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)