Dataset Information

Pioglitazone, but not metformin, reduces liver fat in Type-2 diabetes mellitus independent of weight changes.

ABSTRACT:

Background

Pioglitazone (Pio) treatment induces weight gain in Type 2 diabetes mellitus (T2DM), which could worsen hepatic lipid accumulation, and alter adiponectin and high-sensitivity C-reactive protein (hs-CRP).

Objective

To compare changes in hepatic lipid, serum adiponectin and hs-CRP in diabetics treated with Pio (with and without weight gain) against metformin (Met) treatment, which produces weight loss.

Design

Fifty-one men and women with T2DM, naive to thiazolidinediones, entered a 16-week, open-label, parallel arm study, where participants were randomized to one of three groups: (1) Pio plus the American Diabetes Association diet (Pio+ADA); (2) Pio plus a portion control weight loss diet (Pio+PC), or (3) metformin plus ADA diet (Met+ADA).

Methods

Hepatic lipid was assessed with abdominal computed tomography (CT) and the serum adiponectin and hs-CRP by enzyme-linked immunosorbent assay at baseline and study end.

Results

Forty-eight subjects completed the study. The Pio+ADA group gained (mean+/-S.E.M.) 2.15+/-1.09 kg, while Pio+PC and Met+ADA group lost -2.59+/-1.25 and -3.21+/-0.7 kg, respectively. Pio-treated groups (Pio+ADA and Pio+PC) significantly decreased hepatic fat as indicated by increased liver density on CT scan [10.1+/-2.4: 11.4+/-1.0 Hounsfield units (HU)], compared with Met+ADA group (-2.4+/-3.1 HU). The Pio groups demonstrated significantly increased serum adiponectin, (8.6+/-1.5; 7.4+/-1.6 microg/ml) independent of weight change, compared to Met+ADA (-0.14+/-0.6 microgm/ml) group which lost weight. Serum hs-CRP decreased in groups showing weight loss (Pio+PC, -3.1+/-1.7 mg/l; Met+ADA, -1.5+/-1.2 mg/l) compared to Pio+ADA (1.8+/-3.0 mg/l) group that gained weight.

Conclusions

Pio treatment in T2DM significantly reduced hepatic lipid and increased adiponectin independent of weight change, while decreasing hs-CRP with weight loss.

SUBMITTER: Gupta AK

PROVIDER: S-EPMC2891296 | biostudies-literature | 2010 Sep-Oct

REPOSITORIES: biostudies-literature

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Publications

Pioglitazone, but not metformin, reduces liver fat in Type-2 diabetes mellitus independent of weight changes.

Gupta Alok K AK Bray George A GA Greenway Frank L FL Martin Corby K CK Johnson William D WD Smith Steven R SR

Journal of diabetes and its complications 20090704 5

<h4>Background</h4>Pioglitazone (Pio) treatment induces weight gain in Type 2 diabetes mellitus (T2DM), which could worsen hepatic lipid accumulation, and alter adiponectin and high-sensitivity C-reactive protein (hs-CRP).<h4>Objective</h4>To compare changes in hepatic lipid, serum adiponectin and hs-CRP in diabetics treated with Pio (with and without weight gain) against metformin (Met) treatment, which produces weight loss.<h4>Design</h4>Fifty-one men and women with T2DM, naive to thiazolidine ...[more]

