Estimated Glomerular Filtration Rate and Incident Prediabetes Risk in Normoglycemic Adults with Parental Type 2 Diabetes

Objective We examined glomerular filtration rate (eGFR) in relation to cardiometabolic and glucoregulatory factors and prediabetes risk in healthy subjects. Methods Participants were normoglycemic Black and White offspring of parents with type 2 diabetes followed for 5 years in the Pathobiology of Prediabetes in a Biracial Cohort (POP-ABC) study. Baseline assessments included clinical examination, OGTT, blood chemistries, insulin sensitivity (Si-clamp), insulin secretion and eGFR (derived from CKD-EPI equation). We analyzed baseline eGFR in relation to metabolic syndrome (MetS), glucoregulatory function, and prediabetes risk using linear regression and Cox proportional hazards models. Results The participants (N=296; 73% female; 138 Black, 158 White) were aged 45.5 ± 10.1 years; BMI was 30.5 ± 7.6 kg/m2, and eGFR was 103 ± 18.7 mL/min. Baseline eGFR increased with cumulative MetS components (ANOVA P = 0.0002) and correlated significantly with waist circumference (r=0.39, P<0.0001), HDL cholesterol (r= -0.38, P<0.0001), Si-clamp (r= -0.22; P= 0.003), and insulin secretion (r= 0.22; P= 0.0003). Higher baseline eGFR predicted lower risk of incident prediabetes: hazard ratio (HR) 0.986 [95% CI 0.975-0.997, P= 0.012], adjusted for age, sex, ethnicity, BMI, waist circumference, glucose, insulin sensitivity, insulin secretion and albuminuria. Conclusion eGFR variations within the normal range signify cardiometabolic risk status, glucoregulatory function, and incident prediabetes risk among normoglycemic persons. Further studies are needed to determine the mechanisms linking kidney function and early dysglycemia.