Long-term mortality and retinopathy in type 1 diabetes

The incidence of type 1 diabetes is increasing in Denmark as well as the rest of the world. Due to diabetes-related micro- and macrovascular complications, the morbidity and the mortality is higher among type 1 diabetic patients. The aim of this thesis was to examine a population-based cohort of 727 type 1 diabetic patients from Fyn County, Denmark, with an onset of diabetes before 1 July 1973 in order to: (1) Evaluate the all-cause mortality rates and the influence of sex, duration of diabetes and calendar year of diagnosis in a 33-year follow-up (Paper I). (2) Examine glycaemic regulation, lipids and renal dysfunction as risk factors for all-cause mortality, cardiovascular mortality and IHD (Paper II). (3) Estimate the prevalence of DR as well as the 25-year incidence of PDR and associated risk factors in long-time surviving patients (Paper III). (4) To compare the grading of DR between ETDRS seven standard field 30 degrees stereoscopic colour films and nine field 45 degrees monoscopic digital colour images in long-term surviving patients (Paper IV). In the years 1973-2006 an overall MR of 22.3 per 1000 person-years was found. Furthermore a relative mortality of 3.4 was found as compared to the general population in Denmark. The relative mortality was especially high for patients aged 30-39 (SMR 9.8). There was a tendency towards a better survival for patients diagnosed after 1964. This was especially seen for men. Diabetes was the most common cause of death for those who died in the group. In 1993-1996 blood samples were drawn and glycaemic regulation, lipids and renal markers were subsequently used as predictors of all-cause mortality, cardiovascular mortality and ischaemic heart disease. Glycaemic regulation, dyslipidaemia and creatinine were all significantly associated with all three endpoints. Furthermore, variations in glycaemic control were also identified as a risk factor for overall mortality. Two hundred and one patients were examined for diabetic retinopathy in 1981-1982 and 2007-2008. At follow-up, 97.0% had DR and 42.9% of all patients without PDR at baseline developed this during the follow-up period. Patients who had had a poor glycaemic regulation as well as those who had NPDR at baseline were more likely to develop PDR than the remaining patients. On the other hand, other risk factors such as high blood pressure and proteinuria did not predict PDR. In the comparative study between ETDRS seven standard field 30 degrees stereoscopic colour films and nine field 45 degrees monoscopic digital colour images, 43 eyes of 43 patients were examined in 2008. A poor correlation was found between the two methods: only 29.3% were graded alike. In the remaining, the level of DR was graded higher in the digital photos. Among these, PDR was detected in three eyes using digital photos but remained undetected on all films. This suggests that digital photos with wide fields are the best way to detect DR in long-term type 1 diabetic patients. Overall, it is concluded that mortality is still higher among type 1 diabetic patients. This depends, among other things, on glycaemic regulation, lipid status and, partly, renal dysfunction. Diabetic retinopathy is almost universal in long-term type 1 diabetic patients, and almost half of all patients will develop PDR in 25 years. Nine field digital photos provide the best grading of retinopathy in long-term type 1 diabetic patients.