Epidemiology of DM

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Topic

• Epidemiology of DM
• Diagnosis of DM
• Classification pathogenesis of DM
• Screening of diabetes
• Metabolic syndrome
• Complication of DM
• Goal in management of DM

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Type 2 Diabetes is a CHD Risk FactorDiabetes and
Prior MI Predict Mortality Equally
No Diabetes or MI
100
Diabetes without MI
MI without Diabetes
80
60
Survival ()
Diabetes and MI
40
20
0
3
0
1
2
4
5
6
7
8
Year
Haffner SM, et al. N Engl J Med 1998339229-34.
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Global projections for the diabetes epidemic
20032025
48.4 58.6 17.4
23.0 36.2 36
39.3 81.6 52
7.1 15.0 52.6
15.6 22.5 44
43.0 75.8 43.3
World 2003 194million (5.1) 2025 333 million
(6.3) Increase of 42
Adapted from IDF Diabetes atlast 2005
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Countries with the highest numbers of estimated
cases of diabetes for 2030
Adapted from Wild SH et al. Diabetes Care 2004
27 256970.
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Prevalence of DM in Thaisthe National Health
Survey 1997 2004Population Survey for CHD Risk
2000
population age gt35 yr
1997 DM prevalence 4.8 Males 4.3
Females 5.3 Urban 6.9
Males 6.2 Females 7.6 Rural
3.8 Males 3.5 Females 4.2
2000 9.6 9.1
10.0 11.9 11.1 12.6
8.5 8.2 8.8
2004 10.8

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Topic

• Epidemiology of DM
• Diagnosis of DM
• Classification pathogenesis of DM
• Screening of diabetes
• Metabolic syndrome
• Complication of DM
• Goal in management of DM

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Criteria for Diagnosis of DM
Normal lt 100 lt 140
IFG 100 - 125 IGT
140 -199 DM gt
126 gt 200
Fasting Plasma Glucose (FPG) (mg/dL)
Random Plasma Glucose (mg/dL)
Stage
Pre-diabetes
Testing must be repeated on separate day . FPG
is the preferred test Symptoms of DM IFG
Impaired fasting glucose IGT Impaired
glucose tolerance Diabetes
care 2004 20 7
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Topic

• Epidemiology of DM
• Diagnosis of DM
• Classification pathogenesis of DM
• Screening of diabetes
• Metabolic syndrome
• Complication of DM
• Goal in management of DM

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Normoglycaemia
Hyperglycaemia
Stages
Diabetes Mellitus
Normal glucose tolerance
IGT and/or IFG (Pre-diabetes)
Not insulin requiring
Insulin requiring for control
Insulin requiring for survival
Types

• Type 1
• Autoimmune
• Idiopathic
• Type 2
• Predominantly
• insulin
• resistance
• Predominantly
• insulin
• secretory
• defects
• Other specific
• type
• Gestational
• diabetes

