Lifestyle Intervention Arm Research Articles

Individualised Lifestyle Intervention in Polycystic Ovarian Syndrome Women Who Desire Fertility: A Feasibility Study.

Polycystic ovarian syndrome (PCOS) is one of the common causes of anovulatory infertility among women in the reproductive age group. Women with PCOS and obesity often have difficulty in conceiving, and they are more prone for developing metabolic syndrome. Lifestyle modification plays a key role in women with PCOS, who are overweight or obese and is recommended as a first line management option. The earlier trials evaluating the role of lifestyle intervention in infertile PCOS women had methodological issues, smaller sample size and high dropout rates and none of these trials reported live birth as their outcome. The current study was planned to explore the feasibility of conducting large adequately powered multicentric trial in future in South Asian women with PCOS who desire fertility. The study was done in the Department of Reproductive Medicine and Surgery & the Department of Endocrinology and Metabolism at a university level tertiary care hospital. The study is an open label, single center, randomized controlled trial. A total of 60 PCOS women aged between 18-40 years with body mass index of > 23 kg/m2 who desire fertility, were randomized to individualized lifestyle intervention and usual care. The primary outcome was the dropout rate, and the secondary outcomes were change in body weight, anthropometric parameters, clinical pregnancy rates and the quality of life specific to PCOS after the trial period. All the participants were followed up for 6 months and the outcomes were assessed. Comparison between the intervention and control groups was done using statistical tests using the SPSS and R software. The dropout rates were significantly higher in the individualized lifestyle intervention arm compared to usual care control arm (19/30, 63% vs 9/30, 30%, P=0.019). We did not find any statistically significant difference in anthropometric measurements, pregnancy rates (P=0.57) and clinical pregnancy rates (P=0.21) and quality of life specific to PCOS compared with sixth month visit from baseline visit. The current feasibility study showed significantly higher dropout rates in individualized lifestyle intervention arm compared to usual care control arm. The knowledge gained from the feasibility study has been used to design an adequately powered trial to evaluate effectiveness of individualized lifestyle intervention in women with PCOS who wish to conceive.

The impact of a lifestyle intervention on postpartum weight retention among US Hispanic women with overweight and obesity

IntroductionTo evaluate the effect of a culturally-modified, motivationally-targeted, individually-tailored lifestyle intervention on postpartum weight retention among Hispanic women with overweight/obesity. Materials and methodsProyecto Mamá was a randomized controlled trial conducted in western Massachusetts (2014–2020). Hispanic women with overweight/obese pre-pregnancy BMI (n = 148) were randomized in early pregnancy to a Lifestyle Intervention (LI) or a Health & Wellness (HW) comparison arm. The LI was based upon theoretical concepts, used a low-cost, high-reach strategy, and focused on healthy exercise and diet with follow-up through 12-months postpartum. The primary outcome of change in weight was calculated as the difference between pre-pregnancy weight and 6-week, 6-month, and 12-month postpartum weight. The secondary outcome was achievement of 5 % weight reduction from pre-pregnancy weight. Retention was 68.2 % in the overall postpartum period and 31.0 % at 12-months. ResultsIn intent-to-treat analyses, compared to the HW arm, there was no difference in postpartum weight retention at 6-weeks (0.0 kg, 95 % CI: −3.4, 3.5), 6-months (-1.8 kg, 95 % CI: −5.6, 2.0), or 12-months (-2.0 kg, 95 % CI: −7.0, 3.1). In a secondary complete case analysis, compared to the HW arm, the LI arm had 5.5 times higher odds of meeting the postpartum weight reduction goal (aOR = 5.5, 95 % CI: 1.7, 17.9) adjusting for pre-pregnancy weight. ConclusionsA lifestyle intervention among at-risk Hispanic women with overweight/obesity had no overall impact on postpartum weight, but a beneficial impact among those who completed the trial. Future studies should focus on increasing the feasibility and acceptability of the intervention in this at-risk population.

Cardiovascular effects of weight loss in old adults with overweight/obesity according to change in skeletal muscle mass.

Patients with overweight/obesity and type 2 diabetes are encouraged to lose weight, but not all losing weight gain better cardiovascular health, especially old adults. The change in skeletal muscle mass (SMM) could be the key that explains the heterogenous cardiovascular effects of weight loss. This study aims to assess whether the cardiovascular effects of weight loss vary for those gaining skeletal muscle along with weight loss. The old adults with overweight/obesity and type 2 diabetes in the Look AHEAD study having muscle measurement from dual-energy X-ray absorptiometry were included. Based on the weight change (WC) and SMM change (SMMC) between baseline and the 4-year follow-up, participants were allocated into three groups-weight gain (WG) group, weight loss with muscle loss (WL-ML) group and weight loss with muscle gain (WL-MG) group. Cox proportional hazards regression was performed to evaluate the cardiovascular risk of those gaining or losing SMM with weight loss compared with those gaining weight. Among the participants with weight loss, the ratio of SMMC/WC was calculated, and the association of SMMC/WC with primary cardiovascular outcome was assessed. A total of 491 participants were included in the study with an average age of 64.56±3.81years old. A total of 47.0% were male and 49.9% were from the intensive lifestyle intervention arm. Based on their WC and SMMC, 43 were assigned to the WG group, 373 to the WL-ML group and 75 to the WL-MG group. Over a follow-up of almost 10years, 97 participants encountered the primary endpoint. The WG group had the highest incidence of 25.59%, the WL-MG group had the lowest incidence of 9.33% and the WL-ML group had 21.18% (P=0.040). In the fourth adjusted Cox model, the WL-MG group achieved significantly decreased odds of the primary endpoint compared with the WG group (hazard ratio [HR] 0.33, 95% confidence interval [CI] [0.12, 0.87], P=0.026), whilst the WL-ML group did not (HR 0.91, 95% CI [0.47, 1.78], P=0.670). Among the participants with weight loss, when SMMC/WC reached around 50%, this HR soared to approximately two-fold. The participants gaining SMM along with weight loss achieved the lowest odds of adverse cardiovascular events, whilst those who lost SMM along with weight loss had comparable cardiovascular risk with those gaining weight. The more muscle lost during weight loss, the greater the harm. The cardiovascular effects of weight loss were modulated by whether the participants gained SMM meanwhile losing weight.

