MedicalResearch.com Interview Invitation
Melanie J Davies MB ChB MD FRCP FRCGP
Professor of Diabetes Medicine NIHR Senior Investigator
Leicester Diabetes Unit Leicester Diabetes Centre
Bloom University of Leicester
MedicalResearch: What is the background for this study? What are the main findings? Dr. Davies: This study was designed to test the efficacy and safety of Liraglutide using a dose of 3mg for weight loss among patients with type 2 diabetes. It was a large international study in which we compared once daily subcutaneous Liraglutide at a dose of 3mg to Liraglutide 1.8mg which is the current maximum dose licenced in patients with diabetes and placebo. In all patients we offered a calorie deficit diet and lifestyle advice to increase physical activity. Our main findings were that the dose of 3mg of Liraglutide resulted in greater weight loss than both other arms of the study indeed 54% of patients at 56 weeks achieved more than 5% weight loss and a further 25% were able to achieve more than 10% weight loss. The 3mg of Liraglutide compared to the placebo, there were also significant impacts on HbA1c and other cardiovascular risk factors such as systolic blood pressure and lipids as well as improving patient quality of life particularly physical functioning and patient treatment satisfaction.(more…)
MedicalResearch.com Interview with:
Meera Sheffrin MD
Geriatrics Fellow
Division of Geriatrics | Department of Medicine
San Francisco VA Medical Center
University of California, San Francisco
Medical Research: What is the background for this study? What are the main findings?
Dr. Sheffrin: The main drug treatments for dementia are a class of medications called cholinesterase inhibitors. They have only modest effects on cognition and function in most patients, but since they are one of the few available treatments for dementia and thus very commonly prescribed. However,they are known to cause GI side effects (nausea, vomiting, diarrhea, and anorexia) in many patients when first started. It is plausible they could also caust weight loss, espeically considering they cause nausea and anorexia. However, the data on weight loss from randomized controlled trials is very limited and inconclusive, so we did a very large observational study in a real-world of the VA national healthcare system who were newly started on these medications, to see if they were associated with weight loss.
We found that patient with dementia started on cholinesterase inhibitors had a substantially higher risk of clinically significant weight loss over a 12-month period compared to matched controls.
1,188 patients started on cholinesterase inhibitors were matched to 2,189 similar patients who were started on other new chronic medications. The primary outcome was time to a 10-pound weight loss over a 12-month period, as this represents a degree of loss that would be clinically meaningful – not only noticed by a clinician but would perhaps prompt further action in considering the causes of the weight loss and medical work-up.
We found that starting cholinesterase inhibitors was associated with a 24% greater risk of developing weight loss. Overall, 29% of patients started on cholinesterase inhibitors experienced a weight loss of 10 pounds or more, compared with 23% of the control group. This corresponds to a number needed to harm of 21 over 1 year; meaning only 21 patients need to be treated with a cholinesterase inhibitor over the course of a year for one patient to experience a 10 pound weight loss.
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MedicalResearch.com Interview with:
Candida J. Rebello and Dr. Frank Greenway
Pennington Biomedical Research Center
Baton Rouge, Louisiana
MedicalResearch: What is the background for this study? What are the main findings?Response: Appethyl™ contains concentrated thylakoid membranes extracted from spinach leaves. By interacting with fats and slowing fat digestion thylakoid membranes promote the release of hormones that reduce feelings of hunger and keep consumers full for a prolonged period. In previous studies the spinach extract has been shown to promote reduction of body weight and fat mass (1-3). Studies have also shown that consuming the thylakoid membranes reduces the urge for chocolate and sweet foods in women (2) (4, 5). Research suggests that women tend to crave sweet foods whereas men prefer savory foods. Hence, thylakoids may influence reward mechanisms to promote an inhibition over eating, especially since some of the hormones released in response to delayed fat digestion influence areas of the brain that control reward-induced eating. Further, unlike pharmaceutical drugs such as orlistat, the spinach extract delays but does not prevent fat digestion. Therefore, the excretion of undigested fat which is an unpleasant side effect of these drugs is avoided. Thus, the effect of the extract on reducing the desire to eat is of great interest, especially if its effects are mediated in part through the reward system. Reward mechanisms can be activated outside of conscious control. In the current food environment which is rife with enticing food choices, reward-induced eating assumes importance.
The main findings of the study are that consuming 5 g of the spinach extract reduced hunger and increased fullness over a two hour period. Males in the study ate 126 kcal less under the thylakoid condition compared to the placebo.
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MedicalResearch.com Interview with:Junfeng Jiao, PhD
Assistant Professor, The University of Texas at Austin School of Architecture
Director, Urban Information Lab
Austin, Texas
Medical Research: What is the background for this study? Dr. Jiao: The increase in obesity rates has been explained by dietary changes including the consumption of high-energy, low-nutrient foods. Over the past thirty years, trends reveal increases of eating away from home. Public Health professionals have hypothesized that the heightened exposure to the ubiquitous fast food establishments may be an avenue through which health and diets are impacted. Medical Research: What are the main findings?Dr. Jiao: This study examined whether the reported health impacts of eating at a fast food or quick service establishment on a frequent basis were associated with having such a restaurant near home. Results indicated that eating at a fast food or quick service restaurant two times or more per week was related with perceived poor health status, overweight, and obese. Simply living close to such establishments was not related to negative health outcomes such as being overweight or obese, having cardiovascular disease (CVD) or diabetes.
