Lifestyle intervention in obese patients with type 2 diabetes: impact of the patient's educational background

Objective: To determine whether people with different educational backgrounds respond differently to a lifestyle intervention program for obese patients with type 2 diabetes. Research Methods and Procedures: The study consisted of a 12‐month randomized controlled trial of 147 health plan members with type 2 diabetes who were overweight or obese (BMI ≥ 27 kg/m²). Participants were randomized to lifestyle case management or usual care. Case management (CM) involved group and individual education, support, and referral by registered dietitians. Usual care (UC) participants received educational material. Both groups received ongoing primary care. A post hoc analysis was performed, evaluating the impact of education level on intervention group differences with respect to change in weight and waist circumference. Results: There was a significant education by group interaction for both changes in weight (p = 0.02) and waist circumference (p = 0.01) during the study period. Contrary to expectations, CM participants with less formal education had greater risk reductions compared with more educated participants. Models predicted that, by 12 months, those with less education in the UC group gained 1.71 kg more in weight and 3.67 cm more in waist circumference than those with greater education. However, by 12 months, those in the CM group with less education lost a model‐predicted 3.30 kg more in weight and 4.95 cm more in waist circumference than those with more formal education. Discussion: People with varied educational backgrounds may respond differently to a lifestyle intervention for weight management and diabetes control.     

One-year Weight Losses in the Look AHEAD Study: Factors Associated With Success

This report provides a further analysis of the first year weight losses in the Look AHEAD (Action for Health in Diabetes) study and identifies factors associated with success. Participants were a total of 5,145 men and women with type 2 diabetes who were recruited at 16 sites and randomly assigned to an intensive lifestyle intervention (ILI) or a control condition, Diabetes Support and Education (DSE). During year 1, participants in ILI received comprehensive diet and physical activity counseling in a total of 42 group and individual sessions, compared with three educational sessions for DSE participants. As reported previously, at the end of the year, ILI participants lost 8.6% of initial weight, compared to 0.7% for DSE (P < 0.001). Within the ILI group, all racial/ethnic groups achieved clinically significant weight losses (>5.5%), although there were significant differences among groups. For the year, ILI participants attended an average of 35.4 treatment sessions and reported exercising a mean of 136.6 min/week and consuming a total of 360.9 meal replacement products. Greater self-reported physical activity was the strongest correlate of weight loss, followed by treatment attendance and consumption of meal replacements. The use of orlistat, during the second half of the year, increased weight loss only marginally in those ILI participants who had lost <5% of initial weight during the first 6 months and chose to take the medication thereafter as a toolbox option. The lifestyle intervention was clinically effective in all subsets of an ethnically and demographically diverse population.     

Four-year weight losses in the Look AHEAD study: factors associated with long-term success

This report provides a further analysis of the year 4 weight losses in the Look AHEAD (Action for Health in Diabetes) study and identifies factors associated with long-term success. A total of 5,145 overweight/obese men and women with type 2 diabetes were randomly assigned to an intensive lifestyle intervention (ILI) or a usual care group, referred to as Diabetes Support and Education (DSE). ILI participants were provided approximately weekly group or individual treatment in year 1; continued but less frequent contact was provided in years 2-4. DSE participants received three group educational sessions in all years. As reported previously, at year 4, ILI participants lost an average of 4.7% of initial weight, compared with 1.1% for DSE (P < 0.0001). More ILI than DSE participants lost ≥ 5% (46% vs. 25%, P < 0.0001) and ≥ 10% (23% vs. 10%, P < 0.0001) of initial weight. Within the ILI, achievement of both the 5% and 10% categorical weight losses at year 4 was strongly related to meeting these goals at year 1. A total of 887 participants in ILI lost ≥ 10% at year 1, of whom 374 (42.2%) achieved this loss at year 4. Participants who maintained the loss, compared with those who did not, attended more treatment sessions and reported more favorable physical activity and food intake at year 4. These results provide critical evidence that a comprehensive lifestyle intervention can induce clinically significant weight loss (i.e., ≥ 5%) in overweight/obese participants with type 2 diabetes and maintain this loss in more than 45% of patients at 4 years.     

