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Background/Objectives The effect of a low glycemic load (GL) diet on insulin-like growth factor-1 (IGF-1) concentration is still unknown but may contribute to lower chronic disease risk. We aimed to assess the impact of GL on concentrations of IGF-1 and IGFBP-3. Subjects/Methods We conducted a randomized, controlled crossover feeding trial in 84 overweight-obese and normal weight healthy individuals using two 28-day weight-maintaining high- and low-GL diets. Measures were fasting and post-prandial concentrations of insulin, glucose, IGF-1 and IGFBP-3. 20 participants completed post-prandial testing by consuming a test breakfast at the end of each feeding period. We used paired t-tests for diet-component and linear mixed models for biomarker analyses. Results The 28-day low-GL diet led to 4% lower fasting concentrations of IGF-1 (10.6 ng/mL, p=0.04) and a 4% lower ratio of IGF-1/IGFBP-3 (0.24, p=0.01) compared to the high-GL diet. The low-GL test breakfast led to 43% and 27% lower mean post-prandial glucose and insulin responses, respectively; mean incremental areas under the curve for glucose and insulin, respectively, were 64.3±21.8 (mmol/L/240min) (p<0.01) and 2253±539 (μU/mL/240min) (p<0.01) lower following the low- compared to the high-GL test meal. There was no effect of GL on mean HOMA-IR or on mean integrated post-prandial concentrations of glucose-adjusted insulin, IGF-1 or IGFBP-3. We did not observe modification of the dietary effect by adiposity. Conclusions Low-GL diets resulted in 43% and 27% lower post-prandial responses of glucose and insulin, respectively, and modestly lower fasting IGF-1 concentrations. Further intervention studies are needed to weigh the impact of dietary GL on risk for chronic disease.

Reduced health-related quality of life (HRQOL), depressive symptoms and poor sleep quality are important health issues among postmenopausal women and may be associated with low vitamin D status. Overweight postmenopausal women, with serum 25-hydroxyvitamin D [25(OH)D] 10–32 ng/m, were recruited in Seattle, WA (2010–2012) and randomly assigned to 12 months of weight loss + 2000 IU oral vitamin D3/day or weight loss + daily placebo. The weight-loss program included a reduced-calorie diet and 225 min/week of moderate-to-vigorous aerobic activity. Eight subscales of HRQOL were assessed by the MOS 36-Item Short-Form Health Survey. Depressive symptoms were assessed using the Brief Symptom Inventory-18, and sleep quality was assessed using the Pittsburg Sleep Quality Index (PSQI). Mean 12-month changes in HRQOL, depressive symptoms and sleep quality were compared between groups (intent-to-treat) using generalized estimating equations. Compared to placebo, women receiving vitamin D did not experience any significant change in depressive symptoms (p=0.78), HRQOL subscales (all p>0.05), or overall sleep quality (p=0.21). However, a greater magnitude of change in serum 25(OH)D was associated with an increased need to take medications to sleep (ptrend=0.01) and overall worse sleep quality (ptrend<0.01). Women who became vitamin D replete (≥32 ng/mL) also showed a deterioration in total PSQI sleep quality score compared to women who remained <32 ng/mL despite supplementation, even after adjusting for relevant covariates (Non-Replete: −5.7% vs. Replete: +6.2%, p<0.01). Vitamin D supplementation of 2000 IU/d may result in overall worse sleep quality for postmenopausal women with low circulating vitamin D undergoing weight loss.