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MedicalResearch.com Interview with:Benjamin D. Horne, PhD, MPH, FAHA, FACC
Director, Cardiovascular and Genetic Epidemiology, Intermountain Heart Institute
Adjunct Assistant Professor, Genetic Epidemiology Division, Department of Medicine,
University of Utah
Medical Research: What is the background for this study? What are the main findings?
Dr. Horne: A rapidly expanding set of results from animal studies exists regarding the effects of intermittent fasting among animals. Many pilot studies of intermittent fasting have been performed now, too, but the body of literature regarding the human response to fasting is incomplete. This study sought to determine how preliminary and incomplete the evidence is in humans regarding the health benefits and the harmful side-effects of intermittent fasting. The purpose was to determine how reliable the evidence is that people should be engaging in fasting to improve their health. In particular, one major concern is that diet gurus and even some scientists are marketing intermittent fasting to the public through diet books and other methods that produce additional income for them, but it is unclear whether their claims can be supported.
The main findings of the study are that only three controlled clinical trials of intermittent fasting in humans have been published that were designed rigorously and included a control group in addition to the fasting intervention arm of the study. One of the three had a pre-specified primary outcome (weight loss) and another used the Bonferroni correction to account for inflated false positive results due to multiple hypothesis tests (the third study unfortunately did neither, which is the common approach in human studies of intermittent fasting). These three controlled trials only used surrogate or intermediate endpoints, though, such as weight, cholesterol, or other risk factors for disease. The three trials also have substantial limitations, including small sample sizes (~30 people total), a fasting regimen that was studied for less than three months, and no evaluation of clinical safety outcomes. Only one of the three trials was registered on ClinicalTrials.gov, a site instituted as part of the FDA Modernization Act and a pre-requisite for trials that are published in scientifically sound medical journals and are to be reviewed by the FDA.
Two observational studies of the association of intermittent fasting with clinical events (i.e., coronary artery disease diagnosis and diabetes diagnosis) also have been published. These two studies included 200 patients and 445 patients. They were performed in patients drawn from a general population in which a large proportion of people engage in fasting intermittently over a period of decades. These observational studies provide the only evidence that fasting is associated with a lower risk of disease outcomes. Such studies are limited, though, by adjustment for only known or measured confounders, making it possible that some important factors may be unobserved in the studies that would account for the fasting benefit that was observed. No randomized controlled clinical trial of fasting for clinical events or disease outcomes has been performed, though, thus these five studies are the whole body of reliable evidence that intermittent fasting is beneficial to humans.
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MedicalResearch.com Interview with: Dr. Fumiaki Imamura Ph.D.
MRC Epidemiology Unit
University of Cambridge
Medical Research: What is the background for this study? What are the main findings?
Dr. Imamura: Soft drink consumption is associated with risk of diabetes, but whether or not the association persists after controlling for obesity status is not known. Diet drinks and fruit juice may be good alternatives to soft drinks. However, while obese individuals may consume diet drinks or fruit juice instead of sugar-sweetened soft drinks, evidence was weak to determine whether or not consuming these beverages is associated with risk of diabetes.
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MedicalResearch.com Interview with:
Maya Tabet, MS
Graduate Research Assistant
Saint Louis University
College for Public Health and Social Justice
Department of Epidemiology
St. Louis, MO 63104
MedicalResearch: What is the background for this study? Response: The majority of women in the U.S. have an unhealthy weight before they start pregnancy, most of them being overweight or obese. It is well-known that having an unhealthy weight before pregnancy increases the likelihood of having adverse outcomes for the mother and baby. However, this study is the first to examine the likelihood of adverse outcomes in a second pregnancy among women who had an unhealthy weight before a first pregnancy that had no complications.
MedicalResearch: What are the main findings?Response: Our study involved 121,049 women in Missouri who delivered their first 2 singleton pregnancies between 1989 and 2005. Findings revealed that women who were underweight before a first uncomplicated pregnancy had a 20% increased likelihood of having a shorter gestation and a 40% increased likelihood of having a small baby for gestational age in the second pregnancy, as compared to women who had a healthy weight before their first pregnancy.
Also, women who were obese before a first uncomplicated pregnancy had a 55% increased likelihood of having a large baby for gestational age, a 156% increased likelihood of having preeclampsia, and an 85% increased likelihood of having a cesarean delivery. Babies born to these women also had a 37% increased likelihood of dying in the first 28 days of their life.
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MedicalResearch.com Interview with:
S. Yousuf Zafar, MD, MHS
Associate Professor of Medicine
Duke Cancer Institute
Duke Clinical Research Institute
Medical Research: What is the background for this study? What are the main findings?
