaneous fat accumulation and the risk for atherosclerosis. This study was designed to elucidate whether high visceral fat with low subcu-taneous fat accumulation enhances the risk for atherosclerosis in patients with type 2 diabetes (T2DM). This is a cross-sectional study of 148 patients with T2DM (mean age 65±12 years; 44.5% female). Visceral fat area (VFA, cm2) and subcutaneous fat area (SFA, cm2) were assessed by abdominal computed tomography. Carotid intima media thickness (CIMT, mm) mea-sured by ultrasonography was used for the assessment of atherosclerosis. Patients were divided into 4 groups: SFA <100 and VFA <100 (S(-)V(-)), SFA

using CGM in the hospital to develop new strategies to prevent recurrent severe hypoglycemia. We propose that CGM for all patients with persistent severe hypoglycemia, whether using the device that is able to communicate to a patient’s pump or using an alternate independent device, should be consid-ered for management of recurrent severe hypoglycemia in the hospital.

2132-PUBSelf-Reported Hypoglycemic Rates and Insulin Regimen among 7,289 Insulin-Treated Adult Patients with Diabetes: Results from an International Survey in Nine CountriesANA MARIA GOMEZ MEDINA, ATEF A. BASSYOUNI, YONG M. BEE, IDA A. KSHANTI, MAK OMAR, NAZRUL I. SIDDIQUI, RAMAZAN SARI, ANAND JAIN, VICKY CHAN, SALEM A. BESHYAH, Bogotá, Colombia, Cairo, Egypt, Singapore, Sin-gapore, Jakarta, Indonesia, Overport, South Africa, Mymensingh, Bangladesh, Anta-lya, Turkey, Zurich, Switzerland, Abu Dhabi, United Arab Emirates

Real-world data on hypoglycemia rates are sparse and comparisons among insulin regimens rely heavily on data from randomized clinical trials, particularly in non-western countries. The aim of the non-interventional International Operations Hypoglycemia Assessment Tool (IO HAT) study conducted in Bangladesh, Colombia, Egypt, Indonesia, the Philippines, Sin-gapore, South Africa, Turkey and the UAE was to assess the incidence of hypoglycemia among patients with insulin-treated (premix, short-acting and long-acting) diabetes. Baseline characteristics of patients with type 1 (T1D) and type 2 diabetes (T2D) are shown in Table 1. “Any” and “nocturnal” hypo-glycemia rates, per patient-year (PPY), were highest in patients with T1D on short-acting regimens during retrospective and prospective periods (Any, 81.7 and 123.1; Nocturnal, 35.4 and 22.9 PPY). Rates of any and nocturnal hypoglycemia were lowest in patients with T2D on long-acting regimens (Any, 13.9 and 24.0; Nocturnal, 4.2 and 2.5 PPY). In the pooled population of patients with T1D and T2D, there was a signifi cantly lower (p<0.001) rate ratio (RR, [95% CI)] for any hypoglycemic event in patients using premix (RR 0.57 [0.50:0.64)], long-acting (RR 0.39 [0.34:0.45)] or short- and long-acting insulin (RR 0.70 [0.62:0.79)] compared to those using short-acting insulin.Table 1. Baseline Characteristics.

Supported By: Novo Nordisk Inc.

COMPLICATIONS—MACROVASCULAR—ATHEROSCLEROTIC CARDIOVASCULAR DISEASE AND

HUMAN DIABETES

2133-PUBThe Prognostic Role of High Sensitivity C-Reactive Protein and Trig-lycerides on the New Onset of Left Ventricular Diastolic Dysfunc-tion in Patients with Type 2 DiabetesEVANGELOS FOUSTERIS, ATHANASIA PAPAZAFIROPOULOU, ANASTASIOS THEODOSIS-GEORGILAS, CHRISTOS VERRAS, CHRISTOS TOUNTAS, SPIRIDON MATSAGOS, STILIANOS CHANTANIS, ALEXANDROS KAMARATOS, STEFANOS FOUSAS, ANDREAS MELIDONIS, Piraeus, Greece

Diabetes mellitus is a major risk factor for heart failure through the path of diabetic cardiomyopathy and diastolic dysfunction of left ventricle (LVDD). We enrolled 48 volunteers with type 2 diabetes of mean age 55.4±10.0 years, HbA1c 7.5±1.5%, BMI 29.4±5.1Kg/m2 and diabetes duration 2.8±0.8

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two groups in a randomized controlled manner. Control group received SC Insulin injections to control blood glucose values below 140 mg/dl or 180 mg/dl postprandial. Study group received SC Insulin and Vildagliptin with the same target. Blood glucose values, measured every 4 hours, were cor-rected with SC Insulin. Data was documented for each measuring, mean glucose values per hospitalization day, insulin values given for correction (I.U.s) and any hypoglycemic events. At the 90-days measurement, 89.7% weren’t re-admitted, 8.6% were re-admitted once and 1.7% was re-admit-ted twice. The results of the comparison between the two groups were as follows: A signifi cant statistical difference had been found between Vilda-gliptin treated subjects (M=0.04, SD=0.19) and the control group (M=0.20, SD=0.48) in the average re-admissions after 90 days (Z=-1.64, p=0.05). A signifi cant reduction in the heart failure re-hospitalization rates following Vildagliptin therapy as compared with control in ACS patients hospitalized in ICCU, was demonstrated.

Supported By: Novartis

2140-PUBWaist-to-Height Ratio Predicts Infl ammatory Biomarkers in Young Euglycemic South AsiansMILLIE ARORA, RUPAN BOSE, FAHIM ABBASI, SHRIRAM NALLAMSHETTY, ABHA KHANDELWAL, PRAJAKTA RANADE, MONICA DIVAKARUNI, RANJAN RAY, RAJESH DASH, Pomona, CA, Los Angeles, CA, Stanford, CA

South Asians exhibit a 60% higher prevalence of diabetes and a 4-fold higher risk of cardiovascular disease (CVD) compared to other ethnic groups, suggest-ing a substantial burden of nontraditional risk factors. Although a waist-to-height ratio (WHtR) >0.5 correlates with diabetes (DM) risk in South Asians, it is unknown whether higher WHtRs also denote an infl ammatory state inde-pendent of insulin resistance (IR). We hypothesized that elevations in WHtR associate with nontraditional risk factors in South Asians prior to the onset of PreDM or insulin resistance (IR). We measured WHtR and nontraditional risk factors, and performed oral glucose tolerance tests with insulin levels in 83 young South Asians without coronary disease (mean age: 44±13 yrs) in the Stanford South Asian Translational Heart Initiative (SSATHI) clinic.

In euglycemic patients (no DM/preDM, n=53, Table I) WHtR exhib-ited signifi cant correlations with the following parameters: (1) fasting glucose:Matsuda Index (MI) (r =-0.58*); (2) 2 hr glucose:MI (r =-0.37*); (3) Lp(a) (r=0.65*); and (4) Homocysteine (r=0.53**) (*p<0.01;**p<0.05). In eugly-cemic patients with IR (MI 3.8, n=8), there was a trend toward correlation between WHtR and elevated CRP.

Our fi ndings indicate that elevated WHtR predicts abnormal CVD bio-markers prior to the onset of preDM/IR in South Asians and should prompt assessment of nontraditional CVD risk in addition to preDM/IR.Table 1. Results in a Sample South Asian Study Population.

Supported By: National Institutes of Health; National Heart, Lung, and Blood Institute

≥100 and VFA <100 (S(+)V(-)), SFA <100 and VFA ≥100 (S(-)V(+)), and SFA ≥100 and VFA ≥100 (S(+)V(+)). Linear regression analysis with a stepwise proce-dure was used for the statistical analyses. Among the patients examined, 16.3% were S(-)V(+). Mean (95% confi dence interval) of CIMT adjusting for age and gender were 0.80 (0.69-0.91), 0.86 (0.72-1.01), 1.28 (1.11-1.44) and 0.83 (0.77-0.88) in patients with S(-)V(-), S(+)V(-), S(-)V(+) and S(+)V(+), respec-tively (p <0.001). The S(-)V(+) patients exhibited male predominant (100% male), signifi cantly older than S(-)V(-) patients and those with S(+)V(+) and had a highest VFA-SFA ratio (V/S ratio) among the 4 groups. In multivariate linear regression analysis, S(-)V(+) was signifi cantly associated with CIMT (Standardized β 0.423, p <0.001). Notably, S(+)V(+) was inversely associated with CIMT in the multivariate model. This study provides evidence that high visceral fat with low subcutaneous fat accumulation is an important deter-minant of carotid atherosclerosis and high subcutaneous fat could be protec-tive against atherosclerosis in patients with T2DM.

Supported By: Grants-in-Aid for Scientifi c Research from the Ministry of Educa-tion, Culture, Sports, Science and Technology of Japan

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2138-PUBCardio-Ankle Vascular Index Is Independently Associated with Future Death Events in Outpatients with Metabolic DisordersYUTA SATO, DAIJI NAGAYAMA, ATSUHITO SAIKI, SHOU TANAKA, RENA WATANABE, YASUHIRO WATANABE, HARUKI IMAMURA, TAKASHI YAMAGU-CHI, NORIKO BAN, HIDETOSHI KAWANA, AYAKO NAGUMO, MASAHIRO OHIRA, KEI ENDO, KOHJI SHIRAI, ICHIRO TATSUNO, Sakura, Japan, Oyama, Japan

Objective: We investigated whether cardio-ankle vascular index (CAVI), an arterial stiffness marker, independently predicts future death events in subjects with metabolic disorders.

Methods: 494 outpatients (male 239, mean age 62.8 ± 10.7) underwent CAVI between September 2004 and December 2006 at Toho University, Sakura Medical Center in Chiba, Japan. Subjects were followed until Sep-tember 2011 (follow-up duration 5.2±0.8 years) and analyzed. For underlying diseases, 49.6% of the subjects had diabetes mellitus, 51.6% had hyperten-sion, and 59.7% had dyslipidemia. Baseline CAVI was 9.3±1.7, body mass index (BMI) was 23.8 ± 3.4%, blood pressure was 138.4±23.6/81.6±11.7 mmHg, HbA1c was 6.5 ± 1.6%, total cholesterol was 205 ± 39 mg/dl, triglyc-eride was 141 ± 95mg/dl, and HDL-C was 55 ± 15 mg/dl.

Results: During the observation period, 24 subjects died. Causes of death were pneumonia (6 subjects), malignant tumor (6 subjects), new-onset car-diovascular events (6 subjects), kidney failure (2 subjects), liver failure (1 sub-ject) and unknown (3 subjects). In subjects with future death events, baseline CAVI and age were signifi cantly higher, whereas BMI was signifi cantly lower than in subjects without future death events. In Cox proportional hazards regression analysis, the factors independently associated with higher risk of death events were every 1.0 increment of CAVI [hazard ratio (HR) 1.234, p=0.001], age (HR 1.089, p=0.003), and male gender (HR 4.217, p=0.026). BMI, diabetes mellitus, hypertension and dyslipidemia were not signifi cant independent predictors of future death events.

Conclusion: In individuals with metabolic disorders, CAVI was a predictor of future death events.

