Epidemiology of diabetes mellitus in the north Mediterranean countries

Michele Dalla Vestra, Gaetano Crepaldi
Department of Medical and Surgical Sciences, Clinica Medica I
University of Padova, Italy

Although the projections of a large increase in the prevalence rates of diabetes are concordant, there are discrepancies in the actual rates in some countries (1). It is extremely difficult to describe the epidemiology of diabetes in Europe, since there are no national registries available to assess the number of patients with type 1 or type 2 diabetes. Prevalence of diabetes in adults worldwide was estimated to be 4% in 1995 and it will increase sharply in the future (2). Between 1995 and 2025 the adult population will increase by 64%; the prevalence of diabetes in adults will increase by 35%, and the number of diabetic patients will increase by 122%. For the developed countries there will be an 11% increase in the adult population, a 27% increase in the prevalence of adult diabetes, and a 42% increase in the number of diabetic patients. For the developing countries there will be an 82% increase in the adult population, a 48% increase in the prevalence of adult diabetes, and a 170% increase in the number of diabetic patients (2). Prevalence is higher in developed than in developing countries and will remain so until 2025, although the proportional increase will be greater in the developing countries. Thus diabetes, especially type 2, is evolving as a major health problem in both developed and developing countries.

Type 1 diabetes

The incidence of type 1 diabetes in children younger than 15 years of age has been extensively reported, but few data, and none from Europe, are currently available on the incidence of type 1 diabetes in older age groups. In the Mediterranean and neighboring areas the incidence rates of type 1 diabetes under the age of 15 years show wide variations. In Italy the incidence of type 1 diabetes in children aged 0-14 years is 6-11.7 (per 100 000 per year), while in Sardinia the incidence is 34.4, one of the highest in Europe (3). In general, the highest incidence is among subjects aged 10-14 years and the lowest in children aged 0-5 years for both genders. However an earlier incidence peak in children aged 5-9 years is a common feature of insular Italian areas, but not of Northern Italy (3). In France, Levy-Marchal showed that the annual diabetes incidence rates for 1988 and 1995 were 7.17 and 9.28 per 100,000, respectively; this study included 2 million subjects younger than 20 years of age (4). Similar results have been reported in Spain (8-10.9 per 100 000 per year), in Croatia and Slovenia (7.2 and 7.6 per 100 000 per year, respectively) (3). The incidence in the Mediterranean countries is different from the incidence in Northern Europe; indeed in Finland, Tuomilehto et al reported that for children younger than 14 years, the annual incidence rate in 2000 was 45 per 100 000 (5). In contrast with other European countries, the incidence of the disease in the Mediterranean area does not follow any geographical pattern.

Probably differences in environmental factors, genetic susceptibility or both are important for such a wide variation. The environmental risk factors identified so far can be classified into 3 main groups: diet, toxins and viral infections. Concerning diet, cow’s milk consumption has been shown to be associated with increased incidence of type 1 diabetes (6). Parslow RC et al (7) found that also nitrate concentration in drinking water positively associates with incidence of type 1 diabetes. Different incidence may also be related to viral epidemics or to differences in the virulence of viruses (8). As in other areas of the world, variation in incidence appears to be related to ethnicity, demonstrating the importance of the differential genetic susceptibility in different populations. Indeed Sardinians, who have the highest incidence of type 1 diabetes, together with Finns, in the world, show a high frequency of HLA haplotypes implicated in type 1 diabetes susceptibility and paucity of protective alleles when compared with other Caucasian populations (3). Moreover, the interactions between different genes and environmental factors may be important, as suggested by some studies performed in Israel. In contrast, studies in Sardinian migrants showed that the high incidence of type 1 diabetes is a consequence of their genetic background more than of environmental influences (9). This does not mean that environmental factors are not relevant in the etiology of type 1 diabetes, but rather that environmental triggers may have a major impact on genetically predisposed subjects. Worldwide a female excess is found in low-incidence populations while the reverse is true in several of high-incidence populations. In the Mediterranean countries, the male to female ratio is close to 1.

Type 2 diabetes

Type 2 diabetes is the major component of the worldwide diabetes epidemic. King et al (2) reported that the prevalence of diabetes in adults aged 20 years and over was 7.5% in 1995, 7.8% in 2000 and will be 10% in 2025 in Italy. Also in Spain the prevalence of diabetes will rise from 7.2% in 1995 to 9.5% in 2025. In contrast, the same authors reported that in France and in Croatia there will be only a moderate increase in the prevalence of diabetes in the adult population: from 2.1% in 1995 and 2000 to 2.6% in 2025 in France and from 4.4 to 5.1% in Croatia (2). In these countries, as in all developed world, the majority of people with diabetes is aged ³ 65 years. This study was based on 5-year age and sex specific prevalence rates, from rural and urban areas of various countries. Inclusion criteria were: diagnosis of diabetes made according to the recommendations of WHO expert groups (plasma venous concentration of 11 mmol/L 2 h after a 75 g oral glucose challenge).

There are many factors influencing the increasing prevalence of diabetes. In so-called developed countries, diabetes, especially type 2 diabetes, has evolved as a major health problem, because of increasing life expectancy and because of changes in lifestyle and diet, with increased prevalence of obesity. Industrialization and socioeconomic development are certainly the most important determinant of the diabetic epidemic in developing countries, where improved nutrition, better hygiene, the control of many infectious diseases, and new effective treatments have resulted in increased longevity (10).

