Intensive Lifestyle Intervention Research Articles

Abstract P153: Intensive Lifestyle Intervention in Type 2 Diabetes Mellitus Results in a More Favorable Sex Hormone Profile in Both Post-Menopausal Females and Older Males (The Look AHEAD Trial Sex Hormone Study)

Background: Prior studies showed an association between some adverse cardiometabolic outcomes and lower testosterone in males and higher estrogen in both males and post-menopausal females. However, few studies of sex hormones focused on people with type 2 diabetes (T2DM), assessed hormone changes over time or applied highly sensitive laboratory assays. Given the importance of lifestyle modification (i.e., diet, exercise and weight loss) in preventing cardiometabolic complications in people with T2DM, we examined the impact of an Intensive Lifestyle Intervention (ILI) on sex hormones over time and differences by sex. Methods: The Look AHEAD (Action for Health in Diabetes) Study was a randomized control trial of 5,145 individuals with BMI ≥25 and T2D to evaluate the effect of ILI compared to the Diabetes Support and Education (DSE) control group on incident cardiovascular events. We selected a sample of 472 males and 426 post-menopausal female participants (mean age 60 years [SD 6.3], 20.5% Black) to examine sex hormones (estradiol - E2, total testosterone - T) and sex hormone binding globulin (SHBG) at baseline and year 1. E2 and T were measured using mass spectrometry analysis and SHBG was measured using an immunoassay. Results: In males, ILI increased SHBG by 17.3% and T by 10.6% compared to the DSE group (Table). In postmenopausal females, ILI increased SHBG by 12.0% and decreased E2 by 23.4% compared to the DSE group (Table). The change in the sex hormone levels from baseline to 1-year follow up was attenuated when adjusted for change in BMI. Conclusion: ILI resulting in weight loss increased T in males and decreased E2 in postmenopausal females and increased SHBG in both sexes. We plan further analysis with a larger sample and longer follow-up to examine the role of weight loss either as a co-occurring metabolic process or as a mediator for the change in sex hormones to better understand the impact of lifestyle changes and sex diffrences.

Abstract MP26: Lifestyle, Genetic and Epigenetic Factors Associated With Serum Glyca Levels and Results From a Lifestyle Intervention Trial on This Cardiovascular Risk Biomarker

Introduction: GlycA is a novel biomarker of systemic inflammation and cardiovasculardisease (CVD) risk. It is measured by a signal in the proton nuclear magnetic resonance(NMR) spectra (from the N-acetyl methyl groups of N-acetylglucosamine residues).Epidemiological studies have reported associations between GlycA and increased CVD risk.However, there are few investigations examining the link between GlycA levels and lifestylefactors (diet, physical activity (PA), sleep, etc.), gut microbiota, or genetics at the genome-wide level (GWAS); and even fewer studies have analyzed serum GlycA and genome-widemethylation (EWAS) or the effect of lifestyle intervention on the reduction of GlycA.Therefore, our aims were: i) to investigate lifestyle, genetic, and epigenetic factorsassociated with serum GlycA; ii) to examine changes in serum GlycA after 1-y lifestyleintervention in a Mediterranean population. Methods: Cross-sectional and lifestyleintervention analyses were undertaken in a Mediterranean population at highcardiovascular risk (n=426 older subjects with metabolic syndrome in the PREDIMED-Plus-Valencia trial; ISRCTN89898870). Lifestyle variables were assessed by validatedquestionnaire and quantile-g-computation methods were used to analyze their jointcontribution. Serum GlycA was measured by NMR spectroscopy. Genome-wide genotypingand DNA-methylation were determined by Illumina arrays (OmniExpress and EPIC).Exploratory omics-wide and targeted analyses on GlycA (focusing on autophagy genes andmicrobiome-host-related genes) were undertaken. Changes in serum GlycA levels after a 1-y lifestyle intervention (intensive intervention group with Mediterranean diet and PA versusthe control group) were assessed in a subset of participants. Results: GlycA levels atbaseline (Mean: 1.49+/-0.20 mmol/L) were significantly associated with branched-chainamino acids and a highly atherogenic lipid profile. Also, we obtained an association withdietary factors and PA. Omics analysis suggested novel SNPs (in SFMBT2- DAB1 and TEK)and methylation sites (CpG in RAD50, PPP1R9B, ZDHHC4 and LSP1) associated with GlycA. We also obtained associations with host-microbiome related SNPs in FUT2 and withmethylation signals in selected autophagy genes (STX7, TAX1BP1, ATG9B and ATG10).Moreover, in the intervention trial we detected a significant (P<0.05) decrease in the GlycAlevels after 1 y of intensive lifestyle intervention in comparison with the control group. Conclusions: Serum GlycA levels were strongly associated with cardiometabolic risk factorsin this Mediterranean population and linked to lifestyle variables. Additionally, we haveidentified some genetic and epigenetic factors related to GlycA that may modulate theselevels.