2139-PUBRehospitalization in Type 2 DM ACS Patients Treated with Vilda-gliptin vs. Standard TreatmentIDIT DOBRECKY-MERY, Nahariya, Israel

Hospital readmission is an important contributor to total medical expen-ditures and is an emerging indicator of quality of care. Diabetes, similar to other chronic medical conditions, is associated with increased risk of hos-pital readmission. Assessing the feasibility of DPP-4-I as glucose lowering treatment for type 2 DM patients during ACS while monitoring 90 days re-hospitalization and worsening heart failure 84 T2DM adult patients naïve to DPP-4 Inhibitors were enrolled when admitted to ICCU with ACS diagnosis. Metformin was discontinued during hospitalization and patients divided into

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COMPLICATIONS—MACROVASCULAR—ATHEROSCLEROTIC CARDIOVASCULAR DISEASE AND HUMAN DIABETES

2143-PUBThe Visceral Adiposity Index Predicts Cardiovascular Events Both in Coronary Artery Disease Patients with, and in Coronary Artery Disease Patients without, DiabetesALEXANDER VONBANK, CHRISTOPH H. SAELY, PHILIPP REIN, ANDREAS LEIHERER, DANIELA ZANOLIN, HEINZ DREXEL, Feldkirch, Austria, Triesen, Liech-tenstein, Philadelphia, PA

The visceral adiposity index (VAI) is a validated tool for the evaluation of visceral adiposity, using waist circumference, serum triglycerides, age and gender to diagnose this metabolic abnormality. It has recently been associ-ated with cardiovascular risk in primary care patients. No data are avail-able on the association of the VAI with mortality in patients with estab-lished CAD. We therefore calculated the VAI in 1472 consecutive patients with angiographically proven stable CAD according to the Amato formula. T2DM was defi ned according to the ADA defi nition. The incidence of vascu-lar events was recorded over 10 years. At baseline, the VAI was signifi cantly higher in CAD patients with T2DM than in those without diabetes (362±330 vs. 247±224; p <0.001). Prospectively, 539 vascular events occurred; the event rate were signifi cantly higher in patients with T2DM than in those who did not have diabetes (44.8% vs. 33.7%; p<0.001). The VAI signifi cantly predicted cardiovascular events in CAD patients with T2DM (standardized adjusted hazard ratio (HR) 1.16 [1.01-1.33]; p=0.037) as well as in those with-out T2DM (HR 1.14 [1.02- 1.27]; p=0.018). We conclude that the VAI predicts cardiovascular events both in CAD patients with and in CAD patients with-out diabetes.

2144-PUBCirculating Klotho Levels in Newly Diagnosed Type 2 Diabetes Mel-litusARIF YUKSEL, ALPER SAHIN, GIRAY BOZKAYA, MEHMET CALAN, ESMA YUKSEL, Izmir, Turkey

Context: Klotho is an anti-aging protein with pleiotropic activities. It has been demonstrated that Klotho is associated with improved beta-cell func-tion and with protective effects against vascular atherosclerosis in animal models.

Objective: To investigate circulating Klotho levels in newly diagnosed type 2 diabetic patients and to evaluate the association between insu-lin resistance, carotid intima-media thickness (CIMT) and other metabolic parameters.

Participants: Forty-three subjects with newly diagnosed type 2 diabetes mellitus (T2DM) and 43 age-, gender- and body mass index (BMI)-matched normoglycemic individuals as controls.

Main Outcome Measures: Anthropometric measurements including weight, height, waist circumference and CIMT were recorded. All subjects underwent venous blood drawing after overnight fasting to measure HbA1c, insulin, lipid profi le, hs-CRP, creatinine and Klotho levels. Serum concentra-tions of Klotho were measured using ELISA. CIMT was measured by high resolution B-mode ultrasound. Insulin resistance was calculated using the HOMA-IR method.

Results: Circulating Klotho levels did not signifi cantly differ between the newly diagnosed T2DM and control groups (T2DM=4.25 ± 2.15 vs. Control=4.23 ± 2.65ng/ml, P=0.983). CIMT was found to be higher in sub-jects with T2DM (T2DM=0.81 ± 0.19 vs. Control=0.67 ± 0.11 mm, P<0.001) compared with normoglycemic individuals. Pearson’s correlation analysis showed that there was no correlation between Klotho levels and HOMA-IR, CIMT or other metabolic parameters.

Conclusions: Serum Klotho levels are not associated with insulin resis-tance or CIMT. Although preclinical studies have suggested Klotho as a new therapy for diabetes mellitus and atherosclerosis, our results did not support those studies. We need further preclinical and clinical research to clarify the effect of Klotho on beta-cell function and atherosclerosis.

2145-PUBChallenges in Managing Diabetes Care in Older Adults with Type 1 DiabetesSARIT POLSKY, LAURA PYLE, VIRAL N. SHAH, JANET K. SNELL-BERGEON, Aurora, CO

A growing number of older adults manage type 1 diabetes (T1D) and other diseases of aging. We examined diabetes management and the prevalence of comorbid conditions among a cohort of adults with T1D enrolled in the Coronary Artery Calcifi cation in type 1 diabetes (CACTI) study who have been followed for an average of 14 ± 0.7 years for the development of cardio-vascular and renal complications.

2141-PUBRelationship between Serum Osteocalcin Level and Carotid Intima-media Thickness in a Metabolically Healthy Chinese PopulationYUQI LUO, XIAOJING MA, YAPING HAO, QIN XIONG, YITING XU, XIAOPING PAN, YUQIAN BAO, WEIPING JIA, Shanghai, China

Osteocalcin is a synthetic osteoblast-specifi c protein which is involved in the regulation of bone, glucolipid metabolism and in maintaining homeosta-sis. Recent studies have investigated whether osteocalcin is associated with subclinical and clinical atherosclerotic coronary artery disease, but these studies have yielded inconsistent results. This might be due to different degrees of confounding from factors that are associated with serum osteo-calcin level, such as metabolic-related variables. This study aimed to inves-tigate the relationship between serum osteocalcin level and carotid intima-media thickness (C-IMT) in a metabolically healthy population. A total of 476 subjects with normal values for weight, glucose tolerance, blood pressure, and lipids (age range, 20-75 years; 155 men, 201 premenopausal women, 120 postmenopausal women) from the Shanghai Obesity Study were recruited for this cross-sectional study. Subjects with a history of cardiovascular dis-ease or carotid plaque were excluded. C-IMT was measured by ultrasonog-raphy. Serum osteocalcin level was assessed by an electrochemilumines-cence immunoassay. The median (interquartile range) of serum osteocalcin level in the entire population was 17.02 (13.31-21.47) ng/mL. Serum osteocal-cin level in postmenopausal women was signifi cantly higher than that in men and premenopausal women (all P < 0.001), while the level of serum osteocal-cin in men was also signifi cantly higher than that in premenopausal women (P < 0.001). No signifi cant correlation was found between C-IMT and serum osteocalcin level in either men or postmenopausal women. There was a sig-nifi cant, inverse correlations between C-IMT and serum osteocalcin level in premenopausal women after adjustment of age, but this association was eliminated after adjustment for other confounding factors. Serum osteocal-cin level was not independently associated with C-IMT in a metabolically healthy Chinese population.

Supported By: National Natural Science Foundation of China (81170788); National Basic Research Program of China (2012CB524906); National Key Technol-ogy R&D Program of China (2012BAI02B03); Shanghai Health and Family Planning Commission (2013ZYJB1001); Key Project of Science and Technology of Shanghai (13XD1403000)

2142-PUBDHA/AA Ratio but Not EPA/AA Ratio Is More Strongly Correlated with the Severity of Chronic Obstruction of Coronary Artery in Type 2 Diabetic PatientsSEI-ICHIRO OGAKU, Shiga, Japan

The concentrations of dietary n-3 polyunsaturated fatty acids (PFAs), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) modify the incidence of coronary heart disease (CHD). We investigate which n-3 PFA is more effective on the association of the severity of CHD in type 2 diabetic patients. 184 type 2 diabetic subjects were nominated as poor blood glucose control from April 2008 to September 2014 and aged 40 to 72 years on this trial. We fi rstly calculated fasting plasma PFAs, LDL-cholesterol, HDL cho-lesterol and triglyceride (TG) levels. We excluded the subjects who reported the history of CHD or ECG abnormality consistent with ischemia at base-line survey. Then they had been followed for six years and non-fatal CHD diagnosed using percutaneous coronary intervention. CHD severity was assessed using the Gensini scoring system. Next, we divided them into 2 groups, who were in the presence of CHD (DM-PCI, N=56) or not with CHD (DM, N=70). We also added the data from healthy volunteers as NGT group. These values were analyzed using an ANOVA model, Pearson’s test and mul-tivariate logistic regression models analyses. The average of systolic blood pressure, age, BMI, the concentrations of HbA1c, LDL, HDL and TG were neither different between two groups. Then, we investigated both EPA/AA and DHA/AA levels in each group and found that DHA/AA levels were sig-nifi cantly lower in DM-PCI than those in DM (DHA/AA; 0.69, 0.85 p<0.001, respectively). DHA/AA ratio in DM-PCI was signifi cantly negative correla-tion to Gensini score (r=0.50 p<0.001, respectively). In multivariate logistic regression model, only DHA/AA ratio increased up to 3.08 (95% CI 1.76-5.89) with statistical value of p=0.01. A negative correlation was noted between the severity of CHD and DHA/AA ratio in DM-PCI. These data may suggest that low serum DHA/AA ratios but not EPA/AA constitute an independent chronic obstruction of coronary arteries.

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COMPLICATIONS—MACROVASCULAR—ATHEROSCLEROTIC CARDIOVASCULAR DISEASE AND HUMAN DIABETES

Figure. Circulating Microparticles (MPs) in Patients with Type 1 Diabetes and Healthy Controls.

Supported By: Berth von Kantzow Foundation; Stockholm County Council; Karo-linska Institutet

2148-PUBWITHDRAWN

2149-PUBEvaluation of the Ankle-Brachial Index in Patients with Type 2 Dia-betes Mellitus: Hospital Central of Instituto de Prevision Social, Asuncion, ParaguayELIZABETH VALINOTTI, AMADO E. DENIS, LAURA PAREDES, ROSA N. VEGA, NADIA L. GARCÍA, FABIOLA ROMERO, TANYA PAIVA, MARIA C. MENONI, Asun-ción, Paraguay

Ankle-brachial index (ABI) is an inexpensive, reproducible simple, noninva-sive technique for the diagnosis of peripheral arterial disease (PAD). The util-ity of identifying subjects with PAD, is because is an independent predictor of cardiovascular disease. We found the frequency of PAD by assessing the ABI and its clinical characteristics in 153 diabetic patients attending in the Endocrinology Department of Ingavi Clinic of Instituto de Previsión Social. This is a descriptive exploratory, cross-sectional study in type 2 diabetes patients, in which the ABI was obtained using an 8 MHz vascular doppler. 153 patients were evaluated of which 92 (60%) had PAD, average age 61 years, 38 (41.0%) were in the range of 58-68 years. 70 (76%) patients were female. Mild arterial obstruction by ABI was found in 45 (48, 9%); moder-ate arterial obstruction 8 (8, 6%) patients; severe arterial obstruction: 39 (42, 5%) patients; calcifi cations Monckenberg 11 (7.2%) patients. Of the 92 patients with PAD, the Edinburgh Questionnaire for Vascular Intermit-tent Claudication (CIV), showed 80 patients (87.0%) were asymptomatic; 12 (13.0%) had CIV; 7/12 patients (58.3%) defi ned CIV and 5/12 (41.7%) atypi-cal CIV. Frequency of PAD by ABI assessment of diabetic patients was high (60%). It is common in people over 60 years, most are asymptomatic, making important the evaluation of ABI, and the diagnosis of PAD could be use as a predictor of cardiovascular complications.

2150-PUBEvaluation of Peripheral Artery Disease in Elderly Patients with Type 2 Diabetes MellitusFULDEN SARAC, SEFA SARAC, SUMRU E. SAVAS, FEHMI AKCICEK, Izmir, Turkey

Peripheral arterial disease (PAD) refers to the manifestation of athero-sclerosis in the lower limb distal to the aortic bifurcation. PAD prevalence and incidence are both sharply age-related, rising >10% among patients in their 60s and 70s. The aims of the study were to determine the frequency of peripheral artery disease (PAD) by ankle brachial index (ABI) in patients with type 2 diabetes mellitus (DM), and to compare the risk factors for PAD between patients with age ≥60 years and patients with age <60 years. The study population included 525 (patients with age≥60 years) (mean age; 68.0±6.6) and 284 (patients with age<60 years) (mean age; 51.8±5.8 years) patients with DM. Demographic and biochemical data were collected, retro-spectively. PAD disease was evaluated by ABI. Using the higher values of the ankle and brachial pressures respectively, ABI was calculated and consid-

Study subjects were 71 T1D patients aged 60-71 with a mean diabetes duration of 44 ± 10 years. Subjects reported checking their blood glucose levels 5 ± 2.5 times/day and saw an endocrinologist 2.7 ± 1.3 times in the past year. Most subjects did multiple daily injections (53%) and 38% used a continuous glucose monitor (CGM).