Effects of a Low‐intensity Intervention That Prescribed a Low‐carbohydrate vs. a Low‐fat Diet in Obese,Diabetic Participants

Low‐carbohydrate diets have been associated with significant reductions in weight and HbA_1c in obese, diabetic participants who received high‐intensity lifestyle modification for 6 or 12 months. This investigation sought to determine whether comparable results to those of short‐term, intensive interventions could be achieved over a 24‐month study period using a low‐intensity intervention that approximates what is feasible in outpatient practice. A total of 144 obese, diabetic participants were randomly assigned to a low‐carbohydrate diet (<30 g/day) or to a low fat diet (≤30% of calories from fat with a deficit of 500 kcal/day). Participants were provided weekly group nutrition education sessions for the first month, and monthly sessions thereafter through the end of 24 months. Weight, HbA_1c, glucose, and lipids were measured at baseline and 6, 12, and 24 months. Of the 144 enrolled participants, 68 returned for the month 24 assessment visit. Weights were retrieved from electronic medical records for an additional 57 participants (total, 125 participants) at month 24. All participants with a baseline measurement and at least one of the three other measurements were included in the mixed‐model analyses (n = 138). The low‐intensity intervention resulted in modest weight loss in both groups at month 24. At this time, participants in the low‐carbohydrate group lost 1.5 kg, compared to 0.2 kg in the low‐fat group (P = 0.147). Lipids, glycemic indexes, and dietary intake did not differ between groups at month 24 (or at months 6 or 12) (ClinicalTrials.gov number, NCT00108459).     

The Women on the Move Through Activity and Nutrition (WOMAN) study: final 48-month results

The Women on the Move through Activity and Nutrition (WOMAN) study was designed to test whether a nonpharmacological intervention including qualitative and quantitative dietary changes to induce weight loss and increased physical activity levels would reduce blood triglyceride levels and number of low‐density lipoprotein particles (LDL‐P). Such decreases in lipoproteins and other risk factors could reduce or slow progression of subclinical cardiovascular disease (CVD). Study participants were randomized to either the intervention (Lifestyle Change) or assessment (Health Education) group. Most of the intervention ended at the 30‐month visit. The last 48‐month examination was completed in 9/2008. There was very substantial weight loss and increased exercise during the first 30 months of the trial resulting in significant decreases in CV risk factors. Most of the intervention effect was lost through 48 months. Weight loss was 3.4 kg in Lifestyle Intervention and 0.2 kg in the Health Education at 48 months (P = 0.000). There were no significant changes at 48 months in lipid levels, blood pressure (BP), glucose, insulin, or in the subclinical measures of coronary calcium, carotid intima media thickness, or plaque. There was a significant decrease in long‐distance corridor walk time in the Lifestyle vs. Health Education groups. Significant lifestyle changes can be achieved that result in decreases in CV risk factors. Whether such changes reduce CV outcomes is still untested in clinical trials of weight loss or exercise. Long‐term maintenance of successful lifestyle changes, weight loss and reduced risk factors is the hurdle for lifestyle interventions attempting to prevent CV and other chronic diseases.     

Achieving Weight and Activity Goals Among Diabetes Prevention Program Lifestyle Participants

