Amy E. Rothberg

The impact of a managed care obesity intervention on clinical outcomes and costs: A prospective observational study

To evaluate the impact of a managed care obesity intervention that requires enrollment in an intensive medical weight management program, a commercial weight loss program, or a commercial pedometer‐based walking program to maintain enhanced benefits.

Association Between Metabolic Syndrome Components and Polyneuropathy in an Obese Population

Importance Past studies have shown an association between metabolic syndrome and polyneuropathy, but the precise components that drive this association remain unclear. Objectives To determine the prevalence of polyneuropathy stratified by glycemic status in well-characterized obese and lean participants and investigate the association of specific components of metabolic syndrome with polyneuropathy. Design, Setting, and Participants We performed a cross-sectional, observational study from November 1, 2010, to December 31, 2014, in obese participants (body mass index [calculated as weight in kilograms divided by height in meters squared] of 35 or more with no comorbid conditions or 32 or more with at least 1 comorbid condition) from a weight management program and lean controls from a research website. The prevalence of neuropathy, stratified by glycemic status, was determined, and a Mantel-Haenszel χ2 test was used to investigate for a trend. Logistic regression was used to model the primary outcome of polyneuropathy as a function of the components of metabolic syndrome after adjusting for demographic factors. Participants also completed quantitative sudomotor axon reflex testing, quantitative sensory testing, the neuropathy-specific Quality of Life in Neurological Disorders instrument, and the short-form McGill Pain Questionnaire. Exposures Components of metabolic syndrome (as defined by the National Cholesterol Education Program Adult Treatment Panel III), including glycemic status (as defined by the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus). Main Outcomes and Measures Toronto consensus definition of probable polyneuropathy. Secondary outcomes included intraepidermal nerve fiber density and nerve conduction study parameters. Results We enrolled 102 obese participants (mean [SD] age, 52.9 [10.2] years; 48 men and 54 women; 45 with normoglycemia [44.1%], 31 with prediabetes [30.4%], and 26 with type 2 diabetes [25.5%]) and 53 lean controls (mean [SD] age, 48.5 [9.9] years; 16 men and 37 women). The prevalence of polyneuropathy was 3.8% in lean controls (n = 2), 11.1% in the obese participants with normoglycemia (n = 5), 29% in the obese participants with prediabetes (n = 9), and 34.6% in the obese participants with diabetes (n = 9) (P < .01 for trend). Age (odds ratio, 1.09; 95% CI, 1.02-1.16), diabetes (odds ratio, 4.90; 95% CI, 1.06-22.63), and waist circumference (odds ratio, 1.24; 95% CI, 1.00-1.55) were significantly associated with neuropathy in multivariable models. Prediabetes (odds ratio, 3.82; 95% CI, 0.95-15.41) was not significantly associated with neuropathy. Conclusions and Relevance The prevalence of polyneuropathy is high in obese individuals, even those with normoglycemia. Diabetes, prediabetes, and obesity are the likely metabolic drivers of this neuropathy. Trial Registration clinicaltrials.gov Identifier: NCT02689661.

Endogenous Opioid Mechanisms Are Implicated in Obesity and Weight Loss in Humans

CONTEXT Successful long-term weight loss is challenging. Brain endogenous opioid systems regulate associated processes; however, their role in the maintenance of weight loss has not been adequately explored in humans. OBJECTIVE In a preliminary study, the objective was to assess central μ-opioid receptor (MOR) system involvement in eating behaviors and their relationship to long-term maintenance of weight loss. DESIGN This was a case-control study with follow-up of the treatment group at 1 year after intervention. SETTING The study was conducted at a tertiary care university medical center. PARTICIPANTS Lean healthy (n = 7) and chronically obese (n = 7) men matched for age and ethnicity participated in the study. INTERVENTIONS MOR availability measures were acquired with positron emission tomography and [(11)C]carfentanil. Lean healthy men were scanned twice under both fasted and fed conditions. Obese men were placed on a very low-calorie diet to achieve 15% weight loss from baseline weight and underwent two positron emission tomography scans before and two after weight loss, incorporating both fasted and fed states. MAIN OUTCOME MEASURES Brain MOR availability and activation were measured by reductions in MOR availability (nondisplaceable binding potential) from the fed compared with the fasted-state scans. RESULTS Baseline MOR nondisplaceable binding potential was reduced in obese compared with the lean and partially recovered obese after weight loss in regions that regulate homeostatic, hedonic, and emotional responses to feeding. Reductions in negative affect and feeding-induced MOR system activation in the right temporal pole were highly correlated in leans but not in obese men. A trend for an association between MOR activation in the right temporal pole before weight loss and weight regain 1 year was found. CONCLUSIONS Although these preliminary studies have a small sample size, these results suggest that obesity and diet-induced weight loss impact central MOR binding and endogenous opioid system function. MOR system activation in response to an acute meal may be related to the risk of weight regain.

