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Pierre DROUIN lecture
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Pierre DROUIN (1939-2002)
Born in Nancy (Lorraine)
Professor of Diabetes in 1975 in Nancy
President of ALFEDIAM 1993-1995
President of MGSD 1998-2000
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Epidemiology of type 2 diabetes in Mediterranean countries: critical
analysis of past forecasts; new trends
Dominique SimonINSERM U-780, 94800 Villejuif et Service de Diabétologie de la Pitié, Paris
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Plan of the lecture
Methodological issues on epidemiological features of Type 2 diabetes (T2D)
Available data on T2D incidence/prevalence and their recent evolution in Mediterranean countries
Causes of the new trends of T2D prevalence/Prevention
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Methodological issues on epidemiological
features of T2D
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Methodological issues : how to assess epidemiological features of T2 D ?
Definition of diabetes and T2 DIncidence: nb new T2D cases over a
period of time/nb subjects without T2D at baseline
Prevalence: nb cases T2D/total nb inhabitants
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Definition of diabetes Casual plasma glucose 200 mg/dl (11,1 mM)
Fasting plasma glucose 126 mg/dl (7,0 mM)[until 1999, 140 mg/dl (7,8 mM)]
2-hr plasma glucose after 75-g oral glucose load (OGTT) 200 mg/dl (11,1 mM)
Confirmed by a second abnormal measurement
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Definition of T2D Not type 1 diabetes (immunological or insulin secretion
criteria??) neither secondary diabetes (pancreatitis, Cushing’s syndrome, haemochromatosis) nor MODY type diabetes
All the non insulin-treated diabetic patients and use of an algorithm for insulin-treated patients :
- diabetes diagnosis before 30 yrs (35 yrs? 40 yrs?)
- insulin treatment within 1 (2?) year(s) following D. diagnosis
ENTRED study in France: 92% T2D, 6% T1D, 2%??
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Incidence of T2D Need to have blood glucose (BG) measured at baseline
to select non diabetic subjects Need to follow-up these subjects and to interview for
antidiabetic drug treatment and, if no antidiabetic treatment, to perform new BG measurements
Which BG measurement : fasting, casual, OGTT
data on very few populations: Pima Indians, PPS, DESIR study, Asturias study…
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Prevalence of T2D Cross-sectional study on all the subjects of the studied
population to look for known diabetes and to measure BG using an OGTT then another BG measurement for confirmation, theoretically !
In practice, usually, for epidemiological purposes:- only one BG test abnormal to define diabetes- often only fasting BG measured or 2-steps procedure (casual BG measured to screen for OGTT)- selection of age group at-risk for D. ≥ 30 (40?) yrs
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Prevalence of T2D - Pitfalls
Representativeness of the studied sample?- need to have recent census data- need to have a high response rate ( > 60%? 70?...) from the randomized subjects
Which BG measurement?
Which age group selected ?
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Prevalence of T2D- 2 examples Vietnamese study (Hanoi) in 1990: 4912 subjects ≥ 15
yrs were examined (95.0% of the eligible population); screening used capillary BG before dinner then OGTT if CBG ≥ 105 mg/dl (93.9% of positive screenees)
Caldia study (New Caledonia) in 1993: 9390 subjects aged 30-59 yrs were examined (78.3% of the eligible population); screening used fasting CBG then OGTT if CBG ≥ 110 mg/dl (92.8% of positive screenees) and OGGT in 517 negative screenees
Quoc PS et al. Am J Epidemiol 1994; 139: 713-22
Papoz L et al. Am J Epidemiol 1996; 143: 1018-24
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« Surrogate markers » of T2D prevalence
Health Insurance System database recording nominal information on all antidiabetic drugs reimbursed to the patients accurate data on the prevalence of pharmacologically treated D. but ignores only-diet treated D. patients and undiagnosed D. patients
National database of antidiabetic drugs sales: need to define the prescribed daily dose for each drug
Interview on antidiabetic drug use: need for a representative sample of population; only known D.
