IJE Advance Access originally published online on August 8, 2005
International Journal of Epidemiology 2005 34(5):1123-1128; doi:10.1093/ije/dyi160
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Genetics |
Enhanced Na–Li countertransport: a marker of inherited susceptibility to type 2 diabetes
1 Department of Clinical and Experimental Medicine, Federico II University of Naples, Napoli, Italy
2 School of Public Health and Health Professions, University at Buffalo, Buffalo, NY, USA
3 Nephrology, Second University, Naples, Napoli, Italy
4 Gubbio Hospital, Gubbio, Italy
5 Center of Epidemiological Research, Merck Sharp & Dohme, Italy
* Corresponding author. Department of Clinical and Experimental Medicine, Via S Pansini 5, 80131–Naples, Italy. E-mail: ovaccaro{at}unina.it
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.
Keywords Countertransport, hypertension, insulin resistance
Accepted 14 July 2005