Differential Effect of Glycemia on the Incidence of Hypertension by Sex: The Epidemiology of Diabetes Complications study

OBJECTIVE: Diabetes Control and Complications Trial/Epidemiology of Diabetes Intervention and Complications analyses demonstrated that intensive insulin therapy was inversely associated with incident hypertension. We thus sought to confirm these observations and, given sex differences in other type 1 diabetes complications and risk factors, assessed whether any such associations differ by sex. RESEARCH DESIGN AND METHODS: Participants of a prospective cohort of childhood-onset type 1 diabetes, free of hypertension at study entry (baseline mean age, 28 years; diabetes duration, 19 years), were selected for study (n = 510). Hypertension incidence was defined as blood pressure >140/90 mmHg or use of hypertension medications in two consecutive visits. Intensive insulin therapy was defined as three or more injections (or pump) and four or more glucose tests daily. Baseline predictors of hypertension were examined using Cox proportional hazards models. Models with time-dependent updated means of baseline significant variables were also constructed. RESULTS: Hypertension incidence over 18 years of follow-up was marginally higher in men than in women (43.2 vs. 35.4%, P = 0.07). A significant interaction was noted between sex and HbA(1c), and separate models were constructed by sex. Multivariably, elevated HbA(1c) was a significant predictor only in men (hazard ratio 1.48 [95% CI 1.28–1.71]). In time-dependent models, although a significant effect of HbA(1c) was also seen in women (1.21 [1.00–1.46]), the effect of glycemic control on hypertension development remained stronger in men (1.59 [1.29–1.97], P interaction <0.0001). CONCLUSIONS: Although hyperglycemia is a risk factor for hypertension, its effect is stronger in men compared with women with type 1 diabetes.