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Marie-Pierre St-Onge,1 Gary Zammit,2 David M Reboussin,3 Samuel T Kuna,4 Mark H Sanders,8 Richard Millman,6 Anne B Newman,5 Thomas A Wadden,4 Rena R Wing,6 F Xavier Pi-Sunyer,1 Gary D Foster7 Sleep AHEAD Research Group*1New York Obesity Research Center, St Luke's/Roosevelt Hospital, New York, NY, USA; 2Clinilabs, New York, NY, USA; 3Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA; 4Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA; 5Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA, USA; 6Department of Psychiatry and Human Behavior, Brown University, Providence, RI, USA; 7Center for Obesity Research and Education, Temple University, Philadelphia, PA, USA; 8Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh, PA, USA*A full list of the members of the Sleep AHEAD Research Group is available in an online appendixPurpose: Some studies have found an association between sleep disturbances and metabolic risk, but none has examined this association in individuals with type 2 diabetes. The objective of this study was to determine the relationship between sleep disturbances and metabolic risk factors in obese patients with type 2 diabetes.Patients and methods: This study was a cross-sectional examination of the relationship between sleep parameters (apnea/hypopnea index [AHI], time spent in various sleep stages) and metabolic risk markers (fasting glucose, hemoglobin A1c, lipids) using baseline data of the Sleep AHEAD cohort. Subjects (n = 305) were participants in Sleep AHEAD (Action for Health in Diabetes), a four-center ancillary study of the Look AHEAD study, a 16-center clinical trial of overweight and obese participants with type 2 diabetes, designed to assess the long-term effects of an intensive lifestyle intervention on cardiovascular events. All participants underwent one night of in-home polysomnography and provided a fasting blood sample. Regression analyses estimated the relationship between sleep variables and metabolic risk factors. Models were adjusted for study center, age, sex, race/ethnicity, waist circumference, smoking, alcohol intake, diabetes duration, and relevant medications.Results: Of 60 associations tested, only one was significant: fasting glucose was associated with sleep efficiency (estimate −0.53 ± [standard error] 0.26, P = 0.041). No associations were found between any of the sleep variables and lipid profile or hemoglobin A1c.Conclusions: The present data show only weak associations between select sleep variables and metabolic risk factors and do not provide strong support for a role of sleep on metabolic abnormalities in obese patients with type 2 diabetes.Keywords: obesity, obstructive sleep apnea, metabolic risk, sleep, diabetes

Intentional weight loss has been shown to increase bone loss short term but the long-term effects are not known. Data from the Look AHEAD clinical trial shows that a long term intentional weight loss intervention was associated with greater bone loss at the hip in men.PurposeIntentional weight loss has been shown to increase bone loss short term and increase frailty fracture risk, but the long-term effects on bone mineral density (BMD) are not known.MethodsData from a subgroup from the Look AHEAD (LA) multicenter, randomized clinical trial was used to evaluate whether a long term intentional weight loss intervention would increase bone loss. In a preplanned substudy, BMD was assessed at 5 of the 16 LA clinical centers using dual-energy X-ray absorptiometry at baseline, year 8, and the observational visit 12.6-16.3 years after randomization (year 12-16).ResultsAt year 8, bone density loss (%) was greater in the Intensive Lifestyle Intervention (ILI) group compared with the control group (DSE) for the femoral neck (p = 0.0122) but this finding was not observed at the year 12-16 visit. In analyses stratified by gender, bone density loss (%) was greater at the total hip for men in the ILI group than the DSE group at both the year 8 and year 12-16 visits (year 8 p = 0.0263 and year 12-16 p = 0.0062). This finding was not observed among women.ConclusionLong term intentional weight loss was associated with greater bone loss at the hip in men. These results taken with the previously published Look AHEAD data from the entire clinical trial showing increased frailty fracture risk with weight loss in the ILI group suggest that when intentional weight loss is planned, consideration of bone density preservation and fracture prevention strategies is warranted.Trial registrationClinicaltrials.gov Identifier: NCT00017953. June 21, 2001.