The Figure shows the percentage of older adults at the most recent visit who were hyperglycemic (HbA1c>7%), hypertensive (BP≥140/90), had LDL-cholesterol >100 mg/dl, were overweight or obese (BMI>25 kg/m2), had ele-vated Beck Depression Inventory-II scores, and had at least one episode of moderate or severe hypoglycemia in the prior 6 months. Over 56% of sub-jects had elevated coronary artery calcium (≥100 Agatston units), and 18% had stage 3 chronic kidney disease (estimated glomerular fi ltration rate < 60 ml/min/1.73m2).

Older adults with long-standing T1D had a high burden of CVD risk factors and cardio-renal complications. Increased use of insulin pumps and CGMs in older adults could improve care by reducing hyper- and hypoglycemia.Figure. CVD Risk Factors in Older Adults with T1D.

Supported By: American Diabetes Association (7-13-CD-10 to J.K.S-B.); National Institutes of Health

2146-PUBWITHDRAWN

2147-PUBCirculating Microparticles in Patients with Type 1 DiabetesKARIN BERGEN, FARIBORZ MOBARREZ, GUN JÖRNESKOG, HÅKAN WALLÉN, SARA TEHRANI, Stockholm, Sweden

Microparticles (MPs) are small vesicles released from different cells into body fl uids that serve as mediators in various physiological and pathophysi-ological processes. In the circulation, platelet-derived MPs are the most abundant. Elevated levels of circulating MPs have been associated with vascular disease in nondiabetics and in patients with type 2 diabetes. We investigated total MP and platelet MP levels in patients with type 1 dia-betes. The study included 236 patients with type 1 diabetes with no his-tory of cardiovascular disease and 100 healthy controls matched for age, sex and body mass index. Plasma concentrations of total MPs and platelet MPs were assessed using fl ow cytometry and compared between patients and controls. Levels of total MPs and platelet MPs were higher in patients with type 1 diabetes than in controls (See Figure). Of the 236 patients, 130 had no clinical microangiopathy (except for simplex retinopathy), while 106 patients had microvascular complications. MP levels did not differ between patients with and without microangiopathy. In addition, no associations were found between MP levels and glycemic control or diabetes duration. The increased levels of total MPs and platelet MPs in circulation indicate increased cellular and platelet activation in patients with type 1 diabetes. Further studies are needed to investigate if and how MPs are involved in the development of vascular complications in type 1 diabetes.

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COMPLICATIONS—MACROVASCULAR— COMPLICATIONS—NEPHROPATHY— CELLULAR MECHANISMS OF ATHEROGENESIS IN DIABETES BASIC AND EXPERIMENTAL SCIENCE

eration of VSMCs with intermittent glucose was decreased with gemigliptin treatment (relative ratio 3.82 ± 0.67 vs. 5.96 ± 1.21, p < 0.05) and sitagliptin treatment (relative ratio 4.66 ± 0.91 vs. 5.96 ± 1.21, p < 0.05). In Western blot analysis, phopspho p38 MAPK, PI3 kinase, Nf-κB, phopspho Akt expression were suppressed with gemigliptin and sitagliptin in normal glucose. Phos-pho-p44/42 MAPK (ERK1/2), phospho MEK1/2, phopspho p38 MAPK, PI3 kinase expression were suppressed with gemigliptin in glycemic variablity. In the apoptotic pathway, Bcl-xl, Bax, phospho-Bad, and caspase-3 were not affected by glucose fl uctuations or gemigliptin or sitagliptin for 72 h. Glucose fl uctuations increased the proliferation of OLETF rat VSMCs via the MAPK (ERK1/2, p38 MAPK) and PI3 kinase pathway. These effects were inhibited by antidiabetes agent gemigliptin more than sitagliptin.

2155-PUBAssociation of Endothelial Progenitor Cells with Asymmetric Dim-ethylarginine and Cardiometabolic Risk Factors in PrediabetesANGELIKI ANGELIDI, ATHANASIA PAPAZAFIROPOULOU, JOHN PROTOPSAL-TIS, THEODOROS SERGENTANIS, ANGELOS GRITZAPIS, SPIROS MATSAGOS, PANAGIOTA SPIROPOULOU, ELENI BOUTATI, ANDREAS MELIDONIS, Piraeus, Greece, Athens, Greece

Background: Asymmetric dimethylarginine (ADMA) an endogenous inhibi-tor of nitric oxide synthase is a novel marker of atherosclerosis. Endothelial Progenitor Cells (EPCs) are a potential biological marker of cardiovascular disease. The aim of the study was to investigate the relation of EPC levels with several cardiovascular risk factors including ADMA in prediabetes.

Materials and Methods: 59 participants with prediabetes were enrolled. 33 patients had impaired fasting glucose (IFG), 12 impaired glucose toler-ance (IGT) and 14 IFG and IGT. Medical history and biochemical parameters, including traditional cardiometabolic risk factors and hsCRP, were obtained. Homeostasis model assessment of insulin resistance (HOMA-IR) was esti-mated. ADMA concentrations were determined by ELISA method. Flow cytometry identifi ed and quantifi ed EPCs (CD34+ KDR+CD133+ cells). Statis-tical analysis was performed using STATA 11.1 statistical software.

Results: A correlation was observed between the subclasses of predia-betes with: sex (p=0.05), smoking (p=0.04), presence of metabolic syndrome (p=0.05), age (r=0.385, p=0.003), waist to hip ratio (WHR) (r=0.389, p=0.002) and insulin levels (r=0.260, p=0.05). The IFG+IGT subclass was statistically older people, smokers with more frequent occurrence of metabolic syn-drome, insulin resistance, higher levels of insulin and WHR, followed by IGT and IFG category. Regarding EPCs and prediabetes categories statistically lower levels were observed in IGT group against IFG group (p=0.002) and IGT+IFG group against IFG group (p=0.004). No differences between ADMA and prediabetes categories were noted.

Conclusion: Additional studies have shown a signifi cant correlation between prediabetes and cardiovascular disease with a potential more aggravating correlation of IGT compared to IFG group. The lower EPC levels of IGT group may contribute to this unfavorable cardiovascular profi le of pre-diabetes.

COMPLICATIONS—NEPHROPATHY—BASIC AND EXPERIMENTAL SCIENCE

2156-PUBHigh Glucose and Lipopolysaccharide Activate NOD1-RICK-NF-κB Infl ammatory Signaling in Mesangial CellsYONG XU, WEI HUANG, FANG GOU, Luzhou, China

Systemic and local low-grade infl ammation and release of proinfl amma-tory cytokines are implicated in the development and progression of diabe-tes mellitus (DM) and diabetic nephropathy (DN). The TLR2, TLR4, and NLRP3 infl ammasomes of the innate immune system produce various proinfl amma-tory cytokines and are critically involved in infl ammatory responses in kidney tissues. The NOD-like receptor (NLR) NOD1 is involved in the NF-κB infl am-matory signaling pathway and has an important role in the development of insulin resistance. Extracellular stimuli such as high glucose or lipopolysac-charide (LPS) can induce NOD1-RICK to activate NF-κB, which is associ-ated with diabetes and other chronic infl ammatory conditions. It is currently unknown whether NOD1-RICK-mediated NF-κB signaling is involved in DN pathogenesis. In this study, expression of NOD1, RICK, IκBα, and NF-κB was detected in cultured rat glomerular mesangial cells (rGMCs) stimulated with high concentrations of glucose and LPS. ML130, a NOD1 inhibitor, was used to investigate the role of the NOD1 signaling pathway in DN infl am-mation. Our results showed that high glucose or LPS increased the protein and mRNA expression of NOD1, RICK and NF-κBp65, but attenuated IκBα

ered to be abnormal if less than or equal to 0.9, and normal if higher than 0.9. Abnormal ABI levels were detected in 157 (31.2%) of patients with age ≥60 years and 35 (15.4%) patients with age<60 years (p=0.001). Patients with age≥60 years, mean levels of ABI were found to be 0.69±0.2 in abnormal ABI group and 1.22±0.8 in normal ABI group. However, mean levels of ABI were found to be 0.74±0.5 in abnormal ABI and 1.35±0.9 in normal ABI, in patients with age<60 years. History of cardiovascular disease, history of stroke, dys-lipidemia, hypertension, neuropathy, retinopathy, nephropathy and smoking were statistically signifi cantly associated with ABI in all diabetic patients (p<0.05). The frequency of PAD was higher in patients with age≥60 years than that of patients with age<60 years. Smoking, increased levels of dura-tion of DM, fasting and postprandial glucose, HbA1c, triglyceride and chronic complications such as cardiovascular disease, stroke, dyslipidemia, hyper-tension, neuropathy, retinopathy and nephropathy were associated with risk of PAD in diabetic elderly patients.

2151-PUBThe Relationship between Coronary Artery Lesions and Peripheral Atherosclerosis in Type 2 DiabetesLEI ZHANG, Chengdu, China

Objective: To explore the relationship between coronary artery lesions and peripheral atherosclerosis in type 2 diabetes (T2DM).

Methods: 204 patients with T2DM underwent simultaneous ultrasound scanning of bilateral carotid, lower limb arteries and dual source coronary computed tomography examination, were classifi ed into observation group (with coronary artery lesions) and control group (without coronary artery lesions). Age, gender, hypertension, smoking, A1c, serum lipid levels and other information were recorded and analyzed.

Result: 204 individuals including 143 patients with coronary artery lesions and 61 patients without coronary artery lesions. Groups signifi cantly dif-fered in age, history of hypertension, smoking, A1c, ABI, urinary albumin-cre-atinine ratio and the prevalence of carotid and lower limb atherosclerosis. Logistic regression analysis revealed that age, smoking, ABI, and peripheral atherosclerosis were independent predictors for the presence of coronary artery lesions.

Conclusion: Our fi ndings suggest that T2DM patients with peripheral ath-erosclerosis have an increased risk of coronary artery lesions, these patients should carry on dual source coronary computed tomography examination as early as possible.

2152-PUBWITHDRAWN

COMPLICATIONS—MACROVASCULAR—CELLULAR MECHANISMS OF ATHEROGENESIS IN DIABETES

2153-PUBWITHDRAWN

2154-PUBAntiproliferative Effects of Sitagliptin and Gemigliptin on OLETF Rat Vascular Smooth Muscle Cells Stimulated by Glucose VariabilitySUNG HOON YU, JAE MYUNG YU, Seoul, Republic of Korea

The proliferation of vascular smooth muscle cells (VSMCs) plays a cru-cial role in atherosclerosis. DPP-4 inhibitors have a wide variety of phar-macological activities, however there are not suffi cient data in vascular smooth muscle cells (VSMCs) proliferation. In this study, we demonstrated that the effect of gemigliptin and sitagliptin on the proliferation of VSMCs with normal glucose or glucose fl uctuations. Primary cultures of male OLETF rat VSMCs were obtained from enzymatically dissociated rat thoracic aorta. VSMCs with gemigliptin (100 µM) or sitagliptin (100 µM) were incubated for 72 h with normal glucose (4.8 mmol/L) media or alternating normal (4.8 mmol/L) and high glucose (24.5 mmol/L) media every 12 h. The proliferation of VSMCs, proliferative molecular pathway (including p44/42 MAPK, MEK, p38, JNK, Akt) and apoptotic pathway were analyzed. We found enhanced proliferation of VSMCs incubated with intermittent high glucose medium compared to normal glucose media using the methylthiazoletetrazolium assay (relative ratio 5.96 ± 1.21 vs. 1.00 ± 0.08, p < 0.01). However, the prolif-

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COMPLICATIONS—NEPHROPATHY—CLINICAL AND TRANSLATIONAL RESEARCH

income subsidy and seeing a female provider for T2DM management were associated with increased likelihood of attainment. Compared to individuals that elected a Health Maintenance type plan other plan types had a lower likelihood of attainment. Of all clinical classifi cation groups for ICD-9 and Services and Procedures in the baseline period, 13 clinical and 10 services/procedures groups were signifi cantly associated with attainment. Thus, we have developed a model predicting attainment of KDM quality measure with good discriminant power. This algorithm could be used to identify individuals for programs intended to improve KDM in this population.

