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.

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.

Integrating CHWs as Part of the Team Leading Diabetes Group Visits: A Randomized Controlled Feasibility Study.

Purpose The purpose of the study was to evaluate the feasibility of integrating Community Health Workers (CHWs) as part of the team leading diabetes group visits. Methods This was a randomized controlled study that integrated CHWs as part of the team leading diabetes group visits for low-income Hispanic adults (n = 50). Group visits met for 3 hours each month for a 6-month duration. Main measures included baseline and 6-month clinical outcomes (ie, A1C, lipids), concordance with 8 standard of care guidelines (ie, screens for cervical, breast, and colon cancer) from the US Preventive Task Force and American Diabetes Association, and participant acceptability. Results Compared to control participants, the intervention group resulted in significantly better clinical outcomes or guideline concordance for the following areas: target A1C levels, retinal eye exams, diabetes foot exams, mammograms, and urine microalbumin. Significantly more individuals in the control group gained weight, whereas a greater number of participants in the intervention group lost weight. Intervention participants found the group visits highly acceptable. Conclusions Integrating CHWs as part a comprehensive diabetes group visit program is a feasible and effective system-level intervention to improve glycemic control and achieve guideline concordance.

Mexican American children have differential elevation of metabolic biomarkers proportional to obesity status.

OBJECTIVES: There is a health disparity for obesity among Mexican Americans compared with other racial/ethnic groups. In particular, Mexican American children who are obese are likely to become obese adults. The purpose of this study was to examine traditional and nontraditional risk factors in a subset of Mexican American children before their participation in a larger clinical weight loss study. METHODS: Venous blood samples were collected from self-identified Mexican American children (12-14 years old) who were assigned to 1 of 3 weight groups based on their standardized body mass index; normal weight (N = 66), overweight (N = 23), or obese (N = 39). Serum was analyzed for interleukin-6, tumor necrosis factor-α, C-peptide, ghrelin, glucagon-like protein, gastric inhibitory polypeptide-1, glucagon, insulin, leptin, macrophage chemoattractant protein 1, and pancreatic polypeptide using a Luminex MagPix-based assay. Total cholesterol, high-density lipoprotein-cholesterol, triglycerides, and glucose were analyzed using enzymatic assays. Data were analyzed for significance using separate analysis of variance tests, with significance set at P < 0.05. RESULTS: Relative to normal weight and overweight children, obese children had significantly elevated C-peptide (P < 0.0001), insulin (P < 0.0001), leptin (P < 0.0001), macrophage chemoattractant protein 1 (P = 0.005), and tumor necrosis factor-α (P = 0.006). CONCLUSIONS: We observed that Mexican American children as a function of body weight had elevated serum concentrations of several biomarkers that have been linked to chronic disease development in adults. More research is needed to understand how these differences affect disease risk in adulthood.

Achieving long-term weight maintenance in Mexican-American adolescents with a school-based intervention.

PURPOSE: This study evaluated 24-month outcomes of a school-based intensive lifestyle weight management program targeting overweight Mexican-American adolescents. METHODS: We recruited a total of 71 adolescents (32 males; 45.1%) between the ages of 10 and 14 years, at or above the 85th percentile for body mass index (BMI). Participants were randomized to a 6-month instructor-led intervention (ILI) or a self-help (SH) program. Both interventions were aimed at modifying eating and physical activity behaviors using behavior modification strategies. We assessed changes in participants' standardized BMI and BMI percentile at baseline, 1, and 2 years. RESULTS: Repeated-measures analyses showed that ILI participants showed significantly greater decreases in standardized BMI at 1 and 2 years (F = 8.58, p < .01; and F = 9.27, p < .01, respectively) compared with SH controls. Similar results were found for changes in BMI and BMI percentile. At 2 years, the ILI condition decreased their average BMI percentile by 3.9 percentile points, compared to an increase of 1.6 percentile points in the SH condition. CONCLUSIONS: A school-based intervention resulted in improved weight outcomes in overweight Mexican-American adolescents and results were maintained over 2 years.

Obese Mexican American children have elevated MCP-1, TNF-α, monocyte concentration, and dyslipidemia.

