The Effect of Weight-Loss Interventions on Cervical and Chin Subcutaneous Fat Depots; the CENTRAL Randomized Controlled Trial

Accumulation of cervical and chin subcutaneous adipose tissues (SAT) represent known phenotypes of obesity. We aimed to evaluate the sensitivity of these fat storages to long-term weight-loss directed lifestyle-intervention and to assess their relations to bodily-adiposity, insulin-resistance, and cardiometabolic risk; We randomly assigned 278 participants with abdominal-obesity/dyslipidemia to low-fat or Mediterranean/low-carbohydrate diets +/− physical-activity. All participants underwent an 18 month whole-body magnetic resonance imaging follow-up, from which we assessed cervical and chin SAT-areas; Participants (age = 48 years; 90% men; body-mass-index = 30.9 kg/m2) had an 18-month adherence-rate of 86%. Cervical-SAT and chin-SAT decreased after 6-months (−13.1% and −5.3%, respectively, p < 0.001). After 18-months only cervical-SAT remained decreased compared to baseline (−5%, p < 0.001). Cervical and chin-SAT 18-month changes were associated with changes in weight (r = 0.70, r = 0.66 respectively; <0.001 for both) and visceral-adipose-tissue (VAT; r = 0.35, r = 0.42 respectively; <0.001 for both). After adjustment to VAT, waist-circumference, or weight-changes, chin-SAT 18-month reduction was associated with favorable changes in fasting-glucose (β = 0.10; p = 0.05), HbA1c (β = 0.12; p = 0.03), and homeostasis-model-assessment-of-insulin-resistance (β = 0.12; p = 0.03). Cervical-SAT 18-month reduction was associated with decreased triglycerides (β = 0.16; p = 0.02) and leptin (β = 0.19; p = 0.01) independent of VAT; Cervical and chin-SATs are dynamic fat depots that correspond with weight-loss and are associated with changes in cardiometabolic profile. In long-term, chin-SAT displays a larger rebound compared with cervical-SAT. Chin-SAT accumulation is associated with in insulin-resistance, independent of central obesity. (ClinicalTrials identifier NCT01530724)

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Abstract 14300: The Relationship Between the American Heart Association’s Life Simple 7, Ectopic Fat and Insulin Resistance Among South Asians: The Mediators of Atherosclerosis in South Asians Living in America (MASALA) Study

Circulation ◽

10.1161/circ.142.suppl_3.14300 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Parag A Chevli ◽

Morgana Mongraw-chaffin ◽

Anurag Mehta ◽

Muhammad Imtiaz Ahmad ◽

Alka M Kanaya ◽

...

Keyword(s):

Insulin Resistance ◽

Cell Function ◽

South Asians ◽

Subcutaneous Fat ◽

Ectopic Fat ◽

Model Assessment ◽

Inverse Association ◽

Β Cell ◽

Fat Depots ◽

Intermuscular Fat

Introduction: The inverse association between ideal cardiovascular health (CVH) as measured by AHA’s Life simple 7, and cardiovascular disease (CVD) incidence is well documented. However, research exploring the association between CVH and surrogate markers of cardiometabolic disease, including ectopic fat depots, insulin resistance, and β-cell dysfunction is sparse. Methods: Among 906 South Asian participants (mean age 55 y, SD=9.4, 46% women) in the Mediators of Atherosclerosis in South Asians Living in America (MASALA) cohort, we assigned each LS7 component a score of 0, 1, and 2, and summed these scores to derive an overall CVH score. Visceral, subcutaneous, pericardial, and intermuscular fat and hepatic fat attenuation were measured using computed tomography. We used a homeostasis model assessment for insulin resistance (HOMA-IR) for insulin resistance and HOMA-β for β-cell function. We used multiple linear regression to model the associations between CVH score and natural log-transformed ectopic fat measures, HOMA-IR, and HOMA-β. Results: In adjusted analysis, compared to those with ideal CVH, participants with poor CVH demonstrated 53.9% (95% CI, 39.7 - 69.4) higher visceral fat area, 66.5% (50.5 - 84.2) higher pericardial fat volume, and 35.1% (23.0 - 48.4) higher subcutaneous fat area, but only 8% (3.1 - 13.0) higher intermuscular fat area and 15.9% (11.2 - 20.4) higher intrahepatic fat (all p<0.001). Also, poor CVH was associated with 154% (117.5 - 198) higher HOMA-IR. Similarly, participants with intermediate CVH demonstrated significantly larger measures of ectopic fat and HOMA-IR. There was no significant association between CVH and HOMA-β. Conclusion: We found that poor and intermediate CVH, as defined by LS7 metrics, was associated with significantly higher measures of ectopic fat and insulin resistance among South Asians. Long-term follow-up of the MASALA cohort will examine the association of LS7 metrics with the incident CVD events.

