Metabolic Effects of Testosterone Replacement Therapy in Patients with Type 2 Diabetes Mellitus or Metabolic Syndrome: A Meta-Analysis
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SUBMITTER: Li S
PROVIDER: S-EPMC7545471 | biostudies-literature | 2020 Jan
REPOSITORIES: biostudies-literature
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Project description:Aims. To investigate how circulating microvesicle phenotypes correlate with insulin sensitivity, body composition, plasma lipids, and hepatic fat accumulation. We hypothesized that changes elicited by testosterone replacement therapy are reflected in levels of microvesicles. Methods. Thirty-nine type 2 diabetic males with lowered testosterone levels were assigned to either testosterone replacement therapy or placebo and evaluated at baseline and after 24 weeks. Microvesicles were analysed by flow cytometry and defined as lactadherin-binding particles within the 0.1-1.0??m gate. Microvesicles of platelet, monocyte, and endothelial cell origin were identified by cell-specific markers and their expression of CD36 was investigated. Results. Triglycerides correlated positively with all investigated microvesicle phenotypes in this study (p < 0.05), and indicators of hepatic fat accumulation, alanine aminotransferase, and gamma glutamyltransferase correlated with platelet and endothelial microvesicles and CD36-expressing microvesicles from platelets and monocytes (p < 0.05). BMI, waist circumference, and fat percentage correlated with CD36-expressing monocyte microvesicles (p < 0.05), while insulin sensitivity did not correlate with any microvesicle phenotypes. Microvesicle levels were unaffected by testosterone therapy. Conclusions. Metabolic syndrome components and hepatic fat accumulation correlated with microvesicle phenotypes, supporting the involvement of especially CD36 on monocytes in metabolic syndrome pathogenesis. Although testosterone therapy improved body composition measures, microvesicle phenotype levels were unaffected. This trial was registered at ClinicalTrials.gov (NCT01560546).
| S-EPMC5266820 | biostudies-literature
Project description:ObjectiveThis study evaluated the effects of testosterone replacement therapy (TRT) on insulin resistance, cardiovascular risk factors, and symptoms in hypogonadal men with type 2 diabetes and/or metabolic syndrome (MetS).Research design and methodsThe efficacy, safety, and tolerability of a novel transdermal 2% testosterone gel was evaluated over 12 months in 220 hypogonadal men with type 2 diabetes and/or MetS in a multicenter, prospective, randomized, double-blind, placebo-controlled study. The primary outcome was mean change from baseline in homeostasis model assessment of insulin resistance (HOMA-IR). Secondary outcomes were measures of body composition, glycemic control, lipids, and sexual function. Efficacy results focused primarily on months 0-6 (phase 1; no changes in medication allowed). Medication changes were allowed in phase 2 (months 6-12).ResultsTRT reduced HOMA-IR in the overall population by 15.2% at 6 months (P = 0.018) and 16.4% at 12 months (P = 0.006). In type 2 diabetic patients, glycemic control was significantly better in the TRT group than the placebo group at month 9 (HbA(1c): treatment difference, -0.446%; P = 0.035). Improvements in total and LDL cholesterol, lipoprotein a (Lpa), body composition, libido, and sexual function occurred in selected patient groups. There were no significant differences between groups in the frequencies of adverse events (AEs) or serious AEs. The majority of AEs (>95%) were mild or moderate.ConclusionsOver a 6-month period, transdermal TRT was associated with beneficial effects on insulin resistance, total and LDL-cholesterol, Lpa, and sexual health in hypogonadal men with type 2 diabetes and/or MetS.
| S-EPMC3064036 | biostudies-literature
Project description:A third of men with type 2 diabetes (T2DM) have hypogonadotrophic hypogonadism (HH) and associated increased risk of cardiovascular and all-cause mortality. Men with HH are at increased risk of developing incident T2DM. We conducted MEDLINE, EMBASE, and COCHRANE reviews on T2DM, HH, testosterone deficiency, cardiovascular and all-cause mortality from May 2005 to October 2017, yielding 1,714 articles, 52 clinical trials and 32 randomized controlled trials (RCT). Studies with testosterone therapy suggest significant benefits in sexual function, quality of life, glycaemic control, anaemia, bone density, fat, and lean muscle mass. Meta-analyses of RCT, rather than providing clarification, have further confused the issue by including under-powered studies of inadequate duration, multiple regimes, some discontinued, and inbuilt bias in terms of studies included or excluded from analysis.
