Relationship between sodium–lithium countertransport and insulin sensitivity in mild hypertension

Objectives. To study the relationship between insulin sensitivity and sodium-lithium countertransport (Na⁺-Li⁺ CT) in mild, essential hypertension, and to investigate the effect of metformin and metoprolol, respectively. Design. A double-blind, triple cross-over, placebo-controlled study over a total period of 18 weeks. Setting. A hypertension out-patient clinic and research laboratory at Sahlgrenska University Hospital. Subjects. Seventeen non-obese men with mild essential hypertension and 17 weight-matched, healthy controls. Interventions. Metformin 850 mg b.i.d., metoprolol CR 100 mg once daily and placebo were given during 18 weeks. Each treatment period was 6 weeks. A euglycaemic clamp was performed and erythrocyte Na⁺-Li⁺ CT measured after each 6-week treatment period. Main outcome measures. Insulin sensitivity, erythrocyte Na⁺-Li⁺ CT, their interrelation, and the effect of metformin and metoprolol CR on both variables, respectively. Results. The hypertensive men tended to have an elevated Na⁺-Li⁺ CT compared with the control subjects (0.34±0.03 versus 0.26±0.02 mmol L^-1  h^-1, P<0.1). Glucose disposal rate was similar, but plasma insulin levels higher (P<0.05) among the hypertensives than the controls. Na⁺-Li⁺ CT exhibited a positive relationship to BMI (r=0.53, P=0.03) and a negative correlation to glucose disposal rate (r=-0.66, P=0.008) in the hypertensive subjects. In multiple regression analysis, Na⁺-Li⁺ CT showed a significant correlation to glucose disposal rate only. In the control subjects, there was no relation between glucose metabolism and Na⁺-Li⁺ CT. Neither metformin nor metoprolol influenced Na⁺-Li⁺ CT, glucose disposal rate or plasma insulin. Conclusion. Erythrocyte Na⁺-Li⁺ CT seemed to be closely related to insulin-glucose metabolism in mild hypertension, but was not influenced by metformin or metoprolol.