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Diabetes Diabetes MellitusMellitusin Clinical in Clinical PracticePractice
Dr. Muhieddin OmarDr. Muhieddin OmarDr. Raed Abu Sham’aDr. Raed Abu Sham’a
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Definition of DiabetesDefinition of Diabetes It is a group of It is a group of metabolic diseasesmetabolic diseases
characterized by hyperglycemia characterized by hyperglycemia resulting from defects of resulting from defects of insulin insulin
secretion and/or increased cellular secretion and/or increased cellular resistance to insulinresistance to insulin. .
Chronic hyperglycemiaChronic hyperglycemia and other and other metabolic disturbances of DM lead to metabolic disturbances of DM lead to
long-term tissue and organ damage as long-term tissue and organ damage as well as dysfunction.well as dysfunction.
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Type 2 diabetes is a major clinical and public Type 2 diabetes is a major clinical and public
health problem. health problem.
It is estimated that in the year 2000, 171 It is estimated that in the year 2000, 171 million people worldwide had type 2 diabetesmillion people worldwide had type 2 diabetes
In PalestineIn Palestine, the prevalence of diabetes , the prevalence of diabetes between 9 – 13% of the population.between 9 – 13% of the population.
Type 2 diabetesType 2 diabetesthe modern epidemicthe modern epidemic
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Diabetes in the UK is Diabetes in the UK is increasingincreasing
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
1940 1960 1980 1996 2004 2005 2010
Mill
ions
of p
eopl
e
with
dia
bete
s
Adapted from: 1. Diabetes UK. Diabetes in the UK 2004. Diabetes UK, London, 2004.2. Diabetes UK. State of the Nation 2005. Diabetes UK, London, 2005.
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How we How we
Diagnose Diabetes?Diagnose Diabetes?
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Criteria for the diagnosis of Criteria for the diagnosis of DMDM
1.1. Symptoms of diabetes plus Symptoms of diabetes plus
random plasma glucoserandom plasma glucose
concentration >200 mg/dL.concentration >200 mg/dL.
2.2. Fasting plasma glucoseFasting plasma glucose >126 >126
mg/dL. (Fasting for at least 8 h.)mg/dL. (Fasting for at least 8 h.)
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Criteria for the diagnosis of Criteria for the diagnosis of DMDM
3.3. Two-hour plasma glucoseTwo-hour plasma glucose >200 >200
mg/dL during an mg/dL during an OGTTOGTT (75 g). (75 g).
4.4. HbA1c > 6.5%HbA1c > 6.5% (ADA in 2010)(ADA in 2010)
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Diagnosing Diabetes Using A1CDiagnosing Diabetes Using A1C
Diabetes diagnosed when A1C ≥6.5%Diabetes diagnosed when A1C ≥6.5%
Confirm with a repeat A1C test
Not necessary to confirm in symptomatic
persons with PG >200 mg/dL
If A1C testing not possible, use previous If A1C testing not possible, use previous
teststests
Can not be used during pregnancyCan not be used during pregnancy
because of changes in red cell turnoverbecause of changes in red cell turnover
July 2009, International Committee, American Diabetes Association & International Diabetes Federation
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Diagnosing Diabetes Using A1CDiagnosing Diabetes Using A1C
A1C ≥6.0% should receive preventive A1C ≥6.0% should receive preventive
interventions (pre-diabetes)interventions (pre-diabetes)
A1C: reliable measure of chronic glucose A1C: reliable measure of chronic glucose
levels; values vary less than FPG and testing levels; values vary less than FPG and testing
more convenient for patients (can be done more convenient for patients (can be done
any time of day)any time of day)July 2009, International Committee, American Diabetes Association & International Diabetes Federation
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Ease of testing- non fasting, one timeEase of testing- non fasting, one time
ReproducibilityReproducibility
ReliabilityReliability
Less variable than FBG that has Less variable than FBG that has 6-6-10% 10% intra-individual variability intra-individual variability
and the 2h PG that has variability and the 2h PG that has variability up to up to 15%15%
Diabetes CareDiabetes Care
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Who should be screened for Who should be screened for diabetesdiabetes
All individuals >45 yearsAll individuals >45 years
If normal, repeat every 3 yearsIf normal, repeat every 3 years
Consider testing at a younger age Consider testing at a younger age or more frequently for high-risk or more frequently for high-risk individualsindividuals
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HIGH-RISKHIGH-RISK Individuals Individuals
ObeseObese (BMI >27 kg/m²) (BMI >27 kg/m²)
Having a Having a first-degree relativefirst-degree relative with DMwith DM
High-risk High-risk ethnic populationethnic population
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HIGH-RISKHIGH-RISK Individuals Individuals
Delivered a Delivered a baby weighing >4 kgbaby weighing >4 kg or or
gestational DMgestational DM
HypertensiveHypertensive (>140/90 mmHg) (>140/90 mmHg)
Having Having HDL-C <35HDL-C <35 mg/dL and/or a mg/dL and/or a
Triglyceride >250Triglyceride >250 mg/dL mg/dL
IGTIGT or or IFGIFG on previous testing on previous testing
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In clinical settings . . .In clinical settings . . .