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Body Composition Changes with Long-term Pegvisomant Therapy of Acromegaly

Journal of the Endocrine Society ◽

10.1210/jendso/bvab004 ◽

2021 ◽

Vol 5 (3) ◽

Author(s):

Adriana P Kuker ◽

Wei Shen ◽

Zhezhen Jin ◽

Simran Singh ◽

Jun Chen ◽

...

Keyword(s):

Insulin Resistance ◽

Body Composition ◽

Magnetic Resonance ◽

Whole Body ◽

Resonance Spectroscopy ◽

Model Assessment ◽

Long Term Effects ◽

Body Composition Change ◽

Active Acromegaly

Abstract Context In active acromegaly, the lipolytic and insulin antagonistic effects of growth hormone (GH) excess alter adipose tissue (AT) deposition, reduce body fat, and increase insulin resistance. This pattern reverses with surgical therapy. Pegvisomant treats acromegaly by blocking GH receptor (GHR) signal transduction and lowering insulin-like growth factor 1 (IGF-1) levels. The long-term effects of GHR antagonist treatment of acromegaly on body composition have not been studied. Methods We prospectively studied 21 patients with active acromegaly who were starting pegvisomant. Body composition was examined by whole body magnetic resonance imaging, proton magnetic resonance spectroscopy of liver and muscle and dual-energy x-ray absorptiometry, and endocrine and metabolic markers were measured before and serially during 1.0 to 13.4 years of pegvisomant therapy. The data of patients with acromegaly were compared with predicted and to matched controls. Results Mass of visceral AT (VAT) increased to a peak of 187% (1.56-229%) (P < .001) and subcutaneous AT (SAT) to 109% (–17% to 57%) (P = .04) of baseline. These remained persistently and stably increased, but did not differ from predicted during long-term pegvisomant therapy. Intrahepatic lipid rose from 1.75% to 3.04 % (P = .04). Although lean tissue mass decreased significantly, skeletal muscle (SM) did not change. IGF-1 levels normalized, and homeostasis model assessment insulin resistance and HbA1C were lowered. Conclusion Long-term pegvisomant therapy is accompanied by increases in VAT and SAT mass that do not differ from predicted, stable SM mass and improvements in glucose metabolism. Long-term pegvisomant therapy does not produce a GH deficiency-like pattern of body composition change.

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The Weight Loss Effects of Branched Chain Amino Acids and Vitamin B6: A Randomized Controlled Trial on Obese and Overweight Women

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000511 ◽

2018 ◽

Vol 88 (1-2) ◽

pp. 80-89 ◽

Cited By ~ 3

Author(s):

Zahra Shakibay Novin ◽

Saeed Ghavamzadeh ◽

Alireza Mehdizadeh

Keyword(s):