Objective: The Diabetes Prevention Program (DPP) showed that intensive lifestyle intervention reduced the risk of diabetes by 58%. This paper examines demographic, psychosocial, and behavioral factors related to achieving weight loss and physical activity goals in the DPP lifestyle participants. Research Methods and Procedures: Lifestyle participants (n = 1079; mean age = 50.6, BMI = 33.9, 68% female, and 46% from minority groups) had goals of 7% weight loss and 150 min/wk of physical activity. Goal achievement was assessed at the end of the 16‐session core curriculum (approximately week 24) and the final intervention visit (mean = 3.2 years) as a function of demographic, psychosocial, and behavioral variables. Results: Forty‐nine percent met the weight loss goal and 74% met the activity goal initially, while 37% and 67%, respectively, met these goals long‐term. Men and those with lower initial BMI were more likely to meet activity but not weight loss goals. Hispanic, Asian, and Native Americans were more likely to meet the long‐term activity goals, and whites were more likely to meet the initial weight loss goal. In multivariate analyses, meeting the long‐term weight loss goal and both activity goals increased with age, while psychosocial and depression measures were unrelated to goal achievement. Dietary self‐monitoring was positively related to meeting both weight loss and activity goals, and meeting the activity goal was positively related to meeting the weight loss goal. Participants who met initial goals were 1.5 to 3.0 times more likely to meet these goals long‐term. Discussion: Success at meeting the weight loss and activity goals increased with age. Initial success predicted long‐term success. Self‐monitoring and meeting activity goals were related to achieving and sustaining weight loss.     

A randomized pilot trial of a full subsidy vs. a partial subsidy for obesity treatment

Intensive obesity treatment is mandated by federal health care reform but is costly. A partial subsidy for obesity treatment could lower the cost of treatment, without reducing its efficacy. This study sought to test whether a partial subsidy for obesity treatment would be feasible, as compared to a fully subsidized intervention. The study was a pilot randomized trial. Participants (n = 50) were primary care patients with obesity and at least one comorbid condition (diabetes, hypertension, dyslipidemia, or obstructive sleep apnea). Each participant received eight weight loss counseling visits as well as portion-controlled foods for weight loss. Participants were randomized to full subsidy or partial subsidy (2 vs. 1 meal per day provided). The primary outcome was weight change after 4 months. Secondary outcomes included changes in blood pressure, waist circumference, and health-related quality of life. Participants in the full and partial subsidy groups lost 5.9 and 5.3 kg, equivalent to 5.3% and 5.1% of initial weight, respectively (P = 0.71). Changes in secondary outcomes were similar in the two groups. A partial subsidy was feasible and induced a clinically similar amount of weight loss, compared to a full subsidy. Large-scale testing of economic incentives for weight control is merited given the federal mandate to offer weight loss counseling to obese patients.     

Different screening strategies (single or dual) for the diagnosis of suspected latent tuberculosis: a cost effectiveness analysis

Background

Obesity and asthma have reached epidemic proportions in the US. Their concurrent rise over the last 30 years suggests that they may be connected. Numerous observational studies support a temporally-correct, dose-response relationship between body mass index (BMI) and incident asthma. Weight loss, either induced by surgery or caloric restriction, has been reported to improve asthma symptoms and lung function. Due to methodological shortcomings of previous studies, however, well-controlled trials are needed to investigate the efficacy of weight loss strategies to improve asthma control in obese individuals.

Methods/Design

BE WELL is a 2-arm parallel randomized clinical trial (RCT) of the efficacy of an evidence-based, comprehensive, behavioral weight loss intervention, focusing on diet, physical activity, and behavioral therapy, as adjunct therapy to usual care in the management of asthma in obese adults. Trial participants (n = 324) are patients aged 18 to 70 years who have suboptimally controlled, persistent asthma, BMI between 30.0 and 44.9 kg/m², and who do not have serious comorbidities (e.g., diabetes, heart disease, stroke). The 12-month weight loss intervention to be studied is based on the principles of the highly successful Diabetes Prevention Program lifestyle intervention. Intervention participants will attend 13 weekly group sessions over a four-month period, followed by two monthly individual sessions, and will then receive individualized counseling primarily by phone, at least bi-monthly, for the remainder of the intervention. Follow-up assessment will occur at six and 12 months. The primary outcome variable is the overall score on the Juniper Asthma Control Questionnaire measured at 12 months. Secondary outcomes include lung function, asthma-specific and general quality of life, asthma medication use, asthma-related and total health care utilization. Potential mediators (e.g., weight loss and change in physical activity level and nutrient intake) and moderators (e.g., socio-demographic characteristics and comorbidities) of the intervention effects also will be examined.