Very-low-energy diet for type 2 diabetes: An underutilized therapy?

BACKGROUND Current approaches to the management of type 2 diabetes focus on the early initiation of novel pharmacologic therapies and bariatric surgery. OBJECTIVE The purpose of this study was to revisit the use of intensive, outpatient, behavioral weight management programs for the management of type 2 diabetes. DESIGN Prospective observational study of 66 patients with type 2 diabetes and BMI ≥ 32 kg/m² who enrolled in a program designed to produce 15% weight reduction over 12 weeks using total meal replacement and low- to moderate-intensity physical activity. RESULTS Patients were 53 ± 7 years of age (mean ± SD) and 53% were men. After 12 weeks, BMI fell from 40.1 ± 6.6 to 35.1 ± 6.5 kg/m². HbA1c fell from 7.4% ± 1.3% to 6.5% ± 1.2% (57.4 ± 12.3 to 47.7 ± 12.9 mmol/mol) in patients with established diabetes: 76% of patients with established diabetes and 100% of patients with newly diagnosed diabetes achieved HbA1c <7.0% (53.0 mmol/mol). Improvement in HbA1c over 12 weeks was associated with higher baseline HbA1c and greater reduction in BMI. CONCLUSIONS An intensive, outpatient, behavioral weight management program significantly improved HbA1c in patients with type 2 diabetes over 12 weeks. The use of such programs should be encouraged among obese patients with type 2 diabetes.

Prevalence of Diabetes in the United States: A Glimmer of Hope?

Obesity is a major risk factor for type 2 diabetes. The prevalence of obesity in US adults, defined as a body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) of 30 or greater, changed little instances, total diabetes was defined as the sum of the cases of diagnosed and undiagnosed diabetes. In 2011-2012, using the hemoglobin A1c, FPG, or 2-hour plasma glucose diabetes definition, the unadjusted prevalence was 14.3% for total diabetes, 9.1% for diagnosed diaRelated article page 1021 between 1960 and 1980 (from 13% in 1960 to 15% in betes, and 5.2% for undiagnosed diabetes. The prevalence of total diabetes was higher in older age groups but similar 1980). Subsequently, between 1980 and 2000, the prevalence of obesity in the United States doubled from 15% to 31%.1 Since then, there has been relatively little change in the prevalence of obesity among infants and toddlers, children and adolescents, or adults. Nevertheless, the prevalence of obesity is high with 8% of infants and toddlers, 17% of those aged 2 to 19 years, and 35% of US adults aged 20 years or older estimated to be obese.2,3 An earlier study of trends in diagnosed diabetes among US adults demonstrated stable incidence and prevalence rates between 1980 and 1990 and sharp increases in both incidence and prevalence each year between 1990 and 2008, but a leveling off of diabetes prevalence and a possible decrease in diabetes incidence between 2008 and 2012.4 In this issue of JAMA, Menke and colleagues5 analyzed data from the National Health and Nutrition Examination Survey (NHANES) to estimate the prevalence of total, diagnosed, and undiagnosed diabetes in US adults in 2011-2012 and to update national trends between 1988 and 2012. The authors defined diagnosed diabetes as self-report of a previous diagnosis of diabetes. Depending on the availability of data, they used 2 definitions for undiagnosed diabetes: (1) a hemoglobin A1c level of 6.5% or greater, a fasting plasma glucose (FPG) level of 126 mg/dL or greater, or a 2-hour plasma glucose (2 hours after a 75 g oral glucose load) level of 200 mg/dL or greater or (2) a hemoglobin A1c level of 6.5% or greater or an FPG level of 126 mg/dL or greater. In both among men and women. Compared with non-Hispanic white participants in whom the age-standardized prevalence of total diabetes was 11.3%, the prevalence of total diabetes was higher in non-Hispanic black (21.8%) and Hispanic (22.6%) participants and marginally higher in nonHispanic Asian (20.6%) participants. The percentage of people with diabetes who were undiagnosed was higher among non-Hispanic Asian (50.9%) and Hispanic participants (49.0%) than among non-Hispanic black (36.8%) and non-Hispanic white (32.3%) participants. Using the hemoglobin A1c or FPG diabetes definition, the age-standardized prevalence of total diabetes increased from 9.8% in 1988-1994 to 12.5% in 2007-2008, but remained at approximately 12% between 2008 and 2012. The increase in diabetes prevalence between 1988 and 2012 was due to an increase in diagnosed diabetes. Indeed, the age-standardized percentage of total diabetes that was undiagnosed decreased from 40.3% in 1988-1994 to 31.0% in 2011-2012 in the entire US population. The percentage of total diabetes that was undiagnosed did not decrease significantly in people aged 20 to 44 years (40% in 1988 and 40% in 2012). These findings suggest that the recommendations issued by the US Surgeon General6 and the Institute of Medicine,7 the implementation of food, nutrition, agricultural, and physical activity policies and regulations by federal, state, and local governments,8 and the focus on individual behavioral change related to diet and physical activity by the US Centers for Disease Control and Prevention9 (CDC) have