Results of a 2-year lifestyle intervention for type 2 diabetes: the Reach Ahead for Lifestyle and Health-Diabetes randomized controlled trial.

The Reach Ahead for Lifestyle and Health (REAL HEALTH)-Diabetes study assessed the comparative effectiveness of two Look AHEAD (Action for Health in Diabetes)-adapted lifestyle intervention (LI) arms targeting weight loss in type 2 diabetes compared with medical nutrition therapy (MNT) referral. At 1 year, LI had greater weight loss than MNT. This study reports outcomes at 24 (end of LI) and 36 months. Participants (N=211) with type 2 diabetes and BMI > 25 kg/m2 were randomly assigned to in-person LI, telephone conference call LI, or MNT. The primary outcome was percentage weight change. Secondary outcomes included 5% and 10% weight loss, glycated hemoglobin (HbA1c), and patient-reported outcomes. Participants were 61.7 (SD 10.2) years old; 55% were female; 77% were non-Hispanic White; and had mean (SD) weight of 98 (18.9) kg and mean (SD) HbA1c of 7.7% (1.2%). Mean (SD) weight change at 24 and 36 months was -4.4% (5.9%) and -4.4% (5.4%) in in-person LI, -4.0% (5.8%) and -5.3% (6.4%) in telephone LI, and -3.1% (5.2%) and -5.8% (7.1%) in MNT, with no statistically significant difference in weight or HbA1c at 24 and 36 months. Compared with MNT, LI arms had favorable changes in patient-reported outcomes related to learned dietary skills. There were no differences in weight outcomes among LI participants compared with referral to MNT at the end of intervention or 1 year after its conclusion.

Genetic Predictors of Change in Waist Circumference and Waist-to-Hip Ratio With Lifestyle Intervention: The Trans-NIH Consortium for Genetics of Weight Loss Response to Lifestyle Intervention.

Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) associated with waist circumference (WC) and waist-to-hip ratio (WHR) adjusted for BMI (WCadjBMI and WHRadjBMI), but it remains unclear whether these SNPs relate to change in WCadjBMI or WHRadjBMI with lifestyle intervention for weight loss. We hypothesized that polygenic scores (PS) comprised of 59 SNPs previously associated with central adiposity would predict less of a reduction in WCadjBMI or WHRadjBMI at 8-10 weeks in two lifestyle intervention trials, NUGENOB and DiOGenes, and at 1 year in five lifestyle intervention trials, Look AHEAD, Diabetes Prevention Program, Diabetes Prevention Study, DIETFITS, and PREDIMED-Plus. One-SD higher PS related to a smaller 1-year change in WCadjBMI in the lifestyle intervention arms at year 1 and thus predicted poorer response (β = 0.007; SE = 0.003; P = 0.03) among White participants overall and in White men (β = 0.01; SE = 0.004; P = 0.01). At average weight loss, this amounted to 0.20-0.28 cm per SD. No significant findings emerged in White women or African American men for the 8-10-week outcomes or for WHRadjBMI. Findings were heterogeneous in African American women. These results indicate that polygenic risk estimated from these 59 SNPs relates to change in WCadjBMI with lifestyle intervention, but the effects are small and not of sufficient magnitude to be clinically significant.

250-OR: Higher Genetic Risk Score Predicts Smaller Waist Circumference Change over One Year across Five Lifestyle Intervention Clinical Trials

Lifestyle intervention, combining calorie restriction and physical activity to induce weight loss, is the frontline treatment for overweight or obesity and well-known to reduce waist circumference (WC). Genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) associated with WC adjusted for body mass index (WCadjBMI), but it remains unclear whether these SNPs relate to the change in WCadjBMI with lifestyle intervention. Here, we examined whether 59 SNPs previously associated with WCadjBMI in GWAS predicted change in WCadjBMI at one year in 5 lifestyle intervention trials and at 8-10 weeks in two lifestyle intervention trials. Look AHEAD, Diabetes Prevention Program, Diabetes Prevention Study, DIETFITS, and PrediMed Plus contributed one-year data, and NUGENOB and DiOGenes contributed 8-10 week data. Genetic risk scores (GRS) combined associated alleles for each SNP weighted by association with WCadjBMI from Shungin et al, 2015 and meta-analyses with random effects for each trial were used to pool results. Among White participants, higher GRS related to smaller year one change in WCadjBMI in the lifestyle intervention arms, and thus predicted poorer response (p=0.009). With a point estimate of 0.002 (SE=0.001) across trials, for a person with an initial BMI of 34 and a year 1 reduction in BMI of 2.5, each weighted risk allele in the GRS contributed to a 0.06 cm (SE=0.03) higher WC at year 1. With a 25th%ile, median, and 75th%ile GRS of 42.77, 46.75, and 50.48, this translates to 0.46 cm less change in WC between the 25th%ile and 75th%ile. No significant findings emerged in men and women separately, in the African-American subset, for the 8-10 week outcomes, or for the individuals SNPs after correcting for multiple comparisons. These results may help to define the molecular pathways through which lifestyle intervention impacts central adiposity. Disclosure J. Mccaffery: None. T. Hansen: None. T. O. Kilpelainen: None. D. Corella: None. W. H. M. Saris: Advisory Panel; Self; Friesland Campina International, Consultant; Self; Nutrition et sante. T. I. A. Sørensen: None. J. Tuomilehto: None. R. R. Wing: None. T. Agurs-collins: None. K. A. Jablonski: None. Q. Pan: None. A. Astrup: Consultant; Self; Groupe Éthique et Santé, France, Employee; Self; Novo Nordisk Foundation, Other Relationship; Self; Flaxslim ApS, Denmark, Gelesis, Personalized Weight Management Research Consortium ApS (Gluco-Diet. dk). M. R. Christiansen: None. L. M. Corso: None. J. C. Florez: Consultant; Self; Goldfinch Bio, Inc., Other Relationship; Self; Novo Nordisk. P. W. Franks: Advisory Panel; Self; Zoe Global Limited, Consultant; Self; Eli Lilly and Company, Novo Nordisk. C. D. Gardner: None. Funding WESTAT/National Cancer Institute

