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Effectiveness of HIIE versus MICT in Improving Cardiometabolic Risk Factors in Health and Disease: A Meta-analysis.
Mattioni Maturana, F, Martus, P, Zipfel, S, NIEß, AM
Medicine and science in sports and exercise. 2021;(3):559-573
Abstract
PURPOSE We aimed to investigate differences between high-intensity interval exercise (HIIE, including high-intensity interval training and sprint interval training) and moderate-intensity continuous training (MICT) on physical fitness, body composition, blood pressure, blood lipids, insulin and glucose metabolism, inflammation, and endothelial function. METHODS Differences between HIIE and MICT were summarized using a random-effects meta-analysis on the effect size (Cohen's d). A meta-regression was conducted using the following subgroups: population, age, training duration, men ratio, exercise type, baseline values (clinical relevant ranges), and type of HIIE. Studies were included if at least one of the following outcomes were reported: maximal oxygen uptake (V˙O2max), flow-mediated dilation (FMD), body mass index (BMI), body mass, percent body fat, systolic and diastolic blood pressure, high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides, total cholesterol, C-reactive protein (CRP), fasting glucose and insulin, glycated hemoglobin (HbA1c), and insulin resistance (HOMA-IR). A total of 55 studies were included. RESULTS Overall, HIIE was superior to MICT in improving V˙O2max (d = 0.40, P < 0.001) and FMD (d = 0.54, P < 0.05). Oppositely, MICT was superior to HIIE in improving HbA1c (d = -0.27, P < 0.05). No differences were observed in BMI (d = -0.02), body mass (d = -0.05), percent body fat (d = 0.04), systolic blood pressure (d = -0.04), diastolic blood pressure (d = 0.03), HDL (d = -0.05), LDL (d = 0.08), triglycerides (d = 0.03), total cholesterol (d = 0.14), CRP (d = -0.11), fasting insulin (d = 0.02), fasting glucose (d = 0.02), and HOMA-IR (d = -0.04). Moderator analyses indicated that the difference between HIIE and MICT was affected by different subgroups. CONCLUSION Overall, HIIE showed to be more effective in improving cardiovascular health and cardiorespiratory fitness, whereas MICT was superior in improving long-term glucose metabolism. In the process of personalized training counseling, health-enhancing effects of exercise training may be improved by considering the individual risk profiles.
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Clinical and genetic determinants of urinary glucose excretion in patients with diabetes mellitus.
Monobe, K, Noso, S, Babaya, N, Hiromine, Y, Taketomo, Y, Niwano, F, Yoshida, S, Yasutake, S, Minohara, T, Kawabata, Y, et al
Journal of diabetes investigation. 2021;(5):728-737
Abstract
AIMS/INTRODUCTION Glucosuria is a representative symptom in diabetes patients with poor glycemic control and in those treated with sodium-glucose cotransporter 2 inhibitors. Renal threshold levels of glucose excretion are known to vary among individuals, but factors contributing to glucosuria are not well characterized. The present study aimed to clarify clinical and genetic determinants of glucosuria in individuals with diabetes mellitus. MATERIALS AND METHODS The 24-h urinary glucose excretion was measured in 135 hospitalized patients on admission, with continuous measurement for five consecutive days in 75 patients. Genetic and clinical factors contributing to glucosuria were studied. As a genetic factor, SLC5A2 polymorphism was genotyped. A total of 476 participants (266 participants with type 2 diabetes and 210 healthy controls) were additionally genotyped for the association study of SLC5A2 with type 2 diabetes. A meta-analysis was carried out with the present study and previous association studies. RESULTS Multiple regression analysis showed that the independent variables of average blood glucose (β = 0.41, P = 1.4 × 10-7 ), estimated glomerular filtration rate (β = 0.28, P = 6.0 × 10-5 ), sex (β = 0.28, P = 5.7 × 10-5 ) and SLC5A2 rs9934336 polymorphism (β = 0.17, P = 0.02) were significantly correlated with urinary glucose excretion. The frequency of the A allele of rs9934336 tended to be lower in participants with type 2 diabetes than in controls (odds ratio 0.78, 95% confidence interval 0.53-1.13, not significant), and meta-analysis showed a significant association between the A allele and type 2 diabetes (summary odds ratio for minor allele [A] 0.86, 95% confidence interval 0.78-0.94, P < 0.002). CONCLUSIONS Blood glucose, estimated glomerular filtration rate, sex and SLC5A2 polymorphism were independent determinants of glucosuria in diabetes mellitus.
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Genome-Wide Association Analysis of Pancreatic Beta-Cell Glucose Sensitivity.