Obesity and Diabetes in an Aging Population: Time to Rethink Definitions and Management?

Regardless of pathophysiology and diagnostic criteria, the population of older adults with diabetes is highly heterogeneous. As adults with type 2 diabetes age and develop multiple comorbid health conditions, they may experience many challenges to good diabetes care and self-management. Age of diagnosis and duration of diabetes largely determine the likelihood for comorbidity. Treating such a diverse elderly population may result in inadequate glycemic control either because of overtreatment, leading to hypoglycemia, or because of other complications and preexisting comorbidities. It is imperative that treatment decisions are based on patient preferences, unique and likely evolving health status, and longevity.

Impact of weight loss on waist circumference and the components of the metabolic syndrome

Objective Central adiposity is a component of the metabolic syndrome (MetS). Little is known about the impact of medical weight loss and decreased waist circumference (WC) on the MetS. Our objective was to assess the impact of changes in WC on blood pressure, lipids and glycemia. Research design and methods We studied 430 obese patients enrolled in a 2-year, intensive, behavioral, weight management program. We report results for participants who completed 6-month and 2-year follow-up. Results Participants were 49±9 years of age (mean±SD), 56% were women and 85% were white. Baseline body mass index (BMI) was 41±6 kg/m2 and baseline WC was 120±14 cm. At 6 months, BMI decreased by 6±3 kg/m2 and WC by 14±9 cm. Relative change in WC was defined as the 6-month or 2-year WC minus the baseline WC divided by the baseline WC. Systolic blood pressure decreased by 8 mm Hg for the tertile of participants with the largest relative decrease in WC and by 2 mm Hg for those with the smallest relative decrease in WC (p=0.025). Similar patterns of improvement were observed in total cholesterol (−29 vs −12 mg/dL, p=0.017), low-density lipoprotein-cholesterol (−19 vs −4 mg/dL, p=0.033), and glycated hemoglobin (−1.2 vs −0.3%, p=0.006). At 2 years, BMI decreased by 5±4 kg/m2 and WC by 11±11 cm and similar patterns of improvements were seen in components of the MetS. At both 6 months and 2 years, larger relative decreases in WC were associated with greater improvements in lipids and glycemia independent of sex. Conclusions In obese people, greater relative decreases in WC with medical weight loss are associated with greater improvements in components of the MetS independent of sex.

Evaluation of intensity drift correction strategies using MetaboDrift, a normalization tool for multi-batch metabolomics data

In recent years, mass spectrometry-based metabolomics has increasingly been applied to large-scale epidemiological studies of human subjects. However, the successful use of metabolomics in this context is subject to the challenge of detecting biologically significant effects despite substantial intensity drift that often occurs when data are acquired over a long period or in multiple batches. Numerous computational strategies and software tools have been developed to aid in correcting for intensity drift in metabolomics data, but most of these techniques are implemented using command-line driven software and custom scripts which are not accessible to all end users of metabolomics data. Further, it has not yet become routine practice to assess the quantitative accuracy of drift correction against techniques which enable true absolute quantitation such as isotope dilution mass spectrometry. We developed an Excel-based tool, MetaboDrift, to visually evaluate and correct for intensity drift in a multi-batch liquid chromatography - mass spectrometry (LC-MS) metabolomics dataset. The tool enables drift correction based on either quality control (QC) samples analyzed throughout the batches or using QC-sample independent methods. We applied MetaboDrift to an original set of clinical metabolomics data from a mixed-meal tolerance test (MMTT). The performance of the method was evaluated for multiple classes of metabolites by comparison with normalization using isotope-labeled internal standards. QC sample-based intensity drift correction significantly improved correlation with IS-normalized data, and resulted in detection of additional metabolites with significant physiological response to the MMTT. The relative merits of different QC-sample curve fitting strategies are discussed in the context of batch size and drift pattern complexity. Our drift correction tool offers a practical, simplified approach to drift correction and batch combination in large metabolomics studies.

