Enhanced Na-Li countertransport: A marker of inherited susceptibility to type 2 diabetes

Introduction: The association between type 2 diabetes and hypertension has long been described, but the mechanisms remain unclear. Na-Li countertransport (Na-Li CT) activity is viewed as a marker of inherited pre-disposition to hypertension, especially if associated with other metabolic abnormalities. Aim: To evaluate whether enhanced Na-Li CT activity is a predictor of type 2 diabetes. Methods: Study participants were 2167 men and women, 30-70 years. Na-Li CT activity, glucose, HDL cholesterol, blood pressure, height, and weight were measured. Six years incidence of diabetes (WHO) was assessed. Results: Baseline Na-Li CT activity was significantly higher for people who developed diabetes at follow-up (n = 101) than for those who remained non-diabetic (364 ±184 vs 300 ± 150 μmol/l RBC/ h, P< 0.001). This finding was confirmed after correction for obesity, hypertension, and blood glucose. Six years' incidence of diabetes increased across tertiles of baseline Na-Li CT activity--from 2 to 7%--with a significant linear trend (P< 0.001). In multivariate analyses Na-Li CT is a significant predictor of diabetes independent of age, BMI, HDL cholesterol, hypertension, and plasma glucose; based on exponentiation of the regression coefficient Na-Li CT higher by 154 μmol (i.e. 1 SD of the population mean) was associated with a 36% greater risk of incident diabetes. Conclusions: Prospective data from the present study show for the first time enhanced Na-Li CT activity is a significant predictor of development of diabetes in adults, thus suggesting that it could be viewed as a pre-clinical, possibly genetic, marker of inherited susceptibility to type 2 diabetes.