Prevalence of Diabetic Complications in Europe: Microvascular Diseases, Neuropathy, and Costs of Diabetes

1. Marco Songini Prevalence of diabetic complications in relation to demographics in Europe State-of-the-art in reference to published data Part 2: microvascular diseases, neuropathy and costs of diabetes

2. Dr Marco Songini is the director of the Diabetes Unit at S. Michele Hospital in Cagliari (Sardinia-Italy). He is also the vice-president of ASRIS (Association for the Study of Type 1 Diabetes in Sardinia)

3. DM-MED project is aimed to develop recommendations for public health policy in the Mediterranean countries with emphasis on the prediction, prevention and control of Types 1 and 2 diabetes and their complications. The emphasis of this meeting was on description of the health programs of the participating countries, on the epidemiology of diabetes and its complications in the Mediterranean region, and on the need for methodology of diabetes registries. The present is one of the lectures of the DM-MED meeting.

4. Type 1 diabetes Type 2 diabetes All Epidemiology of diabetes chronic complications Microvascular diseases Retinopathy in Diabetes in Europe 90 80 70 60 % 50 40 30 20 10 0 NE WE EE SE Diabet Med, 14 (S1); 1997

5. % 0 10 20 30 40 50 60 70 Epidemiology of diabetes chronic complications Microvascular diseases Frequency of retinopathy among Eurodiab PCS pts at baseline 1 2 3 4 5 6 Background 7 8 9 10 11 12 Proliferative 13 14 15 16 17 18 19 20 21 22 23

6. Epidemiology of diabetes chronic complications Microvascular diseases Retinopathy in Type 2 diabetes (UKPDS) Relative Risk & 99% CI RR p 0.5 2 1 0 - 3 years 1.03 0.78 0 - 6 years 0.83 0.017 0 - 9 years 0.83 0.012 0.015 0 - 12 years 0.79 Favours intensive therapy(1) Favours conventional therapy(2)

7. Epidemiology of diabetes chronic complications Microvascular diseases Retinopathy in Type 2 diabetes (UKPDS) p=0.004 p=0.019 60 p=0.38 40 % patients - TC 20 - LTC 0 243 461 207 411 152 300 3 years 6 years 9 years Years from randomisation

8. Epidemiology of diabetes chronic complications Type 1 diabetes Type 2 diabetes All Microvascular diseases Nephropathy in Diabetes in Europe 20 15 % 10 5 0 NE WE EE SE Diabet Med, 14 (S1); 1997

9. Epidemiology of diabetes chronic complications Microvascular diseases Frequency of nephropathy (albuminuria) among Eurodiab PCS pts at baseline 1 2 % 3 4 5 6 microalbuminuria 7 8 9 10 11 12 13 14 15 16 macroalbuminuria 17 18 19 20 21 22 23 24 25 26 0 10 20 30 40 50

10. Epidemiology of diabetes chronic complications Microvascular diseases Risk of albuminuria among Eurodiab PCS pts 60 51 % 50 normoalbuminuria at baseline (1,134 pts) 40 % 30 14 % 13% 20 microalbuminuria at baseline (351 pts) 10 2 % 0 Progression to micro Progression to macro Regression to normo

11. Epidemiology of diabetes chronic complications Microvascular diseases Albuminuria among Eurodiab PCS pts Risk factors at baseline for progression From normo to microalbuminuria From micro to macroalbuminuria HbA1c, AER and after adjusting for HbA1c & AER fasting triglycerides, LDL and HDL cholesterol, BMI, WHR, any retinopathy HbA1c, AER and after adjusting for HbA1c& AER GT, WHR, peripheral neuropathy

12. Epidemiology of diabetes chronic complications Microvascular diseases Nephropathy in Type 2 diabetes (UKPDS) Relative Risk & 99% CI RR p 0.5 1 2 0.89 Baseline 0.24 Three years 0.83 0.043 Six years 0.88 0.13 Nine years 0.76 0.00062 Twelve years 0.67 0.000054 Fifteen years 0.70 0.033 Favours Favours intensive therapy(1) conventional therapy(2)

13. Epidemiology of diabetes chronic complications p=0.052 p=0.008 p=0.33 40 33 29 29 30 % patients 24 20 18 20 10 0 317 618 274 543 166 299 3 years 6 years 9 years Microvascular diseases Nephropathy in Type 2 diabetes (UKPDS) -TC -LTC Years from randomisation

14. Type 1 diabetes Type 2 diabetes All Epidemiology of diabetes chronic complications Neuropathy in Diabetes in Europe 70 60 50 % 40 30 20 10 0 NE WE EE SE Diabet Med, 14 (S1); 1997

15. Frequency of neuropathy among Eurodiab PCS pts at baseline Epidemiology of diabetes chronic complications 1 2 % 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 10 20 30 40 50 60 70 80 0

