Association between serum lipids, glucose tolerance, and insulin sensitivity during 12 months of celiprolol treatment

Abstract

The study was undertaken to evaluate the development and association of parameters related to the metabolic syndrome during celiprolol treatment. Hyperinsulinemic euglycemic clamp and independent oral glucose tolerance tests (OGTT) were performed on 25 nondiabetic patients with controlled hypertension and dyslipidemia. The tests were carried out during 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 group in which treatment was kept unchanged. Insulin sensitivity index (ISI), measured by the euglycemic clamp test, increased 35% in the celiprolol group at 6 months and remained at that level at 12 months, independent of the previous treatment (p = 0.03, compared to the change in the control group). During a 2 hour OGTT, incremental glucose area under the curve (AUC) decreased from 4.5 to 1.9 hr x mmol/l during 6 months 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 mU/l, and decreased further to 68 hr x mU/l (p < 0.01). All insulin parameters in OGTT were highly significant (p < 0.0001) and inversely associated with ISI. Insulin AUC had the best linear correlation with ISI (r = -0.682, p < 0.0001). Glucose parameters in OGTT correlated only weakly and 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, clinical, and demographic parameters proved to be independently significant predictors for ISI in multiple regression analysis. These were insulin AUC, fasting insulin levels, triglyceride values, and age. The coefficient of determination in this four-parameter linear model was 69%. In this preliminary, observer-masked trial with a limited control group, celiprolol improved the impaired insulin sensitivity and glucose tolerance of dyslipidemic hypertensive patients. A fairly predictive model can be formulated to evaluate the peripheral insulin sensitivity of hypertensive patients with suspected metabolic syndrome using OGTT with serum insulin determinations.

Antihypertensive agents, insulin sensitivity, and new-onset diabetes

“…In contrast, dilevalol, a 1 -selective blocker with a 2 -agonistic action, that was latter withdrawn from the market, was shown to improve IS in hypertensive patients by approximately 19% [23]. In another study, hypertensive patients treated for 12 months with a 1 blocker with 2 -agonistic effects, celiprolol, showed an increase of 35% [24]. Studies with carvedilol, a nonselective blocker with 1 -blocking properties, in patients with hypertension [25] or hypertension and diabetes [26] also reported a 14% and a 20% significant increase, respectively, in IS estimated with the clamp after 12 and 24 weeks of treatment.…”

Effects of Antihypertensive Therapy on Glucose and Insulin Metabolism and on Left Ventricular Mass

“…In addition, ␤-blockers tend to increase total peripheral resistance, leading to a reduction in skeletal muscle blood flow and glucose uptake, which increases insulin resistance. This theory is reinforced by the findings that the new generation of vasodilating ␤-blockers, such as divedalol, 37 celiprolol, 39 and carvedilol, 38 induce an improvement in peripheral vascular resistance and a slight improvement in insulin sensitivity in nonobese individuals. Finally, ␤-blocker treatment is often associated with a significant weight gain, 40 as was seen in this study.…”

Long-term treatment with nebivolol attenuates renal damage in Zucker diabetic fatty rats

“…However, they are underused in diabetic patients because of possible adverse effects on carbohydrate and lipid metabolism, including insulin resistance, glucose intolerance and dyslipidemia [16]. There are data suggesting that newer b-blockers with vasodilating properties have a different metabolic profile than traditional ones, and could therefore be of particular benefit for patients with type 2 diabetes mellitus [20][21][22][23].…”