The contribution of diabetes duration, both pre- and postpuberty, to the development of microvascular complications and mortality in diabetic subjects was investigated in three study populations from the Children's Hospital of Pittsburgh Insulin-Dependent Diabetes Mellitus (IDDM) Registry. Life-table analyses by total and postpubertal IDDM duration were used to evaluate differences in the prevalence of microvascular complications and diabetes-related mortality in subjects diagnosed before and during puberty, as defined by an age at IDDM onset marker of 11 yr for girls and 12 yr for boys. The prevalence of retinopathy and overt nephropathy in 552 White adult diabetic subjects (population 1, mean IDDM duration 20.8 yr was significantly greater in subjects diagnosed during puberty compared with those diagnosed before puberty. However, similar analyses by postpubertal duration showed no difference in microvascular complication prevalence between the two groups. These findings did not appear to be due to a confounding effect of age. Additional analyses of 239 adolescent diabetic subjects (population 2, mean duration 8.3 yr) revealed the same trend for the prevalence of retinopathy. Finally, results concerning the risk of diabetes-related mortality in a cohort of 1582 subjects (population 3, mean duration 12.9 yr) indicated that postpubertal duration of IDDM may be a more accurate determinant of the development of microvascular complications and diabetes-related mortality than total duration, and it is suggested that the contribution of the prepubertal years of diabetes to long-term prognosis may be minimal.

This ecological analysis suggests that low-level nitrate exposure through drinking water may play a role in the etiology of IDDM, perhaps as a promoter through the generation of free radicals.

Using a case-control study design, we examined the hypothesis that early exposure to cow's milk and solid foods increased the risk of IDDM. An infant diet history was collected from 164 IDDM subjects from the Colorado IDDM Registry with a mean birth year of 1973, and 145 nondiabetic population control subjects who were frequency matched to diabetic subjects on age, sex, and ethnicity. Early exposure was defined as exposure occurring before 3 mo of age. After controlling for ethnicity, birth order, and family income, more diabetic subjects were exposed early to cow's milk (OR 4.5, 95% CI 0.9-21.4) and solid foods (OR 2.5, CI 1.4-4.3) than control subjects. To examine this association while accounting for the genetic susceptibility to IDDM, we defined individuals as high and low risk by an HLA-DQB1 molecular marker. Early exposure to cow's milk was not associated with elevated risk for IDDM in low-risk individuals. Relative to unexposed low-risk individuals, early exposure to cow's milk was strongly associated in individuals with a high risK marker (OR 11.3, CI 1.2-102.0). Similar findings were observed for early exposure to solid foods. These data indicate that early exposure to cow's milk and solid foods may be associated with increased risk of IDDM. The inclusion of HLA-encoded risk in the analyses demonstrates the combined effect of genetic and environmental factors.

The analyses of this study cohort suggest that the observed protective effect of breast-feeding on the risk of IDDM may be related to differences in the age at exposure to breast milk substitutes in blacks but not in whites.