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Dietary calcium intake in relation to type-2 diabetes and hyperglycemia in adults: A systematic review and dose-response meta-analysis of epidemiologic studies.
Hajhashemy, Z, Rouhani, P, Saneei, P
Scientific reports. 2022;(1):1050
Abstract
Several epidemiological studies investigated the relation of Ca intake with type 2 diabetes mellitus (T2DM), but there were inconsistencies in their findings. So, we conducted a systematic review and dose-response meta-analysis to quantify the relation of dietary Ca intake with the risk of T2DM/hyperglycemia in adults. A systematic search was conducted up to May 2021, in MEDLINE (Pubmed), Web of Science (WOS), Scopus electronic databases and Google Scholar, for epidemiological studies that investigated the relation of dietary Ca intake (as the exposure) and T2DM/hyperglycemia (as the outcome) in adults, without restriction in publication date and language. Finally, 8 cohort and 9 cross-sectional studies were included in the analysis. The body of evidence was assessed by the GRADE approach. Combining effect sizes from prospective cohort studies included 255,744 general adult population illustrated that highest level of dietary Ca intake, compared to lowest category, was related to an 18% reduced risk of T2DM (RR: 0.82; 95% CI 0.74-0.92). Based on linear dose-response analysis (including 255,744 healthy individuals and 13,531 patients with T2DM), each 300, 600 and 1000 mg/day increment in dietary Ca intake was respectively associated to 7, 14 and 23% reduced risk of T2DM. There was a steeper reduction in risk of T2DM when dietary Ca intake increased from low levels to 750 mg/day. Nevertheless, meta-analysis of cross-sectional studies revealed an inverse significant association between dietary Ca intake and T2DM/hyperglycemia only in the female population (OR: 0.66; 95% CI 0.50-0.88). This meta-analysis illustrated an inverse association between dietary Ca intake and risk of T2DM in general adult populations in prospective cohort studies, in a dose-response manner. It seems that increasing dietary Ca intake from low levels to around 750 mg/day was inversely related to risk of T2DM. In cross-sectional studies, an inverse relation between dietary Ca intake and T2DM/hyperglycemia was found only in females.
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Anthropometric and adiposity indicators and risk of type 2 diabetes: systematic review and dose-response meta-analysis of cohort studies.
Jayedi, A, Soltani, S, Motlagh, SZ, Emadi, A, Shahinfar, H, Moosavi, H, Shab-Bidar, S
BMJ (Clinical research ed.). 2022;:e067516
Abstract
OBJECTIVE To present a comprehensive review of the association between measures of body weight, waist, and fat, and different ratios of these measures, and the risk of type 2 diabetes. DESIGN Systematic review and dose-response meta-analysis of cohort studies. DATA SOURCES PubMed, Scopus, and Web of Science up to 1 May 2021. REVIEW METHODS Cohort studies looking at the association between general or central adiposity and body fat content and the risk of type 2 diabetes in the general adult population were included. Two of the authors extracted the data in duplicate. Random effects dose-response meta-analyses were performed to estimate the degree of the associations. Curvilinear associations were modelled with a one stage weighted mixed effects meta-analysis. RESULTS 216 cohort studies with 2.3 million individuals with type 2 diabetes among 26 million participants were identified. Relative risks were 1.72 (95% confidence interval 1.65 to 1.81; n=182 studies) for an increase in body mass index of 5 units, 1.61 (1.52 to 1.70; n=78) for a 10 cm larger waist circumference, 1.63 (1.50 to 1.78; n=34) for an increase in waist-to-hip ratio of 0.1 units, 1.73 (1.51 to 1.98; n=25) for an increase in waist-to-height ratio of 0.1 units, 1.42 (1.27 to 1.58; n=9) for an increase in visceral adiposity index of 1 unit, 2.05 (1.41 to 2.98; n=6) for a 10% higher percentage body fat, 1.09 (1.05 to 1.13, n=5) for an increase in body shape index of 0.005 units, 2.55 (1.59 to 4.10, n=4) for a 10% higher body adiposity index, and 1.11 (0.98 to 1.27; n=14) for a 10 cm larger hip circumference. A strong positive linear association was found between body mass index and the risk of type 2 diabetes. Positive linear or monotonic associations were also found in all regions and ethnicities, without marked deviation from linearity at a specific cut-off value. Indices of central fatness, independent of overall adiposity, also had positive linear or monotonic associations with the risk of type 2 diabetes. Positive linear or monotonic associations were also found for total and visceral fat mass, although the number of studies was small. CONCLUSIONS A higher body mass index was associated with a greater risk of developing type 2 diabetes. A larger waist circumference, independent of overall adiposity, was strongly and linearly associated with the risk of type 2 diabetes. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42021255338.
