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John MF Adam
Obesity is defined as a
condition in which there is an
excess of body fat. The
operational definitions of
obesity and overweight
however are based on BMI
which is closely correlated
with body fatness
OBESITY - EPIDEMIOLOGY
The prevalence rate of obesity are increasing in
almost all parts of the world, among male as well
as female.
Although varied between countries, several natio
nal health surveys in Asian countries showed a
rapid increase of overweight and obesity,
Postprandial
Plasma
Glucose
(mg/dl)
126
Fasting
Insulin Resistance
ß-cell
function
(%)
100
Insulin Level
-20 -10 0 10 20 30
Diabetes duration (years)
Adapted from IDC, Minneapolis
WHAT IS PREDIABETES
In 1997,The Expert Committee on the Diagnosis
and Classification of Diabetes Mellitus introduced
the term Prediabetes :
“intermediate group of individuals whose
glucose levels, although not meeting criteria
for diabetes, are nevertheless too high to be
considered normal “
Prediabetes IFG FPG levels 100 – 125 mg/dl
IGT 2-H OGGT values 140 – 199 mg/dl
NEW DIAGNOSTIC CRITERIA
FOR DIABETES IN ADULTS (ADA 2010)
3 **
Adjusted for age and sex
** p<0.01 vs normal
Relat ive Risk
* p<0.05
2 *
CVD
Conclusions :
DPP 2.155 IGT, BMI > 24 kg/m2 51 2.8 Metformin 31 (17- 43)
FPG> 5.3 mmol/L (1.700 mg)
STOP NIDDM 1.419 IGT, FPG > 5.6 54 3.2 Acarbose 25 (10- 37)
Mmol/L (300 mg)
DREAM 5.269 IGT or IFG 55 3.0 Rosiglitazone 60 (54- 65)
(8 mg)
ACT- NOW 602 IGT or IFG 52 2.6 Pioglitazone 81 (61-91)
(45 mg)
Cumulative incidence of
diabetes (%) 30
Metformin 31%
10
0
0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0
Year
Cumulative incidence of diabetes according to study group in the DPP. The incidence of
diabetes differed significantly among the three groups (P < .001 for each comparison).
Knowler WC, et al. N Engl J Med 2002; 346: 393 - 403
Diabetes Prevention Program Research Group.
Reduction in the incidence of type 2 diabetes
with lifestyle intervention or metformin
Knowler WC, et al. N Engl J Med 2002; 346: 393 – 403
Conclusion
Lifestyle change and treatment with metformin both
reduced the incidence of diabetes in persons at high risk.
The lifestyle intervention was more effective than
metformin
STOP-NIDDM Trial Research Group. Acarbose
for prevention of type 2 diabetes mellitus:
the STOP-NIDDM randomized trail
Chiasson JL, et al. Lancet 2002; 359: 2072 – 2077
0.85
0.80 P = 0,0022
0.75
0.70
0.65
0.60
0.55
0.50
0.45
0.40
0 00 00 00 00 00 00 00 00 00 00 00 00
0
1 0 2 3 4 5 6 7 8 9 10 11 12 13
Days after randomization
Effect of acrbose and placebo on the cumulative probability of remaining free of
diabetes during the STOP-NIDDM trial
Chiasson JL, et al. The Lancet 2002; 359: 2072
STOP-NIDDM Trial Research Group. Acarbose
for prevention of type 2 diabetes mellitus:
the STOP-NIDDM randomized trail
Chiasson JL, et al. Lancet 2002; 359: 2072 – 2077
Conclusion
Acarbose could be used, either as an alternative or in
addition to changes in lifestyle, to delay development of
type 2 diabetes in patients with impaired glucose
tolerance
Protection from type 2 diabetes persists
in the TRIPOD cohort eight months after
stopping troglitazone
Buchanan TA, et al. Diabetes 2001; 50 (suppl 2): A81
40
diabetes (%)
Placebo
20 55%
Troglitazone
0
0 12 24 36 48 60
Month trial
Cumulative incidence rates of type 2 diabetes in women who were enrolled in TRIPOD study.
The rate in the troglitazone groups significantly less than the rates in the placebo group (p=
,009)
Buchanan TA, et al. Diabetes 2002; 51: 2798 - 2803
Protection from type 2 diabetes persists
in the TRIPOD cohort eight months after
stopping troglitazone
Buchanan TA, et al. Diabetes 2001; 50 (suppl 2): A81
Conclusion
Treatment with troglitazone delayed or prevented
the onset oft type 2 diabetes in high risk hispanic
women (GDM)
Effect of rosiglitazone on the frequency of diabetes
in patients with impaired glucose tolerance or
impaired fasting glucose: a randomized controlled
trial. The Diabetes Reduction Assessment with
Ramipril and Rosiglitazone Medication
(DREAM Study)
Gerstein HC, et al. Lancet 2006; 368: 1096-1105
Proportional %
50.5
50
43.7
40 P<0.0001 37.9
30.3
30 26.0
20
11.6
10
0
Diabetes IGT, IFG, or Normal +
both FPG < 6.1 mmol/L
60
B 53.5
50 49.8
Proportional
P<0.0001
40 38.6
%
30 26.0
20.5
20
11.6
10
0
Diabetes IGT, IFG, or both Normal +
FPG < 6.1 mmol/L
6.4 8.6
6.2 8.2
Placebo
6 7.8
5.8 7.4
Placebo
5.6 7
5.2
0 0
Base 1 2 3 4 Final Base 2 3 4 Final
Effect of rosiglitazone on the point estimates of (A) fating plasma glucose (FPG) and (B)
2-h plasma glucose (PG) concentrations. Lancet 2006; 368: 1096-1105
0.6
Placebo
Rosiglitazone
0.5
0.4
Cumulative
hazard
0.3
0.2
0.1
0.0
0 1 2 3 4
Years
Conclusion
Rosiglitazone at 8 mg daily for 3 years substantially
reduces incident type 2 diabetes and increases the
likelihood of regression to normoglycaemic in adults
with impaired fasting glucose or impaired glucose
tolerance, or both
ACTos NOW Study for the Prevention
of Diabetes (ACT NOW study)
602 IGT were randomized to receive pioglitazone 45
mg/day or placebo
The primary end point is the conversion of IGT to
type DM based on FPG > 126 mg/dl or 2-OGTT >
200 mg/day
Results (late breaking abstract June 2008):
risk reduction of 81%
TYPE 2 DIABETES: A CHRONIC PROGRESSION DISEASE
Postprandial
Plasma
Glucose
(mg/dl)
126
Fasting
Insulin Resistance
ß-cell
function
(%)
100
Insulin Level
-20 -10 0 10 20 30
Diabetes duration (years)
Adapted from IDC, Minneapolis
THIAZOLIDINDIONE
AND THE PREVENTION OF DIABATES
Tripod study risk reduction 55.0%
DREAM study 60.0%
ACT NOW study 80.0%
15
*
10
5
0
-5
-10 *
-15 *
-20
-25
LDL-C HDL-C
*
Triglycerides Total cholesterol
Pioglitazone + glimepiride
25
Rosiglitazone + glimepiride
20
% change from baseline to 1 year
15 *
10
5
0
-5
-10
-15 *
-20
-25 *
LDL-C HDL-C Triglycerides