Intensive Lifestyle Intervention Research Articles

Abstract 4144573: Cardiac biomarkers, intensive lifestyle intervention, and risk of heart failure subtypes in type 2 diabetes – a post-hoc analysis of the Look AHEAD trial

Background: N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) identify subclinical heart failure (HF) in type 2 diabetes (T2D). The contribution of changes in cardiac biomarkers to HF risk, particularly HF subtypes, is unclear. Whether HF risk associated with cardiac biomarkers is modifiable with an intensive lifestyle intervention (ILI) targeting weight loss is unknown. Methods: Adults with T2D and overweight/obesity in the Look Action for Health in Diabetes (AHEAD) trial without prevalent HF were included. NT-proBNP and hs-cTnT were measured at baseline, 1- and 4-years (Roche Diagnostics). Adjusted Cox models were created to evaluate the associations of baseline, 1- and 4-year change in NT-proBNP and hs-cTnT with risk of HF with preserved and reduced ejection fraction (HFpEF and HFrEF, respectively). Interaction testing was performed to evaluate heterogeneous effects of the ILI vs diabetes support and education (DSE) across baseline cardiac biomarkers. Results: Of the 3,959 participants included, 212 had incident HF (108 HFpEF, 84 HFrEF) over 12 years. Higher baseline NT-proBNP and hs-cTnT were each significantly associated with higher risk of HFpEF and HFrEF ( Table) . Increases in NT-proBNP over 1- and 4-years were significantly associated with higher risk of HFpEF and HFrEF with a similar pattern of association for hs-cTnT and HF subtypes. After accounting for risk factor changes, the association of 1- and 4-year changes in NT-proBNP, but not hs-cTnT, with risk of HF subtypes remained significant. There was a significant interaction between NT-proBNP and ILI for risk of HFpEF but not HFrEF (p-int = 0.001). The ILI reduced HFpEF risk among participants with elevated (≥125 pg/mL) but not non-elevated NT-proBNP (<125 pg/mL) (ILI vs DSE HR [95% CI]: 0.48 [0.25-0.93] and 1.67 [0.94-2.94], respectively). No significant treatment group by hs-cTnT interactions were identified. Conclusions: In T2D, longitudinal changes in cardiac biomarkers, particularly NT-proBNP, are significantly associated with HF risk, independent of risk factor changes. In Look AHEAD, elevated NT-proBNP may identify individuals who are more likely to benefit from the ILI for HFpEF prevention.

Abstract 4141434: Real-World Improvement of Cardiometabolic Risk Factors by Treating Obesity at Scale

Intro: Obesity is a critical risk factor for cardiometabolic disease. A growing body of clinical trial data shows GLP-1 receptor agonist medications (GLP-1s) are not only effective in treating obesity but also demonstrate significant impact on the reduction of cardiovascular risk. Yet current models of care have not been able to reach the >200 million Americans who meet criteria for obesity treatment. To improve access to evidence-based treatment, we established a virtual metabolic health company to provide medically-supervised obesity treatment at scale. Research Question: This real-world evaluation examines the impact of a virtual health program on weight and related cardiometabolic markers. Methods: Data were analyzed for individuals who completed at least 12 months (mos) in the core program and for a subset who continued to 24 mos. Obesity treatment involved GLP-1s combined with a proprietary intensive lifestyle intervention delivered with virtual coaching. Weights were submitted via cellular connected scale. Waist circumference, metabolic labs, and patient-completed surveys were analyzed at baseline and 12 mos. Results: The cohort included 6,766 patients, a subset with structured lab data from a larger population of 16,098 patients who had completed 12 mos in the commercial program. Average weight loss at 12 mos was -16.5% (n=5,932) and -17.8% at 24 os (n=1,171). Improvement was observed for all collected metabolic markers: waist circumference, AST/ALT, lipids, HbA1c, insulin, hs-CRP. Specifically for cardiovascular labs, 12 mos results showed improvement in HDL in 56.3% (n= 3,090), in LDL for 64.8% (n=3,066), in hs-CRP for 82.9% (n=2,446). Of n=825 with abnormal A1c at baseline, 77.1% achieve A1c <5.7%. Average reduction in waist circumference was -5.9 inches (n=3,682). Positive changes were also seen for patient-reported outcomes (PROs). Discussion: In the context of significant obesity and cardiovascular results for GLP-1s in clinical trials, it is important to gather data on the efficacy of approaches to scale treatment in the real world since factors such as medication shortages, gaps in insurance coverage, and challenges with adherence occur with treatment outside of clinical trials. Results from 6,766 patients in a virtual metabolic health program available in 50 states and DC demonstrate clinically significant and sustained weight loss through 24 mos, with improvement in associated key cardiometabolic risk markers, health behaviors, and PROs.