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Available data on T2D incidence/prevalence
and its recent evolution in Mediterranean
countries
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(7) Eur J Clin Invest 2008
Incidence of Type 2 Diabetes in Europe and SpainSpain: 10-19 cases per 1.000 persons-year
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Type 2 diabetes Incidence in France
Paris Prospective Study- recruitment in the 70s- 5042 men - 42-52 yrs- WHO 1980 criteria- follow-up : 3 yrs
Annual incidence : 4.2‰
Charles MA et al. Diabetes 1991; 40: 796-9
DESIR Study- recruitment in the 90s- 1863 men and 1954 women- 30-64 yrs- ADA criteria (FPG)- follow-up : 9 yrs
Annual incidence : 6.5‰
Balkau B et al. 2008; 31: 2056-61
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2.6%
4.0%5.0%
6.3%6.6%
6.6%8.2%
12.0%13.1%
14.0%14.8%
16.1%16.1%16.2%
24.0%26.4%
30% 20% 10% 0
Mauritania - M Ducorps / 1996 (30-64)
Tunisia -Papoz L / 1988
Iraq / 1979
Egypt -Arab, M / 1997 (>20)
Yemen -Abdallah A Gunaid / 2002 (20–85)
Morocco -Tazi / 2003
Syria -Al Bache N / 1999
Palastine -Abdul-Rahim,H / 2001 (30-65)
Lebanon -Ibrahim S. Salti / 1997
Libya -Kadiki OA / 2001
Kuwait -N.Abdella / 1996
Oman -J. A. Al-Lawati / 2000 (30-64)
UAE / 2000 (30-64)
Jordan -Kamel Ajlouni / 2004
Saudi -Nozha / 2004 (>30)
Bahrain -Zurba FI / 1996 (>20)
Comors
Djibouty
Somalia
Algeria - R. MALEK / 2001
Sudan - El-Bagir / 19963.4%
9.4%
Qatar- Mahmoud Zirie15%
PREVALENCE OF DM IN ARAB COUNTRIES
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5.66.4
7.5
9.510.39.810.2
14.7 14.8
8.16.1
5.5
13.21312.6
11.3
0
2
4
6
8
10
12
14
16
PREVALENCE STUDIES OF DIABETESPREVALENCE STUDIES OF DIABETESIN SPAININ SPAIN
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PREVALENCE OF MAJOR CV RFs BY GEOGRAPHICAL PREVALENCE OF MAJOR CV RFs BY GEOGRAPHICAL AREA IN SPAIN (90´s)AREA IN SPAIN (90´s)
NORTH(n=2431)
MEDITERRAN. (n=5260)
CENTRE(n=7678)
SOUTHEAST
(n=4360)
Overall ajusted prevalence *
PrevalenceRatio
p
SMOKING(n=19654) 25.7 28.8 33.6 34.2 32,2 1,33 <0,0001
OBESITY(n=19729) 26.8 19.9 24.2 26.5 22,8 1,34 <0,0001
DIABETES(n=19729) 5.1 7.8 6.0 6.3 6,2 1,53 <0,0001
DISLIPIDEMIATCho>240mg/dl(n=15713)
17.8 20.0 17.1 12.7 17,1 1,57 <0,0001
HYPERTENSION(n=19729) 37.8 35.2 36.6 42.0 37,6 1,19 <0,0001
Highest rates
High-intermediate rates
Intermediate-low ratesLowest rates
*Spanish pop >20 years, INE 2000
Gabriel R. Rev Esp Cardiol 2008;61:1030-40
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MORTALITY FOR DIABETESPREVALENCE OF DIABETES
Atlas municipal de mortalidad en España. 1989-1998. CNE. ISCIIIProyecto ERICE
Rev Esp Cardiol 2008;61:1030-40
Tasas más altasTasas intermedio-altasTasas intermedio-bajasTasas más bajas
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Diabetes Mellitus in Syria 2006 Diabetes Mellitus in Syria 2006 (>25 year)(>25 year)
Aleppo study of prevalence of DM and C.V .Risk Factors, Diabetes Research Unit ,Aleppo University 2006, (SUMETTED DATA)
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T itre du g raphique
02468
1012141618
ة 1 ئ ف ة 2 ئ ف ة 3 ئ ف ة 4 ئ ف
1996
2006
INCREASE OF PREVALENCE OF DM INCREASE OF PREVALENCE OF DM ON ONE DECADEON ONE DECADE
1.1.ALBACHE N.:Diabetes Research & Clinical Practice;2000,50,1ALBACHE N.:Diabetes Research & Clinical Practice;2000,50,122.ZEHOR F., OWESS.S.(MINISTRY OF HEALTH).ZEHOR F., OWESS.S.(MINISTRY OF HEALTH)33..ALBACHE,N ,R Al-Ali, S. Rastam, F. M. Fouad, F.Mzayek, W. Maziak :ALBACHE,N ,R Al-Ali, S. Rastam, F. M. Fouad, F.Mzayek, W. Maziak : Epidemiology of Type 2 Diabetes in Aleppo, Syria Epidemiology of Type 2 Diabetes in Aleppo, Syria ( submetted dada)( submetted dada)