| S-EPMC6305869 | biostudies-other
Project description:OBJECTIVE:Metabolic syndrome refers to a collection of risk factors associated with the development of cardiovascular disease and type 2 diabetes mellitus (T2DM). Canagliflozin, a sodium glucose co-transporter 2 inhibitor, improves glycemic control and reduces body weight and blood pressure (BP) in a broad range of patients with T2DM. This post hoc analysis assessed the effects of canagliflozin on the components of metabolic syndrome in patients with T2DM and metabolic syndrome. METHODS:This analysis was based on data from 2 head-to-head studies of canagliflozin in patients with T2DM on background metformin versus glimepiride (study 1) and background metformin plus sulfonylurea versus sitagliptin 100 mg (study 2). Changes from baseline in glycemic efficacy, anthropometric measures, BP, and lipids were evaluated with canagliflozin versus glimepiride and sitagliptin at week 52 in patients who met ?2 of the criteria for metabolic syndrome (in addition to T2DM): triglycerides ?1.7 mmol/L; high-density lipoprotein cholesterol (HDL-C) <1.0 mmol/L (men) or <1.3 mmol/L (women); waist circumference ?102 cm (non-Asian men), ?88 cm (non-Asian women), >90 cm (Asian men), or >80 cm (Asian women); diagnosis of hypertension or meeting BP-related criteria (systolic BP ?130 mmHg or diastolic BP ?85 mmHg). Safety was assessed based on adverse event reports. RESULTS:In study 1, canagliflozin 100 and 300 mg provided similar and greater HbA1c reductions versus glimepiride, respectively. In study 2, canagliflozin 300 mg provided greater HbA1c lowering versus sitagliptin 100 mg. Canagliflozin also reduced fasting plasma glucose, body weight, body mass index, waist circumference, BP, and triglycerides, and increased HDL-C and low-density lipoprotein cholesterol versus glimepiride and sitagliptin. Canagliflozin was generally well tolerated in each study. CONCLUSION:Canagliflozin was associated with improvements in all components of metabolic syndrome in patients with T2DM and metabolic syndrome, whereas glimepiride and sitagliptin only improved glycemic components over 52 weeks.
| S-EPMC5291455 | biostudies-literature
Project description:BackgroundThe presence of metabolic syndrome among diabetes patients is frequent and is associated with an increased incidence of chronic complications and mortality. Despite several studies have been conducted, there is no overall estimation on the prevalence of metabolic syndrome among type 1 diabetic patients. Therefore, this study aimed to estimate the pooled prevalence of metabolic syndrome among patients with type 1 diabetes mellitus.MethodsMedline via PubMed, CINAHL, ScienceDirect, Ovid, Google Scholar, ResearchGate and African Journals Online were searched by limiting publication period from January 2005 to October 2020. Data were extracted with a standardized format prepared in Microsoft Excel and exported to Stata 16.0 for analyses. The I2 statistic was used to check heterogeneity across the included studies. DerSimonian and Laird random-effects model was applied to estimate pooled prevalence and 95% confidence interval across studies. Funnel plot symmetry, Begg's test and Egger's regression test were used to determine the presence of publication bias. Subgroup and sensitivity analysis as well as meta-regression were conducted to explore the potential sources of heterogeneity. The study protocol is registered on PROSPERO with reference number: CRD42020213435.ResultsIn this meta-analysis, a total of 27 studies with 45,811 study participants were included. The pooled prevalence of metabolic syndrome was 23.7% with substantial heterogeneity (I2 = 98.2%; P < 0.001). Geographical-based subgroup analysis revealed that the highest prevalence was observed in Australia (27.3%). As per meta-analysis of 17 studies, the pooled prevalence of metabolic syndrome in female type 1 diabetes patients (25.9%) was slightly higher than male T1DM patients (22.5%).ConclusionNearly a quarter of the type 1 diabetes mellitus patients were affected by metabolic syndrome. Therefore, more attention should be paid to the prevention and control of the epidemic and for the reduction of the morbidity and mortality associated with metabolic syndrome among type 1 diabetes mellitus patients.
