Weight loss in the treatment of type 2 diabetes

National Institute Of Diabetes And Digestive And Kidney Diseases

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Abstract

We operate two clinical centers of Look AHEAD, a multicenter randomized clinical trial of weight loss for prevention of complications of type 2 diabetes. Since the clinical trial began in 2002, 5,145 volunteers with type 2 diabetes who were 45-76 years of age and overweight or obesity were enrolled in either the intensive lifestyle intervention (ILI) program or the diabetes support and education (DSE) program. The Diabetes Epidemiology and Clinical Research Section clinics enrolled 244 of these participants. The study has reported success in achieving and maintaining weight loss in the ILI group, while there was little weight loss on average in the DSE group. Effects of the weight loss on several health outcomes were reported in previous years. Several more health outcomes were reported during the current fiscal year. Depression symptoms and health-related quality of life. The Action for Health in Diabetes (Look AHEAD) study previously reported that intensive lifestyle intervention (ILI) reduced incident depressive symptoms and improved health-related quality of life (HRQOL) over nearly 10 years of intervention compared with a control group (the diabetes support and education group DSE) in participants with type 2 diabetes and overweight or obesity. The present study compared incident depressive symptoms and changes in HRQOL in these groups for an additional 6 years following termination of the ILI in September 2012. A total of 1,945 ILI participants and 1,900 DSE participants completed at least one of four planned postintervention assessments at which weight, mood (via the Patient Health Questionnaire-9), antidepressant medication use, and HRQOL (via the Medical Outcomes Scale, Short Form-36) were measured. ILI participants and DSE participants lost 3.1 (0.3) and 3.8 (0.3) kg represented as mean (SE); p = 0.10, respectively, during the 6-year postintervention follow-up. No significant differences were observed between groups during this time in incident mild or greater symptoms of depression, antidepressant medication use, or in changes on the physical component summary or mental component summary scores of the Short Form-36. In both groups, mental component summary scores were higher than physical component summary scores. Prior participation in the ILI, compared with the DSE group, did not appear to improve subsequent mood or HRQOL during 6 years of postintervention follow-up. Multimorbidity in type 2 diabetes. Type 2 diabetes mellitus and obesity are sometimes described as conditions that accelerate aging. Multidomain lifestyle interventions have shown promise to slow the accumulation of age-related diseases, a hallmark of aging. However, they have not been assessed among at-risk individuals with these two conditions. We examined the relative impact of 8 years of a multidomain lifestyle intervention on an index of multimorbidity in the Look AHEAD clinical trial. A multimorbidity index that included nine age-related chronic diseases and death was tracked over 8 years of intervention delivery. Among individuals assigned to DSE, the multimorbidity index scores increased by an average of .98 (95% confidence interval CI = .94-1.02) over 8 years, compared with .89 (95% CI = .85-.93) among those in the multidomain ILI, which was a 9% difference (P = .003). Relative intervention effects were similar among individuals grouped by baseline body mass index, age, and sex, and they were greater for those with lower levels of multimorbidity index scores at baseline. In conclusion, increases in multimorbidity over time among adults with overweight or obesity and type 2 diabetes mellitus may be slowed by multidomain ILI. Loneliness and physical function. Little is known about the impact of loneliness on physical health among elderly individuals with diabetes. Here, we examined the relationship of loneliness with disability, objective physical function, and other health outcomes in older individuals with type 2 diabetes and overweight or obesity. Data were analyzed from the Look AHEAD study, a diverse cohort of individuals (ages 61-92) with overweight or obesity and type 2 diabetes measured 5-6 years after a 10-year weight loss randomized, controlled trial. Loneliness scores were significantly associated with greater disability symptoms and slower 4-meter gait speed. Loneliness did not differ across treatment arms. Overall, these results extend prior findings relating loneliness to disability and decreased mobility to older individuals with type 2 diabetes and overweight or obesity. Changes in body weight and waist circumference (WC). A secondary analysis of Look AHEAD was conducted to evaluate the association between change in weight and WC and cardiovascular disease (CVD) outcomes. Participants (N = 5,490) were classified into four categories based on change in weight and WC between baseline and year 1 (both increased, both decreased, etc.). Separate Cox proportional hazards regression models were fit for ILI and DSE (using group that reduced weight/WC as reference), and time to first occurrence of primary and secondary CVD outcomes from year 1 through a median of almost 10 years were compared. Second, time to first event among all four ILI groups relative to DSE was evaluated. In this secondary analysis, increased WC during the first year of ILI, independent of weight change, was associated with higher risk for subsequent cardiovascular outcomes. Test of gene-intervention interaction on physical activity and fitness. Prior studies identified single nucleotide polymorphisms (SNPs) associated with physical activity (PA) level in a natural environment and intervention study: rs978656-DNAPTP6, rs10887741-PAPSS2, rs7279064-C18orf2, and rs6265-BDNF. Using the four SNPs' polygenic score (PGS), we examined whether PGS moderates a life-style intervention's effect on changes in PA level and cardiorespiratory fitness (CRF) in the Look AHEAD clinical trial. Using linear mixed-effects models, level of PA (Paffenbarger PA questionnaire) and treadmill-assessed CRF were each regressed on four SNPs' PGS, study time (baseline, year 1, and year 4), intervention arm, and interactions between the three. Models adjusted for age, sex, body mass index, ancestry principal components (population stratification), and study sites, with Bonferroni corrections for multiple testing ( < .005). Effect modification by age was examined. PGS was not predictive of change in CRF or PA level in response to intervention. In analyses without PGS by intervention by time, the relationships between PGS and PA phenotypes were modified by age (p interaction = .048 for CRF and .058 for PA), such that a 1-unit increase in PGS was associated with 24 kcal wk-1 more in moderate-intensity PA and 0.004 MET higher CRF only among older groups (age >55 years for CRF, >60 years for PA level). In conclusion, the effects of the intervention on PA and CRF were not moderated by the four SNPs. Future studies with extended SNP list should confirm the findings on effect modification by age. Cost-effectiveness (CE) analysis of Look AHEAD. We assessed the 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 Look AHEAD. 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. Over the 9 years studied, the mean cumulati