Dr. Zafar: Multiple studies have suggested that obesity and colorectal cancer are related. For instance, obesity has been linked with an increased incidence of colon cancer. Obesity has also been associated with a greater risk of colon cancer recurrence. To date, no study has looked at the role of obesity in outcomes for patients with metastatic colorectal cancer. In our study of over 6000 patients receiving treatment for metastatic olcolorectal cancer, we found that patients with the lowest body mass index (BMI) were at greatest risk for worse survival. This does not mean that obesity is good. More likely, it means that those who are very underweight are least able to tolerate the best treatment, or being very underweight is a biologic marker of poor prognosis.
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MedicalResearch.com Interview with:
Subhadra Gunawardana DVM, Ph.D
Research Associate Professor
Department of Molecular Physiology & Biophysics
Vanderbilt University Medical Center
Nashville, TN 37232
Medical Research: What is the background for this study? What are the main findings?
Response: For many years the general consensus has been that insulin replacement is essential for treating type 1 diabetes. Recent studies increasingly show that extra-pancreatic hormones, particularly those arising from adipose tissue, can compensate for insulin, or entirely replace the function of insulin under appropriate circumstances. Our work on mouse models show that type 1 diabetes can be effectively reversed without insulin, through subcutaneous transplantation of embryonic brown adipose tissue (BAT). BAT transplantation leads to replenishment of recipients' white adipose tissue; dramatic decrease of inflammation; secretion of a number of beneficial adipokines; and fast and long-lasting euglycemia. Insulin-independent glucose homeostasis is established physiologically, through a combination of endogenously generated hormones arising from the transplant and/or newly-replenished white adipose tissue.
Medical Research: What should clinicians and patients take away from your report?Response: If translated to human patients, this approach could provide a cure for type 1 diabetes that does not require regular exogenous administration of insulin or any other compound, and would thus avoid the many inherent difficulties with such therapies.
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MedicalResearch.com Interview with:
Dr. F. Xavier Pi-Sunyer MDDivision of Endocrinology and Obesity Research Center
Columbia University, New York
Medical Research: What is the background for this study? What are the main findings?
Dr. Pi-Sunye: In a large randomized trial, the drug Liraglutide was compared to placebo in overweight and obese non-diabetic volunteers. Over 52 weeks, in combination with diet and increased physical activity, Liraglutide lowered body weight by 8.4 kg as compared to 2.8 kg in placebo. 63% vs 27% lost at least 5% of baseline weight, 33% vs 10% lost more than 10% of baseline weight.
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MedicalResearch.com Interview with:
Anita P. Courcoulas M.D., M.P.H., F.A.C.S
Professor of Surgery
Director, Minimally Invasive Bariatric & General Surgery
University of Pittsburgh Medical Center
Medical Research: What is the background for this study?
Dr. Courcoulas: This study is a randomized clinical trial that was originally funded through the American Recovery and Reinvestment Act of 2009 (ARRA) as a high priority comparative effectiveness topic; the goal of which was to better understand the role of surgical versus non-surgical treatments for Type 2 diabetes mellitus (T2DM) in people with lower Body Mass Index (BMI) between 30 and 40 kg/m2. This report highlights longer-term outcomes at 3 years following random assignment to either an intensive lifestyle weight loss intervention for 1 year followed by a low-level lifestyle intervention for 2 years or surgical treatments (Roux-en-Y gastric bypass [RYGB] or laparoscopic adjustable gastric banding [LAGB]) followed by low-level lifestyle intervention in years 2 and 3.
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MedicalResearch.com Interview with:
Prof. Karine Clément MD, PhD
Director ICAN - Institute of Cardiometabolism And Nutrition
Hôpital La Pitié-Salpêtrière, Paris
www.ican.paris
k.clement@ican-institute.orgMedical Research: What is the background for this study? What are the main findings?
Dr. Clément: Obesity, associated with insulin resistance, is a chronic inflammatory disease revealed by a moderate but long-term increase in the levels of inflammatory molecules in the blood.
Our groups and others have shown that several organs such as adipose tissues, liver, pancreas and muscles are also sites of inflammation with accumulation of immune cells such as macrophages and lymphocytes. This low-grade inflammatory state perturbs the tissue biology and contributes to the development and/or maintenance of insulin resistance and diabetes. In addition our teams and others showed that the intestinal functions are altered in obesity such as sugar and lipid absorption of and enteroendocrine nutrient signaling to the whole body.
Our teams showed modifications of immunity in the obese intestine, and particularly in the jejunum part where most of sugar and lipid absorption takes place. Obesity increases the absorptive surface of the intestine and the colonization of the epithelium by CD8αβ T lymphocytes not affecting tissue integrity, thus differing from IBD inflammation. The cytokines secreted by the CD8 T cells of obese, but not lean subjects, are able to inhibit insulin action in enterocytes. In these patients, the increase of intestinal CD8 T cell density correlates with sugar absorption capacity and with the level of obesity and associated complications such as liver disease (NASH – Non-Alcoholic SteatoHepatitis) and dyslipidemia.
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MedicalResearch.com Interview with:
Ruopeng An, PhD
Assistant Professor, Department of Kinesiology and Community Health
College of Applied Health Sciences
University of Illinois at Urbana-Champaign
Champaign, IL 61820
Medical Research: What is the background for this study? What are the main findings?
