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Diabetes in the Latino Population:A Case-based Approach to Optimal Management
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Upon completion, attendees should be able to:• List the medical, social, and economic ways in which diabetes
impacts the Latino population;• Describe strategies to overcome barriers to improving diabetes
outcomes in the Latino population;• Utilize current standards of care for the detection of diabetes and
the monitoring of complications of diabetes in the Latino patient;• Assess current treatment options to maximize glycemic control
in order to minimize the complications of diabetes in the Latino population;
• Access appropriate national and local resources available to assist in caring for the Latino patient with diabetes.
Learner Objectives
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Why are We Concerned about Diabetes?
Every 24 hours...
• 3,600 new cases of diabetes are diagnosed• 580 people die of diabetes-related complications• 225 people have a diabetes-related amputation• 120 people with diabetes progress to end-stage renal disease• 55 people with diabetes become blind
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Why Are We Concerned about Diabetes Among Latinos?
• Prevalence of type 2 diabetes is 1.5 times higher than in non-Hispanic whites.
• 2 million Latinos 20 years or older have diabetes.
• Latinos have a greater number of risk factors for diabetes.
• Increased prevalence of retinopathy, nephropathy, and peripheral vascular disease in Mexican Americans.
National Diabetes Information Clearinghouse, NIDDK 2002
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A Constellation of Complications
GastropathGastropathyy
Autonomic Autonomic NeuropathyNeuropathy
Renal Renal DiseaseDisease
Peripheral Peripheral NeuropathyNeuropathy
Retinopathy/ Retinopathy/ Macular Macular
EdemaEdema
HypertensionHypertensionCardiovascular Cardiovascular
DiseaseDisease
DyslipidemiaDyslipidemia
Peripheral Peripheral
Vascular Vascular DiseaseDisease
Erectile Erectile DysfunctionDysfunction
DiabetesDiabetes
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Diabetes Care in the U.S. Improvements NeededGoal Percent at Goal
A1C < 7.0 43% (18% at > 9.5)
LDL < 100 11% (58% at > 130)
BP < 140/90(ADA goal is 130/80)
66%
Dilated Eye Exam 63%
Foot Exam 55%
NHANES III and Behavioral Risk Factors Surveillance Study
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Projected Increase in the US Population with Diagnosed Diabetes by 2020 by Ethnicity
0
20
40
60
80
100
120
Non Latino Whites Non Latino Blacks Latinos
Proj
ecte
d In
crea
se (%
)
Adapted from American Diabetes Association. Diabetes Care. 2003;26:917-932
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Geographic Distribution of Latino Americans
Puerto Rican: 1.6 million
Cuban American: 130,000
Mexican American1 million
Puerto Rican: 500,000Cuban American:
830,000
Mexican American8.4 million
Adapted from U.S. Census Bureau, Current Population Survey, March 2000.
Mexican American5 million
Mexican American1.1 million
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Clinical Discussion• Prevalence of diabetes• Prevalence of complications• Pathophysiology
- obesity- insulin resistance- metabolic syndrome
• Treatment- nonpharmacologic- medications
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Prevalence of Type 2 Diabetes
10
8
6
4
2
0
Age
-adj
uste
d pr
eval
ence
(%
)
Non-Latino African Mexican Non-Latino African Mexican White American American White American American
Harris MI et al. Diabetes Care. 1998;21:518-524.
Previously undiagnosed diabetes Physician-diagnosed diabetes
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Trends in Diabetes Prevalence (1990-1998)
30-39 40-49 50-59 Non-Latino African Mexican White American American
50
40
30
20
10
0
80
70
60
50
40
30
20
10
0
• Prevalence of type 2 diabetes is 2-3 times higher in Latinos than Caucasians
• Highly correlated with prevalence of obesity (r = 0.64, P < 0.001)
% I
n cre
ase
% I
ncre
ase
Age (years) Ethnicity
American Diabetes Association. Facts and Figures. Mokdad et al. Diabetes Care. 2000;23:1278.
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Complications of type 2 diabetes in Minorities
• Disparate and Disproportionate prevalence of longterm complications of type 2 diabetes in minorities vs Whites– lower leg amputations 2-4x
– retinopathy and blindness 2-4x
– stroke 2x
– ESRD 4-6x
Caballero AE. Diabetes in minority populations.