Context: The frequency of remission of type 2 diabetes achievable with lifestyle intervention is unclear.Objective: To examine the association of a long-term intensive weight-loss intervention with the frequency of remission from type 2 diabetes to prediabetes or normoglycemia.Design, Setting, and Participants: Ancillary observational analysis of a 4-year randomized controlled trial (baseline visit, August 2001-April 2004; last follow-up, April 2008) comparing an intensive lifestyle intervention (ILI) with a diabetes support and education control condition (DSE) among 4503 US adults with body mass index of 25 or higher and type 2 diabetes.Interventions: Participants were randomly assigned to receive the ILI, which included weekly group and individual counseling in the first 6 months followed by 3 sessions per month for the second 6 months and twice-monthly contact and regular refresher group series and campaigns in years 2 to 4 (n=2241) or the DSE, which was an offer of 3 group sessions per year on diet, physical activity, and social support (n=2262).Main Outcome Measures: Partial or complete remission of diabetes, defined as transition from meeting diabetes criteria to a prediabetes or nondiabetic level of glycemia (fasting plasma glucose <126 mg/dL and hemoglobin A1c <6.5% with no antihyperglycemic medication). RESULTS Intensive lifestyle intervention participants lost significantly more weight than DSE participants at year 1 (net difference, -7.9%; 95% CI, -8.3% to -7.6%) and at year 4 (-3.9%; 95% CI, -4.4% to -3.5%) and had greater fitness increases at year 1 (net difference, 15.4%; 95% CI, 13.7%-17.0%) and at year 4 (6.4%; 95% CI, 4.7%-8.1%) (P < .001 for each). The ILI group was significantly more likely to experience any remission (partial or complete), with prevalences of 11.5% (95% CI, 10.1%-12.8%) during the first year and 7.3% (95% CI, 6.2%-8.4%) at year 4, compared with 2.0% for the DSE group at both time points (95% CIs, 1.4%-2.6% at year 1 and 1.5%-2.7% at year 4) (P < .001 for each). Among ILI participants, 9.2% (95% CI, 7.9%-10.4%), 6.4% (95% CI, 5.3%-7.4%), and 3.5% (95% CI, 2.7%-4.3%) had continuous, sustained remission for at least 2, at least 3, and 4 years, respectively, compared with less than 2% of DSE participants (1.7% [95% CI, 1.2%-2.3%] for at least 2 years; 1.3% [95% CI, 0.8%-1.7%] for at least 3 years; and 0.5% [95% CI, 0.2%-0.8%] for 4 years).Conclusions: In these exploratory analyses of overweight adults, an intensive lifestyle intervention was associated with a greater likelihood of partial remission of type 2 diabetes compared with diabetes support and education. However, the absolute remission rates were modest. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00017953. [ABSTRACT FROM AUTHOR]

Based on cross-sectional analyses, it was suggested that hip circumference divided by height(1.5) -18 (the body adiposity index (BAI)), could directly estimate percent body fat without the need for further correction for sex or age. We compared the prediction of percent body fat, as assessed by dual-energy X-ray absorptiometry (PBF(DXA)), by BAI, BMI, and circumference (waist and hip) measurements among 1,151 adults who had a total body scan by DXA and circumference measurements from 1993 through 2005. After accounting for sex, we found that PBF(DXA) was related similarly to BAI, BMI, waist circumference, and hip circumference. In general, BAI underestimated PBF(DXA) among men (2.5%) and overestimated PBF(DXA) among women (4%), but the magnitudes of these biases varied with the level of body fatness. The addition of covariates and quadratic terms for the body size measures in regression models substantially improved the prediction of PBF(DXA), but none of the models based on BAI could more accurately predict PBF(DXA) than could those based on BMI or circumferences. We conclude that the use of BAI as an indicator of adiposity is likely to produce biased estimates of percent body fat, with the errors varying by sex and level of body fatness. Although regression models that account for the nonlinear association, as well as the influence of sex, age, and race, can yield more accurate estimates of PBF(DXA), estimates based on BAI are not more accurate than those based on BMI, waist circumference, or hip circumference. [ABSTRACT FROM AUTHOR]