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Recessive Genome-Wide Meta-analysis Illuminates Genetic Architecture of Type 2 Diabetes.
O'Connor, MJ, Schroeder, P, Huerta-Chagoya, A, Cortés-Sánchez, P, Bonàs-Guarch, S, Guindo-Martínez, M, Cole, JB, Kaur, V, Torrents, D, Veerapen, K, et al
Diabetes. 2022;(3):554-565
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Abstract
Most genome-wide association studies (GWAS) of complex traits are performed using models with additive allelic effects. Hundreds of loci associated with type 2 diabetes have been identified using this approach. Additive models, however, can miss loci with recessive effects, thereby leaving potentially important genes undiscovered. We conducted the largest GWAS meta-analysis using a recessive model for type 2 diabetes. Our discovery sample included 33,139 case subjects and 279,507 control subjects from 7 European-ancestry cohorts, including the UK Biobank. We identified 51 loci associated with type 2 diabetes, including five variants undetected by prior additive analyses. Two of the five variants had minor allele frequency of <5% and were each associated with more than a doubled risk in homozygous carriers. Using two additional cohorts, FinnGen and a Danish cohort, we replicated three of the variants, including one of the low-frequency variants, rs115018790, which had an odds ratio in homozygous carriers of 2.56 (95% CI 2.05-3.19; P = 1 × 10-16) and a stronger effect in men than in women (for interaction, P = 7 × 10-7). The signal was associated with multiple diabetes-related traits, with homozygous carriers showing a 10% decrease in LDL cholesterol and a 20% increase in triglycerides; colocalization analysis linked this signal to reduced expression of the nearby PELO gene. These results demonstrate that recessive models, when compared with GWAS using the additive approach, can identify novel loci, including large-effect variants with pathophysiological consequences relevant to type 2 diabetes.
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Nut consumption and type 2 diabetes risk: a systematic review and meta-analysis of observational studies.
Becerra-Tomás, N, Paz-Graniel, I, Hernández-Alonso, P, Jenkins, DJA, Kendall, CWC, Sievenpiper, JL, Salas-Salvadó, J
The American journal of clinical nutrition. 2021;(4):960-971
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Abstract
BACKGROUND Previous meta-analyses, with some methodological controversies, have assessed the relation between nut consumption and type 2 diabetes (T2D) risk and pointed to contradictory results, making desirable the performance of an updated meta-analysis. OBJECTIVES We aimed to systematically review and meta-analyze all the published studies investigating the relations of total nuts and different types of nuts-i.e., walnuts, peanuts, peanut butter, and total tree nuts-with the prevalence and incidence of T2D. METHODS A systematic search was conducted in the PubMed and Cochrane databases through 12 August, 2020. The inverse variance method with fixed-effect models was used to pool data across studies, expressed as risk ratios (RRs) or ORs and 95% CIs for prospective cohort and cross-sectional studies, respectively. The Cochran Q test and I2 statistics were used to test and quantify heterogeneity, respectively. Dose-response meta-analysis was also conducted. RESULTS Eight studies (5 prospective and 3 cross-sectional) were included in the quantitative synthesis. Meta-analyses of cross-sectional studies and prospective cohort studies, comparing the highest with the lowest categories, revealed a nonsignificant association between total nut consumption and T2D. Meta-analyses of prospective cohort studies showed an inverse association between peanut butter consumption and T2D incidence (RR: 0.87; 95% CI: 0.77, 0.98; I2 = 50.6%; Pheterogeneity = 0.16), whereas no association was observed between peanuts or tree nuts and T2D. There was no evidence of a linear dose-response or nonlinear dose-response gradient for total nut and peanut consumption in prospective cohort studies. The certainty of the evidence using NutriGrade was very low for all the exposures. CONCLUSIONS Current results do not demonstrate an association of total nut, peanut, or tree nut consumption with T2D. Peanut butter consumption may be inversely associated with this disease.This review protocol was registered at www.crd.york.ac.uk/prospero/ as CRD42020149756.
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Effects of Anti-Diabetic Drugs on Fracture Risk: A Systematic Review and Network Meta-Analysis.