The The FPGFPG is preferred over the is preferred over the
OGTT due to: OGTT due to:
Ease of administration
Convenience, patient acceptability
Lower cost
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Can we prevent or delay the Can we prevent or delay the
onset of Diabetes?onset of Diabetes?
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Who should start the Who should start the preventionprevention
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Strategies for prevention of Strategies for prevention of type 2 diabetestype 2 diabetes
1.1. Weight loss of 5 – 10%Weight loss of 5 – 10%
2.2. Physical activity ~ 30 min/dayPhysical activity ~ 30 min/day
3.3. Metformin [some patients]Metformin [some patients]
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The Plate MethodThe Plate Method
Fruit Fruit Vegetables Vegetables
BreadsGrains StarchyVeggies
BreadsGrains StarchyVeggies
MeatsProteinsMeatsProteins
Dairy Dairy
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Strategies for prevention of Strategies for prevention of type 2 diabetestype 2 diabetes (Con…) (Con…)
Monitoring for the development of diabetes Monitoring for the development of diabetes should be performed every should be performed every 1–2 years1–2 years..
Close attention and treatment for other Close attention and treatment for other CVD risk factors.CVD risk factors.
Drug therapy should not be routinely used Drug therapy should not be routinely used to prevent diabetes. to prevent diabetes.
However, metformin could be used However, metformin could be used cautiously in selected patients.cautiously in selected patients.
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Management of
Diabetes
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Type 2 Diabetes: Type 2 Diabetes: A Progressive DiseaseA Progressive Disease
LifestyleInterventions
Medical Nutrition Therapy
Alone
orwith Medications
Medical Nutrition Therapy
Medications
Insulin
Meds
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Goals for Glycemic ControlGoals for Glycemic Control
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Goals for Lipid ControlGoals for Lipid Control
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Goals for BP ControlGoals for BP Control
< 130/80 mmHg< 130/80 mmHg
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Stepwise Management Stepwise Management of Type 2 Diabetesof Type 2 Diabetes
Insulin ± oral agents
Oral combination
Oral monotherapy
Diet & exercise
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How to follow up your How to follow up your
diabetic patient?diabetic patient?
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Assessment guidelinesAssessment guidelines
EVERY VISITEVERY VISITBlood pressureBlood pressure
WeightWeight
Visual foot examinationVisual foot examination
QUARTERLYQUARTERLYHemoglobin A1CHemoglobin A1C
BIANNUALBIANNUALDental examinationDental examination
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Assessment guidelinesAssessment guidelines
ANNUALLYANNUALLY
Albumin/creatinine ratioAlbumin/creatinine ratio (unless (unless
proteinuria is documented)proteinuria is documented)
Pedal Pedal pulsespulses and and neurologicneurologic examination examination
EyeEye examination (by ophthalmologist) examination (by ophthalmologist)
Blood Blood lipidslipids
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Correlation of A1C with Average Correlation of A1C with Average GlucoseGlucose
Mean plasma glucoseMean plasma glucose
A1C (%)A1C (%)mg/dlmg/dl
66126126
77154154
88183183
99212212
1010240240
1111269269
1212298298
Diabetes Care 32(Suppl 1):S19, 2009
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Glycemic ControlGlycemic Control
Each 1% reduction in mean HbA1c Each 1% reduction in mean HbA1c
was associated with:was associated with:
21% for deaths related to diabetes 21% for deaths related to diabetes
14% for myocardial infarction 14% for myocardial infarction
37% for microvascular complications 37% for microvascular complications
Stratton IM, Adler AI, Neil HA, et alStratton IM, Adler AI, Neil HA, et alBMJBMJ 2000 Aug 12;321(7258):405-12 2000 Aug 12;321(7258):405-12
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Non-insulin agents in the Non-insulin agents in the management of type 2 management of type 2
diabetesdiabetes
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InsulinInsulin in the Management of in the Management of
Type 2 DiabetesType 2 Diabetes
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Combination between Combination between
InsulinInsulin and other and other
antihyperglycemicsantihyperglycemics
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ConclusionsConclusionsMany, if not most, patients with Many, if not most, patients with
type 2 diabetes will eventually type 2 diabetes will eventually
require insulin to achieve their require insulin to achieve their
glycemic goals.glycemic goals.