Response: Health disparity is a particular type of health difference that is closely linked with social, economic and environmental disadvantage. One fundamental goal in the Healthy People 2020 is to “achieve health equity, eliminate disparities, and improve the health of all groups”. Obesity is a leading risk factor for many adverse health outcomes such as type 2 diabetes, hypertension, dyslipidemia, coronary heart disease, and certain types of cancer. Sweeping across the nation during the past 3 decades, the prevalence of obesity increased from 15% in 1980 to 35% in 2012 among U.S. adults. The obesity epidemic is marked by salient demographic and socioeconomic disparities pertaining to gender, race/ethnicity, education, income and geographic location.
In this study, we examined the annual trends in educational disparity in obesity among U.S. adults 18 years and older from 1984 to 2013 using data from a nationally-representative health survey. We found that the obesity prevalence among people with primary school or lower education increased from 17.46% or 3.41 times the prevalence among college graduates (5.12%) in 1984 to 36.16% or 1.73 times the prevalence among college graduates (20.94%) in 2013. In any given year, the obesity prevalence increased monotonically with lower education level. The obesity prevalence across education subgroups without a college degree gradually converged since early 2000s, whereas that between those subgroups and college graduates diverged since late 1980s. Absolute educational disparity in obesity widened by 60.84% to 61.14% during 1984-2013 based on the Absolute Concentration Index and the Slope Index of Inequality, respectively; meanwhile, relative educational disparity narrowed by 52.06% to 52.15% based on the Relative Index of Inequality and the Relative Concentration Index, respectively. The trends in educational disparity in obesity differed substantially by gender, race/ethnicity, age group, and obesity severity. (more…)
MedicalResearch.com Interview with:
Leslee L. Subak, MD
University of California, San Francisco
Professor, Departments of Obstetrics, Gynecology & Reproductive Sciences, Urology and Epidemiology & Biostatistics
Chief of Gynecology, SF Veterans Affairs Medical Center
UCSF Women's Health Clinical Research Center
MedicalResearch: What is the background for this study? What are the main findings?Dr. Subak: Urinary incontinence is very common, affecting an estimated 30 million adults in the U.S., and may account for as much as $60 billion in annual medical costs. Incontinence can cause significant distress, limitations in daily functioning, and reduced quality of life. Obesity is an important risk factor, with each 5-unit increase in body mass index – a ratio of someone’s weight divided by the square of their height – above normal weight associated with far higher rates of incontinence. The prevalence of incontinence has been reported to be as high as 70 percent among severely obese women, and 24 percent among severely obese men (BMI greater than 40, or more than about 100 pounds greater than ideal body weight).
Since obesity is a risk factor for incontinence, several studies have examined whether weight loss is a treatment for incontinence among obese people with the condition. Clinical trials have shown the low calorie diets, behavioral weight reduction, and bariatric surgery are associated with improvement in incontinence in obese women and men through one year, but evidence on the durability of this effect is lacking.
We performed this study to examine changes in urinary incontinence and identify factors associated with improvement among women and men in the first 3 years following bariatric surgery.
This study included 1987women and men in the Longitudinal Assessment of Bariatric Surgery-2 (LABS-2) study performed at 10 hospitals at 6 clinical centers in the U.S. who underwent bariatric surgery between 2005 and 2009. The study participants ranged in age from 18 to 78 years old – the median age was 47. The analysis controlled for factors such as age, race, smoking status and recent pregnancy. Nearly 79 percent of the participants in the study were women with 49% reporting at least weekly incontinence, compared with 2% of men reporting incontinence.
Following surgery and large weight loss of 29% for women and 26% for men, substantial improvements in incontinence were observed, with a majority of women and men achieving remission at 3 years post-surgery. The more weight lost, the higher the chances of improvement. While the risk of relapse rose with each gain of about 10 pounds, overall there was substantial improvement for both women and men. People who were older, had severe walking limitations or were recently pregnant showed less improvement.
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MedicalResearch.com Interview with:
Dr. Min Du Ph.D
Department of Animal Sciences
Washington Center for Muscle Biology
Washington State University
Pullman, WA
Medical Research: What is the background for this study? What are the main findings?
Response: The beige fat is only recently identified and is highly inducible. we observed that polyphenolic compounds including resveratrol enhances AMPK activity, and hypothesized that resveratrol might enhance the formation of beige fat through activation of AMPK. Therefore, we used resveratrol, a very well characterized polyphenolic compound as a representative of polyphenolic compounds in fruits, to check its effects on the formation of beige fat. We found that resveratrol induced the formation of beige adipocytes both in vitro and in vivo. We further found that the lipid oxidation rate was enhanced due to the formation of beige fat, which is correlated with the anti-obesity effect of resveratrol.
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MedicalResearch.com Interview with:
William S. Yancy, Jr., MD, MHSc
Research Associate
Center for Health Services Research in Primary Care
Durham, NC 27705
Associate Professor Department of Medicine
Duke University Medical Center
Medical Research: What is the background for this study? What are the main findings?