Discussion

This RCT holds considerable potential for illuminating the nature of the obesity-asthma relationship and advancing current guidelines for treating obese adults with asthma, which may lead to reduced morbidity and mortality related to the comorbidity of the two disorders.

Trial registration

NCT00901095     

Night Eating Syndrome Is Associated with Depression,Low Self‐Esteem,Reduced Daytime Hunger,and Less Weight Loss in Obese Outpatients

Objective: The objective of this study was to assess the relationship between the night eating syndrome (NES), measures of depression and self‐esteem, test meal intake, and weight loss in obese participants. Research Methods and Procedures: The study included 76 overweight (body mass index = 36.7 ± 6.5 SD) outpatients (53 women and 23 men; aged 43.5 ± 9.5 years) entering a weight loss program. They completed a Night Eating Questionnaire, the Zung Depression Inventory, and the Rosenberg Self‐Esteem Scale. Based on criteria by Stunkard et al. (Stunkard A, Berkowitz R, Wadden T, Tanrikut C, Reiss E, Young L. Binge eating disorder and the night eating syndrome. Int J Obes Relat Metab Disord. 1996;20:1–6), participants had NES if they reported: (1) skipping breakfast ≥4 d/wk, interpreted as morning anorexia; (2) consuming more than 50% of total daily calories after 7 pm ; and (3) difficulty falling asleep or staying asleep ≥4 d/wk. Eleven (14%) participants met the criteria for NES. After an 8‐hour fast, all participants ingested a nutritionally complete liquid meal through a straw from a large opaque cooler until extremely full. They also completed ratings of hunger and fullness before and after this meal. Results: Night eaters had higher depression (p = 0.04), lower self‐esteem (p = 0.003), and less hunger (p = 0.005), and a trend for more fullness (p = 0.06) before the daytime test meal than the others. However, there were no significant differences in test‐meal intake between groups. Nevertheless, test‐meal intake was greater later in the day only for the night eaters (p = 0.01). Over a 1‐month period, the night eaters lost less weight (4.4 ± 3.2 kg) than the others (7.3 ± 3.2 kg; p = 0.04), after controlling for body mass index. Discussion: NES is a syndrome with distinct psychopathology and increased food intake later in the day, both of which may contribute to poorer weight loss outcome. NES criteria need to be better quantified and NES deserves consideration as a diagnostic eating disorder.     

Weight loss of black, white, and Hispanic men and women in the Diabetes Prevention Program

Objective: To provide the specific weight loss outcomes for African‐American, Hispanic, and white men and women in the lifestyle and metformin treatment arms of the Diabetes Prevention Program (DPP) by race‐gender group to facilitate researchers translating similar interventions to minority populations, as well as provide realistic weight loss expectations for clinicians. Methods and Procedures: Secondary analyses of weight loss of 2,921 overweight participants (22% black; 17% Hispanic; 61% white; and 68% women) with impaired glucose tolerance randomized in the DPP to intensive lifestyle modification, metformin or placebo. Data over a 30‐month period are examined for comparability across treatment arms by race and gender. Results: Within lifestyle treatment, all race‐gender groups lost comparable amounts of weight with the exception of black women who exhibited significantly smaller weight losses (P < 0.01). For example, at 12 months, weight losses for white men (?8.4%), white women (?8.1%), Hispanic men (?7.8%), Hispanic women (?7.1%), and black men (?7.1%) were similar and significantly higher than black women (?4.5%). In contrast, within metformin treatment, all race‐gender groups including black women lost similar amounts of weight. Race‐gender specific mean weight loss data are provided by treatment arm for each follow‐up period. Discussion: Diminished weight losses were apparent among black women in comparison with other race‐gender groups in a lifestyle intervention but not metformin, underscoring the critical nature of examining sociocultural and environmental contributors to successful lifestyle intervention for black women.     

