pierre drouin lecture. pierre drouin (1939-2002) born in nancy (lorraine) professor of diabetes in...
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Pierre DROUIN lecture
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
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
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
Methodological issues on epidemiological
features of T2D
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
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
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%??
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…
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
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 ?
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
« 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.
Available data on T2D incidence/prevalence
and its recent evolution in Mediterranean
countries
(7) Eur J Clin Invest 2008
Incidence of Type 2 Diabetes in Europe and SpainSpain: 10-19 cases per 1.000 persons-year
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
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
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
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
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
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)
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)
Malek R . Méd Mal Métab 2008; 2: 288-302
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
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
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
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
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
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
Prevalence of treated diabetes in France by age and gender in 2007
Adjusted prevalence of treated diabetes by geographical area in 2007 in France
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
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
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
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
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
Causes of the new trends of Type 2 diabetes
prevalence/Prevention
Risk factors for type 2 diabetes
• Ageing (increase in life expectancy)
• Overweight and obesity due to
changes in lifestyle
. nutritional habits
. physical activity
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
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
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)
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
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
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)
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
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
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
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
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)