Reversal of Diabetic Nephropathy with Intensive Lifestyle Intervention: A Case Report

Background: Diabetic nephropathy is a leading cause of chronic kidney disease, and early intervention is very important to prevent the progression of the disease .Case Presentation: A 45-year-old male patient who is a known case of type 2 diabetes mellitus from 10 years and nephropathy from 1 year underwent intensive lifestyle modification, including caloric restriction, high-intensity interval training, and stress management, alongside medication. Results: After 6 months of following the advice , significant improvements were observed:HbA1c decreased from 10.5% to 6.5%, eGFR increased from 45 to 60 ml/min/1.73m, proteinuria reduced from 2.5 to 0.5 g/day, and blood pressure normalized. Conclusion: This case demonstrates the potential for intensive lifestyle intervention to reverse diabetic nephropathy, highlighting the importance of a multidisciplinary approach in managing diabetes and preventing renal complications.

Primary prevention of type 2 diabetes in the EU: A systematic review of interventional studies

Abstract Background The GBD 2019 study revealed that type 2 diabetes caused over 109.000 deaths and accounted for 5.3 million Disability Adjusted Life Years in the EU, with an estimated annual cost of EUR 300 billion in 2014. Interventions for primary prevention are pivotal in preventing diabetes, providing a structured approach to implementing lifestyle modifications or community-based programs. The objective of this study was to demonstrate the effectiveness of primary prevention interventions to prevent or delay the onset of type 2 diabetes in the EU member states. Methods A systematic review on six databases was conducted for relevant interventional studies carried out in the EU-28. The main outcome of the studies was determined by changes in the incidence of type 2 diabetes. Results The search yielded 18.885 records, of which 18 met the eligibility criteria. The following studies reported significant incidence reduction in the intervention groups: The Finnish Diabetes Prevention Study by individualised lifestyle intervention (HR: 0.614, 95%CI: 0.478-0.789), the Spanish CORDIOPREV Study through increased plant protein intake (HR: 0.64, 95%CI: 0.43-0.96), the Spanish PreDE trial by promoting healthy diet and physical exercise (RR: 0.68, 95%CI: 0.47-0.99), the Norfolk Diabetes Prevention Study with intensive diet-exercise counselling (OR: 0.57, 95%CI: 0.38-0.87), the Spanish PREDIMED and PREDIMED-Reus trials by mediterranean diet supplemented with extra virgin olive oil or mixed nuts (HR: 0.60, 95%CI: 0.43-0.85; HR: 0.49, 95%CI: 0.25-0.97; HR: 0.48, 95%CI: 0.24-0.96), and the Dutch SLIM Study with advices on diet and physical activity (RR: 0.53, 95%CI: 0.29-0.97). Conclusions Significantly decreasing the incidence of diabetes is feasible within primary healthcare settings through intensive lifestyle interventions targeting individuals at high risk. Therefore, it would be beneficial to incorporate these findings into the European guidelines for preventing type 2 diabetes. Key messages • Primary care plays an important role in the prevention of type 2 diabetes. • Well-defined primary lifestyle interventions are capable of slowing the progression from prediabetes to diabetes.

Improvement in symptoms of anxiety and depression in individuals with type 2 diabetes: retrospective analysis of an intensive lifestyle modification program

BackgroundType 2 diabetes (T2D) is a chronic metabolic disorder that has a notable influence on mental well-being, contributing to elevated morbidity and mortality rates. Depression and anxiety disorders are the most common mental health concerns among patients with T2D worldwide. Therefore, the present study aimed to assess the impact of an online intensive lifestyle intervention (ILI) on mental health outcomes (depression and anxiety) in patients with T2D in India.Materials and methodsThis retrospective pre-post analysis included adult patients (aged > 18 years) diagnosed with T2D who were enrolled in a diabetes management program in India between June 2021 and June 2023. The intervention consisted of lifestyle modifications such as a customized plant-based diet, regular physical activity, psychological support through group and individual therapy, and medical management. Data were extracted from the electronic database of the clinic, including anthropometry, medical history, biochemical parameters, symptoms of depression, and anxiety (assessed using the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorders-7 (GAD-7) scale) at the start and end of the six-month intervention period.ResultsOf the 1061 eligible patients (177 with prediabetes), 40.3% were female. The mean age, duration of diabetes, and HbA1c levels were 52 ± 10.4 years, 9.8 ± 7.8 years, and 8 ± 1.7%, respectively. The prevalence of symptoms of depression and anxiety (ranging from mild to severe) was 46% and 44.3%, respectively, which reduced to 28.7% and 29.2%, respectively, post-intervention.ConclusionIntegrated ILI successfully improved the symptoms of anxiety and depression, highlighting the importance of a multidisciplinary approach that includes diet, physical activity, psychological support, and medical management in enhancing mental health outcomes among patients with T2D. Future prospective studies are needed to explore the long-term effects of such interventions and develop effective strategies for promoting mental health in diverse populations.Trial registrationThe study was approved by the Freedom from Diabetes Research Foundation Institutional Ethics Committee (approval number FFDRF/IEC/2024/7) and registered in the Clinical Trials Registry of India (CTRI/2024/03/064596, registered on March 21, 2024).

