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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.
Why are physical activity breaks more effective than a single session of isoenergetic exercise in reducing postprandial glucose? A systemic review and meta-analysis.
Gouldrup, H, Ma, T
Journal of sports sciences. 2021;(2):212-218
Abstract
Previous studies revealed that interrupting sitting time with short, frequent physical activity (PA) breaks were more effective than a single session of isoenergetic exercise in reducing postprandial glucose. However, in those studies, the expected glucose-lowering effects of single-session exercises were diminished or even eliminated by exercise-induced glucose counterregulation as evidenced by the higher glucose levels during or after exercise compared to uninterrupted sitting. This study was aimed to investigate whether glucose counterregulation is a potential explanation of PA breaks being more effective than a single session of isoenergetic exercise in reducing postprandial glucose. We meta-analysed the standardized mean differences (SMD) of glucose incremental area under the curve (iAUC). PA breaks were more effective than single-session exercise in reducing glucose iAUC (5 studies, SMD = -0.581; 95% confidence interval [CI], -0.777 to -0.385; P < 0.0001) when exercise-induced glucose counterregulation occurred. There was no significant difference in glucose iAUC between PA breaks and single-session exercises (2 studies, SMD = 0.302; 95% CI, -0.107 to 0.711; P = 0.451) when glucose counterregulation did not occur. We concluded that the exercise-induced glucose counterregulation was a potential explanation of PA breaks being more effective than a single session of isoenergetic exercise in reducing postprandial glucose responses. (PROSPERO ID CRD42020175737).
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3.
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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4.
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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5.
Quantitative efficacy of L-carnitine supplementation on glycemic control in type 2 diabetes mellitus patients.
Wang, DD, Mao, YZ, He, SM, Yang, Y, Chen, X
Expert review of clinical pharmacology. 2021;(7):919-926
Abstract
OBJECTIVES This study aimed to explore the quantitative efficacy of L-carnitine supplementation on glycemic control in type 2 diabetes mellitus patients using model-based meta-analysis (MBMA). METHODS Literatures were retrieved from the public database and data from these trials were extracted. The quantitative efficacy of L-carnitine on fasting plasma glucose (FPG) and glycated hemoglobin (HbA1c) in type 2 diabetes mellitus patients were evaluated by maximal effect (Emax) models with nonlinear mixed effects modeling (NONMEM). RESULTS In the model of FPG, Emax and treatment duration to reach half of the maximal effects (ET50) were -9.8% and 36.1 weeks, respectively. In the model of HbA1c, Emax and ET50 were -19.6% and 106 weeks, respectively. In addition, the durations for achieving 25%, 50%, 75%, 80%, and 90% Emax of L-carnitine on FPG were 13, 36.1, 118, 160, and 390 weeks, respectively. The durations for achieving 25%, 50%, 75%, 80%, and 90% Emax of L-carnitine on HbA1c were 38, 106, 334, 449, and 1058 weeks, respectively. CONCLUSIONS It was the first time to provide valuable quantitative information for efficacy of L-carnitine supplementation on glycemic control in type 2 diabetes mellitus patients.
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6.
The effect of apple cider vinegar on lipid profiles and glycemic parameters: a systematic review and meta-analysis of randomized clinical trials.