BACKGROUND AND OBJECTIVE: Obesity is an independent risk factor for chronic disease. The prevalence of obesity is especially high among Mexican American children. Peripheral blood monocytes are altered with obesity contributing to elevated systemic inflammation and increased risk of chronic disease. In addition, obesity alters the circulating levels of cytokines/chemokines that influence monocyte behavior. The study objective was to investigate alterations in blood monocytes and plasma cytokines/chemokine levels among healthy weight (standardized BMI [zBMI] ≤85th percentile; n = 66), overweight (zBMI 85th-95th percentile; n = 23), and obese (zBMI ≥95th percentile; n = 39) Mexican American children. METHODS: Blood samples were analyzed for total and subset monocyte concentration via flow cytometry. Serum monocyte chemoattractant protein-1 (MCP-1), fractalkine, interleukin-8, and tumor necrosis factor α (TNF-α) were measured by using a Milliplex MagPix assay. Serum cholesterol, high-density lipoproteins, triglycerides, and glucose were measured by using an enzymatic assay. RESULTS: Total monocyte concentration (P = .012), classic monocyte concentration (P = .045), MCP-1 (P = .015), and TNF-α (P = .002) were significantly greater in obese children compared with healthy weight children. Also, overweight and obese children had elevated triglycerides (P = .001) and reduced high-density lipoproteins (P = .033) compared with healthy weight children. CONCLUSIONS: Childhood obesity alters monocytes and circulating chemokines, putting children at a greater risk of developing obesity-related chronic diseases in adulthood. Further characterization of early immune alterations in childhood obesity may provide additional clinical insight into the assessment of obesity-related disease risk.

Development and validation of the Family Health Behavior Scale.

OBJECTIVE: The purpose of the current study was to develop a psychometrically sound, parent-report measure of family and child behaviors related to obesity in children between 5- and 12-years-old. METHODS: Item generation, item selection, and initial exploratory factor analysis yielded a 27-item measure called the Family Health Behavior Scale (FHBS). RESULTS: The FHBS contains four subscales measuring health-promoting family behaviors, obesogenic behaviors, meal-time routines, and family physical activity habits. Parent ratings on the FHBS were shown to predict their child's weight classification. The FHBS also demonstrated adequate internal consistency and temporal stability. CONCLUSIONS: The results of the study suggest that the FHBS is a promising measure of family eating and physical activity habits related to obesity in children.

Weight loss with naltrexone SR/bupropion SR combination therapy as an adjunct to behavior modification: the COR-BMOD trial.

This 56-week, randomized, placebo-controlled trial examined the efficacy and safety of naltrexone plus bupropion as an adjunct to intensive behavior modification (BMOD). A total of 793 participants (BMI = 36.5 ± 4.2 kg/m²) was randomly assigned in a 1:3 ratio to: (i) placebo + BMOD (N = 202); or (ii) naltrexone sustained-release (SR, 32 mg/day), combined with bupropion SR (360 mg/day) plus BMOD (i.e., NB32 + BMOD; N = 591). Both groups were prescribed an energy-reduced diet and 28 group BMOD sessions. Co-primary end points were percentage change in weight and the proportion of participants who lost ≥5% weight at week 56. Efficacy analyses were performed on a modified intent-to-treat population (ITT; i.e., participants with ≥1 postbaseline weight while taking study drug (placebo + BMOD, N = 193; NB32 + BMOD, N = 482)). Missing data were replaced with the last observation obtained on study drug. At week 56, weight loss was 5.1 ± 0.6% with placebo + BMOD vs. 9.3 ± 0.4% with NB32 + BMOD (P < 0.001). A completers analysis revealed weight losses of 7.3 ± 0.9% (N = 106) vs. 11.5 ± 0.6% (N = 301), respectively (P < 0.001). A third analysis, which included all randomized participants, yielded losses of 4.9 ± 0.6 vs. 7.8 ± 0.4%, respectively (P < 0.001). Significantly more NB32 + BMOD- vs. placebo + BMOD-treated participants lost ≥5 and ≥10% of initial weight, and the former had significantly greater improvements in markers of cardiometabolic disease risk. NB32 + BMOD was generally well tolerated, although associated with more reports of nausea than placebo + BMOD. The present findings support the efficacy of combined naltrexone/bupropion therapy as an adjunct to intensive BMOD for obesity.

Effects of a school-based weight maintenance program for Mexican-American children: results at 2 years.

The prevalence of childhood overweight has increased significantly, with the highest rates noted among Mexican Americans. Many negative health outcomes are associated with overweight; thus, there is a need for effective weight-loss interventions tailored to this group. This study evaluated 24-month outcomes of a randomized, controlled trial involving an intensive lifestyle-based weight maintenance program targeting overweight Mexican-American children at a charter school in Houston, Texas. A total of 60 children (33 males, 55%) between the ages of 10 and 14 at or >85th percentile for BMI were recruited. Participants were randomized to an instructor-led intervention (ILI) or a self-help (SH) program, both aimed at modifying eating and physical activity behaviors using behavior modification strategies. Changes in participants' standardized BMI (zBMI) were assessed at baseline, 1, and 2 years. Tricep skinfold, total cholesterol, triglycerides, high-density lipoprotein cholesterol, and calculated low-density lipoprotein were assessed at baseline and 1 year. ILI participants showed significantly greater decreases in zBMI at 1 and 2 years (F = 26.8, P < 0.001, F = 4.1, P < 0.05, respectively) compared to SH controls. ILI participants showed greater improvements in body composition, as measured by tricep skinfold (F = 9.75, P < 0.01). Children in the ILI condition experienced benefits with respect to total cholesterol (F = 7.19, P < 0.05) and triglycerides (F = 4.35, P < 0.05) compared to children in the SH condition. Overall, the school-based intervention resulted in improved weight and clinical outcomes in overweight Mexican-American children, and zBMI was maintained over 2 years.

