diabetes .
DESCRIPTION
Diabetes . . . Common and underdiagnosed Causes macro- and microvascular events Reduces duration and quality of life. Estimated Prevalence of Diabetes in the US Adult Men and Women. 30. Men. Women. 21.1. 20.2. 20. 17.8. 17.5. Percent of Population. 12.9. 12.4. 10. 6.8. 6.1. 1.6. - PowerPoint PPT PresentationTRANSCRIPT
Diabetes . . .
Common and underdiagnosed
Causes macro- and microvascular events
Reduces duration and quality of life
Estimated Prevalence of Diabetes in the USAdult Men and Women
Harris, et al. Diabetes Care. 1998;21:518-24.
0
10
20
30
75+60-7450-5940-4920-39Age (y)
1.6 1.7
6.8 6.1
12.9 12.4
20.217.8
21.1
17.5
MenWomen
Perc
ent o
f Pop
ulat
ion
Diagnosed and Undiagnosed Diabetes in the USEstimated Cases Among Adults, 1997
Harris, et al. Diabetes Care. 1998;21:518-24.
0
2
4
6
8
10
12
UndiagnosedDiagnosed
10.2
5.4
Mill
ions
of C
ases
Retinopathy in Adults not Known to Have Diabetes Rationale for Diagnostic Criteria for DiabetesGlycemic Values in Deciles of Populations
Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 1999;22(Supp 1):S5-S19.
FPG2hPGHbA1c
Ret
inop
athy
(%)
15
10
5
0
US (NHANES III)
42- 87- 90- 93- 96- 98- 101- 104- 109- 120-34- 75- 86- 94- 102- 112- 120- 133- 154- 195-3.3- 4.9- 5.1- 5.2- 5.4- 5.5- 5.6- 5.7- 5.9- 6.2-
FPG (mg/dL)2hPG (mg/dL)
HbA1c (%)
Retinopathy in Adults not Known to Have Diabetes Rationale for Diagnostic Criteria for DiabetesGlycemic Values in Deciles of Populations
Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 1999;22(Supp 1):S5-S19.
50
30
10
0
40
20
Ret
inop
athy
(%) FPG
2hPGHbA1c
Egypt
57- 79- 84- 89- 93- 99- 108- 130- 178- 258-39- 80- 90- 99- 110- 125- 155- 218- 304- 386-2.2- 4.7- 4.9- 5.1- 5.4- 5.6- 6.0- 6.9- 8.5- 10.3-
FPG (mg/dL)2hPG (mg/dL)
HbA1c (%)
Glucose Tolerance Categories
Adapted from The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care. 1997;20:1183-97.
FPG
126 mg/dL
110 mg/dL
7.0 mmol/L
6.1 mmol/L
Impaired FastingGlucose
Normal
2-Hour PG on OGTT
200 mg/dL
140 mg/dL
11.1 mmol/L
7.8 mmol/L
Diabetes Mellitus
Impaired GlucoseTolerance
Normal
Diabetes Mellitus
Diagnosis of DiabetesThree Methods
1. Random plasma glucose >200 mg/dL on 2 separate occasions + symptoms (polyuria, polydipsia,unexplained weight loss)
2. FPG >126 mg/dL on 2 separate occasions
3. 2-hour plasma glucose >200 mg/dL during OGTTon 2 separate occasions
Adapted from The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care. 1997;20:1183-97.
THE FUNAGATA DIABETES STUDY Impaired Glucose Tolerance is a CV Risk Factor
Tominaga M, et al. Impaired glucose tolerance is a risk factor for cardiovascular disease, but not impaired fasting glucose. Diabetes Care 1999;22:920-4.
NormalIGT (2 hr PG 140-200)DM (2 hr PG >200)
1.00
Cumulative Cardiovascular Survival
0.99
0.98
0.97
0.96
0.95
0.94
0
1.00
0.98
0.96
0.94
0.92
0
NormalIFG (FPG 110-126)DM (FPG >126)
0 1 2 3 4 5 6 7 0 1 2 3 4 5 6 7Year Year
FRAMINGHAM STUDY AND JOSLIN PATIENTS
Diabetes is a CV Risk Factor
Krolewski AS, et al. Evolving natural history of coronary disease in diabetes mellitus. Am J Med 1991;90(Supp 2A):56S-61S.