Amino Acids ◽

Weight Loss ◽

Body Composition ◽

Vitamin B6 ◽

Controlled Trial ◽

Density Lipoprotein ◽

Branched Chain Amino Acids ◽

Model Assessment ◽

Waist To Hip Ratio ◽

Branched Chain

Abstract. Branched chain amino acids (BCAA), with vitamin B6 have been reported to improve fat metabolism and muscle synthesis. We hypothesized that supplementation with BCAA and vitamin B6 would result in more weight loss and improve body composition and blood markers related to cardiovascular diseases. Our aim was to determine whether the mentioned supplementation would affect weight loss, body composition, and cardiovascular risk factors during weight loss intervention. To this end, we performed a placebo-controlled randomized clinical trial in 42 overweight and obese women (BMI = 25–34.9 kg/m2). Taking a four-week moderate deficit calorie diet (–500 kcal/day), participants were randomized to receive BCAA (6 g/day) with vitamin B6 (40 mg/day) or placebo. Body composition variables measured with the use of bioelectrical impedance analysis, homeostatic model assessment, and plasma insulin, Low density lipoprotein, High density lipoprotein, Total Cholesterol, Triglyceride, and fasting blood sugar were measured. The result indicated that, weight loss was not significantly affected by BCAA and vitamin B6 supplementation (–2.43 ± 1.02 kg) or placebo (–1.64 ± 1.48 kg). However, significant time × treatment interactions in waist to hip ratio (P = 0.005), left leg lean (P = 0.004) and right leg lean (P = 0.023) were observed. Overall, supplementation with BCAA and vitamin B6 could preserve legs lean and also attenuated waist to hip ratio.

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Effectiveness of a Weight-Loss Intervention in Preventing Frailty and Functional Decline in Community-Dwelling Obese Older People. A Randomized Controlled Trial

Journal of Frailty & Aging ◽

10.14283/jfa.2021.38 ◽

2021 ◽

pp. 1-9

Author(s):

M. Serra-Prat ◽

M. Terradellas ◽

I. Lorenzo ◽

M. Arús ◽

E. Burdoy ◽

...

Keyword(s):

Insulin Resistance ◽

Weight Loss ◽

Functional Performance ◽

Controlled Trial ◽

Functional Decline ◽

Community Dwelling ◽

Weight Loss Intervention ◽

Randomized Controlled ◽

Study Intervention

Background: Obesity is a risk factor for frailty and muscle weakness, so weight loss in obese older adults may prevent frailty and functional decline. Objective: To assess the safety and efficacy of a multimodal weight-loss intervention in improving functional performance and reducing frailty risk in obese older adults. Design: Randomized controlled trial with 2 parallel arms. Setting and participants: Community-dwelling obese adults aged 65-75 years with body mass index (BMI) 30-39 kg/m2. Intervention: 6-month multimodal intervention based on diet and a physical activity program. Control group: Usual care. Main and secondary outcome measures: Frailty (Fried criteria) rate and functional performance at 6, 12, and 24 months of follow-up, respectively. Intermediate outcome measures: Weight loss, body composition changes, and metabolic and inflammatory biomarker changes. Results: N=305. The study intervention increased gait speed at 12 and 24 months of follow-up, but had no significant effect on frailty prevention. It was effective in reducing weight, BMI, fat mass, interleukin 6, and insulin resistance and improving self-reported quality of life. Conclusions: The study intervention was not demonstrated to be effective in preventing frailty in obese people aged 65-75 years at 24 months of follow-up. However, it allowed weight loss and a reduction in inflammatory and insulin resistance markers, which could have a long-term effect on frailty that requires further research.

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Hyperglycemia in the Posttransplant Period: NODAT vs Posttransplant Diabetes Mellitus

Journal of the Endocrine Society ◽

10.1210/js.2018-00227 ◽

2018 ◽

Vol 2 (11) ◽

pp. 1314-1319 ◽

Cited By ~ 2

Author(s):

Suruchi Gupta ◽

Teresa Pollack ◽

Candice Fulkerson ◽

Kathleen Schmidt ◽

Diana Johnson Oakes ◽

...

Keyword(s):