| S-EPMC7923483 | biostudies-literature
Project description:BackgroundWe investigated whether combination therapy with a statin plus a fibrate, as compared with statin monotherapy, would reduce the risk of cardiovascular disease in patients with type 2 diabetes mellitus who were at high risk for cardiovascular disease.MethodsWe randomly assigned 5518 patients with type 2 diabetes who were being treated with open-label simvastatin to receive either masked fenofibrate or placebo. The primary outcome was the first occurrence of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes. The mean follow-up was 4.7 years.ResultsThe annual rate of the primary outcome was 2.2% in the fenofibrate group and 2.4% in the placebo group (hazard ratio in the fenofibrate group, 0.92; 95% confidence interval [CI], 0.79 to 1.08; P=0.32). There were also no significant differences between the two study groups with respect to any secondary outcome. Annual rates of death were 1.5% in the fenofibrate group and 1.6% in the placebo group (hazard ratio, 0.91; 95% CI, 0.75 to 1.10; P=0.33). Prespecified subgroup analyses suggested heterogeneity in treatment effect according to sex, with a benefit for men and possible harm for women (P=0.01 for interaction), and a possible interaction according to lipid subgroup, with a possible benefit for patients with both a high baseline triglyceride level and a low baseline level of high-density lipoprotein cholesterol (P=0.057 for interaction).ConclusionsThe combination of fenofibrate and simvastatin did not reduce the rate of fatal cardiovascular events, nonfatal myocardial infarction, or nonfatal stroke, as compared with simvastatin alone. These results do not support the routine use of combination therapy with fenofibrate and simvastatin to reduce cardiovascular risk in the majority of high-risk patients with type 2 diabetes. (ClinicalTrials.gov number, NCT00000620.)
| S-EPMC2879499 | biostudies-literature
Project description:A meta-analysis was carried out to evaluate the efficacy of yoga in adults with type 2 diabetes mellitus.The PubMed, EMBASE and Cochrane databases were searched to obtain eligible randomized controlled trials. The primary outcome was fasting blood glucose, and the secondary outcomes included glycosylated hemoglobin A1c, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride and postprandial blood glucose. Weighted mean differences and 95% confidence intervals (CIs) were calculated. The I2 statistic represented heterogeneity.A total of 12 randomized controlled trials with a total of 864 patients met the inclusion criteria. The pooled weighted mean differences were -23.72 mg/dL (95% CI -37.78 to -9.65; P = 0.001; I2 = 82%) for fasting blood glucose and -0.47% (95% CI -0.87 to -0.07; P = 0.02; I2 = 82%) for hemoglobin A1c. The weighted mean differences were -17.38 mg/dL (95% CI -27.88 to -6.89; P = 0.001; I2 = 0%) for postprandial blood glucose, -18.50 mg/dL (95% CI -29.88 to -7.11; P = 0.001; I2 = 75%) for total cholesterol, 4.30 mg/dL (95% CI 3.25 to 5.36; P < 0.00001; I2 = 10%) for high-density lipoprotein cholesterol, -12.95 mg/dL (95% CI -18.84 to -7.06; P < 0.0001; I2 = 37%) for low-density lipoprotein cholesterol and -12.57 mg/dL (95% CI -29.91 to 4.76; P = 0.16; I2 = 48%) for triglycerides.The available evidence suggests that yoga benefits adult patients with type 2 diabetes mellitus. However, considering the limited methodology and the potential heterogeneity, further studies are necessary to support our findings and investigate the long-term effects of yoga in type 2 diabetes mellitus patients.