The Impact of a Lifestyle Intervention on Postpartum Weight Retention Among At-Risk Hispanic Women

This study assesses the impact of a culturally modified, motivationally targeted, individually tailored intervention on postpartum weight retention among Hispanic women with abnormal glucose tolerance during pregnancy. Estudio Parto (Project Aiming to Reduce Type twO diabetes) was an RCT conducted in Western Massachusetts (collected 2013‒2017, analyzed 2018-2020). Hispanic women with blood glucose ≥140 mg/dL (7.77 mmol/L) on routine nonfasting oral glucose challenge test were randomized to a Lifestyle Intervention (n=100) focusing on healthy exercise and diet or to a comparison Health and Wellness Intervention (n=104) with no mention of exercise or diet behavior changes. The primary outcome was change in weight, calculated as the difference between prepregnancy weight and 6-week, 6-month, and 12-month postpartum weight. The secondary outcome was achievement of weight reduction to prepregnancy weight if prepregnancy BMI was normal, or a 5% reduction if prepregnancy BMI was overweight/obese. In intent-to-treat analyses, there were no significant differences in weight change pattern between the intervention arms across all follow-up timepoints (β=0.03, 95% CI= -3.38, 3.45). However, at 12 months postpartum, women in the Lifestyle Intervention arm had a statistically significant 2.5-fold higher odds of meeting the secondary weight reduction outcome (OR=2.52, 95% CI=1.09, 5.82) than women in the Health and Wellness arm. Regardless of intervention arm, women who reported higher levels of postpartum sports/exercise had a greater decrease in weight (β= -2.39, 95% CI= -4.66, -0.13, p=0.04) than women reporting lower levels. In this randomized trial among Hispanic women, no significant overall differences in weight change pattern between intervention arms were observed. Higher levels of self-reported physical activity were associated with greater weight loss in both arms.

Association of Baseline and Longitudinal Changes in Body Composition Measures With Risk of Heart Failure and Myocardial Infarction in Type 2 Diabetes: Findings From the Look AHEAD Trial.

Intentional weight loss is associated with lower risk of heart failure (HF) and atherosclerotic cardiovascular disease among patients with type 2 diabetes. However, the contribution of baseline measures and longitudinal changes in fat mass (FM), lean mass (LM), and waist circumference (WC) to the risk of HF and myocardial infarction (MI) in type 2 diabetes is not well established. Adults from the Look AHEAD trial (Action for Health in Diabetes) without prevalent HF were included. FM and LM were predicted using validated equations and compared with dual-energy x-ray absorptiometry measurements in a subgroup. Adjusted Cox models were used to evaluate the associations of baseline and longitudinal changes in FM, LM, and WC over 1- and 4-year follow-up with risk of overall HF, HF with preserved ejection fraction (EF; EF ≥50%), HF with reduced EF (EF <50%), and MI. Among 5103 participants, there were 257 incident HF events over 12.4 years of follow-up. Predicted and measured FM/LM were highly correlated (R2=0.87-0.90; n=1369). FM and LM decreased over 4-year follow-up with greater declines in the intensive lifestyle intervention arm. In adjusted analysis, baseline body composition measures were not significantly associated with HF risk. Decline in FM and WC, but not LM, over 1 year were each significantly associated with lower risk of overall HF (adjusted hazard ratio per 10% decrease in FM, 0.80 [95% CI, 0.68-0.95]; adjusted hazard ratio per 10% decrease in WC, 0.77 [95% CI, 0.62-0.95]). Decline in FM was significantly associated with lower risk of both HF subtypes. In contrast, decline in WC was significantly associated with lower risk of HF with preserved EF but not HF with reduced EF. Similar patterns of association were observed for 4-year changes in body composition and HF risk. Longitudinal changes in body composition were not significantly associated with risk of MI. In adults with type 2 diabetes, a lifestyle intervention is associated with significant loss of FM and LM. Declines in FM and WC, but not LM, were each significantly associated with lower risk of HF but not MI. Furthermore, decline in WC was significantly associated with lower risk of HF with preserved EF but not HF with reduced EF. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00017953.

Abstract 15067: Association of Baseline and Longitudinal Changes in Body Composition Measures With Risk of Heart Failure and Myocardial Infarction in Type 2 Diabetes Mellitus - Findings From the Look Ahead Trial

