Weight Loss - Obesity

[Michael Scally MD]

Moyer VA, Force obotUSPST. Behavioral Counseling Interventions to Promote a Healthful Diet and Physical Activity for Cardiovascular Disease Prevention in Adults: U.S. Preventive Services Task Force Recommendation Statement. Annals of Internal Medicine. Annals of Internal Medicine | Behavioral Counseling Interventions to Promote a Healthful Diet and Physical Activity for Cardiovascular Disease Prevention in Adults: U.S. Preventive Services Task Force Recommendation Statement

Description: Update of the 2003 and 2002 U.S. Preventive Services Task Force (USPSTF) recommendation statements on behavioral counseling to promote a healthful diet and physical activity in adults without preexisting cardiovascular disease or its risk factors.

Methods: The USPSTF reviewed new evidence on whether counseling interventions relevant to primary care for physical activity or a healthful diet modify self-reported behaviors; intermediate physiologic outcomes (for example, reduced lipid levels, blood pressure, weight, and body mass index and increased glucose tolerance); and cardiovascular morbidity and mortality in adults without known cardiovascular disease, hypertension, hyperlipidemia, or diabetes.

Population: General adult population without a known diagnosis of hypertension, diabetes, hyperlipidemia, or cardiovascular disease (CVD).Recommendation: Although the correlation among healthful diet, physical activity, and the incidence of CVD is strong, existing evidence indicates that the health benefit of initiating behavioral counseling in the primary care setting to promote a healthful diet and physical activity is small. Clinicians may choose to selectively counsel patients rather than incorporate counseling into the care of all adults in the general population.

Considerations: Issues to consider include other risk factors for CVD, a patient's readiness for change, social support and community resources that support behavioral change, and other health care and preventive service priorities.

Potential Harms: Harms may include the lost opportunity to provide other services that have a greater health effect.

Grade: This is a grade C recommendation.


Also, see: http://www.uspreventiveservicestaskforce.org/uspstf11/obeseadult/obesesum.pdf

http://www.uspreventiveservicestaskforce.org/uspstf11/obeseadult/obeseart.htm

 

[Michael Scally MD]

Botella-Carretero JI, Balsa JA, Gomez-Martin JM, et al. Circulating free testosterone in obese men after bariatric surgery increases in parallel with insulin sensitivity. J Endocrinol Invest. Journal of Endocrinological Investigation

Background and Aim: Male hypogonadism has been linked to obesity and diabetes. We aimed to study the association of changes in insulin sensitivity and testosterone levels in severe obese patients submitted to bariatric surgery. Subjects and Methods: Prospective intervention study with twenty consecutive patients who underwent bariatric surgery studied before and after significant weight loss. Serum testosterone, sex hormone binding globulin, fasting glucose and insulin were measured among others. Free testosterone was calculated with the Vermeulen formulae and insulin sensitivity by the homeostatic model assessment.

Results: At baseline, thirteen patients had low total testosterone levels, whereas eight of these patients also had free testosterone levels below the reference range obtained from the control group. After bariatric surgery total testosterone, SHBG and free testosterone significantly increased and achieved normal values in all evaluated patients. Insulin sensitivity improved in all of them. Multivariate linear regression showed that changes in fasting glucose (beta = -1.868, P = 0.001), insulin (beta = -3.782, P = 0.001), weight (beta = -0.622, P = 0.002), and SHBG (beta = - 0.635, P = 0.022) were associated with changes in free testosterone (adjusted R2 = 0.936, F = 26.613, P = 0.001). When insulin resistance calculated by HOMA was in the model instead of insulin and glucose, it also was associated (beta = -3.488, P = 0.008) with free testosterone (adjusted R2 = 0.821, F = 11.111, P = 0.005).

Conclusion: Circulating testosterone in obese men increases after bariatric surgery in parallel with an improvement in insulin sensitivity.

