POSSIBLE ROLE OF NUTRITION IN PREVENTION OF SARCOPENIA AND FALLS.

Objective: In this review, we analyze the foundation of sarcopenia as a potentially modifiable risk factor for falls, and we try to formulate practical strategies for nutritional interventions aimed at reducing the risk for sarcopenia and falls in our elderly patients. Methods: An extensive literature search was performed using the PubMed and the Google Scholar databases. Results: Falls are a common and costly source of injury and death in elderly adults. A large proportion of injurious falls are due to a trip or slip, suggesting that muscular factors are major determinants of both fall risk and the risk for fall-related injury. Conclusion: An increasing body of evidence links sarcopenia, the loss of muscle strength and mass that occurs with advancing age, with an increased risk for falls. Nutritional factors, as well as exercise, can help with both prevention and treatment of sarcopenia and may reduce the risk of falls in the elderly. Abbreviations: 25-OHD = 25-hydroxyvitamin D; EAA = essential amino acid; IGF-1 = insulin-like growth factor 1; IU = international units; MPS = muscle protein synthesis; PUFA = polyunsaturated fatty acid.

AGING, DIABETES, AND FALLS.

KEY POINTS Falls are a major health issue for older adults, leading to adverse events and even death. Older persons with type 2 diabetes are at increased risk of falling compared to healthy adults of a similar age. Over 400 factors are associated with falls risk, making identification and targeting of key factors to prevent falls problematic. However, the major risk factors include hypertension, diabetes, pain, and polypharmacy. In addition to age and polypharmacy, diabetes-related loss of strength, sensory perception, and balance secondary to peripheral neuropathy along with decline in cognitive function lead to increased risk of falling. Designing specific interventions to target strength and balance training, reducing polypharmacy to improve cognitive function, relaxation of diabetes management to avoid hypoglycemia and hypotension, and relief of pain will produce the greatest benefit for reducing falls in older persons with diabetes. Abbreviation: DPN = diabetic polyneuropathy.

AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY PROTOCOL FOR STANDARDIZED PRODUCTION OF CLINICAL PRACTICE GUIDELINES, ALGORITHMS, AND CHECKLISTS - 2017 UPDATE.

Clinical practice guideline (CPG), clinical practice algorithm (CPA), and clinical checklist (CC, collectively CPGAC) development is a high priority of the American Association of Clinical Endocrinologists (AACE) and American College of Endocrinology (ACE). This 2017 update in CPG development consists of (1) a paradigm change wherein first, environmental scans identify important clinical issues and needs, second, CPA construction focuses on these clinical issues and needs, and third, CPG provide CPA node/edge-specific scientific substantiation and appended CC; (2) inclusion of new technical semantic and numerical descriptors for evidence types, subjective factors, and qualifiers; and (3) incorporation of patient-centered care components such as economics and transcultural adaptations, as well as implementation, validation, and evaluation strategies. This third point highlights the dominating factors of personal finances, governmental influences, and third-party payer dictates on CPGAC implementation, which ultimately impact CPGAC development. The AACE/ACE guidelines for the CPGAC program is a successful and ongoing iterative exercise to optimize endocrine care in a changing and challenging healthcare environment. ABBREVIATIONS: AACE = American Association of Clinical Endocrinologists ACC = American College of Cardiology ACE = American College of Endocrinology ASeRT = ACE Scientific Referencing Team BEL = best evidence level CC = clinical checklist CPA = clinical practice algorithm CPG = clinical practice guideline CPGAC = clinical practice guideline, algorithm, and checklist EBM = evidence-based medicine EHR = electronic health record EL = evidence level G4GAC = Guidelines for Guidelines, Algorithms, and Checklists GAC = guidelines, algorithms, and checklists HCP = healthcare professional(s) POEMS = patient-oriented evidence that matters PRCT = prospective randomized controlled trial.

A PROMIS Measure of Neuropathic Pain Quality.