A data-driven approach to manage type 2 diabetes mellitus through digital health: The Klivo Intervention Program protocol (KIPDM).

Digital therapeutics, an emerging type of medical approach, is defined as evidence-based therapeutic interventions through qualified software programs that help prevent, manage, or treat chronic diseases such as type 2 diabetes mellitus (T2DM), which has high social and economic burden. Klivo, a startup certified by the Brazilian Society of Diabetes, developed the first digital therapeutic product for managing T2DM in Brazil, reaching 21 of 24 states. Klivo has continuously been improving its model of behavior change on the basis of an intensive lifestyle intervention method that addresses individuals' needs-the Klivo Intervention Program for T2DM (KIPDM). To test the most recent version of the KIPDM, we will evaluate the ongoing management of daily life habits in patients with T2DM by measuring clinically significant outcomes. To improve the transparency of further results, here we will present the study protocol and detail the plan for the research project, including the study design and the analysis strategies. The KIPDM will be sponsored by health plans and healthcare provider organizations and will be free for patients (adults aged ≥ 18 years and <65 years; and glycated hemoglobin ≥ 7%). The program will be based on a 6-month management process that will supervise patients remotely. The program will include educational classes via the Klivo app, text messages, or e-mails. Evaluation will include objectively assessing clinical, laboratory, and behavioral outcomes such as health-related quality of life, mental health, medication adherence, and healthcare utilization. For this, validated electronic questionnaires will be available through the Klivo app. The primary outcome will be glycated hemoglobin (HbA1c) values. The secondary outcome will be time in target blood glucose range (TIR) estimated by capillary glycemia. Other outcomes of interest will be evaluated at baseline and stipulated time points (3 and 6 months after the start of the program). KIPDM patients should present improved HbA1c and TIR along the intervention as compared to baseline values. Findings from this study will provide insights into the health improvement of T2DM and other cardiometabolic conditions such as hypertension, dyslipidemia, and obesity by using a digital therapeutic strategy. By analyzing the patient's health over time, this study will also contribute to understanding comorbidities associated with this chronic condition in the Brazilian population.

Successful naltrexone-bupropion treatment after several treatment failures in a patient with severe monogenic obesity

We describe the therapeutic journey of a 33-year-old patient with early-onset obesity (BMI 56.7kg/m2) and hyperphagia due to a likely pathogenic heterozygous melanocortin-4 receptor (MC4R) gene variant. She was unsuccessfully treated with several intensive lifestyle interventions, gastric bypass surgery (-40kg weight loss, followed by+39.8kg weight regain), liraglutide 3mg (-3.8% weight loss with sustained hyperphagia), and metformin treatment. However, naltrexone-bupropion treatment led to -48.9kg (-26.7%) weight loss, of which -39.9kg (-38.3%) was fat mass, in 17months of treatment. Importantly, she reported improved hyperphagia and quality of life. We describe the potential beneficial effects of naltrexone-bupropion on weight, hyperphagia, and quality of life in a patient with genetic obesity. This extensive journey shows that various anti-obesity agents can be initiated, subsequently terminated when ineffective and substituted with other anti-obesity agents to identify the most efficient anti-obesity treatment.

