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Effects of metformin administration on endocrine-metabolic parameters, visceral adiposity and cardiovascular risk factors in children with obesity and risk markers for metabolic syndrome: A pilot study.

ABSTRACT: BACKGROUND:Metformin treatment (1000-2000 mg/day) over 6 months in pubertal children and/or adolescents with obesity and hyperinsulinism is associated with a reduction in body mass index (BMI) and the insulin resistance index (HOMA-IR). We aimed to ascertain if long-term treatment (24 months) with lower doses of metformin (850 mg/day) normalizes the endocrine-metabolic abnormalities, improves body composition, and reduces the carotid intima-media thickness (cIMT) in pre-puberal and early pubertal children with obesity. METHODS:A pilot double-blind, placebo-controlled trial was conducted on 18 pre-puberal and early pubertal (Tanner stage I-II) children with obesity and risk markers for metabolic syndrome. Patients were randomly assigned (1:1) to receive metformin (850 mg/day) or placebo for 24 months. Clinical, biochemical (insulin, lipids, leptin, and high-sensitivity C-reactive protein [hsCRP]), and imaging (body composition [dual-energy X-ray absorptiometry and magnetic resonance imaging]) parameters as well as cIMT (ultrasonography) were assessed at baseline and at 6, 12, and 24 months. RESULTS:The 12-month treatment tend to cause a reduction in weight standard deviation scores (SDS), BMI-SDS, leptin, leptin-to-high-molecular-weight (HMW) adiponectin ratio, hsCRP, cIMT, fat mass, and liver fat in metformin-treated children compared with placebo. The effect of metformin on the reduction of BMI-SDS, leptin, leptin-to-HMW adiponectin ratio, hsCRP, and liver fat seemed to be maintained after completing the 24 months of treatment. No changes in insulin sensitivity (HOMA-IR) or adverse effects were detected. CONCLUSION:In this pilot study, metformin treatment in pre-puberal and early pubertal children with obesity seemed to improve body composition and inflammation markers. Our data encourage the development of future fully powered trials using 850 mg/day metformin in young children, highlighting its excellent tolerance and potential long-term benefits.

SUBMITTER: Bassols J

PROVIDER: S-EPMC6903728 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Effects of metformin administration on endocrine-metabolic parameters, visceral adiposity and cardiovascular risk factors in children with obesity and risk markers for metabolic syndrome: A pilot study.

Bassols Judit J Martínez-Calcerrada José-María JM Osiniri Inés I Díaz-Roldán Ferran F Xargay-Torrent Silvia S Mas-Parés Berta B Dorado-Ceballos Estefanía E Prats-Puig Anna A Carreras-Badosa Gemma G de Zegher Francis F Ibáñez Lourdes L López-Bermejo Abel A

PloS one 20191210 12

<h4>Background</h4>Metformin treatment (1000-2000 mg/day) over 6 months in pubertal children and/or adolescents with obesity and hyperinsulinism is associated with a reduction in body mass index (BMI) and the insulin resistance index (HOMA-IR). We aimed to ascertain if long-term treatment (24 months) with lower doses of metformin (850 mg/day) normalizes the endocrine-metabolic abnormalities, improves body composition, and reduces the carotid intima-media thickness (cIMT) in pre-puberal and early ...[more]