Hadi, A, Pourmasoumi, M, Najafgholizadeh, A, Clark, CCT, Esmaillzadeh, A
BMC complementary medicine and therapies. 2021;(1):179
Abstract
BACKGROUND Elevated lipid profiles and impaired glucose homeostasis are risk factors for several cardiovascular diseases (CVDs), which, subsequently, represent a leading cause of early mortality, worldwide. The aim of the current study was to conduct a systematic review and meta-analysis of the effect of apple cider vinegar (ACV) on lipid profiles and glycemic parameters in adults. METHODS A systematic search was conducted in electronic databases, including Medline, Scopus, Cochrane Library, and Web of Knowledge, from database inception to January 2020. All clinical trials which investigated the effect of ACV on lipid profiles and glycemic indicators were included. Studies were excluded if ACV was used in combination with other interventions or when the duration of intervention was < 2 weeks. To account for between-study heterogeneity, we performed meta-analysis using a random-effects model. RESULTS Overall, nine studies, including 10 study arms, were included in this meta-analysis. We found that ACV consumption significantly decreased serum total cholesterol (- 6.06 mg/dL; 95% CI: - 10.95, - 1.17; I2: 39%), fasting plasma glucose (- 7.97 mg/dL; 95% CI: - 13.74, - 2.21; I2: 75%), and HbA1C concentrations (- 0.50; 95% CI: - 0.90, - 0.09; I2: 91%). No significant effect of ACV consumption was found on serum LDL-C, HDL-C, fasting insulin concentrations, or HOMA-IR. The stratified analysis revealed a significant reduction of serum TC and TG in a subgroup of patients with type 2 diabetes, those who took ≤15 mL/day of ACV, and those who consumed ACV for > 8-weeks, respectively. Furthermore, ACV consumption significantly decreased FPG levels in a subgroup of studies that administered ACV for > 8-weeks. Further, ACV intake appeared to elicit an increase in FPG and HDL-C concentrations in apparently healthy participants. CONCLUSION We found a significant favorable effect of ACV consumption on FPG and blood lipid levels.
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7.
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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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.
A systematic review and meta-analysis of effects of spironolactone on blood pressure, glucose, lipids, renal function, fibrosis and inflammation in patients with hypertension and diabetes.
Lin, M, Heizati, M, Wang, L, Nurula, M, Yang, Z, Wang, Z, Abudoyreyimu, R, Wu, Z, Li, N
Blood pressure. 2021;(3):145-153
Abstract
PURPOSE Hypertension commonly co-exists with diabetes mellitus (DM), and both are closely related to adverse health outcomes. The activation of aldosterone and mineralocorticoid receptor (MR) may play important roles in this process. Therefore, we aim to evaluate the efficacy of MR antagonists on cardiovascular risk factors, including blood pressure (BP), glucose, lipids, renal function, fibrosis and inflammatory and its safety in patients with both hypertension and DM. METHODS We searched PubMed, Embase, Web of Science and Cochrane databases for clinical trials published until December 31, 2019. Studies comparing the effect of spironolactone to placebo in patients with hypertension and DM were included. Mean difference with 95% confidence intervals was used to report outcomes. RESULTS Eleven randomised placebo-controlled trials with 640 participants were finally included with mean follow-up of 5 months. Compared to placebo, spironolactone significantly reduced office systolic (-6.57, 95%CI: -9.21, -3.93) and diastolic BP (-2.63, 95%CI: -4.25, -1.02) as well as ambulatory BP; increased glycosylated haemoglobin by 0.3 but no clear effect on fasting glucose. Spironolactone induced a significantly reduction of urinary albumin but increased serum creatinine (7.60, 95%CI: 4.94, 10.27) and decreased glomerular filtration rate (-4.28, 95%CI: -6.38, -2.18). Markers of fibrosis and inflammation, including NIIINP, PICP, hs-CRP and TNF-α were also decreased after spironolactone therapy. For lipid metabolism, there was no significant difference between groups. Spironolactone mildly increased serum potassium (0.30, 95%CI: 0.23, 0.37). 2.5% subjects treated with spironolactone experienced mild to moderate hyperkalaemia and received medication or dietary advice and another 1.6% developed severe hyperkalaemia and withdrawn from the studies. CONCLUSION Spironolactone reduced BP and urinary albumin, improve fibrosis and inflammation, whereas slightly increases the glycosylated haemoglobin and serum creatinine in patients with hypertension and diabetes. Long-term RCTs to assess the effects of spironolactone on cardiovascular events in this population are warranted.
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10.
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.