Valuing the Benefits of Weight Loss Programs: An Application of the Discrete Choice Experiment

Objective: Obesity is a leading health threat. Determination of optimal therapies for long‐term weight loss remains a challenge. Evidence suggests that successful weight loss depends on the compliance of weight loss program participants with their weight loss efforts. Despite this, little is known regarding the attributes influencing such compliance. The purpose of this study was to assess, using a discrete choice experiment (DCE), the relative importance of weight loss program attributes to its participants and to express these preferences in terms of their willingness to pay for them. Research Methods: A DCE survey explored the following weight loss program attributes in a sample of 165 overweight adults enrolled in community weight loss programs: cost, travel time required to attend, extent of physician involvement (e.g., none, monthly, every 2 weeks), components (e.g., diet, exercise, behavior change) emphasized, and focus (e.g., group, individual). The rate at which participants were willing to trade among attributes and the willingness to pay for different configurations of combined attributes were estimated using regression modeling. Results: All attributes investigated appeared to be statistically significant. The most important unit change was “program components emphasized” (e.g., moving from diet only to diet and exercise). Discussion: The majority of participants were willing to pay for weight loss programs that reflected their preferences. The DCE tool was useful in quantifying and understanding individual preferences in obesity management and provided information that could help to maximize the efficiency of existing weight loss programs or the design of new programs.     

Evaluating the Cost-Effectiveness of Lifestyle Modification versus Metformin Therapy for the Prevention of Diabetes in Singapore

BackgroundIn Singapore, as diabetes is an increasingly important public health issue, the cost-effectiveness of pursuing lifestyle modification programs and/or alternative prevention strategies is of critical importance for policymakers. While the US Diabetes Prevention Program (DPP) compared weight loss through lifestyle modification with oral treatment of diabetes drug metformin to prevent/delay the onset of type 2 diabetes in pre-diabetic subjects, no data on either the actual or potential cost effectiveness of such a program is available for East or South-east Asian populations. This study estimates the 3-year cost-effectiveness of lifestyle modification and metformin among pre-diabetic subjects from a Singapore health system and societal perspective.MethodologyCost effectiveness was analysed from 2010–2012 using a decision-based model to estimate the rates of getting diabetes, healthcare costs and health-related quality of life. Cost per quality-adjusted life year (QALY) was estimated using costs relevant to the time horizon of the study from Singapore. All costs are expressed in 2012 US dollars.ConclusionBased on adaptation of the DPP data to local conditions, both lifestyle modification and metformin intervention are likely to be cost-effective and worth implementing in Singapore to prevent or delay the onset of type 2 diabetes. However, the cost of lifestyle modification from the societal perspective would have to be reduced in order to match the cost-effectiveness of metformin intervention.     

Geographic Variation in the Prevalence of Obesity,Diabetes, and Obesity‐Related Behaviors**

Objective: To examine the variation in the prevalences of obesity and type 2 diabetes in weight loss counseling by health providers and in other potential obesity‐related determinants in 100 metropolitan statistical areas in the United States. Research Methods and Procedures: We performed a cross‐sectional study using data from the 2000 Behavioral Risk Factor Surveillance System, the largest telephone survey of health behaviors in the United States, of age‐adjusted prevalence of obesity, type 2 diabetes, intake of ≥five servings of fruits and vegetables per day, participation in 150 minutes of leisure‐time physical activity per week, receipt of weight management advice, and reports of trying to lose or maintain weight among men and women more than 18 years old. Results: The age‐adjusted prevalence of obesity ranged from 13.1% to 30.0% and that of type 2 diabetes from 3.3% to 9.2%. Among participants who had visited a physician for a routine checkup in the previous 12 months, 13.1% to 27.1% of all participants recalled receiving advice from a health professional about their weight, and 11.7% to 34.6% of overweight or obese participants recalled receiving advice to maintain or lose weight. Discussion: Significant differences in the prevalence of obesity and self‐reported type 2 diabetes and in medical practice patterns regarding weight management advice exist among metropolitan statistical areas. These results suggest important opportunities to investigate reasons for these variations that could potentially be used to mitigate the current epidemic of obesity and to identify areas where obesity and diabetes prevention efforts may need to be targeted.     

