Dr. G. KRZENTOWSKI, Diabétologue ISPPC – CHU CharleroiPresident Association Belge du Diabète

Diabetes Diabetes

Diabetes Estimates and Projection 1994 - 2010

1994 2000 2010

Type 1 11.5 million 18.1 million 23.7 million

Type 2 98.9 million 157.3 million 215.6 million

TOTAL 110.4 million 175.4 million 239.3 million

Source: Mokdad et al., Diabetes Care 2000;23:1278-83.

Diabetes Trends* Among Adults in the U.S.,(Includes Gestational Diabetes)

BRFSS 1990

No Data <4% 4%-6% 6%-8% 8%-10% >10%

Diabetes Trends* Among Adults in the U.S.,(Includes Gestational Diabetes)

BRFSS 1991-92

Source: Mokdad et al., Diabetes Care 2000;23:1278-83.

No Data <4% 4%-6% 6%-8% 8%-10% >10%

Diabetes Trends* Among Adults in the U.S.,(Includes Gestational Diabetes)

BRFSS 1993-94

Source: Mokdad et al., Diabetes Care 2000;23:1278-83.

No Data <4% 4%-6% 6%-8% 8%-10% >10%

Diabetes Trends* Among Adults in the U.S.,(Includes Gestational Diabetes)

BRFSS 1995-96

Source: Mokdad et al., Diabetes Care 2000;23:1278-83.

No Data <4% 4%-6% 6%-8% 8%-10% >10%

Diabetes Trends* Among Adults in the U.S.,(Includes Gestational Diabetes)

BRFSS 1995

Source: Mokdad et al., Diabetes Care 2000;23:1278-83.

No Data <4% 4%-6% 6%-8% 8%-10% >10%

Diabetes Trends* Among Adults in the U.S.,(Includes Gestational Diabetes)

BRFSS 1997-98

Source: Mokdad et al., Diabetes Care 2000;23:1278-83.

No Data <4% 4%-6% 6%-8% 8%-10% >10%

Diabetes Trends* Among Adults in the U.S.,(Includes Gestational Diabetes)

BRFSS 1999

Source: Mokdad et al., Diabetes Care 2001;24:412.

No Data <4% 4%-6% 6%-8% 8%-10% >10%

Diabetes Trends* Among Adults in the U.S.,(Includes Gestational Diabetes)

BRFSS 2000

Source: Mokdad et al., J Am Med Assoc 2001;286:10.

No Data <4% 4%-6% 6%-8% 8%-10% >10%

Diabetes Trends* Among Adults in the U.S.,(Includes Gestational Diabetes)

BRFSS 2001

Source: Mokdad et al., J Am Med Assoc 2001;286:10.

No Data <4% 4%-6% 6%-8% 8%-10% >10%

Diabète de type 1

Temps

Cell.

0 %

10 %

100 %

Hérédité

Environnement

Auto-immunité

Diabète de type 2

HEREDITE

ENVIRONNEMENT

Cell.B

R. INS.

Pro. Ins./Ins.

Glucotoxicité

M

Foie

ADIP

Stockage

Utilisation

126 mg / dl

• TYPE 1• TYPE 2• GESTATIONNEL• AUTRES

OMS

Classification ADA 1997

20 ans de diabète de type 2 55 ans de diabète de type 1

Un petit diabète ?

Reduction in life expectancy in type 2 diabetes

Age at Diagnostis

Marks & Krall 1971

Goodkin 1975

Panzram & Zabel-Langhennig 1981

10 / 15 (17) 27 -

15 – 19 16 – 17 23 -

20 – 29 12 – 14 16 -

30 – 39 10 – 11 11 -

40 – 49 8 – 9 10 7 – 8

50 – 59 6 – 7 6 5 – 6

60 – 69 4 – 5 5 3 – 4

70 + - - 3

OBESITY

LDL

HDL

Smoking

BP

Sedentarity

– Amélioration du contrôle glycémique : 12 à 76 % de réduction des complications.

– Amélioration du contrôle de la tension artérielle : 24 à 56 % des risques des complications.

– Amélioration du contrôle des lipides : 33 à 62 % de réduction des complications.

Reduction du Risque des Complications chez les Patients Diabétiques

Risk reductions from intervention studies in type 2 diabetes

Clinical Outcomes UKPDS Metformine

n = 753

UKPDS

SU/Ins n = 3867

UKPDS

Captopril Atenolol n =

1148

HOT Felodipine Aspirin n = 1501

4S Simvastatine

n = 202

HOPE Ramipril

n = 3577

Diabetes-related deaths (%)

42 10 32 67 36 37

All-cause mortality (%) 36 6 18 43 43 24

All MI (%) 39 16 21 51 55 22

Fatal MI (%) 50 6 28 - - -

All stroke (%) 41 (+) 11 44 30 62 33

Fatal stroke (%) 25 (+) 17 58 - - -

Follow-up (years) 10.7 10.7 8.4 3.8 5.4 4.5

Myocardialinfarction StrokeDiabetes deaths

42% 39% 41%

Median dose = 2550 mg/day

Clinical outcomes for metformin in the UKPDS

STENO II Study

Multifactorial intervention and cardiovascular

disease in patients with type 2 diabetes.

