Modest weight loss improves leptin to adiponectin ratio and induces insulin and leptin resensitivization in individuals with obesity.

Background Weight loss is important to reduce the risk of metabolic complications in obese individuals, in whom dysregulated adipokines play a central role. This study aims to investigate whether dysregulated adipokines and postprandial triglycerides (TG) improve with a modest weight loss. Methods Individuals with obesity were recruited among patients at the University Hospital of North Norway and the Stamina Health weight loss rehabilitation program. We measured resting energy expenditure (REE), and calculated the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), leptin to adiponectin (L:A) ratio, indirect leptin sensitivity (REE:leptin ratio), postprandial TG clearance at 6 h, and TG response before and after weight loss. The goal of the weight loss intervention was a loss of ≥5% of initial total body weight. Results Of the 28 participants who attended two scheduled assessments, 13 lost ≥5% body weight. HOMA-IR (-23.1%), REE:leptin ratio (+80.1%) and L:A ratio (-45.7%) significantly improved with weight loss, whereas there was no improvement of postprandial TG response or clearance. No significant changes were observed in the non-weight loss group. Conclusion Metabolic dysregulation, as insulin and leptin resistance, but not postprandial TG improve with a modest weight loss in individuals with obesity.

Adherence and Dietary Composition during Intermittent vs. Continuous Calorie Restriction: Follow-Up Data from a Randomized Controlled Trial in Adults with Overweight or Obesity

Although intermittent calorie restriction (ICR) has become popular as an alternative weight loss strategy to continuous calorie restriction (CCR), there is insufficient evidence on diet quality during ICR and on its feasibility over longer time periods. Thus, we compared dietary composition and adherence between ICR and CCR in a follow-up analysis of a randomized trial. A total of 98 participants with overweight or obesity [BMI (kg/m2) 25–39.9, 35–65 years, 49% females] were randomly assigned to ICR, operationalized as a “5:2 diet” (energy intake: ~100% on five non-restricted (NR) days, ~25% on two restricted (R) days), or CCR (daily energy intake: ~80%). The trial included a 12-week (wk) intervention phase, and follow-up assessments at wk24, wk50 and wk102. Apart from a higher proportion of energy intake from protein with ICR vs. CCR during the intervention (wk2: p < 0.001; wk12: p = 0.002), there were no significant differences with respect to changes in dietary composition over time between the groups, while overall adherence to the interventions appeared to be good. No significant difference between ICR and CCR regarding weight change at wk102 was observed (p = 0.63). However, self-reported adherence was worse for ICR than CCR, with 71.1% vs. 32.5% of the participants reporting not to or only rarely have followed the regimen to which they were assigned between wk50 and wk102. These results indicate that within a weight management setting, ICR and CCR were equivalent in achieving modest weight loss over two years while affecting dietary composition in a comparable manner.

Energy Balance Dynamics: Exercise, Appetite, Diet, and Weight Control

Individuals seeking to achieve weight loss are encouraged to achieve a negative energy balance, essentially eat less and move more. The complex relationship between energy expenditure and intake is often overlooked, leaving individuals and practitioners underwhelmed by the results of weight loss efforts. Independently, physical activity and diet interventions can yield modest weight loss and when combined have synergistic effects that promote sustained weight loss. Although physical activity benefits appetite suppression, reduces food rewards, and can be considered a gateway to healthy eating, high levels of daily activity are needed to induce weight loss. Diet is an important component to achieving weight loss, and high-protein diets have the potential for supporting weight loss as well. This column will be focused on the benefits of physical activity in reducing body weight, more specifically, the interdependent relationship between dietary intake and physical activity in achieving weight reduction.