Opioid Use After Gastric Bypass, Sleeve Gastrectomy or Intensive Lifestyle Intervention.

To compare opioid use in patients with obesity treated with bariatric surgery versus adults with obesity who underwent intensive lifestyle modification. Previous studies of opioid use after bariatric surgery have been limited by small sample sizes, short follow-up, and lack of control groups. Nationwide matched cohort study including individuals from the Scandinavian Obesity Surgery Registry and the Itrim health database with individuals undergoing structured intensive lifestyle modification, between August 1, 2007 and September 30, 2015. Participants were matched on Body Mass Index, age, sex, education, previous opioid use, diabetes, cardiovascular disease, and psychiatric status (n = 30,359:21,356). Dispensed opioids were retrieved from the Swedish Prescribed Drug Register from 2 years before to up to 8 years after intervention. During the 2-year period before treatment, prevalence of individuals receiving ≥1 opioid prescription was identical in the surgery and lifestyle group. At 3 years, the prevalence of opioid prescriptions was 14.7% versus 8.9% in the surgery and lifestyle groups (mean difference 5.9%, 95% confidence interval 5.3-6.4) and at 8 years 16.9% versus 9.0% (7.9%, 6.8-9.0). The difference in mean daily dose also increased over time and was 3.55 mg in the surgery group versus 1.17 mg in the lifestyle group at 8 years (mean difference [adjusted for baseline dose] 2.30 mg, 95% confidence interval 1.61-2.98). Bariatric surgery was associated with a higher proportion of opioid users and larger total opioid dose, compared to actively treated obese individuals. These trends were especially evident in patients who received additional surgery during follow-up.

The National Clinical Care Commission Report to Congress: Leveraging Federal Policies and Programs to Prevent Diabetes in People With Prediabetes.

Individuals with an elevated fasting glucose level, elevated glucose level after glucose challenge, or elevated hemoglobin A1c level below the diagnostic threshold for diabetes (collectively termed prediabetes) are at increased risk for type 2 diabetes. More than one-third of U.S. adults have prediabetes but fewer than one in five are aware of the diagnosis. Rigorous scientific research has demonstrated the efficacy of both intensive lifestyle interventions and metformin in delaying or preventing progression from prediabetes to type 2 diabetes. The National Clinical Care Commission (NCCC) was a federal advisory committee charged with evaluating and making recommendations to improve federal programs related to the prevention of diabetes and its complications. In this article, we describe the recommendations of an NCCC subcommittee that focused primarily on prevention of type 2 diabetes in people with prediabetes. These recommendations aim to improve current federal diabetes prevention activities by 1) increasing awareness of and diagnosis of prediabetes on a population basis; 2) increasing the availability of, referral to, and insurance coverage for the National Diabetes Prevention Program and the Medicare Diabetes Prevention Program; 3) facilitating Food and Drug Administration review and approval of metformin for diabetes prevention; and 4) supporting research to enhance the effectiveness of diabetes prevention. Cognizant of the burden of type 1 diabetes, the recommendations also highlight the importance of research to advance our understanding of the etiology of and opportunities for prevention of type 1 diabetes.

The National Clinical Care Commission Report to Congress: Recommendations to Better Leverage Federal Policies and Programs to Prevent and Control Diabetes.