2160-PUBLack of Association between Different Metrics of Glycemic Control with Progression of Nephropathy in Type 2 Diabetes: A Preliminary Observation from a Sri Lankan CohortMETHTHANANDA HERATH, THILAK PRIYANTHA WEERARATHNA, Galle, Sri Lanka

Long-term maintenance of optimal glucose control retards the rate of pro-gression of nephropathy in patients with diabetes mellitus. But, the relative associations between the different metrics of glucose control such as the mean and the variability of glycosylated hemoglobin (HbA1c) with progres-sion of diabetic nephropathy has not been studied in Sri Lankan patients with type 2 diabetes. In a retrospective study, we obtained data on esti-mated glomerular fi ltration rates (eGFR) calculated by the MDRD formula in 146 patients with type 2 diabetes at the enrollment visit and fi ve years after being managed and followed up at the same diabetes clinic. The mean and the variability of HbA1c (intrapersonal SD of serially measured A1c was con-sidered a measure of variability) over the fi ve-year period were estimated. Linear regression was performed on the log10-transformed delta eGFR values to assess the relationship between the mean and the variability of HbA1c with the declining of eGFR over fi ve year period . Mean eGFR at enroll-ment was 74.7 (+/-17.4) and 49.6% patients had deteriorating eGFR during the follow-up period. The mean HbA1c was 7.36 vs. 7.38 (p=0.98) and the coeffi cient of variation for A1c was 0.11 vs. 0.10 (p=0.28) in non-progressive vs. progressive eGFR group respectively. The Pearson correlation coeffi cient between the log10 delta eGFR and the meanHbA1c and the coeffi cient of variation of HbA1c was 0.046 (0.58) and 0.034 (p=0.68) respectively. Despite previous studies showing a positive association, our study reveal no signifi -cant association between either mean or intrapersonal variability of HbA1c with deteriorating renal function in patients with type 2 diabetes. This may suggest greater contribution of non-glycemic factors such as ethnic, geo-graphical or environmental on the progression of nephropathy in patients with diabetes in this region.

2161-PUBGLP-1 Receptor Antagonists Reverse AlbuminuriaAKSHATA DESAI, AJANTHA NITHI, DEEPTHI KUNDURU, NITESH D. KUHADIYA, MANAV BATRA, SANDEEP DHINDSA, ANTOINE MAKDISSI, AJAY CHAUDHURI, HUSAM GHANIM, PARESH DANDONA, Buffalo, NY, Odessa, TX

Exenatide exerts ROS suppressive and anti-infl ammatory effects and pro-motes the Nrf-2 dependent anti-oxidant genes (NQO-1, GST-1P and HO-1). This led us to hypothesize that exenatide and possibly other GLP-1 receptor agonists may be nephroprotective. We have, thus, investigated the evolu-tion of albuminuria in 466 patients with type 2 diabetes who were stud-ied sequentially over a period of 3 years. Over 80% of the patients were on treatment with ACE-inhibitors or angiotensin receptor blockers. Of the patients who were on GLP-1 receptor agonists (on exenatide and liraglutide, group A, n=275) and had macroalbuminuria, 23% became microalbuminu-ric and 2.8% became normoalbuminuric at one year while in those on other antidiabetic drugs (group B, n=191), only 12.3% became microalbuminuric and none became normoalbuminuric (p=0.0005). In those with microalbu-minuria in group A, 25.1% became normoalbuminuric while none developed macroalbuminuria. In microalbuminuric patients in group B, 4.6% developed macroalbuminuria per annum and only 6.9% became normoalbuminuric (p<0.0001). In patients who were normoalbuminuric and in group A, 2.3% became micro-albuminuric and 0.4% developed macroalbuminuria. In com-parison, normoalbuminuric patients in group B, 4.4% developed microalbu-minuria and 0.36% developed macroalbuminuria (p=0.0005). There was no signifi cant difference in HbA1c between those on GLP-1RA and other drugs. The systolic blood pressure at the end of follow up was lower by 3mm in the group on GLP-1RA. The unexpected deterioration of albuminuria in those on GLP-1RA was associated with inadequate glycemic control. Over a 3 year follow up, those in group A had a mean decrease of albuminuria of 39.6 mg/g (from 88.8 to 50.0; p<0.0001) compared with a mean increase of 5.6 mg/g (from 81.1 to 87.2, NS) in group B. On the basis of the above data, it is clear

expression (P < 0.05). These changes were synergistically enhanced by stim-ulating with high glucose and LPS. However, pretreatment with the NOD1 inhibitor ML130 signifi cantly reversed these changes (P < 0.05). These com-bined results support the hypothesis that high glucose and LPS can activate the NOD1-RICK-NF-κB infl ammatory signaling pathway via the NOD1 recep-tor, and may participate in the development of DN.

Supported By: Sichuan International Scientifi c and Technological Cooperation and Exchange Program (14GH0003)

2157-PUBChronic Exposure of Renal Cells to High Glucose/High Inulin Signifi -cantly Decreased Tuberin and Cell Apoptosis, Increased Cell Prolif-eration/Survival, and Increased DNA DamageSAMY L. HABIB, TIFFANIE SALAS, SITAI LIANG, San Antonio, TX

Tuberin is a critical molecule that potentially involved in regulation of the G1 phase of the cell cycle. In the current study, chronic exposure of mouse renal cells to HG (25mM) or HG+HI (25mM+10nM) for 4 days resulted in increased in tuberin phosphorylation/inactivation at Thr1462 with a sharp decrease in total tuberin protein expression. Cells exposed to HG or HG+HI for 2-4 days resulted in signifi cant increased in cell proliferation (measured by H3 Thymidine incorporation assay) and decreased in cell apoptosis (mea-sured by Annexin V binding/PI staining) compared to cells grown in normal glucose (5mM, NG). In addition, cells treated with HG or HG+HI showed sig-nifi cant inactivation/degradation IRS1 protein expression and activation the cell survival kinase Akt measured by the expression of phospho-Akt at Ser473 compared to cells grown in NG. Activation of mTORC1 resulted in increased cell proliferation with associated increase in the expression of Proliferating Cell Nuclear Antigen (PCNA) at 2 and 4 days under HG or HG+HI treatments. Sharp decrease in tuberin is associated with increased in the number of pro-liferative cells and decreased in the number of apoptotic cells suggesting strong role of tuberin in regulating cell proliferation/apoptosis pathways. Moreover, 7- and 10-fold increase in oxidative DNA damage, 8-oxodG, levels was detected in cells treated with HG+HI for 2 and 4 days compared to cells grown in NG, respectively. These data suggest the synergistic effects of HG and HI in regulation of DNA damage pathway. In summary, chronic treatment of cells with HG, or HG+HI are more effective in promoting cell survival/pro-liferation and inhibiting apoptosis signaling cascades that may have a major effect on regulation of the DNA damage/repair mechanisms and induce DNA mutations that predisposes the kidney to cancer.

Supported By: U.S. Department of Veterans Affairs

2158-PUBWITHDRAWN

COMPLICATIONS—NEPHROPATHY—CLINICAL AND TRANSLATIONAL RESEARCH

2159-PUBProvider and Member Factors Predicting Adherence to Kidney Dis-ease Monitoring in Diabetic MembersIBRAHIM ABBASS, JENNA COLLINS, RAYMOND HARVEY, BRANDON SUEHS, CLAUDIA URIBE, EDWARD KIMBALL, JONATHAN BOUCHARD, ANDREW RENDA, TONY DELUZIO, ELSIE ALLEN, Louisville, KY, Plainsboro, NJ

The Centers for Medicare and Medicaid Services (CMS) rates Medicare Part C and D plans on quality measures related to diabetes including kidney disease monitoring (KDM). To develop a predictive model that discriminates KDM attainers from non-attainers, we performed a retrospective cohort study of Medicare Advantage Prescription Drug Plan members with T2DM from 1/1/2010 through 12/31/2011 with an index date of 1/1/2011, exclud-ing patients in long term care facilities >30 days in the pre-index period. Multivariate logistic regression was used to predict the likelihood of attain-ing KDM quality measure in 2011. The fi nal analytic fi le was randomly split into training and test datasets to build and validate the model, respectively. Candidate variables included provider and member demographics, baseline clinical conditions, and health care utilization metrics. Baseline clinical con-ditions and health utilization measures were classifi ed using the Healthcare Cost and Utilization Project Clinical Classifi cation System (CCS) for ICD-9-CM and CCS for Services and Procedures. Of 148,960 members, 134,722 (90%) had their kidney disease monitored. The model demonstrated good discrimi-nation (c-statistic= 0.76). Of nearly 300 candidate variables, 31 were sig-nifi cant predictors of KDM attainment. Older age, race (black), receiving low

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2164-PUBBaseline HbA1c Predicts Estimated Glomerular Filtration Rate DeclineHARUKA TAMURA, YOSHINOBU KONDO, SHINOBU SATOH, YASUO TERAUCHI, Kanagawa, Japan, Yokohama, Japan

To decrease diabetic nephropathy, it is important to diagnose and treat diabetes early. The aim of this study was to examine predictors of kidney function decline in diabetic patients using cystatin C (cysC) variability. The subjects of this study were diabetic patients from our hospital. Patients’ clinical characteristics were retrospectively investigated. Kidney function was assessed by eGFRcysC as estimated by the Chronic Kidney Disease Epidemiology Collaboration equation. eGFR variability per year (ΔeGFRcys/year) was calculated as the difference between the fi rst and last cystatin C measurements and duration between measurements. Among all sub-jects (n =276), there were 152 males and 124 females. The average age was 60.8 ± 13.6 years, average BMI was 24.6 ± 4.9 kg/m2, average HbA1c was 9.1 ± 2.5%, and baseline eGFRcys (eGFRcys [0)] was 102.2 ml/min/1.73m2, respectively. The average follow-up time was 5.8 ± 1.3 years. The most recent eGFRcys (eGFRcys [max)] was 78.8 ml/min/1.73m2. The decline was signifi -cant (P < 0.001). If baseline HbA1c (HbA1c [0)] increased by 1%, ΔeGFRcys/year became -0.54 ml/min/1.73m2 (P < 0.001). Baseline HbA1c was correlated with eGFR variability per year. In multiple linear regression analysis with eGFR variability, baseline HbA1c was the independent variable after clini-cal characteristics adjustments (β = -0.54, SE = 0.21, 95% CI, -0.95 to -0.12, P = 0.01). In the order of baseline HbA1c, highest (H) group was fi rst, fol-lowed by medium (M) and lowest (L) groups. If baseline HbA1c increased by 1%, ΔeGFRcys/year became -6.23 ± 0.45 ml/min/1.73m2 in group H, -3.39 ± 0.43 ml/min/1.73m2 in group M, and -3.21 ± 0.49 ml/min/1.73m2 in group L. ΔeGFRcys/year in group H was signifi cantly lower than those in groups M and L (P < 0.001). In conclusion, it was predicted that eGFR decline was slowed if diabetes was treated early.

2165-PUBAssociation of Glomerular Filtration Rate (GFR) with Leucocyte Telomere Length (LTL) and Human Telomerase Reverse Transcriptase (hTERT) in Subjects with Type 2 Diabetes Mellitus (T2DM) NABILLA ABDELLA, RASHA AL KHALDI, OLUSEGUN MOJIMINIYI, Safat, Kuwait, Kuwait City, Kuwait

Telomeres and telomerase are determinants of biological cell clock linked to aging and T2DM. We explore the hypothesis that differences in intrin-sic biological age could determine susceptibility to declining GFR. Serum hTERT and LTL were measured in 225 T2DM patients and 245 age and sex matched controls. Indices of GFR evaluated are serum urea, creatinine, cre-atinine-derived estimated GFR (eGFR) using CKD-EPI and MDRD equations, serum cystatin C, cystatin C-derived eGFR (eGFRcys). T2DM subjects with shorter LTL (LTL<3.5) had signifi cantly (p<0.05) lower median eGFR (shorter LTL 70 ml/min/1.73m2) vs. longer LTL 86 ml/min/1.73m2). Similarly, median eGFRcys was signifi cantly lower in T2DM subjects with shorter LTL com-pared to subjects with longer LTL (shorter LTL eGFRcys 48 ml/min/1.73m2 vs. longer LTL eGFRcys 89 ml/min/1.73m2). Similar trends were observed with eGFR calculated using CKD-EPI and MDRD Creatinine formulas. Simi-lar signifi cant trends were observed with eGFR calculated using CKD-EPI and MDRD Creatinine formulas. T2DM subjects with lower hTERT levels < 23.5 ng/mol had signifi cantly lower eGFR compared to those who had higher hTERT levels. LTL correlated negatively and signifi cantly with urea (r = -.40), creatinine (r = -.21), and cystatin C (r = -.72). hTERT correlated nega-tively and signifi cantly with urea (r = -.11), creatinine (r = -.13) and cystatin C (r = -.14). LTL and hTERT correlated positively and signifi cantly with eGFR cal-culated using MDRD equation (r = .29 and r = .31) respectively. LTL correlated positively and signifi cantly with eGFRcys (r = .44) but not hTERT. Our data support earlier observation of age-related telomere shortening in renal cell populations and suggest roles for telomeres and telomerase in age-related decline of GFR. Screening T2DM patients with LTL and telomerase may be useful adjunct for identifying subjects susceptible to decline in GFR.

