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1.
A systematic review and meta-analysis of interventions to preserve insulin-secreting β-cell function in people newly diagnosed with type 1 diabetes: Results from intervention studies aimed at improving glucose control.
Narendran, P, Tomlinson, C, Beese, S, Sharma, P, Harris, I, Adriano, A, Maggs, F, Burrows, M, Nirantharakumar, K, Thomas, N, et al
Diabetic medicine : a journal of the British Diabetic Association. 2022;(1):e14730
Abstract
AIMS: Type 1 diabetes is characterised by the destruction of pancreatic β-cells. Significant levels of β-cells remain at diagnosis. Preserving these cells improves glucose control and protects from long-term complications. We undertook a systematic review and meta-analyses of all randomised controlled trials (RCTs) of interventions to preserve β-cell function in people newly diagnosed with type 1 diabetes. This paper reports the results of interventions for improving glucose control to assess whether they preserve β-cell function. METHODS Searches for RCTs in MEDLINE, Embase, Cochrane CENTRAL, ClinicalTrials.gov and WHO International Clinical Trials Registry. Eligible studies included newly diagnosed patients with type 1 diabetes, any intervention to improve glucose control and at least 1 month of follow-up. Data were extracted using a pre-defined data-extraction sheet with 10% of extractions checked by a second reviewer. RESULTS Twenty-eight studies with 1662 participants were grouped by intervention into six subgroups (alternative insulins, subcutaneous and intravenous insulin delivery, intensive therapy, glucose sensing, adjuncts). Only three studies demonstrated an improvement in glucose control as well as β-cell function. These interventions included intensive insulin therapy and use of an alternative insulin. CONCLUSIONS This is the largest comprehensive review of RCTs in this area. It demonstrates a lack of robust evidence that interventions to improve glucose control preserve β-cell function in new onset type 1 diabetes, although analysis was hampered by low-quality evidence and inconsistent reporting of studies. Development of guidelines to support the design of trials in this field is a priority.
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2.
Effects of Sodium/Glucose Cotransporter 2 (SGLT2) Inhibitors on Cardiovascular and Metabolic Outcomes in Patients Without Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized-Controlled Trials.
Teo, YH, Teo, YN, Syn, NL, Kow, CS, Yoong, CSY, Tan, BYQ, Yeo, TC, Lee, CH, Lin, W, Sia, CH
Journal of the American Heart Association. 2021;(5):e019463
Abstract
Background Recent studies have increasingly shown that sodium-glucose cotransporter 2 (SGLT2) inhibitors may have beneficial cardiovascular and metabolic effects in patients without diabetes mellitus. Hence, we conducted a systematic review and meta-analysis to determine the effect of SGLT2 inhibitors on cardiovascular and metabolic outcomes in patients without diabetes mellitus. Methods and Results Four electronic databases (PubMed, Embase, Cochrane, and SCOPUS) were searched on August 30, 2020 for articles published from January 1, 2000 to August 30, 2020, for studies that examined the effect of SGLT2 inhibitors on cardiovascular and metabolic outcomes in patients without diabetes mellitus. A random-effects pairwise meta-analysis model was used to summarize the studies. A total of 8 randomized-controlled trials were included with a combined cohort of 5233 patients. In patients without diabetes mellitus, those with heart failure treated with SGLT2 inhibitors had a 20% relative risk reduction in cardiovascular deaths and heart failure hospitalizations, compared with those who were not treated (risk ratio, 0.78; P<0.001). We additionally found that treatment with SGLT2 inhibitors improved multiple metabolic indices. Patients on SGLT2 inhibitors had a reduction in body weight of -1.21 kg (P<0.001), body mass index of -0.47 kg/m2 (P<0.001), systolic blood pressure of -1.90 mm Hg (P=0.04), and fasting plasma glucose of -0.38 mmol/L (P=0.05), compared with those without. There were no between-group differences in NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels, waist circumference, diastolic blood pressure, glycated hemoglobin, low-density lipoprotein cholesterol levels, and estimated glomerular filtration rates. Across our combined cohort of 5233 patients, hypoglycemia was reported in 22 patients. Conclusions SGLT2 inhibitors improve cardiovascular outcomes in patients without diabetes mellitus with heart failure. In patients without diabetes mellitus, SGLT2 inhibitors showed positive metabolic outcomes in weight and blood pressure control.
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3.
The Type 2 Deiodinase Thr92Ala Polymorphism Is Associated with Higher Body Mass Index and Fasting Glucose Levels: A Systematic Review and Meta-Analysis.