Insulin Resistance ◽

Liver Transplant ◽

Controlled Trial ◽

Organ Transplant ◽

Long Term Outcomes ◽

Term Outcome ◽

Long Term Outcome ◽

Persistent Hyperglycemia

Abstract Objective To characterize the types of hyperglycemia that occur up to 1 year following liver transplant and to clarify the nomenclature for posttransplant hyperglycemia. Design We analyzed 1-year glycemic follow-up data in 164 patients who underwent liver transplant and who had been enrolled in a randomized controlled trial comparing moderate to intensive insulin therapy to determine if patients had preexisting known diabetes, transient hyperglycemia, persistent hyperglycemia, or new-onset diabetes after transplantation (NODAT). Results Of 119 patients with posttransplant hyperglycemia following hospital discharge, 49 had preexisting diabetes, 5 had insufficient data for analysis, 48 had transient hyperglycemia (16 resolved within 30 days and 32 resolved between 30 days and 1 year), 13 remained persistently hyperglycemic out to 1 year and most likely had preexisting diabetes that had not been diagnosed or insulin resistance/insulinopenia prior to transplant, and 4 had NODAT (i.e., patients with transient hyperglycemia after transplant that resolved but then later truly developed sustained hyperglycemia, meeting criteria for diabetes). Conclusions Distinct categories of patients with hyperglycemia following organ transplant include known preexisting diabetes, persistent hyperglycemia (most likely unknown preexisting diabetes or insulin resistance/insulinopenia), transient hyperglycemia, and NODAT. Those with preexisting diabetes for many years prior to transplant may well have very different long-term outcomes compared with those with true NODAT. Therefore, it would be prudent to classify patients more carefully. Long-term outcome studies are needed to determine if patients with true NODAT have the same poor prognosis as patients with preexisting diabetes (diagnosed and undiagnosed) undergoing transplant.

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Proposed trial: safety and efficacy of resveratrol for the treatment of non-alcoholic fatty liver disease (NAFLD) and associated insulin resistance in adolescents who are overweight or obese adolescents — rationale and protocol

Biochemistry and Cell Biology ◽

10.1139/bcb-2014-0136 ◽

2015 ◽

Vol 93 (5) ◽

pp. 522-530 ◽

Cited By ~ 10

Author(s):

Brandy Wicklow ◽

Kristy Wittmeier ◽

Geert W. t’ Jong ◽

Jonathon McGavock ◽

Marni Robert ◽

...

Keyword(s):

Insulin Resistance ◽

Fatty Liver ◽

Outcome Measures ◽

Side Effect ◽

Controlled Trial ◽

Whole Body ◽

Secondary Outcome ◽

Side Effect Profile ◽

Obese Adolescent ◽

Alcoholic Fatty Liver

Non-alcoholic fatty liver (NAFL) disease (NAFLD) affects 30% of overweight adolescents and increases the risk of type 2 diabetes mellitus (T2D). Resveratrol is a naturally occurring compound with potential to reverse NAFL and its associated insulin resistance in adults. The use of resveratrol to reduce risk for T2D through its effect on NAFL has not been examined to date in youth. This paper provides a literature review and protocol for a 30 day proof of principle trial of resveratrol in a population of adolescents at risk for T2D. This randomized double-blind controlled trial is designed with the primary objective of evaluating a twice daily supplementation of 75 mg of resveratrol for safety and tolerability in overweight and obese adolescent subjects (13 to <18 years of age) with NAFL. Secondary objectives are to determine the effect size of the intervention on hepatic steatosis and whole body insulin sensitivity. Adolescents in the intervention arm (n = 10) will receive oral supplementation of resveratrol 75 mg twice daily (with breakfast and dinner) for a total daily dose of 150 mg for the duration of 30 days. The comparison group (n = 10) will receive a placebo twice daily for 30 days. Both cases and controls will receive a standardized lifestyle intervention program. Subjects in both groups will be followed for an additional 30 days post intervention for total study duration of approximately 60 days. Primary outcome measures include a primary side effect profile determined by participant interview, a side effect profile determined by serum biochemistry and vital signs. Secondary outcome measures include an oral glucose tolerance test, liver and cardiac fat content measured by magnetic resonance spectroscopy, anthropometric measures of overweight/obesity, inflammatory markers, and cardiac function and morphology measured with ultrasonography. Additional outcome measures include serum concentrations of resveratrol, compliance to protocol, physical activity, and nutritional assessment. This study will determine the safety and tolerability of resveratrol in an overweight adolescent population and inform the design of a larger randomized controlled trial.

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Effects of self-conditioning techniques in promoting weight loss in patients with severe obesity: a randomized controlled trial protocol

International Journal of Clinical Trials ◽

10.18203/2349-3259.ijct20170304 ◽

2017 ◽

Vol 4 (1) ◽

pp. 20 ◽

Cited By ~ 1

Author(s):

Simona Bo ◽

Farnaz Rahimi ◽

Bice Properzi ◽

Giuseppe Regaldo ◽

Ilaria Goitre ◽

...