Insulin should be offered to patients as Insulin should be offered to patients as
a safe and effective treatment option, a safe and effective treatment option,
not as a punishmentnot as a punishment
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ConclusionsConclusions Insulin doses must be Insulin doses must be adjusted adjusted
frequentlyfrequently until the patient achieves until the patient achieves
the desired target.the desired target.
Treatment is initiated with a Treatment is initiated with a single single
bedtime injection of basal insulinbedtime injection of basal insulin
and the dose is titrated until the and the dose is titrated until the fasting fasting
glucose is normal.glucose is normal.
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ConclusionsConclusions If the If the fasting glucose normalizesfasting glucose normalizes but the but the
A1C remains elevatedA1C remains elevated, additional , additional injections, typically given as injections, typically given as pre-meal pre-meal dosesdoses of rapid-acting insulin, may be of rapid-acting insulin, may be
required.required.
Patients with long-standing diabetes Patients with long-standing diabetes and non-obese, frequently may require and non-obese, frequently may require
multiple daily insulin injections.multiple daily insulin injections.
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Take Home PointsTake Home Points When Oral Agents Fail, Add Basal Insulin When Oral Agents Fail, Add Basal Insulin
While Continuing OralsWhile Continuing Orals
Titrate Basal Insulin Titrate Basal Insulin RapidlyRapidly To Normalize To Normalize FBSFBS
When FBS Normal But A1C Elevated, Add When FBS Normal But A1C Elevated, Add Mealtime Bolus Insulin One Meal At A Mealtime Bolus Insulin One Meal At A
Time Time & Withdraw Sulfonylurea when & Withdraw Sulfonylurea when All Meals CoveredAll Meals Covered
Don’t Forget The ABC’s Don’t Forget The ABC’s
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Complications of Complications of DiabetesDiabetes
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Diabetic NephropathyDiabetic Nephropathy
Optimize glucose controlOptimize glucose control
Optimize blood pressure controlOptimize blood pressure control
Limit protein intake Limit protein intake
Test for microalbuminuria Test for microalbuminuria
Measure serum creatinine annually Measure serum creatinine annually
Treat with either ACE inhibitors or ARBsTreat with either ACE inhibitors or ARBs
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Monitoring and Preventing Monitoring and Preventing HypertensionHypertension
BP should be measured at every routine BP should be measured at every routine
diabetes visit.diabetes visit.
Patients with diabetes should be treated Patients with diabetes should be treated
to a SBP <130/80 mmHg. to a SBP <130/80 mmHg.
Multiple drug therapy is generally Multiple drug therapy is generally
required to achieve targets.required to achieve targets.
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Monitoring and Preventing Monitoring and Preventing HypertensionHypertension
Initial drug therapy for raised BP should Initial drug therapy for raised BP should
be with be with ACE inhibitors or ARBsACE inhibitors or ARBs
All patients with diabetes and All patients with diabetes and
hypertension should be treated with a hypertension should be treated with a
regimen that includes either an regimen that includes either an ACE ACE
inhibitor or an ARBinhibitor or an ARB..
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Monitoring Lipid LevelsMonitoring Lipid Levels
In adults, test for lipid disorders at least In adults, test for lipid disorders at least annually and more often if needed to achieve annually and more often if needed to achieve
goals. goals.
Lifestyle modificationLifestyle modification including reduction including reduction of saturated fat and cholesterol intake, of saturated fat and cholesterol intake,
weight loss, and increased physical activity.weight loss, and increased physical activity.
In individuals without overt CVD, the primary In individuals without overt CVD, the primary goal is an LDL <100 mg/ dL. In those with goal is an LDL <100 mg/ dL. In those with
overt CVD, the goal is <70 mg/dL.overt CVD, the goal is <70 mg/dL.