 

[Michael Scally MD]

Arena Pharma: Weight-Loss Drug Approved!
Arena Pharma: Weight-Loss Drug Approved! - TheStreet

SAN DIEGO (TheStreet) -- U.S. regulators approved Arena Pharmaceuticals'(ARNA_) weight-loss drug Belviq on Wednesday -- the first new prescription diet pill cleared for sale in the U.S. in 13 years.

 

[Michael Scally MD]

Ebbeling CB, et al. Effects of Dietary Composition on Energy Expenditure During Weight-Loss Maintenance. JAMA: The Journal of the American Medical Association 2012;307(24):2627-34. JAMA Network | JAMA: The Journal of the American Medical Association | Effects of Dietary Composition on Energy Expenditure During Weight-Loss MaintenanceDietary Composition During Weight-Loss Maintenance

Context Reduced energy expenditure following weight loss is thought to contribute to weight gain. However, the effect of dietary composition on energy expenditure during weight-loss maintenance has not been studied.

Objective To examine the effects of 3 diets differing widely in macronutrient composition and glycemic load on energy expenditure following weight loss.

Design, Setting, and Participants A controlled 3-way crossover design involving 21 overweight and obese young adults conducted at Children's Hospital Boston and Brigham and Women's Hospital, Boston, Massachusetts, between June 16, 2006, and June 21, 2010, with recruitment by newspaper advertisements and postings.

Intervention After achieving 10% to 15% weight loss while consuming a run-in diet, participants consumed an isocaloric low-fat diet (60% of energy from carbohydrate, 20% from fat, 20% from protein; high glycemic load), low–glycemic index diet (40% from carbohydrate, 40% from fat, and 20% from protein; moderate glycemic load), and very low-carbohydrate diet (10% from carbohydrate, 60% from fat, and 30% from protein; low glycemic load) in random order, each for 4 weeks.

Main Outcome Measures Primary outcome was resting energy expenditure (REE), with secondary outcomes of total energy expenditure (TEE), hormone levels, and metabolic syndrome components.

Results Compared with the pre–weight-loss baseline, the decrease in REE was greatest with the low-fat diet (mean [95% CI], –205 [–265 to –144] kcal/d), intermediate with the low–glycemic index diet (–166 [–227 to –106] kcal/d), and least with the very low-carbohydrate diet (?138 [–198 to –77] kcal/d; overall P = .03; P for trend by glycemic load = .009). The decrease in TEE showed a similar pattern (mean [95% CI], ?423 [–606 to –239] kcal/d; ?297 [–479 to –115] kcal/d; and ?97 [–281 to 86] kcal/d, respectively; overall P = .003; P for trend by glycemic load < .001). Hormone levels and metabolic syndrome components also varied during weight maintenance by diet (leptin,P < .001; 24-hour urinary cortisol, P = .005; indexes of peripheral [P = .02] and hepatic [P = .03] insulin sensitivity; high-density lipoprotein [HDL] cholesterol, P < .001; non-HDL cholesterol,P < .001; triglycerides, P < .001; plasminogen activator inhibitor 1, P for trend = .04; and C-reactive protein, P for trend = .05), but no consistent favorable pattern emerged.

Conclusion Among overweight and obese young adults compared with pre–weight-loss energy expenditure, isocaloric feeding following 10% to 15% weight loss resulted in decreases in REE and TEE that were greatest with the low-fat diet, intermediate with the low–glycemic index diet, and least with the very low-carbohydrate diet.

 

[Michael Scally MD]

AHRQ Healthcare Horizon Scanning System - Priority Area 10: Obesity
http://www.effectivehealthcare.ahrq.gov/ehc/assets/File/10_Obesity_Potential_High_Impact_June_2012.pdf

Based on current definitions, individuals with body mass index (BMI) between 25 and 30 kg/m2 are considered overweight. Individuals with a BMI >30 kg/m2 are considered obese. Individuals with BMI >35 or >40 kg/m2 are considered severely obese and morbidly obese, respectively. According to the U.S. Centers for Disease Control and Prevention (CDC), the prevalence of obesity in the United States increased from 15% of adults in 1980 to about 34% of adults in 2006. By 2008, 68% of the population was deemed overweight, with half of that number being categorized as obese. More than 15 million adults have a body mass index >40 kg/m2 or a BMI of 35 kg/m2 and comorbidities. CDC reports that obesity prevalence among children continues to climb, with about a third of all children 19 years of age and younger categorized as overweight or obese.

