prevention of diabetes mellitus prof. adel el-etriby professor of cardiology ain shams faculty of...
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Prevention of
Diabetes Mellitus
Prof. Adel El-EtribyProfessor of Cardiology
Ain Shams Faculty of Medicine
Rationale for Prevention
The incidence of type 2 of diabetes is increasing in epidemic proportions throughout the world.
Once type 2 diabetes develops, it is difficult to treat.
Prevention of type 2 diabetes would result in a significant reduction in social and economic costs.
Data from World Health Organization. Available at http://www.who.int/ncd/dia/databases3.htm. Accessed April 26, 2003.
Prevalence of IGT in Different Ethnic Populations
African & Asian
% o
f P
op
ula
tio
n
0
2
4
6
8
10
12
14
European Pacific American
MenWomen
30 to 64 Years of Age
Current and Projected Prevalence Rates for Diabetes
80
0
10
20
30
40
50
Africa Americas EasternMediterranean
Europe SoutheastAsia
Est
imat
ed P
reva
l en
ce (
mi l
lio
ns) 1995 2000 2025
60
70
WesternPacific
World Health Organization. World Health Report 1997: Message from the Director-General. Available at www.who.int/whr/1997/message.pdf. Accessed November 8, 2002.
Risk Factors for Type 2 Diabetes
Type 2 Type 2 DiabetesDiabetesType 2 Type 2
DiabetesDiabetes
Gestational diabetes, polycystic ovarian
syndrome, and parity
Increasing age
Genetic factors• Ethnicity• Family history
Central obesity
Physical inactivity
Diet
Risk of type 2 diabetes associated with level of physical activity
0
0.2
0.4
0.6
0.8
1
Q1 Q2 Q3 Q4 Q5
Hu et al., JAMA 282:1433, 1999
Adjusted for age, smoking. hypertension,family history, menopause, high cholesterol
Quartile of physical activity vs Q1
Rel
ativ
e R
isk
-23% -25% -38% -46%
8 year follow-up
U.S. Nurses Health Study
Genetic predisposition
Preclinical state
Normal IGT
DisabilityDeath
Clinical disease
NIDDM DisabilityDeath
Complications
Complications
Primary Secondary Tertiaryprevention prevention prevention
Stages in the natural history of Type 2 diabetes
Recent Prospective Diabetes Prevention Trials Finnish Diabetes Prevention Study (DPS)
Chinese Prevention Trial
US Diabetes Prevention Program (DPP)
Study to Prevent Non–Insulin-Dependent Diabetes Mellitus (STOP-NIDDM trial), Europe
Troglitazone in Prevention of Diabetes Study (TRIPOD), United States
Xenical in the Prevention of Diabetes in Obese Subjects (XENDOS) Study, Sweden
Finnish DPS: Intensive Lifestyle Intervention Reduces Diabetes Risk
Adapted from Tuomilehto J et al. N Engl J Med. 2001;344:1343-1349.
0.5
0.6
0.7
0.8
0.9
1.0
0 1 2 3 4 5 6
Years
Cu
mu
lati
ve P
rob
abil
ity
of
No
Dia
bet
es
Intervention
Control
58% reduction in relative risk
Data from Yang W et al. Chin J Endocrinol Metab. 2001;17:131-136.
Chinese Prevention Trial: Lifestyle Intervention, Acarbose, and Metformin Reduce Risk of Diabetes
0
20
40
60
80
100
120
Control Diet + Exercise Acarbose Metformin
RR
of
Dev
elo
pin
gD
iab
etes
Ove
r 3
y
P = .09
P = .0001
P = .0002
• 43% reduction in relative risk (RR) with diet + exercise• 88% reduction in RR with acarbose• 77% reduction in RR with metformin
DPP: Metformin/Lifestyle Advice Reduces Diabetes Risk
Lifestyle advice: 58% decrease in diabetes incidence
Metformin: 31% decrease in diabetes incidence
Data from DPP Research Group. N Engl J Med. 2002;346:393-403.