DIABETIC MEDICINE, 1998 15 535-553
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Natural History of Type 1 Diabetes
Fasting Glucose
Glucose
Autoimmune B Cell destruction begins
Relative Measure of insulin /insulin action
Islet cell antibodies appear
Genetic background At risk for Type 1 diabetes
Insulin Level
Time (Age dependent)
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Targeting the underlying factors in type 2
diabetes IR and ?-cell dysfunction
Genetic susceptibility obesity, sedentary
lifestyle
IR
?-cell dysfunction
Impaired insulin secretion
? hepatic glucose production
? glucose uptake
Type 2 diabetes
Adapted from DeFronzo RA. Diabetes 1988 37
66787.
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Conversion to type 2 diabetes stratified by
baseline IR and insulin secretion
Insulin resistant good insulin secretion
Insulin sensitive good insulin secretion
1.5
28.5
16
Insulin sensitive low insulin secretion
54
Insulin resistant low insulin secretion
San Antonio Heart Study baseline status for
insulin resistance and insulin secretion in
those converted to type 2 diabetes during 7-year
follow up n 195
Adapted from Haffner SM et al. Circulation 2000
101 97580.
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IR and ?-cell dysfunction are fundamental to
type 2 diabetes
Adapted from Burger HG et al. 2001. Diabetes
Mellitus, Carbohydrate Metabolism, and Lipid
Disorders. In Endocrinology. 4th ed. Edited by LJ
DeGroot and JL Jameson. Philadelphia W.B.
Saunders Co., 2001. Originally published in Type
2 Diabetes BASICS. International Diabetes Center,
Minneapolis, 2000.
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Progression of type2diabetes
Preclinical state
Clinical state
Normal IGT IFG
Type 2DM
Complications
Disability Death
Primary prevention
Secondary prevention
Tertiary prevention
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Decline in ?-cell function is associated with
loss of glycaemic control
Adapted from UKPDS Group. UKPDS 33. Lancet 1998
352 83753.
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Decline of ?-Cell Function in the UKPDS
Illustrates Progressive Nature of Diabetes
Time of diagnosis
100
?
80
60
?-Cell function ( of normal by HOMA)
Pancreatic function 50 of normal
40
20
0
10
9
8
7
6
5
4
3
2
1
0
1
2
3
4
5
6
Time (y)
UKPDSUnited Kingdom Prospective Diabetes Study
HOMAhomeostasis model assessment. Adapted from
Holman RR. Diabetes Res Clin Pract.
199840(suppl)S21-S25. U.K. Prospective Diabetes
Study Group. Diabetes. 1995441249-1258.
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Topic

• Epidemiology of DM
• Diagnosis of DM
• Classification pathogenesis of DM
• Screening of diabetes
• Metabolic syndrome
• Complication of DM
• Goal in management of DM

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SCREENING FOR DM (ADA)

• Who? 1. People gt 45 years old
• 2. People lt 45 yo., obesity
• ( BMI gt 25 kg/m2) with risk factors
• Frequency Every 3 years
• How ? Fasting plasma glucose

ADA 2006
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Screening for diabetes in adult

• Age gt 45 yr
• Overweight (BMI gt25 kg/m2)
• Family of diabetes (1st degree relative)
• Members of a high-risk ethnic population
• Hypertension ( BP gt140/90 mmHg)
• HDLlt35mg/dl or TG gt250mg/dl
• Previous IFG or IGT
• Previous GDM or baby gt 4 kg
• Polycystic ovarian syndrome
• History of vascular disease
• Habitually physically inactive

ADA 2006
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?????????????????????

• ??????????????????? 1 ??? ??????????????????????
  ??
• 1. Fasting plasma glucose (FPG) gt 126 mg/dl
  or
• 2. Casual plasma glucose (CPG) gt 200 mg/dl
• Symptoms
• or
• 3. 2-hour glucose concentration gt 200 mg/dl at
  
• 75 gram oral glucose tolerance test (OGTT)

ADA 2005
WHO 1998
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The Metabolic Syndrome

• In 1988, Reaven proposed the existence of a
  metabolic syndrome
• Constellation of risk factors for CVD
• Use the term
• Metabolic syndrome
• Syndrome X
• Insulin resistance syndrome

Definition of Metabolic Syndrome. Circulation
2004109433-438
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Metabolic syndrome IDF 2005
Central obesity (BMIgt30, waist circ. need not to be measured) waist circumference ?94 cm for Europid men ?80 cm for Europid women, with ethnicity specific values for other groups
gt 2 criteria gt 2 criteria
Plasma glucose Hypertriglyceridemia Low HDL Hypertension gt 100 mg/dl gt 150 mg/dl lt 40 mg/dl (men) lt 50 mg/dl (women) 130/85 mmHg
IDF Consensus Worldwide Definition of the
Metabolic Syndrome. www.idf.org.
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Topic

• Epidemiology of DM
• Diagnosis of DM
• Classification pathogenesis of DM
• Screening of diabetes
• Metabolic syndrome
• Complication of DM
• Goal in management of DM