In the western world, people are living longer but the birth rate is stable. This ageing of the population will itself mean that more people will develop diabetes. Thus, age is an important variable influencing the prevalence of diabetes. Most epidemiological studies show that the prevalence of type 2 diabetes increases with age and then declines in very old people (10). However, recent observations have also shown that there is a large percentage of undiagnosed diabetes in older people. There is also evidence that diabetes is more common in females than in males, although in recent years a greater increase in men diagnosed with diabetes has been observed. As diabetes is an age-related disorder, countries with elderly populations have more diabetes than developing countries with younger populations. The high prevalence of type 2 diabetes depends especially on the high prevalence of obesity. In more than 80% of cases, type 2 diabetic patients are obese and therefore interventions towards reduction in diabetes incidence should be carefully planned in terms of prevention of modifiable risk factors. Not only diet is important, but also the sedentary lifestyle is thought to play an important role in increasing the prevalence of type 2 diabetes, especially in young people (10). Recent evidence showed that diabetes can be prevented in the high risk group of people with impaired glucose tolerance by exercise and diet, confirming the importance of these environmental factors in the etiology of type 2 diabetes (11).

Moreover, several studies have found significantly higher prevalence rates in urban rather than rural environments within the same country. Comparisons of migrant populations living in rural and urban settings in the same country also show an excess of diabetes in urban communities. This aspect is actually very interesting since we witness an important migratory flow from developing countries to Europe.

Since both the prevalence of type 2 diabetes and the mean age of patients are increasing throughout most European countries, there has been a consequent increase in the prevalence of cardiovascular and microvascular complications. Recent intervention trials showed that improved glycemic control and aggressive treatments of hypertension and hyperlipidemia can significantly reduce the risk of macrovascular and microvascular complications (12, 13).

The CODE-2 study was conducted to evaluate the health care costs of people with type 2 diabetes in Europe. In Italy, the yearly medical costs for outpatients care and hospitalization per patient was 525 and 2173 Euro respectively in 1998 (4). Moreover this study showed that costs associated with treatment of type 2 diabetic patients with either micro or macrovascular complications were twice the costs of diabetic patients with no complications. The presence of both complications increased costs more than three-fold.

In conclusion, although there is a paucity of data reported for the European countries, estimates and projections suggest an epidemic expansion of diabetes incidence and prevalence in all European countries. Knowledge of prevalence of diabetes and identification of risk factors are essential for a rational planning of health services, to improve the organization and cost-effectiveness of health care.

Suggested readings
1. King H, Rewers M. Global Estimates for Prevalence of Diabetes Mellitus and Impaired Glucose Tolerance in Adults. Diabetes Care 1993, 16 157-176
2. King H, Aubert R, Herman W. Global Burden of Diabetes, 1995-2025. Diabetes Care 1998, 21: 1414-1431.
3. Muntoni S, Muntoni S. New Insights into the Epidemiology of Type 1 diabetes in Mediterranean Countries. Diabetes Metab Res Rev 1999, 15: 133-140.
4. Passa P. Diabetes trends in Europe. Diabetes Metab Res Rev 2002, 18: S3-S8.
5. Tuomilehto J, Karvonen M, Pitkaniemi J, Virtala E, Kohtamaki K, Toivanen L, Tuomilehto-Wolf E. Record-high incidence of Type 1 (insulin-dependent) diabetes mellitus in Finnish children. The Finnish Childhood Type 1 diabetes Registry group. Diabetologia 1999, 42:655-660.
6. Gerstain HC. Cow’s milk exposure and type 1 diabetes. Diabetes Care 1994, 17: 13-19.
7. Parslow RC, McKinney PA, Law GR, Staines A, Williams R, Bodansky HJ. Incidence of childhood diabetes mellitus in Yorkshire, northern England, is associated with nitrate in drinking water: an ecological analysis. Diabetologia 1997, 40: 550-556.
8. Szopa TM, Titchener PA, Portwood ND, Taylor KW. Diabetes mellitus due to viruses- some recent developments. Diabetologia 1993, 36: 687-695.
9. Muntoni S, Fonte MT, Stoduto S. Marietti G, Bizzarri C, Crino A, Ciampalini P, Multari G, Suppa MA, Matteoli MC, Lucentini L, Sebastiani LM, Visalli N, Pozzilli P, Boscherini B, Muntoni S. Incidence of insulin-dependent diabetes mellitus among Sardinian-heritage children born in Lazio region, Italy. Lancet 1997, 349: 160-162.
10. Gadsby R. Epidemiology of diabetes. Advanced Drug Delivery Reviews 2002, 54: 1165-1172
11. Tuomilehto J, Lindstom MS, Eriksson JG, Valle TT, Hamalainen HH, Hanne-Parikka P. Prevention of type 2 diabetes by changes in lifestyle among subjects with impaired glucose tolerance. N Eng J Med 2001, 344: 1343-1349.
12. UK Prospective Diabetes Study Group. Intensive blood glucose control with sulfonylureas or insulin compared with conventional treatments and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998, 352: 837-853.
13. Gaede P, Vedel P, Parving HH, Pedersen O. Intensified multifactorial intervention in patients with type 2 diabetes mellitus and microalbuminuria: the Steno type 2 randomized trial. Lancet 353; 617-622, 1999.