Introduction: Intentional weight loss is associated with lower risk of heart failure (HF) and atherosclerotic cardiovascular disease among patients with type 2 diabetes mellitus (T2DM). However, the contribution of changes in body composition measures [lean mass (LM), fat mass (FM), waist circumference (WC)] to the risk of HF and myocardial infarction (MI) is not well-known. Methods: Adults with T2DM who had overweight or obesity enrolled in the Look AHEAD (Action for Health in Diabetes) trial without prevalent HF were included. LM and FM were predicted using validated equations and compared with DXA measurements. Adjusted Cox models were used to evaluate the associations of baseline and longitudinal changes in LM, FM, and WC over 1- (Y0 to Y1) and 4-year (Y0 to Y4) follow-up with risk of overall HF, HF with preserved ejection fraction (HFpEF), HF with reduced ejection fraction (HFrEF) and MI. Results: Among 5,103 participants, there were 257 incident HF events over 12.4 years of follow-up. Predicted and measured LM and FM were highly correlated (R 2 =0.87-0.92). LM and FM decreased with greater declines in the intensive lifestyle intervention arm (Figure 1A). In adjusted analyses, baseline measures of body composition were not significantly associated with risk of HF. Decline in FM, but not LM, over 1- and 4-year follow-up was significantly associated with lower risk of HF (Figure 1B). A significant association was observed between decline in WC and risk of overall HF and HFpEF but not HFrEF. Among adults without a history of CVD, changes in body composition were not associated with risk of MI. Conclusions: In adults with T2DM who had overweight or obesity, a lifestyle intervention is associated with significant loss of FM and LM. Decline in FM and WC, but not LM, were each significantly associated with lower risk of HF but not MI. Furthermore, decline in WC was significantly associated with lower risk of HFpEF but not HFrEF.

Lifestyle Intervention With or Without Lay Volunteers to Prevent Type 2 Diabetes in People With Impaired Fasting Glucose and/or Nondiabetic Hyperglycemia

Nearly half of the older adult population has diabetes or a high-risk intermediate glycemic category, but we still lack trial evidence for effective type 2 diabetes prevention interventions in most of the current high-risk glycemic categories. To determine whether a group-based lifestyle intervention (with or without trained volunteers with type 2 diabetes) reduced the risk of progression to type 2 diabetes in populations with a high-risk glycemic category. The Norfolk Diabetes Prevention Study was a parallel, 3-arm, group-based, randomized clinical trial conducted with up to 46 months of follow-up from August 2011 to January 2019 at 135 primary care practices and 8 intervention sites in the East of England. We identified 141 973 people at increased risk of type 2 diabetes, screened 12 778 (9.0%), and randomized those with a high-risk glycemic category, which was either an elevated fasting plasma glucose level alone (≥110 and <126 mg/dL [to convert to millimoles per liter, multiply by 0.0555]) or an elevated glycated hemoglobin level (≥6.0% to <6.5%; nondiabetic hyperglycemia) with an elevated fasting plasma glucose level (≥100 to <110 mg/dL). A control arm receiving usual care (CON), a theory-based lifestyle intervention arm of 6 core and up to 15 maintenance sessions (INT), or the same intervention with support from diabetes prevention mentors, trained volunteers with type 2 diabetes (INT-DPM). Type 2 diabetes incidence between arms. In this study, 1028 participants were randomized (INT, 424 [41.2%] [166 women (39.2%)]; INT-DPM, 426 [41.4%] [147 women (34.5%)]; CON, 178 [17.3%] [70 women (%39.3)]) between January 1, 2011, and February 24, 2017. The mean (SD) age was 65.3 (10.0) years, mean (SD) body mass index 31.2 (5) (calculated as weight in kilograms divided by height in meters squared), and mean (SD) follow-up 24.7 (13.4) months. A total of 156 participants progressed to type 2 diabetes, which comprised 39 of 171 receiving CON (22.8%), 55 of 403 receiving INT (13.7%), and 62 of 414 receiving INT-DPM (15.0%). There was no significant difference between the intervention arms in the primary outcome (odds ratio [OR], 1.14; 95% CI, 0.77-1.7; P = .51), but each intervention arm had significantly lower odds of type 2 diabetes (INT: OR, 0.54; 95% CI, 0.34-0.85; P = .01; INT-DPM: OR, 0.61; 95% CI, 0.39-0.96; P = .033; combined: OR, 0.57; 95% CI, 0.38-0.87; P = .01). The effect size was similar in all glycemic, age, and social deprivation groups, and intervention costs per participant were low at $153 (£122). The Norfolk Diabetes Prevention lifestyle intervention reduced the risk of type 2 diabetes in current high-risk glycemic categories. Enhancing the intervention with DPM did not further reduce diabetes risk. These translatable results are relevant for current diabetes prevention efforts. ISRCTN Registry Identifier: ISRCTN34805606.

SUN-LB69 A Comparison Between Weight Loss Associated Bone Loss From Lifestyle Measures Versus Bariatric Surgery

