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The Long-term Effectiveness of a Lifestyle Intervention in Severely Obese Individuals

      Abstract

      Objective

      Severe obesity (body mass index [BMI] ≥40 kg/m2) is a serious public health concern. Although bariatric surgery is an efficacious treatment approach, it is limited in reach; thus, nonsurgical treatment alternatives are needed. We examined the 4-year effects of an intensive lifestyle intervention on body weight and cardiovascular disease risk factors among severely obese, compared with overweight (25 ≤BMI <30), class I (30 ≤BMI <35), and class II obese (35 ≤BMI <40) participants.

      Methods

      There were 5145 individuals with type 2 diabetes (45-76 years, BMI ≥25 kg/m2) randomized to an intensive lifestyle intervention or diabetes support and education. The lifestyle intervention group received a behavioral weight loss program that included group and individual meetings, a ≥10% weight loss goal, calorie restriction, and increased physical activity. Diabetes support and education received a less intense educational intervention. Four-year changes in body weight and cardiovascular disease risk factors were assessed.

      Results

      Across BMI categories, 4-year changes in body weight were significantly greater in lifestyle participants compared with diabetes support and education (Ps <.05). At year 4, severely obese lifestyle participants lost 4.9%±8.5%, which was similar to class I (4.8%±7.2%) and class II obese participants (4.4%±7.6%), and significantly greater than overweight participants (3.4%±7.0%; P <.05). Four-year changes in low-density-lipoprotein cholesterol, triglycerides, diastolic blood pressure, HbA1c, and blood glucose were similar across BMI categories in lifestyle participants; however, the severely obese had less favorable improvements in high-density-lipoprotein cholesterol (3.1±0.4 mg/dL) and systolic blood pressure (−1.4±0.7 mm Hg) compared with the less obese (Ps <.05).

      Conclusion

      Lifestyle interventions can result in important long-term weight losses and improvements in cardiovascular disease risk factors among a significant proportion of severely obese individuals.

