scholarly journals Interaction of Diet/Lifestyle Intervention and TCF7L2 Genotype on Glycemic Control and Adiposity among Overweight or Obese Adults: Big Data from Seven Randomized Controlled Trials Worldwide

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Tao Huang ◽  
Zhenhuang Zhuang ◽  
Yoriko Heianza ◽  
Dianjianyi Sun ◽  
Wenjie Ma ◽  
...  

Objective. The strongest locus which associated with type 2 diabetes (T2D) by the common variant rs7903146 is the transcription factor 7-like 2 gene (TCF7L2). We aimed to quantify the interaction of diet/lifestyle interventions and the genetic effect of TCF7L2 rs7903146 on glycemic traits, body weight, or waist circumference in overweight or obese adults in several randomized controlled trials (RCTs). Methods. From October 2016 to May 2018, a large collaborative analysis was performed by pooling individual-participant data from 7 RCTs. These RCTs reported changes in glycemic control and adiposity of the variant rs7903146 after dietary/lifestyle-related interventions in overweight or obese adults. Gene treatment interaction models which used the genetic effect encoded by the allele dose and common covariates were applicable to individual participant data in all studies. Results. In the joint analysis, a total of 7 eligible RCTs were included (n=4,114). Importantly, we observed a significant effect modification of diet/lifestyle-related interventions on the TCF7L2 variant rs7903146 and changes in fasting glucose. Compared with the control group, diet/lifestyle interventions were related to lower fasting glucose by -3.06 (95% CI, -5.77 to -0.36) mg/dL (test for heterogeneity and overall effect: I2=45.1%, p<0.05; z=2.20, p=0.028) per one copy of the TCF7L2 T risk allele. Furthermore, regardless of genetic risk, diet/lifestyle interventions were associated with lower waist circumference. However, there was no significant change for diet/lifestyle interventions in other glycemic control and adiposity traits per one copy of TCF7L2 risk allele. Conclusions. Our findings suggest that carrying the TCF7L2 T risk allele may have a modestly greater benefit for specific diet/lifestyle interventions to improve the control of fasting glucose in overweight or obese adults.

2020 ◽  
Author(s):  
Jean-Charles ROY ◽  
Chloé Rousseau ◽  
Alexis Jutel ◽  
Florian Naudet ◽  
Gabriel Robert

Abstract Background. Duloxetine is an antidepressant which benefits from a wide range of approval in elderly population while its safety of use in elderly population, compared to younger adults, is not clearly assessed. A comparison of tolerability of duloxetine between elderly and younger adults would help to rule on this issue. Methods and Design. This protocol outlines a systematic review and meta-analysis of individual participant data (IPD) of all double-blind randomized controlled trials comparing the number of serious adverse events among individuals taking duloxetine in comparison to placebo between participants at least 65 years and younger adults in conditions approved by the European Medical Agency (EMA) and the Food Drug Administration (FDA). Secondarily, will be compared the number of any adverse events, clinical efficacy and quality of life between elderly and younger adults under duloxetine, in comparison to placebo. Relevant studies were selected on ClinicalTrials.gov, Clinicaltrialsregister.eu, data sharing platforms, FDA and EMA websites, and from systematic reviews and meta-analyses of duloxetine on PubMed, following Cochrane’s recommendations. Sponsors and authors from eligible studies were invited to share IPD on data sharing platform or directly with our research team. As data cannot be aggregate into a unique database, a two step-approach meta-analysis will be undertaken. Qualitative results from available data. 77 eligible randomized controlled trials were identified, representing 25303 participants. From online available data, 35 trials were assessed as being at an overall low risk of bias, 31 trials at an unclear risk of bias and 1 at high risk of bias. Evaluation of risk of bias was not feasible for 10 studies. Conclusion. This study would represent the first meta-analysis investigating the safety of duloxetine in elderly population across all conditions approved by European and American regulatory authorities with an overall low risk of bias. Registration. PROSPERO: 2019 CRD42019130488.