Wang, X, Chen, K, Zhang, C, Wang, H, Li, J, Wang, C, Teng, W, Shan, Z, Lai, Y
BioMed research international. 2021;:9914009
Abstract
BACKGROUND Type 2 deiodinase (Dio2) is a selenoenzyme that is mainly expressed in the endoplasmic reticulum of the central nervous system, brown adipose tissue, and placenta and is responsible for outer ring deiodination of thyroxine (T4) to form biologically active triiodothyronine (T3). The Thr92Ala polymorphism of Dio2 has been found to be a potential risk factor for various diseases beyond the hypothalamus-pituitary-thyroid (HPT) axis. METHODS We searched the relevant studies in the PubMed, Embase, and Cochrane Library databases and Google Scholar. A systematic review and meta-analysis of studies on the Thr92Ala polymorphism and metabolic parameters beyond the HPT axis (e.g., BMI, fasting glycemic traits, plasma lipid levels, and hypertension risk) were performed. RESULTS Six eligible studies that analyzed the relationship between the Thr92Ala polymorphism and metabolic parameters beyond the thyroid were identified. All selected studies excluded patients with thyroid dysfunction, and diabetic patients were also excluded when fasting glucose and fasting insulin levels were meta-analyzed. The Thr92Ala polymorphism was found to be a significant risk factor for higher BMI (Std. mean difference 0.31 (0.01, 0.60), p = 0.04) and higher fasting glucose levels (Std. mean difference 1.18 (0.05, 2.31), p = 0.04). However, fasting insulin levels, plasma lipid levels, and hypertension risk showed a nonsignificant association with the Thr92Ala polymorphism. CONCLUSION Compared with euthyroid noncarriers (Thr/Thr), euthyroid Ala92-Dio2 carriers showed increased BMI levels, and Ala92-Dio2 carriers also had higher fasting plasma glucose levels than matched euthyroid nondiabetic noncarriers.
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4.
Effects of Tea Consumption on Anthropometric Parameters, Metabolic Indexes and Hormone Levels of Women with Polycystic Ovarian Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Shen, W, Pan, Y, Jin, B, Zhang, Z, You, T, Qu, Y, Han, M, Yuan, X, Zhang, Y
Frontiers in endocrinology. 2021;:736867
Abstract
OBJECTIVE Our aim was to conduct a systematic review and meta-analysis to assess the effectiveness and safety of tea supplements for patients with polycystic ovary syndrome (PCOS). METHODS We conducted searches of the published literature in PubMed, EMBASE, Cochrane Library, Web of Science, Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure (CNKI), VIP database, and Wanfang Database in 1985 to September 2021. Data from randomized controlled trials (RCTs) were obtained to assess the effects of tea versus placebo in women with PCOS. Weighted mean differences (WMDs) were pooled using a random-effects model or risks ratios (RRs) using a random-effects model. RESULTS Six RCTs (235 participants) were included in our systematic review. Tea supplements as adjuvant therapy led to greater improvement in body weight (WMD -2.71, 95% CI -4.95 to -0.46, P = 0.02, I2 = 0%), fasting blood glucose (FBG: WMD -0.40, 95% CI -0.59 to -0.20, P < 0.0001, I2 = 0%) and fasting insulin (FINS: WMD -3.40, 95% CI -4.76 to -2.03, P < 0.00001, I2 = 0%) when compared with placebo. There were no significant differences of body mass index, waist circumference, hip circumference, waist-to-hip ratio (WHR), body fat rate, total testosterone, free testosterone (FT), dehydroepiandrosterone, luteinizing hormone or follicular-stimulating hormone (FSH) between the two groups. In addition, subgroup analysis suggested that green tea was effective on body weight, FINS, FBG, FT, and FSH, and herbal tea can also reduce FT levels, tea supplements had a significant impact on FBG and FSH in trials with intervention duration ≥ 3 months, and intervention lasting less than 3 months can improve FINS. Tea had significant effect on reducing WHR, FBG and FSH in Asian PCOS patients, but not in Caucasians. And there was no statistically significant effect of tea on weight and FINS in Asians, but it was effective for Caucasian participants. Compared with placebo, tea supplements did not cause significant adverse reactions (RR 1.45, 95% CI 0.30 to 6.90, P = 0.65, I2 = 0%). CONCLUSION This meta-analysis suggests that consumption of tea supplementation in women with PCOS could significantly decrease the levels of FBG and FINS as well as reduce body weight. Especially green tea, not only has the above effects, but also has a significant effect on improving a variety of reproductive hormone indexes. Furthermore, tea supplementation is a relatively safe therapy for PCOS patients. SYSTEMATIC REVIEW REGISTRATION PROSPERO https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=212755, identifier CRD42021249196.