      Keywords

      In 2009-2010, it was estimated that 6.3% of the United States adult population was severely obese (body mass index [BMI] ≥40 kg/m2).
      • Flegal K.M.
      • Carroll M.D.
      • Kit B.K.
      • Ogden C.L.
      Prevalence of obesity and trends in the distribution of body mass index among US adults, 1999-2010.
      Moreover, it is expected that the prevalence of severe obesity will nearly double over the next 2 decades.
      • Finkelstein E.A.
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      • Thompson H.
      • et al.
      Obesity and severe obesity forecasts through 2030.
      This shift in the population weight distribution toward the more extreme ends of obesity is concerning, given the increased risk for cardiovascular disease and all-cause mortality that is associated with this magnitude of excess body weight.
      • Flegal K.M.
      • Carroll M.D.
      • Kit B.K.
      • Ogden C.L.
      Prevalence of obesity and trends in the distribution of body mass index among US adults, 1999-2010.
      • McTigue K.
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      Mortality and cardiac and vascular outcomes in extremely obese women.
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      The disease burden associated with overweight and obesity.
      • Sturm R.
      Increases in morbid obesity in the USA: 2000-2005.
      Thus, there is urgency in determining how best to treat this obesity sub-group. While bariatric surgery is a highly efficacious modality,
      • Buchwald H.
      • Estok R.
      • Fahrbach K.
      • et al.
      Weight and type 2 diabetes after bariatric surgery: systematic review and meta-analysis.
      • Sjostrom L.
      • Narbro K.
      • Sjostrom C.D.
      • et al.
      Effects of bariatric surgery on mortality in Swedish obese subjects.
      it currently treats <1% of the eligible population.
      • Flegal K.M.
      • Carroll M.D.
      • Kit B.K.
      • Ogden C.L.
      Prevalence of obesity and trends in the distribution of body mass index among US adults, 1999-2010.
      • Buchwald H.
      • Oien D.M.
      Metabolic/bariatric surgery Worldwide 2008.
      • Intensive lifestyle interventions can result in significant long-term reductions in body weight among a considerable proportion of severely obese individuals with type 2 diabetes.
      • Modest reductions in body weight, even despite persistent severe obesity, can significantly improve cardiovascular disease risk factors in this population.
      • Behavioral weight loss programs should not be ignored as a potential treatment strategy for individuals with a body mass index ≥40 kg/m2.
      Consequently, there has been renewed interest in examining the efficacy of lifestyle interventions for the treatment of severe obesity and related comorbidities.
      • Blackburn G.L.
      • Wollner S.
      • Heymsfield S.B.
      Lifestyle interventions for the treatment of class III obesity: a primary target for nutrition medicine in the obesity epidemic.
      Goodpaster et al
      • Goodpaster B.H.
      • Delany J.P.
      • Otto A.D.
      • et al.
      Effects of diet and physical activity interventions on weight loss and cardiometabolic risk factors in severely obese adults: a randomized trial.
      reported that an intensive lifestyle intervention for severely obese individuals resulted in a 12.1-kg weight loss and significant improvements in numerous cardiovascular disease risk factors at 1 year. Furthermore, we reported similar findings in Look AHEAD (Action for Health in Diabetes), a multicenter randomized controlled trial examining the long-term effects (up to 13.5 years) of an intensive lifestyle intervention on weight loss and cardiovascular morbidity and mortality in overweight or obese individuals with type 2 diabetes.
      • Ryan D.H.
      • Espeland M.A.
      • Foster G.D.
      • et al.
      Look AHEAD (Action for Health in Diabetes): design and methods for a clinical trial of weight loss for the prevention of cardiovascular disease in type 2 diabetes.
      At 1 year, the severely obese lost 11.2 kg, or 9.0% of initial body weight, which was similar to class I (BMI 30 to <35 kg/m2) and class II (BMI 35 to <40 kg/m2) obese individuals and greater than the overweight (BMI 25 to <30 kg/m2). In addition, the improvements in blood pressure, glucose control, and lipids at 1 year were similar across BMI categories.
      • Unick J.L.
      • Beavers D.
      • Jakicic J.M.
      • et al.
      Effectiveness of lifestyle interventions for individuals with severe obesity and type 2 diabetes: results from the Look AHEAD trial.
      Together these findings suggest that in the short term, lifestyle interventions are an efficacious treatment approach for individuals with severe obesity. However, whether lifestyle interventions can be an effective long-term weight control strategy for this population remains unclear.
      Previous studies in non-severely obese cohorts have demonstrated less than optimal rates of long-term weight maintenance.
      • Jeffery R.W.
      • Drewnowski A.
      • Epstein L.H.
      • et al.
      Long-term maintenance of weight loss: current status.
      • Turk M.W.
      • Yang K.
      • Hravnak M.
      • Sereika S.M.
      • Ewing L.J.
      • Burke L.E.
      Randomized clinical trials of weight loss maintenance: a review.
      • Wing R.R.
      • Phelan S.
      Long-term weight loss maintenance.
      However, to our knowledge, the only study to examine the long-term effects of a behavioral weight loss program in a severely obese cohort was the Louisiana Obese Subjects Study.
      • Ryan D.H.
      • Johnson W.D.
      • Myers V.H.
      • et al.
      Nonsurgical weight loss for extreme obesity in primary care settings: results of the Louisiana Obese Subjects Study.
      This 2-year randomized controlled trial assessed whether primary care physicians could effectively implement a lifestyle weight loss program in this population. Severely obese individuals who completed the program achieved a 13.1% weight loss at 1 year and regained approximately one quarter of lost weight by Year 2 (9.6% weight loss from baseline), despite continued monthly group meetings and the use of prescription weight loss medications. However, these data were derived from completers' analyses and are undermined by poor retention rates (51%) at Year 2.
      The purpose of the present study was to examine the effects of an intensive lifestyle intervention on body weight and cardiovascular disease risk factors in severely obese individuals over a longer, 4-year period. Moreover, the severely obese were compared with the less obese on each of these parameters. However, it should be noted that our aim was not to compare lifestyle interventions with bariatric surgery. Indeed, bariatric surgery results in larger weight losses and improvements in cardiovascular disease risk factors long term.
      • Buchwald H.
      • Estok R.
      • Fahrbach K.
      • et al.
      Weight and type 2 diabetes after bariatric surgery: systematic review and meta-analysis.
      • Sjostrom L.
      • Narbro K.
      • Sjostrom C.D.
      • et al.
      Effects of bariatric surgery on mortality in Swedish obese subjects.
      However surgical procedures may be limited in reach and many individuals may prefer a less aggressive treatment approach.
      • Flegal K.M.
      • Carroll M.D.
      • Kit B.K.
      • Ogden C.L.
      Prevalence of obesity and trends in the distribution of body mass index among US adults, 1999-2010.
      • Buchwald H.
      • Oien D.M.
      Metabolic/bariatric surgery Worldwide 2008.
      • Livingston E.H.
      • Burchell I.
      Reduced access to care resulting from centers of excellence initiatives in bariatric surgery.
      • Strømmen M.
      • Kulseng B.
      • Vedul-Kjelsås E.
      • Johnsen H.
      • Johnsen G.
      • Mårvik R.
      Bariatric surgery or lifestyle intervention? An exploratory study of severely obese patients' motivation for two different treatments.
      Thus, it also is important that nonsurgical treatment approaches to severe obesity also are empirically tested and continually improved upon.

      Methods

      Participants

      As previously reported, 5145 individuals from 16 centers were enrolled in the Look AHEAD trial.
      • Pi-Sunyer X.
      • Blackburn G.
      • Brancati F.L.
      • et al.
      Reduction in weight and cardiovascular disease risk factors in individuals with type 2 diabetes: one-year results of the look AHEAD trial.
      Participants had type 2 diabetes, were 45-76 years of age, and had a BMI ≥25 kg/m2 (or ≥27 kg/m2 if taking insulin). Individuals passed a maximal exercise test at baseline and completed 2 weeks of self-monitoring to demonstrate behavioral adherence. Further inclusion criteria were HbA1c ≤11%, triglycerides <600 mg/dL, and systolic and diastolic blood pressure ≤160 and ≤100 mm Hg, respectively. Participants provided written informed consent and study procedures were approved by the Institutional Review Board at each site.