In: Joslin’s Diabetes Mellitus. LW & W; 2005. 14th Ed. p 505-524
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Klein et al. In: Harris et al, eds. Diabetes in America, 2nd ed. 1995. Reiber et al. In: Harris et al, eds. Diabetes in America, 2nd ed. 1995. USRDS. Am J Kidney Dis. 1994;24:879.
Caucasian African-American Mexican-American
Prevalence of Complications in Type 2 Diabetes
40–59 years 60 years
0
20
40
Pat
ien
ts (
%)
New Cases of End-Stage Renal Disease
100
200
300
(per
mil
lion
/pop
ula
tion
)
0
Prevalence of Retinopathy in Type 2 Diabetes
Age Range of Amputations per 10,000 DM patients
0
40
80
120
160
200
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• Latinos- more insulin resistance/diabetes but no higher rates for CAD when compared to Whites
• A true Hispanic paradox?• Data are not conclusive - some studies may be
influenced by changes in the population due to migration factors
Lerman-Garber I, Villa A.R, Caballero AE.. Diabetes and Cardiovascular Disease. Is there a true Hispanic Paradox? Rev Invest Clinic. 2004; 56 (3): 282-296 Available at: www.imbiomed.com.mx
Cardiovascular Disease in Latinos with Diabetes
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15Hamman RF et al. Diabetes. 1989; 38;1231. Hamman RF et al. Diabetes Care. 1991;14(suppl 3):655.
No Difference In Complications When Good Control Is Achieved
San Luis Valley Study Caucasian and Latino (n=279)
- Similar glucose control in both study groups
- Similar severity of retinopathy, nephropathy and diabetic neuropathy
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Normal Normal -cell -cell functionfunction
CompensatoryCompensatoryhyperinsulinemiahyperinsulinemia
NormoglycemiaNormoglycemia
Relative insulin deficiencyRelative insulin deficiency
HyperglycemiaHyperglycemia
Type 2 diabetesType 2 diabetes
Abnormal Abnormal -cell -cell functionfunction
Diabetes: Dual ImpairmentInsulin Resistance and Impaired b-Cell Function
InsulinInsulinresistanceresistance
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Insulin Resistance
• Genetic• Acquired
Central obesity Medications
• In 80-90% of type 2 patients• Clusters with metabolic disease syndrome• Associated with increased macrovascular disease
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Increased Visceral Fat
InsulinResistance
Endothelial Dysfunction
Modified from Caballero AE. Current Diabetes Reports 2004; 4: 237- 246
Visceral Fat, Insulin Resistance and Endothelial Dysfunction
Cytokines, SubstratesHormones
HyperglycemiaHypertensionDyslipidemia
IL1, IL6, TNF- , FFA,, PAI-1, RAS,
leptin, resistin Adiponectin
GenesGenesGenesGenes
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Insulin Sensitivity in Healthy Subjects in Various Ethnic Groups
0
1
2
3
4
5
6
7
NH White African Am Asian Am Mexican AmN=34 N=9N=9 N=18 N=16
Insu
lin
Sen
siti
vity
Ind
ex
(m
ol•
L-1•
m-2•
min
-1•
pmol
-1•
L-1)†
*P =0.0023 vs. Caucasians. †Data are geometric means. Adapted from: Chiu KC, et al. Diabetes Care. 2000;23(9):1353-1358.
**** **
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Prevalence of the Insulin Resistance Syndrome in the US Population
0
5
10
15
20
25
30
35
40
Men Women
White
African American
Mexican American
Other
*Age adjusted ≥ 20 years of age
Pre
vale
nce
(% o
f ad
ults
)
Ford ES et al. JAMA. 2002;287:356-359
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Progressive Nature of Type 2 Diabetes Progressive Nature of Type 2 Diabetes
Endogenous InsulinEndogenous Insulin
Fasting Blood Glucose
Fasting Blood Glucose
Postprandial Blood Glucose
Postprandial Blood Glucose
Normal Blood Glucose
Normal Blood Glucose
Normal Normal
YearsYears
IGTIGT DiabetesDiabetes
Avg Dx
9-12 yrs*
Avg Dx
9-12 yrs*
Insulin ResistanceInsulin Resistance
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UKPDS: Glucose Control Study Results
Change in risk P value
Any diabetes-related endpoint 12% 0.029 Diabetes-related deaths 10% NSMyocardial infarction 16% 0.052Microvascular disease 25% 0.0099Stroke 14% NS
Adapted from UKPDS Group. Lancet. 1998; 352:837-853.