Deshmukh, HA, Madsen, AL, Viñuela, A, Have, CT, Grarup, N, Tura, A, Mahajan, A, Heggie, AJ, Koivula, RW, De Masi, F, et al
The Journal of clinical endocrinology and metabolism. 2021;(1):80-90
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Abstract
CONTEXT Pancreatic beta-cell glucose sensitivity is the slope of the plasma glucose-insulin secretion relationship and is a key predictor of deteriorating glucose tolerance and development of type 2 diabetes. However, there are no large-scale studies looking at the genetic determinants of beta-cell glucose sensitivity. OBJECTIVE To understand the genetic determinants of pancreatic beta-cell glucose sensitivity using genome-wide meta-analysis and candidate gene studies. DESIGN We performed a genome-wide meta-analysis for beta-cell glucose sensitivity in subjects with type 2 diabetes and nondiabetic subjects from 6 independent cohorts (n = 5706). Beta-cell glucose sensitivity was calculated from mixed meal and oral glucose tolerance tests, and its associations between known glycemia-related single nucleotide polymorphisms (SNPs) and genome-wide association study (GWAS) SNPs were estimated using linear regression models. RESULTS Beta-cell glucose sensitivity was moderately heritable (h2 ranged from 34% to 55%) using SNP and family-based analyses. GWAS meta-analysis identified multiple correlated SNPs in the CDKAL1 gene and GIPR-QPCTL gene loci that reached genome-wide significance, with SNP rs2238691 in GIPR-QPCTL (P value = 2.64 × 10-9) and rs9368219 in the CDKAL1 (P value = 3.15 × 10-9) showing the strongest association with beta-cell glucose sensitivity. These loci surpassed genome-wide significance when the GWAS meta-analysis was repeated after exclusion of the diabetic subjects. After correction for multiple testing, glycemia-associated SNPs in or near the HHEX and IGF2B2 loci were also associated with beta-cell glucose sensitivity. CONCLUSION We show that, variation at the GIPR-QPCTL and CDKAL1 loci are key determinants of pancreatic beta-cell glucose sensitivity.
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Effects of alpha-glucosidase-inhibiting drugs on acute postprandial glucose and insulin responses: a systematic review and meta-analysis.
Alssema, M, Ruijgrok, C, Blaak, EE, Egli, L, Dussort, P, Vinoy, S, Dekker, JM, Denise Robertson, M
Nutrition & diabetes. 2021;(1):11
Abstract
BACKGROUND/OBJECTIVES Despite considerable literature supporting the potential health benefits of reducing postprandial glucose (PPG), and insulin (PPI) exposures, the size of a clinically relevant reduction is currently unknown. We performed a systematic review and meta-analysis to quantify effects of alpha-glucosidase-inhibiting (AGI) drugs on acute PPG and PPI responses. METHODS We searched EMBASE and MEDLINE until March 13, 2018 for controlled studies using AGI drugs together with a standardized carbohydrate load or mixed meal. The mean incremental PPG and PPI levels were calculated as outcomes. Meta-analyses, stratified by diabetes state, were performed by using random effects models. RESULTS The 66 included publications comprised 127 drug-control comparisons for PPG, and 106 for PPI, mostly testing acarbose or miglitol. The absolute effects on PPG were larger among individuals with diabetes (-1.5 mmol/l mean PPG [95% CI -1.9, -1.1] by acarbose, and -1.6 [-1.9, -1.4] by miglitol) as compared to individuals without diabetes (-0.4 [95% CI -0.5, -0.3] by acarbose, and -0.6 [-0.8, -0.4] by miglitol). Relative reductions in PPG by both drugs were similar for diabetic and non-diabetic individuals (43-54%). Acarbose and miglitol also significantly reduced mean PPI, with absolute and relative reductions being largest among individuals without diabetes. CONCLUSIONS The present meta-analyses provide quantitative estimates of reductions of PPG and PPI responses by AGI drugs in diabetes and non-diabetic individuals. These data can serve as benchmarks for clinically relevant reductions in PPG and PPI via drug or diet and lifestyle interventions.
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Differences in the Effects of Anthocyanin Supplementation on Glucose and Lipid Metabolism According to the Structure of the Main Anthocyanin: A Meta-Analysis of Randomized Controlled Trials.