P. Gaede et al. N.E.J.M. 348 (5) : 383-393, 2003

315 type 2 diabetic patients with microalbuminuria

160 randomised

Intensive Conventional

12 deceased

7 CVD

2 cancer

3 other

15 deceased

7 CHD

5 cancer

3 other

67 patients 63 patients

Mean follow up

7.8 years

Treatment objectives

Conventional Intensive

1993-99 2000-01 1993-99 2000-01

Systolic BP (mmHg) < 160 < 135 < 140 < 130

HbA1c (%) < 7.5 < 6.5 < 6.5 < 6.5

Cholesterol (mmol/l) < 6.5 < 4.9 < 4.9 < 4.5

Tryglycerides (mmol/l) < 2.2 < 2.0 < 1.7 < 1.7

ACE-I independent of BP No Yes Yes Yes

Aspririn

Known ischemia Yes Yes Yes Yes

Inferior limb

Arteriopathy

No No Yes Yes

No peripheral or central ischemic disease

No No No yes

• Dietary – < 30 % calorie intake as fat– < 10 % calorie intake as saturated fat– Vitamin supplements

• Vit C 250 mg/d

• D-alpha-tocopherol 100 mg/d

• Folate 400 g/d

• Chromium 100 g/d

• Exercise – 30 minutes brisk walk 3 to 5 days/week

Intensive Intervention Modalities

• Smoking cessation

• ACE-I (captopril 50 mg x 2/d) or AT-II if

contraindication

• Statine and/or fibrate

• Aspirin (150 mg/d)

• OAD, mixed schema (bedtime NPH) or intensive insulin

• Follow up every 3 months

Intensive Intervention Modalities (Ctd)

Number of Patients reaching the Objectives (%)

Intensive Conventional

HbA1c < 6.5 % 15 % < 5 %

Cholesterol < 4.5 mmol/l 75 % 25 %

Triglycérides < 1.7 mmol/l

60 % 45 %

Systolic BP < 130 mmHg 47 % 20 %

Diastolic BP < 80 mmhg 75 % 60 %

Added benefit of intensive treatment at the end of

the study :

• Systolic BP : - 11 mmHg

• Total cholesterol : - 1.21 mmol/l

• LDL : - 0.87 mmol/l

• HbA1c : - 0.7 %

Estimated differences between Groups at the End of the Study

• Primary objective :

Cardiovascular events (death, MI, CABG, PTCA, percutaneous angioplasty, peripheral vascular surgery)

– 24 % vs 44 %

– Adjusted relative risk : 0.45 (0.23 – 0.91)

NNT in 7.8 years to prevent ONE accident : 5

• Secondary objectives :

Nephropathy : RR 0.39 (0.17 – 0.87)

Retinopathy : RR 0.42 (0.21 – 0.86)

Autonomic neuropathy : RR 0.37 (0.18 – 0.79)

Peripheral neuropathy : RR 1.09 (0.54 – 2.22)

Results

A multifactorial approach targeting multiple risk factors

at once in microalbuminuric type 2 diabetic patients

Results in a reduction of cardiovascular and

microvascular events by approximately 50 %

Conclusion

Prévention primaire du diabète de type 2

Etudes Nombres Interventions Durée (ans)

Résultats

MALMO 6 956 (260 IGT) Lifestyle 5 RR Diabetes 0.37

DA QING 110 660 (530 IGT)

Lifestyle 6 Diabetes – 42 %

FINNISH 522 IGT Lifestyle 4 Diabetes – 58 %

DPP 3 234 (IGT ; IFG)

Lifestyle and Metformine

3 Diabetes – 58 %

Diabetes – 31 %

TRIPOD 266 (Previous gestational diabetes)

TrogIitazone 2.5 Diabetes : Placebo 12,1 %

Troglitazone 5,4

STOP-NIDDM 1 429 IGT Acarbose 4 RR Diabetes 0.75

XENDOS 3 304 Obèses (21 % IGT)

Orlistat 4 Diabetes – 37 %

ADO :

– Biguanide

– Acarbose

– Sulfonylurées

– Glinides

– Glitazones

Traitement du diabète E

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Traitement du diabète

INSULINE :

– Rapides

– Retards

– Mélanges

– Analogues

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And on the belgian field…