Obesity is a major contributor to many diseases, including type 2 diabetes mellitus (T2DM), cardiovascular disease, hypertension, and sleep apnea. Obesity also increases the risk of several types of cancer including colorectal, endometrial, esophageal, renal, and postmenopausal breast cancers.
Waist circumference, which measures abdominal fat, predicts obesity-related risk factors for disease. Men with a waist larger than 40 inches and women with a waist measuring more than 35 inches are at increased risk for obesity-related health consequences. Current data suggest that risk of overweight/obesity-related morbidity and mortality increases as BMI increases past 25 kg/m2. Research indicates that individuals can reduce their risk of obesity-related adverse health conditions by decreasing their total body weight by about 10%.

CDC also reported that researchers calculated that U.S. medical expenditures attributed to obesity totaled about $147 billion in 2008 dollars and stated that taxpayers, through Medicare and Medicaid programs, paid more than half of these costs.

Only one surgical treatment has definitively demonstrated long-term efficacy for morbidly obese patients (gastric bypass surgery), and only one pharmacotherapy is available for long-term treatment of overweight and obesity. The surgery carries significant risks of morbidity and mortality, and the drug therapy has undesired side effects and limited efficacy in achieving sufficient weight loss. Additional treatment options are highly desired. Some new options are in development, but have had a long and sometimes circuitous path to marketing approval.

Concerns over lack of availability of pharmacotherapies approved by the U.S. Food and Drug Administration (FDA) for treating obesity were expressed in September 2011 by the U.S. Congressional Committee on Appropriations. The committee stated, “the lack of obesity medications is a significant unmet medical need.” This committee directed FDA to develop a pathway by March 30, 2012, to support development of antiobesity treatments. This prompted the FDA to work more closely with manufacturers.

In addition, liraglutide (Victoza®, Novo Nordisk a/s, Bagsvaerd, Denmark), an FDA-approved drug for management of T2DM, appears to be of interest for off-label use in treating obesity.

Two drugs considered for this iteration of the High Impact Report but not deemed high impact by experts pose different mechanisms of action. Their approval submissions were initially rejected by FDA. They are lorcaserin (Lorgess®, Arena Pharmaceuticals, Inc., San Diego, CA) and naltrexone HCl/bupropion HCl combination therapy (Contrave®, Orexigen Therapeutics, Inc., La Jolla, CA in collaboration with Takeda Pharmaceutical Co., Ltd., Osaka, Japan).

Lorcaserin is an investigational 5-hydroxytryptamine type 2C (5-HT2C) receptor agonist believed to selectively stimulate the 5-HT2C serotonin receptors in the brain, which are involved in controlling appetite and metabolism. In May 2012, the FDA Endocrinologic and Metabolic Drugs Advisory Committee voted 18-4 in favor of recommending approval for lorcaserin.

Naltrexone/bupropion drug is a combination oral, sustained-release drug intended to fight the body's tendency to regain weight after weight loss through the combined mechanism of bupropion, which activates the pro-opiomelanocortin neurons in the brain to release a hormone called alpha-MSH, and naltrexone, which inhibits beta-endorphin, a natural opiate believed to increase food intake; a revised new drug application submission is under way.

Liraglutide is a synthetic analog of the peptide hormone glucagon-like peptide-1 (GLP-1), which has been shown to suppress appetite and energy intake as well as delay gastric emptying, which may induce a feeling of satiety. A new drug application for treating obesity has not been submitted as of this writing.


Phentermine/Topiramate (Qnexa) for Obesity

Key Facts: Currently, orlistat is the only FDA-approved antiobesity drug available for long-term use in the United States and for use in adolescents. Many patients discontinue treatment with orlistat because of its unpleasant side effects. New drug treatment options are needed for obese patients seeking medical therapy for weight loss.

