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 micromol/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 micromol (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.
Vaccaro
Olga
O
Department of Clinical and Experimental Medicine, Federico II University of Naples, Napoli, Italy. ovaccaro@unina.it
Cuomo
Vincenzo
V
Trevisan
Maurizio
M
Cirillo
Massimo
M
Panarelli
Walter
W
Laurenzi
Martino
M
Mancini
Mario
M
Riccardi
Gabriele
G
D000328:Adult; D000368:Aged; D017920:Antiporters / Q000235:genetics / Q000378:metabolism*; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure / Q000502:physiology; D015992:Body Mass Index; D008076:Cholesterol, HDL / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D015994:Incidence; D008094:Lithium / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*
D017920:Antiporters; D001786:Blood Glucose; D008076:Cholesterol, HDL; D005819:Genetic Markers; C045885:sodium-lithium countertransporter; D008094:Lithium; D012964:Sodium