Professional practice committee

The Professional Practice Committee (PPC) of the American Diabetes Association (ADA) is responsible for the “Standards of Medical Care in Diabetes” position statement, referred to as the “Standards of Care.” The PPC is a multidisciplinary expert committee comprised of physicians, diabetes educators, registered dietitians, and others who have expertise in a range of areas, including adult and pediatric endocrinology, epidemiology, public health, lipid research, hypertension, preconception planning, and pregnancy care. Appointment to the PPC is based on excellence in clinical practice and research. Although the primary role of the PPC is to review and update the Standards of Care, it is also responsible for overseeing the review and revision of ADA’s position statements and scientific statements. The ADA adheres to the Institute of Medicine Standards for Developing Trustworthy Clinical Practice Guidelines. All members of the PPC are required to disclose potential conflicts of interest with industry and/or other relevant organizations. These disclosures are discussed at the onset of each Standards of Care revision meeting. Members of the committee, their employer, and their disclosed conflicts of interest are listed in the “Professional Practice Committee Disclosures” table (see p. S130). For the current revision, PPC members systematically searched MEDLINE for human studies related to each section and published since 1 January 2016. Recommendations were revised based on new evidence or, in some cases, to clarify the prior recommendation or match the strengthof thewording to the strength of theevidence.A table linking the changes in recommendations to new evidence can be reviewed at http://professional .diabetes.org/SOC. As for all position statements, the Standards of Care position statement was approved by the Executive Committee of ADA’s Board of Directors, which includes health care professionals, scientists, and lay people. Feedback from the larger clinical communitywas valuable for the 2017 revision of the Standards of Care. Readers who wish to comment on the 2017 Standards of Care are invited to do so at http://professional.diabetes.org/SOC. The ADA funds development of the Standards of Care and all ADA position statements out of its general revenues and does not use industry support for these purposes. The PPC would like to thank the following individuals who provided their expertise in reviewing and/or consulting with the committee: Conor J. Best, MD; William T. Cefalu, MD; Mary de Groot, PhD; Gary D. Hack, DDS; Silvio E. Inzucchi, MD; Meghan Jardine, MS, MBA, RD, LD, CDE; Victor R. Lavis, MD; Mark E. Molitch, MD; Antoinette Moran, MD; Matt Petersen; Sean Petrie; Louis H. Philipson, MD, PhD; Margaret A. Powers, PhD, RD, CDE; Desmond Schatz, MD; Philip R. Schauer, MD; Sonali N. Thosani, MD; and Guillermo E. Umpierrez, MD.

Improvement in the Spatial Distribution of Pain, Somatic Symptoms, and Depression After a Weight Loss Intervention

Weight loss is known to improve pain localized to weight-bearing joints but it is not known how weight loss affects the spatial distribution of pain and associated somatic symptoms like fatigue. We sought to determine if weight loss using a low-calorie diet improves pain, affect, and somatic symptoms commonly associated with chronic pain conditions in an observational study. We also documented changes in inflammatory markers in serum before and after weight loss. Participants were 123 obese individuals undergoing a 12- to 16-week calorie restriction weight loss intervention. The spatial distribution of pain, symptom severity (eg, fatigue, sleep difficulties), depression, and total fibromyalgia scale scores were measured before and after weight loss. Pain (P = . 022), symptom severity (P = .004), depression (P < .001), and fibromyalgia scores (P = .004) improved after weight loss; men showed greater improvement than women on somatic symptoms and fibromyalgia scores (both P < .01). Those who lost at least 10% of body weight showed greater improvement than those who lost <10%. Levels of the regulatory cytokine interleukin-10 increased after the intervention (P = .002). Weight loss may improve diffuse pain and comorbid symptoms commonly seen in chronic pain participants. PERSPECTIVE This article presents the effect of a weight loss intervention on characteristics of chronic pain, including the spatial distribution of pain and comorbid somatic symptoms. Weight loss appeared to produce larger improvements in somatic symptoms for men.