      Interventions

      Participants were assigned randomly within each center to an intensive lifestyle intervention or diabetes support and education intervention. Complete details of the intensive lifestyle intervention have been described elsewhere.
      • Wadden T.A.
      • West D.S.
      • Delahanty L.
      • et al.
      The Look AHEAD study: a description of the lifestyle intervention and the evidence supporting it.
      In short, the lifestyle intervention participants were seen weekly during the first 6 months (3 group and 1 individual meeting), 3 times/month during months 7-12 (2 group and 1 individual meeting), and received one individual face-to-face contact with an interventionist and one telephone contact/month during years 2-4. In addition, 2-3 times/year participants reported to the center weekly for a 6- to 8-week weight loss refresher course. The lifestyle participants were given an initial weight loss goal of ≥10% of initial body weight, with a study-wide goal of ≥7%. They also received a strong behavioral intervention that utilized strategies such as self-monitoring, problem-solving, goal-setting, and relapse prevention to modify dietary and exercise behaviors. Individuals were given a calorie goal of 1200-1800 kcal/day and were instructed to reduce dietary fat intake to <30% of total calories from fat, with <10% from saturated fat. To increase dietary adherence, liquid meal replacements also were provided and utilized. Participants were given a 6-month physical activity goal of ≥175 min/week of moderate- to vigorous-intensity exercise similar to brisk walking and were instructed to accumulate this exercise in bouts ≥10 minutes in duration.
      A detailed description of the diabetes support and education treatment arm has been published previously.
      • Wesche-Thobaben J.A.
      The development and description of the comparison group in the Look AHEAD trial.
      During each of the first 4 years, diabetes support and education participants were invited to 3 group sessions/year to promote retention. These sessions focused on diet, physical activity, and social support, but did not include the use of behavioral strategies, nor were participants weighed at meetings. Both diabetes support and education participants and intensive lifestyle intervention participants received usual medical care from their personal physicians.

      Assessments

      Assessments were conducted annually and were completed by certified, blinded staff members. Height, weight, BMI, and blood pressure were measured using standard procedures.
      • Pi-Sunyer X.
      • Blackburn G.
      • Brancati F.L.
      • et al.
      Reduction in weight and cardiovascular disease risk factors in individuals with type 2 diabetes: one-year results of the look AHEAD trial.
      Serum measures were analyzed by the Central Biochemistry Laboratory (Northwest Lipid Research Laboratories, University of Washington, Seattle, Wash). Frozen specimens were shipped for the analysis of HbA1c, fasting serum glucose, total triglycerides, high-density lipoproteins (HDL) and low-density lipoproteins (LDL) using methods described elsewhere.
      • Pi-Sunyer X.
      • Blackburn G.
      • Brancati F.L.
      • et al.
      Reduction in weight and cardiovascular disease risk factors in individuals with type 2 diabetes: one-year results of the look AHEAD trial.

      Statistical Analyses

      Participants were divided into baseline BMI categories as follows: overweight (BMI 25 to <30); class I obese (BMI 30 to <35), class II obese (BMI 35 to <40), and class III obese (BMI ≥40). To yield unbiased estimates of the intervention effect on outcome measures, participants who underwent gastric bypass surgery were excluded from all analyses on visits occurring after the date of surgery. The number of affected participants at each visit is not presented due to the need to maintain the blinding of investigators. All statistical tests are adjusted by race, sex, and age at baseline. Mixed linear models were used to estimate and compare means of continuous variables across baseline BMI groups. Achievement of weight loss and American Diabetes Association (ADA) goals were analyzed using logistic regression at baseline and 4-year visits, testing for interactions when appropriate. Given that the change in medication usage from years 1-4 was similar across BMI categories but the proportion using medications differed at baseline, models analyzing cardiovascular disease risk factor outcomes at 1 and 4 years were adjusted when appropriate for baseline medication usage and baseline cardiovascular disease risk factor values. Repeated-measures logistic regression models were utilized to analyze Year 4 goal attainment based on progression from baseline goal status. All pairwise comparisons between groups were adjusted for multiple comparisons using the Bonferroni method.