cc
PREVALENCE OF DM IN SYRIA IN 1996PREVALENCE OF DM IN SYRIA IN 1996 (1,2)(1,2)& & 20062006((33))
(>25 YEAR) (>25 YEAR)
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Malek R . Méd Mal Métab 2008; 2: 288-302
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Diabetes in Malta (≥ 15 yrs)
Sex Age (years)
Year Popul T2D Prev.
M F 15-44 45-64 ≥ 65 Total
1996 293000 7.7% 8174 14529 1306 10474 10923 22703
2000 305000 8.1% 8813 15779 1313 11296 11983 24592
2020 336000 9.5% 11833 19966 1305 11656 18888 31849
Schranz AG Diabetes Care 1999; 22: 650
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Type 2 Diabetes Prevalence in Greece, Cyprus and Portugal
Year Age (yrs) Criteria Area T2 D.
Prev (%)
Greece1
(Attica)
2002 20-89 ADA urban M : 7.6
F : 5.9
Greece2
(Salamis)
2002 ≥ 20 Self-reported
urban 8.2
2006 9.5
Cyprus3 2004 20-80 OGTT national 10.3
Portugal4 2008 20-79 OGTT national 11.7
1-Diabetic Med 2005; 2-Diabetes Res Clin Pract 2008; 3-Diabetes Care 2006; 4-subm. EASD
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Type 2 Diabetes Prevalence in Italy and Turkey
Year Age (yrs)
Criteria Area T2 D.
Prev (%)
Italy1
(Emilia)
2000 ? database
(exemption)
regional 2.4
Italy2
(Sardinia)
1998 ≥ 20 fasting
serum
glucose
regional 9.1
2003 14.4
Italy3
(Turin)
2003 ? 3 databases regional 4.8
Turkey4 1997-8 ≥ 20 OGTT (2h) national 7.2
1-BEN 2002; 2-Acta Diabetol 2009; 3- Nutr Metab Cardiov Dis 2008; 4-Diabetes Care 2002
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Data from the French Health Insurance System (CNAMTS) in 2005
INSEE population : 62 500 000
Général Insurance System population :55 500 000
Général Insurance System population (minus SLM) :47 100 000
Sample 1/600ème :75 000
Anti-diabetic drugs(> 2 reimbursements during the year) :
2 980
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Extrapolation of prevalenceto all the Health Insurance Systems
(Metropolitan France )
2000 2005
INSEE population
Diabetes prevalence (%)
58 825 000
2.9
60 702 000
3.8
Nb treated diabetic patients 1 706 000 2 307 000
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Evolution of treated-diabetes prevalence in France
3,61%
3,48%
3,75%
2,92%
3,11%
3,28%
3,47%
2,73%
2,61%
2,80%
2,98%
3,15%
3,34%
3,60%
3,41%
3,23%
3,04%
2,84%
2,50%
2,60%
2,70%
2,80%
2,90%
3,00%
3,10%
3,20%
3,30%
3,40%
3,50%
3,60%
3,70%
3,80%
3,90%
4,00%
2000 2001 2002 2003 2004 2005
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Prevalence of treated diabetes in France by age and gender in 2007
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Adjusted prevalence of treated diabetes by geographical area in 2007 in France
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Evolution of antidiabetic treatment in France
2000
2001
2002
2003
2004
2005
OAD alone (% ) 79,0 79,2 78,9 77,7 76,1 76,1
Insulin ± OAD (% ) 21,0 20,8 21,1 22,3 23,9 23,9
Sulfonylureas (%) 66,1 63,4 60,0 58,9 56,8 54,6
Biguanides (%) 50,1 50,3 53,9 53,8 55,5 58,0
GI (%) 18,3 18,2 17,0 15,3 14,0 11,9
Glinides (%) 2,1 6,0 7,4 8,3 8,6 8,1
TZDs (%) 0,0 0,0 0,3 1,5 4,2 8,9
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Nb of diabetic patients free of charge for D. treatment (ALD 30) in France and cost for the
Health Insurance SystemYear Nb D.