Dr. Yancy: A number of studies have compared different diet approaches for weight management with many of these finding that several different diets can result in significant weight loss. This has led many experts to advise that we should offer a choice among these diet options to our patients who are seeking to lose weight. We know that adherence is the best predictor of weight loss during dietary interventions, so the thought is that patients will adhere better to a diet that they prefer, resulting in more successful weight loss. In addition, allowing choice enhances patient autonomy, which is patient-centered and has been shown to increase treatment adherence. However, the previous studies of various diet approaches did not let people choose a diet, so we don’t actually know if letting them choose will lead to better weight loss. Our study specifically tested this assumption. We randomized participants to a condition where they were allowed to choose between 2 common weight loss diets or to a condition where they were randomly assigned to one of the diets. The 2 diets we used were a low-carbohydrate diet without calorie restriction and a low-fat diet combined with calorie restriction. Participants received counseling about the diets, and about behavioral strategies and physical activity, in 19 group sessions over the span of 12 months. They also received 6 phone calls with motivational counseling in the latter half of the program.
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MedicalResearch.com Interview with:Theresa A Lawrie
World Health Organization
Department of Reproductive Health and Research
Geneva, Switzerland
MedicalResearch: What is the background for this study?Response: Excessive weight gain in pregnancy is associated with various undesirable outcomes in pregnancy. The aim of the review was to assess data from all relevant clinical trials in the field, to determine whether diet and/or exercise interventions during pregnancy were effective in reducing the chance of excessive weight gain in pregnancy. We also wanted to know whether these interventions could reduce the chance of having large babies (macrosomia), as this is associated with difficult labor, c/section, postpartum hemorrhage, birth injuries and other complications.
MedicalResearch: What are the main findings?
Response:Altogether 49 trials contributed data to the review. Approximately half the trials recruited women of any pre-pregnancy weight, the other half recruited women who were overweight or obese at the start of pregnancy. Most of the trials were conducted in high income countries. Interventions varied, some involved individual counseling, others group sessions, some were counseling interventions only, other programs were actively supervised by fitness trainers. Health outcomes for women receiving the intervention programs in addition to routine antenatal care (the intervention group) were compared with those of women receiving the routine antenatal care only (the control group).
We found that diet or exercise or combined interventions led to an average 20% reduction in the number of women gaining excessive weight in pregnancy. This reduction was fairly consistent across the different types of interventions, although the largest effect was observed for combined diet and supervised exercise interventions. Overall findings suggested a small reduction in caesarean section (of about 5%) and in large babies (of about 7%). However, a bigger reduction in large babies (in the region of a 19% reduction) was noted for exercise-only interventions, which were more likely to be supervised interventions.
Other findings: We also found no difference in the risk of preterm birth between groups. Fewer women in the intervention group were assessed as having high blood pressure during pregnancy (although we assessed this as low quality evidence). Low quality evidence also suggested that women in the intervention group were likely to retain less weight at six months postpartum compared with the control group. Interestingly, data from two studies suggested that women receiving diet and exercise interventions were less likely to have babies with breathing difficulties at birth. These findings will hopefully be corroborated by other studies. A limitation of the review, is that we did not include gestational diabetes as an outcome as this is partly covered in a separate Cochrane review. Our exploratory analyses, however, suggested that there may be a reduction in gestational diabetes for certain types of interventions, and we hope to include these data in future review updates.
In general, we did not find differences in outcomes for women according to pre-pregnancy weight or BMI.
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MedicalResearch.com Interview with: Katie Becofsky Ph.D.
Weight Control and Diabetes Research Center
The Miriam Hospital
Providence, RI
Medical Research: What is the background for this study? What are the main findings?Dr. Becofsky: Previous research has provided clear evidence of a relationship between social relations (e.g., frequency of social participation, perceived social support) and mortality risk. We investigated two specific aspects of social relations- source of social support and size of weekly social network- in more detail. The purpose of our study was to examine the associations between different sources of social support (relative, friend, and partner support), as well as size (and source) of weekly social network, on mortality risk in a large cohort of patients from the Aerobics Center Longitudinal Study. We found that perceived support from one’s spouse/partner and relatives, as well as weekly social interaction with a network of 6-7 friends, was associated with lower long-term mortality risk. When the sources were reversed, the effects did not stand- perceived social support from friends did not affect mortality risk, nor did the quantity of weekly familial contacts. (more…)
MedicalResearch.com Interview with:
Aidan Gribbon M.Sc., CSEP-CEP
From the Healthy Active Living and Obesity Research Group
Children’s Hospital of Eastern Ontario Research Institute
Ottawa, Ontario, Canada
Medical Research: What is the background for this study?
Response: The background for the study is that sedentary pursuits, such as video games, are omni-present in the daily lives of adolescents. Manufacturers of active video games (AVG) have been marketing them as a ‘healthy’ alternative to seated video games, with the possibility of preventing/treating obesity in this age group. Although, active video games have been shown to acutely increase energy expenditure over their seated counterparts, no study has examined their compensatory adjustments in energy expenditure or energy intake.
Medical Research: What are the main findings?
Response: The main finding of this paper was that although active video games are not associated with an increased food intake, they are compensated for by a decrease in physical activity such that their benefit of a reduction in the energy gap underlying weight gain is offset within 24 hours.