DiabetesNo Diabetes
60Men
0-3Duration of Follow-up (Years)
50
40
30
20
10
0
Women
4-7 8-11 12-15 16-19 20-23
60
0-3Duration of Follow-up (Years)
50
40
30
20
10
04-7 8-11 12-15 16-19 20-23
Mor
talit
y R
ate
Per
1000
Mor
talit
y R
ate
Per
1000
2x
4-5x
MRFIT Type 2 Diabetes is a CV Risk FactorAdditive Effects of Hypertension, Hypercholesterolemia, and Smoking
Stamler J, et al. Diabetes, other risk factors, and 12-year cardiovascular mortality for men screened in the Multiple Risk Factor Intervention Trial. Diabetes Care 1993;16:434-44.
0
20
40
60
Number of Risk FactorsNone One Two All Three
No DiabetesDiabetes
Age
Adj
uste
d C
V D
eath
Rat
ePe
r 10
,000
Per
son
Yea
rs
80
100
120
140
Type 2 Diabetes is a CV Risk FactorDiabetes and Prior MI Predict Mortality Equally
Haffner SM, et al. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med 1998;339:229-34.
100
Year3
Surv
ival
(%)
80
60
40
20
00 1 2 4 5 6 7 8
No Diabetes or MIDiabetes without MIMI without Diabetes
Diabetes + MI
Reduced Life-expectance with DiabetesUS Adults Aged 55 to 64 in 1971 to 1975
Gu K, et al. Mortality in adults with and without diabetes in a national cohort of the US population, 1971-1993.Diabetes Care 1998;21:1138-45.
0
10
20
30Median Life Expectance
Women Men
No Diabetes
DiabetesY
ears25
1718
10
Lifetime Microvascular Events in Type 2 Diabetes Predictions from a Statistical Model
Eastman RC, et al. Model of complications of non-insulin dependent diabetes mellitus. II analysis of the health benefits and cost-effectiveness of treating NIDDM with the goal of normoglycemia. Diabetes Care 1997;20:735-44.
Standard Care Comprehensive Care PercentageHbA1c 10% HbA1c 7.2% Change
Blindness 19% 5% -72
Renal failure 17% 2% -87
Symptomaticneuropathy 31% 10% -68
Amputation 15% 5% -67
Treatment Improves Outcomes
KUMAMOTO STUDY
Effect of Treatment on HbA1c
Ohkubo Y, et al. Intensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with non-insulin-dependent diabetes mellitus. A randomized prospective 6-year study. Diab Res Clin Pract 1995;28:103-17.
ConventionalIntensive
Years
9
0
HbA
1c (%
)12
11
10
8
6
5
7
1 2 3 4 5 6
2.3%HbA1c
KUMAMOTO STUDY
Risk Reduction of Microvascular Complications
Ohkubo Y, et al. Intensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with non-insulin-dependent diabetes mellitus. A randomized prospective 6-year study. Diab Res Clin Pract 1995;28:103-17.
Cum
ulat
ive
Perc
ent P
rogr
essi
ng
5040302010
0
5040302010
0
40302010
0
403020100
Years0 1 2 3 4 5 6
Years0 1 2 3 4 5 6
RetinopathyPrimary Prevention
NephropathyPrimary Prevention
RetinopathySecondary Intervention
NephropathySecondary Intervention
-62%P=0.032
-70%P=0.039
-52%P=0.049
-52%P=0.044
ConventionalIntensive
UKPDS MAIN STUDY
Effect of Treatment on HbA1c
Adapted from UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998;352:837-53.
Conventional(10-y cohort)
9
8
7
6
00 3 6
6.2% upper limit of normal range
ADA goal
ADA action
9 12 15Time From Randomization (y)
Intensive(all patients)
Conventional(all patients)
Intensive(10-y cohort)
Med
ian
HbA
1c (%
)
UKPDS MAIN STUDY
Risk Reduction of Microvascular Complications
UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998;352:837-53.
% o
f Pat
ient
s With
an
Eve
nt
Risk Reduction 25%P=0.0099
Conventional Intensive
0 3 6
0
10
20
30
9 12 15
Time From Randomization (y)
UKPDS MAIN STUDY
Risk Reduction of Various Endpoints
UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998;352:837-853.