Prevalence, Characteristics and Risk Factors Analysis of Prediabetes: A Cross-Sectional Study

Background Prediabetes, a reversible condition before the onset of diabetes, is a significant concern in healthcare globally. The global prediabetes epidemic has emerged and has considerably impacted health expenditures. Various risk factors play important roles in the progression of prediabetes to diabetes. Intensive lifestyle and pharmacological interventions can significantly reduce the risk of diabetes progression. Objective This study aimed to determine the prevalence, characteristics, and risk factors of prediabetes state of Medan in August 2023. Methods The sample consisted of 89 participants. This was an analytical cross-sectional study in the community that met the inclusion and exclusion criteria. The determination of prediabetes is based on the results of blood tests, namely, the examination of fasting blood sugar levels (FBGL), 2-hour postprandial oral glucose tolerance test (OGTT), and hemoglobin A1c (HbA1C). Other examinations included lipid profiling (total cholesterol, HDL-C, LDL-C, and triglycerides). Data processing was performed using SPSS via univariate and bivariate analyses (chi-square test). Results Of the 89 participants, the prevalence of prediabetes based on HbA1c, FBGL and 2-hours OGTT levels was 28.1%, 50.6%, and 28.1%, respectively. 82% of the participants were female, and 53.9% were overweight or obese based on body mass index (BMI). The risk factors for prediabetes were age >64 years, female, physical inactivity, and diastolic blood pressure ≥90 mmHg (p<0.05). Other risk factors such age <45-64 years, consumption of vegetables/fruits, BMI, HDL, LDL, trygliceride, total cholesterol, systolic blood pressure, achantosis nigricans, and waist-hip circumference did not associate significantly (p>0.05). Conclusion This study found that the prevalence of prediabetes was 67.4% in Medan. Age >64 years, female, physical inactivity, and diastolic blood pressure ≥90 mmHg were the most important risk factors for prediabetes.

The Effect of a 30-Day Outpatient Intensive Lifestyle Intervention on Cardiometabolic Health

Background: Lifestyle modifications are a first-line treatment to prevent and reverse chronic disease. Lifestyle interventions with a holistic approach can rapidly address multiple risk factors, although adherence can be challenging. This study examined a 30-day, outpatient, intensive lifestyle intervention and its impact on multiple cardiovascular and metabolic risk factors. Methods: This retrospective, observational study included patients at a primary care practice who participated in an innovative, 30-day program consisting of a multifaceted approach to intense lifestyle intervention including a whole food, plant-based diet, daily aerobic exercise, sleep hygiene, and mindfulness-based stress reduction education with regular follow-up and guidance from both lifestyle coaches and physicians. Patients’ pre- and post-program vital signs and lab results were retrospectively reviewed and analyzed for individuals who completed the program from September 2015 to June 2022. Results: Of the 112 participants who met the study criteria, there were a total of 42 males and 70 females with a mean age of 54.8 ± 11.9 years. Participants experienced an average decrease in systolic blood pressure of 11.6 ± 17.4 mmHg (p<0.0001), decrease in diastolic blood pressure of 3.4 ± 10.9 mmHg (p<0.01), and weight loss of 13.6 ± 8.0 lbs (p<0.0001). Lab values showed an average decrease in total cholesterol of 32.2 ± 33.2 mg/dL (p<0.0001), low-density lipoprotein of 19.5 ± 29.3 mg/dL (p<0.0001), A1c of 0.6 ± 0.8% (p<0.01), and high-sensitivity C-reactive protein of 0.9 ± 4.3 mg/L (p = 0.045). Medication deprescribing at onset of intervention occurred in 34 of 41 participants on anti-hypertensives, 14 of 16 participants on lipid-lowering medications, and 12 of 12 participants on anti-diabetic medications. In addition, some participants reported resolution of chronic symptoms including gastroesophageal reflux disease, fatigue, nocturia, and insomnia. Conclusion: A 30-day, outpatient, intensive lifestyle intervention program for primary care patients was successful at improving numerous health vital signs and metabolic risk factors. The intervention allowed for medication deprescribing in most patients on anti-hypertensive, lipid-lowering, and anti-diabetic medications. Future directions should include longitudinal follow-up of sustained impact.

7138 Testosterone Modulation of Muscle Transcriptome Profile During Intensive Lifestyle Intervention in Older Men With Obesity and Hypogonadism