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MedicalResearch.com Interview with:
Nia S. Mitchell, MD, MPH
Assistant Professor
Division of General Internal Medicine
Department of Medicine
University of Colorado Anschutz Medical Campus
Medical Research: What is the background for this study? What are the main findings?Dr. Mitchell: Despite decades of obesity research two issues remain elusive in weight management: significant, long-term weight loss and weight loss maintenance and widely accessible programs. There are numerous weight loss programs out there, but there is little evidence of the long-term effectiveness of many programs. Furthermore, these programs may not be accessible to the general population because they are too expensive and may not be geographically available.
I chose to evaluate the Take Off Pounds Sensibly (TOPS) program because I thought it had the potential to address these issues. TOPS is a nationally-available, nonprofit, low-cost, peer-led weight loss program. It costs only $92 per year--$32 is the annual fee plus local chapter dues that average about $5 per month--and any four people can start a TOPS chapter, so it can be implemented and disseminated widely.
The main objective of this study was to determine the weight change for individuals who consecutively renewed their membership in TOPS. We looked at people who joined TOPS from 2005 to 2011, so they could have been followed for up to seven years. We found that people who join TOPS and consecutively renew their annual membership can lose a clinically significant amount of weight and maintain the weight loss for up to seven years. Clinically significant weight loss is defined as weight loss of at least 5% of initial weight, because with a 5% weight loss people with weight-related medical conditions, such as diabetes, can see an improvement in their conditions. Therefore, a diabetic who weighs 200 pounds may see an improvement in her blood sugar control if she loses 10 pounds.
In our study, fifty percent of individuals had clinically significant weight loss in their first year in the program, and 62% of those renewed their annual membership consecutively for seven years had clinically significant weight loss at seven years. This was exciting because many people who lose weight tend to gain it back. I often say that the unfortunate natural history of weight loss tends to be weight re-gain. However, the majority of these individuals maintained a clinically significant weight loss.
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MedicalResearch.com Interview with:
Catarina Rendeiro Ph.D.
Post-doctoral Research Associate
Rhodes lab University of Illinois
Urbana, Illinois
Medical Research: What is the background for this study? What are the main findings?
Dr. Rendeiro: The motivation for this study emerges in the context of understanding the link between sugar intake, particularly fructose, and the rising obesity epidemic that we are currently facing. Overeating and lack of physical activity certainly play major roles in obesity, but the sources of calories are also important. Fructose, a simple monosaccharide found in fruit and vegetables, and composing half of sucrose (i.e., table sugar), has been on the increase in Western diets. In our rodent study, 18% of dietary calories were derived from sugar, either fructose or glucose. This level is similar to typical American diets. However, the fructose diet resulted in increased weight gain and fat deposition and reduced physical activity even though food intake was similar between the two groups. It is also important to note that our animals were consuming their regular amount of calories, not overeating. Only the source of sugar was different between experimental groups, and still calorie-for-calorie, fructose caused greater weight gain and less physical activity than glucose.
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MedicalResearch.com Interview with:
Christopher X WongMBBS MSc PhD
Clinical Research Fellow | Clinical Trial Service Unit, Oxford
Clinical Senior Lecturer | Centre for Heart Rhythm Disorders, Adelaide
Clinical Trial Service Unit, University of Oxford
Roosevelt Drive, Oxford
Medical Research: What is the background for this study? What are the main findings?Dr. Wong: Atrial fibrillation is an increasingly common heart rhythm disorder. This study demonstrates that even small increments in obesity are associated with a significantly increased risk of atrial fibrillation. Our data suggest that for every 1 unit reduction in body mass index there may be a 3-5% reduction in atrial fibrillation; for every 5 unit reduction, there may be 10-29% reductions. It should also be noted that this is likely to be a significant underestimate of the effect of weight reduction on atrial fibrillation rates as weight control has favourable effects on other risk factors for atrial fibrillation, such as hypertension and diabetes. Given the more than 45 million people with atrial fibrillation worldwide, even small but widespread reductions in obesity would thus help contain this ‘epidemic’ of atrial fibrillation.
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MedicalResearch.com interviewDorota Kaminska, MSc
Department of Clinical Nutrition
University of Eastern FinlandMedicalResearch: What is the background for this study? What are the main findings?Response: The prevalence of obesity is increasing worldwide, making it one of the biggest health problems currently facing both developed and developing countries. Obesity is considered a primary risk factor for developing type 2 diabetes. While the majority of people with type 2 diabetes are obese, most of obese people do not develop diabetes, indicating that obesity is not the only risk factor for type 2 diabetes. Both obesity and type 2 diabetes are multifactorial complex diseases that are caused by a combination of genetic, environmental, and lifestyle factors. Results from twin studies suggest that genetic factors explain 50% to 90% of the variance in body mass index (BMI) and from 45% to 85% of the diabetes risk. However genetic variations identified by genome wide association studies (GWAS) explain only 2-4% of the obesity risk and 5-10% of the type 2 diabetes risk. Several options have been debated to be a source of so called “missing heritability”, including, among others, structural DNA variations, gene-gene and gene-environment interactions, epigenetic modifications and RNA splicing.
We used adipose tissue samples from Kuopio Obesity Surgery (KOBS), very low calorie diet (VLCD), Metabolic Syndrome in Men (METSIM) and European Network on Functional Genomics of Type 2 Diabetes (EUGENE2) studies to determine alternative splicing pattern of selected genes.