Supported By: Kuwait University (YM06 11); Kuwait Foundation for the Advance-ment of Science (2011-1302-01)

that treatment with GLP-1RA not only helps to reverse established albuminu-ria, but also prevents development of albuminuria when compared to other antidiabetic drugs.

2162-PUBReduced Insulin Sensitivity Is Associated with Increased Glomeru-lar Filtration Rate in Healthy Nondiabetic Individuals, Independent of Body Mass Index, Adiposity, and Blood PressureNEGAR NADERPOOR, JASMINE G. LYONS, GEORGIA SOLDATOS, AYA MOUSA, JOSEPHINE M. FORBES, BARBORA DE COURTEN, Melbourne, Australia, Wool-loongabba, Australia

Glomerular hyperfi ltration predicts incidence of diabetes and faster pro-gression to diabetic nephropathy. It has been shown to be associated with obesity, insulin resistance, and systolic blood pressure (SBP). However, pre-vious studies have been limited by confounders such as pre-existing diabe-tes or hypertension, or have used indirect measures of insulin sensitivity. We aimed to evaluate the relationship between glomerular fi ltration rate (GFR) and insulin sensitivity in a relatively young and healthy population. We investigated the relationships between GFR (CKD-EPI formula) and mea-sures of adiposity (body mass index (BMI), waist-to-hip ratio (WHR), % body fat by dual energy X-ray absorptiometry), infl ammation (CRP, WBC), and insu-lin sensitivity (euglycaemic clamp) in 80 nondiabetic, normotensive individu-als with normal GFR. Participants included 34 females and 46 males aged 18 to 50 years (mean age 31.1 ± 9.30). Eighty-two percent of the sample (n=66) were overweight or obese (mean BMI 29.3 ± 4.6). Males had a higher GFR, WHR, fasting plasma glucose level, SBP, and lower % body fat compared to females. Insulin sensitivity and BMI were not signifi cantly different between genders. There was an inverse association between insulin sensitivity and GFR independent of age, sex, SBP and % body fat (adjusted R2:0.38, P=0.001). This relationship remained signifi cant after replacing % body fat with BMI or waist circumference in the linear regression model. There were no correlations between GFR and WBC or CRP. In conclusion, higher glomeru-lar fi ltration rate in young healthy individuals with normal renal function was associated with reduced insulin sensitivity. This may indicate a role for insu-lin sensitivity in the pathophysiology of obesity-related nephropathy. Causal associations and clinical implications of this fi nding need to be investigated by interventional studies.

Supported By: National Health and Medical Research Council of Australia

2163-PUBSitagliptin Increases Circulating Endothelial Progenitor Cells in Patients with Type 2 Diabetes and Advanced Chronic Kidney Dis-easeROSALIA BELLANTE, DANIELA LUCCHESI, LAURA GIUSTI, MONIA GAROFOLO, VERONICA SANCHO-BORNEZ, ANGELA DARDANO, RAFFAELE CAPRIOLI, MARIA F. EGIDI, ROBERTO MICCOLI, STEFANO DEL PRATO, GIUSEPPE PENNO, Pisa, Italy

T2DM shows impaired mobilization of hematopoietic and endothelial pro-genitor cells (EPCs). By upregulation of SDF-1α, sitagliptin increases circu-lating EPCs and might expand EPCs pool and improve their function also in subjects with renal failure. Forty-nine T2DM, 18 CKD3b, 17 CKD4-5 and 14 on hemodialysis (HD) [age 73±8 yrs (IQR 69-78), DD 18±14 yrs (10-30), HbA1c 7.4±1.4% (6.5-8.1), eGFR (CKD-EPI) 23.4±14.6 ml/min/1, 73m2 (range 3.8-51.3)] have been randomized (2:1) to sitagliptin (SITA; n. 32) or insulin (INS; n. 17). Circulating levels (fl ow cytometry) and function (adhesion to fi bronectin and migratory capacity of EPCs) of stem and progenitor cells were evaluated at baseline and after 4, 13, 26 and 52 weeks of treatment. Groups did not differ for age, DD, BMI, BP, lipids, HbA1c, CV events, retinopathy or lipid- and BP-lowering treatments. CD34+ and CD34+CD133+ cells decreased from CKD3b to CKD4-5 (p=0.023 e p=0.033) with a small increase of CD34+ (p=0.058) in HD and no differences for CD34+KDR+ and CD34+KDR+CD133+. eGFR (OR 1.077), HD (OR 12.800) and BMI (OR 1.185) independently contributed to CD34+ and CD34+CD133+ levels. No differences in EPCs adhesion and migration. INS had longer DD, higher HbA1c (8.2±1.9 vs. 7.0±1.0%, p=0.025), lower eGFR (18.5±11.8 vs. 27.2±15.2 ml/min/1, 73m2, p=0.034) and higher rate of HD. Through follow-up BMI, BP, lipids and eGFR did not change in INS and SITA. HbA1c decreased in INS (8.2±1.9 to 7.3±1.4%, p=0.058) and was steady in SITA (7.1±1.0 a 6.9±0.8%). CD34+ levels did not change in both groups. Whereas CD34+CD133+, CD34+KDR+ e CD34+KDR+CD133+ did not change in INS, CD34+CD133+ (618±434 to 997±913 cell/ml; p=0.029), CD34+KDR+ (239±147 to 391±287 cell/ml; p=0.022) and CD34+KDR+CD133+ (116±94 to 206±158 cell/ml; p=0.021) increased in SITA with no effects on EPCs adhe-sion and migration. In T2DM with advanced CKD sitagliptin but not insulin increases stem/progenitor cells levels independently of glycaemic control.

Supported By: Regione Toscana, Italy (CUP D55E11002680005)

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2169-PUBSerum AST/ALT Ratio Is Associated with Peripheral Nerve Function in Patients with Type 2 DiabetesCONGRONG WANG, YINAN ZHANG, LU LI, WEIPING JIA, Shanghai, China

This study was to explore the associations between serum liver enzymes and peripheral nerve function in Chinese patients with T2DM. In stage 1 of the study, the associations between peripheral nerve function and liver enzymes, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), the AST/ALT ratio, alkaline phosphatase and gamma-glutamyltransferase, were analyzed in 460 T2DM patients from rural area of Shanghai. In stage 2 of the study, the liver enzymes that were shown to be associated with nerve conduction parameters in stage 1 were replicated in an independent popula-tion of 828 T2DM participants from urban area of Shanghai. In stage 1, after adjustment for age, sex, duration of diabetes and HbA1c level, the AST/ALT ratio was negatively correlated with the composite Z-scores of conduction velocity (CV) (β =-0.161, P = 0.001), amplitude (β = -0.129, P = 0.012) and total Z-score (β = -0.161, P = 0.001) and was positively correlated with the com-posite Z-score of latency (β = 0.152, P = 0.003), indicating that patients with a higher AST/ALT ratio may have worse peripheral nerve function. In stage 2, we found the same signifi cant associations between the AST/ALT ratio and peripheral nerve function in terms of the composite Z-scores of CV (β =-0.103, P = 0.001), latency (β = 0.073, P = 0.025) and total Z-score (β = -0.084, P = 0.014) even after adjustment for covariates.Figure.

COMPLICATIONS—RETINOPATHY

2170-PUBLow Paraoxonase Activity in Diabetes Mellitus as Predictors of Proliferative Diabetic Retinopathy and Macular EdemaNARIN NASIROGLU IMGA, HILAL BITEN, ZELIHA YAZAR, MEHMET ONEN, CANAN TOPCUOGLU, SERHAT HAYME, DILEK BERKER, SERHAT GULER, Ankara, Turkey, Kars, Turkey, Çorum, Turkey

Serum Paraoxonase 1 (PON1) has antiatherogenic properties. We aimed to investigate the levels of serum PON1 activity, HbA1c, lipid profi le, hsCRP, Homocysteine (Hcy), Neutrophil-Lymphocyte ratio (NLR) levels in patients with and without diabetic retinopathy (DR) when compared to controls. Also these parameters compared patients with proliferative DR (PDR) or nonproliferative DR (NPDR); and with or without diabetic macular edema (DME). We evaluated randomly 91 type 2 DM patients and 40 controls. Ini-tially DM patients were divided into two groups according to whether they had retinopathy or not. After the evaluation of these groups, DR patients were classifi ed as either PDR or NPDR; and based on the presence of macu-lar edema. In patients with DR and without DR, the HbA1c, LDL, NLR, Hcy, hsCRP levels were found signifi cantly higher than healthy control group (p<0.0001, <0.0001, <0.0001, <0.0001, 0.03; respectively). The serum PON1 activity did not differ between the three groups (p=0.112). But PON1 activ-ity was found signifi cantly lower in patients with PDR and DME (p<0.001, p<0.001; respectively). Serum PON1 activity levels tended to decrease in

2166-PUBSerum NGAL and Cystatin C Comparison with Urinary Albumin Cre-atinine Ratio and Infl ammatory Biomarkers as Early Predictors of Renal Dysfunction in Type 2 Diabetes PatientsMARCELO R. BACCI, ETHEL Z. CHEHTER, LIVIA Y. VASCONCELOS, LIGIA A. AZALIS, BEATRIZ C. ALVES, FERNANDO LUIZ A. FONSECA’, Santo Andre, Brazil, Diadema, Brazil

Diabetic nephropathy is associated with specifi c histological changes. An early detection of the depletion of the glomerular and tubular function can be done with biomarkers of diabetic disease. The aim of this study was to evalu-ate the accuracy of early kidney dysfunction biomarkers in type 2 diabetes.Patients with type 2 diabetes were split according to their levels of glycated hemoglobin. Their urine and blood samples were taken to measure Cystatin C (CysC), Neutrophil Gelatinase-Associated Lipocalin (NGAL), Beta-Trace Pro-tein (BTP) and the fi rst morning void Albumin-Creatinine Ratio (ACR). Patients in end stage renal disease or in dialysis were not included. Receiver-Oper-ating characteristic Curves (ROC) were generated and the Areas Under the Curve (AUCs) were compared with the performance of the biomarkers that were used in the early detection of kidney dysfunction in type 2 diabetic patients. Ninety patients with type 2 diabetes were chosen. CysC was posi-tively correlated with creatinine (p<0.001), Estimated Glomerular Filtration Rate (eGFR) (p<0.001) and urinary βTP (p=0.01). The AUC for CysC was 0.635, 0.621 for the serum NGAL and 0.660 for the ACR. The crude logistics regres-sion model observed a positive association between serum CysC (p=0.01) and serum NGAL (p<0.001). The linear regression model showed a positive association between serum CysC, creatinine and eGFR (p<0.001) but did not show a positive association with Glicated Hemoglobin (p=0.892). NGAL and serum CysC were positively associated with the presence of renal dysfunc-tion and better performance on the ROC analysis in relation to other markers evaluated in patients with T2D without kidney dysfunction.

Supported By: São Paulo Research Foundation

COMPLICATIONS—NEUROPATHY

2167-PUBCombined Retinal/Neuropathy Screening Service: An Effective Model for the Early Detection of Diabetes Distal Symmetrical Poly-neuropathyOLIVER BINNS-HALL, DINESH SELVARAJAH, DEBORA SANGER, JEREMY WALKER, ADRIAN SCOTT, SOLOMON TESFAYE, Sheffi eld, United Kingdom

Aims: Diabetic foot ulceration and amputations are physically and emo-tionally devastating as well as being expensive. In the UK, high-uptake ret-inal-screening has resulted in retinopathy no longer being the commonest cause of working-age blindness. In contrast, diabetic distal symmetrical polyneuropathy (DPN) is diagnosed late using the 10g monofi lament (10gMF), foot clinics are bursting with patients and amputations are increasing year-on-year. A more effective model of foot-screening is therefore required.