Abstract Disclosure: V. Viola: None. T. Samanta: None. M. Duremdes Nava: None. A. Celli: None. R.C. Villareal: None. N.H. Nguyen: None. G. Colleluori: None. Y. Barnouin: None. N. Napoli: None. C. Qualls: None. B.A. Kaipparettu: None. D.T. Villareal: None. Background: We reported that testosterone replacement added to lifestyle therapy can mitigate weight loss-induced reduction of muscle mass and bone mineral density (BMD) in older men with obesity and hypogonadism (Barnouin et al., J Clin Endocrinol Metab, 2021). Objective: To investigate the molecular mechanisms underlying the mitigation of muscle and BMD loss in response to testosterone replacement therapy during intensive lifestyle intervention in this at-risk population. Materials and Methods: Among the 83 older (≥ 65 y) men with obesity (BMI ≥ 30 kg/m2) and hypogonadism (early AM testosterone persistently <300 ng/dl) associated with frailty (PPT score ≤ 31) who were randomized into 26-week lifestyle therapy plus testosterone (LT+Test) or placebo (LT+Pbo), 38 underwent serial muscle biopsies for the muscle transcriptomics substudy. Results: Despite a similar 9% weight loss, lean body mass and thigh muscle volume decreased less in LT+Test than LT+Pbo (both -2% vs -4%, respectively; p=0.04). Hip BMD was preserved in LT+Test compared with LT+Pbo (0.4% vs -1.1%; p=0.03). Muscle strength increased similarly in LT+Test and LT+Pbo (23% vs 24%; p=0.95). Total testosterone increased more in LT+Test than LT+Pbo (133% vs 32%; p=0.01). Based on Next Generation Sequencing, of the 39,160 and 39,115 genes detected in LT+Test and LT+Pbo, respectively, 151 genes were differentially expressed (DEGs) in LT+Test and 114 in LT+Pbo group. Gene Ontology enrichment analyses revealed that in the LT+Test group, just four muscle-related terms (muscle organ development, muscle organ morphogenesis, regulation of skeletal muscle contraction, muscle atrophy) were downregulated, and one term (muscle system process) was upregulated while in the LT+Pbo, nine terms related to muscle (muscle system process, muscle tissue development, muscle organ development, skeletal muscle tissue development, skeletal muscle organ development, skeletal muscle cell differentiation, muscle organ morphogenesis, response to stimuli involved in regulation of muscle adaptation, muscle atrophy), and one term related to bone (bone mineralization involved in bone maturation) were downregulated. Notably, muscle system process was upregulated in the LT+Test but downregulated in the LT+Pbo. The RT-PCR analyses showed that LT+Test resulted in a higher expression of MYOD1 (p=0.02) and WNT4 (p= 0.08), key genes involved in muscle and bone metabolism, respectively, compared to LT+Pbo. Furthermore, we observed significantly higher mRNA expression of MYBPH (p=0.01), SCN3B (p=0.02), and DSC2 (p=0.01), genes involved in the muscle system process, in response to LT+Test compared to LT+Pbo. Conclusion: The addition of testosterone replacement to lifestyle therapy mitigates the weight loss-induced reduction of muscle mass and BMD via countering the weight loss-induced downregulation of genes involved in muscle and bone anabolism. Presentation: 6/2/2024

8366 Weight Reduction is Associated with Improved Quality of Life in Patients in SURMOUNT-3

Abstract Disclosure: T.H. Gibble: Employee; Self; Eli Lilly & Company. Stock Owner; Self; Eli Lilly & Company. D. Cao: Employee; Self; Eli Lilly & Company. Stock Owner; Self; Eli Lilly & Company. T.D. Forrester: Employee; Self; Eli Lilly & Company. Stock Owner; Self; Eli Lilly & Company. J.F. Brumm: Employee; Self; Eli Lilly & Company. Stock Owner; Self; Eli Lilly & Company. Tirzepatide, a once-weekly glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, is approved in the US for treatment of type 2 diabetes and obesity. In SURMOUNT-3, a phase 3, 72-week, randomized, double-blind clinical trial in adults with obesity/overweight, after 12 weeks intensive lifestyle intervention, treatment with tirzepatide resulted in significantly greater weight reduction than placebo. This post-hoc analysis assessed whether weight reduction was associated with patient-reported outcomes (PRO) improvements in adults treated with tirzepatide. Of 806 adults with obesity (body mass index [BMI] ≥30 kg/m2)/overweight (BMI ≥27 kg/m2) + ≥1 obesity-related complication enrolled in SURMOUNT-3, 579 achieved ≥5% weight reduction with 12 weeks of intensive lifestyle intervention and were randomized to placebo (N=292) or tirzepatide (10/15mg, N=287) for 72 weeks. Adults completed patient-reported outcomes (PRO) questionnaires at randomization and endpoint (72 weeks or early discontinuation), including Short Form-36 Version 2 Health Survey acute form (SF-36v2) and Impact of Weight on Quality of Life-Lite Clinical Trials Version (IWQOL-Lite-CT). Mean change in SF-36v2 norm-based and IWQOL-Lite-CT scores from randomization to endpoint were summarized descriptively by weight reduction targets (≥5%, ≥10%, ≥15%, ≥20%, ≥25%) for adults who received TZP, using the last observation carried forward method. At endpoint, adults with weight reduction showed improvements from randomization in most PRO scores. For SF-36v2, improvements by weight reduction target were seen for General Health (≥5%, 2.6; ≥10%, 2.7; ≥15%, 3.0; ≥20%, 3.3; ≥25%, 3.4), Physical Functioning (3.4, 3.4, 3.8, 4.4, 4.3), Mental Health (0.4, 0.4, 0.7, 0.8, 0.4), Bodily Pain (2.3, 2.5, 3.1, 3.7, 3.9), Role-Physical (1.9, 1.8, 2.2, 2.9, 2.8), Vitality (1.3, 1.3, 1.5, 1.8, 1.4), Social Functioning (0.8, 0.9, 1.1, 2.2, 2.4), Role-Emotional (0.9, 0.8, 1.0, 1.5, 0.9), and Physical Component Score (3.2, 3.3, 3.8, 4.5, 4.7); improvements were less consistent for Mental Component Score (-0.1, -0.2, -0.1, 0.3, -0.2). For IWQOL-Lite-CT, improvements by weight reduction target were seen for total (18.2, 18.6, 19.7, 22.9, 24.1), Physical Function composite (13.6, 14.1, 14.9, 17.1, 17.3), Physical Composite (14.3, 14.9, 15.7, 18.3, 19.3), Physical Pain/Discomfort Composite (16.0, 16.7, 17.8, 21.1, 24.1), and Psychosocial Composite Scores (20.3, 20.6, 21.8, 25.3, 26.7). Adults meeting greater weight reduction targets generally showed greater improvements from randomization in PRO scores. Weight reduction was associated with improvement in most domains of health-related quality of life, including those relating to physical function and mental health. Adults who lost the most weight generally showed the greatest quality of life improvements. Presentation: 6/1/2024

Four-year follow-up of weight loss maintenance using electronic medical record data: The PROPEL trial.