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Monitoring Lipid LevelsMonitoring Lipid Levels
For those over the age of 40 years, For those over the age of 40 years, statinstatin
therapy to achieve an therapy to achieve an LDL reduction of 30–LDL reduction of 30–
40% regardless of baseline LDL levels40% regardless of baseline LDL levels..
Lower Lower LDL cholesterolLDL cholesterol to <100 mg/dL to <100 mg/dL
Lower Lower triglyceridestriglycerides to <150 mg/dL to <150 mg/dL
Raise Raise HDL cholesterolHDL cholesterol to >40 mg/dL. to >40 mg/dL.
In women, an HDL goal should be >50 mg/dL.In women, an HDL goal should be >50 mg/dL.
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The The AAction to ction to CControl ontrol
CCardiardiOOvascular vascular RRisk in isk in
DDiabetesiabetes
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STUDY HYPOTHESIS:STUDY HYPOTHESIS:
A therapeutic strategy that targets HbA1c < 6.0%
reduces the rate of CVD events more than a
strategy that targets HbA1c 7.0% to 7.9%
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ACCORDACCORD
257 Deaths257 Deaths In Intensive Arm In Intensive Arm
203 Deaths203 Deaths In Conventional Arm In Conventional Arm
Not Due To HypoglycemiaNot Due To Hypoglycemia
Not Due To MedicationNot Due To Medication
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The ACCORD Study Group. N Engl J Med. 2008;358:2545-2559.The ACCORD Study Group. N Engl J Med. 2008;358:2545-2559.
ACCORD: Primary OutcomeACCORD: Primary Outcome
2525
Pat
ien
ts W
ith
Eve
nts
(%
)P
atie
nts
Wit
h E
ven
ts (
%)
1515
2020
1010
55
0000 11 22 33 44 55 66
YearsYears
PP=0.16=0.16
StandardStandard
IntensiveIntensive
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ACCORD: All-Cause ACCORD: All-Cause MortalityMortality
2525P
atie
nts
Wit
h E
ven
ts (
%)
Pat
ien
ts W
ith
Eve
nts
(%
)
1515
2020
1010
55
0000 11 22 33 44 55 66
YearsYears
The ACCORD Study GroupThe ACCORD Study Group. N Engl J Med. N Engl J Med. 2008;358:2545-2559.. 2008;358:2545-2559.
PP=0.04=0.04
StandardStandard
IntensiveIntensive
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ADVANCEADVANCEAction In Diabetes And Vascular Disease:Action In Diabetes And Vascular Disease:
Preterax And Diamicron MR Controlled Preterax And Diamicron MR Controlled EvaluationEvaluation
11,140 Patients, Age ~66, With Type 2 11,140 Patients, Age ~66, With Type 2 DM, And High CV RiskDM, And High CV Risk
Intensive (Intensive (A1c 6.4%A1c 6.4%) vs Conventional ) vs Conventional ((A1c 7%A1c 7%))
NoNo Excess Mortality In Intensive GroupExcess Mortality In Intensive Group
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P=0.28
Advance Collaborative Group. New Engl. J. Med. 2008;358:2572.
ADVANCE: All-Cause MortalityADVANCE: All-Cause Mortality
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P=0.32
Advance Collaborative Group. New Engl. J. Med. 2008;358:2572.Advance Collaborative Group. New Engl. J. Med. 2008;358:2572.
ADVANCE: Macrovascular EventsADVANCE: Macrovascular Events
Pts
Wit
h A
CV
Eve
nt
Pts
Wit
h A
CV
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nt
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VADTVADTVeterans Affairs Diabetes TrialVeterans Affairs Diabetes Trial
Glycemic Control And CV EventsGlycemic Control And CV Events
Somewhat Less Intense Glycemic Somewhat Less Intense Glycemic Separation Separation ((6.9% vs 8.4%6.9% vs 8.4%))
Optimal CV Risk Factor ControlOptimal CV Risk Factor Control
Completed May And Presented At The Completed May And Presented At The ADA June, 2008ADA June, 2008
NoNo Excess Mortality In Intensive GroupExcess Mortality In Intensive Group
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Hazard Ratio & CLHazard Ratio & CL
0.868 (0.728, 1.036) 0.868 (0.728, 1.036) PP=0.12=0.12
00 11 22 33 44 55 66 770.00.0
0.20.2
0.40.4
0.60.6
0.80.8
1.01.0
Follow-Up (years)Follow-Up (years)
Pro
po
rtio
n F
ree
of
Pri
mar
y O
utc
om
eP
rop
ort
ion
Fre
e o
f P
rim
ary
Ou
tco
me
Duckworth WC. ADA 68Duckworth WC. ADA 68thth Scientific Sessions; June 8, 2008; San Francisco, CA. Scientific Sessions; June 8, 2008; San Francisco, CA.