Araki, R, Yada, A, Ueda, H, Tominaga, K, Isoda, H
Nutrients. 2021;(6)
Abstract
The effectiveness of anthocyanins may differ according to their chemical structures; however, randomized clinical controlled trials (RCTs) or meta-analyses that examine the consequences of these structural differences have not been reported yet. In this meta-analysis, anthocyanins in test foods of 18 selected RCTs were categorized into three types: cyanidin-, delphinidin-, and malvidin-based. Delphinidin-based anthocyanins demonstrated significant effects on triglycerides (mean difference (MD): -0.24, p < 0.01), low-density lipoprotein cholesterol (LDL-C) (MD: -0.28, p < 0.001), and high-density lipoprotein cholesterol (HDL-C) (MD: 0.11, p < 0.01), whereas no significant effects were observed for cyanidin- and malvidin-based anthocyanins. Although non-significant, favorable effects on total cholesterol (TC) and HDL-C were observed for cyanidin- and malvidin-based anthocyanins, respectively (both p < 0.1). The ascending order of effectiveness on TC and LDL-C was delphinidin-, cyanidin-, and malvidin-based anthocyanins, and the differences among the three groups were significant (both p < 0.05). We could not confirm the significant effects of each main anthocyanin on glucose metabolism; however, insulin resistance index changed positively and negatively with cyanidin- and delphinidin-based anthocyanins, respectively. Therefore, foods containing mainly unmethylated anthocyanins, especially with large numbers of OH groups, may improve glucose and lipid metabolism more effectively than those containing methylated anthocyanins.
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New-onset glucose disorders in peritoneal dialysis patients: a meta-analysis and systematic review.
Xue, C, Gu, YY, Cui, CJ, Zhou, CC, Wang, XD, Ruan, MN, Huang, LX, Chen, SX, Yang, B, Chen, XJ, et al
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2020;(8):1412-1419
Abstract
BACKGROUND Peritoneal dialysis (PD) patients are at high risk of developing glucose metabolism disturbance (GMD). The incidence and prevalence of new-onset GMD, including diabetes mellitus (DM), impaired glucose tolerance (IGT) and impaired fast glucose (IFG), after initiation of PD, as well as their correlated influence factors, varies among studies in different areas and of different sample sizes. Also, the difference compared with hemodialysis (HD) remained unclear. Thus we designed this meta-analysis and systematic review to provide a full landscape of the occurrence of glucose disorders in PD patients. METHODS We searched the MEDLINE, Embase, Web of Science and Cochrane Library databases for relevant studies through September 2018. Meta-analysis was performed on outcomes using random effects models with subgroup analysis and sensitivity analysis. RESULTS We identified 1124 records and included 9 studies involving 13 879 PD patients. The pooled incidence of new-onset DM (NODM) was 8% [95% confidence interval (CI) 4-12; I2 = 98%] adjusted by sample sizes in PD patients. Pooled incidence rates of new-onset IGT and IFG were 15% (95% CI 3-31; I2 = 97%) and 32% (95% CI 27-37), respectively. There was no significant difference in NODM risk between PD and HD [risk ratio 0.99 (95% CI 0.69-1.40); P = 0.94; I2 = 92%]. PD patients with NODM were associated with an increased risk of mortality [hazard ratio 1.06 (95% CI 1.01-1.44); P < 0.001; I2 = 92.5%] compared with non-DM PD patients. CONCLUSIONS Around half of PD patients may develop a glucose disorder, which can affect the prognosis by significantly increasing mortality. The incidence did not differ among different ethnicities or between PD and HD. The risk factor analysis did not draw a definitive conclusion. The glucose tolerance test should be routinely performed in PD patients.
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Improvement of glucose metabolism in pregnant women through probiotic supplementation depends on gestational diabetes status: meta-analysis.
Łagowska, K, Malinowska, AM, Zawieja, B, Zawieja, E
Scientific reports. 2020;(1):17796
Abstract
The aim of this study was to assess the effects of probiotic and synbiotic supplementation on glucose metabolism in pregnant women using data from randomized controlled trials. Furthermore, this meta-analysis examines whether the observed effects depend on the presence or absence of gestational diabetes mellitus (GDM), and if the effect is dependent on the type of supplement used (probiotic or synbiotic). We performed a literature search of databases (Medline, Scopus, Web of Knowledge, and Cochrane Library) and identified all relevant randomized controlled trials (RCTs) published prior to May 2019. We compared the effects of probiotic supplementation with the administration of placebos in pregnant women with and without GDM. The systematic review and meta-analysis protocol were registered in the International Prospective Register of Systematic Reviews as number CRD 42019111467. 1119 study participants from 15 selected studies were included. The participants in four studies did not have GDM (being recruited to the study before week 20 of pregnancy) and the participants in the rest of the studies were diagnosed with GDM between weeks 24 and 28 of gestation. The meta-analysis showed that supplementation lowers serum glucose, insulin levels, and HOMA-IR index, but only in pregnant women with GDM. Moreover, both probiotics and synbiotics lower serum insulin level and HOMA-IR index, but the glucose lowering effect is specific only to probiotics and not synbiotics. Probiotic supplementation may improve glucose metabolism in pregnant women with GDM. There is a need for more RCT studies with larger groups to better estimate this effect.
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Integration of genomics and transcriptomics predicts diabetic retinopathy susceptibility genes.