Short-term weight loss is possible in a variety of settings. However, long-term, free-living weight loss maintenance following structured weight loss interventions remains elusive. The purpose was to study body weight trajectories over 2years of intensive lifestyle intervention (ILI) and up to 4years of follow-up versus usual care (UC). Data were obtained from electronic medical records (EMRs) from participating clinics. Baseline (Day 0) was established as the EMR data point closest but prior to the baseline date of the trial. The sample included 111 ILI and 196 UC patients. The primary statistical analysis focused on differentiating weight loss trajectories between ILI and UC. The ILI group experienced significantly greater weight loss compared with the UC group from Day 100 to Day 700, beyond which there were no significant differences. Intensive lifestyle intervention patients who maintained ≥5% and ≥10% weight loss at 24months demonstrated significantly greater weight loss (p<0.001) across the active intervention and follow-up. Following 24months of active intervention, patients with ILI regained weight toward their baseline to the point where ILI versus UC differences were no longer statistically or clinically significant. However, patients in the ILI who experienced ≥5% or ≥10% weight loss at the cessation of the active intervention maintained greater weight loss at the end of the follow-up phase. ClinicalTrials.gov: NCT02561221.

Exploratory analysis of the variable response to an intensive lifestyle change program for metabolic syndrome

BackgroundSubstantial variability in response to lifestyle interventions has been recognized for many years, and researchers have begun to disentangle sources of error from inherent differences in individual responsiveness. The objective of this secondary analysis of an intensive lifestyle intervention (diet and exercise) for metabolic syndrome (MetS) was to identify potentially important differences among study completers grouped by treatment response as measured by change in a continuous metabolic syndrome score (Gurka/MetS).MethodsAll study completers from a 12-month primary care study were categorized into one of five groups according to change in the Gurka/MetS score. A change of 0.4 in z-score defined clinically relevant change in line with results of previous studies. Repeated measures analysis of variance was used to examine cardiovascular disease risk and individual clinical indicators of MetS over 12 months, looking for differences in response over time by the five groups.ResultsOf 176 participants, 50% (n = 88) had stable scores, 10% (n = 18) had relevant change scores in the first 3 months only and reverted toward baseline, 20% (n = 35) achieved meaningful change over the whole study, 11% (n = 20) had a delayed response at 3–12 months, and 9% (n = 15) demonstrated worsening scores. Significant differential patterns were noted for groups over the duration of the intervention (p < .001). Improvement in diet quality and fitness scores were similar across all groups. Other available variables were tested and did not account for the differences.ConclusionWork is needed to identify key factors that account for differences in responses to lifestyle interventions that can be used to guide treatment decisions for intensive lifestyle interventions for this common condition.Trial RegistrationClinicalTrials.gov Identifier: NCT01616563; first registered June 12, 2012.

A whole-food, plant-based intensive lifestyle intervention improves glycaemic control and reduces medications in individuals with type 2 diabetes: a randomised controlled trial

Abstract Aims/hypothesis We conducted the largest and longest clinical trial comparing a whole-food, plant-based intervention with standard medical care (SMC) in individuals with type 2 diabetes. Methods We randomised (parallel-arm; computerised 1:1 randomisation ratio) 169 adults aged 18–75 years with type 2 diabetes in the Marshall Islands to an intensive whole-food, plant-based intervention with moderate exercise (PB+Ex) or SMC for 24 weeks. The PB+Ex intervention included 12 weeks of meals, exercise sessions and group classes. Primary outcomes were glycaemic control (HbA1c, glucose, insulin and HOMA-IR) and glucose-lowering medication use. Secondary outcomes included lipids, blood pressure, heart rate and C-reactive protein. Only lab analysts were blinded. Results Compared with SMC (n=90 randomised; n=70 analysed), the PB+Ex (n=79 randomised; n=66 analysed) intervention decreased HbA1c by an additional 14 mmol/mol (1.3%) at week 12 (−22 vs −7 mmol/mol [−2.0% vs −0.7%]; p&lt;0.0001) and 8 mmol/mol (0.7%) at week 24 (−16 vs −8 mmol/mol [−1.4% vs −0.7%]; p=0.01). Concomitantly, 63% of medicated PB+Ex participants reduced their glucose-lowering medications (vs 24%; p=0.006), and 23% of PB+Ex participants with a baseline HbA1c &lt;75 mmol/mol (&lt;9%) achieved remission. Additionally, the PB+Ex intervention reduced weight (−2.7 kg; p&lt;0.0001), C-reactive protein (−11 nmol/l; p=0.005) and cardiovascular medication use compared with SMC. At intermediate timepoints, it improved glucose, insulin, HOMA-IR, cholesterol, triglycerides and heart rate, but not at week 24. Conclusions/interpretation A whole-food, plant-based lifestyle intervention was more effective for improving glycaemic control than SMC. It also reduced the need for diabetes and cardiovascular medications and induced diabetes remission in some participants. Therefore, it is an effective, evidence-based lifestyle option for individuals with type 2 diabetes. Trial registration ClinicalTrials.gov NCT03862963 Funding This research was funded by the Department of the Army (W81XWH-05-1-0547). CJH received support through a National Institutes of Health Predoctoral T32 Obesity Fellowship (T32 HL105349). Graphical Abstract