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5.
Effect of extra virgin olive oil consumption on glycemic control: A systematic review and meta-analysis.
Dehghani, F, Morvaridzadeh, M, Pizarro, AB, Rouzitalab, T, Khorshidi, M, Izadi, A, Shidfar, F, Omidi, A, Heshmati, J
Nutrition, metabolism, and cardiovascular diseases : NMCD. 2021;(7):1953-1961
Abstract
AIMS: Several health benefits are contributed to extra virgin olive oil (EVOO). The polyphenol fraction of EVOO may be responsible for its cardioprotective impacts. This systematic review and meta-analysis aimed to investigate the effect of EVOO intake on glycemic parameters. Electronic literature searched through 1 September 2020 across MEDLINE/PubMed, Web of Science, and SCOPUS databases to find all clinical trials that reported the effect of EVOO intake on glycemic parameters [FBS(fasting blood glucose), insulin, HOMA-IR (Homeostatic Model Assessment for Insulin Resistance) and HbA1c (glycated hemoglobin A1c)] vs. control. DATA SYNTHESIS We pooled standardized mean differences (SMD) and 95% confidence intervals (CIs) from randomized clinical trials (RCTs) using random-effects models. Heterogeneity was assessed by Cochran Q-statistic and quantified (I2). We found 13 related trials comprising a total of 633 subjects. In pooled analysis, EVOO intake had no effect on FBS (SMD: -0.07; 95% CI: -0.20, 0.07; I2 = 0.0%), insulin (SMD: -0.32; 95% CI: -0.70, 0.06; I2 = 38.0%), and HOMA-IR (SMD: -0.32; 95% CI: -0.75, 0.10; I2 = 51.0%). However, a decreasing trend was observed in these effects. Subgroup analysis based on age, health status, dose, and EVOO intake duration also did not significantly change results. CONCLUSION Although EVOO seems a promising hypoglycemic effects, we did not find any significant evidence that EVOO consumption impacts glucose homeostasis. Furthermore, well-designed RCTs with longer durations are still needed to evaluate the EVOO's efficacy on glycemic parameters.
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6.
Effect of Dietary Acetic Acid Supplementation on Plasma Glucose, Lipid Profiles, and Body Mass Index in Human Adults: A Systematic Review and Meta-analysis.
Valdes, DS, So, D, Gill, PA, Kellow, NJ
Journal of the Academy of Nutrition and Dietetics. 2021;(5):895-914
Abstract
BACKGROUND Acetic acid is a short-chain fatty acid that has demonstrated biomedical potential as a dietary therapeutic agent for the management of chronic and metabolic illness comorbidities. In human beings, its consumption may improve glucose regulation and insulin sensitivity in individuals with cardiometabolic conditions and type 2 diabetes mellitus. Published clinical trial evidence evaluating its sustained supplementation effects on metabolic outcomes is inconsistent. OBJECTIVE This systematic review and meta-analysis summarized available evidence on potential therapeutic effects of dietary acetic acid supplementation via consumption of acetic acid-rich beverages and food sources on metabolic and anthropometric outcomes. METHODS A systematic search was conducted in Medline, Scopus, EMBASE, CINAHL Plus, and Web of Science from database inception until October 2020. Randomized controlled trials conducted in adults evaluating the effect of dietary acetic acid supplementation for a minimum of 1 week were included. Meta-analyses were performed using a random-effects model on fasting blood glucose (FBG), triacylglycerol (TAG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), glycated hemoglobin (HbA1c), body mass index (BMI), and body fat percentage. Statistical heterogeneity was assessed by calculation of Q and I2 statistics, and publication bias was assessed by calculation of Egger's regression asymmetry and Begg's test. RESULTS Sixteen studies were included, involving 910 participants who consumed between 750 and 3600 mg acetic acid daily in interventions lasting an average of 8 weeks. Dietary acetic acid supplementation resulted in significant reductions in TAG concentrations in overweight and obese but otherwise healthy individuals (mean difference [MD] = -20.51 mg/dL [95% confidence intervals = -32.98, -8.04], P = .001) and people with type 2 diabetes (MD = -7.37 mg/dL [-10.15, -4.59], P < .001). Additionally, acetic acid supplementation significantly reduced FBG levels (MD = -35.73 mg/dL [-63.79, -7.67], P = .01) in subjects with type 2 diabetes compared with placebo and low-dose comparators. No other changes were seen for other metabolic or anthropometric outcomes assessed. Five of the 16 studies did not specify the dose of acetic acid delivered, and no studies measured blood acetate concentrations. Only one study controlled for background acetic acid-rich food consumption during intervention periods. Most studies had an unclear or high risk of bias. CONCLUSION Supplementation with dietary acetic acid is well tolerated, has no adverse side effects, and has clinical potential to reduce plasma TAG and FBG concentrations in individuals with type 2 diabetes, and to reduce TAG levels in people who are overweight or obese. No significant effects of dietary acetic acid consumption were seen on HbA1c, HDL, or anthropometric markers. High-quality, longer-term studies in larger cohorts are required to confirm whether dietary acetic acid can act as an adjuvant therapeutic agent in metabolic comorbidities management.