Methods: Hospital and community-based, one-stop, combined eye/DPN/renal screening service is undergoing a feasibility assessment. Patients attending retinal-screening have their feet assessed by a podiatrist whilst the instilled medriatic eye-drop is working. Assessments included: 1.) gold-standard Toronto Clinical Neuropathy Score (TCNS, takes 15 minutes), 2.) the 10gMF and 3.) two state-of-the art, validated, objective and quick measures of neuropathy: DPN-Check, a hand-held device that measures sural nerve conduction velocity and amplitude (3 minutes) and SUDOSCAN that mea-sures sudomotor function (3 minutes).

Results: 146 consecutive diabetic patients, 19% of whom have never had their feet examined previously, have so far been evaluated. The prevalence of DPN using TCNS was 35%, massively underestimated by 10 gMF (10%). The prevalence of DPN using DPN-check was 54% (87% sensitivity, 73% specifi city), 35% using SUDOSCAN (73% sensitivity, 52% specifi city) and 50.3% using abnormality in either (78% sensitivity, 73% specifi city). Both devices co-related with TCNS (p<0.001). New diagnosis of painful-DPN was made in 15%. Participants rated the service very highly (p<0.00).

Conclusions: Combined eye, DPN and renal screening has high uptake, reduces clinic visits, leads to an early diagnosis of DPN, unmasks painful DPN, and has a huge potential for the early diagnosis/management of DPN and foot complications.

Supported By: Sheffi eld Teaching Hospitals

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DIABETIC DYSLIPIDEMIA

Multiple linear regression analysis showed that GDM was inversely associ-ated with ApoA II (β:-94.47, P<0.01), ApoC III (β:-22.86, P<0.01) and was posi-tively associated with ApoB100 (β:0.03, P=0.019). Meanwhile, GDM increased the risk of macrosomia (OR=6.75, P<0.01) and was positively associated with neonatal weight (β:0.25, P=0.0198), chest circumference (β:2.81, P<0.01), abdo-men circumference (β:2.09, P<0.01), shoulder width (β:0.58, P=0.012) and total skinfolds (β:5.64, P<0.01). ApoA II was inversely associated with neonatal abdomen circumference (β:-0.01, P<0.01) and total skinfolds (β:-0.035, P<0.01), while ApoC III was inversely associated with neonatal chest circumference (β:-0.08, P<0.01). So we suggested GDM can cause neonatal dyslipidemia, higher fat mass and may affect neonatal physical growth at birth. Further studies are needed to elucidate the possible mechanism.

2176-PUBAtorvastatin Improved Glomerular Endothelial Cell Function Ex Vivo under Hyperglycemic Conditions and Reduced the Oxidation of Low-Density Lipoprotein Isolated from Different Racial GroupsR. PRESTON MASON, ROBERT F. JACOB, HAZEM DAWOUD, HAIDAR ALHUMAID, FARINA J. MAHMUD, SAMUEL C.R. SHERRATT, TADEUSZ MALINSKI, Boston, MA, Beverly, MA, Athens, OH

Atorvastatin has been shown to reduce cardiovascular events in dia-betic patients of diverse ethnicity through cholesterol-lowering as well as cholesterol-independent pathways. To better understand the basis for pleiotropic benefi ts, we tested the effects of atorvastatin (active) metabo-lite (ATM) on glomerular endothelial cells (ECs) isolated from WKY rats and exposed ex vivo to hyperglycemic conditions. ECs were incubated with oxi-dized low-density lipoprotein (oxLDL) and glucose at 11 mg/dL and 300 mg/dL, respectively, and assayed for nitric oxide (NO) and peroxynitrite (ONOO–) release following treatment with ATM (10.0 µM) vs. vehicle. Changes in NO and ONOO− release were measured using porphyrinic nanosensors fol-lowing stimulation with calcium. We also measured the effects of ATM on copper-induced oxidation of LDL isolated from Asian, Hispanic and Cauca-sian subjects. LDL oxidation was monitored by measuring the formation of malondialdehyde (MDA). Exposure to oxLDL and high glucose levels reduced endothelial NO release by 81% and increased ONOO− release by 212% as compared to vehicle-treated controls (p<0.001). The NO/ONOO− ratio, an indicator of eNOS coupling effi ciency, decreased by 90% (2.9 to 0.3; p<0.001) following exposure to oxLDL and hyperglycemic conditions. Treatment with ATM reversed these changes, increasing NO release by 205% (p<0.001) and reducing ONOO− release by 27% (p<0.05). ATM also reduced LDL oxidation in plasma samples from Asian, Hispanic and Caucasian subjects by >80% (p<0.001) while other statins (rosuvastatin, pravastatin and simvastatin) had no signifi cant effect. These data suggest that ATM may improve endothe-lial function under disease-like conditions by inhibiting glucose- and oxLDL-induced oxidative stress pathways. Such benefi ts may be of particular inter-est in the medical management of type 2 diabetes.

2177-PUBPrevalence and Determinants of Atherogenic Dyslipidemia in Sub-Saharan Africans with T2DM Using a Downward Revised Threshold for HypertriglyceridemiaMICHEL P. HERMANS, SYLVIE A. AHN, MICHEL F. ROUSSEAU, Brussels, Belgium

The prevalence and determinants of atherogenic dyslipidemia (AD; the joint presence of low HDL-C and high triglycerides (TG)) are poorly documented in patients with T2DM from sub-Saharan Africa (SAA), confounded by lower TG levels endemic in black Africans or African diaspora’s minorities.

We compared the cardiometabolic phenotype of 202 patients with T2DM (1st generation migrants from SAA to Belgium) according to the absence/presence of AD, defi ned as HDL-C <40 mg/dL (<50 in females) plus fasting TG >100 mg/dL. The latter threshold was set one-third lower than that used for Caucasian populations on the basis of ethnically-different TG distributions.

The prevalence of AD was 16% (AD [+] group, n=33). AD [+] patients had higher BMI (+7%); waist circumference (+6%); and fat mass (+15%), and lower muscle mass (-10%) than AD [-] (n=169); all p<0.02. Mean (1 SD) HDL-C and TG levels were 37 (6) and 186 (127) mg/dL in AD [+] vs. 62 (19) and 94 (49) mg/dL in AD [-], respectively. Small-dense LDL and HDL particles were more prevalent in AD [+]: 1.04 [LDL/apolipoprotein B100 (apoB) ratio] and 0.27 [HDL-C/apoA-I ratio] vs. 1.17 [LDL-C/apoB] and 0.39 [HDL-C/apoA-I] in AD [-]; p 0.0004 and <0.0001.

AD [+] patients did not differ from AD [-] in terms of: age; gender; diabe-tes duration; education; smoking; ethanol; exercise; hypertension; renal func-tion; hepatic steatosis; insulin sensitivity; β-cell function and loss rate. The 2 groups did not differ either regarding glucose-lowering or CV drugs (eg. statins/fi brates); HbA1c; TSH; fT4; LDL-C; apoB; and Lp(a). Overall micro- and macroan-

state of high oxidative stress such as DR. We suggest that the lower PON1 activity may be a risk factor for PDR and DME and can be useful for further evaluation.

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2172-PUBIncreased Serum Apolipoprotein B48 Concentrations after Oral Glu-cose Ingestion in Patients with Diabetes MellitusDAISAKU MASUDA, OKUBO MANABU, HIROYUKI HANADA, MASAHIKO MATSUI, YOH HIDAKA, YASUSHI SAKATA, SHIZUYA YAMASHITA, Suita, Japan

Aim: Postprandial hyperglycemia is important for the development of car-diovascular diseases, the rationale of its atherogenicity is still unclear. The accumulation of chylomicron remnants (CMR) in the postprandial state has been observed in patients with diabetes mellitus (DM). High concentration of apolipoprotein B48 (apoB48) which is a constituent of chylomicrons and CMR is related to coronary artery stenosis, we investigated whether apoB48 concentrations were altered during the oral glucose tolerance test (OGTT).

Methods: By a 75-g OGTT of 85 subjects, 28 were diagnosed as normal glucose tolerance (NGT) and 57 were diagnosed as DM. Biochemical markers of lipid metabolism including apoB48 concentration were measured during the OGTT, compared between two groups, and evaluated for any correlation with the increased apoB48 concentration by a multiple regression analysis.

Results: After glucose ingestion, serum apoB48 but not apoB100, concen-trations signifi cantly increased in both groups, while triglyceride concentra-tions decreased in both groups. The incremental areas under the curve of serum apoB48 concentration (iAUC-apoB48) was signifi cantly higher in DM subjectss than NGT subjects (1.53±0.24, 0.65±0.35, p<0.05, respectively) and correlated with AUC-glucose, fasting serum insulin, HOMA-IR, HDL-C, log-LPL mass, and apoC2/apoC3 in all subjects. While there was no correla-tion between iAUC-apoB48 level and any parameters in NGT subjects, sig-nifi cant correlations were observed between iAUC-apoB48 level and fasting serum insulin, HOMA-IR and apoC2/apoC3 in DM subjects. Multiple regres-sion analysis indicated that the signifi cant determinants of the increased iAUC-apoB48 were HOMA-IR and apoC2/apoC3 in all subjects and fasting serum insulin and apoC2/apoC3 were in DM subjects.

Conclusions: These results suggesting that postprandial hyperglycemia may induce a postprandial accumulation of CMR, which are thought to be potentially atherogenic.

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2175-PUBThe Impact of Gestational Diabetes Mellitus on Neonatal Lipid Metabolism and GrowthQIAN REN, YUHANG MA, SU CHEN, YUFAN WANG, Shanghai, China

To investigate the impact of gestational diabetes mellitus (GDM) on neo-natal lipid metabolism and physical growth. Pregnant women were enrolled and divided into two groups: 50 with normal glucose tolerant (NGT group) and 55 with GDM (GDM group). Glucose level and lipid profi les (TG, TC, HDL-C, LDL-C, ApoA II, ApoB100, ApoC III) were determined in maternal serum antepar-tum and cord blood. Neonatal anthropometry (length, weight, head circumfer-ence, chest circumference, abdomen circumference, upper arm circumference, shoulder width, total skinfolds) were performed within 24 h of birth. Compared with NGT group: Women of GDM group had decreased level of all lipid com-ponents (P<0.01) except for TG, and increased level of GA and HbA1c (P<0.01). Infants of GDM group had increased ApoB100 (P<0.05), decreased ApoA II, ApoC III (P<0.01), increased risk of macrosomia (P<0.05) and larger chest circumfer-ence, abdomen circumference, shoulder width and total skinfolds (P<0.01).

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and hypertension. Low uric acid partly predicted high HbA1c levels, and the causal effect of serum uric acid has not been observed as a risk of high HbA1c in male young diabetic patients.

2181-PUBApplication of the 2013 ACC/AHA Cholesterol Guideline to the Korean National Health and Nutrition Examination Surveys from 1998 to 2012YOUNG SHIN SONG, TAE JUNG OH, KYOUNG MIN KIM, JAE HOON MOON, SUNG HEE CHOI, HAK CHUL JANG, KYONG SOO PARK, NAVEED A. SATTAR, SOO LIM, Seoul, Republic of Korea, Seongnam, Republic of Korea, Glasgow, United Kingdom

Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of death worldwide. The 2013 American College of Cardiology/American Heart Association (ACC/AHA) guideline for the treatment of blood cholesterol rec-ommends statin therapy for individuals at high risk of ASCVD.

The aim of this study was to investigate serial trends in the percentages of Korean adults considered eligible for statin therapy according to the new ACC/AHA cholesterol guideline.

Data from the Korean National Health and Nutrition Examination Survey (KNHANES) I (1998, n = 7,698), II (2001, n = 5,654), III (2005, n = 5,269), IV (2007 to 2009, n = 15,727), and V (2010 to 2012, n = 16,304), which used a stratifi ed, multistage, probability sampling design, were used as representa-tive of the entire Korean population. We assessed the percentages of adults who were eligible for classifi cation into statin benefi t groups based on the ACC/AHA cholesterol guideline.