Background Despite improvement in many metabolic outcomes, bone loss remains a concern with weight loss (WL). In this prospective study, we compared the effects of WL from lifestyle intervention (LI) and bariatric surgery (BS) on WL-associated bone loss. We hypothesize that the higher WL from bariatric surgery will result in a greater decline in bone mineral density (BMD) and bone quality. Methods Twenty-nine obese subjects (BMI > 30 kg/m2; weight: 107±19.3 kg) were included in the study; 13 participated in a LI study of WL (supervised diet+exercise) and 16 underwent BS. Assessments were done at 10% WL and at 6 months. Areal BMD and body composition were evaluated by DXA; bone micro-architecture and bone strength by microfinite element analysis-derived parameters as failure load (f.load) and stiffness at the distal radius and distal tibia were evaluated by high resolution peripheral quantitative computed tomography. Serum bone turnover markers, adipokines and cytokines were measured by Elisa. Results Participants in the LI arm were significantly older (71.3±4 vs 48.2±10 y.o., p < 0.001) and lighter (93.4 ± 8 vs. 118.5±18 kg, P=0.001) compared to the BS arm. Analysis adjusted for baseline age and weight showed no significant differences in areal BMD at all sites, volumetric BMD and bone microarchitectural features of the radius and tibia, except for higher cortical porosity (Ct.Po) at the tibia in the LI arm compared to the BS arm (3.0±0.3 vs 1.7±0.3%, p=0.04, respectively). The average WL at 6 months were -11.87±4.7 vs.-15.96±5.1%, p=0.07, for LI and BS, respectively. At 10%WL, the LI arm had a reduction in trabecular volumetric BMD (tb.vBMD) at the radius (-2.2±1.2 vs. 3.1±4.8% P=0.05) and tibia (-2.2±1.4 vs. 2.2±3.9 % P=0.02, respectively) compared to BS arm which had increases in this parameter. There was also a trend for reduced radius trabecular number and thickness in the LI arm at 10% WL. Meanwhile, there was a trend for reduction in total hip BMD, f.load and stiffness at the radius in the BS arm only. At 6 months, tb.vBMD at the radius was reduced in LI (-2.7±0.9%) relative to the increase in BS group (5.7±2.0%), p=0.008. There was a reduction in F.load (-5.3±2.4 vs 0.6±1.2%, p=0.09) and stiffness (-6.1±2.7 vs. 0.8±1.4%, p=0.08) of borderline significance at the tibia in the BS compared to no change in LI arm. BS arm showed a greater increase in serum C- telopeptide (28.1±48 vs. 81.3±30%, P=<0.05), an index of bone resorption, and in adiponectin (-0.7±8 vs.36.2±22.1%, P=0.01) compared to LI at 6 months. There were no significant differences in changes in lean and fat mass at 6 months in both arms. Conclusion: Although WL from LI resulted in reduced radial tb.vBMD, BS was associated with a greater increase in bone resorption and a trend for reduction in bone strength at the weight-bearing tibia at 6 months compared to LI. Results from this pilot project need confirmation in a larger study with longer duration of follow-up.

Abstract P437: Early Insulin Resistance Responds To Lifestyle Interventions: The Premier Study

Introduction: Compensatory hyperinsulinemia (CH) is the metabolic response to early insulin resistance. Elevated blood insulin compensates for insulin resistance in tissues, maintaining normal fasting glucose and lipid levels. Therefore, CH is undetected by conventional screening tests for diabetes and cardiovascular risk. Our prior work showed that CH is prevalent in the U.S., especially in teenagers, young adults and Hispanic populations. Moreover, CH in young adults doubles the risk for diabetes later in life, independent of other known risk factors. The current study tested the hypothesis that markers of early insulin resistance improve with behavioral lifestyle interventions. Methods: The parent PREMIER study was a randomized controlled trial to evaluate the effect of lifestyle interventions on blood pressure. Many subjects also had insulin resistance, prediabetes (PreD) and/or metabolic syndrome (MetS). The interventions included increased physical activity, weight loss, reduced sodium and alcohol intake, and the DASH diet (Dietary Approaches to Stop Hypertension). A total of 810 subjects were randomized into three intervention arms: “established”, “established plus DASH” and “advice only”. Established refers to the above interventions, except for DASH. The subjects were 62% women and 34% African Americans; the mean age was 50.0±8.9 years. Inclusion criteria were age ≥25, elevated BP and BMI of 18.5-45.0 kg/m 2 . Exclusion criteria were diabetes, history of cardiovascular event, heart failure, cancer or psychiatric hospitalization within the last 2 years. Here, the analysis of covariance method was used to determine whether markers of insulin resistance at 6 months improved in the established or established plus DASH arms compared with the advice-only arm, after adjusting for baseline values. The results are reported as geometric means and 95% confidence intervals (CI). Results: Subjects in the lifestyle intervention arms showed reduced fasting insulin and increased insulin sensitivity compared with the advice-only arm. The mean fasting insulin levels after 6 months of the established and established plus DASH interventions were 9.8 μIU/mL (95% CI: 9.3, 10.3) and 10.1 (9.6, 10.7), respectively, compared with 12.0 (11.4, 12.6) for advice only. After excluding subjects with PreD and/or MetS at baseline, insulin levels for established and established plus DASH were 8.0 (7.3, 8.7) and 8.3 (7.3, 9.0), respectively, as compared with 9.8 (9.1, 10.6) for advice only. Likewise, HOMA2 %S increased to 101.2 (92.5, 110.6) and 93.3 (85.6, 101.8), respectively, compared with 79.0 (73.0, 85.5) in the advice-only arm. Conclusion: Markers of insulin resistance improved with the PREMIER lifestyle interventions, even in subjects who did not meet the clinical criteria for prediabetes or metabolic syndrome. Early screening and intervention may improve diabetes prevention outcomes.

The LISA randomized trial of a weight loss intervention in postmenopausal breast cancer

Obesity has been associated with poor breast cancer (BC) outcomes. We investigated whether a standardized, telephone-based weight loss lifestyle intervention in the adjuvant setting would impact BC outcomes. We conducted a multicenter trial randomizing women 1:1 to mail-based educational material alone (control) or combined with a standardized, telephone-based lifestyle intervention that focused on diet, physical activity, and behavior and involved 19 calls over 2 years to achieve up to 10% weight loss. In all, 338 (of 2150 planned) T1-3, N0-3, M0 hormone receptor positive BC patients with body mass index (BMI) ≥24 kg/m2 receiving adjuvant letrozole were randomized (enrolment ended due to funding loss). The primary outcome was disease-free survival (DFS); secondary outcome was Overall Survival (OS). At 8 years’ median follow-up, in a planned analysis, DFS and OS were compared using the Kaplan–Meier method. Baseline BMI and other characteristics were similar between study arms. In all, 22 of 171 (12.9%) in the lifestyle intervention arm versus 30 of 167 (18.0%) in the education had DFS events; the hazard ratio (HR) was 0.71 (95% confidence interval [CI]: 0.41–1.24, p = 0.23). Although loss of funding reduced sample size, we view these hypothesis generating results as compatible with our hypothesis of a potential beneficial effect of a lifestyle intervention on DFS. They provide support for completion of ongoing randomized controlled trials of the effect of lifestyle interventions in BC outcomes.

