www.drsarma.in
Prof. Dr. Sarma VSN Rachakonda
M.D., M.Sc., (Canada), FCGP, FIMSA, FRCP (Glasgow),
FCCP (USA).,
Senior Consultant Physician, Cardio-metabolic & Chest
Specialist,
Visiting Professor of Internal Medicine, SBMC, FLL, iDRF,
Chennai
The Outline of the Presentation
Burden, Diagnostic criteria
Who should be screened
Significance Prediabetes
Evidence from research studies
Risk Scores - Application
Primary prevention of T2DM
How Big is the Problem?
35% of adults over 20 years
50% of those over 65 years
79 million Americans in 2010
Double the number in India
CDC. National Diabetes Fact Sheet: National estimates and
general information on diabetes and Prediabetes in the United States, 2011.
Natural History of T2D
Obesity
IGT*
Diabetes
Uncontrolled
Hyperglycemia
Post-meal
Glucose
Plasma
Glucose
Fasting Glucose
120 (mg/dL)
Relative -Cell
Function
Insulin Resistance
100 (%)
Insulin Level
-20
-10
Endocrinol Metab Clin North Am.1997;26:659-677;
0
10
20
Years of T2DM
30
ADA Diagnostic Criteria for Diabetes
Clinical Practice Recommendations 2010
1. A1C ≥6.5%. The test should be performed as per
NGSP method and standardized to the DCCT
assay.*
2. FPG ≥126 mg/dl. – No caloric intake for at least 8
h.*
3. 2-h plasma glucose ≥200 mg/dl OGTT performed
using 75 anhydrous glucose dissolved in water.*
4. Random plasma glucose ≥200 mg/dl + classic
symptoms of hyperglycemia or hyperglycemic crisis.
* In the absence of unequivocal hyperglycemia, criteria 1–3 should be confirmed by repeat testing
Diagnostic Cut Points
Category
A1C
FPG (mg/dL)
Normal
5.7
< 100
Prediabetes
- 6.4
100 -125
140 -199
5.7
> 126**
> 200 **
>
Diabetes
6.5
2h 75g OGTT
< 140
Or patients with classic hyperglycaemic
Diabetes Care 34:Supplement 1, 2011
symptoms with plasma glucose >200
<
How is Prediabetes Diagnosed ?
Categories of increased risk for diabetes
Impaired Fasting Glucose [IFG]
FPG of 100–125 mg/dl
Impaired Glucose Tolerance [IGT]:
2-hour Plasma Glucose on the 75-g Oral
Glucose Tolerance Test 140–199 mg/dl
A1C 5.7 – 6.4%
For all three tests, risk is continuous, extending below the lower limit of the
range and becoming disproportionately greater at higher ends of the range.
Gestational Diabetes (GDM)
Overnight fast
75g OGTT
• Fasting
>92 mg/dl
• 1 h post glucose
>180 mg/dl
• 2 h post glucose
mg/dl
>153
Any ONE abnormal value is
adequate
Diabetes Care 34:Supplement 1, 2011 Diabetes Care 2010; 33: 676–682
Risk Factors for the Development of
Prediabetes and Type 2 Diabetes
• Age 45 or older
• Overweight – BMI
>25
• HT and/or on Rx for
HT
• Previous Prediabetes
• Physical Inactivity
• TG > 200, HDL < 35
• Asian or African
ethnicity
• Acanthosis Nigricans
• Family H/o of
Diabetes
• Excess abdominal fat
• PCOS, IR, Waist
Circum
• H/o GDM, CVD
• Had macrosomic
Modifiable Risk Factors for T2DM
• Obesity, Body fat distribution
• Increased waist circumference
• Physical inactivity
• Elevated fasting and 2 hr glucose levels
• Dyslipidemia and Hypertension
• Smoking and Alcohol
Physical Inactivity and TV watching
3.0
2.5
RR
2.0
1.5
1.0
<10.0
10.0-23.5
0.5
23.6-45.9
0
>15.0
8.1-15.0
Quartiles of no. of hours
watching TV per week
46.0
3.6-8.0
Hu et al. Arch Intern Med. 2001;161:1542.
3.5
Quartiles of
MET - hours per week
Natural History of IGT
25% • IGT
IGT -after
10 years
25% • Normal
50% • T2DM
Does Prediabetes Predict Diabetes?
Progression of IGT/IFG to DM in11year follow up
Persons with IGT
Persons with IFG
Stephen Twigg. Pre diabetes Symposium ADS & ADEA Annual Scientific Meeting Sydney 2004
Risk of Cardiovascular Disease is
elevated prior to diagnosis of T2DM
% with CVD
CVD Risk 3.2 higher adjusting
for all CVD risk factors
Adapted from: Hu F, et al. Diabetes Care. 2002;25:1129-1134.