OBJECTIVES: Neuropathic pain (NP) is a consequence of many chronic conditions. This study aimed to develop an unidimensional NP scale with scores that represent levels of NP and distinguish between individuals with NP and non-NP conditions. METHODS: A candidate item pool of 42 pain quality descriptors was administered to participants with osteoarthritis, rheumatoid arthritis, diabetic neuropathy, and cancer chemotherapy-induced peripheral neuropathy. A subset of pain quality descriptors (items) that best distinguished between participants with and those without NP conditions were identified. Dimensionality of pain descriptors was evaluated in a development sample and cross-validated in a holdout sample. Item responses were calibrated using an item response theory model, and scores were generated on a T-score metric. NP scale scores were evaluated in terms of the reliability, validity, and ability to distinguish between participants with and without conditions typically associated with NP. RESULTS: Of the 42 initial items, 5 were identified for the Patient-Reported Outcome Measurement Information System (PROMIS) Neuropathic Pain Quality Scale. T scores exhibited good discriminatory ability on the basis of receiver-operator characteristic analysis. Score thresholds that optimize sensitivity and specificity were identified. Construct, criterion, and discriminant validity, and reliability of scale scores were supported. CONCLUSIONS: The five-item Patient-Reported Outcome Measurement Information System (PROMIS PQ-Neuro) Neuropathic Pain Quality Scale is a short and practical measure that can be used to identify patients more likely to have NP and to distinguish levels of NP. The data collected will support future research that targets other unidimensional pain quality domains (e.g., nociceptive pain).

American Association of Clinical Endocrinologists and American College of Endocrinology Protocol for Standardized Production of Clinical Practice Guidelines, Algorithms, and Checklists--2014 Update and the AACe G4G Program.

In 2010, the American Association of Clinical Endocrinologists (AACE) published an update to the original 2004 guidelines. This update hybridized strict evidence-based medicine methods with subjective factors and improved the efficiency of clinical practice guidelines (CPG) production, clinical applicability, and usefulness. Current and persistent shortcomings involving suboptimal implementation and protracted development timelines are addressed in the current 2014 update. The major advances include 1) formulation of an organizational educational strategy, represented by the AACE Council on Education, to address relevant teaching and decision-making tools for clinical endocrinologists, and to generate specific clinical questions to drive CPG, clinical algorithm (CA), and clinical checklist (CC) development; 2) creation and prioritization of printed and online CAs and CCs with a supporting evidence base; 3) focus on clinically relevant and question-oriented topics; 4) utilization of "cascades," where there can be more than 1 recommendation for 1 clinical question; and 5) incorporation of performance metrics to validate, optimize, and effectively update CPG, CAs, and CCs. Efforts continue to translate these clinical tools to electronic formats that can be integrated into a paperless healthcare delivery system, as well as applying them to diverse clinical settings by incorporating transcultural factors.

The association between cystic fibrosis-related diabetes and periodontitis in adults: A pilot cross-sectional study.

OBJECTIVES: Periodontitis is a highly prevalent complication of diabetes. However, the association between cystic fibrosis-related diabetes (CFRD) and periodontitis has not yet been evaluated. The objective of this study was to assess if: 1) CFRD is associated with periodontitis among adults with CF, and 2) periodontitis prevalence differs by CF and diabetes status. METHODS: This was a pilot cross-sectional study of the association between CFRD and periodontitis in adults with cystic fibrosis (CF) (N = 32). Historical non-CF controls (N = 57) from the U.S. National Health and Nutrition Examination Survey (NHANES) dataset were frequency matched to participants with CF on age, sex, diabetes status, and insulin use. We defined periodontitis using the U.S. Centers for Disease Control and Prevention and the American Academy of Periodontology (CDC/AAP) case definition, as the presence of two or more interproximal sites with CAL ≥3 mm and two or more interproximal sites with PD ≥4 mm (not on the same tooth) or one site with PD ≥5 mm. Because NHANES periodontal data were only available for adults ages ≥30 years, our analysis that included non-CF controls focused on this age group (CF N = 19, non-CF N = 57). Based on CF and diabetes status, we formed four groups: CFRD, CF and no diabetes, non-CF with diabetes, and non-CF and no diabetes (healthy). We used the Fisher's exact test for hypotheses testing. RESULTS: There was no association between CFRD and periodontitis for participants with CF ages 22-63 years (CFRD 67% vs. CF no diabetes 53%, P = 0.49), this was also true for those ages ≥30 years (CFRD 78% vs. CF no diabetes 60%, P = 0.63). For the two CF groups, the prevalence of periodontitis was significantly higher than for healthy controls (CFRD 78% vs. healthy 7%, P<0.001; CF no diabetes 60% vs. healthy 7%, P = 0.001) and not significantly different than the prevalence for non-CF controls with diabetes (CFRD 78% vs. non-CF with diabetes 56%, P = 0.43; CF no diabetes 60% vs. non-CF with diabetes 56%, P = 0.99). CONCLUSION: Among participants with CF, CFRD was not associated with periodontitis. However, regardless of diabetes status, participants with CF had increased prevalence of periodontitis compared to healthy controls.

