1. diabetic complications in relation to demographics in Europe
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
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. Epidemiology of diabetes chronic complications Microvascular diseases
Retinopathy in Diabetes in Europe 90 80 70 60
Type 1 diabetes
Type 2 diabetes
All % 50 40 30
NE - Northern Europe
WE - Western Europe
EE - Eastern Europe
SE - Southern Europe 20 10 NE WE EE SE
Diabet Med, 14 (S1); 1997

5. Microvascular diseases Frequency of retinopathy
Epidemiology of diabetes chronic complications
Microvascular diseases
Frequency of retinopathy
among Eurodiab PCS pts at baseline 10 20 30 40 50 60 70 % 1 2 3 4 5 6
Background 7 8 9 10 11 12
Proliferative 13 14 15
Over 8 years of follow up, 50% of individual showed a progression, of whom 13% to the proliferative form The risk factors for progression were: duration of the disease, HbA1c, AER, fasting tryglicerides, HDL and WHR. (data unpublished)
1 Vienna 19 Cork
2 Luxembourg 20 Helsinki
3 Turin 21 Zagreb
4 Nth France 22 Lisbon
5 Perugia 23 Leiden
6 Pisa
7 Bari
8 Cagliari
9 Verona
10 Athens
11 Padua
12 Milan
13 Gent
14 Munich
15 Rome
16 Thessaloniki
17 England
18 Dusseldorf 16 17 18 19 20 21 22 23

6. Microvascular diseases Retinopathy in Type 2 diabetes (UKPDS)
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
1 - Intensive therapy (FPG < 108 mg/dL)
2 - Conventional therapy (FPG < 270 mg/dL)
years
0.79
0.015
Favours intensive therapy(1)
Favours
conventional
therapy(2)

7. Microvascular diseases Retinopathy in Type 2 diabetes (UKPDS)
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
TC - Tight blood pressure control
BP < 150/85 mmHg
LTC - Less tight blood pressure control
BP < 180/105 mmHg
- LTC
243
461
207
411
152
300
3 years
6 years
9 years
Years from randomisation

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

9. Microvascular diseases Frequency of nephropathy (albuminuria)
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
1 Perugia 18 Bari
2 Pisa Nth France
3 Milan 20 Turin
4 Athens 21 Gent
5 Rome 22 Helsinki
6 Budapest 23 Thessaloniki
7 Vienna 24 Lisbon
8 Munich 25 Bucharest
9 Cagliari 26 Zagreb
10 England
11 Luxembourg
12 Verona
13 Krakow
14 Leiden
15 Cork
16 Padua
17 Dusseldorf 19 20 21 22 23 24 25 26 10 20 30 40 50

10. Microvascular diseases Risk of albuminuria among Eurodiab PCS pts
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 % 20
13%
microalbuminuria
at baseline (351 pts) 10
2 %
Progression
to micro
Progression
to macro
Regression
to normo

11. Risk factors at baseline for progression
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. Microvascular diseases Nephropathy in Type 2 diabetes (UKPDS)
Epidemiology of diabetes chronic complications
Microvascular diseases
Nephropathy in Type 2 diabetes (UKPDS)
Relative Risk
& 99% CI RR p
0.5 1 2
Baseline
0.89
0.24
Three years
0.83
0.043
Six years
0.88
0.13
Nine years
0.76
Twelve years
0.67
1 - Intensive therapy (FPG < 108 mg/dL)
2 - Conventional therapy (FPG < 270 mg/dL)
Fifteen years
0.70
0.033
Favours
Favours
intensive
therapy(1)
conventional
therapy(2)

13. Microvascular diseases Nephropathy in Type 2 diabetes (UKPDS)
Epidemiology of diabetes chronic complications
Microvascular diseases
Nephropathy in Type 2 diabetes (UKPDS)
% patients
317
618
274
543
166
299 10 20 30 40 24 18 29 33
3 years
6 years
9 years
p=0.008
p=0.052
p=0.33
-TC
-LTC
TC - Tight blood pressure control
BP < 150/85 mmHg
LTC - Less tight blood pressure control
BP < 180/105 mmHg
Years from randomisation

14. Neuropathy in Diabetes in Europe
Epidemiology of diabetes chronic complications
Neuropathy in Diabetes in Europe 70 60 50
Type 1 diabetes
Type 2 diabetes
All % 40 30 20
NE - Northern Europe
WE - Western Europe
EE - Eastern Europe
SE - Southern Europe 10 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
1 Pisa 19 Budapest
2 Rome 20 Athens
3 Munich 21 Turin
4 Perugia 22 Lisbon
5 Thessaloniki 23 Padua
6 Cagliari 24 Bari
7 Nth France 25 Zagreb
8 Dusseldorf 26 Bucharest
9 Luxembourg
10 Cork
11 Leiden
12 Vienna
13 England
14 Helsinki
15 Krakow
16 Milan
17 Verona
18 Gent 19 20 21 22 23 24 25 26 10 20 30 40 50 60 70 80

16. Incidence of neuropathy among Eurodiab PCS pts over the follow up
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
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. Direct Costs of Diabetes in the USA
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
1965
1970
1975
1980
1985
1990
1995
* Taylor AK, Diabetes Care, 1987

20. The Costs of Diabetes in Europe
England and Wales: Direct costs for Type 1 diabetes (Gray et al,1995)
£ 1,024 per pt /year
England and Wales: Total costs for diabetes (Laing W et al, 1989)
5% of total expenditure of the National Health Service
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 20107
1995 6 5
2000 % 4 3
2010 2 1
World
Africa
Asia
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.