Risk Reduction (%)
P=0.000054
P=0.015
P=0.052
P=0.0099
P=0.029
0 5 10 15 20 25 30 35
Diabetes-relatedend points
Myocardialinfarction
Albuminuria
Retinopathy
Microvascular 25%
21%
16%
33%
12%
UKPDS METFORMIN SUBSTUDY
Effect of Treatment on HbA1c
Adapted from UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998;352:854-65.
Med
ian
HbA
1c (%
)
Conventional (200)Insulin (199)Chlorpropamide (129)Glyburide (148)Metformin (181)
0 2 406
7
8
9
6 8 10Time From Randomization (y)
Upper limit of normal range (6.2%)
ADA goal
ADA action
UKPDS METFORMIN SUBSTUDY
Gain of Weight During Treatment
Adapted from UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998;352:854-65.
Mea
n C
hang
e (k
g)
Conventional (200)Insulin (199)Chlorpropamide (129)Glyburide (148)Metformin (181)
0 2 4-5
0
5
10
6 8 10Time From Randomization (y)
Baseline = 85 kg
UKPDS METFORMIN SUBSTUDY
Risk-Reduction of Microvascular Complications
Adapted from UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998;352:854-65.
% o
f Pat
ient
s With
Eve
ntConventional (411)Intensive (951)Metformin (342)
0 3 60
10
20
30
9 12 15Time From Randomization (y)
P=0.19 M vs. C
P=0.39M vs. I
UKPDS METFORMIN SUBSTUDY
Diabetes-Related Deaths
Adapted from UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998;352:854-865.
Patients at RiskConventionalMetforminIntensive
404339930
378321870
304267701
132123319
232861
Conventional (411)
Metformin (342)Intensive (951)
Prop
ortio
n W
ith E
vent
(%)
30
20
10
00 3 6 9 12 16
Time From Randomization (y)
M vs. CP=.017
M vs. IP=.11
UKPDS HYPERTENSION SUBSTUDY
Effect of Atenolol or Captopril on Blood Pressure
UK Prospective Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. BMJ 1998;317:703-13.
Less Tight ControlTight Control withAtenolol or Captopril
Years from Randomization0
Mea
n B
lood
Pre
ssur
e (m
m H
g)160
1 2 3 4 5 6 7 8 9
140
120
100
80
0
Systolic
Diastolic
UKPDS HYPERTENSION SUBSTUDY
Risk-Reduction of Microvascular Endpoints
UK Prospective Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. BMJ 1998;317:703-13.
Years from Randomization0
Patie
nts W
ith E
vent
s (%
)20
1 2 3 4 5 6 7 8 9
10
0
Less Tight ControlTight Control
Risk-Reduction 37%P=0.0092
UKPDS HYPERTENSION SUBSTUDY
Risk-Reduction of Stroke
UK Prospective Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. BMJ 1998;317:703-13.
0
Patie
nts W
ith E
vent
s (%
)20
1 2 3 4 5 6 7 8 9
10
0
Years from Randomization
Risk-Reduction 44%P=0.013
Less Tight ControlTight Control
UKPDS HYPERTENSION SUBSTUDY
Diabetes-Related Deaths
UK Prospective Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. BMJ 1998;317:703-13.
Years from Randomization0
Mor
talit
y (%
)40
1 2 3 4 5 6 7 8 9
20
0
30
10
Less Tight ControlTight Control
Risk-Reduction 32%P=0.019
UKPDS HYPERTENSION SUBSTUDY
Diabetes-Related Deaths: Atenolol vs. Captopril
UK Prospective Study Group. Efficacy of atenolol and captopril in reducing risk of macrovascular and microvascualr complications in type 2 diabetes.: UKPDS 39. BMJ 1998;317:713-720.
Years from Randomization0
Mor
talit
y (%
)20
1 2 3 4 5 6 7 8 9
10
0
15
5
Less Tight ControlCaptoprilAtenolol
P=0.28
SYSTOLIC HYPERTENSION IN THE ELDERLY PROGRAM (SHEP)
Diabetes Subgroup AnalysisEffect of Thiazide-Based Treatment on Blood Pressure
Curb JD, et al. Effect of diuretic-based antihypertensive treatment on cardiovascular disease risk in older diabetic patients with isolated systolic hypertension. JAMA 1996;276:1886-92.