Periodontitis Risk Factors in Adults with Cystic Fibrosis: A pilot study.

Purpose Individuals with cystic fibrosis (CF) present with multiple condition-specific risk factors for periodontitis including CF-related diabetes, chronic inhaled treatments that induce xerostomia, and increased systemic inflammation because of frequent lung infections. General factors like age, oral hygiene, and diet may also contribute to the risk of periodontitis. However the relative importance of these specific risk factors and periodontitis in individuals with CF has not yet been evaluated. The purpose of this pilot study was to assess the associations between CF condition-specific and general risk factors and the prevalence of periodontitis in adults with CF.Methods This cross-sectional pilot study was designed to assess a multifactorial model of periodontitis risk factors in a population in adults with CF who were recruited from the University of Washington Adult CF center. Periodontitis was defined using the Centers for Disease Control and Prevention and the American Academy of Periodontology (CDC/AAP) case definition. Risk factors included condition-specific and general factors. Differences between participants with moderate/severe periodontitis and those with no/mild periodontitis was assessed using the Mann-Whitney test, the Fisher's exact test, and the exact chi-square test (α=0.05).Results Thirty-two participants were enrolled. Twenty-eight percent of the participants had moderate periodontitis, 72% had no/mild periodontitis; none of the participants had severe periodontitis. There were no significant differences in condition-specific factors between between the two study groups. Participants with moderate periodontitis were older (p=0.028) and reported daily flossing in higher proportions than those with no/mild periodontitis (p=0.023).Conclusions The findings from this pilot study suggest that future research is needed to determine whether sociodemographic and other general risk factors are more important contributors to periodontitis risk than CF-specific factors.

Glucose time in range and peripheral neuropathy in type 2 diabetes mellitus and chronic kidney disease.

​OBJECTIVE: Compared with hemoglobin A1c (HbA1c), continuous glucose monitoring (CGM) may better capture risk of diabetes complications in patients with chronic kidney disease (CKD), including diabetic peripheral neuropathy (DPN). We hypothesized that glucose time in range (TIR), measured by CGM, is associated with DPN symptoms among participants with type 2 diabetes mellitus (type 2 DM) and moderate-to-severe CKD. ​RESEARCH DESIGN AND METHODS: We enrolled 105 people with type 2 DM treated with insulin or sulfonylurea, 81 participants with CKD (estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2) and 24 matched control participants with eGFR ≥60 mL/min/1.73 m2. Each participant wore a CGM for two 6-day periods. Calculated glycemic measures included TIR (glucose 70-180 mg/dL) and glucose management indicator (GMI). DPN symptoms were assessed using the Michigan Neuropathy Screening Instrument (MNSI) questionnaire, with a positive MNSI score defined as ≥2 symptoms. ​RESULTS: Participants with CKD had a mean age of 68 years, diabetes duration 20 years, eGFR 38 mL/min/1.73 m2 and HbA1c 7.8%, 61 mmol/mol. Sixty-two participants reported ≥2 DPN symptoms, 51 (63%) with CKD and 11 (46%) controls. Less TIR and higher GMI were associated with higher risk of MNSI questionnaire score ≥2 (OR 1.25 (95% CI 1.02 to 1.52) per 10% lower TIR, and OR 1.79 (95% CI 1.05 to 3.04) per 1% higher GMI, adjusting for age, gender and race). Similar results were observed when analyses were restricted to participants with CKD. In contrast, there was no significant association of HbA1c with DPN symptoms. ​CONCLUSIONS: Symptoms of DPN were common among participants with long-standing type 2 DM and CKD. Lower TIR and higher GMI were associated with DPN symptoms.

Continuous Glucose Monitoring and Use of Alternative Markers To Assess Glycemia in Chronic Kidney Disease.