The percentage of people in statin benefi t groups increased with time: 17.0%, 19.0%, 20.8%, 20.2%, and 22.0% in KNHANES I, II, III, IV, and V, respectively (p = 0.022). The prevalence of ASCVD was 1.4% in KNHANES I and increased to 3.3% in KNHANES V. The percentage of diabetic patients aged 40 to 75 years with a low-density lipoprotein cholesterol levels of 70 to 189 mg/dl increased from 4.8% in KNHANES I to 6.1% in KNHANES V. People with an estimated 10-year ASCVD risk ≥7.5% and aged 40 to 75 years accounted for the largest percentage among the 4 statin benefi t groups: 9.1% in KNHANES I and 11.0% in KNHANES V.

We believe these are the fi rst serial data on statin eligibility in the context of an Asian nation.

2182-PUBEffect of Saroglitazar on Metabolic Parameters in Indian Patients with Diabetic Dyslipidemia: A 40-Week, Retrospective AnalysisSANJAY CHATTERJEE, ANIRBAN MAJUMDER, SUBIR RAY, Kolkata, India

Saroglitazar, a novel dual peroxisome proliferator-activated receptor (α/γ) agonist, is available in India for the treatment of diabetic dyslipidemia (DD) since July 2013. This study was a multicenter, retrospective analysis of patients with type 2 diabetes mellitus and dyslipidemia. All patients were prescribed saroglitazar 4 mg once daily. Objective of this study was to evaluate the effi cacy and safety of saroglitazar in Indian DD patients. Baseline patient (n=74) demographics were: age 52.36 ± 9.61 yr (mean ± SD), body weight 68 ± 10.46 kg (mean ± SD); male 46, female 28. At baseline, all patients were on antihyperglycemic medication and 65% patients were on statin therapy. Mean duration of follow-up was 40 weeks. After 40 weeks of follow up, there were statistically signifi cant changes in lipid and glyce-mic parameters (Table). Liver enzyme, alanine aminotransferase (ALT) was signifi cantly reduced from 43.19±24.24 U/L to 30.23±17.71 U/L (mean ± SD; p<0.0001). No serious adverse events were reported during entire study fol-low-up. Adverse effects reported were mild and transient. No signifi cant change was observed in body weight and serum creatinine level. These results are consistent with previous report with smaller number of patient and smaller duration of study. In conclusion, saroglitazar is effective and safe for the treatment of type 2 diabetes with dyslipidemia.

Table. Effect of Saroglitazar on Metabolic Parameters: Mean Follow-up Period 40 Weeks.Parameters Baseline Follow-up Mean change

after 40 weeksP-value

FPG (mg/dL) 151.9 ± 57.58 120.51 ± 33.44 -31.39 <0.0001HbA1c (%) 7.83 ± 1.66 6.83 ± 1.13 -1.00 0.0001Cholesterol (mg/dL) 186.28 ± 50.8 149.69 ± 43.06 -36.59 <0.0001Triglycerides (mg/dL) 343.27 ± 211.65 168.88 ± 152.45 -193.58 <0.0001HDLc (mg/dL) 38.30 ± 10.59 38.21 ± 10.07 -0.086 0.94LDLc (mg/dL) 105.22 ± 41.98 90.74 ± 31.28 -14.48 0.0039Non HDLc (mg/dL) 150.18 ± 50.37 111.69 ± 43.86 -38.48 <0.0001

giopathy was similar in both groups: microangiopathy: 38% (AD [+)] vs. 35% (AD [-)]; and macroangiopathy: 18% (AD [+)] vs. 16% (AD [-)]. Even after use of a lowered threshold for TG, AD prevalence was low in T2DM Africans. Unlike Caucasians and notwithstanding sarcopenic obesity, AD did not adversely impact on β-cell function; glycemic control; or vascular complications.

2178-PUBEicosapentaenoic Acid, but Not Other TG-lowering Agents, Reversed Hyperglycemia-induced Rat Endothelial Cell Dysfunction and Enhanced the Benefi ts of Atorvastatin Active Metabolite Ex VivoR. PRESTON MASON, ROBERT F. JACOB, HAZEM DAWOUD, HAIDAR ALHUMAID, FARINA J. MAHMUD, SAMUEL C.R. SHERRATT, TADEUSZ MALINSKI, Boston, MA, Beverly, MA, Athens, OH

Endothelial cell (EC) dysfunction occurs early in atherosclerosis and car-diovascular disease. Eicosapentaenoic acid (EPA), an omega-3 fatty acid, and atorvastatin are often used together to treat dyslipidemia and may have addi-tional benefi ts for EC function, particularly under hyperglycemic conditions. We compared the effects of EPA ± atorvastatin active metabolite (ATM) to niacin or fenofi brate in glomerular ECs from WKY rats exposed ex vivo to high glucose. ECs were exposed to 300 mg/dL glucose, followed by each of the various treatments (10 µM) vs. vehicle for 1 hr, and then assayed for nitric oxide (NO) and peroxynitrite (ONOO–) release using porphyrinic nanosensors. High glucose treatment reduced NO release by 69% (631 ± 23 to 195 ± 16 nM), increased ONOO− release by 92% (218 ± 17 to 418 ± 33 nM), and decreased the NO/ONOO− ratio, an indicator of eNOS coupling effi ciency, by 84% (2.89 to 0.47) compared to vehicle-treated controls (p<0.001). EPA increased NO release by 143% (474 ± 19 nM), reduced ONOO− release by 35% (272 ± 22 nM), and increased the NO/ONOO− ratio by 270% compared to glucose-treated con-trols (p<0.01). Independently ATM and docosahexaenoic acid (DHA) each had smaller but statistically similar effects. EPA + ATM increased NO release by 173% (532 ± 35 nM), decreased ONOO− release by 39% (254 ± 29.7 nM), and increased the NO/ONOO− ratio by 345% (2.09) as compared to glucose-treated controls (p<0.01). The effects of EPA and ATM combination treatment on NO and NO/ONOO− were signifi cantly greater than those of ATM alone (p<0.05). Niacin and fenofi brate produced a modest increase in NO release with no sig-nifi cant effects on ONOO− or the NO/ONOO− ratio. These data suggest that EPA and ATM may provide independent endothelial benefi ts under disease-like conditions, with the effects of EPA additive to those of ATM and unique among other TG-lower agents, which may be of particular interest to patients with diabetes or impaired glucose metabolism.

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2180-PUBWorse Glycaemic and Lipid Metabolism in Chinese Male Young Type 2 Diabetic PatientsYAN LI, MANNA ZHANG, JIE ZHU, WENJIE CUI, SHARVAN RAMPERSAD, ZIWEI LIN, PENG YANG, HONG LI, CHUNJUN SHENG, XIAOYUN CHENG, SHEN QU, Shanghai, China

Objective: To investigate the clinical characteristics, lipid and glycaemic metabolism of young-onset T2DM male patients.

Methods: We collected 102 young-onset male patients (diagnosed at and before 35 years old) and 237 late-onset T2DM men (diagnosed after 35 years old) at admission during the period of Jan 2012 to Dec 2014. Clinical characteris-tics as height, weight, and body mass index (BMI); blood pressure and presence of nonalcohol fatty liver (NAFLD) were collected. Uric acid (UA), total choles-terol (TC), triglyceride (TG), free fatty acid (FFA), high-density lipoprotein (HDL), low-density lipoprotein (LDL), glycosylated hemoglobin A1c (HbA1c) and fasting glucose were measured. Student’s t test/Mann Whitney U test, Spearman’s rank correlation test and binary logistic analysis were performed to analyse the relationship between two parameters and risk factors in different groups.

Results: Compared with late-onset group, male patients with young-onset T2DM were more likely to have hypertension and NAFLD. Patients with young-onset T2DM showed signifi cantly higher BMI, TC, TG, LDL, FFA, UA, HbA1c and fasting glucose, and lower HDL. UA had the negative rela-tionship with HbA1c (r=-0.254, P=0.012). Binary logistic regression analysis demonstrated NAFLD is an independent risk of poor glycaemic metabolism in the total cohort, and the odds ratio of UA in the young-onset group esti-mate was 0.987 (0.977~0.998).

Conclusion: Male patients with young-onset T2DM had poorer glycae-mic and lipid metabolism control, and they were more likely to have NAFLD

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FOOT CARE—LOWER EXTREMITIES

2186-PUBEvaluation of the Prevalence and Treatment Trends of Peripheral Neuropathy among Patients with Diabetes in a Rural PopulationLAUREN G. DAIGLE, MATTHEW STRUM, MICHAEL WARREN, JOHN BENTLEY, Jackson, MS

Evidence for adherence to the American Diabetes Association’s (ADA) screening and treatment guidelines for various health complications of dia-betes in rural populations is limited. The ADA recommends annual foot and eye exams and supports the use of the Semmes-Weinstein monofi lament (SWM) to detect signs of peripheral neuropathy (PN). This study evaluated the prevalence and treatment trends of PN among patients with diabetes in a rural population. Fifty-two individuals over the age of 18, with known type 1 or type 2 diabetes mellitus, were recruited as subjects. Subjects were asked to respond to a survey about how their diabetes is monitored and managed. A monofi lament exam was then done on each subject using a 10g SWM to detect signs of PN. Six locations on the foot were tested with the 10g SWM, and a pedal pulse was recorded. The results of the 10g SWM exam were compared to the survey responses for each corresponding sub-ject. Survey responses indicated that 21.2% of subjects had been diagnosed with PN. Although not statistically signifi cant due to limited sample size, 17.3% of subjects were identifi ed by the SWM exam to have PN but were currently undiagnosed by their physician. Furthermore, 12.0% of subjects had not had an eye exam in over a year, and 28.8% did not have regular foot exams. Subjects whose physicians performed regular foot exams were 3.0 times as likely to have an eye exam within the last year compared to sub-jects whose physicians did not perform regular foot exams, demonstrating a positive correlation between foot and eye exams. The health consequences of undiagnosed sequelae of diabetes can be devastating. More specifi c data related to diabetes management and prevention of disease complications in underserved areas is warranted; however, this study suggests that rural populations need greater attention and targeted educational programs to enhance the level of care.

2187-PUBTrial of Vacuum-Assisted Closure in Patients with Chronic Non-healing Leg Ulcers in Type 2 Diabetes MellitusBHUPENDER SIHAG, CHITRESH CHAHAR, JUGAL K. SHARMA, RAJENDRA P. AGRAWAL, Bikaner, India, New Delhi, India

Objective: To assess the effi cacy of Vacuum Assisted Closure therapy as compared with conventional dressing in chronic leg ulcer in type 2 diabetes mellitus.

Methods: 100 patients were included in this case-control study and ran-domly assigned in equal numbers to receive either VAC therapy once weekly or conventional dressing once daily in addition to the standard treatment for good glycemic control by insulin and control of infection by appropriate antibiotics and debridement, if needed. Effect was observed every week to see the response up to a maximum of 12 weeks. Primary endpoint of ulcer healing was measured by reduction in the ulcer area of the two longest per-pendicular diameters from baseline and defi ned as complete, partial (>50% reduction), non-complete (<50% reduction) and non-responder.

Results: Findings at sixth week revealed complete healing in 15 (30%) among study group compared to 4 (8%) in controls with statistically signifi -cant association. After 12 weeks, 10 (20%) cases in control group had com-plete healing 19 (38%) had partial healing, 16 (32%) had non-complete heal-ing, 5 (10%) were non responders/drop-out while in study group 27 (54%) had complete healing, 15 (30%) had partial healing, 4 (8%) had non-complete and 4 (8%) were non responders/drop-out with the differences being statistically signifi cant (X2=15.593; p<0.001).

Conclusion: Application of VAC therapy appears to be more effi cacious than conventional dressing for treatment of diabetic foot ulcer.