The National Clinical Care Commission (NCCC) was established by Congress to make recommendations to leverage federal policies and programs to more effectively prevent and treat diabetes and its complications. The NCCC developed a guiding framework that incorporated elements of the Socioecological and Chronic Care Models. It surveyed federal agencies and conducted follow-up meetings with representatives from 10 health-related and 11 non-health-related federal agencies. It held 12 public meetings, solicited public comments, met with numerous interested parties and key informants, and performed comprehensive literature reviews. The final report, transmitted to Congress in January 2022, contained 39 specific recommendations, including 3 foundational recommendations that addressed the necessity of an all-of-government approach to diabetes, health equity, and access to health care. At the general population level, the NCCC recommended that the federal government adopt a health-in-all-policies approach so that the activities of non-health-related federal agencies that address agriculture, food, housing, transportation, commerce, and the environment be coordinated with those of health-related federal agencies to affirmatively address the social and environmental conditions that contribute to diabetes and its complications. For individuals at risk for type 2 diabetes, including those with prediabetes, the NCCC recommended that federal policies and programs be strengthened to increase awareness of prediabetes and the availability of, referral to, and insurance coverage for intensive lifestyle interventions for diabetes prevention and that data be assembled to seek approval of metformin for diabetes prevention. For people with diabetes and its complications, the NCCC recommended that barriers to proven effective treatments for diabetes and its complications be removed, the size and competence of the workforce to treat diabetes and its complications be increased, and new payment models be implemented to support access to lifesaving medications and proven effective treatments for diabetes and its complications. The NCCC also outlined an ambitious research agenda. The NCCC strongly encourages the public to support these recommendations and Congress to take swift action.

Hybrid model of intensive lifestyle intervention is potentially effective in patients with diabetes & obesity for post-COVID era.

The Weight Achievement and Intensive Treatment (Why WAIT) program is a 12-week multidisciplinary intensive lifestyle intervention (ILI) for patients with diabetes and obesity in real-world clinical practice that has led to long-term weight loss maintenance for up to 10 years. During COVID-19, we reported that a virtual model (VM) of the program was equally effective in reducing body weight and improving glycemic control. Here, we test a newly-introduced hybrid model (HM), to accommodate ongoing restrictions of the pandemic. We evaluated 56 participants: 18 from HM, 16 from VM and 22 from the in-person model (iPM). At 12 weeks, mean change in body weight from baseline for HM was -8.2 ± 5.0kg; p<0.001. Mean change in A1C for HM was -0.6 ± 0.6%; p=0.002. There were no significant differences in body weight reduction (p=0.7) or A1C reduction (p=0.6) between groups. Blood pressure, lipid profile, and all other parameters showed improvements without significant differences between groups. Overall, HM is as effective as VM and iPM in reducing body weight and A1C after 12 weeks. Given its scalability, HM could be offered to more patients with diabetes and obesity who may benefit from its increased flexibility and enhanced accountability without compromising the multidisciplinary approach for a post-COVID era.

Effect of intensive lifestyle intervention on the association between weight variability and major adverse cardiovascular events in overweight or obese adults with type 2 diabetes mellitus

Weight variability is associated with cardiovascular outcomes in diabetic patients. However, whether the guideline-recommended intensive lifestyle intervention (ILI) will affect this association in overweight or obese adults with diabetes is not well established. In 3,859 participants from the Action for Health in Diabetes (Look AHEAD) trial, the associations of 4 year weight variability measured by variability independent of the mean (VIM) with major adverse cardiovascular event (MACE) and secondary outcomes in ILI and diabetes support & education (DSE) arm were evaluated. During a median follow-up of 9.6 years, 255 (12.9%) participants in the ILI arm and 247 (13.2%) participants in the DSE arm developed MACE. Participants with the highest quartile of weight variability (VIM Q4) experienced a 2.23-fold higher risk of MACE compared with the lowest quartile (VIM Q1) in the DSE arm (hazard ratio [HR] 2.23; 95% CI 1.51-3.30). Compared with the lowest weight variability (VIM Q1), participants with the highest weight variability (VIM Q4) were associated with higher risks of secondary cardiovascular composite outcome (HR 1.88; 95% CI 1.20-2.95), all-cause mortality (HR 3.19; 95% CI 1.75-5.82), and myocardial infarction (HR 1.95; 95% CI 1.12-3.37) in the DSE arm. Among the overweight or obese individuals with type 2 diabetes mellitus, rising weight variability was independently associated with increased MACE risks in the DSE arm. Therefore, a guideline-recommended ILI strategy for weight loss should be adopted to improve cardiovascular outcomes without worrying about the effect of weight fluctuations.