OBJECTIVE: In chronic kidney disease, glycated albumin and fructosamine have been postulated to be better biomarkers of glycemic control than HbA1c. We evaluated the accuracy, variability, and covariate bias of three biomarkers (HbA1c, glycated albumin, and fructosamine) compared with continuous glucose monitoring (CGM)-derived measurement of glycemia across estimated glomerular filtration rate (eGFR) in type 2 diabetes. RESEARCH DESIGN AND METHODS: A prospective cohort study was conducted of 104 participants with type 2 diabetes, 80 with eGFR <60 mL/min/1.73 m2 (not treated with dialysis) and 24 frequency-matched control subjects with eGFR ≥60 mL/min/1.73 m2. Participants wore a blinded CGM for two 6-day periods separated by 2 weeks, with blood and urine collected at the end of each CGM period. HbA1c, glycated albumin, and fructosamine were measured by high-performance liquid chromatographic, enzymatic, and colorimetric nitroblue tetrazolium methods, respectively. RESULTS: Within-person biomarker values were strongly correlated between the two CGM periods (r = 0.92-0.95), although no marker fully captured the within-person variability of mean CGM glucose. All markers were similarly correlated with mean CGM glucose (r = 0.71-77). Compared with mean CGM glucose, glycated albumin and fructosamine were significantly biased by age, BMI, serum iron concentration, transferrin saturation, and albuminuria; HbA1c was underestimated in those with albuminuria. CONCLUSIONS: Glycated albumin and fructosamine were not less variable than HbA1c at a given mean CGM glucose level, with several additional sources of bias. These results support measuring HbA1c to monitor trends in glycemia among patients with eGFR <60 mL/min/1.73 m2. Direct measurements of glucose are necessary to capture short-term variability.

Continuous glucose monitoring technology for personal use: an educational program that educates and supports the patient.

PURPOSE: The purpose of this article is to describe the development and implementation of an educational program for the initiation of real-time continuous glucose monitoring (CGM) technology for personal use, not 3-day CGMS diagnostic studies. The education program was designed to meet the needs of patients managing their diabetes with either diabetes medications or insulin pump therapy in an outpatient diabetes education center using a team-based approach. METHODS: Observational research, complemented by literature review, was used to develop an educational program model and teaching strategies. Diabetes educators, endocrinologists, CGM manufacturer clinical specialists, and patients with diabetes were also interviewed for their clinical observations and experience. RESULTS: The program follows a progressive educational model. First, patients learn in-depth about real-time CGM technology by attending a group presensor class that provides detailed information about CGM. This presensor class facilitates self-selection among patients concerning their readiness to use real-time CGM. If the patient decides to proceed with real-time CGM use, CGM initiation is scheduled, using a clinic-centered protocol for both start-up and follow-up. CONCLUSIONS: Successful use of real-time CGM involves more than just patient enthusiasm or interest in a new technology. Channeling patient interest into a structured educational setting that includes the benefits and limitations of real-time CGM helps to manage patient expectations.

Rates of Cardiac Rhythm Abnormalities in Patients with CKD and Diabetes.

BACKGROUND AND OBJECTIVES: Cardiac arrhythmias increase mortality and morbidity in CKD. We evaluated the rates of subclinical arrhythmias in a population with type 2 diabetes and patients with moderate to severe CKD who were not on dialysis. DESIGN, SETTING, PARTICIPANTS & MEASUREMENTS: This is a prospective observational study, using continuous ambulatory cardiac monitors to determine the rate of atrial and ventricular arrhythmias, as well as conduction abnormalities in this group. RESULTS: A total of 38 patients (34% women), with mean eGFR of 38±13 ml/min per 1.73 m2, underwent ambulatory cardiac monitoring for 11.2±3.9 days. The overall mean rate of any cardiac arrhythmia was 88.8 (95% confidence interval [95% CI], 27.1 to 184.6) episodes per person-year (PY). A history of cardiovascular disease was associated with a higher rate of detected arrhythmia (rate ratio, 5.87; 95% CI, 1.37 to 25.21; P<0.001). The most common arrhythmia was atrial fibrillation, which was observed in two participants with known atrial fibrillation and was a new diagnosis in four patients (11%), none of whom experienced symptoms. Overall, atrial fibrillation episodes occurred at a rate of 37.6 (95% CI, 2.4 to 112.3) per PY. Conduction abnormalities were found in eight patients (21%), a rate of 26.5 (95% CI, 4.2 to 65.5) per PY. Rates of ventricular arrhythmias were low (14.5 per PY; 95% CI, 4.3 to 32.0) and driven by premature ventricular contractions. CONCLUSIONS: Cardiac rhythm abnormalities are common in patients with diabetes with moderate to severe CKD not requiring dialysis. Rates of atrial fibrillation are high and episodes are asymptomatic. Future studies are needed to determine the role of screening and upstream therapy of cardiac arrhythmias in this group.

