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Genetic risk score of common genetic variants for impaired fasting glucose and newly diagnosed type 2 diabetes influences oxidative stress.

ABSTRACT: We tested the hypothesis that the cumulative effects of common genetic variants related to elevated fasting glucose are collectively associated with oxidative stress. Using 25 single nucleotide polymorphisms (SNPs), a weighted genetic risk score (wGRS) was constructed by summing nine risk alleles based on nominal significance and a consistent effect direction in 1,395 controls and 718 patients with impaired fasting glucose (IFG) or newly diagnosed type 2 diabetes. All the participants were divided into the following three groups: low-wGRS, middle-wGRS, and high-wGRS groups. Among the nine SNPs, five SNPs were significantly associated with IFG and type 2 diabetes in this Korean population. wGRS was significantly associated with increased IFG and newly diagnosed type 2 diabetes (p?=?6.83?×?10-14, odds ratio?=?1.839) after adjusting for confounding factors. Among the IFG and type 2 diabetes patients, the fasting serum glucose and HbA1c levels were significantly higher in the high-wGRS group than in the other groups. The urinary 8-epi-PGF2? and malondialdehyde concentrations were significantly higher in the high-wGRS group than in the other groups. Moreover, general population-level instrumental variable estimation (using wGRS as an instrument) strengthened the causal effect regarding the largely adverse influence of high levels of fasting serum glucose on markers of oxidative stress in the Korean population. Thus, the combination of common genetic variants with small effects on IFG and newly diagnosed type 2 diabetes are significantly associated with oxidative stress.

SUBMITTER: Kim M

PROVIDER: S-EPMC5959868 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Genetic risk score of common genetic variants for impaired fasting glucose and newly diagnosed type 2 diabetes influences oxidative stress.

Kim Minjoo M Kim Minkyung M Huang Limin L Jee Sun Ha SH Lee Jong Ho JH

Scientific reports 20180518 1

We tested the hypothesis that the cumulative effects of common genetic variants related to elevated fasting glucose are collectively associated with oxidative stress. Using 25 single nucleotide polymorphisms (SNPs), a weighted genetic risk score (wGRS) was constructed by summing nine risk alleles based on nominal significance and a consistent effect direction in 1,395 controls and 718 patients with impaired fasting glucose (IFG) or newly diagnosed type 2 diabetes. All the participants were divid ...[more]

PMID: 29777116

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Project description:BackgroundAround 308 million people worldwide are estimated to have impaired glucose tolerance (IGT); 25% to 75% of these will develop diabetes within a decade of initial diagnosis. At diagnosis, half will have tissue-related damage and all have an increased risk for coronary heart disease.ObjectivesThe objective of this review was to assess the effects and safety of Chinese herbal medicines for the treatment of people with impaired glucose tolerance or impaired fasting glucose (IFG).Search strategyWe searched the following databases: The Cochrane Library, PubMed, EMBASE, AMED, a range of Chinese language databases, SIGLE and databases of ongoing trials.Selection criteriaRandomised clinical trials comparing Chinese herbal medicines with placebo, no treatment, pharmacological or non-pharmacological interventions in people with IGT or IFG were considered.Data collection and analysisTwo authors independently extracted data. Trials were assessed for risk of bias against key criteria: random sequence generation, allocation concealment, blinding of participants, outcome assessors and intervention providers, incomplete outcome data, selective outcome reporting and other sources of bias.Main resultsThis review examined 16 trials lasting four weeks to two years involving 1391 participants receiving 15 different Chinese herbal medicines in eight different comparisons. No trial reported on mortality, morbidity or costs. No serious adverse events like severe hypoglycaemia were observed. Meta-analysis of eight trials showed that those receiving Chinese herbal medicines combined with lifestyle modification were more than twice as likely to have their fasting plasma glucose levels return to normal levels (i.e. fasting plasma glucose <7.8 mmol/L and 2hr blood glucose <11.1 mmol/L) compared to lifestyle modification alone (RR 2.07; 95% confidence intervall (CI) 1.52 to 2.82). Those receiving Chinese herbs were less likely to progress to diabetes over the duration of the trial (RR 0.33; 95% CI 0.19 to 0.58). However, all trials had a considerable risk of bias and none of the specific herbal medicines comparison data was available from more than one study. Moreover, results could have been confounded by rates of natural reversion to normal glucose levels.Authors' conclusionsThe positive evidence in favour of Chinese herbal medicines for the treatment of IGT or IFG is constrained by the following factors: lack of trials that tested the same herbal medicine, lack of details on co-interventions, unclear methods of randomisation, poor reporting and other risks of bias.

Project description:ObjectiveTo determine insulin resistance and response in patients with polycystic ovary syndrome (PCOS) and normal glucose tolerance (NGT), impaired fasting glucose (IFG), impaired glucose tolerance, and combined glucose intolerance (CGI).Research design and methodsIn this cross-sectional study, 143 patients with PCOS (diagnosed on the basis of National Institutes of Health criteria) underwent oral glucose tolerance testing (OGTT), and 68 patients also had frequently sampled intravenous glucose tolerance tests. Changes in plasma glucose, insulin, cardiovascular risk factors, and androgens were measured.ResultsCompared with patients with NGT, those with both IFG and CGI were significantly insulin resistant (homeostasis model assessment 3.3 +/- 0.2 vs. 6.1 +/- 0.9 and 6.4 +/- 0.5, P < 0.0001) and hyperinsulinemic (insulin area under the curve for 120 min 973 +/- 69 vs. 1,470 +/- 197 and 1,461 +/- 172 pmol/l, P < 0.0001). Insulin response was delayed in patients with CGI but not in those with IFG (2-h OGTT, insulin 1,001 +/- 40 vs. 583 +/- 45 pmol/l, P < 0.0001). Compared with the NGT group, the CGI group had a lower disposition index (1,615 +/- 236 vs. 987 +/- 296, P < 0.0234) and adiponectin level (11.1 +/- 1.1 vs. 6.2 +/- 0.8 ng/ml, P < 0.0096). Compared with the insulin-resistant tertile of the NGT group, those with IFG had a reduced insulinogenic index (421 +/- 130 vs. 268 +/- 68, P < 0.05). Compared with the insulin-sensitive tertile of the NGT group, the resistant tertile had higher triglyceride and high-sensitivity C-reactive protein (hs-CRP) and lower HDL cholesterol and sex hormone-binding globulin (SHBG). In the entire population, insulin resistance correlated directly with triglyceride, hs-CRP, and the free androgen index and inversely with SHBG.ConclusionsPatients with PCOS develop IFG and CGI despite having significant hyperinsulinemia. Patients with IFG and CGI exhibit similar insulin resistance but very different insulin response patterns. Increases in cardiac risk factors and free androgen level precede overt glucose intolerance.

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Genetic risk score of common genetic variants for impaired fasting glucose and newly diagnosed type 2 diabetes influences oxidative stress.

Publications

Genetic risk score of common genetic variants for impaired fasting glucose and newly diagnosed type 2 diabetes influences oxidative stress.

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