Clinical Risk Factors Differ by Sex for Kidney Complications but Not Retinopathy in Type 1 Diabetes: The Pittsburgh Epidemiology of Diabetes Complications Cohort

OBJECTIVE: Data on sex-specific risk factors for type 1 diabetes microvascular complications are limited. We assessed sex-specific associations of longitudinal clinical risk factors and 30-year retinopathy and kidney end point incidence in the Pittsburgh Epidemiology of Diabetes Complications type 1 diabetes cohort. RESEARCH DESIGN AND METHODS: The cohort (n = 325 women and 333 men; mean baseline age 27 years; diabetes duration 19 years) was followed from 1986-1988 to 2016-2018 for the following: incident proliferative diabetic retinopathy (PDR) (Early Treatment of Diabetic Retinopathy Study grade ≥60 or laser photocoagulation); severely increased albuminuria (SIA) (albumin excretion rate ≥200 µg/min); and estimated glomerular filtration rate < 60 mL/min/1.73 m2 (chronic kidney disease [CKD] G3). Associations between longitudinal risk factors and time to each event were assessed by sex in multivariable joint models in those who were complication free at baseline. RESULTS: PDR incidence was similar by sex (57% in women vs. 59% in men; P = 0.54). SIA incidence was lower in women (18% vs. 25% in men; P = 0.10); and CKD G3 was higher in women (28% vs. 21% in men; P = 0.11). In both sexes, independent risk factors for PDR included HbA1c and blood pressure (BP) (women's systolic BP: hazard ratio [HR] 1.27 [95% CI 1.12, 1.45]; men's diastolic BP: HR 1.40 [95% CI 1.15, 1.70]). For SIA, HbA1c was associated in both sexes, but other factors differed, including triglyceride levels (HR 1.38 per log1.2; 95% CI 1.06, 1.78) and BMI (HR 0.87; 95% CI 0.76, 1.00) in women and smoking (HR 3.46; 95% CI 1.07, 11.24) in men. For CKD G3, HbA1c was a risk factor in both sexes; smoking was also associated in men. CONCLUSIONS: Although HbA1c and BP are important risk factors for retinopathy regardless of sex, sex-specific clinical targets warrant further research to optimize kidney protection in type 1 diabetes.