Effect of pioglitazone on insulin secretion in patients with both impaired fasting glucose and impaired glucose tolerance
Medical Research Unit in Clinical Epidemiology, Hospital of Specialties, Medical Unit of High Specialty, West National Medical Center, Mexican Institute of Social Security, Guadalajara, Mexico. Diabetes Research and Clinical Practice
(Impact Factor: 2.54).
02/2007; 75(1):115-8. DOI: 10.1016/j.diabres.2006.05.003
To evaluate the effect of a thiazolidinedione, pioglitazone, on insulin secretion in patients with both impaired fasting glucose and impaired glucose tolerance.
A randomized, double-blind, placebo-controlled clinical trial was carried out in 18 overweight or obese patients with both impaired fasting glucose and impaired glucose tolerance. Pharmacological intervention consisted of an oral morning administration of pioglitazone (30 mg) or a placebo with a similar presentation for 30 days. Before and after the intervention, glucose, creatinine, lipid profile and uric acid concentrations were measured. To evaluate insulin secretion (early, late and total phases) and insulin sensitivity, a hyperglycemic-hyperinsulinemic clamp was also performed.
There were significant reductions (p=0.008) in fasting insulin concentration (121 versus 45 pmol/l), late (565 versus 307 pmol/l) and total insulin secretion (474 versus 254 pmol/l), as well as, in 2h postload glucose levels (9.7 versus 6.9 mmol/l, p=0.028), with an increment in insulin sensitivity after pioglitazone administration (7.5 versus 9.9).
Pioglitazone administration during a period of 4 weeks decreased late and total insulin secretion phases, fasting insulin and 2h postload glucose levels, and improved insulin sensitivity in patients with both impaired fasting glucose and impaired glucose tolerance.
Available from: ajpendo.physiology.org
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ABSTRACT: Thiazolidinediones (TZDs) improve glycemic control and insulin sensitivity in patients with type 2 diabetes mellitus (T2DM). There is growing evidence from in vivo and in vitro studies that TZDs improve pancreatic beta-cell function. The aim of this study was to determine whether TZD-induced improvement in glycemic control is associated with improved beta-cell function. We studied 11 normal glucose-tolerant and 53 T2DM subjects [age 53+/-2 yr; BMI 29.4+/-0.8 kg/m2; fasting plasma glucose (FPG) 10.3+/-0.4 mM; Hb A1c 8.2+/-0.3%]. Diabetic patients were randomized to receive placebo or TZD for 4 mo. Subjects received 1) 2-h OGTT with determination of plasma glucose, insulin, and C-peptide concentrations and 2) two-step euglycemic insulin (40 and 160 mU.m-2.min-1) clamp with [3-(3)H]glucose. T2DM patients were then randomized to receive 4 mo of treatment with pioglitazone (45 mg/day), rosiglitazone (8 mg/day), or placebo. Pioglitazone and rosiglitazone similarly improved FPG, mean plasma glucose during OGTT, Hb A1c, and insulin-mediated total body glucose disposal (Rd) and decreased mean plasma FFA during OGTT (all P<0.01, ANOVA). The insulin secretion/insulin resistance (disposition) index [DeltaISR(AUC)/Deltaglucose(AUC)/IR] was significantly improved in all TZD-treated groups: +1.8+/-0.7 (PIO+drug-naïve diabetics), +0.7+/-0.3 (PIO+sulfonylurea-treated diabetics), and 0.7+/-0.2 (ROSI+sulfonylurea-withdrawn diabetics) vs. -0.2+/-0.3 in the two placebo groups (P<0.01, all TZDs vs. placebo, ANOVA). Improved insulin secretion correlated positively with increased body weight, fat mass, and Rd and inversely with decreased plasma glucose and FFA during the OGTT. In T2DM patients, TZD treatment leads to improved beta-cell function, which correlates strongly with improved glycemic control.
AJP Endocrinology and Metabolism 03/2007; 292(3):E871-83. DOI:10.1152/ajpendo.00551.2006 · 3.79 Impact Factor
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ABSTRACT: Insulin resistance and hyperglycemia characterize type 2 diabetes mellitus. Type 2 diabetes mellitus is usually accompanied by concomitant disorders, such as dyslipidemia, hypertension and atherosclerosis. Thiazolidinediones are antidiabetic drugs that increase insulin sensitivity by activating the peroxisome proliferator-activated receptor gamma. There is evidence that thiazolidinediones exert a number of pleiotropic effects that may play an important role in the treatment of type 2 diabetes mellitus.
The purpose of the present article was to review the 'pleiotropic' effects of thiazolidinediones (i.e., their effects beyond glucose lowering).
The study involved searching PubMed up to February 2008 using relevant keywords.
Thiazolidinediones favorably alter fat distribution and improve cardiovascular risk factors, such as blood pressure, inflammation markers and uric acid and they may also delay the progression of atherosclerosis. The effects on the lipid profile differ between the two thiazolidinediones studied with pioglitazone having more positive effects compared with rosiglitazone. Furthermore, thiazolidinediones improve diabetic complications, such as diabetic nephropathy and non-alcoholic fatty liver disease. Thiazolidinediones may also play a role in other diseases, such as polycystic ovary syndrome. These pleiotropic effects may prove to be clinically relevant. There has been recent debate about the possible differences between the two thiazolidinediones in terms of cardiovascular disease outcome. In this context, differences in the lipid effects between the two drugs may be relevant.
Expert Opinion on Pharmacotherapy 06/2008; 9(7):1087-108. DOI:10.1517/146565220.127.116.117 · 3.53 Impact Factor
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ABSTRACT: The aim of this meta-analysis of randomized clinical trials (RCT) was to assess whether pioglitazone is also associated with increased cardiovascular risk, as recently reported for rosiglitazone.
RCT of pioglitazone were retrieved from Medline (any date up to 31 August 2007; English language only). Unpublished RCT were identified through http://www.clinicaltrials.gov or http://www.fda.gov websites, and results on cardiovascular outcomes were retrieved from investigators and/or sponsors, whenever possible. RCT were included in meta-analysis if pioglitazone was compared with other treatments (placebo, active comparators or no treatment) for at least 4 weeks. Ninety-four trials, 10 of which were unpublished, were retrieved; those included in the analysis, which excluded PROspective PioglitAzone Clinical Trial In MacroVascular Events (PROACTIVE), enrolled 11 268 and 9912 patients in the pioglitazone and comparator groups respectively. Data for analysis, extracted independently by two observers, included all-cause and cardiovascular mortality and incidence of non-fatal coronary events and heart failure. Proportions of outcome measures across treatment groups were compared by odds ratios (ORs) and 95% confidence interval.
Pioglitazone was associated with reduced all-cause mortality [OR 0.30 (0.14-0.63); p < 0.05], with no relevant effect on non-fatal coronary events. The observed increase in incidence of non-fatal heart failure was not statistically significant [OR 1.38 (0.90-2.12)].
The use of pioglitazone does not appear to be harmful in terms of cardiovascular events and all-cause deaths.
Diabetes Obesity and Metabolism 12/2008; 10(12):1221-38. DOI:10.1111/j.1463-1326.2008.00892.x · 6.36 Impact Factor
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