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Acute Complications of Diabetes Mellitus
- Hypoglycemia - Diabetic Ketoacidosis
(DKA) - Hyperosmolar Nonketotic Diabetic coma
(HONK) Hyperosmolar hyperglycemic state
(HHS) - Infection
30
50 of type 2 diabetes patients have
complications at the time of diagnosis1
MICROVASCULAR
MACROVASCULAR
Retinopathy, glaucoma or cataracts
Cerebrovascular disease
Coronary heart disease
Nephropathy
Peripheral vascular disease
Neuropathy
1UK Prospective Diabetes Study Group. UKPDS 33.
Lancet 1998 352 83753.
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Diabetes Is Associated With Significant Global
Morbidity and Mortality

• Morbidity1,2
• CVD
• 2-4 times more likely to develop myocardial
  infarction or stroke
• Neuropathy
• Up to 50 of persons with diabetes
• A leading cause of amputation
• Retinopathy
• A leading cause of blindness
• After 15 years of diabetes
• 2 blindness
• 10 severe visual handicap
• Nephropathy
• A leading cause of kidney failure
• Accelerates CVD

• Mortality2
• Annual diabetes-associated deaths worldwide
• gt800,000 directly attributed to diabetes
• 4 million attributed to complications of
  diabetes
• 50 of deaths in persons with diabetes in
  industrialised countries are due to CVD

• CVDcardiovascular disease.
• International Diabetes Federation. Available at
  http//www.idf.org/home/index.cfm?node201.
  Accessed 15 May 2004.
• World Health Organization. Available at
  http//www.who.int/hpr/NPH/docs/gs_diabetes.pdf.
  Accessed 11 April 2004.

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A 1 decrease in HbA1c significantly reduces
microvascular and macrovascular complications
Any diabetes-related endpoint
Diabetes- related death
All cause mortality
Peripheral vascular disease
Microvascular disease
Cataract extraction
MI
Stroke
0
5
21
21
14
14
12
43
37
19
10

15


20

Percentage reduction in relative risk
corresponding to a 1 fall in HbA1c


25
30
35

40
45

50
Lower extremity amputation or fatal peripheral
vascular disease P lt 0.0001 P 0.035
Adapted from Stratton IM et al. UKPDS 35. BMJ
2000 321 40512.
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Tight BP Control
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UKPDS Risk Factors for Coronary Artery Disease
in Type 2 Diabetes

• Identified 5 major risk factors for CAD
• Dyslipidemia
• (High LDL, Low HDL)
• Hyperglycemia
• Hypertension
• Smoking

Turner, RC et al. BMJ 316823-8, 1998
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Multifactorial Intervention and Cardiovascular
Disease in Patients with Type 2 Diabetes
STENO 2
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Multifactorial Intervention and Cardiovascular
Disease in Patients with Type 2 Diabetes( STENO
2 )

• Randomized study to evaluate effect on CVD of an
  intensified, targeted, multifactorial
  intervention in T2DM with microalbuminuria
• 160 patients follow up means 7.8 years
• Interventions dietary, exercise, ACEI or ARB,
  vitamin mineral supplement, 150 mg ASA, tight
  glycemic, BP and lipid control

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Steno-2 effect of intensive versus conventional
treatment on cardiovascular complications
n Conventional 80 72 70 63 59 50 44 42 13 Intensiv
e 80 78 74 71 66 63 61 59 19
Primary composite endpoint of death from
cardiovascular causes, non-fatal MI, CABG,
percutaneous coronary intervention, non-fatal
stroke, amputation or surgery for peripheral
atherosclerotic artery disease
Gaede P et al. N Engl J Med 2003 348 38393.
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Percentage of patients who reached the
intensive-treatment goals at a mean of 7.8
y
P lt0.001
P 0.21
P 0.19
P 0.001
Patients
P0.06
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DCCT/EDIC Glycaemic control reduces the risk of
non-fatal MI, stroke or death from CVD in type 1
diabetes
9
Conventional treatment
HbA1C ()
8
Intensive treatment
7
0
Years
1
6
2
3
4
5
7
8
9
11
12
13
14
15
16
17
10
DCCT (intervention period) EDIC (observational
follow-up)