PlaceboTreatment
Years
Blo
od P
ress
ure
(mm
Hg)
180160140120100
80604020
0
180160140120100
80604020
00 1 2 3 4 5 0 1 2 3 4 5
YearsB
lood
Pre
ssur
e (m
m H
g)
Diastolic
Systolic Systolic
Diastolic
No Diabetes Diabetes
SYSTOLIC HYPERTENSION IN THE ELDERLY PROGRAM (SHEP)
Diabetes Subgroup AnalysisEffect of Thiazide-Based Treatment on CV Events
Curb JD et al. Effect of diuretic-based antihypertensive treatment on cardiovascular disease risk in older diabetic patients with isolated systolic hypertension. JAMA 1996;276:1886-92.
0
10
20
40 Risk Reduction 34%
No Diabetes(n=4736)
Diabetes(n=583)
PlaceboTreatment
Perc
ent W
ith E
vent
s at 5
Yea
rs
18.4
13.3
31.5
21.4
30
Risk Reduction 34%
SCANDINAVIAN SIMVASTATIN SURVIVAL STUDY (4S)
Diabetes Subgroup AnalysisReduction of LDL-Cholesterol
Pyorala K et al. Cholesterol lowering with simvastatin improves prognosis of diabetic patients with coronary heart disease. Diabetes Care 1997;20:614-20.
No Diabetes Diabetes
n 4242 202
Baseline mmol/L 4.88 4.80 mg/dL 189 186
Reduction 34% 36%
SCANDINAVIAN SIMVASTATIN SURVIVAL STUDY (4S)
Diabetes Subgroup AnalysisReduction of Major Recurrent CV Events
Pyorala K et al. Cholesterol lowering with simvastatin improves prognosis of diabetic patients with coronary heart disease. Diabetes Care 1997;20:614-20.
Years Since Randomization
Prop
ortio
n W
ith M
ajor
CH
D E
vent 0.60
0
0.50
0.40
0.30
0.20
0.10
0.001 2 3 4 5 6
Placebo Simvastatin
Diabetes
Years Since Randomization
Prop
ortio
n W
ith M
ajor
CH
D E
vent 0.60
0
0.50
0.40
0.30
0.20
0.10
0.001 2 3 4 5 6
No DiabetesPlacebo Simvastatin
Risk Reduction 32% P=0.0001
Risk Reduction 55% P=0.002
CARE TRIAL
Diabetes Subgroup AnalysisReduction of LDL-Cholesterol by Pravastatin
Goldberg RB, et al. Cardiovascular events and their reduction with pravastatin in diabetic and glucose-intolerant myocardial infarction survivors with average cholesterol levels. Subgroup analysis in the Cholesterol And Recurrent Events (CARE) Trial. Circulation 1998;98:2513-19.
No Diabetes Diabetes
n 3573 586
Baseline mmol/L 3.59 3.52 mg/dL 139 136
On Pravastatin 40 mg mmol/L 2.56 2.48 mg/dL 99 96
Reduction 29% 29%
CARE TRIAL
Diabetes Subgroup AnalysisReduction of Recurrent CV Events
Goldberg RB et al. Cardiovascular events and their reduction with pravastatin in diabetic and glucose-intolerant myocardial infarction survivors with average cholesterol levels. Subgroup analysis in the Cholesterol And Recurrent Events (CARE) Trial. Circulation 1998;98:2513-19.
Years of Follow-up0
Perc
ent W
ith E
vent
45
PlaceboPravastatin
1 2 3 4 5
4035302520151050
0
Perc
ent W
ith E
vent
45
1 2 3 4 5
4035302520151050
PlaceboPravastatin
No Diabetes DiabetesRisk Reduction 23%P<0.001
Risk Reduction 25%P<0.05
CV Risk-Reduction With Antiplatelet TherapyHigh-Risk PatientsDiabetes Subgroup Meta-analysis
Antiplatelet Trialists Collaboration. Collaborative overview of randomized trials of antiplatelet therapy I: prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patient. BMJ 1994;308:71-2.
No Diabetes Diabetes
n 21,197 21,136
Vascular events Control 16.4% 22.3%
Antiplatelet Rx (usually ASA) 12.8% 18.5%
Risk Reduction 28% 21%
Targets and Tacticsfor
Typical Patients
UKPDS
Metabolic Profile at Diagnosis of Type 2 Diabetes
UK Prospective Diabetes Study Group. UK Prospective Diabetes Study 27. Plasma lipids and lipoproteins at diagnosis of NIDDM by age and sex. Diabetes Care 1997;20:1683-7.