PMID: 31821361

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Project description:AimsMetabolic syndrome (MS) is a global health problem associated with an increased risk of diabetes mellitus (DM), cardiovascular disease (CVD), and cancer. Body composition parameters, including obesity, visceral adiposity, and sarcopenia contribute to the development of MS and CVD. Previous studies have investigated the association of individual body composition parameters with MS. Studies analyzing the association between multiple body composition parameters and MS have been rare. We aimed to investigate the association between MS and multiple body composition parameters, including obesity, visceral adiposity, and sarcopenia.MethodsA total of 13,620 subjects who underwent voluntary routine checkups at the Health Care Center of our institution between October 2014 and December 2019 were enrolled. Only data from the first examination of subjects who underwent repeated checkups were included. Clinical and laboratory data were collected. Skeletal muscle mass and visceral fat area (VFA) were measured using bioelectrical impedance analysis. Appendicular skeletal muscle mass (ASM) was divided by body weight (in kg) and expressed as a percentage (calculated as, ASM% = ASM × 100/Weight). Data were compared between the groups based on obesity, VFA, and ASM%. Logistic regression analysis was performed to determine the risk of MS in each group.ResultsBody mass index and VFA were significantly higher in subjects with MS than in those without MS. ASM% was significantly lower in subjects with MS than in those without MS. Subjects with obesity, visceral adiposity, or sarcopenia had a higher prevalence of MS than those without. As the number of metabolic components increased from 0 to 5, we identified a decreasing trend of ASM% and an increasing trend of VFA and BMI (P for trend < 0.001 for all). In the paired analyses, all the three body composition parameters showed additive effects in predicting MS. In the logistic regression analysis, the three parameters were associated with an increased risk of MS after adjustment for age, sex, hypertension, DM, dyslipidemia, smoking, alcohol intake, and C-reactive protein.ConclusionsObesity, visceral adiposity, and sarcopenia showed additive effects on MS prediction. Subjects with obesity, visceral adiposity, or sarcopenia were significantly associated with the increased risk of MS after adjustment for multiple confounders. Increasing skeletal muscle and reducing visceral fat may be strategies for the prevention or treatment of MS.

Project description:Smallanthus sonchifolius (yacon), a native plant of South America, was observed to improve lipid profile in rodents and humans. This study aimed to investigate the antiobesity properties of yacon roots in a high-fat-diet (HFD) model and the underlying mechanisms. A total of 30 Wistar male rats were divided into five groups (n=6): the standard chow diet (SD) group was fed a SD; the HFD group was fed a HFD; and the HFD Y340 and HFD Y680 groups were fed a HFD plus yacon flour (340 and 680 mg FOS/kg b. w./day, respectively). HFD Y340 and HFD Y680 rats exhibited marked attenuation of weight gain, a decrease in visceral fat pad weight, a restoration of the serum lipid profile and atherogenic index in a dose-dependent manner, being the higher dose more effective (p < 0.05). In addition, we found that HFD Y680 rats showed lower glucose and insulin levels, improved glucose tolerance, and insulin sensitivity (p < 0.5). A downregulation of several adipocyte specific-transcription factors, including peroxisome proliferator-activated receptor gamma2 (PPAR-γ2), CCAAT/enhancer binding protein a (C/EBP-a) and activating protein (aP2) mRNA levels, was determined in the visceral adipose tissue of HFD Y680 rats (p < 0.05). An improvement of adipokine profile in HFD Y680 rats and decreased serum proinflammatory cytokine levels (p < 0.05) were determined by ELISA. Decreased macrophage infiltration and F4/80 and MCP-1 expression in the visceral adipose tissue of HFD Y680 rats (p < 0.5), together with a higher pAkt/Akt expression (p < 0.05) were also observed by immunofluorescence and immunoblotting. A significant increase in glucagon (Gcg) and PYY mRNA levels in distal ileum of HFD Y680 rats (p < 0.05) were also detected. In the second approach, we determined that yacon supplementation potentiates the effects of the HFD reversion to a standard diet. In conclusion, yacon showed antiobesity properties by inhibiting adipogenesis and improving the visceral adipose tissue function.