Phentermine/topiramate (Qnexa®, Vivus, Inc., Mountain View, CA) is a controlled-release formulation of two separate FDA-approved drugs. This drug combination acts on the central nervous system as an appetite suppressant.

Phentermine is a central norepinephrine-releasing drug that was approved by FDA in 1959 as an appetite suppressant for short-term (3 months or less) treatment of obesity at a dose of 37.5 mg/day.

Topiramate is a gamma aminobutyric acid agonist that was approved by FDA in 1996 for treating epilepsy at a dose of approximately 400 mg/day and has been known to have weight loss as a side effect.

Phentermine/topiramate might promote weight loss while avoiding side effects potentially caused by high doses of either drug. In November 2011, FDA accepted a revised new drug application, but in early 2012, it extended the decision date from April 17, 2012, to July 17, 2012. Nonetheless, obesity drug market analysts expressed optimism about its likelihood of approval. Most payers do not cover antiobesity drugs, so patients would likely bear the cost of this drug, unless payers decide to cover it for individuals with comorbidities that could be improved by weight loss achieved with this drug. Out-of-pocket expenses for phentermine/topiramate are projected to be $1,000–$2,000.

Key Expert Comments: Experts generally expressed optimism about this intervention’s ability to meet the need of obese patients for a medical solution for moderate weight loss, given the lack of pharmacotherapy interventions and failure of dietary and lifestyle modifications to achieve the needed weight loss among overweight individuals. Experts generally indicated that both patient and clinician acceptance would be high for this drug because the potential to eliminate long-term sequelae of obesity-related diseases is critically important. However, experts opined that the increase in per-patient costs of care might serve as barriers to acceptance for some patients because payers generally do not reimburse for antiobesity drugs.

Potential for High Impact: High

 

[Michael Scally MD]

New diet drug helps heavy patients lose 10% of weight
New diet drug helps heavy patients lose 10% of weight | Statesman Journal | statesmanjournal.com

A new prescription diet drug OK'd today by the government is expected to help heavy patients drop about 10% of their weight — more than any other approved obesity medication.

Qsymia (pronounced kyoo-sim-ee-uh), which suppresses appetite and increases the feeling of fullness, boosts patients' weight loss when used along with a diet and exercise plan. Until now, the drug had been called Qnexa.

This is the second medication to fight obesity that the Food and Drug Administration has approved this summer after going for more than a decade without OK'ing a diet drug.

Qsymia from Vivus Inc. of Mountain View, Calif., is designed for people who are obese, which is roughly 30 or more pounds over a healthy weight, or those who are overweight and have other weight-related health issues such as high blood pressure, type 2 diabetes or high cholesterol. "It's not for patients who want to lose a few pounds," says Peter Tam, president of Vivus.

 

[Michael Scally MD]

FDA approves weight-management drug Qsymia
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm312468.htm


HIGHLIGHTS OF PRESCRIBING INFORMATION
http://www.qsymiarems.com/full-prescribing-information.pdf

 

[Michael Scally MD]

Risk Evaluation and Mitigation Strategy (REMS) for QSYMIA
http://www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM312598.pdf

 

[Michael Scally MD]

America's Obesity Crisis
America's Obesity Crisis - Institute of Medicine

The Weight of the Nation sheds new light on the facts and myths of this urgent public health issue and explore how obesity is impacting our nation and the health care system. This multipronged project features a series of four documentary films, a three-part HBO Family series, 14 bonus short films, a social media campaign, a companion book, and a nationwide community-based outreach campaign. The four-part documentary series and other facets of the initiative were developed with expert input from the IOM as well as CDC and NIH.

 

[deathdodger]

Interesting the end all to weight loss is diet and exercise.