BackgroundCertain eating behaviors are common among women with obesity. Whether these behaviors influence outcomes in weight loss programs, and whether such programs affect eating behaviors, is unclear.MethodsOur aim was to examine the effect of baseline eating behaviors on intervention adherence and weight among postmenopausal women with overweight or obesity, and to assess intervention effects on eating behaviors.Four hundred and 39 women (BMI ≥25 kg/m2) were randomized to 12 months of: i) dietary weight loss with a 10% weight loss goal (‘diet’; n = 118); ii) moderate-to-vigorous intensity aerobic exercise for 225 mins/week (‘exercise’; n = 117); iii) combined dietary weight loss and exercise (‘diet + exercise’; n = 117); or iv) no-lifestyle change control (n = 87). At baseline and 12 months, restrained eating, uncontrolled eating, emotional eating and binge eating were measured by questionnaire; weight and body composition were assessed. The mean change in eating behavior scores and weight between baseline and 12 months in the diet, exercise, and diet + exercise arms were each compared to controls using the generalized estimating equation (GEE) modification of linear regression adjusted for age, baseline BMI, and race/ethnicity.ResultsBaseline restrained eating was positively associated with change in total calories and calories from fat during the dietary intervention but not with other measures of adherence. Higher baseline restrained eating was associated with greater 12-month reductions in weight, waist circumference, body fat and lean mass. Women randomized to dietary intervention had significant reductions in binge eating (− 23.7%, p = 0.005 vs. control), uncontrolled eating (− 24.3%, p < 0.001 vs. control), and emotional eating (− 31.7%, p < 0.001 vs. control) scores, and a significant increase in restrained eating (+ 60.6%, p < 0.001 vs. control); women randomized to diet + exercise reported less uncontrolled eating (− 26.0%, p < 0.001 vs. control) and emotional eating (− 22.0%, p = 0.004 vs. control), and increased restrained eating (+ 41.4%, p < 0.001 vs. control). Women randomized to exercise alone had no significant change in eating behavior scores compared to controls.ConclusionsA dietary weight loss intervention helped women modify eating behaviors. Future research should investigate optimal behavioral weight loss interventions for women with both disordered eating and obesity.Trial registrationNCT00470119 (https://clinicaltrials.gov). Retrospectively registered May 7, 2007.

Objectives To compare 12 months of vitamin D3 supplementation versus placebo on lean mass, bone mineral density and muscle strength in overweight or obese postmenopausal women completing a structured weight-loss program. Design Double-blind, placebo-controlled randomized clinical trial. Setting Fred Hutchinson Cancer Research Center, Seattle, WA. Participants 218 postmenopausal (50-75 y) women, BMI ≥25 kg/m2, with serum 25-hydroxyvitamin D (25(OH)D) concentrations ≥10 −<32 ng/mL (i.e. insufficient). Intervention 2000 IU/day oral vitamin D3 or placebo in combination with a lifestyle-based weight loss intervention consisting of 500-1000 kcal/day reduction and 225 mins/week of moderate-to-vigorous intensity aerobic exercise. Measurements Serum 25(OH)D, body composition and muscle strength were measured pre-randomization (baseline) and at 12 months. Mean changes were compared between groups (intent-to-treat) using generalized estimating equations. Results Change in 25(OH)D was significantly different between vitamin D and placebo groups at 12 months (+13.6 vs −1.3 ng/mL, p<0.0001); however, no differences in change in lean mass (Vit D:−0.8 kg vs P:−1.1 kg, p=0.53), bone mineral density of the spine (Vit D:−0.01 g/cm2 vs P:0.0 g/cm2, p=0.82) or right femoral neck (both −0.01 g/cm2, p=0.49) were detected between groups. Leg strength decreased significantly in the vitamin D group compared to placebo (Vit D:−2.6 lbs vs P:+1.8 lbs, p=0.03). Among women randomized to vitamin D, achieving repletion (25(OH)D ≥32 ng/mL) did not alter results. Conclusion Vitamin D3 supplementation during weight-loss decreased leg strength but did not alter changes in lean mass or bone mineral density compared to placebo among postmenopausal women with vitamin D insufficiency.

Background The Step Study found that men who had sex with men (MSM) who received an adenovirus type 5 (Ad5) vector-based vaccine and were uncircumcised or had prior Ad5 immunity had a higher HIV incidence than MSM who received placebo. We investigated whether differences in HIV exposure, measured by reported sexual risk behaviors, may explain the increased risk. Methods Among 1,764 MSM in the trial, 724 were uncircumcised, 994 had prior Ad5 immunity and 560 were both uncircumcised and had prior Ad5 immunity. Analyses compared sexual risk behaviors and perceived treatment assignment among vaccine and placebo recipients, determined risk factors for HIV acquisition and examined the role of insertive anal intercourse in HIV risk among uncircumcised men. Findings Few sexual risk behaviors were significantly higher in vaccine vs. placebo recipients at baseline or during follow-up. Among uncircumcised men, vaccine recipients at baseline were more likely to report unprotected insertive anal intercourse with HIV negative partners (25.0% vs. 18.1%; p=0.03). Among uncircumcised men who had prior Ad5 immunity, vaccine recipients were more likely to report unprotected insertive anal intercourse with partners of unknown HIV status (46.0% vs. 37.5%; p=0.05). Vaccine recipients remained at higher risk of HIV infection compared to placebo recipients (HR =2.8; 95% CI:1.7, 6.8) controlling for potential confounders. Interpretation These analyses do not support a behavioral explanation for the increased HIV infection rates observed among uncircumcised men in the Step Study. Identifying biologic mechanisms to explain the increased risk is a priority. This study is registered with ClinicalTrials.gov, number NCT00095576.