The effect of training in reduced energy density eating and food self-monitoring accuracy on weight loss maintenance

Background: Failure to maintain weight losses in lifestyle change programs continues to be a major problem and warrants investigation of innovative approaches to weight control. Objective: The goal of this study was to compare two novel group interventions, both aimed at improving weight loss maintenance, with a control group. Methods and Procedures: A total of 103 women lost weight on a meal replacement‐supplemented diet and were then randomized to one of three conditions for the 14‐week maintenance phase: cognitive‐behavioral treatment (CBT); CBT with an enhanced food monitoring accuracy (EFMA) program; or these two interventions plus a reduced energy density eating (REDE) program. Assessments were conducted periodically through an 18‐month postintervention. Outcome measures included weight and self‐reported dietary intake. Data were analyzed using completers only as well as baseline‐carried‐forward imputation. Results: Participants lost an average of 7.6 ± 2.6 kg during the weight loss phase and 1.8 ± 2.3 kg during the maintenance phase. Results do not suggest that the EFMA intervention was successful in improving food monitoring accuracy. The REDE group decreased the energy density (ED) of their diets more so than the other two groups. However, neither the REDE nor the EFMA condition showed any advantage in weight loss maintenance. All groups regained weight between 6‐ and 18‐month follow‐ups. Discussion: Although no incremental weight maintenance benefit was observed in the EFMA or EFMA + REDE groups, the improvement in the ED of the REDE group's diet, if shown to be sustainable in future studies, could have weight maintenance benefits.     

Willingness to pay for obesity pharmacotherapy

Several treatments for obesity have received regulatory approval, but health insurers and other payers typically refuse to support access to them. Thus, patients are left to bear significant out-of-pocket costs for obesity pharmacotherapy. This study aimed to assess preferences and willingness to pay (WTP) for obesity medications among people seeking weight loss in the United States and United Kingdom. An online survey was developed based on literature review, clinician interviews, and profiles of available therapies. Participants indicated their preference for hypothetical treatments which varied by seven attributes: percentage of weight loss, long-term health risk reduction, time to noticeable weight loss, delivery mode, side effects, lifestyle modification, and cost; 502 obese participants completed the survey (mean BMI 37.12 kg/m(2) (±4.63); 73.5% female; 47.7 (±12.9) years of age). The participants deemed weight loss of >21 kg (United Kingdom) and >28 kg (United State) as "acceptable". All treatment attributes were important (P < 0.001) except "time to noticeable weight loss." The survey found that percentage weight loss was the most important factor for patients and a reduction in long-term health risk was relatively less important. Patients were willing to pay ￡6.51/$10.49 per month per percentage point of weight loss that a pharmacotherapy could provide. Participants also highly valued therapies that did not require substantial lifestyle modifications and were willing to pay ￡17.78/$30.77 more per month for a one-pill-per-day treatment vs. a weekly injectable. Participants placed a high value on weight loss and avoiding changes to their lifestyle, and less value on reducing long-term risks to health.     