| S-EPMC5334310 | biostudies-other
Project description:AimThe aim of this systematic review was to assess the effect of periodontal therapy (PT) on serum levels of inflammatory markers in people with type 2 diabetes mellitus (T2DM).Methods of study selectionA literature search was carried out using MEDLINE via Pubmed, EMBASE, LILACS and Cochrane Central Register of Controlled Trials (CENTRAL) databases. Randomized-controlled trials (RCTs) and controlled clinical trials (CCTs) evaluating the effect of PT on systemic inflammatory markers were deemed eligible. Case series (CS), reports and pilot trials were excluded. Study quality was assessed using the Cochrane Collaboration's risk assessment tool. Meta-analysis was carried out using random effect methods.ResultsThe search strategy identified 3,164 potential studies of which 61 were assessed for eligibility and 9 (6 RCTs and 3 CCTs) were included in this systematic review. Three RCTs were classified by the authors as being at low risk of bias and three were "unclear" and classified as uncertain risk of bias. All CCTs were considered to be at a high risk of bias. The meta-analysis showed a statistically significant mean difference (MD) for TNF- ? (-1.33 pg/ml, 95% CI: -2.10; -0.56, p<0.001) and CRP (-1.28 mg/l, 95% CI: -2.07; - 0.48, p<0.001) favoring periodontal intervention versus control.ConclusionThe results of this meta-analysis support the hypothesis that PT reduces serum levels of TNF- ? and CRP in T2DM individuals. The decrease of inflammatory burden has important implications for metabolic control and can, in part, explain the mechanisms linking periodontitis and increased risk for complications in people with T2DM.
| S-EPMC4444100 | biostudies-literature
Project description:ContextMale hypogonadism is associated with low bone mineral density (BMD) and increased fragility fracture risk. Patients with type 2 diabetes (T2D) have relatively higher BMD, but greater fracture risk.ObjectiveEvaluate the skeletal response to testosterone therapy in hypogonadal men with T2D compared with hypogonadal men without T2D.MethodsSingle arm, open-label clinical trial (NCT01378299) involving 105 men (40-74 years old), with average morning testosterone <300 ng/dL. Subjects were injected intramuscularly with testosterone cypionate (200 mg) every 2 weeks for 18 months. Testosterone and estradiol were assessed by liquid chromatography/mass spectrometry; serum C-terminal telopeptide of type I collagen (CTX), osteocalcin and sclerostin by enzyme-linked immunosorbent assay; glycated hemoglobin (HbA1c) by high-performance liquid chromatography, areal BMD (aBMD) and body composition by dual-energy x-ray absorptiometry; tibial volumetric BMD (vBMD) and bone geometry by peripheral quantitative computed tomography.ResultsAmong our population of hypogonadal men, 49 had T2D and 56 were non-T2D. After 18 months of testosterone therapy, there were no differences in circulating testosterone and estradiol between the groups. Hypogonadal men with T2D had increased osteocalcin, reflecting increased osteoblast activity, compared with non-T2D men (P < .01). T2D men increased lumbar spine aBMD (P < .05), total area at 38% tibia (P < .01) and periosteal and endosteal circumferences at the same site (P < .01 for both). T2D men had reduced tibial vBMD (P < .01), but preserved bone mineral content (P = .01). Changes in HbA1c or body composition were similar between the 2 groups.ConclusionTestosterone therapy results in greater improvements in the skeletal health of hypogonadal men with T2D than their nondiabetic counterparts.
| S-EPMC8599870 | biostudies-literature
Project description:Controversies surround the usefulness of identifying patients with the metabolic syndrome (MetS). Many of the components are accepted risk factors for cardiovascular disease (CVD). Although the MetS as defined includes many men with insulin resistance, insulin resistance is not universal. The low total testosterone (TT) and sex hormone binding globulin (SHBG) levels in these men are best explained by the hyperinsulinism and increased inflammatory cytokines that accompany obesity and increased waist circumference. It is informative that low SHBG levels predict future development of the MetS. Evidence is strong relating low TT levels to CVD in men with and without the MetS; however, the relationship may not be causal. The recommendations of the International Diabetes Federation for managing the MetS include cardiovascular risk assessment, lifestyle changes in diet, exercise, weight reduction and treatment of individual components of the MetS. Unfortunately, it is uncommon to see patients with the MetS lose and maintain a 10% weight loss. Recent reports showing testosterone treatment induced dramatic changes in weight, waist circumference, insulin sensitivity, hemoglobin A1c levels and improvements in each of the components of the MetS are intriguing. While some observational studies have reported that testosterone replacement therapy increases cardiovascular events, the Food and Drug Administration in the United States has reviewed these reports and found them to be seriously flawed. Large, randomized, placebo-controlled trials are needed to provide more definitive data regarding the efficacy and safety of this treatment in middle and older men with the MetS and low TT levels.
| S-EPMC4650473 | biostudies-literature