Within-Trial Cost-Effectiveness of a Structured Lifestyle Intervention in Adults With Overweight/Obesity and Type 2 Diabetes: Results From the Action for Health in Diabetes (Look AHEAD) Study.

OBJECTIVE: To assess the cost-effectiveness (CE) of an intensive lifestyle intervention (ILI) compared with standard diabetes support and education (DSE) in adults with overweight/obesity and type 2 diabetes, as implemented in the Action for Health in Diabetes study. RESEARCH DESIGN AND METHODS: Data were from 4,827 participants during their first 9 years of study participation from 2001 to 2012. Information on Health Utilities Index Mark 2 (HUI-2) and HUI-3, Short-Form 6D (SF-6D), and Feeling Thermometer (FT), cost of delivering the interventions, and health expenditures was collected during the study. CE was measured by incremental CE ratios (ICERs) in costs per quality-adjusted life year (QALY). Future costs and QALYs were discounted at 3% annually. Costs were in 2012 U.S. dollars. RESULTS: Over the 9 years studied, the mean cumulative intervention costs and mean cumulative health care expenditures were $11,275 and $64,453 per person for ILI and $887 and $68,174 for DSE. Thus, ILI cost $6,666 more per person than DSE. Additional QALYs gained by ILI were not statistically significant measured by the HUIs and were 0.07 and 0.15, respectively, measured by SF-6D and FT. The ICERs ranged from no health benefit with a higher cost based on HUIs to $96,458/QALY and $43,169/QALY, respectively, based on SF-6D and FT. CONCLUSIONS: Whether ILI was cost-effective over the 9-year period is unclear because different health utility measures led to different conclusions.

Intensive Weight Loss Intervention and Cancer Risk in Adults with Type 2 Diabetes: Analysis of the Look AHEAD Randomized Clinical Trial.

OBJECTIVE: This study was designed to determine whether intensive lifestyle intervention (ILI) aimed at weight loss lowers cancer incidence and mortality. METHODS: Data from the Look AHEAD trial were examined to investigate whether participants randomized to ILI designed for weight loss would have reduced overall cancer incidence, obesity-related cancer incidence, and cancer mortality, as compared with the diabetes support and education (DSE) comparison group. This analysis included 4,859 participants without a cancer diagnosis at baseline except for nonmelanoma skin cancer. RESULTS: After a median follow-up of 11 years, 684 participants (332 in ILI and 352 in DSE) were diagnosed with cancer. The incidence rates of obesity-related cancers were 6.1 and 7.3 per 1,000 person-years in ILI and DSE, respectively, with a hazard ratio (HR) of 0.84 (95% CI: 0.68-1.04). There was no significant difference between the two groups in total cancer incidence (HR, 0.93; 95% CI: 0.80-1.08), incidence of nonobesity-related cancers (HR, 1.02; 95% CI: 0.83-1.27), or total cancer mortality (HR, 0.92; 95% CI: 0.68-1.25). CONCLUSIONS: An ILI aimed at weight loss lowered incidence of obesity-related cancers by 16% in adults with overweight or obesity and type 2 diabetes. The study sample size likely lacked power to determine effect sizes of this magnitude and smaller.

Weight Change 2 Years After Termination of the Intensive Lifestyle Intervention in the Look AHEAD Study.

OBJECTIVE: This study evaluated weight changes after cessation of the 10-year intensive lifestyle intervention (ILI) in the Look AHEAD (Action for Health in Diabetes) study. It was hypothesized that ILI participants would be more likely to gain weight during the 2-year observational period following termination of weight-loss-maintenance counseling than would participants in the diabetes support and education (DSE) control group. METHODS: Look AHEAD was a randomized controlled trial that compared the effects of ILI and DSE on cardiovascular morbidity and mortality in participants with overweight/obesity and type 2 diabetes. Look AHEAD was converted to an observational study in September 2012. RESULTS: Two years after the end of the intervention (EOI), ILI and DSE participants lost a mean (SE) of 1.2 (0.2) kg and 1.8 (0.2) kg, respectively (P = 0.003). In addition, 31% of ILI and 23.9% of DSE participants gained ≥ 2% (P < 0.001) of EOI weight, whereas 36.3% and 45.9% of the respective groups lost ≥ 2% of EOI weight (P = 0.001). Two years after the EOI, ILI participants reported greater use of weight-control behaviors than DSE participants. CONCLUSIONS: Both groups lost weight during the 2-year follow-up period, but more ILI than DSE participants gained ≥ 2% of EOI weight. Further understanding is needed of factors that affected long-term weight change in both groups.