Objective: We examined whether a 1-year intensive lifestyle intervention (ILI) for weight loss reduced elevated high-sensitivity C-reactive protein (hs-CRP) levels in obese individuals with diabetes and identified metabolic and fitness predictors of hs-CRP change.Research Design and Methods: Look AHEAD (Action for Health in Diabetes) is an ongoing multicenter clinical trial examining the effects of weight loss achieved through ILI on cardiovascular events and overall mortality in obese/overweight adults with type 2 diabetes. We report on 1,759 Look AHEAD participants who had hs-CRP and fitness data at baseline and 1 year. Subjects were randomly assigned to ILI or to usual care (diabetes support and education [DSE]). ILI involved frequent counseling to increase moderate-intensity exercise to 175 min/week, reduce caloric and saturated fat intake, and change macronutrient composition to improve glycemic control.Results: ILI reduced median hs-CRP by 43.6% from baseline to 1 year, compared with a 16.7% reduction with DSE (P<0.001). ILI decreased weight (8.8%), A1C (0.7%), and triglycerides (17%) and increased fitness (19%) and HDL cholesterol (7.5%) (P<0.0001 vs. changes with DSE). Changes in adiposity and glucose control with ILI remained independent predictors of hs-CRP change at 1 year (P<0.0001 for each) after adjustment for demographics, smoking, cardiovascular history, statin and thiazolidinedione use, and changes in fitness and lipid control. Neither statin nor insulin therapy modified the association between ILI and hs-CRP.Conclusions: A 1-year lifestyle intervention for weight loss in obese individuals with diabetes was associated with substantial reductions in hs-CRP. Improved glycemic control and reduced adiposity had comparable effects on hs-CRP change. [ABSTRACT FROM AUTHOR]

BACKGROUND: Greater central adiposity is related to the risk of diabetes. OBJECTIVE: We aimed to test the hypothesis that central adiposity measured by computed tomography (CT) is a better predictor of the risk of diabetes than is body mass index (BMI), waist circumference (WC), waist/hip ratio (WHR), or waist/height ratio. DESIGN: Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were measured at the L2-3 and L4-5 disc spaces in 1106 of the 3234 participants in the Diabetes Prevention Program. Sex-specific proportional hazards models were used to evaluate the association between VAT and SAT at both cuts, BMI, and other measures of central adiposity as predictors of the development of diabetes. RESULTS: Men had more VAT than did women. White subjects had more VAT at both cuts than did other ethnic groups. The ratio of VAT to SAT was lowest in African Americans of both sexes. Among men in the placebo group, VAT at both cuts, WC, BMI, waist/height ratio, and WHR predicted diabetes (hazard ratio: 1.79-1.44 per 1 SD of variable). Among women in the lifestyle group, VAT at both cuts predicted diabetes as well as did BMI, and L2-3 was a significantly better predictor than was WC or WHR. SAT did not predict diabetes. None of the body fat measurements predicted diabetes in the metformin group. CONCLUSIONS: In the placebo and lifestyle groups, VAT at both cuts, WHR, and WC predicted diabetes. No measure predicted diabetes in the metformin group. CT provided no important advantage over these simple measures. SAT did not predict diabetes. Copyright © 2008 American Society for Nutrition [ABSTRACT FROM AUTHOR]

