Dataset Information

Effect and cardiovascular safety of adding rosiglitazone to insulin therapy in type 2 diabetes: A meta-analysis.

ABSTRACT:

Aims/introduction

Recently, the use of rosiglitazone has been limited or withdrawn from the market as a result of cardiovascular risk. However, theoretically adding rosiglitazone to insulin could help insulin to decrease the glucose level. The present meta-analysis was designed to investigate the effect and safety of adding rosiglitazone to insulin therapy in type 2 diabetes.

Materials and methods

We searched published and unpublished databases through to March 2012. Randomized controlled trials (RCTs) comparing rosiglitazone in combination with insulin (RSG + INS) vs insulin alone (INS) in type 2 diabetes with outcomes including glycated hemoglobin levels, insulin dose, lipid parameters, blood pressure, edema and cardiovascular adverse events were selected.

Results

Nine RCTs with durations of 24-26 weeks involving 1,916 patients were included. The RSG + INS group showed significantly decreased glycated hemoglobin levels by 0.89% (P < 0.00001) with an 8.48-U reduction in daily insulin dose (P <0.00001). However, the risks of hypoglycemia and edema were more frequent in the RSG+INS group (P < 0.0001; P = 0.03, respectively). Total cholesterol level was significantly increased in the RSG+INS group (P < 0.00001), but none of the high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol or triglyceride levels were significantly different between groups. There were no significant differences between groups with regard to the risks of myocardial infarction, heart failure, cardiovascular death or all-cause death.

Conclusions

Rosiglitazone could help type 2 diabetes patients with poorly controlled glucose with insulin therapy to decrease glucose levels and reduce their daily insulin dose, but at the cost of increased total cholesterol level, hypoglycemia and edema risk. Compared with insulin therapy, adding rosiglitazone to insulin did not increase the risks of myocardial infarction, heart failure, cardiovascular death or all-cause death.

SUBMITTER: Lu Y

PROVIDER: S-EPMC4296706 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature

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Publications

Effect and cardiovascular safety of adding rosiglitazone to insulin therapy in type 2 diabetes: A meta-analysis.

Lu Yu Y Ma Delin D Xu Weijie W Shao Shiying S Yu Xuefeng X

Journal of diabetes investigation 20140618 1

<h4>Aims/introduction</h4>Recently, the use of rosiglitazone has been limited or withdrawn from the market as a result of cardiovascular risk. However, theoretically adding rosiglitazone to insulin could help insulin to decrease the glucose level. The present meta-analysis was designed to investigate the effect and safety of adding rosiglitazone to insulin therapy in type 2 diabetes.<h4>Materials and methods</h4>We searched published and unpublished databases through to March 2012. Randomized co ...[more]

PMID: 25621136

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Project description:In the present study, candidate genes affected by rosiglitazone to exert glycemic control in the treatment of type 2 diabetes mellitus (T2DM) and associated with its adverse cardiovascular effects were identified using a bioinformatics analysis. The gene expression profiles of the dataset GSE36875 from the Gene Expression Omnibus database, including heart samples from 5 non-diabetic control mice (NC), 5 untreated diabetic mice (NH) and 5 rosiglitazone-treated diabetic mice (TH), were used to identify differentially expressed genes (DEGs) in the NC vs. NH, NC vs. TH and TH vs. NH groups. Subsequently, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enriched by the DEGs were determined. Furthermore, genes associated with the action of rosiglitazone were identified using Short Time-series Expression Miner, which were then subjected to enrichment analysis in gene ontology (GO) terms in the category biological process (BP), and networks of the GO terms, KEGG pathways and genes associated with the action of rosiglitazone were constructed. Finally, biological abnormalities associated with these genes were identified using WebGestalt. A set of 791 DEGs in three groups (NC vs. NH, NC vs. TH and NH vs. TH) were identified. Subsequently, 72 DEGs [e.g., apolipoprotein (Apo)A1, ApoA5, cytochrome P450 (Cyp)2c37, Cyp2J5, Cyp2b9 and Cyp2b10] were identified as genes associated with the action of rosiglitazone. In addition, a network of 13 GO terms in the category BP, 6 KEGG pathways and 41 genes associated with the action of rosiglitazone was constructed, with major terms/pathways including oxidation/reduction, lipid transport, peroxisome proliferator-activated receptor signaling pathway and metabolism of xenobiotics by Cyp. Finally, 15 biological abnormalities (including abnormal triglyceride levels, abnormal cholesterol homeostasis, abnormal lipid homeostasis) associated with these genes were identified. ApoA1, ApoA5, Cyp2c37, Cyp2J5, Cyp2b9 and Cyp2b10 were differently expressed after rosiglitazone treatment, which may be accountable for affecting cardiovascular outcomes and glycemic control in T2DM. The present results may expand the current understanding of the mechanism of action of rosiglitazone to exert glycemic control in T2DM, as well as its effects on the cardiovascular system.

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Dataset Information

Effect and cardiovascular safety of adding rosiglitazone to insulin therapy in type 2 diabetes: A meta-analysis.

Aims/introduction

Materials and methods

Results

Conclusions

Publications

Effect and cardiovascular safety of adding rosiglitazone to insulin therapy in type 2 diabetes: A meta-analysis.

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