Racial Differences in Glucose Handling and Function With Obesity Reduction: Preliminary Findings

Blacks have higher rates of obesity and are twice as likely to develop diabetes as non-Hispanic whites. Obesity reduction can improve metabolic health, but physical function and glucose handling may be threatened by concomitant loss of muscle mass. These preliminary findings from a 4-mo. randomized controlled trial assess the racial differences in glucose handling and physical function in obese, older adults with prediabetes (Fasting Plasma Glucose (FPG) ≥95&lt;126 mg/dL or HbA1c 5.7-6.4%) following obesity reduction. At 4 mo. endpoint, participants (n = 31; age = 68.1±5.4 years, BMI =36.0±4.7 kg/m2) had reduced (p&lt;0.05) body weight in both Blacks (5.1%) and Whites (4.1%); HbA1c levels were also reduced (Blacks = -0.3 ±0.3; Whites = -0.1±0.3) with no difference by race. However, FPG was reduced for Blacks compared to Whites (-7.9±9.5 vs. -2.8±6.2 mg/dL; p&lt;0.05). Short Physical Performance Battery (SPPB) score was lower for Blacks than Whites at both baseline (9.8±1.5 vs 10.9±1.2; p&lt;0.05) and 4 mo. (10.17±1.4 vs 11.21±1.3; p&lt;0.05), respectively. A trend towards improvement (p=0.08) in meters walked in 6 minutes was present in both Blacks (13.3±60.8) and Whites (20.0±36.3) with no between-group difference. Interestingly, at baseline, 41% of participants said they modified their behaviors due to a fear of falling despite having a mean SPPB score of 10.3±1.5. Following the intervention, fear of falling was reduced, with 35% of the participants reporting this behavior. Our findings illustrate that modest weight loss improves glucose handling, physical function and perceived fall risk for both Black and White older adults with prediabetes.

A Two-Year Follow-Up Cohort Study—Improved Clinical Control over CVD Risk Factors through Weight Loss in Middle-Aged and Older Adults

Modest weight loss enhances clinical control over cardiovascular disease (CVD) risk factors in overweight and obese individuals. This study aimed to assess the associations between individual weight loss and predefined criteria for clinical improvement in blood pressure, lipid levels, and glycemia. A two-year follow-up study involved 3388 (37.9% men) aged 45−64 years, BMI ≥ 25 kg/m2. Changes in body weight were calculated as a percentage of baseline weight; outcome variables: systolic (SBP), diastolic (DBP) blood pressure, high-density (HDL-C) and low-density (LDL-C) lipoproteins, fasting blood glucose (FBG), and triglycerides (TG) were construed as the differences between baseline and outcome values. Clinically significant improvement was defined as SBP/DBP reduction by 5 mm/Hg, FBG−20 mg/dL, LDL-C-10 mg/dL, TG−40 mg/dL, and HDL-C increase by 5 mg/dL. Apart from LDL-C, a modest 5%–10% weight loss was associated with clinically significantly improved outcomes. The incident rate ratios and 95% confidence intervals for clinical improvement of SBP were: 1.27 (1.14–1.40), DBP/1.30 (1.12–1.50), HDL/1.54 (1.18–2.02), and TG/1.69 (1.32–2.17). In the higher category of weight loss, associations were still manifest, although the results proved diagnostically challenging (low number of cases). Even though modest weight loss does enhance clinical control over CVD risk factors, offering regular medical guidance to patients is postulated to further boos the anticipated outcomes.

Supplemental Text Message Support With the National Diabetes Prevention Program: Pragmatic Comparative Effectiveness Trial