The Prevalence of T2DM & Obesity
Diabetes
Mean body weight
$ spent on fast food
78
7.0
(110)
77
6.5
65% of US adults
are overweight
76
6.0
75
kg
Prevalence (%)
7.5
5.5
74
5.0
4.5
73
4.0
1990
72(70)
1992
1994
1996
1998
2000
Year
JAMA.1999;282:1519-1522 & JAMA.2001;286:1195-1200.
Prevalence of
obesity, increased
by 61% since 1991
BMI and weight
gain
major risk factors
for diabetes
What are the Health Risks
Associated with Prediabetes?
• Progression to diabetes: 11% of people
with pre-diabetes develop T2DM each year
(DPP)
• Other studies: majority with Prediabetes
develop T2DM in 10 years
• Microvascular complications at onset of DM
• 50% higher risk of CVD, CAD and Stroke
Feasibility of Preventing T2DM
• There is a long period of glucose intolerance that
precedes the development of diabetes
• Screening tests can identify persons at high risk
• Predicts high risk for development of diabetes
• Predicts high risk for development of atherosclerotic
vascular disease
• There are safe, potentially effective interventions
that can prevent the above modifiable risk factors
such as lifestyle and pharmacologic interventions
Diabetes Prevention Program DPP
Progression to Type 2 Diabetes
Cases/100 person-years
Average follow-up of 2.8 years
 31%*
 58%*
Placebo
Metformin
Intensive
lifestyle
*All pairwise comparisons significantly different by group;
The Diabetes Prevention Program Research Group. N Eng. J Med. 2002;346:393.
Mean Change in Physical Activity
Lifestyle
MET-hours/week
8
6
4
Metformin
2
Placebo
0
0
1
2
Years from Randomization
The DPP Research Group, NEJM 346:393-403,2002
3
4
Mean Weight Change
Placebo
Metformin
Lifestyle
The DPP Research Group, NEJM 346:393-403, 2002
Percent of
developing
diabetes in DPP
Incidence
Diabetes
Placebo (n=1082)
All participants
Metformin (n=1073, p<0.001 vs. Placebo)
Lifestyle (n=1079, p<0.001 vs. Met , p<0.001 vs. Plac )
Lifestyle
(n=1079,
p<0.001
vs. Metformin
Metformin
(n=1073,
p<0.001
vs. Plac) ,
Placebo (n=1082)p<0.001 vs. Placebo)
Cumulative incidence (%)
40
30
Risk reduction
31% by metformin
58% by lifestyle
20
10
0
0
1
2
Years from randomization
The DPP Research Group, NEJM 346:393-403, 2002
3
4
Mean Change in HbA1c
Placebo
HbA1c (%)
6.1
6.0
Metformin
Lifestyle
5.9
5.8
0
1
2
Years from Randomization
The DPP Research Group, NEJM 346:393-403, 2002
3
4
A Decade Later….DPPOS
The Lancet, Oct 2009
• At end of DPP: participants 16-session program of intensive TLC
Parameter
Placebo
Metformin 850 mg
bid
TLC: MNT, PA
Weight Loss
<2 lbs
5 lbs
5 lbs
11%
7.8%
4.8%
Diabetes at 2.8 yrs
Diabetes at 10 yrs
5-6%
Percent reduction
-
18
34
Delay in diabetes
-
2 yrs
4 yrs
• Lifestyle group: 34% reduction in diabetes risk maintained
• More favorable CV risk factors: BP and TG’s, despite fewer drugs
• Benefits more pronounced in elderly: 50% reduction in age >60
The Finnish Diabetes Prevention Study
Lifestyle Modifications
• 522 overweight individuals with IGT randomized to
– Control: diet instruction at the onset of study
– Individualized advice given 7 times in the first year and
every 3 months thereafter with goals of
» Weight loss 5%
» Reducing fat intake to <30% of energy consumption
» Increasing fiber intake to 15 g/1000 kcal
» Exercising at a moderate level for 30 min/d
• Primary end point: Prevention of diabetes, assessed by
OGTT
Tuomilehto et al. N Engl J Med. 2001;344:1343.
Indian Diabetes Prevention Program
Ramachandran et al, IDDP-1, Diabetologia (2006) 49: 289–297.
Cumulative Incidence of Diabetes
Low BMI
High IR
High incidence of DM
Ramachandran et al, IDDP-1, Diabetologia (2006) 49: 289–297.
Incidence of diabetes
(cases/1000 person-years)
The Finnish Diabetes Prevention Study
Lifestyle Modifications (cont’d)
Tuomilehto et al. N Engl J Med. 2001;344:1343.