Intensive Blood- Glucose Control
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Effect of Each 1% Rise in A1C on Risk of Developing Complications
Incidence of retinopathy
Progression of retinopathy
Progression to PDR
Visual loss
Proteinuria
Amputation
Ischemic heart death
0.5 1 1.5 2 2.5
Risk Ratio and 95% CIKlein. Diabetes Care 18:258-268, 1995
10-Year follow-up in older-onset patients
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Why Aren’t Patients Achieving Blood Glucose Goals?
• Physicians not setting appropriate glycemic targets• Type 2 diabetes is progressive - what works now
may not work in the future• Type of medications used and/or doses not
appropriate• Insulin therapy only used as a “threat”
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American Diabetes Association
Standards of Care
Clinical Practice Recommendations 2004. Diabetes Care, 27(Suppl1):S15-36.
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Diagnosing Diabetes
Fasting Plasma Casual Plasma Oral Glucose Test Glucose (FPG)* Glucose * Tolerance Test*
(Preferred Test) Stage
Diabetes FPG >126 mg/dl Casual plasma Two-hour plasma glucose >200 mg/dl glucose (2hPG)
(plus symptoms >200 mg/dl Impaired Impaired Fasting Impaired Glucose Glucose Glucose (IFG)=FPG Tolerance (IGT) = Homeostasis >100 and <126 mg/dl 2hPG >140 and
<200 mg/dl
Normal FPG <100 mg/dl 2hPG <140 mg/dl
*In the absence of unequivocal hyperglycemia, these need to be repeated on the second day
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Goals for Glycemic Control
A1C* < 7.0% 43% achieve goal
Pre- Prandial glucose 90-130 mg/dl
Postprandial plasma glucose
< 180 mg/dl
*For non-pregnant individuals
Diabetes Care, 27: Supp.1.S19, 2004
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Goals for Blood Pressure, Lipids and Microalbumin
Blood Pressure <130/80mmHg 66% achieve goal
Lipids (mg/dl)LDL-C <100 (<70) 11% achieve goal
HDL C <40 (male) HDL-C >50 (female) Triglycerides <150
Microalbumin <30 (mg/g creatinine)
Diabetes Care, 27: Sup 1. S19, 2004
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Monitoring Parameters for Control of Complications
Every visit Blood PressureFoot Exam (55% achieve goal)
______________________________________________
3-6 months A1C- Every 3 months if treatment changes or not meeting goals- Every 6 months if stable
_______________________________________________
Annual Dilated Eye Examination (63% achieve goal)Lipid Levels*Microalbumin
_______________________________________________________________*Every 2 years if levels fall in lower risk categories
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Goals of Medical Nutrition Therapy
• Achieve blood glucose goals
• Achieve optimal lipid levels
• Provide appropriate calories for:- Reasonable weight
- Normal growth and development
- Pregnancy and lactation
• Prevent, delay or treat nutrition-related complications
• Improve health through optimal nutrition
Diabetes Care 22(1):S42-S45,1999
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Non-pharmacological Medical Therapy for Type 2 Diabetes
Optimize BG Control Improve blood lipids Control blood pressure
Consistent carbohydrate intake
Monitor blood glucose to adjust therapy
Moderate weight loss
Increase physical activity
Space meals
Modify fat and calorie content
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ADA Nutrition Recommendations
Total Daily Energy Intake
• Carbohydrate – 60-70%
• Protein – 15-20%
• Fat- 10% from polyunsaturated fats
- < 10% from saturated fats
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Preventing or Delaying Type 2 Diabetes
• Exercise can lower risk, delay or prevent, type 2 diabetes
• Important for individuals with risk factors- Obesity
- Sedentary lifestyle
- Family history of type 2 diabetes
- Native American, Hispanic, African American, Asian American, Pacific Islander
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Effects of Exercise
• Increased insulin sensitivity
• Improved lipids
• Lower blood pressure
• Weight control
• Improved blood glucose control in type 2 diabetes
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Exercise Precautions for Type 2 Diabetes
• Check with referral source for medical clearance
• Lower VO2max may require a gradual training program