      Results

      The baseline characteristics of study participants stratified by BMI category have previously been reported,
      • Unick J.L.
      • Beavers D.
      • Jakicic J.M.
      • et al.
      Effectiveness of lifestyle interventions for individuals with severe obesity and type 2 diabetes: results from the Look AHEAD trial.
      and selected ones are shown in the Table. In short, severely obese participants were younger, had lower physical activity and fitness, a larger proportion were female, and a similar percentage were classified as being non-Hispanic white (64.1%), compared with those with a BMI <40. Outcome assessments were completed in ≥95% of participants in each BMI category at Year 4 (see primary outcomes manuscript
      • Pi-Sunyer X.
      • Blackburn G.
      • Brancati F.L.
      • et al.
      Reduction in weight and cardiovascular disease risk factors in individuals with type 2 diabetes: one-year results of the look AHEAD trial.
      for Consort diagram).
      TableFour-Year Changes (mean±SE) in Cardiovascular Disease Risk Factors for Intensive Lifestyle Intervention Participants
      Overweight (n=395)Class I (n=892)Class II (n=654)Severe (n=562)P Value for Group Mean Differences
      Body weight (kg)
       Baseline79.7±0.6a92.1±0.4b104.5±0.5c123.8±0.5d<.001
       Year 477.2±0.7a87.8±0.5b99.8±0.6c117.2±0.6d<.001
       Δ (4 year – BL)−2.8±0.4a−4.4±0.3b−4.6±0.3b−6.1±0.4c<.001
      BMI (kg/m2)
       Baseline28.3±0.1a32.6±0.1b37.4±0.1c44.7±0.1d<.001
       Year 427.5±0.2a31.2±0.1b35.9±0.2c42.6±0.2d<.001
       Δ (4 year – BL)−0.8±0.2a−1.4±0.1b−1.5±0.1b−2.0±0.1c<.001
      LDL cholesterol (mg/dL)
       Baseline114.4±1.6a111.1±1.0a112.0±1.2a113.8±1.3a.216
       Year 496.4±1.6a94.0±1.1a94.3±1.3a98.2±1.4a.084
       Δ (4 year – BL)−16.6±1.5a−17.6±1.0a−17.7±1.2a−15.3±1.3a.461
      HDL cholesterol (mg/dL)
       Baseline45.6±0.6a42.6±0.4ab43.2±0.5b43.5±0.5a,b<.001
       Year 450.1±0.7a46.7±0.5b47.2±0.5b46.6±0.6b<.001
       Δ (4 year – BL)4.8±0.4a4.0±0.3a,b3.9±0.3a,b3.1±0.4b.023
      Triglycerides (mg/dL)
       Baseline171.1±5.8a184.8±3.8a189.5±4.5a180.9±5.0a.078
       Year 4153.8±6.0a161.5±4.0a159.3±4.7a159.2±5.2a.767
       Δ (4 year – BL)−24.0±5.5a−21.6±3.6a−25.6±4.3a−22.4±4.7a.909
      Systolic blood pressure (mm Hg)
       Baseline124.3±0.9a126.9±0.6a129.4±0.7b131.6±0.7b<.001
       Year 4121.6±0.9a122.1±0.6a123.9±0.7a127.8±0.8b<.001
       Δ (4 year – BL)−4.8±0.9a−5.5±0.6a−4.6±0.7a−1.4±0.7b<.001
      Diastolic blood pressure (mm Hg)
       Baseline69.2±0.5a70.3±0.3a70.0±0.4a69.8±0.4a.335
       Year 466.8±0.5a66.6±0.3a66.7±0.4a67.2±0.4a.741
       Δ (4 year – BL)−2.9±0.4a−3.6±0.3a−3.3±0.3a−2.5±0.4a.145
      HbA1c (%)
       Baseline7.2±0.1a7.2±0.0a7.3±0.0a7.3±0.0a.144
       Year 47.0±0.1a7.0±0.0a7.1±0.1a7.2±0.1a.067
       Δ (4 year – BL)−0.21±0.06a−0.24±0.04a−0.15±0.05a−0.13±0.05a.338
      Serum glucose (mg/dL)
       Baseline150.2±2.3a150.8±1.5a154.9±1.7a153.2±1.9a.189
       Year 4139.1±2.5a141.1±1.7a143.8±2.0a145.8±2.2a.153
       Δ (4 year – BL)−12.7±2.4a−10.2±1.6a−8.6±1.9a−6.1±2.1a.183
      BL=baseline; BMI=body mass index; HDL=high-density lipoprotein; LDL=low-density lipoprotein.
      Values with similar superscripts across columns are similar to one another (P <.05). Baseline and Year-4 cardiovascular disease risk factors adjusted for baseline medication usage. Four-year cardiovascular risk change values adjusted for baseline medication usage and baseline values. BMI and weight are unadjusted.

      Weight Change at Year 4

      Figure 1 illustrates the trajectory of percent weight change from baseline to Year 4 for both lifestyle intervention and diabetes support and education participants stratified by BMI category. At all BMI levels, lifestyle participants achieved significantly larger weight losses compared with diabetes support and education participants, and the interaction between BMI category and treatment arm was not significant (P=.684). Moreover, the percent body weight lost by severely obese lifestyle participants at Year 4 (4.9%) was similar to class I (4.8%) and class II obese participants (4.4%), and significantly greater than those who were overweight at baseline (3.4%; P <.05).
      Figure thumbnail gr1
      Figure 1Percent change in body weight for intensive lifestyle intervention and diabetes support and education participants stratified by body mass index (BMI) category. Solid lines represent diabetes support and education (DSE) participants and dashed lines represent intensive lifestyle intervention (ILI) participants. BMI categories defined as follows: overweight (25 ≤BMI <30), class I obese (30 ≤BMI <35), class II obese (35 ≤BMI <40), severely obese (BMI ≥40).
      Figure 2 demonstrates the percentage of lifestyle participants achieving a weight loss ≥5%, ≥7%, or ≥10% at Year 4, stratified by BMI category. There was no significant difference between BMI categories using the ≥5% weight loss threshold; however, a significantly higher percentage of severely obese participants achieved a ≥7% weight loss when compared with those who were overweight (38% vs 32%, P <.05), and more severely obese participants achieved a ≥10% weight loss compared with overweight and class I obese participants (26% vs 14% or 22% respectively; P <.05).
      Figure thumbnail gr2
      Figure 2Percentage of intensive lifestyle intervention participants in each body mass index (BMI) category achieving a weight loss ≥5%, 7%, and 10% at Year 4. *Indicates that severely obese are significantly different from overweight (P <.05); + indicates that severely obese are significantly different from class I obese (P <.05).

      Changes in Weight from Year 1 to 4

      Although weight regain occurred between Year 1 and 4 in each BMI group, on average, severely obese lifestyle participants regained 40.7% of the weight lost at Year 1, whereas the magnitude of regain was 56.5%, 46.7%, and 47.5% for overweight, class I, and class II obese participants, respectively. In addition, 47% of severely obese participants who lost ≥10% of their initial body weight at Year 1 maintained this magnitude of weight loss at Year 4. This was similar to class I (40%) and class II obese (41%) participants and significantly greater than those who were overweight (38%, P <.05). Finally, of those severely obese individuals who lost <10% of their initial body weight at Year 1, 13% also achieved ≥10% at Year 4, compared with only 3.9% in the overweight group (P <.01).