patients treated
Rate in ALD 30
(%)
Mean cost per D.
patient in ALD30
(Euros 2004)
Total cost for all D.
patients in ALD30
(Billion Euros 2004)
1994
1999
2004
1 277 000
1 846 000
2 175 000
66.1
69.7
78.9
4 427
5 107
5 910
3.7
6.6
10.1
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Cost of diabetes in France
Annual increase of 8.7% between 1998 and 2000 According to complications :
- no complication = 1 769 Euros/yr- microvascular complications = 2 048 Euros/yr- macrovascular complications = 5 126
Euros/yr- both types of complications = 6 407 Euros/yr
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Fagot-Campagna A, et al. BMJ 2001; 322:377–378.
Increasing incidence of type 2 diabetes in children and
adolescentsUntil recently, most children presenting with diabetes had type 1 diabetes
Type 2 diabetes is now increasingly reportedCase reports in children from many countries, including US, Canada, Japan, Hong Kong, Australia, New Zealand, Libya and Bangladesh
Accounts for up to 45% of recently recognized cases of diabetes among children and adolescents in the US
Most cases of type 2 diabetes in children and adolescents are attributable to obesity
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Worldwide prevalence of diabetes in 2000
Number of persons
< 5,0005,000–74,00075,000–349,000350,000–1,499,0001,500,000–4,999,000> 5,000,000No data available
World Health Organization, 2003 http://www.who.int/diabetes/facts/world_figures/en/ (accessed September 2004).
Worldwide prevalence of diabetes in 2030 (projected)
Total cases > 370 million adults
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Causes of the new trends of Type 2 diabetes
prevalence/Prevention
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Risk factors for type 2 diabetes
• Ageing (increase in life expectancy)
• Overweight and obesity due to
changes in lifestyle
. nutritional habits
. physical activity
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Diabetes type 2 in Rural and Urban population
19.50%
4.70%
8.10%
2.62%
25.5%
8.9%
13.3%
3.9%
0%
5%
10%
15%
20%
25%
30%
Saudi Egypt Morocco Sudan
Al-Nozha /2004
Arab, M / 1997 Belkhadir J El-Bagir / 1996
rural urban
PREVALENCE OF DM IN ARAB COUNTRIESIN URBAN & RURAL AREAS
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Influence of genetic and environmental factors on type 2 diabetes prevalence
Arizona Pimas
(n = 888)
MexicanPimas
(n = 224)Mexicans(n = 193)
Body Mass Index (kg/m2) 34.6 ± 7.9 25.1 ± 4.2 25.8 ± 4.4
Calorie intake (kCal/day) 1751 ± 788 2485 ± 563 2593 600
Lipid intake (%) 34.5 9.5 26.3 6.3 25.4 5.8
Physical activity (hr/wk) 7 ± 3 27 ± 2 27 1
Type 2 diabetes (%) 38.1 7.1 2.6
Schulz LO et al. Diabetes Care 2006; 29: 1866-71
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Prevalence of obesity in men in different countries
BMI > 30 kg/m2 (%)
0
5
10
15
20
25
30
USA (20 - 74 ans) Allemagne (25 - 69 ans) Grande-Bretagne (16 - 64 ans)
Finland (20 - 75 ans) Spain (20 - 64 yrs) France (> 18 yrs)
Netherlands (> 20 yrs) Sweden (16 - 84 yrs)
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Obesity In Arab World
15.7%
27%31.2% 31.5%
37.9%
