Genetic and Environmental Factors for Type 1 Diabetes: Data from the province of Oristano, Sardinia, Italy

The exact role of genetic susceptibility and environmental factors in determining type 1 diabetes has not been clarified. The island of Sardinia has one of the highest rates of type 1 diabetes in the world (1). The contribution of genetic susceptibility to the etiology of type 1 diabetes has been investigated in several studies of migrants of Sardinian origin who live in various regions of Italy (2,3,4). However, few data are available on the risk of type 1 diabetes among immigrants of mainland origin who live in Sardinia (5).

To further examine the contribution of genetic and environmental factors to type 1 diabetes in Sardinia, we enrolled all incident cases of type 1 diabetes diagnosed in the province of Oristano aged 0–29 years between 1993 and 2000 (5). Data sources included the local pharmaceutical service, which provides patients with insulin syringes and other material needed for daily therapy (primary source), a register of individuals with chronic conditions that are exempt from health service fees, and the pediatric department of Oristano’s provincial hospital. Finally, our data were checked with the Eurodiab Ace Sardinian Registry. We used the capture-recapture method to assess the completeness of our sources, and we used the population data supplied annually to the Public Health Service by the 78 municipalities of the province to calculate rates.

The primary source completeness was 100%. As of 31 December 2000, 303 patients aged 0–29 years who were residents of the Oristano province had been identified, including 10 with secondary diabetes who were excluded from further analysis. The point prevalence was 5.4 per 1,000 (95% CI 4.8–6.0). The incidence rate, standardized by age (direct method; reference population with a uniform age distribution) from 1993 to 2000, was 52.7 per 100,000 person-years (95% CI 42.4–63.0) in the 0- to 14-year age-group, 21.5 (16.0–26.9) in the 15- to 29-year age-group, and 37.1 (31.2–42.7) in the overall 0- to 29-year age-group.

Incidence was not stable in the 8-year period of the study. In particular, we observed a peak in the 0- to 14-year age-group in 1998, with 24 cases observed (incidence rate 105.2/100,000, 95% CI 70.5–157.0), as compared with 13 cases expected, resulting in a standardized incidence ratio (SIR) of 1.92 (95% CI 1.23–3.01, P = 0.004; Wald test). In 1994, five cases were observed (incidence rate 19.6/100,000, 8.2–47.1), far lower than the 14.5 cases that were expected, resulting in a SIR of 0.35 (0.14–0.88, P = 0.03).

When the overall 0–29 year age-group was considered, annual fluctuations were less dramatic, with SIRs of 1.56 (95% CI 1.06–2.30, P = 0.02) in 1998 and 0.44 (0.26–0.74, P = 0.002) in 1994. These data suggest that there is an interaction between type 1 diabetes and age.

When we examined geographic variations, no cases were reported in the municipality of Arborea among the population aged 0–29 years (1,571 inhabitants, 8.5 cases expected, P = 0.0005; Fisher’s exact test). According to previous observations (5), this is likely explained by the fact that ∼65% of the Arborea population is of non-Sardinian origin; most were originally from the Veneto Region of Italy. Also, data on the incidence of type 1 diabetes in the previous 12 years (our data plus data for 1989–1992, published by the Regional Department of Epidemiology) (6) support our findings of a lower-than-expected rate in Arborea (0 cases of 20,896 person-years in the 0- to 29-year age-group vs. 234 cases of 718,739 person-years in the remaining province, P = 0.002; Fisher’s exact test).

In conclusion, our data further support the findings of others that type 1 diabetes is determined by genetic and environmental factors. The rapid fluctuations in incidence during the study period suggest a role of environmental factors, whereas the absence of observed cases among a population mainly of non-Sardinian origin suggests the role of genetic risk factors.