Daytime Sleepiness Is Associated with Lower Cognitive Scores: The Look AHEAD Study.

Daytime sleepiness is common in older adults and may result from poor nighttime sleep due to sleep disordered breathing, fragmented sleep, or other sleep disorders. Daytime sleepiness may be associated with cognition in older adults. We investigated the association between self-reported daytime sleepiness and cognitive function in the Look AHEAD clinical trial. Observational follow-up of a randomized clinical trial of an intensive lifestyle intervention. Clinic. Participants (n=1,778) aged 45-76 years at baseline with type 2 diabetes and overweight or obesity. Participants were randomized to an intensive lifestyle intervention for weight loss or a control condition of diabetes support and education. Participants provided self-reported levels of daytime sleepiness at baseline and years 12-13. Cognitive function was assessed with a neurocognitive battery at years 12-13 and 18-20. Participants who reported having frequent daytime sleepiness (often or always) performed significantly worse than others on the cognitive composite (-0.35; p-value=0.014) after controlling for covariates. When stratified by intervention arm, participants assigned to the intensive lifestyle intervention who reported often/always having daytime sleepiness performed worse on Digit Symbol Coding (-0.63; p-value=0.05) and Trail Making Part-B (-0.56; p-value=0.02) after controlling for covariates. Statistical interactions revealed associations between daytime sleepiness and the following covariates: race and ethnicity, APOE ε4 carrier status, baseline history of cardiovascular disease, and depression. Daytime sleepiness over ~13 years predicted poorer cognitive performance in older individuals who, by virtue of having diabetes and overweight/obesity, are at high risk for sleep disorders and cognitive impairment.

EIGHT-YEAR CHANGES IN DEFICIT ACCUMULATION FRAILTY: RELATION TO GLYCEMIC CONTROL AND DIABETES MEDICATION USE

Abstract Type 2 diabetes mellitus (T2DM) has been linked to accelerated biological aging and the accumulation of health deficits. It is unknown whether glycemic control can slow the progression of aging, as expressed by deficit accumulation frailty indices (FIs). We examined the cross-sectional and longitudinal associations that glycemic control, diabetes medication use, and weight change (predictors) had with a FI calculated as the percent of 36 deficits in behavioral, functional, and clinical characteristics (outcome). We drew data from 4177 participants across 8 years of follow-up in the Look AHEAD clinical trial of a multidomain intensive lifestyle intervention in individuals aged 45-76 years with T2DM and overweight or obesity. At baseline, the means(SD) FI(as a percent) for participants grouped as HbA1c&amp;lt; 7%, 7-7.9%, and &amp;gt;8% were: 19.93(6.45), 20.82(6.89), and 21.53(7.27), p&amp;lt; 0.001. Compared with HbA1c&amp;gt;8%, HbA1c&amp;lt; 7% at baseline was associated with 23% less mean 8-year FI progression: 2.42(7.35) vs 3.14(8.02), p&amp;lt; 0.001). Maintaining average HbA1c&amp;lt; 7% vs &amp;gt;8% during follow-up was associated with 47% less 8-year FI progression: 2.05(7.35) vs 3.14(8.02), p&amp;lt; 0.001. With adjustment for HbA1c, sustained weight loss &amp;gt;5% compared with weight gain &amp;gt;5% was associated with an 81% reduction in 8-year FI progression: 1.18(7.25) vs 3.89(8.09), p&amp;lt; 0.001. Use of metformin across &amp;gt;50% of annual visits was associated with a 30% reduction in 8-year progression of FI as compared with less use or no use: 2.25(7.27) vs 3.22(7.90), p=0.002. We conclude that better control of HbA1c, and sustained weight loss (&amp;gt;5%) and metformin use, may slow the accelerated aging associated with T2DM.