Zhang, YS, Zheng, YD, Yuan, Y, Chen, SC, Xie, BC
Frontiers in endocrinology. 2021;:735824
Abstract
PURPOSE Available data on the effects of anti-diabetic drugs on fracture risk are contradictory. Therefore, our study aimed to analyze all available data on the effects of anti-diabetic drugs on fracture risk in type 2 diabetes mellitus (T2DM) patients. METHODS Embase, Medline, ClinicalTrials.gov, and Cochrane CENTRAL were searched for relevant trials. All data analyses were performed with STATA (12.0) and R language (3.6.0). Risk ratio (RR) with its 95% confidence interval (CI) was calculated by combining data for the fracture effects of anti-diabetic drugs, including sodium-glucose co-transporter 2 (SGLT2) inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, meglitinides, α-glucosidase inhibitors, thiazolidinediones, biguanides, insulin, and sulfonylureas. RESULTS One hundred seventeen eligible randomized controlled trials (RCTs) with 221,364 participants were included in this study. Compared with placebo, trelagliptin (RR 3.51; 1.58-13.70) increased the risk of fracture, whereas albiglutide (RR 0.29; 0.04-0.93) and voglibose (RR 0.03; 0-0.11) decreased the risk of fracture. Other medications were comparable in terms of their effects on fracture risk, and no statistical significance was observed. In terms of fractures, voglibose (0.01%) may be the safest option, and trelagliptin (13.64%) may be the worst. Sensitivity analysis results were consistent with those of the main analysis. No statistically significant differences were observed in the regression coefficients of age (1.03; 0.32-2.1), follow-up duration (0.79; 0.27-1.64), and sex distribution (0.63; 0.15-1.56). CONCLUSIONS We found varied results on the association between the use of anti-diabetic drugs and fracture risk. Specifically, trelagliptin raised the risk of fracture, whereas voglibose and albiglutide showed benefit with statistical difference. Other drugs were comparable in terms of their effects on fracture risk. Some drugs (omarigliptin, sitagliptin, vildagliptin, saxagliptin, empagliflozin, ertugliflozin, rosiglitazone, pioglitazone, and nateglinide) may increase the risk of fracture, while others (such as dulaglutide, exenatide, liraglutide, semaglutide, lixisenatide, linagliptin, alogliptin, canagliflozin, dapagliflozin, glipizide, gliclazide, glibenclamide, glimepiride, metformin, and insulin) may show benefits. The risk of fracture was independent of age, sex distribution, and the duration of exposure to anti-diabetic drugs. When developing individualized treatment strategies, the clinical efficacy of anti-diabetic drugs must be weighed against their benefits and risks brought about by individual differences of patients. SYSTEMATIC REVIEW REGISTRATION This Systematic Review was prospectively registered on the PROSPERO (https://www.crd.york.ac.uk/PROSPERO/, registration number CRD42020189464).
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Tolerability and Efficacy of Ipragliflozin in The Management of Inadequately Controlled Type 2 Diabetes mellitus: A Systematic Review and Meta-analysis.
Elgebaly, A, Abdelazeim, N, Abdelazeim, B, El Ashal, G, Mattar, O, Namous, L, Nasreldin, N
Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association. 2021;(1):56-72
Abstract
AIM: Ipragliflozin is a new antidiabetic agent that works through enhancing renal glucose excretion. We aim to synthesize evidence from published randomized controlled trials (RCTs) on the safety and efficacy of ipragliflozin in the management of type 2 diabetes mellitus (T2DM). METHODS We searched PubMed, Scopus, Web of Science, and Cochrane Central register of clinical trials using relevant keywords. Records were screened for eligible studies and data were extracted and synthesized using Review Manager Version 5.3 for windows. Subgroup and sensitivity analyses were conducted. RESULTS We included 13 RCTs (N=2535 patients) in the final analysis. The overall effect estimates favoured ipragliflozin 50mg monotherapy group over placebo in terms of: HbA1c (Standardized mean difference (SMD)=-1.20%, 95% Confidence interval (95% CI)=[-1.47, -0.93]; p<0.001), fasting plasma glucose (SMD=-1.30 mg/dL, 95% CI [-1.93, -0.67]; p<0.001), fasting serum insulin (SMD=-1.64 μU/mL, 95% CI [-2.70, -0.59]; p=0.002), and body weight (SMD=-0.85 kg, 95% CI [-1.19, -0.51]; p<0.001). Similarly, better glycemic control and significant body weight reduction compared to placebo were attained in ipragliflozin 50 mg combination with metformin, insulin with/without dipeptidyl peptidase-4 inhibitor, sulfonylurea, and pioglitazone. Ipragliflozin, either alone or in combination, exhibits acceptable safety profile. CONCLUSION The presented meta-analysis provides class one evidence that ipragliflozin is safe and effective in the management of T2DM either as monotherapy or an add-on.