2018 ◽  
Vol 50 (11) ◽  
pp. 783-790 ◽  
Author(s):  
Amin Doosti-Irani ◽  
Vahidreza Ostadmohammadi ◽  
Naghmeh Mirhosseini ◽  
MohammadAli Mansournia ◽  
Russel Reiter ◽  
...  

AbstractThis systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to clarify the effect of melatonin supplementation on glycemic control. Databases including PubMed, MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials were searched until July 30th, 2018. Two reviewers independently assessed study eligibility, extracted data, and evaluated the risk of bias for included trials. Heterogeneity among included studies was assessed using Cochran’s Q test and I-square (I2) statistic. Data were pooled using random-effect models and standardized mean difference (SMD) was considered as the overall effect size. Twelve trials out of 292 selected reports were identified eligible to be included in current meta-analysis. The pooled findings indicated that melatonin supplementation significantly reduced fasting glucose (SMD=–6.34; 95% CI, –12.28, –0.40; p=0.04; I2: 65.0) and increased the quantitative insulin sensitivity check index (QUICKI) (SMD=0.01; 95% CI, 0.00, 0.02; p=0.01; I2: 0.0). However, melatonin administration did not significantly influence insulin levels (SMD=–1.03; 95% CI, –3.82, 1.77; p=0.47; I2: 0.53), homeostasis model assessment of insulin resistance (HOMA-IR) (SMD=–0.34; 95% CI, –1.25, 0.58; p=0.37; I2: 0.37) or HbA1c levels (SMD=–0.22; 95% CI, –0.47, 0.03; p=0.08; I2: 0.0). In summary, the current meta-analysis showed a promising effect of melatonin supplementation on glycemic control through reducing fasting glucose and increasing QUICKI, yet additional prospective studies are recommended, using higher supplementation doses and longer intervention period, to confirm the impact of melatonin on insulin levels, HOMA-IR and HbA1c.


2018 ◽  
Vol 24 (27) ◽  
pp. 3184-3199 ◽  
Author(s):  
Reza Tabrizi ◽  
Sina Vakili ◽  
Kamran B. Lankarani ◽  
Maryam Akbari ◽  
Naghmeh Mirhosseini ◽  
...  

Background: This systematic review and meta-analysis of randomized controlled trials (RCTs), were performed to determine the effects of curcumin intake on glycemic control and lipid profiles among patients with metabolic syndrome (MetS) and related disorders. Methods: We searched the following databases up until January 2018: MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials. The relevant data were extracted and evaluated for quality of the studies in accordance with the Cochrane risk of bias tool. Data were pooled using the inverse variance method and expressed as standardized mean difference (MDs) with 95% confidence intervals (95% CI). Results: Twenty-six trials with 1890 participants were included in the current meta-analysis. The findings demonstrated the significant association between curcumin intake and reduced fasting glucose levels (SMD -0.78; 95% CI, -1.20, -0.37; P<0.001), homeostasis model of assessment-estimated insulin resistance (SMD -0.91; 95% CI, -1.52, -0.31; P=0.003) and HbA1c (SMD -0.92; 95% CI, -1.37, -0.47; P<0.001). In addition, curcumin supplementation was significantly associated with triglyceride (SMD -1.21; 95 % CI, -1.78, -0.65; P<0.001) and total cholesterol reduction (SMD -0.73; 95 % CI, -1.32, -0.13; P= 0.01). However, curcumin intake significantly increased insulin levels (SMD 0.92; 95% CI, 0.06, 1.78; P=0.036). We found no significant effect of curcumin supplementation on LDL- (SMD -0.52; 95% CI, -1.14, 0.11; P=0.10) and HDL-cholesterol levels (SMD 0.28; 95% CI, -0.22, 0.77; P=0.27). Conclusion: Overall, curcumin consumption was associated with a significant reduction in fasting glucose, HOMA-IR, HbA1c, triglycerides and total cholesterol levels among patients with MetS and related disorders, but did not affect LDL- and HDL-cholesterol levels.


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