The study focused on determining the effects of obesity and weight loss on alternative splicing of metabolically active genes (TCF7L2 and INSR). We showed that alternative splicing of both genes is dysregulated in obesity and type 2 diabetes, resulting in impaired insulin action in adipose tissue. Additionally we demonstrated, that obesity induced changes in splicing can be reversed by weight loss induced by gastric bypass surgery or very low calorie diet.
Furthermore, the study identified alternatively spliced genes in the genomic regions associated with obesity risk, demonstrating that splicing of the MSH5 gene in subcutaneous fat is regulated by weight loss. The study also found that body mass index is a main determinant of TRA2B, BAG6 and MSH5 splicing in subcutaneous fat; however, the functional consequences of this finding require further investigation. These findings imply that the obesity-associated gene variants might act through regulation of splicing which in turn might underlie the pathogenesis of obesity in individuals carrying the risk variants.
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MedicalResearch.com Interview with:
Michelle Schmiegelow, MD, PhD-student
Hjertemedicinsk Forskning
Gentofte Universitetshospital
Hellerup
Medical Research: What is the background for this study?
Dr. Schmiegelow: Obesity has become a worldwide epidemic, but the excess cardiovascular risk observed in obese individuals may primarily be attributable to metabolic mediators, rather than obesity per se. Several studies conducted in primarily non-Hispanic white populations suggest that obese individuals without the metabolic syndrome, defined as metabolically healthy obese, have a cardiovascular risk similar to that of normal weight metabolically healthy individuals.
We used prospectively collected data from the Women’s Health Initiative studies to evaluate whether obesity unaccompanied by metabolic abnormalities was associated with increased risk of cardiovascular disease (CVD) across racial/ethnic subgroups in postmenopausal women. Additionally, we examined whether the use of the metabolic syndrome to define the metabolically healthy obese applied to the various racial/ethnic subgroups by quantifying the number and type of metabolic syndrome components.
All women were classified by obesity level and metabolic health status at baseline. The women were thus categorized according to body mass index (BMI, kg/m2) into normal weight (BMI 18.5-24.9 kg/m2), overweight (25-29.9 kg/m2) and obese (30.0 kg/m2) women. Metabolic health status was first defined by presence of the metabolic syndrome (yes/no), and second by number of metabolic syndrome components. In accordance with the International Diabetes Federation and the American Heart Association/National Heart, Lung, and Blood Institute we defined the metabolic syndrome as any two of the following (criteria for women): increased waist circumference ≥80 cm; increased level of triglycerides ≥150 mg/dL (≥1.7 mM); decreased level of HDL-C <50 mg/dL (<1.3 mM); increased blood pressure with either systolic blood pressure ≥130 mmHg or diastolic blood pressure ≥85 mmHg, or treatment with antihypertensive drugs; and impaired fasting serum glucose ≥100 mg/dL (6.1 mM).
Medical Research: What are the main findings?Dr. Schmiegelow: The study population comprised 14,364 women without diabetes or prior cardiovascular disease. The women had a median age of 64 years (interquartile range 57–69), and 47% were white, 36% were black and 18% were Hispanic. Over a median follow-up of 13 years (interquartile range 12–14 years), 1,101 women (7.7%) had a first cardiovascular event.
The main findings of this study were that metabolic abnormalities appeared to confer more cardiovascular risk among black women than among white women. Consistent with other studies, among white women without the metabolic syndrome, obesity was not associated with increased cardiovascular risk compared with normal weight women. Conversely, black overweight and black obese women had increased cardiovascular risk compared with normal weight black women without the metabolic syndrome, even in absence of the metabolic syndrome.
According to number of metabolic syndrome components, black overweight or obese women with just two metabolic abnormalities had increased risk of cardiovascular disease, although they would be considered “metabolically healthy” based on the standard definition, particularly since one of these abnormalities were abdominal obesity for 79% of overweight and 98% of obese women, irrespective of race/ethnicity. White obese women with three metabolic abnormalities did not have a statistically significantly increased cardiovascular risk compared with normal weight metabolically healthy women. Thus, cardiovascular disease risk appeared to be elevated in black women by the presence of only two or three metabolic abnormalities to a degree that would require four or more metabolic abnormalities among white women. These findings did not appear to be driven by any particular combination of metabolic abnormalities.
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MedicalResearch.com Interview with:
Martin Reinhardt, MD
Postdoctoral Fellow
PECRB, NIDDK, NIH
Phoenix, AZ 85016
Medical Research: What is the background for this study? What are the main findings?
Dr. Reinhardt: It can be very difficult for some people with obesity to lose weight despite great efforts. There is an immense deal of individual variability in weight loss success. Beyond differences in diet adherence, it is not clear what causes this variability in weight loss.
Through a study conducted at our facilities at the National Institutes of Health in Phoenix, Arizona, we have now shown that individual differences in biology – more precisely, differences in the amount of energy bodies use during fasting – make it difficult for certain obese people to lose weight.
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MedicalResearch.com Interview with:
Edward "Ted" Weiss, Ph.D.
Associate Professor
Department of Nutrition and Dietetics
Saint Louis University Saint Louis MO
Medical Research: What is the background for this study? What are the main findings?
