Effect of Torcetrapib on Glucose, Insulin, and Hemoglobin A _1c in Subjects in the Investigation of Lipid Level Management to Understand its Impact in Atherosclerotic Events (ILLUMINATE) Trial

Abstract

Background-High-density lipoproteins have antidiabetic properties in vitro. Furthermore, elevated high-density lipoprotein levels accompanying a genetic deficiency of cholesteryl ester transfer protein are associated with decreased levels of plasma glucose. We now investigate effects on glucose homeostasis of inhibiting cholesteryl ester transfer protein with torcetrapib. Methods and Results-A post hoc analysis of the Investigation of Lipid Level Management to Understand its Impact in Atherosclerotic Events (ILLUMINATE) trial was conducted to investigate effects of the cholesteryl ester transfer protein inhibitor torcetrapib on glycemic control in the 6661 diabetic patients in the trial. At baseline, there were no differences between the 2 treatment arms with respect to plasma glucose, insulin, hemoglobin A 1c , or the homeostasis model assessment of insulin resistance. After 3 months, the diabetic subjects taking the combination of torcetrapib plus atorvastatin had plasma glucose levels 0.34 mmol/L lower (PϽ0.0001) and insulin levels 11.7 U/mL lower (PϽ0.0001) than in those receiving atorvastatin alone. Homeostasis model assessment of insulin resistance values decreased from 49.1 to 47.3 (PϽ0.0001) in the torcetrapib/atorvastatin arm compared with an increase in homeostasis model assessment of insulin resistance in the atorvastatin arm. At the 6-month time point, the mean hemoglobin A 1c level in the atorvastatin arm was 7.29% compared with 7.06% in the torcetrapib/atorvastatin arm (PϽ0.0001). These effects of torcetrapib remained apparent for up to 12 months. Torcetrapib also lowered both glucose and insulin levels in the participants without diabetes mellitus, although the effects were not as great as in those with diabetes mellitus. Conclusions-Treatment with torcetrapib improves glycemic control in atorvastatin-treated patients with type 2 diabetes mellitus. It remains to be determined whether this effect is the consequence of raising high-density lipoprotein.at Clinical Trial Registration-http:www.clinicaltrials.gov. Unique identifier: NCT00134264. (Circulation. 2011;124:555-562.)

In vivo PET imaging with [18F]FDG to explain improved glucose uptake in an apolipoprotein A-I treated mouse model of diabetes

“…Therapeutic interventions that increase plasma HDL levels improve glycaemic control in patients with type 2 diabetes [2,3], and treatment with HDL or apoA-I has been shown to increase glucose uptake into skeletal muscle [4,5] and adipose tissue [6]. Furthermore, treatment with HDL or apoA-I increases insulin secretion and production in isolated pancreatic islets and insulinoma beta cell lines [7,8].…”

Low Levels of High-Density Lipoprotein Cholesterol Do Not Predict the Incidence of Type 2 Diabetes in an Iranian High-Risk Population: The Isfahan Diabetes Prevention Study

“…In another trial, torcetrapib, a plasma lipid transfer protein inhibitor that also raised HDLC levels, improved glycemic control [27]. In a recent observational study, irrespective of the possible limitations of the study design, patients with hypercholesterolemia appeared less likely to develop T2D than unaffected relatives, suggesting a link between LDL receptor-mediated transmembrane cholesterol transport and T2D [36].…”

“…Although increasing plasma HDLC levels have been suggested to reduce the risk of T2D [25], a recent trial showed that treatment with niacin, which raised HDLC, also raised blood glucose and T2D risk [26]. In another trial, treatment with torcetrapib, a plasma lipid transfer protein inhibitor which also raised HDLC concentrations, improved glycemic control [27], but the role of HDLC in reducing the risk of T2D remains poorly defined.…”

The biological activity of high-density lipoprotein fractions and their role in the development of cardiovascular diseases

“…Островитянова, 1; тел. : +7(967)24406461; e-mail: babinzevajana@ mail.ru существенным и независимым образом связан с повышенным риском развития ИБС [5,6]. Отрицательная корреляция концен-трации ХС ЛПВП с показателями риска развития ССЗ привела к созданию методов лечения ССЗ при помощи повышения уровня ХС ЛПВП.…”