Effects of a Lifestyle Intervention in Young Women with GDM and Subsequent Diabetes.

The purpose of this study was to examine whether a 9-month intensive lifestyle intervention could lead to weight loss and improve cardiovascular risk factors among young women with both gestational diabetes mellitus (GDM) and newly diagnosed diabetes. A total of 83 young women, who had GDM and were subsequently diagnosed as type 2 diabetes at an average of 2.6 years after delivery, participated in a 9-month intensive lifestyle intervention and a follow-up survey at 6-9 years postintervention. After the 9-month intervention, these women had a weight loss of 2.90 kg (-4.02% of initial weight), decreased waist circumference (-3.12 cm), body fat (-1.75%), diastolic blood pressure (-3.49 mmHg), fasting glucose (-0.98 mmol/L) and HbA1c (-0.72%). During the 6-9 years postintervention period, they still had lower weight (-3.71 kg; -4.62% of initial weight), decreased waist circumference (-4.56 cm) and body fat (-2.10%), but showed a slight increase in HbA1c (0.22%). The prevalence of using glucose-lowering agents increased from 2.4% at baseline to 34.6% after the 9-month lifestyle intervention, and to 48.4% at 6-9 years postintervention. A 9-month intensive lifestyle intervention can produce beneficial effects on body weight, HbA1c and other cardiovascular risk factors among young women with previous GDM who subsequently developed new diabetes.

Is the Long‐term Impact of a Multidomain Lifestyle Intervention on Cognitive Function Mediated by Changes in Leptin and Vascular Endothelial Growth Factor Concentrations?

AbstractBackgroundThe 10‐year intensive lifestyle intervention (ILI) of the Look AHEAD study resulted in a legacy of relative deficits in cognitive function among participants who entered the clinical trial with a history of cardiovascular disease or current obesity, as compared to participants assigned to the diabetes support and education (DSE) intervention. We hypothesized that levels of two weight‐sensitive proangiogenic cytokines, leptin and vascular endothelial growth factor (VEGF), which have been previously reported to be associated with cognitive function, may have been altered by the ILI and account for this concerning finding.MethodConcentrations of leptin and VEGF were determined using stored serum collected from 1,279 participants at Look AHEAD baseline, proximal to cessation of the intervention (Epoch 1), and an average of 4 years later (Epoch 2). Masked clinic staff conducted up to four standardized assessments of cognitive function at times ranging from 8 to 18 years after baseline. A composite score was derived from tests of attention, executive function, and memory. Mixed effects models were used to assess relative differences in leptin and VEGF concentrations between intervention groups and whether these accounted for changes in cognitive composite scores, overall and within subgroups defined by baseline history of cardiovascular disease or obesity.ResultIn both intervention groups, leptin concentrations increased from baseline to Epoch 1, and further between Epochs 1 and 2 (p&lt;0.001). VEGF concentrations decreased between enrollment and Epoch 2 in both groups, and decreased substantially more between Epoch 1 and 2 in ILI than in DSE (p = 0.04). Overall, there was little evidence that leptin and VEGF concentrations were related to cognitive functioning. ILI‐DSE differences in VEGF, but not leptin, concentrations varied depending on baseline history of cardiovascular disease and obesity, but neither leptin or VEGF concentrations accounted for the relative decrements in cognitive function evident during long‐term follow‐up in participants assigned to ILI.ConclusionAmong persons with type 2 diabetes and either a history of cardiovascular disease or obesity, long‐term relative deficits in cognitive function associated with intensive lifestyle intervention are not related to differences in two weight‐sensitive proangiogenic cytokines.

Mid- and long-term changes in satiety-related hormones, lipid and glucose metabolism, and inflammation after a Mediterranean diet intervention with the goal of losing weight: A randomized, clinical trial.

