ASSOCIATION BETWEEN SERUM-LIPIDS, GLUCOSE-TOLERANCE, AND INSULIN SENSITIVITY DURING 12 MONTHS OF CELIPROLOL TREATMENT

The study was undertaken to evaluate the development and association o f parameters related to the metabolic syndrome during celiprolol treat ment. Hyperinsulinemic euglycemic clamp and independent oral glucose t olerance tests (OGTT) were performed on 25 nondiabetic patients with c ontrolled hypertension and dyslipidemia. The tests were carried out du ring the patients' previous antihypertensive monotherapy (beta- or Ca- blocker, or an ACE inhibitor), and after 6 and 12 months of celiprolol treatment. About one third of patients were randomized to a control g roup in which treatment was kept unchanged. Insulin sensitivity index (ISI), measured by the euglycemic clamp test, increased 35% in the cel iprolol group at 6 months and remained at that level at 12 months, ind ependent of the previous treatment (p = 0.03, compared to the change i n the control group). During a 2 hour OGTT, incremental glucose area u nder the curve (AUG) decreased from 4.5 to 1.9 hr x mmol/l during 6 mo nths of celiprolol treatment, and decreased further to 1.5 hr x mmol/l at 12 months (p < 0.001). Insulin AUC decreased from 113 to 72 hr x m U/l, and decreased further to 68 hr x mU/l (p < 0.01). All insulin par ameters in OGTT were highly significant (p < 0.0001) and inversely ass ociated with ISI. Insulin AUC had the best linear correlation with ISI (r = -0.682, p < 0.0001). Glucose parameters in OGTT correlated only weakly acid inversely with insulin sensitivity. From the fasting serum lipids, triglycerides showed an inverse (p < 0.001) and HDL a weak (p < 0.05) positive association with ISI. Four out of 20 metabolic, clin ical, and demographic parameters proved to be independently significan t predictors for ISI in multiple regression analysis. These were insul in AUG, fasting insulin levels, triglyceride values, and age. The coef ficient of determination in this four-parameter linear model was 69%. In this preliminary, observer-masked trial with a limited control grou p, celiprolol improved the impaired insulin sensitivity and glucose to lerance of dyslipidemic hypertensive patients. A fairly predictive mod el can be formulated to evaluate the peripheral insulin sensitivity of hypertensive patients with suspected metabolic syndrome using OGTT wi th serum insulin determinations.