VADTVADT : Primary Outcome : Primary Outcome
StandardStandard
IntensiveIntensive
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77Follow-Up (years)Follow-Up (years)
VADT: Total MortalityVADT: Total Mortality
Duckworth WC. ADA 68Duckworth WC. ADA 68thth Scientific Sessions; June 8, 2008; San Francisco, CA. Scientific Sessions; June 8, 2008; San Francisco, CA.
Hazard Ratio & CLHazard Ratio & CL
1.065 (0.801, 1.416) 1.065 (0.801, 1.416) PP=0.67=0.67
00 11 22 33 44 55 660.00.0
0.20.2
0.40.4
0.60.6
0.80.8
1.01.0
Pro
po
rtio
n F
ree
of
All
Dea
ths
Pro
po
rtio
n F
ree
of
All
Dea
ths
StandardStandard
IntensiveIntensive
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VA Diabetes TrialVA Diabetes TrialEnd of Trial Median End of Trial Median
ValuesValues BPBP LDLLDL
VADTVADT 127/69 127/69 72 72
ADVANCE 137/74ADVANCE 137/74 102 102
Abraira CA. ADA 68Abraira CA. ADA 68thth Scientific Sessions; June 8, 2008; San Francisco, CA. Scientific Sessions; June 8, 2008; San Francisco, CA.
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ConclusionsConclusionsThe Overall Effect Of Glycemic Target The Overall Effect Of Glycemic Target
On On Macrovascular Events, If Any, Is Macrovascular Events, If Any, Is SmallSmall
Extremely Tight Glycemic Control In Extremely Tight Glycemic Control In Very Very High Risk Patients Is Not BenignHigh Risk Patients Is Not Benign
Lipid And BP Control, Smoking Cessation Lipid And BP Control, Smoking Cessation And Anti-platelet Therapy Remain And Anti-platelet Therapy Remain
Most Most Important For Reducing CVD Important For Reducing CVD Risk In Risk In Diabetes Diabetes
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ADA Standards for Control
A1c
Normal < 6%
Goal <7%
Fasting: 90-130; HS 110-140
Goal <6.5%
Post-prandial < 140 mg
AACE Standards for Control
A1c As Close to Normal A1c As Close to Normal Without HypoglycemiaWithout HypoglycemiaAnd Goals Need to Be And Goals Need to Be
Individualized!Individualized!
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Relative Risk of Progression of Relative Risk of Progression of Diabetic Complications Diabetic Complications
DCCT Research Group, N Engl J Med 1993, 329:977-986.
1
3
5
7
9
11
13
15
6 7 8 9 10 11 12
Retinop
Neph
Neurop
RELA
TIV
E
RIS
K
Mean A1C
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UKPDS 35. BMJ 2000; 321: 405-12
Glycemic control and complicationsGlycemic control and complicationsUKPDS studyUKPDS study
0
20
40
60
80
0 5 6 7 8 9 10 11
Myocardialinfarction
Microvasculardisease
Updated mean HbA1c (%)
Inci
denc
e pe
r10
00 p
atie
nt-y
ears
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The patients agenda may not be The patients agenda may not be yours ! ! ! !yours ! ! ! !
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So remember…So remember…
Type 2 diabetes is largely Type 2 diabetes is largely asymptomatic and the treatments are asymptomatic and the treatments are inconvenient, impose on daily life and inconvenient, impose on daily life and
employmentemploymentThe patient’s agenda may be very The patient’s agenda may be very
different from yoursdifferent from yoursLifestyle change is the most important Lifestyle change is the most important
but the most difficult to achievebut the most difficult to achieveIn insulin-treated patients, In insulin-treated patients,
hypoglycaemia is a major risk, hypoglycaemia is a major risk, especially in the young and elderly.especially in the young and elderly.
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SummarySummary
Most patients with type 2 diabetes still die of Most patients with type 2 diabetes still die of
cardiovascular disease regardless of their cardiovascular disease regardless of their
blood glucose control. blood glucose control.
Patients with highest HbA1c have most to Patients with highest HbA1c have most to
gain from any improvement in blood glucose gain from any improvement in blood glucose
controlcontrol
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