Abstract GS5-03: Lifestyle Intervention and Effect on Disease-free Survival in Early Breast Cancer Pts: Interim Analysis from the Randomized SUCCESS C Study

Abstract Background: Recent trials have provided evidence that obesity and a low level of physical activity are not only associated with a higher risk of developing breast cancer, but also with an increased risk for recurrence and reduced survival in breast cancer patients (pts). The SUCCESS C study is the first randomized Phase III trial to evaluate the effect of an intensive lifestyle intervention program, focusing on both physical activity and healthy diet following adjuvant chemotherapy on disease-free survival in women with early breast cancer. Methods: SUCCESS C is a German multicenter, 2×2 factorial design, randomized phase III study comparing disease-free survival (DFS) in pts with HER2-negative early breast cancer treated with either 3 cycles of epirubicine, fluorouracil, cyclophosphamide chemotherapy followed by 3 cycles of docetaxel (FEC-D) or 6 cycles of docetaxel-cyclophosphamide (DC). The second randomization compares DFS in pts with a body mass index (BMI) of 24—40 kg/m2 receiving either a telephone-based individualized lifestyle intervention (LI) program aiming at moderate weight loss for 2 years (LI arm) or general recommendations for a healthy lifestyle alone (non-LI arm). DFS according to lifestyle intervention was analyzed using both univariable cox regressions and multivariable cox regressions adjusted for age (years, continuous), BMI (kg/m2, continuous), menopausal status (premenopausal, postmenopausal), tumor size (pT1, pT2, pT3/pT4), nodal stage (pN0, pN1, pN2, pN3), hormone receptor status (positive, negative), grading (G1, G2, G3), histological type (ductal, lobular, other) and chemotherapy randomization (FEC-D, DC). Median follow-up was 64.2 months. Results: Overall, 2292 of the 3643 pts recruited for the SUCCESS C study were randomized for the lifestyle intervention program (1146 pts in both the non-LI arm and the LI arm). The Intention-to-treat analysis revealed no difference in DFS between the two treatment arms (LI vs. non-LI) in univariable analysis (hazard ratio [HR] 0.99, 95% confidence interval [CI] 0.76 — 1.28, p = 0.922) and in adjusted multivariable cox regression (HR 0.91, 95% CI 0.70 — 1.18, p = 0.48). At the 2-year follow up, pts in the LI arm lost on average 1.0 kg weight compared to the start of the LI program, while pts in the non-LI arm gained on average 0.95 kg (p &amp;lt; 0.001). Overall, 1477 pts completed the 2-year LI program (non-LI arm: 80.7%, 925 of 1146 pts; LI arm: 48.2%, 552 of 1146 pts; p &amp;lt; 0.001). Pts that completed the 2-year LI program had a significant better DFS than non-completers (HR 0.35, 95% CI 0.27 — 0.45, p &amp;lt; 0.001). Among completers, pts in the LI arm had a significantly better DFS than pts in the non-LI arm both in univariable analysis (HR 0.53, 95% CI 0.35 — 0.82, p = 0.004) and in adjusted multivariable cox regression (HR 0.51, 95% CI 0.33 — 0.78, p = 0.002). Conclusions: This explorative and non-planned interim analysis indicates that the completion of a systematic telephone life style intervention program may positively impact patient outcome in early breast cancer. Citation Format: Janni W, Rack BK, Friedl TW, Müller V, Lorenz R, Rezai M, Tesch H, Heinrich G, Andergassen U, Harbeck N, Schochter F, De Gregorio A, Tzschaschel M, Huober J, Hepp P, Fehm TN, Schneeweiss A, Lichtenegger W, Blohmer J, Hauner D, Beckmann MW, Häberle L, Fasching PA, Hauner H. Lifestyle Intervention and Effect on Disease-free Survival in Early Breast Cancer Pts: Interim Analysis from the Randomized SUCCESS C Study [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr GS5-03.

Abstract PD6-04: Lifestyle intervention study (LISA) in early breast cancer (BC): An RCT of the effects of a telephone-based weight loss intervention (with educational materials) vs educational materials alone on disease-free survival (DFS)

Abstract Background: Obesity has been associated with poor BC outcomes. We investigated whether a standardized, telephone-based weight loss lifestyle intervention in recently diagnosed BC patients would lower recurrence and death rates. Methods: We conducted a multicenter RCT comparing mail-based educational material alone (control arm) or combined with a standardized, telephone-based lifestyle intervention (19 calls over 2 years, (intervention arm) that focused on diet (500-100 kcal/day deficit), physical activity (150-200 minutes of moderate-intensity activity per week) and behavior (compliance, relapse prevention) to achieve up to 10% weight loss. 338 (of 2150 planned) T1-3, N0-3, M0 ER/PgR+ BC patients with body mass index (BMI) ≥ 24 kg/m2 receiving adjuvant letrozole were randomized Aug 2007 to Jan 2010 (enrolment ended due to funding loss). Primary outcome was DFS; secondary outcome OS. Weight loss (5.3 vs 0.7% at 6 months and 3.6 vs 0.4% at 24 months in the intervention vs control arms, respectively) has been reported (JCO 2014;32:2331). At 8 years median follow-up (May 2018), DFS and OS were compared using Cox proportional hazards regression. Results: Mean age was 61.6 vs 60.4 years, mean BMI 31.4 vs 31.0 kg/m2 and adjuvant chemotherapy was received by 56.1 vs 57.5% in intervention vs controls arms respectively. T1/T2/T3 66.7/27.5/5.9% vs 61.7/33.5/3.6% and N0/1/2+ 62.6/28.7/8.8 vs 63.5/32.3/4.2% in intervention vs controls arms respectively. HER2+ in 8.8 vs 15.0% (intervention vs control). 20 of 171 (11.7%) in the lifestyle intervention arm vs 30 of 167 (18.0%) in the mail-based arm had DFS events, HR 0.71, 95%CI 0.41-1.24, p=0.23). DFS curves separated at 2 yrs; beyond 3-3.5 yrs separation approximated 5%. In a landmark DFS analysis of women alive at 24 months, DFS HR=0.68 (0.34-1.37, p=0.28). Conclusions: We identified fewer DFS events in the lifestyle intervention arm. Although loss of funding reduced sample size and lowered power, these results are consistent with a potential beneficial effect of a lifestyle intervention on DFS in postmenopausal ER/PgR+ BC patients. They provide strong support for completion of ongoing RCTs (e.g. BWEL) that will provide definitive evidence regarding the effect of lifestyle based weight loss on BC outcomes. Funded by Novartis Pharmaceuticals Inc.; Sponsored by the Ontario Clinical Oncology Group Citation Format: Goodwin PJ, Segal R, Vallis M, Ligibel JA, Pond GR, Robidoux A, Findlay BP, Gralow JR, Mukherjee SD, Levine MN, Pritchard KI. Lifestyle intervention study (LISA) in early breast cancer (BC): An RCT of the effects of a telephone-based weight loss intervention (with educational materials) vs educational materials alone on disease-free survival (DFS) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr PD6-04.