Keyword(s):

Weight Loss ◽

Standard Care ◽

Traditional Approach ◽

Controlled Trial ◽

Well Being ◽

Control Group ◽

Randomized Controlled ◽

Rapid Induction ◽

Conditioning Approach

Background: Obesity is a worldwide epidemic; most obese individuals who lose weight after lifestyle educative treatments, soon regain it. Our aim is to evaluate the effectiveness of a training to teach self-conditioning technique (self-hypnosis) added to standard care in determining weight loss compared with standard care in patients with obesityMethods: This randomized controlled open trial will recruit 120 obese patients (BMI 35-50 Kg/m2), aged 20-70 years. The control group will receive a traditional approach: diet + exercise + behavioral recommendations. The experimental group will receive self-conditioning techniques + traditional approach.Three individual sessions of hypnosis with rapid-induction techniques will be administered by trained personnel. All the participants of both groups will be assessed at three, six, nine and twelve months after randomization. The primary outcome is weight loss difference between groups at 12 months after randomization; secondary outcomes are changes in adherence to dietetic and exercise recommendations, appetite and satisfaction/well-being, waist circumference and body fat, blood pressure and blood metabolic and inflammatory variables.Conclusions: The results of this trial will assess whether a self-conditioning approach, based on self-hypnosis, is able to help participants to modulate unhealthy patterns of eating and sustain weight loss in the long term.

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Clinical outcome of metformin treatment in patients of acanthosis nigricans with insulin resistance

IMC Journal of Medical Science ◽

10.3329/imcjms.v10i1.31101 ◽

2017 ◽

Vol 10 (1) ◽

pp. 18-23

Author(s):

Tahmina Akter ◽

Md. Reza Bin Zaid ◽

Zeenat Farzana Rahman ◽

M. Abu Sayeed

Keyword(s):

Insulin Resistance ◽

Acanthosis Nigricans ◽

Controlled Trial ◽

Treatment Modalities ◽

Therapeutic Effects ◽

Model Assessment ◽

Metformin Therapy ◽

Insulin Resistant ◽

Homeostatic Model Assessment ◽

Anatomic Locations

Background: Acanthosis nigricans (AN) is known to be associated with obesity, insulin resistance (IR) and other systemic morbid conditions. Proper treatment modalities of AN has not been established yet. Metformin may have some therapeutic effects on AN by reducing IR. Objective of the study was to examine the effect of metformin on AN in insulin resistant cases.Methodology and Results: This prospective, controlled trial was conducted in Dermatology OPD of BIRDEM General Hospital, Dhaka from September 2012 to August 2013. All the participants of the study had clinical presentation of AN on different anatomic locations such as neck, axilla, elbow, knuckle and knee and biochemical evidence of IR. Participants were of either sex with age ranging from 18 to 80 years. Any case who had contraindications to metformin therapy were excluded. Severity of AN was examined and assessed by a quantitative scale for measuring acanthosis nigricans. After detecting IR by Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), cases and controls were selected by random sampling method. Randomization was done for metformin in ratio of 2:1. Every third patient was a control. Forty study participants were assigned to receive tablet metformin 500mg thrice daily after meal for three months and twenty control participants were continued on their existing therapy. To maintain a static metabolic status, patients were allowed to remain with their previous diet and lifestyle habit. After 3 months of metformin therapy, improvement was assessed and was compared with control group.Mean age of the participants in case of male: 19.75±2.36 and in case of female: 26.58±9.38, M:F= 1:14, BMI of male: 32.15±4.15 and female: 33.18± 8.05. Mean baseline neck severity score of AN: 3.57 ± 0.78 and after metformin therapy: 2.65 ± 1.02, t-test value: 4.53. Baseline neck texture score of AN: 1.87±0.80, after metformin therapy: 1.25 ± 0.86, ttest value: 3.30. Baseline AN on axilla: 3.05 ± 0.94, after metformin therapy: 2.10 ± 0.98, ttest value: 4.56. Significant improvement of AN was observed clinically on neck and axilla (P<0.005) when compared with control. However, in case of AN on knuckle, elbow and knee, improvement rates were not statistically significant. No side-effect except nausea in 4 patients was reported during study period.Conclusion: Metformin therapy for AN with IR had a significant beneficial effect clinically and was safe and well-tolerated. The effect was more pronounced in neck and axilla.IMC J Med Sci 2016; 10(1): 18-23

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Mangosteen Shows a Potent Insulin Sensitizing Effect in Obese Female Patients: A Prospective Randomized Controlled Pilot Study

10.20944/preprints201804.0049.v1 ◽

2018 ◽

Author(s):

Mikiko Watanabe ◽

Elena Gangitano ◽

Davide Francomano ◽

Eliana Addessi ◽

Raffaella Toscano ◽

...