Obesity and vitamin D deficiency are associated with risk for several cancers, possibly through inflammation and adipokine-related pathways. 218 postmenopausal women with BMI>25 kg/m2 and low serum 25-hydroxyvitamin D (25(OH)D; ≥10-<32 ng/mL), were randomized to 12-months of either (i) weight-loss intervention + 2000 IU/day oral vitamin D3 or (ii) weight-loss intervention + daily placebo. Serum adiponectin, leptin, tumor necrosis factor-alpha (TNF-α), Interleukin (IL)-6; IL-1β; IL-8 and IL-10, were measured by immunoassay, and a composite inflammatory biomarker score calculated. Using generalized estimating equations, mean changes in outcomes were compared between arms (intent-to-treat), adjusted for possible confounders. Analyses were also stratified by weight-loss (gained/no weight-loss; <5%; 5-10%; ≥10%). At 12-months, there were no significant differences in analyte changes between arms. In stratified analyses, participants randomized to vitamin D3who lost 5-10% of baseline weight, vs. participants who gained weight/had no weight-loss, had significantly greater decreases in levels of IL-6 compared to those randomized to placebo: absolute change -0.75 pg/mL (-17.2%) Placebo vs. -1.77 pg/mL (-37.3%) Vitamin D, P=0.004. Similar but attenuated results were observed for participants who lost ≥10% of baseline weight: -0.41 pg/mL (-13.6%) Placebo vs. -0.67 pg/mL (-17.3%) Vitamin D, P=0.02. Effects of vitamin D3 supplementation on levels of IL-1β were inconsistent when stratified by weight loss. There were no intervention effects on IL-10, TNF-α, IL-8, the composite score, adiponectin or leptin, when stratified by weight-loss. In conclusion, Vitamin D3 supplementation in combination with weight-loss of at least 5% of baseline weight was associated with significant reductions in levels of IL-6.

Obese and sedentary persons have an increased risk for cancer, but underlying mechanisms are poorly understood. Angiogenesis is common to adipose tissue formation and remodeling, and to tumor vascularization. 439 overweight/obese, healthy, postmenopausal women (body mass index (BMI)>25 kg/m2) aged 50-75 years, recruited between 2005-2008 were randomized to a 4-arm 12-month randomized controlled trial, comparing a caloric restriction diet arm (goal: 10% weight-loss, N=118), aerobic exercise arm (225 min/week of moderate-to-vigorous activity, N=117), a combined diet+exercise arm (N=117), or control (N=87) on circulating levels of angiogenic biomarkers. Vascular endothelial growth factor (VEGF), plasminogen activator inhibitor-1 (PAI-1); and pigment epithelium-derived factor (PEDF) were measured by immunoassay at baseline and 12-months. Changes were compared using generalized estimating equations, adjusting for baseline BMI age, and race/ethnicity. Participants randomized to the diet+exercise arms had statistically significantly greater reductions in PAI-1 at 12-months compared to controls (-19.3% vs. +3.48% respectively, P<0.0001). Participants randomized to the diet and diet+exercise arms had statistically significantly greater reductions in PEDF (-9.20%, -9.90% respectively, both P<0.0001) and VEGF (-8.25%, P=0.0005; -9.98%, P<0.0001, respectively) compared to controls. There were no differences in any of the analytes in participants randomized to the exercise arm compared to controls. Increasing weight-loss was statistically significantly associated with linear trends of greater reductions in PAI-1, PEDF and VEGF. Weight-loss is significantly associated with reduced circulating VEGF, PEDF and PAI-1, and could provide incentive for reducing weight as a cancer prevention method in overweight and obese individuals.