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2183-PUBEffi cacy of Low- and Moderate-Potency Statins in Plasma LDL-C Reduction and Target Achievement in Thai Type 2 Diabetic PatientsNUNTAKORN THONGTANG, CHAIYUTH SITTHANANUN, SUTIN SRIUSSADAPORN, Bangkok, Thailand

Previous studies showed that statin therapy resulted in greater plasma LDL-C reductions in Asians than in Caucasians. Eighty nine percent of patients in our diabetic (DM) clinic were prescribed with low potency statins (LS) or moderate potency statins (MS) according to the ACC/AHA guidelines. This retrospective cohort study was aimed to examine plasma LDL-C reduc-tion and LDL-C target achievement in response to LS and MS in Thai type 2 DM patients. Four hundred type 2 DM patients who were on LS or MS were randomly recruited from our clinic. Clinical factors associated with greater plasma LDL-C reductions were also studied. Subjects were divided into 2 groups according to plasma LDL-C reductions after statins; good responders (LDL-C reduction by ≥50% from baseline) and poor responders (LDL-C reduc-tion by <50%). Mean baseline plasma lipids before statins were as follows (n=393): total cholesterol 219.3±45.6 mg/dl, triglyceride 157.3±78.7 mg/dl, HDL-C 51±15.1 mg/dl, and LDL-C 138.9±37.6 mg/dl. LDL-C targets of <100 mg/dl, and <70 mg/dl were achieved in 84.3% and 38%, respectively. MS group (n=235) had signifi cantly (p <0.001) higher baseline lipid values than LS group (n=165). There were no signifi cant differences in the percentages of patients achieving LDL-C targets between LS and MS users (46% vs. 34% for LDL-C target of <70 mg/dl, and 87.3% vs. 82.1% for LDL-C target of <100 mg/dl). LS and MS resulted in plasma LDL-C reduction by >50% in 38.4% of the patients. Factors associated with good LDL-C reductions were older age (>65 years), longer duration of statin use, and lower baseline HbA1c. In summary, Thai diabetic patients responded well with low to moderate potency statins. Older patients, longer duration of statin use and better glycemic controls were the predictors of good statin responder.

Supported By: Siriraj Hospital; Mahidol University

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2185-PUBThe Cardiometabolic Phenotype of T2DM with High Lp(a) Is Charac-terized by Lesser Insulin Resistance, Lower Triglycerides, and Left-HandednessMICHEL P. HERMANS, SYLVIE A. AHN, MICHEL F. ROUSSEAU, Brussels, Belgium

There is a renewed interest on lipoprotein(a) [Lp(a)], the most harm-ful genetic risk factor for CVD, with a view to pharmacologically modulate PCSK9. Metabolic factors underlying elevated Lp(a) are poorly understood.

We characterized the cardiometabolic phenotype of 497 T2DM Cauca-sians with normal (n=365; 73% [Normal-Lp(a) group)] or elevated (>70 mg/dL) Lp(a) levels (n=132; 27% [Hyper-Lp(a) group)] to identify further determinants that may contribute to macroangiopathy.

Mean (1SD) Lp(a) level was 22 (19) mg/dL in [Normal-Lp(a)] vs. 139 (72) mg/dL in [Hyper-Lp(a)]. There was no difference between groups in LDL-C, non-HDL-C and apoB. Neither did the 2 groups differ in age; gender; diabetes duration; BMI; metabolic syndrome; hypertension; glucose-lowering and CV drugs (including statins/fi brates); and HbA1c.

A family history of early-onset CHD (EOCHD) was more often (+80%) reported in [Hyper-Lp(a)], at 18% vs. 10% in [Normo-Lp(a)] (p 0.0257). [Hyper-Lp(a)] had a 35% higher prevalence of macroangiopathy (42% vs. 31% in [Normal-Lp(a)]; p 0.0316); whereas microangiopathy was similar in both groups at 48%. [Hyper-Lp(a)] had a higher (+19% relative increase) insulin sensitivity (63% vs. 53%; p 0.0179), and lower (-21%) triglyceride levels than [Normal-Lp(a)] at 138 vs. 167 mg/dL (p 0.0312).

An unexpected fi nding was that left-handedness happened to be mark-edly more frequent (+70% relative increase) in [Hyper-Lp(a)] patients, at 17% vs. 10% in [Normo-Lp(a)] (p 0.0408). The modulation of Lp(a) levels by lat-erality was considerable, as left-handed T2DM patients (n=58; 12%) had a +44% relative increase in mean Lp(a) level compared to right-handed T2DM (n=439; 88%), at 73 mg/dL vs. 50 mg/dL (p 0.0103).

The cardiometabolic phenotype of T2DM with elevated Lp(a) is character-ized by: (i) a strong family history of EOCHD; (ii) lesser insulin resistance; (iii) lower triglycerides; and (iv) a perplexing overrepresentation of left-handed patients.

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informant interviews with 24 community leaders. Participants were recruited from local community centers, health centers, and a church, in African Ameri-can and Hispanic communities in a Midwestern city. The focus groups were led by two facilitators, one coordinated participation and the second docu-mented detailed notes. Facilitators analyzed the notes using an iterative coding method to identify common themes. Study results highlight effective strategies that can be used to improve Standard 2 and Standard 6 of DSME/S programs. One theme emerged for Standard 2: community-identifi ed needs can inform external input for the formal advisory board. Four themes emerged for Standard 6 which identifi ed a lack of culturally-appropriate health educa-tion for weight management and stress reduction: 1.) incorporating nutritional management into lifestyle; 2.) incorporating physical activity into lifestyle; 3.) developing personal strategies to address psychosocial issues and concerns; and 4.) developing personal strategies to promote health and behavior change. The results of this study indicate the need for effective, affordable and cul-turally-focused choices for healthy lifestyles. Recommended strategies could be adopted and integrated into other clinical and community-based DSME/S programs with a focus on mind, body and spirit.

Supported By: Advancing a Healthier Wisconsin

2193-PUBManagement of Type 2 Diabetes in Western India: Attitudes and Practices among Physicians Leading the Forefront of Diabetes CareHEMANT THACKER, SANJIV SHAH, MANOJ CHADHA, RAJIV KOVIL, MANOJ CHAWLA, SUNIL GUPTA, NAVNEET WADHWA, Mumbai, India, Nagpur, India

There are too many gaps in knowledge with guidelines changing with the evolving evidences. Seven validated questionnaires with 41 items (SUMMIT) encompassing screening, diagnosis, management, complications was devel-oped using former studies with validated questionnaires and implemented through electronic voting system, across 139 leading diabetes care profes-sionals in a voluntary, interactive, evidence based continuing medical edu-cation program, through a quasi-experimental design. The screening and the diagnosis module of program additionally evaluated the immediate behav-ioural impact of the lecture. Chi-square test was used for statistical analy-sis. The change in choice of test by the participants from HbA1c to fasting plasma glucose for both screening and diagnosis of diabetes was statisti-cally signifi cant (p< 0.0001). 96% participants opine that sulfonylurea as one of mainstay therapeutic option, 92% believe that sulfonylurea controversies are actually related to the older SUs and 77% prefer glimepiride or gliclazide in T2DM with CVD. 63% recommend statins in all diabetics. This comprehen-sive survey provides contemporary evidence that the beliefs and practices can be better through education for the diabetes care which would further help defi ne the educational model and continue to transform physicians to deliver better diabetes care in India.

Table. Objective Assessment of the Practices for Screening, Monitoring, and Management of T2DM.Questions Preferred choices (%) -

in decreasing order Relevant guideline for managing T2DM from Indian perspective

ADA (32) IDF (28) AACE (2) NICE (2)

Preferred second line OAD Sulfonylurea (62) DPP 4 Inhibitor (23) AGI (7) SGLT 2 Inhibitor (4) Preferred test to screen for CVD ECG (62) Stress test (24) CIMT (9) CoronaryArtery Calcium (5) Preferred test to screen for PVD ABI Index (54) Dorsalis pedis pulse (32) Doppler Imaging (11) Temp. difference (3)

Preferred test to screen for diabetic nephropathy

Albumin/ Creatinine ratio (46)

Urine albumin (34) e GFR (15) Serum creatinine (5)

Preferred test to screen for diabetic neuropathy

Monofi lament (73) Vibration threshold (23) Pin prick (5) Heat and cold (0)

Preferred CV risk calculator ASCVD risk (44) None (29) WHO (18) QRISK (9)

2194-PUBOlder Women and Their Families Diabetes Learning StoryFATEMEH ADILI, ISABEL HIGGINS, TINA KOCH, Brisbane, Australia, Newcastle, Australia

The purpose of this study was to research alongside older women and their families immediately post diagnosis with type 2 diabetes and explore how the consequences of living with this chronic condition had impact on a family’s life. When people are diagnosed with diabetes they are expected to dramatically modify their lives but the way in which these changes take place has not been researched. There are few papers exploring a person’s learning experiences to live with diabetes and none that invite family mem-bers to have a say.

2189-PUBAssociation between Obesity and Diabetic Foot Ulcer among Patients with Type 2 Diabetes MellitusSEO JIN PARK, JIN HEE KIM, TAE YOUNG YANG, SANG YONG KIM, TAE HYUN KIM, JUN YOUNG LEE, NAM DONG LEE, BYUNG SOON PARK, THEETANITTHA CHATBENJANAN, EUN CHONG LEE, Gwangju, Republic of Korea

Purpose: This study was to investigate the infl uencing factors of Diabetic foot ulcer (DFU) and to identify the relationship between Body Mass Index (BMI) and DFU among patients with type 2 diabetes mellitus (DM).

Method: Data were collected from the subjects who were 30 years old and older exclusion BMI < 18.5 Kg/m2, who had DM after diagnosed 6 months. Directly 1:1 questionnaires and physical examinations were used to collect data, and IBM SPSS program version 20.0 was used for analysis. Univariate logistic regression was performed to understand the relationship between BMI and DFU, and multiple logistic regression analysis was performed with adjustment for several confounding factors.

Results: The subjects mean BMI was 20.95Kg/m2 (SD=±1.16) in normal group (n=48), 24.13Kg/m2 (SD=±0.53) in overweight group (n=34), 27.58Kg/m2 (SD=±2.58) in obesity group (n=45). Duration of DM, exercise and hyper-tension by BMI were associated with DFU. After adjustment for duration of DM, exercise and hypertension were not associated with increased BMI.

Conclusion: There were no relationship between BMI and prevalence of DFU among type 2 DM in Korea.

2190-PUBKeller Arthroplasty: A Cure for the Chronic Hallux Ulceration, a Ret-rospective Study of 16 PatientsROBERT G. FRYKBERG, JAMINELLI BANKS, EDWARD TIERNEY, DANE K. WUKICH, Phoenix, AZ, Pittsburgh, PA

Diabetic foot ulcerations (DFU) of the great toe are fairly common com-plications in patients with neuropathy. Frequently they are associated with restricted motion of the 1st metatarsal-phalangeal (MTP) joint and can be recalcitrant to conservative care with recurrences also common. We herein present the results of our experience with the Keller (1st MTP) arthroplasty to treat such conditions in our clinic population. We retrospectively evaluated 16 patients undergoing fi rst MTP arthroplasty procedures, all of which were performed as a curative measure for plantar ulcers of the hallux. Eighty-eight percent (14/16) of patients had diabetes (two had nondiabetes related neu-ropathy). All subjects were males with an average age of 66.9 years. Only 2/16 had an open ulcer at the time of the procedure while all patients had his-tory of hallux ulceration. Fourteen (88%) procedures healed uneventfully. No patients underwent a hallux amputation during our 112 ± 21 month follow up period. At the time of surgery, average HgA1C was 7.8%. Nine (56%) patients developed post-operative surgical site wound dehiscences and/or surgical site infections. The median healing time for the incision was 25 days (range 11-129 days). Average healing time for the plantar hallux ulcer was 22 days post procedure. We have shown a high degree of success when performing the Keller arthroplasty for recalcitrant hallux ulcers, although complications are common. Though many of our patients experienced post-operative wound dehiscences, all eventually healed and no amputations were necessary. Com-plications can be anticipated in neuropathic patients, but the long term suc-cessful outcomes seem to justify this curative procedure.

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2192-PUBA Community Perspective on Patient-Centered Weight Manage-ment and Mindfulness-based Stress Reduction to Improve Diabetes Self-Management Education and SupportLAILA AZAM, TOURETTE A. JACKSON, COURTNEY BARRY, DAVID A. NELSON, JOHN MEURER, Milwaukee, WI

Diabetes self-management education and support (DSME/S) programs pro-vide a structured process to foster teaching strategies for diabetes self-care. The purpose of this study was to elicit the perspective of community members on weight management and stress reduction within the patients’ social con-text. We offer a practical application of the DSME/S framework focusing on Standard 2 (External Input) and Standard 6 (Curriculum) that incorporates a cul-turally relevant context. We conducted 8 focus groups with 59 adults and key