History of Cardiovascular Disease, Intensive Lifestyle Intervention, and Cardiovascular Outcomes in the Look AHEAD Trial.

OBJECTIVE: To examine the effects of an intensive lifestyle intervention (ILI) on cardiovascular disease (CVD), the Action for Health in Diabetes (Look AHEAD) trial randomized 5,145 participants with type 2 diabetes and overweight/obesity to a ILI or diabetes support and education. Although the primary outcome did not differ between the groups, there was suggestive evidence of heterogeneity for prespecified baseline CVD history subgroups (interaction P = 0.063). Event rates were higher in the ILI group among those with a CVD history (hazard ratio 1.13 [95% CI: 0.90-1.41]) and lower among those without CVD (hazard ratio 0.86 [95% CI: 0.72-1.02]). METHODS: This study conducted post hoc analyses of the rates of the primary composite outcome and components, adjudicated cardiovascular death, nonfatal myocardial infarction (MI), stroke, and hospitalization for angina, as well as three secondary composite cardiovascular outcomes. RESULTS: Interaction P values for the primary and two secondary composites were similar (0.060-0.064). Of components, the interaction was significant for nonfatal MI (P = 0.035). This interaction was not due to confounding by baseline variables, different intervention responses for weight loss and physical fitness, or hypoglycemic events. In those with a CVD history, statin use was high and similar by group. In those without a CVD history, low-density lipoprotein cholesterol levels were higher (P = 0.003) and statin use was lower (P ≤ 0.001) in the ILI group. CONCLUSIONS: Intervention response heterogeneity was significant for nonfatal MI. Response heterogeneity may need consideration in a CVD-outcome trial design.

Physical Function Following a Long-Term Lifestyle Intervention Among Middle Aged and Older Adults With Type 2 Diabetes: The Look AHEAD Study.

Background: Lifestyle interventions have been shown to improve physical function over the short term; however, whether these benefits are sustainable is unknown. The long-term effects of an intensive lifestyle intervention (ILI) on physical function were assessed using a randomized post-test design in the Look AHEAD trial. Methods: Overweight and obese (body mass index ≥ 25 kg/m2) middle-aged and older adults (aged 45-76 years at enrollment) with type 2 diabetes enrolled in Look AHEAD, a trial evaluating an ILI designed to achieve weight loss through caloric restriction and increased physical activity compared to diabetes support and education (DSE), underwent standardized assessments of performance-based physical function including a 4- and 400-m walk, lower extremity physical performance (expanded Short Physical Performance Battery, SPPBexp), and grip strength approximately 11 years postrandomization and 1.5 years after the intervention was stopped (n = 3,783). Results: Individuals randomized to ILI had lower odds of slow gait speed (<0.8 m/s) compared to those randomized to DSE (adjusted OR [95% CI]: 0.84 [0.71 to 0.99]). Individuals randomized to ILI also had faster gait speed over 4- and 400-m (adjusted mean difference [95% CI]: 0.019 [0.007 to 0.031] m/s, p = .002, and 0.023 [0.012 to 0.034] m/sec, p < .0001, respectively) and higher SPPBexp scores (0.037 [0.011 to 0.063], p = .005) compared to those randomized to DSE. The intervention effect was slightly larger for SPPBexp scores among older versus younger participants (0.081 [0.038 to 0.124] vs 0.013 [-0.021 to 0.047], p = .01). Conclusions: An intensive lifestyle intervention has modest but significant long-term benefits on physical function in overweight and obese middle-aged and older adults with type 2 diabetes. ClinicalTrials.gov Identifier: NCT00017953.

The Effect of Intentional Weight Loss on Fracture Risk in Persons With Diabetes: Results From the Look AHEAD Randomized Clinical Trial.