OBJECTIVE: The purpose of this study was to evaluate the efficacy and safety of vildagliptin in elderly patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Efficacy data from five double-blind, randomized, placebo- or active-controlled trials of >or=24 weeks' duration were pooled. Effects of 24-week vildagliptin monotherapy (100 mg daily) were compared in younger (<65 years, n = 1,231) and older (>or=65 years, n = 238) patients. Safety data from eight controlled clinical trials of >or=12-weeks' duration were pooled; adverse event profiles in younger (n = 1,890) and older (n = 374) patients were compared. RESULTS: Mean baseline A1C and fasting plasma glucose (FPG) were significantly lower in older (70 years: 8.3 +/- 0.1% and 9.6 +/- 0.1 mmol/l, respectively) than in younger (50 years: 8.7 +/- 0.0% and 10.5 +/- 0.1 mmol/l, respectively) patients. Despite this, the adjusted mean change from baseline (AMDelta) in A1C was -1.2 +/- 0.1% in older and -1.0 +/- 0.0% in younger vildagliptin-treated patients (P = 0.092), and the AMDelta in FPG was significantly larger in older (-1.5 +/- 0.2 mmol/l) than in younger (-1.1 +/- 0.1 mmol/l, P = 0.035) patients. Body weight was significantly lower at baseline in older (83.4 +/- 1.0 kg) than in younger (92.0 +/- 0.6 kg) patients. Weight decreased significantly in the older subgroup (AMDelta -0.9 +/- 0.3 kg, P = 0.007), whereas smaller, nonsignificant decreases occurred in younger patients (AMDelta -0.2 +/- 0.1 kg). Adverse event rates were slightly higher in older than in younger subgroups but were lower among older, vildagliptin-treated subjects (63.6%) than in the pooled active comparator group (68.1%). Vildagliptin treatment did not increase adverse events among older patients with mild renal impairment (62.0%). Hypoglycemia was rare (0.8%) in the elderly patients, and no severe events occurred. CONCLUSIONS: Vildagliptin monotherapy was effective and well tolerated in treatment-naive elderly patients. [ABSTRACT FROM AUTHOR]

This 24-week, double-blind, randomized, multicenter, placebo-controlled, parallel-group study performed in 354 drug-naïve patients with type 2 diabetes (T2DM) assessed efficacy and tolerability of vildagliptin (50mg qd, 50mg bid, or 100mg qd). The primary assessment was change from baseline to endpoint in hemoglobin A1c (A1C), comparing vildagliptin to placebo by ANCOVA. Baseline A1C averaged 8.4% and the between-treatment difference (vildagliptin-placebo) in adjusted mean change (AMDelta) in A1C was -0.5+/-0.2% (P=0.011), -0.7+/-0.2% (P<0.001), and -0.9+/-0.2% (P<0.001) in patients receiving vildagliptin 50mg qd, 50mg bid, or 100mg qd, respectively. Baseline FPG averaged 10.5mmol/L; the between-treatment difference in AMDelta FPG was -0.6+/-0.4mmol/L in patients receiving vildagliptin 50mg qd and -1.3+/-0.4mmol/L (P=0.001) in both groups receiving 100mg daily. Relative to baseline, body weight did not change significantly in any of the three vildagliptin groups and decreased by 1.4+/-0.4kg in the placebo group. Adverse events (AEs) occurred with similar frequency in each group: 55.8%, 59.3%, 59.3%, and 57.6% of patients receiving vildagliptin 50mg qd, 50mg bid, 100mg qd, or placebo, respectively, experienced an AE. No confirmed hypoglycemia was reported. Conclusion: Vildagliptin is effective and well-tolerated in drug-naïve patients with T2DM and 100mg vildagliptin provides similar clinical benefit whether given as single or in divided doses. [ABSTRACT FROM AUTHOR]