      Cardiovascular Disease Risk Factors

      Changes in cardiovascular disease risk factors at Year 4 have been reported previously for diabetes support and education participants and intensive lifestyle intervention participants.
      • Wing R.R.
      Long-term effects of a lifestyle intervention on weight and cardiovascular risk factors in individuals with type 2 diabetes mellitus: four-year results of the Look AHEAD trial.
      The Table compares 4-year changes in cardiovascular disease risk factors for lifestyle participants only, stratified by BMI category. The 4-year change in LDL cholesterol, triglycerides, diastolic blood pressure, HbA1c, and blood glucose did not differ across BMI categories; however, the improvement in HDL cholesterol was less in the severely obese compared with the overweight (P <.05). Moreover, the severely obese had a smaller reduction in systolic blood pressure from baseline to Year 4 compared with all other BMI categories (P <.05).
      Lifestyle participants were categorized based upon whether they achieved the ADA goal for HbA1c (<7%), LDL cholesterol (<100 mg/dL), or blood pressure (<130/80 mm Hg) at 4 years. For all 3 ADA goals, time (Ps <.001) and BMI category (Ps=.02-.001) significantly predicted goal attainment at Year 4. However, the time×BMI category interaction was not significant (Ps=.42-.87), suggesting that the probability of goal attainment increased over time among lifestyle participants, with no differences observed across BMI categories. Moreover, severely obese individuals who achieved a 4-year weight loss ≥10% were more likely to meet the goals at Year 4 compared with severely obese individuals who remained weight stable (± 2%). Achievement of a ≥10% weight loss at Year 4 significantly increased the likelihood of achieving the ADA goal for HbA1c (odds ratio [OR] 3.12; 95% CI, 1.8-5.4; P <.001) and blood pressure (OR 2.10; 95% CI, 1.23-3.59; P <.01) compared with severely obese individuals who were weight stable. However, a ≥10% weight loss did not impact the likelihood of achieving the ADA goal for LDL cholesterol (OR 0.99; 95% CI, 0.58-1.69; P=.97). The above-reported OR analyses for achievement of ADA goals among severely obese lifestyle participants were similar to the ORs observed among those in lower BMI categories when similar analyses were performed (Ps >.05).

      Discussion

      This study demonstrates that severely obese individuals with type 2 diabetes can be treated effectively using an intensive lifestyle intervention, with a significant proportion of individuals meeting weight loss and cardiovascular disease risk factor goals at 4 years. The mean 4.9% weight loss achieved by severely obese lifestyle participants at Year 4 was similar, if not better, than their lighter counterparts. Furthermore, 26% of severely obese lifestyle participants achieved a ≥10% weight loss at Year 4, which was significantly greater than the percentage of overweight or class I obese participants achieving this weight loss goal. Moreover, the magnitude of weight regain between Years 1 and 4 was similar or slightly lower in the severely obese compared with the less overweight. Together, these findings suggest that lifestyle interventions are equally effective at reducing body weight long term in severely obese and less obese individuals.
      Although this was the first study to examine the long-term effects of an outpatient behavioral weight loss program on weight outcomes in a severely obese cohort, the magnitude of weight loss seen at Year 4 (4.9%) was very close to the 4.6% reported by Christiansen et al
      • Christiansen T.
      • Bruun J.M.
      • Madsen E.L.
      • Richelsen B.
      Weight loss maintenance in severely obese adults after an intensive lifestyle intervention: 2- to 4-year follow-up.
      at 4 years following a 21-week residential weight loss camp for the severely obese. Moreover, 29% of those who participated in the weight loss camp maintained a ≥10% weight loss at Year 4, which is in line with the 26% seen following lifestyle treatment in the current study. These similar weight-related findings across studies may favor less-intensive outpatient lifestyle interventions as a more practical option for severely obese individuals who do not have the necessary financial resources or are unable or unwilling to commit to living in a residential treatment setting. Future studies should directly compare these approaches.
      Examination of 4-year changes in cardiovascular disease risk factors revealed that the severely obese and less obese experienced similar improvements in the majority of risk factors, with the exception of HDL cholesterol and systolic blood pressure. Moreover, the probability of achieving the ADA goal for HbA1c, LDL cholesterol, and blood pressure increased over time among all intensive lifestyle intervention participants, with no differences observed across BMI categories. Importantly, although the majority of those in the severely obese category remained severely obese at Year 4, they still experienced significant and similar improvements in cardiovascular disease risk factors compared with their less obese counterparts. These findings provide support for the use of lifestyle interventions to reduce cardiovascular disease risk in severely obese individuals.
      Given that a ≥10% weight loss has improved cardiovascular disease risk consistently in nonseverely obese populations,
      National Heart, Lung, and Blood Institute (NHLBI)
      Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults: the evidence report.
      • Wadden T.A.
      • Stunkard A.J.
      Handbook of Obesity Treatment.
      this study also examined whether this relationship exists in the severely obese. Achievement of ≥10% weight loss at Year 4 increased the likelihood of meeting the ADA goal for blood pressure and HbA1c by 200% and 300%, respectively, compared with those who remained weight stable over the 4-year period. This finding is clinically meaningful given that lifestyle interventions will likely not result in reductions to normal weight, or even overweight status in this population. However, even modest reductions (≥10%) in body weight among the severely obese can result in significant improvements in health outcomes.
      Although the lifestyle intervention favorably influenced body weight and health outcomes among all weight categories, the severely obese experienced smaller improvements in HDL cholesterol and systolic blood pressure at Year 4 compared with the less obese. Explanations for this finding are unclear. However, it is possible that a larger magnitude of weight loss is necessary to produce larger improvements in these specific risk parameters and achieve normalization of all cardiovascular disease risk factor values. Indeed, larger weight losses (eg, ≥10%) in this obesity sub-group significantly improved the likelihood of normalizing cardiovascular disease risk factor values. Thus, the goal of future interventions should focus on increasing the proportion of individuals meeting or exceeding this magnitude of weight loss to improve outcomes at the group level. One possible strategy would be to identify individuals who fail to meet specific weight loss goals early in the intervention, and develop and implement novel intervention strategies, tailored toward their individual needs.
      This study is strengthened by the large sample of severely obese individuals (n=577) who were treated with a lifestyle intervention and the high rates of retention (≥95%) at Year 4. However, there are several limitations. First, findings from this study may not be generalizable to the entire severely obese population, given that participants in this study were older (45-76 years), had type 2 diabetes, and were at the lower end of the severe obesity range (95% of participants had a BMI between 40 and <52.5 kg/m2). Moreover, participants were highly motivated, completing a behavioral run-in and passing a maximal exercise test before acceptance into the study. Finally, severely obese and less obese individuals were treated in the same group meetings; thus, it is unclear whether similar outcomes would be observed had the severely obese individuals been treated separately.
      In conclusion, this study provides initial evidence that an intensive lifestyle intervention can result in significant long-term reductions in body weight among a considerable proportion of individuals with severe obesity. Moreover, modest weight reductions (≥10%) can have a beneficial impact on several cardiovascular disease risk factors even within the context of persistent severe obesity. However, for some severely obese participants, risk factors remain elevated even following weight loss and lifestyle treatment. Further research is needed to examine how to improve upon existing lifestyle interventions such that a greater proportion of individuals with severe obesity achieve larger sustained weight losses and related improvements in health outcomes.