Intentional weight loss is an important treatment option for overweight persons with type 2 diabetes mellitus (DM), but the effects on long-term fracture risk are not known. The purpose of this Look AHEAD analysis was to evaluate whether long-term intentional weight loss would increase fracture risk in overweight or obese persons with DM. Look AHEAD is a multicenter, randomized clinical trial. Recruitment began in August 2001 and follow-up continued for a median of 11.3 years at 16 academic centers. A total of 5145 persons aged 45 to 76 years with DM were randomized to either an intensive lifestyle intervention (ILI) with reduced calorie consumption and increased physical activity designed to achieve and maintain ≥7% weight loss or to diabetes support and education intervention (DSE). Incident fractures were ascertained every 6 months by self-report and confirmed with central adjudication of medical records. The baseline mean age of participants was 59 years, 60% were women, 63% were white, and the mean BMI was 36 kg/m2 . Weight loss over the intervention period (median 9.6 years) was 6.0% in ILI and 3.5% in DSE. A total of 731 participants had a confirmed incident fracture (358 in DSE versus 373 in ILI). There were no statistically significant differences in incident total or hip fracture rates between the ILI and DSE groups. However, compared to the DSE group, the ILI group had a statistically significant 39% increased risk of a frailty fracture (HR 1.39; 95% CI, 1.02 to 1.89). An intensive lifestyle intervention resulting in long-term weight loss in overweight/obese adults with DM was not associated with an overall increased risk of incident fracture but may be associated with an increased risk of frailty fracture. When intentional weight loss is planned, consideration of bone preservation and fracture prevention is warranted. © 2017 American Society for Bone and Mineral Research.

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.

Changes in adipose tissue depots and metabolic markers following a 1-year diet and exercise intervention in overweight and obese patients with type 2 diabetes.

OBJECTIVE: We aim to characterize the effects on total body fat and distribution of a 1-year intensive lifestyle intervention (ILI) for weight loss in overweight and obese adults with type 2 diabetes and to examine whether changes in adipose tissue (AT) depots were associated with changes in metabolic biomarkers. RESEARCH DESIGN AND METHODS: Participants were 54 females and 38 males (age 57.8 ± 6.7 years [mean ± SD]; BMI 31.7 ± 3.5 kg/m(2)) enrolled in the Look AHEAD (Action for Health in Diabetes) trial randomized to ILI or diabetes support and education (DSE) from whom baseline and 1-year MRI measures of total AT (TAT) and regional (arm, trunk, leg) AT, including subcutaneous AT (SAT), visceral AT (VAT), and intermuscular AT (IMAT), were acquired. We tested whether mean changes in ILI and DSE were equal and, within groups, whether changes were different from zero. Regression models tested whether changes in AT compartments were associated with metabolic variable changes. RESULTS: Body weight changed -0.52 ± 3.62 kg (P = 0.31) in DSE and -7.24 ± 5.40 kg (P < 0.0001) in ILI. Mean ILI changes were different from DSE (P < 0.001 for TAT, SAT, and IMAT and P < 0.01 for VAT in females). Within ILI, SAT and VAT decreased in males and females (P < 0.0001), but IMAT was unchanged (0.00 ± 0.54 kg; P = 0.99). In DSE, SAT and VAT did not change, but IMAT increased by 0.46 ± 0.55 kg (P < 0.001). Controlling for weight loss, reduction of specific AT depots was associated with improvement in metabolic biomarkers. CONCLUSIONS: Weight loss of 7-10% from an ILI over 1 year reduced SAT and VAT and prevented an increase in IMAT. Reductions in AT depots were associated with improvements in biomarkers.

Impact of an intensive lifestyle intervention on use and cost of medical services among overweight and obese adults with type 2 diabetes: the action for health in diabetes.

OBJECTIVE: To assess the relative impact of an intensive lifestyle intervention (ILI) on use and costs of health care within the Look AHEAD trial. RESEARCH DESIGN AND METHODS: A total of 5,121 overweight or obese adults with type 2 diabetes were randomly assigned to an ILI that promoted weight loss or to a comparison condition of diabetes support and education (DSE). Use and costs of health-care services were recorded across an average of 10 years. RESULTS: ILI led to reductions in annual hospitalizations (11%, P = 0.004), hospital days (15%, P = 0.01), and number of medications (6%, P < 0.001), resulting in cost savings for hospitalization (10%, P = 0.04) and medication (7%, P < 0.001). ILI produced a mean relative per-person 10-year cost savings of $5,280 (95% CI 3,385-7,175); however, these were not evident among individuals with a history of cardiovascular disease. CONCLUSIONS: Compared with DSE over 10 years, ILI participants had fewer hospitalizations, fewer medications, and lower health-care costs.