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Sodium-glucose cotransporter protein-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists for type 2 diabetes: systematic review and network meta-analysis of randomised controlled trials.
Palmer, SC, Tendal, B, Mustafa, RA, Vandvik, PO, Li, S, Hao, Q, Tunnicliffe, D, Ruospo, M, Natale, P, Saglimbene, V, et al
BMJ (Clinical research ed.). 2021;:m4573
Abstract
OBJECTIVE To evaluate sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists in patients with type 2 diabetes at varying cardiovascular and renal risk. DESIGN Network meta-analysis. DATA SOURCES Medline, Embase, and Cochrane CENTRAL up to 11 August 2020. ELIGIBILITY CRITERIA FOR SELECTING STUDIES Randomised controlled trials comparing SGLT-2 inhibitors or GLP-1 receptor agonists with placebo, standard care, or other glucose lowering treatment in adults with type 2 diabetes with follow up of 24 weeks or longer. Studies were screened independently by two reviewers for eligibility, extracted data, and assessed risk of bias. MAIN OUTCOME MEASURES Frequentist random effects network meta-analysis was carried out and GRADE (grading of recommendations assessment, development, and evaluation) used to assess evidence certainty. Results included estimated absolute effects of treatment per 1000 patients treated for five years for patients at very low risk (no cardiovascular risk factors), low risk (three or more cardiovascular risk factors), moderate risk (cardiovascular disease), high risk (chronic kidney disease), and very high risk (cardiovascular disease and kidney disease). A guideline panel provided oversight of the systematic review. RESULTS 764 trials including 421 346 patients proved eligible. All results refer to the addition of SGLT-2 inhibitors and GLP-1 receptor agonists to existing diabetes treatment. Both classes of drugs lowered all cause mortality, cardiovascular mortality, non-fatal myocardial infarction, and kidney failure (high certainty evidence). Notable differences were found between the two agents: SGLT-2 inhibitors reduced admission to hospital for heart failure more than GLP-1 receptor agonists, and GLP-1 receptor agonists reduced non-fatal stroke more than SGLT-2 inhibitors (which appeared to have no effect). SGLT-2 inhibitors caused genital infection (high certainty), whereas GLP-1 receptor agonists might cause severe gastrointestinal events (low certainty). Low certainty evidence suggested that SGLT-2 inhibitors and GLP-1 receptor agonists might lower body weight. Little or no evidence was found for the effect of SGLT-2 inhibitors or GLP-1 receptor agonists on limb amputation, blindness, eye disease, neuropathic pain, or health related quality of life. The absolute benefits of these drugs vary substantially across patients from low to very high risk of cardiovascular and renal outcomes (eg, SGLT-2 inhibitors resulted in 3 to 40 fewer deaths in 1000 patients over five years; see interactive decision support tool (https://magicevidence.org/match-it/200820dist/#!/) for all outcomes. CONCLUSIONS In patients with type 2 diabetes, SGLT-2 inhibitors and GLP-1 receptor agonists reduced cardiovascular and renal outcomes, with some differences in benefits and harms. Absolute benefits are determined by individual risk profiles of patients, with clear implications for clinical practice, as reflected in the BMJ Rapid Recommendations directly informed by this systematic review. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42019153180.
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Effect of green tea on glycemic control in patients with type 2 diabetes mellitus: A systematic review and meta-analysis.
Asbaghi, O, Fouladvand, F, Gonzalez, MJ, Ashtary-Larky, D, Choghakhori, R, Abbasnezhad, A
Diabetes & metabolic syndrome. 2021;(1):23-31
Abstract
BACKGROUND AND AIMS Several studies have investigated the potential beneficial effects of green tea in patients with type 2 diabetes mellitus (T2DM). Therefore, we aimed to perform a systematic review and meta-analysis of the randomized controlled trials (RCTs) that assessed the effect of supplementary intake of green tea on fasting plasma glucose (FPG), fasting insulin, hemoglobin A1c (HbA1c) and HOMA-IR in patients with T2DM. METHODS A systematic search was performed in Web of Science, PubMed and Scopus without any language and time restriction up to June 2019, to retrieve the related RCTs. Meta-analysis was carried out using both the random and fixed effects model where appropriate. I2 index was used to evaluate the heterogeneity. RESULTS Initial search yielded 780 publications. Fourteen articles were eligible. Our meta-analysis indicated that the supplementary intake of green tea had no significant effect on FPG, fasting insulin, HbA1c and HOMA-IR in patients with T2DM. CONCLUSION Results of the present systematic review and meta-analysis indicated that the supplementary intake of green tea had no significant effect on FPG, fasting insulin, HbA1c and HOMA-IR in patients with T2DM.