 

[Michael Scally MD]

Pontzer H, Raichlen DA, Wood BM, Mabulla AZP, Racette SB, Marlowe FW. Hunter-Gatherer Energetics and Human Obesity. PLoS ONE 2012;7(7):e40503. PLoS ONE: Hunter-Gatherer Energetics and Human Obesity

Western lifestyles differ markedly from those of our hunter-gatherer ancestors, and these differences in diet and activity level are often implicated in the global obesity pandemic. However, few physiological data for hunter-gatherer populations are available to test these models of obesity. In this study, we used the doubly-labeled water method to measure total daily energy expenditure (kCal/day) in Hadza hunter-gatherers to test whether foragers expend more energy each day than their Western counterparts. As expected, physical activity level, PAL, was greater among Hadza foragers than among Westerners. Nonetheless, average daily energy expenditure of traditional Hadza foragers was no different than that of Westerners after controlling for body size. The metabolic cost of walking (kcal kg?1 m?1) and resting (kcal kg?1 s?1) were also similar among Hadza and Western groups. The similarity in metabolic rates across a broad range of cultures challenges current models of obesity suggesting that Western lifestyles lead to decreased energy expenditure. We hypothesize that human daily energy expenditure may be an evolved physiological trait largely independent of cultural differences.

 

[Michael Scally MD]

In summary, peripherally restricted CB1R inverse agonists have therapeutic potential in obesity. Their high efficacy in normalizing the related metabolic abnormalities, including insulin resistance and fatty liver, would warrant their testing as monotherapy in these conditions. A key component in the mode of action of CB1R inverse agonism is reversal of leptin resistance. An important issue in obesity treatment is inability to maintain weight loss, due to the perception by the brain of weight loss as a relative leptin-deficient state, which triggers an anabolic response promoting the regain of lost weight. Thus, by sensitizing the body to endogenous leptin, peripheral CB1R blockade may not only promote weight loss, but could help maintain it.


Tam J, Cinar R, Liu J, et al. Peripheral Cannabinoid-1 Receptor Inverse Agonism Reduces Obesity by Reversing Leptin Resistance. Cell Metabolism. ScienceDirect.com - Cell Metabolism - Peripheral Cannabinoid-1 Receptor Inverse Agonism Reduces Obesity by Reversing Leptin Resistance

Obesity-related leptin resistance manifests in loss of leptin’s ability to reduce appetite and increase energy expenditure. Obesity is also associated with increased activity of the endocannabinoid system, and CB1receptor (CB1R) inverse agonists reduce body weight and the associated metabolic complications, although adverse neuropsychiatric effects halted their therapeutic development. Here we show that in mice with diet-induced obesity (DIO), the peripherally restricted CB1R inverse agonist JD5037 is equieffective with its brain-penetrant parent compound in reducing appetite, body weight, hepatic steatosis, and insulin resistance, even though it does not occupy central CB1R or induce related behaviors. Appetite and weight reduction by JD5037 are mediated by resensitizing DIO mice to endogenous leptin through reversing the hyperleptinemia by decreasing leptin expression and secretion by adipocytes and increasing leptin clearance via the kidney. Thus, inverse agonism at peripheral CB1R not only improves cardiometabolic risk in obesity but has antiobesity effects by reversing leptin resistance.

 

[lawrenceconner]

Interesting the end all to weight loss is diet and exercise.

Well, that is correct. Self discipline is the best formula for weight loss, the others will follow.

 

[Michael Scally MD]

Naukkarinen J, Rissanen A, Kaprio J, Pietilainen KH. Causes and consequences of obesity: the contribution of recent twin studies. Int J Obes 2012;36(8):1017-24. International Journal of Obesity - Causes and consequences of obesity: the contribution of recent twin studies

Obesity is a genetically complex disorder that produces a myriad of health problems. Most of the recognized complications of obesity are not only strongly influenced by lifestyle factors, but also present with independent genetic predispositions that are notoriously difficult to disentangle in humans. Most studies on the causes and consequences of acquired obesity are encumbered by the incomplete ability to control for genetic influences. However, utilizing a unique experiment of nature, namely monozygotic twins (MZ) discordant for obesity as ‘clonal controls’ of obese and non-obese individuals has enabled the fine characterization of the effects and possible antecedents of acquired obesity while controlling for the genetic background, as well as pointed to novel obesity predisposing candidate genes. This review is a distillation of the findings from more than 10 years of research done in an exceptionally well-characterized collection of MZ and dizygotic (DZ) twins, based on the Finnish Twin Cohorts. Topics covered include the nature of development of obesity from the childhood onwards, the role of exercise in modifying the genetic susceptibility, the resulting inflammatory, prediabetic and preatherosclerotic changes in whole body and adipose tissue physiology, as well as the newest insights provided by the omics revolution.

