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IJE Advance Access published online on August 8, 2005
International Journal of Epidemiology, doi:10.1093/ije/dyi160
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Published by Oxford University Press on behalf of the International Epidemiological Association © The Author 2005; all rights reserved.
Accepted July 14, 2005

Original paper

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

Olga Vaccaro 1*, Vincenzo Cuomo 1, Maurizio Trevisan 2, Massimo Cirillo 3, Walter Panarelli 4, Martino Laurenzi 5, Mario Mancini 1, Gabriele Riccardi 1, and On behalf of the Gubbio Study Research Group

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

* To whom correspondence should be addressed.
Olga Vaccaro, E-mail: ovaccaro{at}unina.it


  Abstract

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.
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