Hypoglycemia in People with Type 2 Diabetes and CKD.

BACKGROUND AND OBJECTIVES: Among people with diabetes mellitus, CKD may promote hypoglycemia through altered clearance of glucose-lowering medications, decreased kidney gluconeogenesis, and blunted counter-regulatory response. We conducted a prospective observational study of hypoglycemia among 105 individuals with type 2 diabetes treated with insulin or a sulfonylurea using continuous glucose monitors. DESIGN, SETTING, PARTICIPANTS & MEASUREMENTS: We enrolled 81 participants with CKD, defined as eGFR<60 ml/min per 1.73 m2, and 24 control participants with eGFR≥60 ml/min per 1.73 m2 frequency-matched on age, duration of diabetes, hemoglobin A1c, and glucose-lowering medications. Each participant wore a continuous glucose monitor for two 6-day periods. We examined rates of sustained level 1 hypoglycemia (<70 mg/dl) and level 2 hypoglycemia (<54 mg/dl) among participants with CKD. We then tested differences compared with control participants as well as a second control population (n=73) using Poisson and linear regression, adjusting for age, sex, and race. RESULTS: Over 890 total days of continuous glucose monitoring, participants with CKD were observed to have 255 episodes of level 1 hypoglycemia, of which 68 episodes reached level 2 hypoglycemia. Median rate of hypoglycemic episodes was 5.3 (interquartile range, 0.0-11.7) per 30 days and mean time spent in hypoglycemia was 28 (SD 37) minutes per day. Hemoglobin A1c and the glucose management indicator were the main clinical correlates of time in hypoglycemia (adjusted differences 6 [95% confidence interval, 2 to 10] and 13 [95% confidence interval, 7 to 20] fewer minutes per day per 1% higher hemoglobin A1c or glucose management indicator, respectively). Compared with control populations, participants with CKD were not observed to have significant differences in time in hypoglycemia (adjusted differences 4 [95% confidence interval, -12 to 20] and -12 [95% confidence interval, -29 to 5] minutes per day). CONCLUSIONS: Among people with type 2 diabetes and moderate to severe CKD, hypoglycemia was common, particularly with tighter glycemic control, but not significantly different from groups with similar clinical characteristics and preserved eGFR.

Immunosuppressive agents: effects on glucose and lipid metabolism.

Immunosuppressive therapies are critical elements in successful organ transplantation. Although immunosuppressant drugs are essential in preventing graft rejection and graft maintenance after transplantation, their use is complicated by adverse effects, many being detrimental to graft and even patient long-term survival. Commonly used agents are associated with dysregulated glucose metabolism and dyslipidemia. This article focuses on the effects of immunosuppressive agents on glucose and lipid metabolism. Adrenal effects of these drugs, where known, also are discussed.

Diabetic neuropathy, the great masquerader: truncal neuropathy manifesting as abdominal pseudohernia.

OBJECTIVE: To describe a patient with diabetic truncal neuropathy and suggest a helpful diagnostic approach to this entity. METHODS: We present a case report, with a focus on physical, computed tomographic, and electromyographic findings. RESULTS: Because of an extensive differential diagnosis, diabetic truncal neuropathy is a rarely recognized and often misdiagnosed condition in patients with diabetes mellitus. In a 55-year-old man with a 13-year history of diabetes but no retinopathy, vasculopathy, or nephropathy, pain and a visible bulge in the left lower abdominal quadrant prompted radiographic assessment of the abdomen. A computed tomographic scan of the abdomen disclosed no mass but a weakening of the abdominal musculature suggestive of a pseudohernia. Subsequent electromyography showed evidence of polyradicular neuropathy. The patient was given treatment for pain control, and the pseudohernia resolved within 1 year. CONCLUSION: In patients with diabetes who have a painful abdominal mass, the potential presence of a diabetic truncal neuropathy should be considered.