Context: Rimonabant, a selective cannabinoid-1 receptor blocker, may reduce body weight and improve cardiometabolic risk factors in patients who are overweight or obese.Objective: To compare the efficacy and safety of rimonabant with placebo each in conjunction with diet and exercise for sustained changes in weight and cardiometabolic risk factors over 2 years.Design, Setting, and Participants: Randomized, double-blind, placebo-controlled trial of 3045 obese (body mass index > or =30) or overweight (body mass index >27 and treated or untreated hypertension or dyslipidemia) adult patients at 64 US and 8 Canadian clinical research centers from August 2001 to April 2004.Intervention: After a 4-week single-blind placebo plus diet (600 kcal/d deficit) run-in period, patients were randomized to receive placebo, 5 mg/d of rimonabant, or 20 mg/d of rimonabant for 1 year. Rimonabant-treated patients were rerandomized to receive placebo or continued to receive the same rimonabant dose while the placebo group continued to receive placebo during year 2.Main Outcome Measures: Body weight change over year 1 and prevention of weight regain during year 2. Additional efficacy measures included changes in waist circumference, plasma lipid levels, and other cardiometabolic risk factors.Results: At year 1, the completion rate was 309 (51%) patients in the placebo group, 620 (51%) patients in the 5 mg of rimonabant group, and 673 (55%) patients in the 20 mg of rimonabant group. Compared with the placebo group, the 20 mg of rimonabant group produced greater mean (SEM) reductions in weight (-6.3 [0.2] kg vs -1.6 [0.2] kg; P<.001), waist circumference (-6.1 [0.2] cm vs -2.5 [0.3] cm; P<.001), and level of triglycerides (percentage change, -5.3 [1.2] vs 7.9 [2.0]; P<.001) and a greater increase in level of high-density lipoprotein cholesterol (percentage change, 12.6 [0.5] vs 5.4 [0.7]; P<.001). Patients who were switched from the 20 mg of rimonabant group to the placebo group during year 2 experienced weight regain while those who continued to receive 20 mg of rimonabant maintained their weight loss and favorable changes in cardiometabolic risk factors. Use of different imputation methods to account for the high rate of dropouts in all 3 groups yielded similar results. Rimonabant was generally well tolerated; the most common drug-related adverse event was nausea (11.2% for the 20 mg of rimonabant group vs 5.8% for the placebo group).Conclusions: In this multicenter trial, treatment with 20 mg/d of rimonabant plus diet for 2 years promoted modest but sustained reductions in weight and waist circumference and favorable changes in cardiometabolic risk factors. However, the trial was limited by a high drop-out rate and longer-term effects of the drug require further study. Clinical Trials Registration ClinicalTrials.gov Identifier: NCT00029861. [ABSTRACT FROM AUTHOR]

AIMS: Liraglutide (NN2211) is a long-acting GLP-1 analogue, with a pharmacokinetic profile suitable for once-daily administration. This multicentre, double-blind, parallel-group, double-dummy study explored the dose-response relationship of liraglutide effects on bodyweight and glycaemic control in subjects with Type 2 diabetes. METHODS: Subjects (BMI 27-42 kg/m(2)) with Type 2 diabetes who were previously treated with an OAD (oral anti-diabetic drug) monotherapy (69% with metformin), and had HbA(1c) < or = 10% were enrolled. After a 4-week metformin run-in period, 210 subjects (27-73 years, 60% female) were randomised to receive liraglutide (0.045-0.75 mg) once daily or continued on metformin 1000 mg b.d. for 12 weeks. RESULTS: Mean baseline values for the six treatment groups ranged from 6.8 to 7.5% for HbA(1c), and 8.06-9.44 mmol/l (145-170 mg/dl) for fasting plasma glucose. After 12-week treatment, a weight change of -0.05 to -1.9% was observed for the six treatment groups. Mean HbA(1c) changes from baseline for 0.045, 0.225, 0.45, 0.6, 0.75 mg liraglutide and metformin were +1.28%, +0.86%, +0.22%, +0.16%, +0.30% and +0.09%, respectively. No significant differences in HbA(1c) were observed between liraglutide and metformin groups at the three highest liraglutide dose levels (0.45, 0.6 and 0.75 mg). The lowest two liraglutide doses (0.045 mg and 0.225 mg) were not sufficient to maintain the fasting plasma glucose values achieved by metformin. No major hypoglycaemic episodes were reported. Episodes of nausea and/or vomiting were reported by 11 patients (6.3%) receiving liraglutide and three (8.8%) receiving metformin. CONCLUSIONS: Once-daily liraglutide improved glycaemic control and weight, in a comparable degree to metformin. Liraglutide appeared to be safe and generally well tolerated. Higher doses of liraglutide merit study in future clinical trials. [ABSTRACT FROM AUTHOR]