Lead-in calorie restriction enhances the weight-lowering efficacy of incretin hormone-based pharmacotherapies in mice

ObjectivesThe potential benefits of combining lifestyle changes with weight loss pharmacotherapies for obesity treatment are underexplored. Building on recent clinical observations, this study aimed to determine whether “lead-in” calorie restriction before administering clinically approved weight loss medications enhances the maximum achievable weight loss in preclinical models. MethodsDiet-induced obese mice (DIO) were exposed to 7 or 14 days of calorie restriction before initiating treatment with semaglutide (a glucagon-like peptide-1 receptor (GLP-1R) agonist), tirzepatide (a GLP-1R/glucose insulinotropic peptide receptor (GIPR) co-agonist), or setmelanotide (a melanocortin-4 receptor (MC4R) agonist). Follow-up assessments using indirect calorimetry determined the contributions of energy intake and expenditure linked to consecutive exposure to dieting followed by pharmacotherapy. ResultsCalorie restriction prior to treatment with semaglutide or tirzepatide enhanced the weight loss magnitude of both incretin-based therapies in DIO mice, reflected by a reduction in fat mass and linked to reduced energy intake and a less pronounced adaptive drop in energy expenditure. These benefits were not observed with the MC4R agonist, setmelanotide. ConclusionsOur findings provide compelling evidence that calorie restriction prior to incretin-based therapy enhances the achievable extent of weight loss, as reflected in a weight loss plateau at a lower level compared to that of treatment without prior calorie reduction. This work suggests that more intensive lifestyle interventions should be considered prior to pharmacological treatment, encouraging further exploration and discussion of the current standard of care.

The relationship between sarcopenia and related bioindicators and changes after intensive lifestyle intervention in elderly East-China populations

BackgroundAs populations live longer, there is a progressive increase in chronic degenerative diseases, particularly those related to the musculoskeletal system. Sarcopenia is characterized by loss of skeletal muscle mass, muscle strength, and loss of physical function. It is a common disease in older adults associated with various adverse health outcomes. There is a lack of bioindicators to screen for sarcopenia. Albumin and lymphocyte counts are commonly used to assess the degree of malnutrition, and blood routine, lipids, and thyroid function are relatively easy to obtain as part of a routine physical examination. Therefore, finding blood markers that can screen for sarcopenia is essential. Our primary aim was to explore whether the bioindicators of body composition, lymphocytes, albumin, lipids, and thyroid hormones are associated with sarcopenia, and a secondary aim was to investigate changes in these indicators after an intensive lifestyle intervention preliminarily.Methods60 subjects were selected from Runda and Bailian community health centers in Suzhou, China. They underwent body composition analysis and tested lymphocyte, albumin, lipid, and thyroid hormone levels. The 30 sarcopenia subjects underwent a 3-month intensive lifestyle intervention program. At the end of the intervention, we rechecked the bioindicators. Statistical analyses were performed in IBM SPSS v26.0.ResultsThe blood indices of sarcopenia subjects were generally lower in albumin, non-high-density lipoprotein cholesterol (non-HDL-C), and free triiodothyronine (FT3). Body mass index (BMI)(r = 0.6266, p < 0.0001), fat-free mass (r = 0.8110, p < 0.0001), basal metabolism (r = 0.7782, p < 0.0001), and fat mass (r = 0.3916, p = 0.0020) were positively correlated with appendicular skeletal muscle index (ASMI). Higher BMI and FT3 were associated with lower odds of sarcopenia, while higher fat mass was associated with higher odds of sarcopenia. After a 3-month intensive intervention, sarcopenia subjects had a significant increase in BMI, ASMI, lymphocyte, and albumin levels, and an increase in FT3, but with a non-significant difference (p = 0.342).ConclusionsLow BMI, FT3, and high fat mass were associated with sarcopenia. Intensive lifestyle intervention can significantly improve ASMI, BMI, lymphocytes, albumin, and FT3 in sarcopenia subjects, which is favorable for delaying the progression of sarcopenia.Trial registrationThis study was retrospectively registered on ClinicalTrials.gov, registration number NCT06128577, date of registration: 07/11/2023.

Weight Loss Differentially Impacts Sex Hormones in Women and Men with Type 2 Diabetes: Look AHEAD Sex Hormone Study.