Obesity is produced by the enlargement of the adipose tissue. Functioning as an endocrine organ, it releases and receives information through a complex network of cytokines, hormones, and substrates contributing to a low-chronic inflammation environment. Diet and healthy habits play key roles in the prevention of obesity and its related pathologies. In this regard, there is a need to switch to healthier and more appetizing diets, such as the Mediterranean one. To compare the mid-and long-term effects of two Mediterranean diet (MedDiet) interventions, one energy-reduced plus physical activity promotion versus a non-restrictive diet, on peripheral satiety-related hormones, weight loss, glucose/lipid metabolism, and pro-inflammatory markers in subjects with obesity/overweight and metabolic syndrome. A randomized, lifestyle intervention was conducted in 23 Spanish centers, with a large cohort of patients presenting metabolic syndrome. Our study is a subproject set in IMIM (Hospital del Mar Research Institute). Participants were men and women, aged 55-75 and 60-75, respectively, who at baseline met at least three metabolic syndrome components. Subjects were assigned to two intervention groups: (1) an intensive lifestyle intervention with an energy-reduced MedDiet and physical activity promotion (intervention group) with the aim of weight loss; and (2) a normocaloric MedDiet (control). We quantified in a subsample of 300 volunteers from Hospital del Mar Research Institute (Barcelona), following analytes at baseline, 6 months, and 1 year: glucose, HbA1c, triglycerides, total cholesterol, high-density lipoprotein cholesterol, LDL cholesterol, C-peptide, ghrelin, GLP-1, glucagon, insulin, leptin, PAI-1, resistin, and visfatin. Anthropometric and classical cardiovascular risk factors were also determined. A multivariate statistical model was employed to compare the two groups. Linear mixed-effect models were performed to compare changes in risk factors and biomarkers between intervention groups and over time. Compared to participants in the control group, those in intervention one showed greater improvements in weight, waist circumference, insulin (P < 0.001), glucose metabolism-related compounds (P < 0.05), triglyceride-related lipid profile (P < 0.05), leptin, blood pressure, and pro-inflammatory markers such as PAI-1 (P < 0.001) at mid-and/or long-term. High-sensitivity C-reactive protein, resistin, and vifastin also decreased in both groups. A weight loss intervention employing a hypocaloric MedDiet and physical activity promotion has beneficial effects on adiposity, glucose metabolism, lipid profile, leptin, and pro-inflammatory markers, such as PAI-1 in both mid-and long-term.

Lessons Learned from the ISCHEMIA Trial for the Management of Patients with Stable Ischemic Heart Disease.

The recent landmark International Study of Comparative Health Effectiveness With Medical and Invasive Approaches (ISCHEMIA) trial was undertaken to assess whether stable angina patients with moderate to severe baseline ischemia would benefit from an invasive approach with revascularization versus a conservative approach of intensive lifestyle intervention and pharmacologic secondary prevention. This trial addressed the hypothesis that treating ischemia with an invasive approach would reduce major adverse cardiac events more than a noninvasive pharmacologic and lifestyle approach. ISCHEMIA is discussed in detail, along with current implications for contemporary management of this very common cardiac disorder afflicting millions of patients worldwide.

Long-term Effect of Lifestyle Interventions on the Cardiovascular and All-Cause Mortality of Subjects With Prediabetes and Type 2 Diabetes: A Systematic Review and Meta-analysis.