Improving Type 2 Diabetes Patient Health Outcomes with Individualized Continuing Medical Education for Primary Care.

INTRODUCTION: This study provided physicians with continuing medical education (CME) related to type 2 diabetes and evaluated the effect on patient health outcomes. METHODS: Physicians participated in multi-platform CME (live and online programs) and completed a 25 item questionnaire for patient baseline (3-months pre-CME activity) and follow-up visits (≥6-months post-CME activity). Changes in physician knowledge and patient health outcomes were evaluated. RESULTS: 34 physicians completed both phases of the CME curricula and submitted data for 264 patients. Significant improvements were observed in physician knowledge after the live (p < 0.05) and online programs (p < 0.0005). Mean patient glycated hemoglobin (HbA1c) absolute reduction of 1.15% (p < 0.0001) was reported. CONCLUSIONS: CME is an effective tool to close established practice gaps and potentially help improve patient health outcomes.

Association of the magnitude of weight loss and changes in physical fitness with long-term cardiovascular disease outcomes in overweight or obese people with type 2 diabetes: a post-hoc analysis of the Look AHEAD randomised clinical trial.

BACKGROUND: Findings from the Look AHEAD trial showed no significant reductions in the primary outcome of cardiovascular disease incidence in adults with type 2 diabetes randomly assigned to an intensive lifestyle intervention for weight loss compared with those randomly assigned to diabetes support and education (control). We examined whether the incidence of cardiovascular disease in Look AHEAD varied by changes in weight or fitness. METHODS: Look AHEAD was a randomised clinical trial done at 16 clinical sites in the USA, recruiting patients from Aug 22, 2001, to April 30, 2004. In the trial, 5145 overweight or obese adults aged 45-76 years with type 2 diabetes were assigned (1:1) to an intensive lifestyle intervention or diabetes support and education. In this observational, post-hoc analysis, we examined the association of magnitude of weight loss and fitness change over the first year with incidence of cardiovascular disease. The primary outcome of the trial and of this analysis was a composite of death from cardiovascular causes, non-fatal acute myocardial infarction, non-fatal stroke, or admission to hospital for angina. The secondary outcome included the same indices plus coronary artery bypass grafting, carotid endartectomy, percutaneous coronary intervention, hospitalisation for congestive heart failure, peripheral vascular disease, or total mortality. We adjusted analyses for baseline differences in weight or fitness, demographic characteristics, and risk factors for cardiovascular disease. The Look AHEAD trial is registered with ClinicalTrials.gov, number NCT00017953. FINDINGS: For the analyses related to weight change, we excluded 311 ineligible participants, leaving a population of 4834; for the analyses related to fitness change, we excluded 739 participants, leaving a population of 4406. In analyses of the full cohort (ie, combining both study groups), over a median 10·2 years of follow-up (IQR 9·5-10·7), individuals who lost at least 10% of their bodyweight in the first year of the study had a 21% lower risk of the primary outcome (adjusted hazard ratio [HR] 0·79, 95% CI 0·64-0·98; p=0·034) and a 24% reduced risk of the secondary outcome (adjusted HR 0·76, 95% CI 0·63-0·91; p=0·003) compared with individuals with stable weight or weight gain. Achieving an increase of at least 2 metabolic equivalents in fitness change was associated with a significant reduction in the secondary outcome (adjusted HR 0·77, 95% CI 0·61-0·96; p=0·023) but not the primary outcome (adjusted HR 0·78, 0·60-1·03; p=0·079). In analyses treating the control group as the reference group, participants in the intensive lifestyle intervention group who lost at least 10% of their bodyweight had a 20% lower risk of the primary outcome (adjusted HR 0·80, 95% CI 0·65-0·99; p=0·039), and a 21% lower risk of the secondary outcome (adjusted HR 0·79, 95% CI 0·66-0·95; p=0·011); however, change in fitness was not significantly associated with a change in the primary outcome. INTERPRETATION: The results of this post-hoc analysis of Look AHEAD suggest an association between the magnitude of weight loss and incidence of cardiovascular disease in people with type 2 diabetes. These findings suggest a need to continue to refine approaches to identify individuals who are most likely to benefit from lifestyle interventions and to develop strategies to improve the magnitude of sustained weight loss with lifestyle interventions. FUNDING: US National Institute of Diabetes and Digestive and Kidney Diseases.