Epidemiological studies on complications in type 1 diabetes

Abstract: The main threat to the health of patients with type 1 diabetes (T1DM) is its complications. This thesis aimed to assess the risks of hip fracture, non-trauma lower extremity amputation (LEA) and myocardial infarction in patients with T1DM as well as the fertility in women with T1DM. In the Swedish Inpatient Register, we identified a population-based cohort of T1DM patients who were first hospitalized for diabetes before age 31. Follow-up for outcomes of interest was done through cross-linkage of the Inpatient Register or linkage to the Causes of Death, Multi-Generation or Medical Birth Register. Standardized Hospitalization / Incidence / Fertility Ratios (SHRs, SIRs and SFRs) with 95% Confidence Interval (CI), were used to estimate relative rates. Poisson Regression modeling was used to compare the relative effects of the SHRs/SIRs/SFRs and the risk of LEAs in different calendar periods. The Kaplan-Meier method was used to estimate the cumulative probability of the outcome of interest. Compared with the general population, more than 7-fold and 9-fold excess risks for hip fracture were observed in men and women, respectively. The cumulative probability of hip fracture was 6.58% until age 65. The risk of LEAs had decreased by 40% in the most recent calendar period (2000-2004) compared to the previous period. However, these patients still had an extremely high risk compared with the general population. By the age of 65, the cumulative probability of a LEA was 11.0% for women, and 20.7% for men. The SIRs for myocardial infarction among T1DM patients decreased from 32.3 for the period 1975-1984 to 15.3 for 1985-1994, and then decreased further to 9.7 for 1995-2004. The relative risk during the follow-up period 1995-2004 decreased by 50% compared to 1975-1984. Similar trends were observed for men and women, non-fatal and fatal myocardial infarction, although excess risks were notable for fatal myocardial infarction in women. No excess risk of myocardial infarction was observed for their non-DM brothers, while a modest excess risk was noted for their non-DM sisters. At age 65 the cumulative probability of a myocardial infarction was 28% for T1DM patients, while the corresponding figure for their non-T1DM siblings was 6%. The presence of diabetes complications conferred much higher risks for hip fracture, non-trauma LEAs and myocardial infarction. Reduced fertility was confined to women first hospitalized before 1985 and a normalization of fertility was observed in women who were first hospitalized after 1985. The presence of diabetes complications was associated with subfertility in all calendar-year strata. The proportions of newborns with congenital malformations decreased from 11.7% during 1973 1984 to 6.9% during 1995 2004, but were still higher compared to that of the women in the general Swedish population. In conclusion, although relative risks for myocardial infarction, non-trauma LEAs decreased markedly with time and also fertility normalized in recent period, T1DM patients are still at increased risk for these complications, especially among those with diabetes complications. Better treatment of hyper-glycemia and hyper-lipidemia as well as hypertension are most probably the cause of the reduced risks. Effective early preventive programs should be further designed and implemented.