Effects of weight loss, weight cycling, and weight loss maintenance on diabetes incidence and change in cardiometabolic traits in the Diabetes Prevention Program.

This study examined specific measures of weight loss in relation to incident diabetes and improvement in cardiometabolic risk factors. This prospective, observational study analyzed nine weight measures, characterizing baseline weight, short- versus long-term weight loss, short- versus long-term weight regain, and weight cycling, within the Diabetes Prevention Program (DPP) lifestyle intervention arm (n = 1,000) for predictors of incident diabetes and improvement in cardiometabolic risk factors over 2 years. Although weight loss in the first 6 months was protective of diabetes (hazard ratio [HR] 0.94 per kg, 95% CI 0.90, 0.98; P < 0.01) and cardiometabolic risk factors (P < 0.01), weight loss from 0 to 2 years was the strongest predictor of reduced diabetes incidence (HR 0.90 per kg, 95% CI 0.87, 0.93; P < 0.01) and cardiometabolic risk factor improvement (e.g., fasting glucose: β = -0.57 mg/dL per kg, 95% CI -0.66, -0.48; P < 0.01). Weight cycling (defined as number of 5-lb [2.25-kg] weight cycles) ranged 0-6 times per participant and was positively associated with incident diabetes (HR 1.33, 95% CI 1.12, 1.58; P < 0.01), fasting glucose (β = 0.91 mg/dL per cycle; P = 0.02), HOMA-IR (β = 0.25 units per cycle; P = 0.04), and systolic blood pressure (β = 0.94 mmHg per cycle; P = 0.01). After adjustment for baseline weight, the effect of weight cycling remained statistically significant for diabetes risk (HR 1.22, 95% CI 1.02, 1.47; P = 0.03) but not for cardiometabolic traits. Two-year weight loss was the strongest predictor of reduced diabetes risk and improvements in cardiometabolic traits.

Plasma 25-hydroxyvitamin D and risk of metabolic syndrome: an ancillary analysis in the Diabetes Prevention Program.

Low blood levels of 25-hydroxyvitamin D (25OHD) have been associated with cardiometabolic disease but results are inconsistent. The objective of the study was to investigate the association of 25OHD with metabolic syndrome in a population at increased risk for diabetes. Using baseline data from the placebo and lifestyle intervention arms of the Diabetes Prevention Program (N=2000), multivariable logistic regression models were used to estimate the odds of prevalent metabolic syndrome and each of its individual components across 25OHD tertiles. Multivariable linear regression was used to estimate the adjusted mean difference of insulin secretion and sensitivity across the same 25OHD tertiles. In participants free of metabolic syndrome at baseline (N=546), incident metabolic syndrome in the first 2 years of follow-up was assessed using discrete-time proportional hazards regression to test its association with 25OHD concentration. After multivariate adjustment, participants in the highest tertile of 25OHD had lower odds of prevalent metabolic syndrome (odds ratio=0.62; 95% confidence interval (CI)=0.45-0.84), smaller waist circumference, higher high-density lipoprotein and lower fasting plasma glucose compared with participants in the lowest tertile of 25OHD. Higher plasma 25OHD concentration was associated with greater insulin sensitivity and lower insulin secretion. After multivariate adjustment, there was a nonsignificant lower risk of metabolic syndrome in the highest tertile of 25OHD (hazard ratio=0.79; 95% CI=0.48-1.32) compared with the lowest tertile. In a population at increased risk for diabetes, higher plasma 25OHD concentration was inversely associated with prevalent metabolic syndrome and nonsignificantly with incident metabolic syndrome.

Predictors of Sustained Reduction in Energy and Fat Intake in the Diabetes Prevention Program Outcomes Study Intensive Lifestyle Intervention