• Concept of Glucose memory the better the control
  of glucose early in disease, the less the risk of
  complications later even when control is less
  satisfactory. in type 1 diabetes without
  insulin resistance etc

0.06 0.04 0.02 0.00
57 risk reduction in non-fatal MI, stroke or
CVD death(P 0.02 95 CI 1279)
Conventionaltreatment
Cumulative incidence of non-fatal MI, stroke or
death from CVD
Intensivetreatment
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
19 20 21
Years
DCCT (intervention period) EDIC
(observational follow-up)
Intensive versus conventional treatment
Adapted from DCCT. N Engl J Med 1993
329977986. DCCT/EDIC. JAMA 2002
28725632569. DCCT/EDIC. N Engl J Med 2005
35326432653.
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UKPDSRisk ReductionGlucose Control Study (After
median 8.5 yr. post-trial follow- up)
Legacy effect
1997 2002 2007
Any diabetes related end point 12 P0.029 10 P0.033 9 P0.040
Microvascular disease 25 p 0.009 28 p 0.001 24 p 0.001
Myocardial infarction 16 p 0.052 14 p 0.042 15 P0.014
All cause mortality 6 p 0.440 11 p 0.071 13 P0.007
Concept of glucose? memory valid in type 2
diabetes
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Topic

• Epidemiology of DM
• Diagnosis of DM
• Classification pathogenesis of DM
• Screening of diabetes
• Metabolic syndrome
• Complication of DM
• Goal in management of DM

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Aim of Diabetic therapy

• Prevention of S/S of hyper/hypoglycemia
• Prevention of acute and chronic complications
• Good quality of life

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Current recommendations of the Canadian and
American Diabetes Associations
Diabetes must be . . . diagnosed earlier. And
once diagnosed, all types of diabetes must then
be managed much more aggressively Canadian
Diabetes Association Therefore, the results of
the UKPDS mandate that treatment of type 2
diabetes include aggressive efforts to lower
blood glucose levels as close to normal as
possibleADA
Canadian Diabetes Association. Can J Diabetes
2003 27 (Suppl 2) 1163 ADA. Diabetes Care
2003 26 S2832.
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GOAL
Goal
Plasma glucose  - Average pre-prandial PG
(mg/dl) 90-130 - Peak postprandial PG
(mg/dl) lt180 - HbA1C () 
lt7 (6.5) Lipid  - Total Chol (mg/dl)
lt200 (180) - Triglyceride
(mg/dl)  lt150 - HDL-C (mg/dl)
Mgt40,Fgt50 - LDL-C - age
lt40, total chol gt135 risk factor lt
100 mg/dl - age gt40, total chol gt135 ,
30-40 of LDL-C (lt 100) - overt
CVD ( very high risk) lt70 BP
(mmHg) lt130/lt80
ADA 2006
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Goals of Glycemic Control

• ADA ACCE EASD
  IDF
• HbA1c (4.0-6.0) lt 7.0 6.5 6.5
  6.5
• FPG (preprandial) lt 130 110 110
  110
• Postprandial lt 180 140 135
  135
• Bedtime PG lt 150 ? ? ?

1. ADA. Diabetes Care 2004 27 S1535 2. ADA
Diabetes Care 2002 25 S35493. Feld S.
Endocrine Pract 2002 8 (Suppl 1) 4082 4.
Asian-Pacific Type 2 Diabetes Policy Group. Type
2 diabetes Practical targetsand treatment. 3rd
Edn Hong Kong Asian-Pacific Type 2 Diabetes
Policy Group, 2002.
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2008
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2008
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UKPDS