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Effects of lifestyle modification and metformin on irisin and FGF21 among HIV-infected subjects with the metabolic syndrome.

ABSTRACT: Few studies have investigated irisin and FGF21 to elucidate the role of these hormones to regulate 'beiging' in HIV-infected patients.Fifty HIV-infected subjects with the metabolic syndrome were previously recruited and randomized to receive lifestyle modification (LSM) and/or metformin over 12 months. In the current study, we assessed FGF21 and irisin at baseline and after intervention. In addition, we assessed circulating FGF21 and irisin in relationship to brown adipose tissue (BAT) gene expression in dorsocervical subcutaneous fat biopsies from 13 HIV-infected subjects.At baseline, prior to intervention, HIV-infected subjects demonstrated increased log FGF21 (2·13 ± 0·06 vs 1·98 ± 0·05 pg/ml, P = 0·05) and log irisin (0·33 ± 0·02 vs 0·17 ± 0·04 ?g/ml, P = 0·003) compared with healthy controls well matched based on waist circumference. After 12 months, HIV-infected subjects randomized to LSM demonstrated a relative reduction in FGF21 compared with those not randomized to LSM (-10 [-35,22] vs 40 [0,94] %change, P = 0·01). Changes in FGF21 were inversely associated with improved parameters of energy homoeostasis, including increased REE (? = -0·34, P = 0·046) and max VO2 (? = -0·38, P = 0·02), and reduced RQ (? = 0·40, P = 0·02) among all HIV-infected subjects. Increased UCP-1 (r = 0·75, P = 0·003), DIO2 (r = 0·58, P = 0·04) and CideA (r = 0·73, P = 0·01) gene expression in dorsocervical fat was significantly associated with FGF21 in HIV-infected subjects.HIV-infected subjects with metabolic complications demonstrate increases in FGF21 in relationship to BAT gene expression. Relative reductions in FGF21 in those receiving long-term LSM relate to overall improvements in energy expenditure parameters. In contrast, irisin levels are elevated in HIV-infected subjects, but are not influenced by LSM nor associated with BAT gene expression.

SUBMITTER: Srinivasa S

PROVIDER: S-EPMC4475409 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

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Effects of lifestyle modification and metformin on irisin and FGF21 among HIV-infected subjects with the metabolic syndrome.

Srinivasa Suman S Wong Kimberly K Fitch Kathleen V KV Wei Jeffrey J Petrow Eva E Cypess Aaron M AM Torriani Martin M Grinspoon Steven K SK

Clinical endocrinology 20141008 5

<h4>Objective</h4>Few studies have investigated irisin and FGF21 to elucidate the role of these hormones to regulate 'beiging' in HIV-infected patients.<h4>Design</h4>Fifty HIV-infected subjects with the metabolic syndrome were previously recruited and randomized to receive lifestyle modification (LSM) and/or metformin over 12 months. In the current study, we assessed FGF21 and irisin at baseline and after intervention. In addition, we assessed circulating FGF21 and irisin in relationship to bro ...[more]

PMID: 25130061

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Project description:BackgroundTo evaluate the effect of lifestyle modifications on metabolic syndrome (MetS) as assessed by its resolution and improved values for its components.MethodsThis was a systematic review and meta-analysis. Searches were performed of MEDLINE and the Cochrane Database from January 1966 to October 2011 to identify randomized controlled trials (RCTs) related to the study objective. The included studies were RCTs restricted to the English language, with a follow-up period of 6 months or more, which reported overall resolution of MetS or values of MetS components (fasting blood glucose, waist circumference, high-density lipoprotein (HDL), triglycerides, and systolic and diastolic blood pressure (SBP, DBP)). Two investigators independently assessed study eligibility. The effect sizes were the relative proportion of patients with resolved MetS and mean differences in MetS component values from baseline to 1-year follow-up in a lifestyle-modification intervention (LMI) group versus a control (conventional lifestyle education or no treatment) group. Meta-analyses were conducted using a random-effects model.ResultsEleven interventions in eight RCTs were used for the meta-analyses. The relative proportion of patients with resolved MetS in the intervention group was approximately 2.0 (95% CI 1.5 to 2.7) times greater in the intervention group compared with the control group (7 interventions, n = 2.839). LMI (5 interventions, n = 748) significantly reduced mean values for SBP by -6.4 mmHg (95% CI -9.7 to -3.2), DBP by -3.3 mmHg (95% CI -5.2 to -1.4), triglycerides by -12.0 mg/dl (95% CI -22.2 to -1.7), waist circumference by -2.7 cm (95% CI -4.6 to -0.9), and fasting blood glucose by -11.5 mg/dl (95% CI -22.4 to -0.6) (5 interventions), but reductions were not significant for HDL (1.3 mg/dl; 95% CI -0.6 to 3.1).ConclusionsThe LMI was effective in resolving MetS and reducing the severity of related abnormalities (fasting blood glucose, waist circumference, SBP and DBP, and triglycerides) in subjects with MetS.