Keyword(s):

Insulin Resistance ◽

Weight Loss ◽

Pilot Study ◽

Behavioral Therapy ◽

Antioxidant Properties ◽

Model Assessment ◽

Female Patients ◽

Inflammatory Status ◽

Obese Female ◽

Treatment Of Obesity

Insulin resistance is the most important underlying cause of obesity and type 2 Diabetes (T2DM), and insulin sensitizing treatments have proved effective in preventing diabetes and inducing weight loss. Obesity and T2DM are also associated with increased inflammation. Mangosteen is a tropical tree, whose fruits, widely known for their antioxidant properties, have been recently suggested having a possible further role in the treatment of obesity and T2DM. The objective of this pilot study has been to evaluate safety, compliance and efficacy of mangosteen on insulin resistance, weight management, and inflammatory status in obese female patients with insulin resistance. 22 patients were randomized 1:1 to behavioral therapy alone or behavioral therapy and mangosteen and 20 completed the 26-week study. The mangosteen group reported a significant improvement in insulin sensitivity (HOmeostatic Model Assessment-Insulin Resistance, HOMA-IR -53.22% vs -15.23%, p=.0037), and a trend decrease in inflammation markers serum levels, together with trend greater weight loss and trend increased HDL levels. No side effect attributable to treatment was reported. Given the positive preliminary results we report and the excellent safety profile, we suggest a possible role of mangosteen in the treatment of obesity, insulin resistance and inflammation.

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Serum and urinary concentrations of calprotectin as markers of insulin resistance and type 2 diabetes

Acta Endocrinologica ◽

10.1530/eje-12-0374 ◽

2012 ◽

Vol 167 (4) ◽

pp. 569-578 ◽

Cited By ~ 34

Author(s):

Francisco J Ortega ◽

Mónica Sabater ◽

José M Moreno-Navarrete ◽

Neus Pueyo ◽

Patricia Botas ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Weight Loss ◽

Lipid Metabolism ◽

Inflammatory Markers ◽

Low Grade ◽

Model Assessment ◽

Glucose And Lipid Metabolism ◽

Obese Subjects

ObjectiveIncreased circulating calprotectin has been reported in obese subjects but not in association with measures of insulin resistance and type 2 diabetes (T2D). The main aim of this study was to determine whether calprotectins in plasma and urine are associated with insulin resistance.DesignWe performed both cross-sectional and longitudinal (diet-induced weight loss) studies.MethodsCirculating calprotectin concentrations (ELISA), other inflammatory markers, homeostasis model assessment of insulin resistance (HOMA-IR), and parameters of glucose and lipid metabolism were evaluated in 298 subjects (185 with normal (NGT) and 62 with impaired (IGT) glucose tolerance and 51 T2D subjects). Calprotectin was also evaluated in urine samples from 71 participants (50 NGT and 21 subjects with IGT). Insulin sensitivity (SI, Minimal Model) was determined in a subset of 156 subjects, and the effects of weight loss were investigated in an independent cohort of obese subjects (n=19).ResultsCirculating calprotectin was significantly increased in IGT–T2D (independently of BMI) and positively associated with HOMA-IR, obesity measures, inflammatory markers, and parameters of glucose and lipid metabolism. Similar findings were reported for calprotectin concentrations in urine. In the subset of subjects, the association of calprotectin withSIwas independent of BMI and age. In fact,SItogether with C-reactive protein contributed to 27.4% of calprotectin variance after controlling for age and blood neutrophils count. Otherwise, weight loss led to decreased circulating calprotectin in parallel to fasting glucose and HOMA-IR.ConclusionThese findings suggest that circulating and urinary concentrations of calprotectin are linked to chronic low-grade inflammation and insulin resistance beyond obesity.

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