PMID: 19577936

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Project description:AimsTo examine the effect of pioglitazone on epicardial (EAT) and paracardial adipose tissue (PAT) and measures of diastolic function and insulin sensitivity in patients with type 2 diabetes mellitus (T2DM).MethodsTwelve patients with T2DM without clinically manifest cardiovascular disease and 12 subjects with normal glucose tolerance (NGT) underwent cardiac magnetic resonance imaging to quantitate EAT and PAT and diastolic function before and after pioglitazone treatment for 24 weeks. Whole-body insulin sensitivity was measured with a euglycaemic insulin clamp and the Matsuda Index (oral glucose tolerance test).ResultsPioglitazone reduced glycated haemoglobin by 0.9% (P < 0.05), increased HDL cholesterol by 7% (P < 0.05), reduced triacylglycerol by 42% (P < 0.01) and increased whole-body insulin-stimulated glucose uptake by 71% (P < 0.01) and Matsuda Index by 100% (P < 0.01). In patients with T2DM, EAT (P < 0.01) and PAT (P < 0.01) areas were greater compared with subjects with NGT, and decreased by 9% (P = 0.03) and 9% (P = 0.09), respectively, after pioglitazone treatment. Transmitral E/A flow rate and peak left ventricular flow rate (PLVFR) were reduced in T2DM versus NGT (P < 0.01) and increased following pioglitazone treatment (P < 0.01-0.05). At baseline normalized PLVFR inversely correlated with EAT (r = -0.45, P = 0.03) but not PAT (r = -0.29, P = 0.16). E/A was significantly and inversely correlated with EAT (r = -0.55, P = 0.006) and PAT (r = -0.40, P = 0.05). EAT and PAT were inversely correlated with whole-body insulin-stimulated glucose uptake (r = -0.68, P < 0.001) and with Matsuda Index (r = 0.99, P < 0.002).ConclusionPioglitazone reduced EAT and PAT areas and improved left ventricular (LV) diastolic function in T2DM. EAT and PAT are inversely correlated (PAT less strongly) with LV diastolic function and both EAT and PAT are inversely correlated with measures of insulin sensitivity.

Project description:BackgroundDiabetes has long been recognised as a strong, independent risk factor for cardiovascular disease, a problem which accounts for approximately 70% of all mortality in people with diabetes. Prospective studies show that compared to their non-diabetic counterparts, the relative risk of cardiovascular mortality for men with diabetes is two to three and for women with diabetes is three to four. The two biggest trials in type 2 diabetes, the United Kingdom Prospective Diabetes Study (UKPDS) and the University Group Diabetes Program (UGDP) study did not reveal a reduction of cardiovascular endpoints through improved metabolic control. Theoretical benefits of the newer peroxisome proliferator activated receptor gamma (PPAR-gamma) activators like pioglitazone on endothelial function and cardiovascular risk factors might result in fewer macrovascular disease events in people with type 2 diabetes mellitus.ObjectivesTo assess the effects of pioglitazone in the treatment of type 2 diabetes.Search strategyStudies were obtained from computerised searches of MEDLINE, EMBASE and The Cochrane Library. The last search was conducted in August 2006.Selection criteriaStudies were included if they were randomised controlled trials in adult people with type 2 diabetes mellitus and had a trial duration of at least 24 weeks.Data collection and analysisTwo authors independently assessed trial quality and extracted data. Pooling of studies by means of random-effects meta-analysis could be performed for adverse events only.Main resultsTwenty-two trials which randomised approximately 6200 people to pioglitazone treatment were identified. Longest duration of therapy was 34.5 months. Published studies of at least 24 weeks pioglitazone treatment in people with type 2 diabetes mellitus did not provide convincing evidence that patient-oriented outcomes like mortality, morbidity, adverse effects, costs and health-related quality of life are positively influenced by this compound. Metabolic control measured by glycosylated haemoglobin A1c (HbA1c) as a surrogate endpoint did not demonstrate clinically relevant differences to other oral antidiabetic drugs. Occurrence of oedema was significantly raised. The results of the single trial with relevant clinical endpoints (Prospective Pioglitazone Clinical Trial In Macrovascular Events--PROactive study) have to be regarded as hypothesis-generating and need confirmation.Authors' conclusionsUntil new evidence becomes available, the benefit-risk ratio of pioglitazone remains unclear. Different therapeutic indications for pioglitazone of the two big U.S. and European drug agencies should be clarified to reduce uncertainties amongst patients and physicians.

Dataset Information

Pioglitazone, but not metformin, reduces liver fat in Type-2 diabetes mellitus independent of weight changes.

Background

Objective

Design

Methods

Results

Conclusions

Publications

Pioglitazone, but not metformin, reduces liver fat in Type-2 diabetes mellitus independent of weight changes.

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