Despite sex differences in T2D, few studies have examined the role of sex hormones. We sought to assess the impact of weight loss, the cornerstone of T2D management, on sex hormone levels. This was an ancillary study to the Look AHEAD (Action for Health In Diabetes) Study (n=850 postmenopausal females, n=890 males, with T2D and BMI ≥25 kg/m2). We measured total testosterone (T), estradiol (E2) and sex hormone binding globulin (SHBG) and calculated bioavailable T (bioT). We examined the effect of the intensive lifestyle intervention (ILI) on hormone changes, whether changes were mediated by waist circumference and sex differences in treatment effect. The baseline mean age was 60 years with a higher proportion of Black females (21%) vs. males (9%) and higher mean BMI in females vs. males (36.3 vs. 34.8 kg/m2). At year 1 in females, ILI decreased E2 by 15% and bioT by 13% and increased SHBG by 21%. At year 1 in males, ILI did not change E2 levels, but increased T by 14% and increased SHBG by 18%. The effect was attenuated over 4 years, there were statistically significant sex differences in treatment effect and change in waist circumference due to ILI at year 1 was a significant mediator of sex hormone changes. Weight loss in T2D resulted in sex hormone changes, which varied by sex and were mediated by changes in WC. Changes in sex hormone due to weight loss in T2D should be considered in the context of an individual's health risks, including cardiovascular, bone health, menopausal symptoms and cognition.

Association between geospatial disparities in food security with weight loss and nutritional outcomes of metabolic surgery

BackgroundFood insecurity has been linked to higher rates of obesity. It has also been shown to diminish the effectiveness of weight loss strategies, including intensive lifestyle interventions. One essential component of food insecurity is having a geospatial disadvantage in access to healthy, affordable food, such as living within a food desert. This study aims to determine if food insecurity also impacts weight loss and nutritional outcomes in patients who underwent Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG).MethodsClinical outcomes of patients who underwent RYGB or SG at Cleveland Clinic or affiliate regional hospitals in the United States from 2010 to 2018 were collected. Modified Retail Food Environmental Index (mRFEI) data was collected from the Center for Disease Control and merged with patient census tract data, allowing the patient cohort to be divided into those living in areas identified as food secure (mRFEI > 10%), food swamps (mRFEI = 1–10%), or food deserts (mRFEI = 0). Postoperative weight change was evaluated with quadratic growth mixture models and stratified by surgery type.ResultsA total of 5097 patients were included in this study cohort, including 3424 patients who underwent RYGB and 1673 who underwent SG. The median duration of follow-up was 2.3 years (IQR 0.89–3.6 years). Food security status was not associated with postoperative weight change (RYGB p = 0.73, SG p = 0.60), weight loss nadir (RYGB p = 0.60, SG p = 0.79), or weight regain (RYGB p = 0.93, SG p = 0.85). Deficiencies in nutritional markers at 1–2 years after surgery were also not significantly different between food security groups.ConclusionDespite the established relationship between food insecurity and obesity, food insecurity does not negatively impact weight loss or nutritional outcomes following RYGB or SG, demonstrating metabolic surgery as a powerful and equitable tool for treating obesity.Level of EvidenceIV.

Very-low-calorie diet-based intensive lifestyle intervention for remission of type 2 diabetes: Real-world experience in a South Asian population.

Very low-calorie diet (VLCD) can induce weight loss and diabetes remission (DR) amongst people with obesity and recent-onset type 2 diabetes (T2D). We aimed to determine the effectiveness and acceptability of VLCD in achieving DR amongst Sri Lankan adults with T2D. A retrospective analysis was conducted in a diabetes practice where VLCD-based Diabetes Remission Programme (VDRP) was offered for adults (>18 years) with T2D for <3 years and body mass index over 25 kg/m2. VLCD (~800 kcal/day, provided with/without diet replacement formula) was offered for 8-12 weeks, followed by gradual food reintroduction and exercise. DR was defined as HbA1c <6.5% at least 3 months after stopping glucose-lowering medications. A total of 170 participants who enrolled in the VDRP (mean age 38.4 years [±11.1], men 68%, mean baseline HbA1c 86.9 [±18.1] mmol/mol (10.1 [±2.1]%), median duration of T2D 2 years [IQR 1-2]) and 87 (51%) of them followed the programme (attended at least one follow-up visit). Amongst the individuals who followed the VDRP, 40.2% achieved DR (35/87), compared with 2.4% (2/83) amongst those who did not follow the VDRP (aHR 9.3, 95% CI 2.2-16.4, p = 0.002). The proportion achieving normoglycaemia (HbA1c < 6.5%) but continued to take glucose-lowering medication was 20/87 among VDRP followers and 20/85 amongst VDRP non-followers. The commonest reasons for not following the VDRP were too restrictive dietary quantity (92%) and difficulties in finding recommended food items (67%). Majority (79%) would recommend VDRP to others. VDRP is effective in achieving T2D remission amongst Sri Lankan adults with recently diagnosed T2D and obesity. Over half of the participants followed the programme and over 75% would recommend it to others, indicating good acceptability.