Project description:OBJECTIVES:The visceral adiposity index (VAI), an indirect marker of visceral adipose tissue, serves as a model associated with cardiometabolic risk, but has limitations regarding the Asian population. We sought to develop a new VAI (NVAI) for the Korean population and compare it to VAI for prediction of atherosclerotic cardiovascular disease (ASCVD) risk and development of major cardiovascular diseases (CVD) and stroke. METHODS:Patients (969) who underwent visceral fat area measurement were analyzed. After exclusion, 539 patients (142 men, 397 women) were randomly divided into internal (n = 374) and external validation (n = 165) data set. The NVAI was developed using univariate and multivariate logistic regression with backward selection of predictors. Receiver operating characteristic (ROC) curve analysis and comparison of the area under the curve (AUC) verified the better predictor of ASCVD risk score. Additionally, nationwide population-based cross-sectional survey data (Korean National Health and Nutrition Examination Survey [KNHANES] 2008-2010, n = 29,235) was used to validate the NVAI's ability to predict ASCVD risk and major CVD and stroke. RESULTS:The NVAI better reflected visceral fat area in internal and external data sets, with AUCs of 0.911 (95% confidence interval [CI]: 0.882-0.940) and 0.879 (95% CI: 0.828-0.931), respectively. NVAI better discriminated for ASCVD risk (AUC = 0.892, 95% CI: 0.846-0.938) compared to VAI (0.559, 95% CI: 0.439-0.679). The NVAI also better predicted MI or angina, and stroke with AUCs of 0.771 (95% CI: 0.752-0.789), and 0.812 (95% CI: 0.794-0.830), respectively, compared with waist circumference (WC), body mass index (BMI), TG to HDL ratio, and VAI via KNHANES, in a statistically significant manner. CONCLUSIONS:The NVAI has advantages as a predictor of visceral obesity and is significantly associated with ASCVD risks and development of major CVD and stroke in the Korean population. The NVAI could be a screening tool for improved risk estimation related to visceral obesity.

Project description:ObjectivesThis study sought to evaluate differential effects of visceral fat (VF) and subcutaneous fat and their effects on metabolic syndrome (MetS) risk across body mass index (BMI) categories.BackgroundThe regional distribution of adipose tissue is an emerging risk factor for cardiometabolic disease, although serial changes in fat distribution have not been extensively investigated. VF and its alterations over time may be a better marker for risk than BMI in normal weight and overweight or obese individuals.MethodsWe studied 1,511 individuals in the MESA (Multi-Ethnic Study of Atherosclerosis) with adiposity assessment by computed tomography (CT). A total of 253 participants without MetS at initial scan underwent repeat CT (median interval 3.3 years). We used discrete Cox regression with net reclassification to investigate whether baseline and changes in VF area are associated with MetS.ResultsHigher VF was associated with cardiometabolic risk and coronary artery calcification, regardless of BMI. After adjustment, VF was more strongly associated with incident MetS than subcutaneous fat regardless of weight, with a 28% greater MetS hazard per 100 cm(2)/m VF area and significant net reclassification (net reclassification index: 0.44, 95% confidence interval [CI]: 0.29 to 0.60) over clinical risk. In individuals with serial imaging, initial VF (hazard ratio: 1.24 per 100 cm(2)/m, 95% CI: 1.08 to 1.44 per 100 cm(2)/m, p = 0.003) and change in VF (hazard ratio: 1.05 per 5% change, 95% CI: 1.01 to 1.08 per 5% change, p = 0.02) were associated with MetS after adjustment. Changes in subcutaneous fat were not associated with incident MetS after adjustment for clinical risk and VF area.ConclusionsVF is modestly associated with BMI. However, across BMI, a single measure of and longitudinal change in VF predict MetS, even accounting for weight changes. Visceral adiposity is essential to assessing cardiometabolic risk, regardless of age, race, or BMI, and may serve as a marker and target of therapy in cardiometabolic disease.