      Acknowledgements

      Some of the information contained herein was derived from data provided by the Bureau of Vital Statistics, New York City Department of Health and Mental Hygiene.

      Trial Personnel

      Clinical Sites

      The Johns Hopkins Medical Institutions: Frederick L. Brancati, MD, MHS1; Lee Swartz2; Lawrence Cheskin, MD3; Jeanne M. Clark, MD, MPH3; Kerry Stewart, EdD3; Richard Rubin, PhD3; Jean Arceci, RN; Suzanne Ball; Jeanne Charleston, RN; Danielle Diggins; Mia Johnson; Joyce Lambert; Kathy Michalski, RD; Dawn Jiggetts; Chanchai Sapun.
      Pennington Biomedical Research Center: George A. Bray, MD1; Kristi Rau2; Allison Strate, RN2; Frank L. Greenway, MD3; Donna H. Ryan, MD3; Donald Williamson, PhD3; Brandi Armand, LPN; Jennifer Arceneaux; Amy Bachand, MA; Michelle Begnaud, LDN, RD, CDE; Betsy Berhard; Elizabeth Caderette; Barbara Cerniauskas, LDN, RD, CDE; David Creel, MA; Diane Crow; Crystal Duncan; Helen Guay, LDN, LPC, RD; Carolyn Johnson, Lisa Jones; Nancy Kora; Kelly LaFleur; Kim Landry; Missy Lingle; Jennifer Perault; Cindy Puckett; Mandy Shipp, RD; Marisa Smith; Elizabeth Tucker.
      The University of Alabama at Birmingham: Cora E. Lewis, MD, MSPH1; Sheikilya Thomas MPH2; Monika Safford, MD3; Vicki DiLillo, PhD; Charlotte Bragg, MS, RD, LD; Amy Dobelstein; Stacey Gilbert, MPH; Stephen Glasser, MD3; Sara Hannum, MA; Anne Hubbell, MS; Jennifer Jones, MA; DeLavallade Lee; Ruth Luketic, MA, MBA, MPH; L. Christie Oden; Janet Raines, MS; Cathy Roche, RN, BSN; Janet Truman; Nita Webb, MA; Casey Azuero, MPH; Jane King, MLT; Andre Morgan.