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.

Inflammatory markers are elevated in overweight Mexican-American children.

OBJECTIVE: The purpose of the present study was to determine the effect of body weight on blood lipid profile, insulin resistance and inflammatory biomarkers in Mexican-American children. METHODS: Children (13.3+/-0.1 year) were recruited from a local school and assigned to one of three groups as a volunteer sample: healthy weight (HW) (> or =10th and <85th BMI percentile; n=42), at risk of overweight (RO) (> or =85th and <95th; n =25) or overweight (OW) (> or =95th; n=42). Plasma concentrations of hsCRP, sCD14, sIL-6R, sTNF-alphaR1, sTNF-alphaR2, IL-6 and TNF-alpha were determined by ELISA. RESULTS: OW children had significantly greater plasma concentrations of hsCRP (P =0.003), sCD14 (P =0.013), sIL-6R (P =0.010), sTNF-alphaR1 (P<0.001), sTNF-alphaR2 (P=0.005), insulin (P=0.001), TC:HDL ratio (P<0.001) and triglycerides (P <0.001) than HW children. Also plasma concentrations of hsCRP, sIL-6R and sTNF-alphaR1 were significantly greater in OW compared with RO children. CONCLUSION: Overweight Mexican-American children had a higher concentration of inflammatory biomarkers than healthy weight children. To our knowledge, this is the first study to report that sCD14 is elevated in overweight compared with healthy weight Mexican-American children.

The role of lifestyle modification in dysmetabolic syndrome management.

Lifestyle modification should be the primary therapeutic intervention in individuals with the dysmetabolic syndrome, given the fact that obesity, unhealthy diet, and physical inactivity are primary underlying risk factors for its development. Most individuals with the dysmetabolic syndrome need to lose weight through dietary changes and increases in physical activity. Modest weight losses may significantly improve all aspects of the syndrome. Because individuals differ in their lifestyles, tailoring interventions to meet the specific needs of each person will maximize the chances of success. Assessment of the individual with the dysmetabolic syndrome involves quantification of obesity, diets and dietary patterns, physical activity, emotional problems, and motivation. To help individuals make lifestyle changes, a number of behavior modification strategies have shown good efficacy. These strategies include a tailored problem-solving intervention, involving goal-setting, self-monitoring, stimulus control, cognitive restructuring, stress management, relapse prevention, social support, and contracting. The frequency of self-monitoring is an especially important strategy for continued success. Research studies have clearly demonstrated the power of lifestyle modification for long-term behavioral change. Lifestyle modification appears effective in delaying or preventing the development of the dysmetabolic syndrome.

Need for lifestyle intervention: how to begin.

The metabolic syndrome is the fastest growing disease entity in the world. Prevention and effective treatment emphasize lifestyle intervention, including healthful diet, physical activity, and pharmacologic agents to target specific risk factors. Weight loss improves all aspects of the metabolic syndrome and is a primary intervention target. Effective weight management also helps prevent the development of the metabolic syndrome. Lifestyle change strategies--including setting reasonable goals, raising awareness, confronting barriers to change, managing stress, cognitive restructuring, preventing relapse, and providing support--are the keys to long-term success.

Migration history, health behaviors, and cardiovascular disease risk factors in overweight Mexican-American women.

PURPOSE: This research examined whether the migration history of overweight Mexican-American women had an independent effect on cardiovascular risk factors, or whether it was mediated by health behavior changes. DATA AND METHODS: Cross-sectional data from 390 overweight, non-diabetic Mexican-American women (aged 18 to 65 years), all recruited from Starr County, Texas, were used for this analysis. Migration history was inferred from birthplaces of subjects and relatives, and length of residence in the United States. Health behaviors included tobacco and alcohol use, sleeping, exercise, and dietary practices. The cardiovascular disease risk factor variables (CDRFVs) studied were plasma glucose, abdominal obesity, blood pressures, and blood lipids. A migration history score (MHS) was developed from factor analysis, almost equally contributed to by the 9 migration history variables. Healthy habits were defined by 6 variables, and 3 factors (blood pressures, lipids/glucose, and body fat/glucose) were used for the CDRFVs. FINDINGS AND CONCLUSION: MHS was correlated positively with socioeconomic status, and negatively with family stress. Older women had healthier drinking and sleeping habits. Women with a higher migration history score exhibited poorer exercise habits, and increased blood pressures. After adjusting for the effect of healthy exercise habits on blood pressures, the impact of migration history on blood pressures became non-significant (P>.05), leading to the conclusion that healthy exercise behaviors mediated the negative relationship of MHS with blood pressures. Age was independently positively correlated with all CDRFVs. Age also weakly moderated the negative relationship of MHS and healthy exercise habits.