Impact of intensive lifestyle intervention on depression and health-related quality of life in type 2 diabetes: the Look AHEAD Trial.

OBJECTIVE: We examined the effects of an intensive lifestyle intervention (ILI), compared with a diabetes support and education (DSE) control intervention, on long-term changes in depression symptoms, antidepressant medication (ADM) use, and health-related quality of life (HRQoL) in overweight/obese individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS: Look AHEAD was a multisite randomized controlled trial of 5,145 overweight/obese participants assigned to ILI (designed to produce weight loss) or DSE and followed for a median of 9.6 years. The Beck Depression Inventory (BDI) was administered at baseline, annually at years 1-4, and again at year 8. Mean BDI scores and incidence of BDI scores ≥10, indicative of likely mild or greater depression, were examined. Annually through year 10, participants reported their ADM use and completed the Medical Outcomes Study Short Form 36 (SF-36) questionnaire, which yields physical component summary (PCS) and mental component summary (MCS) scores. RESULTS: ILI significantly reduced the incidence of mild or greater depression symptoms (BDI scores ≥10) compared with DSE (hazard ratio [HR] = 0.85; 95% CI 0.75-0.97; P = 0.0145). Although SF-36 PCS scores worsened over time in both groups, ILI participants reported better physical function than DSE throughout the first 8 years (all P values <0.01). There were no significant differences between treatment arms in the proportion of participants who used ADMs or in SF-36 MCS scores. CONCLUSIONS: ILI for overweight/obese patients with type 2 diabetes may reduce the risk of developing clinically significant symptoms of depression and preserve physical HRQoL. These findings should be considered when evaluating the potential benefits of ILIs.

Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes.

BACKGROUND: Weight loss is recommended for overweight or obese patients with type 2 diabetes on the basis of short-term studies, but long-term effects on cardiovascular disease remain unknown. We examined whether an intensive lifestyle intervention for weight loss would decrease cardiovascular morbidity and mortality among such patients. METHODS: In 16 study centers in the United States, we randomly assigned 5145 overweight or obese patients with type 2 diabetes to participate in an intensive lifestyle intervention that promoted weight loss through decreased caloric intake and increased physical activity (intervention group) or to receive diabetes support and education (control group). The primary outcome was a composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for angina during a maximum follow-up of 13.5 years. RESULTS: The trial was stopped early on the basis of a futility analysis when the median follow-up was 9.6 years. Weight loss was greater in the intervention group than in the control group throughout the study (8.6% vs. 0.7% at 1 year; 6.0% vs. 3.5% at study end). The intensive lifestyle intervention also produced greater reductions in glycated hemoglobin and greater initial improvements in fitness and all cardiovascular risk factors, except for low-density-lipoprotein cholesterol levels. The primary outcome occurred in 403 patients in the intervention group and in 418 in the control group (1.83 and 1.92 events per 100 person-years, respectively; hazard ratio in the intervention group, 0.95; 95% confidence interval, 0.83 to 1.09; P=0.51). CONCLUSIONS: An intensive lifestyle intervention focusing on weight loss did not reduce the rate of cardiovascular events in overweight or obese adults with type 2 diabetes. (Funded by the National Institutes of Health and others; Look AHEAD ClinicalTrials.gov number, NCT00017953.).

Neighborhood socioeconomic status, depression, and health status in the Look AHEAD (Action for Health in Diabetes) study.

BACKGROUND: Depression and diminished health status are common in adults with diabetes, but few studies have investigated associations with socio-economic environment. The objective of this manuscript was to evaluate the relationship between neighborhood-level SES and health status and depression. METHODS: Individual-level data on 1010 participants at baseline in Look AHEAD (Action for Health in Diabetes), a trial of long-term weight loss among adults with type 2 diabetes, were linked to neighborhood-level SES (% living below poverty) from the 2000 US Census (tracts). Dependent variables included depression (Beck Inventory), and health status (Medical Outcomes Study (SF-36) scale). Multi-level regression models were used to account simultaneously for individual-level age, sex, race, education, personal yearly income and neighborhood-level SES. RESULTS: Overall, the % living in poverty in the participants' neighborhoods varied, mean =11% (range 0-67%). Compared to their counterparts in the lowest tertile of neighborhood poverty (least poverty), those in the highest tertile (most poverty) had significantly lower scores on the role-limitations(physical), role limitations(emotional), physical functioning, social functioning, mental health, and vitality sub-scales of the SF-36 scale. When evaluating SF-36 composite scores, those living in neighborhoods with more poverty had significantly lower scores on the physical health (beta-coefficient [beta]= -1.90 units, 95% CI: -3.40,-0.039), mental health (beta= -2.92 units, -4.31,-1.53) and global health (beta= -2.77 units, -4.21,-1.33) composite scores. CONCLUSION: In this selected group of weight loss trial participants, lower neighborhood SES was significantly associated with poorer health status. Whether these associations might influence response to the Look AHEAD weight loss intervention requires further investigation.