Dr. Weiss: Results from one of our previous study yielded a surprising result that diet-induced weight loss improved insulin sensitivity (major diabetes risk factor) by the same amount as exercise induced weight loss. We thought that the exercise-induced weight loss would have yielded benefits from the weight loss itself but also from a weight loss-independent benefit that has been reported in other studies. One explanation for dietary restriction providing the same benefit of exercise was that it also provides benefits besides those that are attributable to weight loss. Our recently completed/published study was designed to evaluate this possibility and the finding do suggest what we hypothesized... i.e. that dietary restriction provides benefits above and beyond that which are attributable to weight loss.
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MedicalResearch.com Interview with: Dr Margaret Ashwell OBE, FAfN, RNutr (Public Health)
Ashwell Associates
Ashwell, Hertfordshire, United Kingdom.
Visiting Research Fellow, Oxford Brookes University
MedicalResearch: What are the main findings from this study?
Dr. Ashwell: In this study, the authors explore the differences in CVD risk factors between overweight and non-overweight people (by BMI) according to their shape (waist-to-height ratio -WHtR) Data for their analysis was taken from the Health Survey for England 2009 (HSE). They found significant differences in levels of total cholesterol (TC) and glycated haemoglobin (HbA1c—a measure of blood sugar control used to diagnose diabetes).
Out of 2917 people aged 16 years and over, 346 classified as ‘normal’ by BMI, have WHtR exceeding 0.5 (12% of the total,sample, or 34% of normal weight people). These could be called non-overweight ‘apples’, who have a lot of fat around the waist but not a high BMI.
The researchers classified the HSE population into four groups (2×2) using standard boundary values of BMI (above or below 25kg/m2) and WHtR (above or below 0.5). The group with ‘low/normal BMI but high WHtR (non-overweight ‘apples’) had significantly higher mean TC than the group with high BMI but low WHtR (overweight ‘pears’—people with a higher than normal BMI but less fat around the waist): 5.73mmol/L vs. 4.98mmol/L. Similarly, HbA1c levels were higher among non-overweight ‘apples’ than among overweight ‘pears’ (5.62% vs. 5.33%). These differences were similar and also significant in both sexes.
MedicalResearch: Why do you say that piece so string can be used for primary screening?
Dr. Ashwell: Since a good boundary value for waist-to-height ratio is 0.5, you don't even need a tape measure to screen those at risk. It can be done with a piece of string. Measure the height of child with string, fold it in half and see if it fits around his/her waist. If it doesn't, that child should proceed to the next stage of screening.
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MedicalResearch.com Interview with:
Matthew Pearce
NHS Gloucestershire Clinical Commissioning Group
UK
Medical Research: What is the background for this study? What are the main findings?
Response: Despite evidence to suggest that the prevalence of childhood obesity in the UK has stabilized in recent years, we know that approximately one in five children start their school life either overweight or obese, increasing to one in three children by the last year in primary school. Our research was the first to undertake an in-depth analysis on the UK’s National Child Measurement Programme (NCMP) and retrospectively track the weights of individual children over a 7-year period. Our study included a sample of 1863 children in South Gloucestershire, Bristol in the UK.
Our results were found to be similar to cross sectional data with obesity prevalence approximately doubling between the first (4/5yrs old) and last year (10/11yrs old) of primary school. Our findings provide little reassurance that those children who are obese in early childhood ‘grow out of ’ excess adiposity. Including overweight, we found that 84% of obese children at Reception year went on to be either overweight or obese by Year 6. Although previous studies have failed to identify any significant differences in BMI change between boys and girls during mid-childhood, our research found that more boys than girls dropped a weight category (from overweight or obese) by the time they reached Year 6. We found that the odds ratios of being overweight (BMI ?85th percentile) or obese (?95th percentile) based on BMI at Reception were similar to published literature. Our data found children who are within the upper range of the healthy weight category (75th–85th percentile) at Reception had an increased risk of being overweight or obese by the time they reach year 6. (more…)
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MedicalResearch.com Interview Invitation
Melanie J Davies MB ChB MD FRCP FRCGP
Professor of Diabetes Medicine
NIHR Senior Investigator
Leicester Diabetes Unit
Leicester Diabetes Centre
Bloom
University of Leicester
MedicalResearch: What is the background for this study? What are the main findings?
Dr. Davies: This study was designed to test the efficacy and safety of Liraglutide using a dose of 3mg for weight loss among patients with type 2 diabetes. It was a large international study in which we compared once daily subcutaneous Liraglutide at a dose of 3mg to Liraglutide 1.8mg which is the current maximum dose licenced in patients with diabetes and placebo. In all patients we offered a calorie deficit diet and lifestyle advice to increase physical activity. Our main findings were that the dose of 3mg of Liraglutide resulted in greater weight loss than both other arms of the study indeed 54% of patients at 56 weeks achieved more than 5% weight loss and a further 25% were able to achieve more than 10% weight loss. The 3mg of Liraglutide compared to the placebo, there were also significant impacts on HbA1c and other cardiovascular risk factors such as systolic blood pressure and lipids as well as improving patient quality of life particularly physical functioning and patient treatment satisfaction. (more…)
