Dataset Information

The effects of metformin on insulin resistance in overweight or obese children and adolescents: A PRISMA-compliant systematic review and meta-analysis of randomized controlled trials.

ABSTRACT:

Background

Metformin has shown its effectiveness in reducing body mass index (BMI) in obese children and adolescents, but relevant evidence for improving insulin resistance in overweight or obese children and adolescents is inconclusive.

Objectives

This study aimed to assess whether metformin could effectively and safely improve homeostasis model assessment insulin resistance index (HOMA-IR) and other related laboratory indicators including fasting glucose, fasting insulin, high-density lipoprotein cholesterol (HDL-C), and low density lipoprotein-cholesterol (LDL-C).

Methods

Searches were carried out in PubMed, CENTRAL, Web of Science, EMBASE, CBM, Chinese National Knowledge Infrastructure (CNKI), and WanFang from their inception until March 2018. Randomized controlled trials (RCTs) comparing metformin alone with placebo in overweight or obese children and adolescents were included. The Cochrane risk of bias tool was applied to assess the methodological quality of every study and Meta-analysis was carried out with a random effects model or a fixed effects model. Publication bias was evaluated by the Begg and Egger tests.

Results

A total of 11 trials with a total of 865 participants met the inclusion criteria. Participants were between 4 and 18 years old. The time span of these studies ranged from 2001 to 2017. The daily dose of metformin was from 1000?mg to 2000?mg and the duration of intervention was 8 weeks to 18 months. Compared with placebo, metformin with lifestyle intervention reduced the level of LDL-C (P?=?008, MD = - 4.29, 95% confidence interval [CI]: -7.45, -1.12). However, there was no obvious differences in improving insulin resistance, fasting glucose, and HDL-C.

Conclusion

Metformin may improve the level of LDL-C, but it has no significant effect on insulin resistance. The use of metformin may be a new approach to lipid metabolism management in overweight or obese children and adolescents.

Registration number

CRD42018092059.

SUBMITTER: Sun J

PROVIDER: S-EPMC6358324 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The effects of metformin on insulin resistance in overweight or obese children and adolescents: A PRISMA-compliant systematic review and meta-analysis of randomized controlled trials.

Sun Juan J Wang Ya Y Zhang Xiaoyi X He Hong H

Medicine 20190101 4

<h4>Background</h4>Metformin has shown its effectiveness in reducing body mass index (BMI) in obese children and adolescents, but relevant evidence for improving insulin resistance in overweight or obese children and adolescents is inconclusive.<h4>Objectives</h4>This study aimed to assess whether metformin could effectively and safely improve homeostasis model assessment insulin resistance index (HOMA-IR) and other related laboratory indicators including fasting glucose, fasting insulin, high-d ...[more]

PMID: 30681616

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Project description:AIMS/HYPOTHESIS:A genetic risk score (GRS) consisting of 53 insulin resistance variants (GRS53) was recently demonstrated to associate with insulin resistance in adults. We speculated that the GRS53 might already associate with insulin resistance during childhood, and we therefore aimed to investigate this in populations of Danish children and adolescents. Furthermore, we aimed to address whether the GRS associates with components of the metabolic syndrome and altered body composition in children and adolescents. METHODS:We examined a total of 689 children and adolescents who were overweight or obese and 675 children and adolescents from a population-based study. Anthropometric data, dual-energy x-ray absorptiometry scans, BP, fasting plasma glucose, fasting serum insulin and fasting plasma lipid measurements were obtained, and HOMA-IR was calculated. The GRS53 was examined for association with metabolic traits in children by linear regressions using an additive genetic model. RESULTS:In overweight/obese children and adolescents, the GRS53 associated with higher HOMA-IR (β = 0.109 ± 0.050 (SE); p = 2.73 × 10-2), fasting plasma glucose (β = 0.010 ± 0.005 mmol/l; p = 2.51 × 10-2) and systolic BP SD score (β = 0.026 ± 0.012; p = 3.32 × 10-2) as well as lower HDL-cholesterol (β = -0.008 ± 0.003 mmol/l; p = 1.23 × 10-3), total fat-mass percentage (β = -0.143 ± 0.054%; p = 9.15 × 10-3) and fat-mass percentage in the legs (β = -0.197 ± 0.055%; p = 4.09 × 10-4). In the population-based sample of children, the GRS53 only associated with lower HDL-cholesterol concentrations (β = -0.007 ± 0.003 mmol/l; p = 1.79 × 10-2). CONCLUSIONS/INTERPRETATION:An adult-based GRS comprising 53 insulin resistance susceptibility SNPs associates with insulin resistance, markers of the metabolic syndrome and altered fat distribution in a sample of Danish children and adolescents who were overweight or obese.

Project description:ObjectiveThe intestinal flora of gut microbiota in obese Chinese children and adolescents with and without insulin resistance (IR) was analyzed, as well as associations between the gut microbiota and two serum cytokines related to glucose metabolism, adropin and angiopoietin-like 4 (ANGPTL4).MethodsClinical data, fecal bacterial composition, glucose-related hormones, and serum adipokines (adropin and ANGPTL4) were analyzed in 65 Chinese children with exogenous obesity. The composition of the gut microbiota was determined by 16S rRNA-based metagenomics and IR was calculated using the homeostasis model assessment (HOMA).ResultsThe 65 obese subjects were divided into two groups: insulin sensitive (IS) (n=40, 57.5% males) or IR (n=25, 60% males). Principal coordinates analysis revealed that the gut microbiota samples from the IS group clustered together and separated partly from the IR group (p=0.008). By Mann-Whitney U-test, at a phylum level, a reduction of Firmicutes and an increase of Bacteroidetes in the IR subjects was observed. LEfSe analysis revealed that IS subject, when compared to their IR counterparts, harbored members of the order Coriobacteriales, Turicibacterales, Pasteurellales and family Turicibacteraceae, that were significantly more abundant. In contrast, the IR subjects had members of family Peptococcaceae that were significantly more prevalent than the IS subjects (all p<0.05). Spearman's correlation analysis revealed that serum ANGPTL4 was positively associated with genus Bacteroides, Butyricimonas, and Alistipes, and adropin was positively associated with genus Anaerostipes and Alistipes, and negatively associated with genus Blautia (all p<0.05).ConclusionIn obese children, the gut microbiome in IR subjects was significantly discordant from the IS subjects, and the abundance of some metabolism-related bacteria correlated with the serum concentrations of adropin and ANGPTL4. These observations infer that the gut microbiota may be involved in the regulation of glucose metabolism in obesity.

Dataset Information

The effects of metformin on insulin resistance in overweight or obese children and adolescents: A PRISMA-compliant systematic review and meta-analysis of randomized controlled trials.

Background

Objectives

Methods

Results

Conclusion

Registration number

Publications

The effects of metformin on insulin resistance in overweight or obese children and adolescents: A PRISMA-compliant systematic review and meta-analysis of randomized controlled trials.

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