Prevalence, Characteristics and Risk Factors Analysis of Prediabetes: A Cross-Sectional Study

Background Prediabetes, a reversible condition before the onset of diabetes, is a significant concern in healthcare globally. The global prediabetes epidemic has emerged and has considerably impacted health expenditures. Various risk factors play important roles in the progression of prediabetes to diabetes. Intensive lifestyle and pharmacological interventions can significantly reduce the risk of diabetes progression. Objective This study aimed to determine the prevalence, characteristics, and risk factors of prediabetes state of Medan in August 2023. Methods The sample consisted of 89 participants. This was an analytical cross-sectional study in the community that met the inclusion and exclusion criteria. The determination of prediabetes is based on the results of blood tests, namely, the examination of fasting blood sugar levels (FBGL), 2-hour postprandial oral glucose tolerance test (OGTT), and hemoglobin A1c (HbA1C). Other examinations included lipid profiling (total cholesterol, HDL-C, LDL-C, and triglycerides). Data processing was performed using SPSS via univariate and bivariate analyses (chi-square test). Results Of the 89 participants, the prevalence of prediabetes based on HbA1c, FBGL and 2-hours OGTT levels was 28.1%, 50.6%, and 28.1%, respectively. 82% of the participants were female, and 53.9% were overweight or obese based on body mass index (BMI). The risk factors related to the prevalence of prediabetes were HbA1c level, impaired FBGL, and impaired 2-hours OGTT. Other risk factors such as age, sex, daily exercise, diet, BMI, waist-hip ratio, acanthosis nigricans, lipid profile, and blood pressure did not correlate significantly with the risk factors (p&gt;0.05). Conclusion This study found that the prevalence of prediabetes was 67.4% in Medan, 82% of the participants were female, and more than 50% of participants were overweight or obese. HbA1c, FBGL, and 2-hour postprandial OGTT were the most important risk factors for prediabetes.

Cross-sectional and longitudinal associations among healthcare costs and deficit accumulation.

Type 2 diabetes mellitus and overweight/obesity increase healthcare costs. Both are also associated with accelerated aging. However, the contributions of this accelerated aging to increased healthcare costs are unknown. We use data from a 8-year longitudinal cohort followed at 16 U.S. clinical research sites. Participants were adults aged 45-76 years with established type 2 diabetes and overweight or obesity who had enrolled in the Action for Health in Diabetes clinical trial. They were randomly (1:1) assigned to either an intensive lifestyle intervention focused on weight loss versus a comparator of diabetes support and education. A validated deficit accumulation frailty index (FI) was used to characterize biological aging. Discounted annual healthcare costs were estimated using national databases in 2012 dollars. Descriptive characteristics were collected by trained and certified staff. Compared with participants in the lowest tertile (least frail) of baseline FI, those in the highest tertile (most frail) at Year 1 averaged $714 (42%) higher medication costs, $244 (22%) higher outpatient costs, and $800 (134%) higher hospitalization costs (p < 0.001). At Years 4 and 8, relatively greater increases in FI (third vs. first tertile) were associated with an approximate doubling of total healthcare costs (p < 0.001). Mean (95% confidence interval) relative annual savings in healthcare costs associated with randomization to the intensive lifestyle intervention were $437 ($195, $579) per year during Years 1-4 and $461 ($232, $690) per year during Years 1-8. These were attenuated and the 95% confidence interval no longer excluded $0 after adjustment for the annual FI differences from baseline. Deficit accumulation frailty tracks well with healthcare costs among adults with type 2 diabetes and overweight or obesity. It may serve as a useful marker to project healthcare needs and as an intermediate outcome in clinical trials.

Metformin in diabetes management: expanding benefits. Review

We have conducted a narrative review based on a structured search strategy, focusing on the effects of metformin on the progression of non‑diabetic hyperglycemia to clinical type 2 diabetes mellitus. The principal trials that demonstrated a significantly lower incidence of diabetes in at‑risk populations randomized to metformin (mostly with impaired glucose tolerance) were published mainly from 1999 to 2012. Metformin reduced the 3‑year risk of diabetes by ‑31% in the randomized phase of the Diabetes Prevention Program (DPP), vs.‑ 58% for intensive lifestyle intervention. Metformin was most effective in younger, heavier subjects. Diminishing but still significant reductions in diabetes risk for subjects originally randomized to these groups were present in the trial’s epidemiological follow‑up, the DPP Outcomes Study (DPPOS) at 10 years (‑18 and ‑34%, respectively), 15 years (‑18 and ‑27%), and 22 years (‑18 and ‑25%). Long‑term weight loss was also seen in both groups, with better maintenance under metformin. Subgroup analyses from the DPP/DPPOS have shed important light on the actions of metformin, including a greater effect in women with prior gestational diabetes, and a reduction in coronary artery calcium in men that might suggest a cardioprotective effect. Improvements in long‑term clinical outcomes with metformin in people with non‑diabetic hyperglycemia («prediabetes») have yet to be demonstrated, but cardiovascular and microvascular benefits were seen for those in the DPPOS who did not vs. did develop diabetes mellitus. Multiple health economic analyses suggest that either metformin or intensive lifestyle intervention is cost‑effective in a community setting. Long‑term diabetes prevention with metformin is feasible and is supported in influential guidelines for selected groups of subjects. Future research will demonstrate whether intervention with metformin in people with non‑diabetic hyperglycemia will improve long‑term clinical outcomes.