BACKGROUND: Limited research has been done to explore differences between ethnic groups, including Hispanic Americans (HAs), in the association between percentage body fat (PBF) and body mass index (BMI; in kg/m(2)); the numbers of HAs are increasing in the US population. OBJECTIVE: We investigated whether the relation between PBF and BMI in adult HAs differed from that of African Americans (AAs) and European Americans (EAs). DESIGN: We used a multiple regression model in which PBF measured with dual energy X-ray absorptiometry was predicted by the reciprocal of BMI (1/BMI; in m(2)/kg) in a sample of 487 men (n(EA) = 192, n(AA) = 148, and n(HA) = 147) and 933 women (n(EA) = 448, n(AA) = 304, and n(HA) = 181). RESULTS: For men, our results showed no significant differences between HAs and EAs, AAs and EAs, or HAs and AAs in the slope of the line relating 1/BMI to PBF. In women, there were significant differences in PBF as predicted by BMI between HAs and EAs (P < 0.002) and AAs and HAs (P = 0.020), but not between AAs and EAs. When PBF was estimated on the basis of predicting equations, the trend of the predicted PBF value in women differed according to ethnic group and BMI category. At a BMI < 30, HAs tended to have more body fat than did EAs and AAs, and at a BMI > 35, EAs tended to have more body fat than did the other groups. CONCLUSIONS: Our results show that the relation between PBF and BMI in HA women differs from that of EA and AA women. [ABSTRACT FROM AUTHOR]

Background: Elevated blood homocysteine is a risk factor for cardiovascular disease. A 5-Rmol/L increase is associated with an approximately 70% increase in relative risk of cardiovascular disease in adults. For patients with established risk factors, this risk is likely even greater. Objective: Effects of increased dietary folate and recommended intakes of vitamins B-12 and B-6 on serum total homocysteine (tHcy) were assessed in individuals at high risk of cardiovascular disease. Design: This trial was conducted at 10 medical research centers in the United States and Canada and included 491 adults with hypertension, dyslipidemia, type 2 diabetes, or a combination thereof. Participants were randomly assigned to follow a prepared meal plan (PMP; n = 244) or a self-selected diet (SSD; ii = 247) for 10 wk, which were matched for macronutrient content. The PMP was fortified to provide >/= 100% of the recommended dietary allowances for 23 micronutrients, including folate. Results: Mean folate intakes at 10 wk were 601 +/= 143 mu g/d with the PMP and 270 +/= 107 mu g/d with the SSD. With the PMP, serum tHcy concentrations fell from 10.8 +/= 5.8 to 9.3 +/= 4.9 mu mol/L (P < 0.0001) between weeks 0 and 10 and the change was associated with increased intakes of folate, vitamin B-12, and vitamin B-6 and with increased serum and red blood cell folate and serum vitamin B-12 concentrations. tHcy concentrations did not change significantly with the SSD. Conclusions: The PMP resulted in increased intakes and serum concentrations of folate and vitamin B-12. These changes were associated with reduced serum tHcy concentrations in persons at high risk of cardiovascular disease. Copyright (c) 1999 American Society for Clinical Nutrition [ABSTRACT FROM AUTHOR]

OBJECTIVE: To describe the measurement challenges faced and to evaluate the measurement quality obtained with massively obese individuals. METHOD: A cross-sectional analysis of 107 individuals with body mass indices (kg/m2) > or = 50 was conducted. Individuals had their body fat measured via bioimpedance analysis (BIA), their serum leptin levels measured via radioimmunoassay (RIA), and height and weight measured via both laboratory scales and self-report. RESULTS: Serum leptin appeared to be measured accurately, provided the serum was diluted prior to conducting the RIA. Difficulties remained, however, in evaluating what was an unusual or expected value of leptin among individuals this large. Measures of impedance appeared to provide reasonable ordinal indications of body fatness. However, currently available equations for converting measures of impedance to estimates of percent body fat were highly inaccurate. Self-reported height and weight were reasonably good proxies of measured height and weight among individuals who reported their height and weight. However, a substantial proportion were unable to provide estimates. DISCUSSION: The above results suggest there are substantial challenges when trying to obtain meaningful measurements regarding obesity-related variables among massively obese individuals. Other logistic challenges also are discussed. It is hoped future research is directed at overcoming some of these challenges. [ABSTRACT FROM AUTHOR]

The days of restrictive diets for patients with diabetes have given way to a more reasoned and flexible approach that tailors the daily meal plan to the person's circumstances and treatment goals. [ABSTRACT FROM AUTHOR]