Skol, AD, Jung, SC, Sokovic, AM, Chen, S, Fazal, S, Sosina, O, Borkar, PP, Lin, A, Sverdlov, M, Cao, D, et al
eLife. 2020
Abstract
We determined differential gene expression in response to high glucose in lymphoblastoid cell lines derived from matched individuals with type 1 diabetes with and without retinopathy. Those genes exhibiting the largest difference in glucose response were assessed for association with diabetic retinopathy in a genome-wide association study meta-analysis. Expression quantitative trait loci (eQTLs) of the glucose response genes were tested for association with diabetic retinopathy. We detected an enrichment of the eQTLs from the glucose response genes among small association p-values and identified folliculin (FLCN) as a susceptibility gene for diabetic retinopathy. Expression of FLCN in response to glucose was greater in individuals with diabetic retinopathy. Independent cohorts of individuals with diabetes revealed an association of FLCN eQTLs with diabetic retinopathy. Mendelian randomization confirmed a direct positive effect of increased FLCN expression on retinopathy. Integrating genetic association with gene expression implicated FLCN as a disease gene for diabetic retinopathy.
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Effect of Perioperative Glucose-Insulin-Potassium Therapy in Patients Undergoing On-Pump Cardiac Surgery: A Meta-Analysis.
Li, Q, Yang, J, Zhang, J, Yang, C, Fan, Z, Yang, Y, Zheng, T, Yang, J
The heart surgery forum. 2020;(1):E063-E069
Abstract
OBJECTIVE The role of glucose-insulin-potassium (GIK) infusion during cardiac surgery has held interest for so many years without a clear answer. The aim of this meta-analysis was to evaluate the effect of GIK therapy on outcomes in patients undergoing on-pump cardiac surgery. METHODS A comprehensive online review was performed in The Web of Science, Embase, Medline, PubMed, and The Cochrane Library databases from 2000 to 2019. Eligible studies included randomized controlled trials (RCTs) that compared GIK treatment with placebo or standard care during on-pump cardiac surgery. Risk ratios (RR) were used for binary outcomes and mean difference (MD) was used for continuous variables; both with their 95% confidence intervals (CI). RESULTS A total of 18 RCTs involving 2,131 patients met the inclusion criteria. Compared with the control group, the GIK treatment significantly reduced in-hospital mortality (RR = 0.56, 95% CI: 0.32-0.97; P = .04), postoperative myocardial infarctions (MI) (RR = 0.71, 95% CI: 0.56-0.91; P = .006), the use of inotropic support (RR = 0.53, 95% CI: 0.45-0.63; P < .00001), and length of stay in the intensive care unit (ICU) (MD = -0.33, 95% CI: -0.52--0.14; P = .0007). Moreover, GIK treatment seemed to be associated with fewer postoperative atrial fibrillation (AF) (RR = 0.81, 95% CI: 0.64-1.03; P = .09). CONCLUSIONS In patients undergoing on-pump cardiac surgery, GIK infusion has a beneficial role in mortality during hospital stay and demonstrates superior efficacy versus standard care for reduction in postoperative MI, AF, ICU length of stay as well as inotropic agent requirements.
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Effects of probiotic supplementation during pregnancy on metabolic outcomes: A systematic review and meta-analysis of randomized controlled trials.
Masulli, M, Vitacolonna, E, Fraticelli, F, Della Pepa, G, Mannucci, E, Monami, M
Diabetes research and clinical practice. 2020;:108111
Abstract
AIM: To perform a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the effect of probiotics in pregnancy on the incidence of gestational diabetes (GDM) and fasting plasma glucose (FPG). METHODS A MEDLINE, EMBASE, Scopus and Cochrane search (up to May 30th, 2019) was performed to identify RCTs of comparison of probiotics with placebo/active comparators in pregnant women. Principal endpoints were the incidence of GDM and the change of FPG. Other maternal and fetal outcomes were secondary endpoints. Mantel-Haenszel Odds Ratio with 95% CI (MH-OR) was calculated for dichotomous outcomes, whereas standardized differences in means was calculated for continuous variables. (PROSPERO registration CRD42019139889). FINDINGS A total of 17 RCTs, all versus placebo, was identified. The overall quality of the trials was satisfactory. No effect of probiotics on incidence of GDM (MH-OR: 0.77[0.51,1.16], p = 0.21,I2:62%) was observed, with a small but significant reduction of FPG (mean difference -1.01 [-1.96, -0.06]mg/dl, p = 0.02, I2:46%). Among secondary endpoints, a significant reduction of maternal insulin (both in women with or without diabetes) was observed in the probiotics group. INTERPRETATION Probiotics during pregnancy do not reduce the incidence of GDM, with a very little (statistically but not clinically significant) reduction of fasting plasma glucose.