Project description:BackgroundLifestyle interventions, such as fasting, diet, and exercise, are increasingly used as a treatment option for patients with metabolic syndrome (MS). This study assesses the efficacy and safety of fasting followed by lifestyle modification in patients with MS compared to lifestyle modification only.MethodsSingle-blind, multicenter, parallel, randomized controlled trial in two German tertiary referral hospitals in metropolitan areas.Interventions(a) 5-day fasting followed by 10 weeks of lifestyle modification (modified DASH diet, exercise, mindfulness; n = 73); (b) 10 weeks of lifestyle modification only (n = 72).Main outcomes and measuresCo-primary outcomes were ambulatory systolic blood pressure and the homeostasis model assessment (HOMA) index at week 12. Further outcomes included anthropometric, laboratory parameters, and the PROCAM score at weeks 1, 12, and 24.ResultsA total of 145 patients with metabolic syndrome (62.8% women; 59.7 ± 9.3 years) were included. No significant group differences occurred for the co-primary outcomes at week 12. However, compared to lifestyle modification only, fasting significantly reduced HOMA index (Δ = -0.8; 95% confidence interval [CI] = -1.7, -0.1), diastolic blood pressure (Δ = -4.8; 95% CI = -5.5, -4.1), BMI (Δ = -1.7; 95% CI = -2.0, -1.4), weight (Δ = -1.7; 95% CI = -2.0, -1.4), waist circumference (Δ = -2.6; 95% CI = -5.0, -0.2), glucose (Δ = -10.3; 95% CI = -19.0, -1.6), insulin (Δ = -2.9; 95% CI = -5.3, -0.4), HbA1c (Δ = -0.2; 95% CI = -0.4, -0.05;), triglycerides (Δ = -48.9; 95% CI = -81.0, -16.9), IL-6 (Δ = -1.2; 95% CI = -2.5, -0.005), and the 10-year risk of acute coronary events (Δ = -4.9; 95% CI = -9.5, -0.4) after week 1. Fasting increased uric acid levels (Δ = 1.0; 95% CI = 0.1, 1.9) and slightly reduced eGRF (Δ = -11.9; 95% CI = -21.8, -2.0). Group differences at week 24 were found for weight (Δ = -2, 7; 95% CI = -4.8, -0.5), BMI (Δ = -1.0; 95% CI = -1.8, -0.3), glucose (Δ = -7.7; 95% CI = -13.5, -1.8), HDL (Δ = 5.1; 95% CI = 1.5, 8.8), and CRP (Δ = 0.2; 95% CI = 0.03, 0.4). No serious adverse events occurred.ConclusionsA beneficial effect at week 24 was found on weight; fasting also induced various positive short-term effects in patients with MS. Fasting can thus be considered a treatment for initializing lifestyle modification for this patient group; however, it remains to be investigated whether and how the multilayered effects of fasting can be maintained in the medium and longer term.

Project description:Childhood obesity is a serious health concern affecting over 155 million children in developed countries worldwide. Childhood obesity is associated with significantly increased risk for development of type 2 diabetes, cardiovascular disease and psychosocial functioning problems (i.e., depression and decreased quality of life). The two major strategies for management of obesity and associated metabolic abnormalities are lifestyle modification and pharmacologic therapy. This paper will provide the background rationale and methods of the REACH childhood obesity treatment program.The REACH study is a 2-year multidisciplinary, family-based, childhood obesity treatment program. Seventy-two obese adolescents (aged 10-16 years) and their parents are being recruited to participate in this randomized placebo controlled trial. Participants are randomized to receive either metformin or placebo, and are then randomized to a moderate or a vigorous intensity supervised exercise program for the first 12-weeks. After the 12-week exercise program, participants engage in weekly exercise sessions with an exercise facilitator at a local community center. Participants engage in treatment sessions with a dietitian and social worker monthly for the first year, and then every three months for the second year. The primary outcome measure is change in body mass index and the secondary outcome measures are changes in body composition, risk factors for type 2 diabetes and cardiovascular disease, changes in diet, physical activity, and psychosocial well-being (e.g., quality of life). It is hypothesized that participants who take metformin and engage in vigorous intensity exercise will show the greatest improvements in body mass index. In addition, it is hypothesized that participants who adhere to the REACH program will show improvements in body composition, physical activity, diet, psychosocial functioning and risk factor profiles for type 2 diabetes and cardiovascular disease. These improvements are expected to be maintained over the 2-year program.The findings from this study will advance the knowledge regarding the long-term efficacy and sustainability of interventions for childhood obesity.ClinicalTrials.gov number NCT00934570.

Dataset Information

Effects of lifestyle modification and metformin on irisin and FGF21 among HIV-infected subjects with the metabolic syndrome.

Publications

Effects of lifestyle modification and metformin on irisin and FGF21 among HIV-infected subjects with the metabolic syndrome.

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