 

[Michael Scally MD]

Thomas DM, Bouchard C, Church T, et al. Why do individuals not lose more weight from an exercise intervention at a defined dose? An energy balance analysis. Obes Rev. Why do individuals not lose more weight from an exercise intervention at a defined dose? An energy balance analysis - Thomas - 2012 - Obesity Reviews - Wiley Online Library

Weight loss resulting from an exercise intervention tends to be lower than predicted. Modest weight loss can arise from an increase in energy intake, physiological reductions in resting energy expenditure, an increase in lean tissue or a decrease in non-exercise activity. Lower than expected, weight loss could also arise from weak and invalidated assumptions within predictive models. To investigate these causes, we systematically reviewed studies that monitored compliance to exercise prescriptions and measured exercise-induced change in body composition. Changed body energy stores were calculated to determine the deficit between total daily energy intake and energy expenditures. This information combined with available measurements was used to critically evaluate explanations for low exercise-induced weight loss. We conclude that the small magnitude of weight loss observed from the majority of evaluated exercise interventions is primarily due to low doses of prescribed exercise energy expenditures compounded by a concomitant increase in caloric intake.

 

[Michael Scally MD]

Taghva A, Corrigan JD, Rezai AR. Obesity and Brain Addiction Circuitry: Implications for Deep Brain Stimulation. Neurosurgery 2012;71(2):224-38. Obesity and Brain Addiction Circuitry: Implications for Dee... : Neurosurgery

Obesity is a growing health problem worldwide and is responsible for a significant proportion of health expenditures in developed nations. It is also notoriously difficult to treat. Prior attempts at pharmacological or neurological modulation, including deep brain stimulation, have primarily targeted homeostatic mechanisms of weight control centered in the hypothalamus. To date, these attempts have had limited success. Multiple lines of independent data suggest that dysregulated reward circuitry in the brain underlies behaviors leading to obesity. Here, we review the existing data and related neurocircuitry, as well as the scope of obesity and currently available treatments. Finally, we suggest a neuromodulation strategy geared toward regulating these dysfunctional circuits, primarily by alteration of frontolimbic circuits.

 

[Michael Scally MD]

Rosenblatt A, Faintuch J, Cecconello I. Sexual hormones and erectile function more than 6 years after bariatric surgery. Surg Obes Relat Dis. ScienceDirect.com - Surgery for Obesity and Related Diseases - Sexual hormones and erectile function more than 6 years after bariatric surgery

BACKGROUND: The long-term effect of bariatric intervention on androgenic hormones and erectile function is not well known. In a prospective comparative study, the profile of sexual function was ascertained. The setting was a large public academic hospital.

METHODS: A total of 51 patients were included in the present study. Of these, 23 were in the bariatric surgery cohort (with 6-14 yr of follow-up), 14 were obese controls, and 14 were lean controls, aged 30-65 years. The groups were matched for age and, in the case of obese controls, the current body mass index. The measurements included orchidometry, an assessment of gynecomastia, the International Index of Erectile Function, the Aging Males Symptoms questionnaire, the measurement of 12 hormones, and general biochemical measurements.

RESULTS: Bariatric patients lost substantial weight (59.8 +/- 12.1 versus 35.1 +/- 7.7 kg/m(2)), albeit residual obesity was the rule, with varying degrees of sleep apnea, hypertension, and glucose/lipid aberrations. The total and free testosterone and sex hormone-binding globulin levels were greater in the gastric bypass patients than in the obese controls and comparable to those of lean individuals. The International Index of Erectile Function final score revealed no differences; however, the domains of erectile dysfunction (P = .015) and overall satisfaction (P = .028) were better than those in the obese controls, although still lower than those in the lean group. The correlation between the body mass index and the International Index of Erectile Function score in the entire population (n = 51) was negative, as expected, with, however, low r and r(2) indexes (.354 and .125, respectively).