• Autonomic neuropathy or blood pressure meds do not allow for increased heart rate perceived exertion important
• Blood pressure may go higher, avoid exercise if systolic BP >180-200
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Exercise Precautions Related to Complications of Diabetes
• Peripheral neuropathy can cause loss of sensation in feet
• Pre-existing CVD can cause arrhythmias, myocardial ischemia, or infarction during exercise
• Proliferative retinopathy does not increase risk for retinal or vitreous hemorrhage with exercise
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Treatment of Type 2 Diabetes
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Principles of Diabetes Treatment
• Define target goal
• Diabetes education is essential
• Monitoring glycemic control is necessary
• Lifestyle modification
• Stepwise and combination pharmacologic therapy
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ADA Recommendations • Glycemic goals should be individualized
• Certain populations (children, pregnant women, and elderly) require special
considerations
• Less intensive glycemic goals may be indicated in patients with severe or
frequent hypoglycemia
• More stringent glycemic goals (i.e. a normal A1C, 6%) may further reduce
complications at the cost of increased risk of hypoglycemia.
• Postprandial glucose may be targeted if A1C goals are not met despite
reaching pre-prandial glucose goals.
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Targeted Glucose Control
• Therapy based on glycemic goals
• Monotherapy usually not effective long-term
• Step-wise approach
• Whatever therapy is necessary to achieve glycemic goals
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Pharmacologic Therapy
Selection of therapy should be
individualized based upon potential
side effects.
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Therapeutic Agents for Type 2 Diabetes
Mechanism of Action Agent
1. Sensitize the body to insulin Thiazolidinediones, Biguanides
2. Control hepatic glucose production Biguanides, Thiazolidnediones
3. Stimulate the pancreas to Sulfonylureas
make more insulin Meglitinides
4. Slow the absorption of starches Alpha-glucosidase
inhibitors
5. Decreases hepatic glucose Insulin
production and increases
peripheral glucose uptake
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Impact of Therapies on A1C Levels
Therapy A1C Reduction
Diet and Exercise 0.5 - 2.0% Sulfonylureas and Glitinides 1.0 - 2.0% Metformin 1.0 - 2.0% -Glycosidase Inhibitors 0.5 - 1.0 % Thiazolidinedione 0.5- 1.0% Insulin >5.0%
Nathan, D. Oct 2002. N Engl J Med, Vol. 347, No.17
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Biguanides
Decrease hepatic glucose production and secondarily may increase insulin-mediated peripheral glucose uptake
• Efficacy- decrease blood glucose ~ 60 mg/dl- reduce HbA1c 1.0 - 2.0%- cause small decrease in LDL-C and triglycerides- no specific effect on blood pressure- no weight gain
• Other Effects- diarrhea and abdominal discomfort- lactic acidosis if inappropriately prescribed- contraindicated in patients with impaired renal function
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Sulfonylureas
Increase endogenous insulin secretion• Efficacy
- decrease blood glucose ~ 60 mg/dl- reduce HbA1c 1.0 - 2.0 %- no specific effect on plasma lipids or
blood pressure
• Other Effects- hypoglycemia- weight gain
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Thiazolidinediones
Potentiate insulin action on muscle and adipose tissue• Efficacy
- decrease FPG ~ 25 - 40 mg/dl- reduce HbA1c ~ 0.5 - 1%- combined with sulfonylureas reduce HbA1c ~ 0.8 - 1.0 %
- combined with insulin reduce HbA1C by 0.8 - 1.4% - Beneficial effect on lipids - Possible cardiovascular effects
• Other Effects- contraindicated with abnormal liver function- weight gain, edema
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MeglitinidesNon-sulfonylurea insulin releasing agent; taken before each meal
Rapid onset of action with a duration of action of several hours
• Efficacy- decrease peak postprandial glucose
- decrease blood glucose 60 - 70 mg/dl
- reduce HbA1c 1.0 - 2.0 %
• Other Effects- hypoglycemia
- weight gain
- safe at higher levels of creatinine than sulfonylureas