Project description:BackgroundExcess visceral adiposity induces chronic subclinical inflammation resulting in the metabolic syndrome. Whether excess visceral adiposity impacts posttraumatic inflammatory profiles more is unknown. We hypothesized that obese patients (body mass index >30 kg/m) with higher visceral to subcutaneous adipose tissue distribution would have increased inflammatory outcomes.MethodsA secondary analysis of a prospective cohort of adult trauma patients requiring >48 hours of intensive care unit care over a 55-month period was analyzed. Body fat distribution was determined by radiologist review of computed tomography scans at L1. Concentric freeform regions were defined manually, and area was calculated. Visceral adiposity was defined as subcutaneous fat area: visceral area >1.35 (the median), whereas subcutaneous adiposity was defined as a ratio <1.35. Primary outcomes were proinflammatory biomarkers known to be associated with chronic visceral obesity (white blood cell count, interleukin 1, 2, 4, 6, 8, 10, and tumor necrosis factor alpha). Secondary outcomes were all-cause in-hospital mortality, adult respiratory distress syndrome, and nosocomial infections.ResultsTwo hundred eighty-one (19%) obese patients with available computed tomography scans from 1,510 trauma patients were included. Visceral adiposity included 140 patients, subcutaneous adiposity included 141 patients. The two groups were similar in regards to age, Trauma Injury Severity Score, and Acute Physiology and Chronic Health Evaluation II score. There was no difference (p > 0.05) in proinflammatory biomarkers. Patients with visceral adiposity had similar clinical outcomes including mortality (p = 0.56), adult respiratory distress syndrome (p = 0.69), and infection (0.43).ConclusionsVisceral body fat distribution in obese patients is not associated with increased inflammatory profiles or clinical outcomes after trauma. The impact of injury severity on acute inflammation likely overwhelms the metabolic disturbances and subclinical inflammation associated with visceral obesity in the chronic setting.

Project description:BackgroundVisceral adiposity is an important risk factor for cardiometabolic diseases.ObjectiveTo determine whether the Metabolic Score for Visceral Fat (METS-VF) is more effective than other adiposity indices in predicting visceral fat area (VFA).MethodsIn this single-center and cross-sectional study, we included patients aged 20-50 years, without diabetes and coronary artery disease, who underwent computed tomography (CT) including the third lumbar vertebra. Age, blood pressure, waist circumference (WC), hip circumference, fasting lipids, and glucose were assessed. VFA was measured by cross-sectional examination of CT. The correlation of WC, body mass index (BMI), waist-hip ratio (WHR), lipid accumulation product (LAP), visceral adiposity index (VAI), a body shape index (ABSI), body roundness index (BRI), and METS-VF with VFA was analyzed by correlation analysis. The cut-off values and area under the curve (AUC) for identifying increased VFA (>130 cm2) were determined.ResultsWe included 185 individuals with mean age 38.2 ± 8 and female predominance (58.4%). There was a significant positive correlation between all indices and VFA (p<0.001). ROC analysis revealed that METS-VF and WC demonstrated the highest predictive value for identifying increased VFA. In both men (p=0.001) and women (p<0.001), METS-VF (AUC 0.922 and 0.939, respectively) showed a significant superiority over ABSI (AUC 0.702 and 0.658, respectively), and VAI (AUC 0.731 and 0.725, respectively). Additionally, in women, its superiority over WHR (AUC 0.807) was also statistically significant (p=0.003). We identified a METS-VF cut-off point >6.4 in males >6.5 in females and WC cut-off point >88 cm in males (AUC 0.922), >90.5 cm in females (AUC 0.938).ConclusionMETS-VF is strongly associated with visceral adiposity and better to predict increased VFA. However, its superiority over WC, BMI, BRI, and LAP was not significant. The results emphasize that WC is more appealing as screening indicator for visceral adiposity considering its easy use.Clinical trial registry nameClinicaltrials.gov (http://www.clinicaltrials.gov).Clinical trial registry urlhttps://clinicaltrials.gov/ct2/show/NCT05648409.Clinical trial registry numberNCT05648409.

Dataset Information

Effects of metformin administration on endocrine-metabolic parameters, visceral adiposity and cardiovascular risk factors in children with obesity and risk markers for metabolic syndrome: A pilot study.

Publications

Effects of metformin administration on endocrine-metabolic parameters, visceral adiposity and cardiovascular risk factors in children with obesity and risk markers for metabolic syndrome: A pilot study.

Similar Datasets

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