75%
47%
41%
51.4%
57.0%
66.0%
22%27% 27% 27.7%
59.4%
0%
10%
20%
30%
40%
50%
60%
70%
80%
Om
an -F
irdosi/1995,
UE
A -el M
ugamer /1
995
Yem
en /200
0
Bah
rain -F
arouq/1996,
Sau
di -T
aha / 1998
Ku
wait / K
ofo Rotim
i
Qatar
Syria -A
l Bache 200
6
Palestin
ian -A
bdul-R
ahim
/ 2001
Jord
an - A
jlouni /20
04
Iraq/1979
Leb
ano
n -Ibrahim
S/1997,
Mau
ritania - M
Ducorps / 19
96
Eg
ypt -H
erman/1997
Mo
rocco
- Tazi / 2003
Tu
nisia -G
hannem
/1997
Lib
ya -Kad
iki/1990
Alg
eria
Co
mo
ros
Djib
ou
ti
So
malia
Su
dan
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Prevention of type 2 diabetes
In subjects identified as at high risk for type 2 diabetes, prevention of type 2 diabetes can be implemented by : • changes in lifestyle (nutritional habits,
physical exercise)
• pharmacological intervention
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Incidence of type 2 diabetes in IGT subjects- The Da Qing Study -
Pan et al., Diabetes Care 1997; 20: 537-44
0
5
10
15
20
Controls Diet Exercise Diet +exercise
< 25 kg/m2
> 25 kg/m2
Incidence (per 100 subject-years)
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Prevention of Type 2 Diabetes by intervention on lifestyle
RRR (%)
Study Duration (yrs)
n Diet Exercise Diet + exercise
Da Qing 1 6,0 577 31* 46*** 42** Finnish DPS 2 3,2 522 58*** DPP 3 2,8 3234 58***
* p<0,05 ;** p<0,01 ;*** p<0,001
1. Pan et al., Diabetes Care 1997; 20: 537-442. Tuomilehto et al., NEJM 2001; 344: 1343-503. DPP Research Group. NEJM 2002; 346: 393-403
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Prevention of Type 2 Diabetes by pharmacological intervention
RRR (%) Study Drug Durati
on (yrs)
n vs controls
vs lifestyle
DPP 1 metformine 2,8 3234 31** -39** Stop-NIDDM 2 acarbose 3,3 1368 25** TRIPOD 3 troglitazone 2,5 266
Hispanic women
55**
** p<0,01 1. DPP Study Group. NEJM 2002; 346: 393-4032. Chiasson et al., Lancet 2002; 359: 2072-73. Buchanan et al., Diabetes 2002; 51: 2796-803
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Conclusions (1) To collect valid epidemiological data on T2D is
difficult A choice has to be done in the processing and
designing of epidemiological studies on T2D :
- either to conduct a specific study in order to assess accurately T2D prevalence
- either to use routine statistics data, less precise to estimate T2D prevalence, but cheaper and providing additional data interesting for Public Health
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Conclusions (2) T2D is becoming an « epidemic » disease in the Mediterranean countries T2D can be prevented at least in the short-term in at-high risk subjects by :
- changes in lifestyle
- pharmacological intervention
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Thanks for their kind collaboration to :- Nizar ALBACHE (Syria)- Eveline BERNARD (Servier – France)- Davide CARVALHO (Portugal)- Taner DAMCI (Turkey)- Rafael GABRIEL (Spain)- Vasilios KARAMANOS (Greece)- Rachid MALEK (Algeria)- Philippe RICORDEAU (France)- Gojka ROGLIC (Croatia – WHO Geneva)- Charles SAVONA-VENTURA (Malta)- Antoine SCHRANZ (Malta)- Philippe TUPPIN (France)- Josanne VASSALO (Malta)- Alain WEILL (France)