BackgroundFew lifestyle intervention studies examine long-term sustainability of dietary changes. ObjectiveTo describe sustainability of dietary changes over 9 years in the Diabetes Prevention Program and its outcomes study, the Diabetes Prevention Program Outcomes Study, among participants receiving the intensive lifestyle intervention. DesignOne thousand seventy-nine participants were enrolled in the intensive lifestyle intervention arm of the Diabetes Prevention Program; 910 continued participation in the Diabetes Prevention Program Outcomes Study. Fat and energy intake derived from food frequency questionnaires at baseline and post-randomization Years 1 and 9 were examined. Parsimonious models determined whether baseline characteristics and intensive lifestyle intervention session participation predicted sustainability. ResultsSelf-reported energy intake was reduced from a median of 1,876 kcal/day (interquartile range [IQR]=1,452 to 2,549 kcal/day) at baseline to 1,520 kcal/day (IQR=1,192 to 1,986 kcal/day) at Year 1, and 1,560 kcal/day (IQR=1,223 to 2,026 kcal/day) at Year 9. Dietary fat was reduced from a median of 70.4 g (IQR=49.3 to 102.5 g) to 45 g (IQR=32.2 to 63.8 g) at Year 1 and increased to 61.0 g (IQR=44.6 to 82.7 g) at Year 9. Percent energy from fat was reduced from a median of 34.4% (IQR=29.6% to 38.5%) to 27.1% (IQR=23.1% to 31.5%) at Year 1 but increased to 35.3% (IQR=29.7% to 40.2%) at Year 9. Lower baseline energy intake and Year 1 dietary reduction predicted lower energy and fat gram intake at Year 9. Higher leisure physical activity predicted lower fat gram intake but not energy intake. ConclusionsIntensive lifestyle intervention can result in reductions in total energy intake for up to 9 years. Initial success in achieving reductions in fat and energy intake and success in attaining activity goals appear to predict long-term success at maintaining changes.

Genetic Modulation of Lipid Profiles following Lifestyle Modification or Metformin Treatment: The Diabetes Prevention Program

Weight-loss interventions generally improve lipid profiles and reduce cardiovascular disease risk, but effects are variable and may depend on genetic factors. We performed a genetic association analysis of data from 2,993 participants in the Diabetes Prevention Program to test the hypotheses that a genetic risk score (GRS) based on deleterious alleles at 32 lipid-associated single-nucleotide polymorphisms modifies the effects of lifestyle and/or metformin interventions on lipid levels and nuclear magnetic resonance (NMR) lipoprotein subfraction size and number. Twenty-three loci previously associated with fasting LDL-C, HDL-C, or triglycerides replicated (P = 0.04–1×10−17). Except for total HDL particles (r = −0.03, P = 0.26), all components of the lipid profile correlated with the GRS (partial |r| = 0.07–0.17, P = 5×10−5–1×10−19). The GRS was associated with higher baseline-adjusted 1-year LDL cholesterol levels (β = +0.87, SEE±0.22 mg/dl/allele, P = 8×10−5, P interaction = 0.02) in the lifestyle intervention group, but not in the placebo (β = +0.20, SEE±0.22 mg/dl/allele, P = 0.35) or metformin (β = −0.03, SEE±0.22 mg/dl/allele, P = 0.90; P interaction = 0.64) groups. Similarly, a higher GRS predicted a greater number of baseline-adjusted small LDL particles at 1 year in the lifestyle intervention arm (β = +0.30, SEE±0.012 ln nmol/L/allele, P = 0.01, P interaction = 0.01) but not in the placebo (β = −0.002, SEE±0.008 ln nmol/L/allele, P = 0.74) or metformin (β = +0.013, SEE±0.008 nmol/L/allele, P = 0.12; P interaction = 0.24) groups. Our findings suggest that a high genetic burden confers an adverse lipid profile and predicts attenuated response in LDL-C levels and small LDL particle number to dietary and physical activity interventions aimed at weight loss.

Can we out-run the diabetes epidemic?

According to the WHO, the worldwide prevalence of diabetes in 2030 is expected have doubled from the year 2000 estimate of 171 million [1]: by all estimates, the prevalence of type 2 diabetes has already reached epidemic proportions in the developed world. Observational studies have demonstrated that, with few exceptions, overweight and obesity are almost ubiquitous in type 2 diabetes, and the relatively large projected growth in the prevalence of diabetes in the developing world is largely attributable to the spread of overweight and obesity. Intervention programmes to prevent the development of diabetes should therefore focus on reversing overweight and obesity, which underlie this devastating disease. When the findings from the Diabetes Prevention Program (DPP) were first announced in 2002 [2], the scientific community was not surprised to learn that study participants in the intensive lifestyle intervention arm had a lower risk of developing diabetes than their counterparts in the placebo arm. The surprising finding was that intensive lifestyle intervention, based on dietary energy restriction and encouragement to engage in moderate physical activity on most days of the week, with a goal of achieving 7% weight loss [3], performed better than metformin in preventing high-risk participants from developing diabetes. Later evidence that the intensive lifestyle intervention was a cost-effective alternative to pharmacological therapy [4] reemphasised the benefits of diet and exercise in the prevention of diabetes. If lifestyle intervention is such a resounding success, why is it important to determine whether it is diet or physical activity that is driving the success? The answer to that question lies in the difficulty individuals have in adopting lifestyle changes. Compliance with lifestyle intervention certainly varies between individuals, but inter-individual variability in the physiological responses to diet and exercise is even greater. By simplifying interventions to focus on the most effective component, or the component that is easiest to adopt (as the two are not often the same), we might improve compliance with the intervention and thus achieve greater success in preventing disease. In this issue of Diabetologia, Yates et al. [5] report on a systematic review of clinical trials to determine whether the physical activity component of lifestyle interventions prevents the development of diabetes or lowers fasting or 2-h blood glucose levels in participants with impaired fasting glucose or impaired glucose tolerance. The stated goal of the review is to determine whether physical activity demonstrates a protective association with incident diabetes, independently of dietary energy restriction. The authors summarise the findings from eight controlled trials and report that lifestyle interventions reduced the incidence of diabetes by approximately 50%, but that there was little decrease in blood glucose during the intervention period. None of the studies could determine whether the reduction in risk was independent of weight loss. Based on these results, Yates and colleagues conclude that the evidence for exercise interventions in preventing the development of diabetes is equivocal. Further, the authors advance the hypothesis that the reduction in diabetes incidence is probably attributable to factors other than increased physical activity since, when measured, actual changes in physical activity were minimal. Diabetologia (2007) 50:1113–1115 DOI 10.1007/s00125-007-0673-5