      Harvard Center

      Massachusetts General Hospital: David M. Nathan, MD1; Enrico Cagliero, MD3; Kathryn Hayward, MD3; Heather Turgeon, RN, BS, CDE2; Linda Delahanty, MS, RD3; Ellen Anderson, MS, RD3; Laurie Bissett, MS, RD; Valerie Goldman, MS, RD; Virginia Harlan, MSW; Theresa Michel, DPT, DSc, CCS; Mary Larkin, RN; Christine Stevens, RN; Kylee Miller, BA; Jimmy Chen, BA; Karen Blumenthal, BA; Gail Winning, BA; Rita Tsay, RD; Helen Cyr, RD; Maria Pinto.
      Joslin Diabetes Center: Edward S. Horton, MD1; Sharon D. Jackson, MS, RD, CDE2; Osama Hamdy, MD, PhD3; A. Enrique Caballero, MD3; Sarah Bain, BS;
      Elizabeth Bovaird, BSN, RN; Barbara Fargnoli, MS, RD; Jeanne Spellman, BS, RD; Ann Goebel-Fabbri, PhD; Lori Lambert, MS, RD; Sarah Ledbury, MEd, RD; Maureen Malloy, BS; Kerry Ovalle, MS, RCEP, CDE.
      Beth Israel Deaconess Medical Center: George Blackburn, MD, PhD1; Christos Mantzoros, MD, DSc3; Ann McNamara, RN; Kristina Spellman, RD.
      University of Colorado Health Sciences Center: James O. Hill, PhD1; Marsha Miller, MS, RD2; Brent Van Dorsten, PhD3; Judith Regensteiner, PhD3; Ligia Coelho, BS; Paulette Cohrs, RN, BSN; Susan Green; April Hamilton, BS, CCRC; Jere Hamilton, BA; Eugene Leshchinskiy; Lindsey Munkwitz, BS; Loretta Rome, TRS; Terra Worley, BA; Kirstie Craul, RD, CDE; Sheila Smith, BS.
      Baylor College of Medicine: John P. Foreyt, PhD1; Rebecca S. Reeves, DrPH, RD2; Henry Pownall, PhD3; Ashok Balasubramanyam, MBBS3; Peter Jones, MD3; Michele Burrington, RD, RN; Chu-Huang Chen, MD, PhD3; Allyson Clark Gardner, MS, RD; Molly Gee, MEd, RD; Sharon Griggs; Michelle Hamilton; Veronica Holley; Jayne Joseph, RD; Julieta Palencia, RN; Jennifer Schmidt; Carolyn White.
      The University of Tennessee Health Science Center
      University of Tennessee East: Karen C. Johnson, MD, MPH; Carolyn Gresham, RN; Stephanie Connelly, MD, MPH; Amy Brewer, RD, MS; Mace Coday, PhD; Lisa Jones, RN; Lynne Lichtermann, RN, BSN; Shirley Vosburg, RD, MPH; and J. Lee Taylor, MEd, MBA.
      University of Tennessee Downtown: Abbas E. Kitabchi, PhD, MD; Ebenezer Nyenwe, MD3; Helen Lambeth, RN, BSN; Amy Brewer, MS, RD, LDN; Debra Clark, LPN; Andrea Crisler, MT; Debra Force, MS, RD, LDN; Donna Green, RN; Robert Kores, PhD.
      University of Minnesota: Robert W. Jeffery, PhD1; Carolyn Thorson, CCRP2; John P. Bantle, MD3; J. Bruce Redmon, MD3; Richard S. Crow, MD3; Scott Crow, MD3; Susan K Raatz, PhD, RD3; Kerrin Brelje, MPH, RD; Carolyne Campbell; Jeanne Carls, MEd; Tara Carmean-Mihm, BA; Julia Devonish, MS; Emily Finch, MA; Anna Fox, MA; Elizabeth Hoelscher, MPH, RD, CHES; La Donna James; Vicki A. Maddy, BS, RD; Therese Ockenden, RN; Birgitta I. Rice, MS, RPh, CHES; Tricia Skarphol, BS; Ann D. Tucker, BA; Mary Susan Voeller, BA; Cara Walcheck, BS, RD.
      St. Luke's Roosevelt Hospital Center: Xavier Pi-Sunyer, MD1; Jennifer Patricio, MS2; Stanley Heshka, PhD3; Carmen Pal, MD3; Lynn Allen, MD; Lolline Chong, BS, RD; Marci Gluck, PhD; Diane Hirsch, RNC, MS, CDE; Mary Anne Holowaty, MS, CN; Michelle Horowitz, MS, RD; Nancy Rau, MS, RD, CDE; Dori Brill Steinberg, BS.
      University of Pennsylvania: Thomas A. Wadden, PhD1; Barbara J Maschak-Carey, MSN, CDE2; Robert I. Berkowitz, MD3; Seth Braunstein, MD, PhD3; Gary Foster, PhD3; Henry Glick, PhD3; Shiriki Kumanyika, PhD, RD, MPH3; Stanley S.Schwartz, MD3; Michael Allen, RN; Yuliis Bell; Johanna Brock; Susan Brozena, MD; Ray Carvajal, MA; Helen Chomentowski; Canice Crerand, PhD; Renee Davenport; Andrea Diamond, MS, RD; Anthony Fabricatore, PhD; Lee Goldberg, MD; Louise Hesson, MSN, CRNP; Thomas Hudak, MS; Nayyar Iqbal, MD; LaShanda Jones-Corneille, PhD; Andrew Kao, MD; Robert Kuehnel, PhD; Patricia Lipschutz, MSN; Monica Mullen, RD, MPH.
      University of Pittsburgh: John M. Jakicic, PhD1, David E. Kelley, MD1; Jacqueline Wesche-Thobaben, RN, BSN, CDE2; Lewis H. Kuller, MD, DrPH3; Andrea Kriska, PhD3; Amy D. Otto, PhD, RD, LDN3, Lin Ewing, PhD, RN3, Mary Korytkowski, MD3, Daniel Edmundowicz, MD3; Monica E. Yamamoto, DrPH, RD, FADA 3; Rebecca Danchenko, BS; Barbara Elnyczky; David O. Garcia, MS; George A. Grove, MS; Patricia H. Harper, MS, RD, LDN; Susan Harrier, BS; Nicole L. Helbling, MS, RN; Diane Ives, MPH; Juliet Mancino, MS, RD, CDE, LDN; Anne Mathews, PhD, RD, LDN; Tracey Y. Murray, BS; Joan R. Ritchea; Susan Urda, BS, CTR; Donna L. Wolf, PhD.
      The Miriam Hospital/Brown Medical School: Rena R. Wing, PhD1; Renee Bright, MS2; Vincent Pera, MD3; John Jakicic, PhD3; Deborah Tate, PhD3; Amy Gorin, PhD3; Kara Gallagher, PhD3; Amy Bach, PhD; Barbara Bancroft, RN, MS; Anna Bertorelli, MBA, RD; Richard Carey, BS; Tatum Charron, BS; Heather Chenot, MS; Kimberley Chula-Maguire, MS; Pamela Coward, MS, RD; Lisa Cronkite, BS; Julie Currin, MD; Maureen Daly, RN; Caitlin Egan, MS; Erica Ferguson, BS, RD; Linda Foss, MPH; Jennifer Gauvin, BS; Don Kieffer, PhD; Lauren Lessard, BS; Deborah Maier, MS; JP Massaro, BS; Tammy Monk, MS; Rob Nicholson, PhD; Erin Patterson, BS; Suzanne Phelan, PhD; Hollie Raynor, PhD, RD; Douglas Raynor, PhD; Natalie Robinson, MS, RD; Deborah Robles; Jane Tavares, BS.
      The University of Texas Health Science Center at San Antonio: Steven M. Haffner, MD1; Helen P. Hazuda, PhD1; Maria G. Montez, RN, MSHP, CDE2; Carlos Lorenzo, MD3; Charles F. Coleman, MS, RD; Domingo Granado, RN; Kathy Hathaway, MS, RD; Juan Carlos Isaac, RC, BSN; Nora Ramirez, RN, BSN; Ronda Saenz, MS, RD.
      VA Puget Sound Health Care System/University of Washington: Steven Kahn, MB, ChB1; Brenda Montgomery, RN, MS, CDE2; Robert Knopp, MD3; Edward Lipkin, MD3; Dace Trence, MD3; Terry Barrett, BS; Joli Bartell, BA; Diane Greenberg, PhD; Anne Murillo, BS; Betty Ann Richmond, MEd; Jolanta Socha, BS; April Thomas, MPH, RD; Alan Wesley, BA.
      Southwestern American Indian Center, Phoenix, Arizona and Shiprock, New Mexico: William C. Knowler, MD, DrPH1; Paula Bolin, RN, MC2; Tina Killean, BS2; Cathy Manus, LPN3; Jonathan Krakoff, MD3; Jeffrey M. Curtis, MD, MPH3; Justin Glass, MD3; Sara Michaels, MD3; Peter H. Bennett, MB, FRCP3; Tina Morgan3; Shandiin Begay, MPH; Paul Bloomquist, MD; Teddy Costa, BS; Bernadita Fallis RN, RHIT, CCS; Jeanette Hermes, MS, RD; Diane F. Hollowbreast; Ruby Johnson; Maria Meacham, BSN, RN, CDE; Julie Nelson, RD; Carol Percy, RN; Patricia Poorthunder; Sandra Sangster; Nancy Scurlock, MSN, ANP-C, CDE; Leigh A. Shovestull, RD, CDE; Janelia Smiley; Katie Toledo, MS, LPC; Christina Tomchee, BA; Darryl Tonemah, PhD.
      University of Southern California: Anne Peters, MD1; Valerie Ruelas, MSW, LCSW2; Siran Ghazarian Sengardi, MD2; Kathryn (Mandy) Graves Hillstrom, EdD, RD, CDE; Kati Konersman, MA, RD, CDE; Sara Serafin-Dokhan.