Background The evidence-based National Diabetes Prevention Program (NDPP) is now widely disseminated, yet strategies to increase its effectiveness are needed, especially for underserved populations. The yearlong program promotes lifestyle changes for weight loss and can be offered in-person, online, via distance learning, or a combination of modalities. Less is known about which delivery features are optimal and may help address disparities in outcomes for subgroups. We previously demonstrated the efficacy of a stand-alone text messaging intervention based on the NDPP (SMS4PreDM) in a randomized controlled trial in a safety net health care system. Upon broader dissemination, we then showed that SMS4PreDM demonstrated high retention and modest weight loss at a relatively low cost, suggesting the potential to improve in-person NDPP delivery. Objective In this study, we aim to compare the effectiveness of in-person NDPP classes with and without supplementary SMS4PreDM on attendance and weight loss outcomes to determine whether text messaging can enhance in-person NDPP delivery for a safety net patient population. Methods From 2015 to 2017, patients with diabetes risks were identified primarily from provider referrals and enrolled in NDPP classes, SMS4PreDM, or both per their preference and availability. Participants naturally formed three groups: in-person NDPP with SMS4PreDM (n=236), in-person NDPP alone (n=252), and SMS4PreDM alone (n=285). This analysis compares the first two groups to evaluate whether supplemental text messaging may improve in-person NDPP outcomes. Outcomes for SMS4PreDM-only participants were previously reported. NDPP classes followed standard delivery guidelines, including weekly-to-monthly classes over a year. SMS4PreDM delivery included messages promoting lifestyle change and modest weight loss, sent 6 days per week for 12 months. Differences in characteristics between intervention groups were assessed using chi-square and t tests. Differences in NDPP attendance and weight loss outcomes were analyzed with multivariable linear and logistic regressions. Results The mean age was 50.4 years (SD 13.9). Out of a total of 488 participants, 76.2% (n=372) were female and 59.0% (n=288) were Hispanic. An additional 17.2% (n=84) were non-Hispanic white and 12.9% (n=63) were non-Hispanic black. A total of 48.4% (n=236) of participants elected to receive supplemental text message support in addition to NDPP classes. Participants who chose supplemental text message support were on average 5.7 (SD 1.2) years younger (P<.001) than the 252 participants who preferred in-person classes alone. Relatively more women and Hispanic individuals enrolled in the NDPP with supplemental text messages than in NDPP classes alone, 83.9% (n=198) vs 69.0% (n=174, P<.001) and 68.6% (n=162) vs 50.0% (n=126, P=.001), respectively. Attendance and weight loss outcomes were comparable between groups. Conclusions Despite its appeal among priority populations, supplemental text messaging did not significantly increase attendance and weight loss for the in-person NDPP. Further research is needed to identify optimal strategies to improve the effectiveness of the NDPP.

S90. A SYSTEMATIC REVIEW AND META-ANALYSIS OF PHARMACOLOGICAL INTERVENTIONS FOR REDUCTION OF WEIGHT GAIN IN PEOPLE WITH SCHIZOPHRENIA: 2019 UPDATE

Background Weight gain and obesity are common problems encountered by patients with schizophrenia. This is partially attributable to use of second-generation antipsychotics that are associated with weight gain and other metabolic disturbances. The significance of this prevalence and its impact on premature mortality and morbidity requires better consensus on its management. The objective of this review is to determine the effects of adjunctive pharmacological interventions aimed at reducing weight gain in schizophrenia. Methods We searched the Cochrane Schizophrenia Group’s Trials Register which is based on regular searches of CINAHL, BIOSIS, AMED, EMBASE, PubMed, MEDLINE, PsycINFO, and registries of clinical trials. Inclusion criteria consisted of all randomized controlled trials examining any adjunctive pharmacological intervention for weight loss in patients with schizophrenia or schizophrenia-like illnesses. The primary outcome of each study had to be body weight or a weight related measure. We reliably selected, quality assessed, and extracted data from studies. As endpoint and change data was combined in the analysis, mean differences (MD) of the change from baseline were calculated using Review Manager 5.3. Results Sixty-one randomized controlled trials met inclusion criteria for this review (pooled n = 3328). Metformin is effective in bringing about modest weight loss (Weight: MD -3.40 kg, 95% CI -4.63 to -2.16; participants = 731; studies = 12; BMI: MD -1.39, 95% CI -1.94 to -0.85; participants = 879; studies = 13). Heterogeneity was reduced by dividing populations into first episode psychosis (FEP) and chronic populations, where FEP patients appeared to benefit most from early metformin intervention (Weight: MD -5.18 kg, 95% CI -6.22 to -4.14; BMI: MD -1.87 kg/m2, 95% CI -2.19 to -1.56; participants = 214; studies = 3) as compared to chronic patients (Weight: MD -2.22 kg, 95% CI -3.07 to -1.37; participants = 517; studies = 9; BMI: MD -1.18 kg/m2, 95% CI -1.89 to -0.48; participants = 665; studies = 10). However, ethnicity could be a confounder for the apparent effect of illness stage, as all first episode metformin intervention studies were conducted in patients with Chinese ethnicity. Metformin as a treatment for weight gain may be associated with additional adaptive changes in fasting insulin levels and insulin resistance. The frequency of adverse effects did not differ between metformin and placebo groups. Moreover, glucagon-like peptide agonists (GLP-1RAs), such as liraglutide and exenatide, were also effective in reducing weight (Weight: MD -3.95 kg, 95% CI -7.08 to -0.83; participants = 165; studies = 3; BMI -1.26 kg/m2, 95% CI -2.21 to -0.30; participants = 165; studies = 3; waist circumference: MD -3.25, 95% CI -5.93 to -0.57; participants = 165, studies = 3). The frequency of adverse effects did not differ between GLP-1RA and placebo groups. Topiramate 200 mg was also effective for weight reduction (Weight: MD=-6.61 kg, 95% CI -9.62 to -3.61; BMI: MD=-2.72, 95% CI -3.25 to -2.20; participants = 181, studies = 3). Discussion This review highlights the promise of pharmacological interventions for decreasing weight gain associated with antipsychotic use. Of the drugs studied, metformin has the most evidence and was most effective in bringing about modest weight loss. Topiramate and GLP-1RA also have accumulating evidence supporting efficacy in reducing weight. Interpretation for other agents is limited by the small number of studies, sample size, and short study duration. Future studies that are adequately powered, with longer treatment duration, will be needed in evaluating the efficacy and safety of interventions for managing weight gain further.