0
10
20
30
40
Placebo Metformin Lifestyle
Cu
mu
lati
ve I
nci
den
ce
of
Dia
bet
es a
t 3
y (%
)
P <.001
P <.001
STOP-NIDDM: Acarbose Reduces Diabetes Risk
Adapted from Chiasson J-L et al. Lancet. 2002;359:2072-2077.
0.40
0.50
0.60
0.70
0.80
0.90
1.00
0 100 200 300 400 500 600 700 800 900 1000 1100 1200 1300
Days After Randomization
Cu
mu
lati
ve P
rob
abil
ity
of
No
Dia
bet
es
Acarbose
Placebo
P = .0022
• 25% reduction in RR
TRIPOD: Troglitazone Reduces Diabetes Risk
Data from Buchanan TA et al. Diabetes. 2002;51:2796-2803.
0
5
10
15
20
25
Placebo Troglitazone
An
nu
al I
nci
den
ce o
f D
iab
etes
(%
)
P <.01
• 55% reduction in RR (30 mo on drug)
XENDOS: Orlistat Reduces Diabetes Risk
Sjöström L et al. Poster presented at: Ninth International Congress on Obesity. São Paulo, Brazil. August 24-29, 2002.
0
2
4
6
8
10
Placebo Orlistat
Cu
mu
lati
ve I
nci
den
ce o
f T
ype
2 D
iab
etes
(%
)
P = .0032
• 37% reduction in RR
New-Onset Diabetes in Trials Using Inhibitors of the RAAS
HOPE: Heart Outcomes Prevention Evaluation Study
CAPPP: Captopril Prevention Project
SOLVD: Studies of Left Ventricular Dysfunction
LIFE: Losartan Intervention for Endpoint Reduction Study
HOPE Study: ACE Inhibitor Ramipril Reduces Risk of Cardiovascular Disease and Diabetes in High-Risk Patients
Data from HOPE Study Investigators. N Engl J Med. 2000;342:145-153.
33% risk reduction33% risk reduction
0
5
10
15
20
Primary End Point: Composite of MI,Stroke, Death from CV Causes
Pa
tie
nts
(%
)
P <.001
0
5
10
New Diagnosis of Diabetes
P <.001
Placebo Ramipril
CAPPP Study: Results
Data from Hansson L et al. Lancet. 1999;353:611-616.
13% risk reduction13% risk reduction
0
5
10
15
20
Primary End Point: Composite ofFatal and Nonfatal MI, Stroke, Death
from CV Causes
Pa
tien
ts (
%)
P = NS
0
5
10
Incidence of Diabetes
P <.04
Conventional Captopril
SOLVD: Enalapril Reduces New-Onset Diabetes Risk in CHF Patients
0
6
12
18
24
30
36
Placebo Enalapril
P <.0001
• 16.5% absolute risk reduction in development of diabetes
No
. of
New
Dia
bet
es C
ases
N = 291
Vermes E et al. Circulation. 2003;107:1291-1296.
LIFE Study: Results
Dahlöf B et al. Lancet. 2002;359:995-1003.
0
5
10
15
20
25
30
Primary Endpoint: CV Death, MI,and Stroke
New-Onset Diabetes
Eve
nts
/100
0 P
atie
nt-
Yea
rs Atenolol
Losartan
P <.001
P <.05
• 25% reduction in RR
ALLHAT: Incidence of New-Onset Diabetes at 4 Years*
*43.2% lower onset of new diabetes with lisinopril compared to chlorthalidone (P .001 at 4 y).ALLHAT Officers and Coordinators. JAMA. 2002;288:2981-2997.
0
5
10
15
Chlorthalidone Amlodipine Lisinopril
P .001
P = .04
11.6%
9.8%8.1%
%
Summary
Type 2 diabetes and CVD are common chronic diseases that cause suffering to millions and are a major drain on healthcare resources
Disease prevention is possible and desirable
Patients with IGT at high risk of diabetes and CVD are ideal population for type 2 diabetes prevention trials
Intensive lifestyle interventions may not be broadly applicable or sustained; effective pharmacological therapies must also be identified
Several drug classes have been shown to reduce incidence of type 2 diabetes
Summary
It seems that the combination of an
insulin sensitizer and a RAAS is the
best tool for prevention and future
studies will clarify this fact.