16. Epidemiology of diabetes chronic complications Incidence of neuropathy among Eurodiab PCS pts over the follow up Symptoms Absence of reflexes 40 Abnormal VPT 35 Abnormal autonomic function 30 25 % 20 Neuropathy (2 or more abnormal of symptoms, reflexes, VPT, autonomic function) 15 10 5 0 The prevalence raised from 26% at baseline to 34% at the end of follow up

17. The Costs of Diabetes (1) - Direct costs (43-50% of total costs) Personal costs - Hospital services - Physician in-patient service - Out-patient care (services and GPs, nursing home, home care) - Travel (ambulances) - Supplies (oral hypoglycaemic drugs, insulin, syringes, cotton swabs, glucose and urine test strips) Non-personal costs - Research (biomedical and social sciences) - Health education - Support services Diabetes in Europe, Ed Rhys Williams, 1993

18. The Costs of Diabetes (2) Indirect costs - Income losses due to illness and disability - Present value of future earning lost by those who died prematurely as a result of diabetes - Psychological costs to diabetic patients and their families (Intangible costs) Diabetes in Europe, Ed Rhys Williams, 1993

19. The Costs of Diabetes Direct Costs of Diabetes in the USA 50 * US$ 15,114 per diabetic /yearly (compare to US$ 548 for others /yearly) 40 30 $ billion 20 10 1995 1965 1970 1975 1980 1985 1990 * Taylor AK, Diabetes Care, 1987

20. The Costs of Diabetes in Europe England and Wales: Total costs for diabetes (Laing W et al, 1989) 5% of total expenditure of the National Health Service England and Wales: Direct costs for Type 1 diabetes (Gray et al,1995) £ 1,024 per pt /year UK: Direct costs for type 2 diabetes (Moore P, 2000) 4.7 % of total expenditure of the National Health Service Sweden: Total costs for diabetes (Olsson J et al, 1987) $ 8,400 per pt /year Finland: Direct costs for diabetes (Kangas T et al, 1989) 5.8% of total expenditure of the National Health Service France: Total costs for diabetes (Triomphe A et al, 1988) Type 1 diabetes FF 12,178 per pt /year Type 2 diabetes FF 6,908 per pt /year

21. Global estimates and projections of diabetes prevalences from 1995 to 2010 7 1995 6 5 2000 4 % 3 2010 2 1 0 Asia World Africa Europe Oceania Nth America Latin America Diabet Med, 14 (S1); 1997

22. Eurodiab-PCS: summary (1) There is no sex difference for the risk of CHD in people with type 1 diabetes. Independently of age and HbA1c, the risk factors for CHD in men and women are different. In fact in men CHD is strongly associated with AER, smoking, WHR, whilst in women duration of the disease, systolic BP, AER, fasting triglycerides play a major role. The incidence of neuropathy over approximately a 7 year period is 25%. Risk factors for incidence, independent of age and HbA1c were cholesterol, fasting triglycerides, presence of CVD at baseline and presence of retinopathy at baseline. Existence of previous CVD increased the risk of neuropathy 3 times.

23. Eurodiab-PCS: summary (2) Regression from micro to normoalbuminuria was significantly related to HbA1c, AER, WHR and peripheral neuropathy. These results emphasise the importance of good glycaemic control to prevent nephropathy, and indicate that markers of insulin resistance, such as triglycerides and WHR, need to be strictly monitored. There are not still data reporting the incidence of retinopathy among this cohort. At baseline retinopathy was present in about one third of the patients (mostly background).

24. UKPDS: summary Intensive therapy aimed to reduce fasting glycaemia to normal values (less than 108 mg/dl vs less than 270 mg/dl) is worthwhile as it reduces risk of complications, the greatest effect being on microvascular complications. A tight blood pressure control is worthwhile as it reduces risk of complications, particularly evident in heart failure and stroke after 3 years from randomisation. All these data indicate that the reduction in risk of complications of diabetes is not a dream but it is a realisable goal.

25. Conclusions (1) The prevalence of diabetes, either type 1 and type 2, is increasing worldwide. The interaction between some genetic components and some environmental factors is responsible for the etiopathogenesis of these diseases. However, the environmental factors for type 1 diabetes have still to be largely identified whilst, as far as type 2 diabetes, overweight, low levels of habitual physical activity and some aspects of westernized diet have been already recognised as to be important for developing the disease. Independently of the type of diabetes, the incidence and prevalence of chronic complications are tightly related not only to glyco-metabolic control but also to other risk factors, such as blood lipids and blood pressure, which can be easily prevented by early monitoring and treatment.

26. Conclusions (2) It is of note that, independently of the different design and period of follow up of the studies so far reported, the risk for developing diabetes complications is also dependent from a genetic background, which varies among the different areas and populations investigated. Furthermore, the same complications could be related to different risk factors according to the population analysed. 49

27. Conclusions (3) These findings suggest that, across different countries, the prevalence of diabetic complications may be widely variable, and that the efforts for their prevention must be oriented and differentiated according to the data emerging form their own investigations and to their own risk factors involved. The interpretation of these differences could be carried out only by setting out large and reliable epidemiological investigations where data will be collected uniformly among the different geographical areas.