Women Men
N 1574 2139
Age years 53 52
BMI kg/m2 30.8 28.3
FPG mmol/L 12.4 11.6 mg/dL 223 209
HbA1c % 9.3 9.0
BP mm/Hg 140/84 134/82
LDL-cholesterol mmol/L 3.90 3.35 mg/dL 151 139
ADA Glycemic Targets
American Diabetes Association. Standards of Medical Care for Patients with Diabetes Mellitus. Diabetes Care 1999;22(Suppl):S32-S41.
Normal Goal ActionLevel
HbA1c (%) <6 <7 >8
Fasting and preprandialblood glucose mmol/L <6.1 4.4 to 6.7 >7.8 mg/dL <110 80 to 120 >140
ADA Blood Pressure Targets
American Diabetes Association. Standards of Medical Care for Patients with Diabetes Mellitus. Diabetes Care 1999;22(Suppl):S32-S41.
Goal mm Hg
Usual patient <130/85
Isolated systolic hypertension If ≥180 <160 If 160 to 179 Reduce by 20
ADA LDL-Cholesterol Targets
American Diabetes Association. Standards of Medical Care for Patients with Diabetes Mellitus. Diabetes Care 1999;22(Suppl):S32-S41 & S56-S59.
Medical Nutrition Therapy Drug TherapyBegin Rx Goal Begin Rx Goal
With CV disease >100 ≤100 >100 ≤100
No CV disease >100 ≤100 >130 ≤100
Tactics for Reaching Glycemic Targets
Medical Management of Type 2 Diabetes, Fourth Edition, Zimmerman BR ed, American Diabetes Association, Alexandria, VA, 1998.
Lifestyle intervention Oral monotherapy Oral combination Oral-insulin combinations Multiple insulin injections
Tactics for Reaching Blood Pressure Targets
Kaplan NM. Hypertension in patients with diabetes. In Current Management of Diabetes Mellitus, ed. De Fronzo RA, Mosby, 1998.American Diabetes Association. Implications of the United Kingdom Prospective Diabetes Study. Diabetes Care 1999;22(Suppl):S56-S59.
Lifestyle Intervention Control weightLimit sodium and alcoholOptimize activity
Initial Drug Choices ACE-inhibitor or-blocker or Low-dose diuretic
Combinations Two or three of the aboveOther options• -blockers • Calcium antagonists• Hydralazine
Calcium Antagonists vs. Other AntihypertensivesControversy Over Use in Diabetes
Pahor M et al. Treatment of hypertensive patients with diabetes. Lancet 1998;351:690-1.
Trial Comparison Calcium RiskDrug Antagonist Ratio
ABCD Enalapril Nisoldipine 1/5.5
FACET Fosinopril Amilodipine 1/2.4
MIDAS Hydrochlorothiazide Isradipine 1/2.7
Tactics for Reaching Lipid Targets
American Diabetes Association. Management of Dyslipidemia in Adults with Diabetes. Diabetes Care 1999;22(Suppl):S56-S59.
Lifestyle Intervention Control weightLimit fatOptimize activity
Initial Drug Choices Usual patient• StatinTriglyceride >400 mg/dL• Fibric acid derivative
Combinations Statin + fibric acid derivativeOther options• Bile acid binding resins• Nicotinic acid
THE CURVES STUDY
LDL Reduction With Various Statins
Jones P et al. Comparative dose efficacy of atorvastatin versus simvastatin, pravastatin, lovastatin, and fluvastatin in patients with hypercholesterolemia. Am J Cardiol 1998;81:582-7.
Total Daily Dose (mg)
Mea
n %
Cha
nge
in L
DL
-C-10
10 mg 20 mg 40 mg 80 mg
-30
-60
-20
-50
-40
FluvastatinPravastatinLovastatinSimvastatinAtorvastatin
Summary
Epidemiologic and interventional evidence defines these targets HbA1c 7% Blood Pressure 130/85 mm Hg LDL-cholesterol 100 mg/dL
Basic treatment tactics include For glycemic control
– Oral and oral-insulin combinations For blood pressure control
– ACE-inhibitor, -blocker, and diuretic combinations For LDL-cholesterol control
– Statins For vascular protection
– ASA 81-325 mg daily