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Alpha-Glucosidase InhibitorsCompetitive inhibitor of alpha glucosidase enzymes in small intestines; taken
before meals
• Efficacy- decrease fasting plasma glucose 20-30 mg/dl
- decrease peak postprandial glucose 40-50 mg/dl
- no specific effect on lipids or blood pressure
- reduce HbA1c 0.5-1.0%
• Other Effects- abdominal discomfort and flatulence
- contraindicated with inflammatory bowel disease or cirrhosis
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Insulin
Decreases hepatic glucose production and increases uptake and use of glucose by muscle and adipose tissue
• Efficacy- can lower plasma glucose to any level - reduces HbA1c > 5.0%- limited by hypoglycemia
• Other Effects- hypoglycemia- weight gain
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Anticipated Response to Treatment
Agent Time to Response SMBG Indicator
Secretatogogues Long-acting Rapid-acting
7 – 10 days Immediate
Fasting Postprandial
Metformin 2 – 3 weeks Fasting
Glitazones 6 – 8 weeks AGIs Immediate Postprandial
Insulin Rapid Acting Long-acting
Immediate Immediate
Postprandial Fasting
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Insulin Therapy in Type 2 Diabetes
• Most patients with type 2 diabetes will eventually
need insulin.
• As insulin deficiency progresses, a more physiologic
multi-component insulin regimen will be required to
adequately replace normal insulin secretion.
- Basal insulin
- Meal-Related (prandial, bolus) insulin
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Indications for Insulin Therapy in Type 2 Diabetes
• Severe hyperglycemia at glucose toxicity
• To meet glycemic goals
• Hyperglycemia despite maximum doses of oral
agents
• Most patients with type 2 diabetes will
eventually need insulin
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Insulin Action Comparison Insulins Onset Peak Duration
Lispro* orAspart ~15 minutes 1– 2 hours 4 – 6 hours
Human Regular 30 – 60 minutes 2 – 4 hours 6 – 10 hours
Human
NPH or Lente 2 – 4 hours 6 – 12 hours 12 – 20 hours
HumanUltralente 4 – 6 hours Unpredictable 18 – 24 hours
Glargine* 2– 4 hours Peakless 20 – 26 hours*Insulin analogs
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Profiles of Human Insulins and Analogs
0 2 4 6 8 10 12 14 16 18 20 22 24
Plas
ma
insu
lin
leve
ls
Regular (6–10 hours)
NPH (12–20 hours)
Ultralente (18–24 hours)
Hours
Glargine (20-26 hours)
Aspart, lispro (4–6 hours)
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STEP 1• Add metformin or insulin secretagogue
STEP 2• If on metformin, add insulin secretagogue• If on insulin secretagogue, add metformin
continued
Pharmacologic TherapyPossible Treatment StepsPharmacologic TherapyPossible Treatment Steps
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STEP 3
• Add insulin
• Switch to insulin
• Add a thiazolidinedione
STEP 4
• Add an oral drug to insulin
• Use multiple component insulin therapy
Pharmacologic TherapyPossible Treatment StepsPharmacologic TherapyPossible Treatment Steps
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Studies Aimed at Prevention of Type 2 DMLifestyle Modification Studies DPP (Diabetes Prevention Program) DPS (Diabetes Prevention Study, Finnish
Study) Da Qing (Chinese Study) Malmo Study (Males, Sweden)
Drug Intervention Studies DPP Stop-NIDDM (Acarbose) - Prevention Evaluation
(Ramipril) TRIPOD Study (Troglitazone) DREAm Study (Rosiglitazone
Ramipril)* Navigator Study (Nateglinide,
Valsartan) Xendos trial (Orlistat)* Sibutramine Study*
*Trial still underway
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Summary
• The Latino Population is the largest minority group in the country
• The prevalence of diabetes and its complications is higher in Latinos when compared to the non-Latino White group
• Genetic and environmental factors influence the development of obesity, metabolic syndrome and type 2 diabetes in Latinos
continued
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Summary
• Multiple cultural factors influence diabetes care in Latinos
• Goals for glycemic control, BP, weight, lipids and smoking cessation need to be established
• Aggressive Management to reach these goals is important
• Early use of available pharmacologic treatment tools needs to be considered