CONCLUSION: The findings are consistent with long-term normalization of androgenic hormones but less than complete normalization of erectile function. This seeming contradiction might be explained by the remaining or relapsing obesity or its co-morbidities.

 

[Michael Scally MD]

Bhatt SP, Nigam P, Misra A, et al. Association of the myostatin gene with obesity, abdominal obesity and low lean body mass and in non-diabetic asian indians in north India. PLoS One 2012;7(8):e40977. PLoS ONE: Association of the Myostatin Gene with Obesity, Abdominal Obesity and Low Lean Body Mass and in Non-Diabetic Asian Indians in North India

BACKGROUND: To determine the association of the A55T and K153R polymorphisms of the Myostatin gene with obesity, abdominal obesity and lean body mass (LBM) in Asian Indians in north India.

MATERIALS AND METHODS: A total of 335 subjects (238 men and 97 women) were assessed for anthropometry, % body fat (BF), LBM and biochemical parameters. Associations of Myostatin gene polymorphisms were evaluated with anthropometric, body composition and biochemical parameters. In A55T polymorphism, BMI (p = 0.04), suprailiac skinfold (p = 0.05), total skinfold (p = 0.008), %BF (p = 0.002) and total fat mass (p = 0.003) were highest and % LBM (p = 0.03) and total LBM (Kg) were lowest (p = 0.04) in subjects with Thr/Thr genotype as compared to other genotypes. Association analysis of K153R polymorphism showed that subjects with R/R genotype had significantly higher BMI (p = 0.05), waist circumference (p = 0.04), %BF (p = 0.04) and total fat mass (p = 0.03), and lower %LBM (p = 0.02) and total LBM [(Kg), (p = 0.04)] as compared to other genotypes. Using a multivariate logistic regression model after adjusting for age and sex, subjects with Thr/Thr genotype of A55T showed high risk for high %BF (OR, 3.92, 95% Cl: 2.61-12.41), truncal subcutaneous adiposity (OR, 2.9, 95% Cl: 1.57-6.60)] and low LBM (OR, 0.64, 95% CI: 0.33-0.89) whereas R/R genotype of K153R showed high risk of obesity (BMI; OR, 3.2, 95% CI: 1.2-12.9; %BF, OR, 3.6, 95% CI: 1.04-12.4), abdominal obesity (OR, 2.12, 95% CI: 2.71-14.23) and low LBM (OR, 0.61, 95% CI: 0.29-0.79).

CONCLUSIONS/SIGNIFICANCE: We report that variants of Myostatin gene predispose to obesity, abdominal obesity and low lean body mass in Asian Indians in north India.

 

[Michael Scally MD]

 

[Michael Scally MD]

Musso G, Gambino R, Cassader M. Interactions between gut microbiota and host metabolism predisposing to obesity and diabetes. Annu Rev Med 2012;62:361-80. An Error Occurred Setting Your User Cookie

Novel, culture-independent, molecular and metagenomic techniques have provided new insight into the complex interactions between the mammalian host and gut microbial species. It is increasingly evident that gut microbes may shape the host metabolic and immune network activity and ultimately influence the development of obesity and diabetes. We discuss the evidence connecting gut microflora to obesity and to type 1 and type 2 diabetes, and we present recent insights into potential mechanisms underlying this relationship: increased nutrient absorption from the diet, prolonged intestinal transit time, altered bile acid entero-hepatic cycle, increased cellular uptake of circulating triglycerides, enhanced de novo lipogenesis, reduced free fatty acid oxidation, altered tissue composition of biologically active polyunsaturated fatty acid, chronic low-grade inflammation triggered by the endotoxin toll-like receptor 4 axis, and altered intestinal barrier function.