Neighborhood and weight-related health behaviors in the Look AHEAD (Action for Health in Diabetes) study.

BACKGROUND: Previous studies have shown that neighborhood factors are associated with obesity, but few studies have evaluated the association with weight control behaviors. This study aims to conduct a multi-level analysis to examine the relationship between neighborhood SES and weight-related health behaviors. METHODS: In this ancillary study to Look AHEAD (Action for Health in Diabetes) a trial of long-term weight loss among individuals with type 2 diabetes, individual-level data on 1219 participants from 4 clinic sites at baseline were linked to neighborhood-level data at the tract level from the 2000 US Census and other databases. Neighborhood variables included SES (% living below the federal poverty level) and the availability of food stores, convenience stores, and restaurants. Dependent variables included BMI, eating patterns, weight control behaviors and resource use related to food and physical activity. Multi-level models were used to account for individual-level SES and potential confounders. RESULTS: The availability of restaurants was related to several eating and weight control behaviors. Compared to their counterparts in neighborhoods with fewer restaurants, participants in neighborhoods with more restaurants were more likely to eat breakfast (prevalence Ratio [PR] 1.29 95% CI: 1.01-1.62) and lunch (PR = 1.19, 1.04-1.36) at non-fast food restaurants. They were less likely to be attempting weight loss (OR = 0.93, 0.89-0.97) but more likely to engage in weight control behaviors for food and physical activity, respectively, than those who lived in neighborhoods with fewer restaurants. In contrast, neighborhood SES had little association with weight control behaviors. CONCLUSION: In this selected group of weight loss trial participants, restaurant availability was associated with some weight control practices, but neighborhood SES was not. Future studies should give attention to other populations and to evaluating various aspects of the physical and social environment with weight control practices.

Reduction in weight and cardiovascular disease risk factors in individuals with type 2 diabetes: one-year results of the look AHEAD trial.

OBJECTIVE: The effectiveness of intentional weight loss in reducing cardiovascular disease (CVD) events in type 2 diabetes is unknown. This report describes 1-year changes in CVD risk factors in a trial designed to examine the long-term effects of an intensive lifestyle intervention on the incidence of major CVD events. RESEARCH DESIGN AND METHODS: This study consisted of a multicentered, randomized, controlled trial of 5,145 individuals with type 2 diabetes, aged 45-74 years, with BMI >25 kg/m2 (>27 kg/m2 if taking insulin). An intensive lifestyle intervention (ILI) involving group and individual meetings to achieve and maintain weight loss through decreased caloric intake and increased physical activity was compared with a diabetes support and education (DSE) condition. RESULTS: Participants assigned to ILI lost an average 8.6% of their initial weight vs. 0.7% in DSE group (P < 0.001). Mean fitness increased in ILI by 20.9 vs. 5.8% in DSE (P < 0.001). A greater proportion of ILI participants had reductions in diabetes, hypertension, and lipid-lowering medicines. Mean A1C dropped from 7.3 to 6.6% in ILI (P < 0.001) vs. from 7.3 to 7.2% in DSE. Systolic and diastolic pressure, triglycerides, HDL cholesterol, and urine albumin-to-creatinine ratio improved significantly more in ILI than DSE participants (all P < 0.01). CONCLUSIONS: At 1 year, ILI resulted in clinically significant weight loss in people with type 2 diabetes. This was associated with improved diabetes control and CVD risk factors and reduced medicine use in ILI versus DSE. Continued intervention and follow-up will determine whether these changes are maintained and will reduce CVD risk.