      Coordinating Center

      Wake Forest University: Mark A. Espeland, PhD1; Judy L. Bahnson, BA, CCRP3; Lynne E. Wagenknecht, DrPH3; David Reboussin, PhD3; W. Jack Rejeski, PhD3; Alain G. Bertoni, MD, MPH3; Wei Lang, PhD3; Michael S. Lawlor, PhD3; David Lefkowitz, MD3; Gary D. Miller, PhD3; Patrick S. Reynolds, MD3; Paul M. Ribisl, PhD3; Mara Vitolins, DrPH3; Haiying Chen, PhD3; Delia S. West, PhD3; Lawrence M. Friedman, MD3; Brenda L. Craven, MS, CCRP2; Kathy M. Dotson, BA2; Amelia Hodges, BS, CCRP2; Carrie C. Williams, MA, CCRP2; Andrea Anderson, MS; Jerry M. Barnes, MA, Mary Barr; Daniel P. Beavers, PhD; Tara Beckner; Cralen Davis, MS; Thania Del Valle-Fagan, MD; Patricia A. Feeney, MS; Candace Goode; Jason Griffin, BS; Lea Harvin, BS; Patricia Hogan, MS; Sarah A. Gaussoin, MS; Mark King, BS; Kathy Lane, BS; Rebecca H. Neiberg, MS; Michael P. Walkup, MS; Karen Wall, AAS; Terri Windham.

      Central Resources Centers

      DXA Reading Center, University of California at San Francisco. Michael Nevitt, PhD1; Ann Schwartz, PhD2; John Shepherd, PhD3; Michaela Rahorst; Lisa Palermo, MS, MA; Susan Ewing, MS; Cynthia Hayashi; Jason Maeda, MPH.
      Central Laboratory, Northwest Lipid Metabolism and Diabetes Research Laboratories. Santica M. Marcovina, PhD, ScD1; Jessica Chmielewski2; Vinod Gaur, PhD4.
      ECG Reading Center, EPICARE, Wake Forest University School of Medicine: Elsayed Z. Soliman, MD, MSc, MS1; Ronald J. Prineas, MD, PhD1; Charles Campbell2; Zhu-Ming Zhang, MD3; Teresa Alexander; Lisa Keasler; Susan Hensley; Yabing Li, MD.
      Diet Assessment Center, University of South Carolina, Arnold School of Public Health, Center for Research in Nutrition and Health Disparities: Robert Moran, PhD1.
      Hall-Foushee Communications, Inc.: Richard Foushee, PhD; Nancy J. Hall, MA.

      Federal Sponsors

      National Institute of Diabetes and Digestive and Kidney Diseases: Mary Evans, PhD; Barbara Harrison, MS; Van S. Hubbard, MD, PhD; Susan Z.Yanovski, MD; Robert Kuczmarski, PhD.
      National Heart, Lung, and Blood Institute: Lawton S. Cooper, MD, MPH; Peter Kaufman, PhD, FABMR.
      Centers for Disease Control and Prevention: Edward W. Gregg, PhD; David F. Williamson, PhD; Ping Zhang, PhD.
      1Principal Investigator.
      2Program Coordinator.
      3Co-Investigator.
      All other Look AHEAD staffs are listed alphabetically by site.

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