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Effect of Statin Therapy on Diabetes Retinopathy in People With Type 2 Diabetes Mellitus: A Meta-Analysis.
Liu, J, Wu, YP, Qi, JJ, Yue, ZP, Hu, CD
Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis. 2021;:10760296211040109
Abstract
Objective: We tried to find the relationship between statin and diabetes retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM). Methods: We searched the databases of PubMed, EMBASE, and the Cochrane Library for eligible studies reporting on the relationships between statin use and DR, from inception to September 25, 2020. The terms searched including Diabetes Mellitus, Type 2, Hydroxymethylglutaryl-CoA Reductase Inhibitors, and Diabetic Retinopathy. We expressed the results as the odds ratios (ORs) with 95% confidence intervals (CIs) which were calculated using a random-effects model. Results: A total of 6 eligible studies, including 43 826 patients, were included in the meta-analysis. The meta-analysis showed that statin was not associated with elevated risk of DR [OR = 0.96 (95% CI: 0.80-1.16), P = .68]. Similarly, no differences were found between statin and placebo in participants ≥500 [OR = 0.98 (95% CI: 0.80-1.21)] or participants <500 [OR = 0.90 (95% CI: 0.49-1.66)]. Further, we conducted a meta-analysis to study the effect of statin therapy on DR in people with type 2 diabetes according to age and found that statin use was associated with a decreased risk of DR in patients with type 2 diabetes 40 years of age or older [OR = 0.87 (95% CI: 0.82-0.92)]. Conclusion: Our meta-analysis revealed that statin was not associated with elevated risk of DR in patients with T2DM. Moreover, statin use was associated with a lower incidence of DR in patients with type 2 diabetes 40 years of age or older.
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Regional variation of effects of new antidiabetic medications in cardiovascular outcome trials.
Cotter, G, Davison, BA, Edwards, C, Senger, S, Teerlink, JR, Zannad, F, Nielsen, OW, Metra, M, Mebazaa, A, Chioncel, O, et al
American heart journal. 2021;:73-80
Abstract
BACKGROUND In international trials, glucagon-like protein-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2Is) were effective in improving cardiovascular (CV) outcomes. METHODS We assessed the effect of GLP-1RAs and SGLT2Is treatment effect on CV endpoints by geographical region in multiple international trials using random effects weighted least squares meta-regressions. RESULTS The estimated effects of both SGLT2Is and GLP-1RAs on major adverse CV events (MACE) in North America (SGLT2Is n = 12,399, HR 0.90, 95% CI 0.81-1.01; GLP-1RAs n = 12,515, HR 0.95, 95% CI 0.83- 1.09) and in Europe (SGLT2Is n = 19,435, HR 0.93, 95% CI 0.85-1.02; GLP-1RAs n = 22,812, HR 0.88, 95% CI 0.79-0.99) were numerically lower but not statistically different to the rest of the world (ROW) (SGLT2Is n = 15,127, HR 0.83, 95% CI 0.75-0.92, p-value for interaction 0.26; GLP-1RAs n = 17,494, HR 0.82, 95% CI 0.73-0.92, p-value for interaction 0.28). Effects of SGLT2Is on heart failure readmission or CV death varied significantly by region (P = 0.0094). The effect of SGLT2Is was significantly smaller in Europe (n = 18,653, HR 0.86, 95% CI 0.78-0.95) than in the ROW (n = 12,463, HR 0.68, 95% CI 0.61-0.76, P = 0.0024). The smaller effect in North America (n = 9776, HR 0.76, 95% CI 0.66-0.87) did not differ significantly from that in the ROW (P = 0.2370). CONCLUSION The effects of SGLT2Is on HF events are larger in the ROW. Further analyses and studies are needed to better elucidate the differential effects of SGLTIs and GLP-1RAs by geographical regions.