 58%
Cumulative incidence of diabetes
at 6 years Da Qing Chinese Study
Data from: Pan et al, Diabetes Care, 1997; 20: 537-44
NAVIGATOR Study
Effect of Nateglinide & Valsartan on Incidence of T2DM
and CV Events - 9306 persons with IGT, CVD or CV risk
followed for 5 years
• Nateglinide: A postprandial glucose-lowering
approach; incidence of diabetes 36% vs. 34%;
composite CV outcome 14.2% vs. 15.2%;
increased the risk of hypoglycemia
• Valsartan: incidence of diabetes 33.1% vs.
36.8% (RR 14%); 38 fewer cases per 1000 pts
treated for 5 years; no reduction in rate of CV
events
NEJM online, March 14, 2010
Prevention Studies in People with IGT
Downstream strategies
• Lifestyle interventions
– Da Qing :
Diet and Exercise
– Malmo study : Diet and exercise
– Finish Diabetes Prevention Study Lifestyle
– DPP (Diabetes Prevention Study) Lifestyle, MF
(Glitazone)
• Lifestyle interventions with pharmacological agents
– FHS (Fasting Hyperglycaemia Study) Healthy Living &
SU
– EDIT (Early Diabetes Intervention Study): Acarbose and
MF
– STOP NIDDM : Acarbose
How to Ascertain the Risk ?
• Low Risk - 3 to 9 points
• Maintain healthy wt.
• High Risk 10+ points
• Regular exercise
• High risk for diabetes
• Keep it up regularly
• Medical evaluation
• Take steps to improve
score
Framingham DM Risk Score
Prediction of Incident DM in Adults
Variable
Points
Fasting glucose level 100-126 mg/dL
10
BMI 25.0-29.9
2
BMI >30.0
5
HDL-C level <40 mg Men, <50 mg
Women
5
Parental H/o of Diabetes Mellitus
3
Triglyceride level >150 mg/dL
3
Blood pressure >130/85 mm or on Rx.
2
Points
8 yr. Risk%
≤10
<3
11
4
12
4
13
5
14
6
15
7
16
9
17
11
18
13
19
15
20
18
21
21
22
25
23
29
24
33
≥25
>35
Wilson, P. W. F., J. B. Meigs, et al. (2007). Arch Intern Med 167(10): 1068-1074.
Based on CUREs study Chennai
Indian Diabetes Risk Score (IDRS)
Parameter
Score
Age in years
< 35
0
35 - 49
20
≥ 50
30
Abdominal obesity
Waist <80 cm (F), <90 (M)
0
Waist 80-89 cm (F), 90-99 (M)
10
Waist .>90 cm (F), >100 (M)
20
Physical Activity
Exercise (regular) + strenuous work
0
Exercise (regular) or strenuous work
20
No exercise and sedentary work
30
Family History of DM
No family history
0
One parent
10
Both parents
20
A1c Level and Future Risk of T2DM
A1C
Risk of
Diabetes
<5.0%
0.1%
5.0 -5.4%
5.4%
5.5-6.0%
9 - 25%
>6.0-6.5%
25 - 50%
• Meta-analysis of 16 studies
• 44,203 participants
• Follow-up 5.6 years
Zhang, X., E. W. Gregg, et al. (2010). Diabetes Care 33(7): 1665-73.
Prediabetes and Risk of CVD
Definition of
Pre-diabetes
Risk of
CVD
IFG (100-125 mg/dl)
1.18
IFG (110-125 mg/dl)
1.20
IGT
1.20
• Meta-analysis of 18
studies
• 175,152 participants
Ford, E. S., G. Zhao, et al. (2010). J Am Coll Cardiol 55(13): 1310-7.
ADA Consensus Statement
Preventive treatment in high risk
individuals with Prediabetes
• In addition to lifestyle modification, the following
individuals should be considered
for
treatment with metformin:
– those who have both IFG and IGT, and
– at least one additional risk factor (age < 60, BMI
≥35, F H/o of diabetes,  TGs,  HDL, or A1C >
6%
Diabetes Care 2007
Prevention of Diabetes
Recommendations to reduce risk of type 2 diabetes
– Regular physical activity
– Interventions to reduce obesity
» Waist circumference,
» body weight and body mass index (BMI)
» identify individuals for weight management program
– Individuals at risk should have dietary intake assessed
and receive individualised dietary advice and continued
diet advice
Evidence Based Guideline for the Prevention of Type 2 Diabetes.
Australian Government NHMRC www.diabetesaustralia.com.au
Prevention of Diabetes
Recommendations to reduce risk of type 2 diabetes
–Identification of women with GDM would allow:
»Postnatal clinical interventions in those with
diabetes
»Option to use preventive methods to
DM
the risk of
–Diet and exercise education in children should include
»Parental involvement
»Behavioral techniques
Evidence Based Guideline for the Prevention of Type 2 Diabetes.
Australian Government NHMRC www.diabetesaustralia.com.au
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Thank you all