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7.
Multi-omics analysis identifies CpGs near G6PC2 mediating the effects of genetic variants on fasting glucose.
Chung, RH, Chiu, YF, Wang, WC, Hwu, CM, Hung, YJ, Lee, IT, Chuang, LM, Quertermous, T, Rotter, JI, Chen, YI, et al
Diabetologia. 2021;(7):1613-1625
Abstract
AIMS/HYPOTHESIS An elevated fasting glucose level in non-diabetic individuals is a key predictor of type 2 diabetes. Genome-wide association studies (GWAS) have identified hundreds of SNPs for fasting glucose but most of their functional roles in influencing the trait are unclear. This study aimed to identify the mediation effects of DNA methylation between SNPs identified as significant from GWAS and fasting glucose using Mendelian randomisation (MR) analyses. METHODS We first performed GWAS analyses for three cohorts (Taiwan Biobank with 18,122 individuals, the Healthy Aging Longitudinal Study in Taiwan with 1989 individuals and the Stanford Asia-Pacific Program for Hypertension and Insulin Resistance with 416 individuals) with individuals of Han Chinese ancestry in Taiwan, followed by a meta-analysis for combining the three GWAS analysis results to identify significant and independent SNPs for fasting glucose. We determined whether these SNPs were methylation quantitative trait loci (meQTLs) by testing their associations with DNA methylation levels at nearby CpG sites using a subsample of 1775 individuals from the Taiwan Biobank. The MR analysis was performed to identify DNA methylation with causal effects on fasting glucose using meQTLs as instrumental variables based on the 1775 individuals. We also used a two-sample MR strategy to perform replication analysis for CpG sites with significant MR effects based on literature data. RESULTS Our meta-analysis identified 18 significant (p < 5 × 10-8) and independent SNPs for fasting glucose. Interestingly, all 18 SNPs were meQTLs. The MR analysis identified seven CpGs near the G6PC2 gene that mediated the effects of a significant SNP (rs2232326) in the gene on fasting glucose. The MR effects for two CpGs were replicated using summary data based on the European population, using an exonic SNP rs2232328 in G6PC2 as the instrument. CONCLUSIONS/INTERPRETATION Our analysis results suggest that rs2232326 and rs2232328 in G6PC2 may affect DNA methylation at CpGs near the gene and that the methylation may have downstream effects on fasting glucose. Therefore, SNPs in G6PC2 and CpGs near G6PC2 may reside along the pathway that influences fasting glucose levels. This is the first study to report CpGs near G6PC2, an important gene for regulating insulin secretion, mediating the effects of GWAS-significant SNPs on fasting glucose.
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8.
Potential Therapeutic Effects of Curcumin on Glycemic and Lipid Profile in Uncomplicated Type 2 Diabetes-A Meta-Analysis of Randomized Controlled Trial.
Altobelli, E, Angeletti, PM, Marziliano, C, Mastrodomenico, M, Giuliani, AR, Petrocelli, R
Nutrients. 2021;(2)
Abstract
Diabetes mellitus is an important issue for public health, and it is growing in the world. In recent years, there has been a growing research interest on efficacy evidence of the curcumin use in the regulation of glycemia and lipidaemia. The molecular structure of curcumins allows to intercept reactive oxygen species (ROI) that are particularly harmful in chronic inflammation and tumorigenesis models. The aim of our study performed a systematic review and meta-analysis to evaluate the effect of curcumin on glycemic and lipid profile in subjects with uncomplicated type 2 diabetes. The papers included in the meta-analysis were sought in the MEDLINE, EMBASE, Scopus, Clinicaltrials.gov, Web of Science, and Cochrane Library databases as of October 2020. The sizes were pooled across studies in order to obtain an overall effect size. A random effects model was used to account for different sources of variation among studies. Cohen's d, with 95% confidence interval (CI) was used as a measure of the effect size. Heterogeneity was assessed while using Q statistics. The ANOVA-Q test was used to value the differences among groups. Publication bias was analyzed and represented by a funnel plot. Curcumin treatment does not show a statistically significant reduction between treated and untreated patients. On the other hand, glycosylated hemoglobin, homeostasis model assessment (HOMA), and low-density lipoprotein (LDL) showed a statistically significant reduction in subjects that were treated with curcumin, respectively (p = 0.008, p < 0.001, p = 0.021). When considering HBA1c, the meta-regressions only showed statistical significance for gender (p = 0.034). Our meta-analysis seems to confirm the benefits on glucose metabolism, with results that appear to be more solid than those of lipid metabolism. However, further studies are needed in order to test the efficacy and safety of curcumin in uncomplicated type 2 diabetes.