MON-132 Implementation of a Diabetes Prevention Program in the San Francisco Safety Net

Background: We examine the implementation of a DPP in the San Francisco Health Network, a safety net serving over 140,000 patients. We also evaluate the success of patients referred to a YMCA DPP, including the role of incentives (gym memberships and food vouchers). Methods: Overweight patients with prediabetes were referred, screened for eligibility and readiness, and invited to participate in a CDC-approved digital or in-person DPP. The YMCA’s DPP groups were led by a trained lifestyle coach, in English or Spanish, with 16 weekly core sessions followed by nine maintenance sessions over a year. Sessions were held at health care sites or at a YMCA (3 of 5 sites had gyms). Gym memberships were offered at no cost to all participants. Continued membership required meeting attendance metrics. Food vouchers became available to participants in Spring 2019. Results: From August 2017 to October 2019, 650 patients were referred to the DPP, 168 (25.8%) were reached, passed a readiness assessment and chose to participate. Of those, 110 patients expressed interest in the YMCA and 73 have registered for one of eight classes that are now past 16 weeks. Of those 73 patients, 64 officially enrolled (e.g. attended at least one session in the first four weeks). Enrolled patients were majority female (78.1%) and 45.3% reported a family history of DM. Average age was 47.9 ± 12.2 y, BMI 37.7 ± 8.4, A1c 5.8% ± 0.3. More than half (56.3%) were Hispanic/Latino, 17.2% Black, 9.4% Asian. Exactly half were English- and half Spanish-speaking. Of the 64 enrolled patients, 42 were retained in the DPP (e.g. attended four or more sessions). These patients attended an average of 11.8 ± 3.4 of the core 16 sessions. At wk 16, average weight loss was 2.2% ± 3.9 (N=40, range -4.4, 16.7); 20% of patients lost at least 5% of their initial body weight. Regarding incentives, 76% of the retained patients activated their gym membership. Average monthly gym attendance was 9.1 ± 9.1 visits with monthly visits maintained over 180 days. Gym visits positively correlated with weight loss (r2= 0.42) and there was a non-significant trend towards more frequent gym visits by patients enrolled at sites with a gym (11.8 ± 10.9 vs 6.5 ± 6.2). Comparison of Spanish-speaking participants who received food vouchers to those who did not showed a non-significant trend towards improved attendance (12.1 ± 3.0 vs 9.6 ± 3.7 of 16) and 16 wk weight loss (2.2% ± 3.4 vs 0.3% ± 2.4). Additional follow-up data at 36 wks available on 19 patients showed a sustained weight loss of 3.8% ± 6.6 compared to 2.4% ± 4.3 at 16 wks. Conclusion: While DPPs have been widely promoted, real-world implementation has been challenging. Understanding the delivery of DPPs in safety net populations is important given barriers to attendance. Our results show early modest weight loss in those enrolled in the YMCA DPP and suggest incentives such as gym memberships and food vouchers may improve attendance and weight loss.