Glucocentricity or adipocentricity: a critical view of consensus and clinical guidelines for the treatment of type 2 diabetes mellitus

Eighty percent of patients with type 2 diabetes mellitus (T2DM) are overweight or obese, which in turn is associated with other cardiovascular risk factors and an increased risk of cancer. Large intervention studies focused on intensive glycemic control have failed to show a reduction of cardiovascular events in T2DM patients. The two major concerns in these studies were weight gain and severe hypoglycemia in the arms of intensive intervention, which could have mitigated the potential beneficial effect of glycemic control. On the contrary, weight loss in diabetic patients through changes in lifestyle, drugs and/or surgery simultaneously improves all cardiovascular risk factors including hyperglycemia. Bariatric surgery has shown an early resolution of T2DM in a large percentage of patients and a decrease of diabetes-specific mortality. Despite this, all consensus and recommendations for the treatment of T2DM focus their decisions on the glycated hemoglobin value. This article aims to open a debate on the need to replace the glucose-centered therapeutic strategy for a weight-centered strategy.     

Intensive Lifestyle Intervention in General Practice to Prevent Type 2 Diabetes among 18 to 60-Year-Old South Asians: 1-Year Effects on the Weight Status and Metabolic Profile of Participants in a Randomized Controlled Trial

Aim

To study 1-year effectiveness of an intensive, culturally targeted lifestyle intervention in general practice for weight status and metabolic profile of South-Asians at risk of type 2 diabetes.

Methods

536 South-Asians at risk of type 2 diabetes were randomized to an intervention (n = 283) or control (n = 253) group. The intervention, which was targeted culturally to the South-Asian population, consisted of individual lifestyle counselling, a family session, cooking classes, and supervised physical activity programme. All components of the intervention were carried out by professionals as part of their daily clinical practice. The control group received generic lifestyle advice. Change in weight status and metabolic profile were assessed after 1 year.

Results

After 1 year, 201 participants were lost to follow-up. Remaining participants in intervention (n = 177) and control (n = 158) group had similar baseline characteristics. Weight loss in the intervention group was 0.2±3.3 kg, weight gain in the control group was 0.4±3.1 kg (p = 0.08). Changes in other weight-related measurements did not differ significantly between groups. Furthermore, there were no differences between groups in changes of metabolic profile. All results remained similar after repeating analyses in a multiple imputed dataset.

Discussion

An intensive, culturally targeted, lifestyle intervention of 1 year did not improve weight status and metabolic profile of South-Asians at risk of type 2 diabetes. The laborious recruitment, high drop-out, and lack of effectiveness emphasise the difficulty of realising health benefits in practice and suggest that this strategy might not be the optimal approach for this population.

Trial Registration

Nederlands Trial Register NTR1499     

Association of type 2 diabetes susceptibility loci with one-year weight loss in the look AHEAD clinical trial

The importance of lifestyle intervention for the prevention and treatment of type 2 diabetes (T2D) has been underscored by the limited benefit of pharmacologic therapies. We sought to determine whether genetic variants that contribute to T2D risk modify the response of weight and waist circumference to an intensive lifestyle intervention (ILI) in patients with obesity and T2D. Look AHEAD (Action for Health in Diabetes) is a randomized clinical trial comparing an ILI with a control condition on the risk of cardiovascular disease in overweight adults with T2D. We analyzed 28 single-nucleotide polymorphisms (SNPs) at/near 17 T2D-susceptibility genes in 3,903 consented participants. We genetically characterized the cohort by assessing whether T2D-susceptibility loci were overrepresented compared with a nondiabetic community-based cohort (N = 1,016). We evaluated the association of individual variants and a composite genetic risk score (GRS) with anthropometric traits at baseline and after 1-year of intervention. Look AHEAD subjects carried more T2D-susceptibility alleles than the control population. At baseline, TCF7L2 risk alleles and the highest GRS were associated with lower BMI and waist circumference. Nominally significant genotype-by-intervention interactions were detected for 1-year change in waist circumference with JAZF1, MTNR1B, and IRS1, and BMI with JAZF1. Highest GRS was associated with a greater reduction in waist circumference at year 1, although the variance in change attributable to the GRS was small. This study shows that the genetic burden associated with T2D risk does not undermine the effect of lifestyle intervention and suggests the existence of additional genomic regions, distinct from the T2D-susceptibility loci, which may enhance or mitigate weight loss.