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9.
Efficacy and safety of the newer oral hypoglycemic agents in patients with T2DM during Ramadan: A systematic review and meta-analysis.
Gad, H, Hayat, T, Al-Muhannadi, H, Malik, BR, Mussleman, P, Malik, RA
Diabetes research and clinical practice. 2021;:108562
Abstract
AIMS: This systematic review and meta-analysis aims to evaluate the safety and efficacy of the newer glucose lowering treatments on glycemic control, weight, blood pressure and hypoglycemia in patients with T2DM during Ramadan. METHODS A literature search was done in PubMed, Embase, and the Cochrane Library. Quality assessment was done using the ROBINS-I and Cochrane tools for risk of bias and analyses were performed using RevMan version 5.3. RESULTS A total of 20 studies were included in the meta-analysis. Dipeptidyl peptidase-4 inhibitors (DPP-4i) led to a significant reduction in HbA1c (%) (SMD -0.25) and a non-significant decrease in weight (kg) (SMD -1.06) during Ramadan. Glucagon-like peptide (GLP-1) agonist therapy was associated with a significant decrease in HbA1c (%) (SMD -0.68) and a non-significant decrease in weight (kg) (SMD -2.57) and systolic blood pressure (SBP) (mmHg) (SMD -3.50) after Ramadan. Sodium-glucose co-transporter 2 inhibitor (SGLT-2i) therapy was associated with a significant decrease in HbA1c (%) (SMD -0.51) and a non-significant decrease in weight (kg) (SMD -1.41), SBP (SMD -1.10) and diastolic blood pressure (DBP) (mmHg) (SMD -2.08) after Ramadan. CONCLUSIONS This systematic review and meta-analysis shows clinical benefits with the newer glucose lowering medications in patients with T2DM who fast during Ramadan.
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10.
Effects of interrupting prolonged sitting on postprandial glycemia and insulin responses: A network meta-analysis.
Quan, M, Xun, P, Wu, H, Wang, J, Cheng, W, Cao, M, Zhou, T, Huang, T, Gao, Z, Chen, P
Journal of sport and health science. 2021;(4):419-429
Abstract
PURPOSE This study aimed to evaluate the effectiveness of physical activity (PA) interrupting prolonged sitting (PS) on postprandial glycemia and insulin responses among adults. METHODS PubMed, EMBASE, Cochrane Library, Web of Science, CINAHL, PsycINFO, and the China National Knowledge Infrastructure databases were searched through September 30, 2020. Randomized controlled trials (RCTs) that examined the effect of all forms of PA interrupting PS on postprandial glycemia and/or insulin responses among adults without chronic diseases were included in this study. The risk of bias of included studies was evaluated based on the Cochrane tool. A network meta-analysis was performed to estimate the summary standardized mean differences (SMDs) with 95% confidence intervals (95%CIs) with random effects. RESULTS Thirty crossover RCTs were included in our review. These RCTs included 9 types of interventions that interrupted PS. When compared to PS by itself, light-intensity PA intermittent interrupting (LPA-INT) PS and moderate-intensity PA intermittent interrupting (MPA-INT) PS significantly lowered postprandial glycemia (SMD = -0.46, 95%CI: -0.70 to -0.21; SMD = -0.69, 95%CI: -1.00 to -0.37, respectively) and significantly reduced postprandial insulin response (SMD = -0.46, 95%CI: -0.66 to -0.26; SMD = -0.47, 95%CI: -0.77 to -0.17, respectively). Results of the clustered ranking plot indicated that MPA-INT was the most effective intervention in lowering postprandial glycemia and insulin responses. CONCLUSION Replacing PS with MPA-INT or LPA-INT has a positive effect in reducing postprandial glycemia and insulin responses, with MPA-INT being the optimal intervention strategy.