Lifestyle interventions improve the metabolic control of individuals with hyperglycemia. We aimed to determine the effect of lifestyle interventions on cardiovascular and all-cause mortality in this population. Searches were made through MEDLINE, Cochrane CENTRAL, Embase, and Web of Science (no date/language restriction, until 15 May 2022). We included randomized clinical trials (RCTs) of subjects with prediabetes and type 2 diabetes, comparing intensive lifestyle interventions with usual care, with a minimum of 2 years of active intervention. Data from the 11 RCTs selected were extracted in duplicate. A frequentist and arm-based meta-analysis was performed with random-effects models to estimate relative risk (RR) for mortality, and heterogeneity was assessed through I2 metrics. A generalized linear mixed model (GLMM) was used to confirm the findings. Lifestyle interventions were not superior to usual care in reducing cardiovascular (RR 0.99; 95% CI 0.79-1.23) or all-cause (RR 0.93; 95% CI 0.85-1.03) mortality. Subgroup, sensitivity, and meta-regression analyses showed no influence of type of intervention, mean follow-up, age, glycemic status, geographical location, risk of bias, or weight change. All of these results were confirmed with the GLMM. Most studies had a low risk of bias according to the RoB 2.0 tool and the certainty of evidence was moderate for both outcomes. Most studies had a low risk of bias according to the RoB 2.0 tool, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach resulted in moderate certainty of evidence for both outcomes. Differences in lifestyle programs and in usual care between the studies should be considered in the interpretation of our results. Intensive lifestyle interventions implemented so far did not show superiority to usual care in reducing cardiovascular or all-cause mortality for subjects with prediabetes and type 2 diabetes.

Impact of an intensive lifestyle program on low attenuation plaque and myocardial perfusion in coronary heart disease: A randomised clinical trial protocol

IMPORTANCE: The evidence that maintaining a healthy body weight in conjunction with healthier eating patterns, exercise training, and reduced stress can improve clinical outcomes in patients with atherosclerotic cardiovascular disease is substantial. However, little is known about the magnitude and temporal effects of a comprehensive lifestyle treatment on coronary artery anatomy, myocardial inflammation, and fibrosis in people affected by coronary heart disease. OBJECTIVE: To conduct a randomised clinical trial to determine the impact of a 12-month intense lifestyle intervention delivered via an mHealth platform (in the form of a mobile App) versus standard clinical care on low attenuation plaque volume and structure, stress myocardial perfusion, and diastolic function. DESIGN: A single centre, parallel-group, randomised controlled trial. The co-primary endpoints are: 1-Low Attenuation Plaque (LAP) volume (mm3) using coronary computed tomography angiography (CCTA) at 12 months, and 2-Adenosine stress myocardial blood flow (stress MBF, mL/min/g) using cardiovascular magnetic resonance imaging (MRI) at 12 months. Other key measurements include liver steatosis by MRI, subclinical abnormalities detected by advanced electrocardiography, arterial stiffness, endothelial function, genomic, metabolomic, and gut microbiome-related adaptations to these structural changes. An intention-to-treat principle will be used for all analyses. SETTING: Participants will be recruited from a large academic cardiology office practice (Central Sydney Cardiology) and Royal Prince Alfred Hospital (RPAH) Departments of Cardiology and Radiology. All clinical investigations will be undertaken within the Charles Perkins Centre-RPAH clinic. PARTICIPANTS: Individuals (n = 150) with stable coronary heart disease who have low attenuation plaque based on a CCTA within the past 3 months, will be randomised to a lifestyle intervention program comprising a 5:2 pesco-vegetarian diet, exercise training, and mindfulness-based stress reduction (n = 75) or usual care (n = 75). DISCUSSION: This trial will represent the single most detailed and integrated analysis of the effects of a comprehensive lifestyle intervention targeting multiple metabolic pathways, delivered via a customized mHealth App on smart devices, on coronary macro- and microcirculation, heart physiology, and cardiometabolic risk. It will provide a new framework for allowing clinicians and individuals to optimise metabolic health for the prevention and management of atherosclerotic cardiovascular diseases that is epidemic in modern society.

Mediators of weight change in underserved patients with obesity: exploratory analyses from the Promoting Successful Weight Loss in Primary Care in Louisiana (PROPEL) cluster-randomized trial

Intensive lifestyle interventions (ILIs) stimulate weight loss in underserved patients with obesity, but the mediators of weight change are unknown. We aimed to identify the mediators of weight change during an ILI compared with usual care (UC) in underserved patients with obesity. The PROPEL (Promoting Successful Weight Loss in Primary Care in Louisiana) trial randomly assigned 18 clinics (n=803) to either an ILI or UC for 24 mo. The ILI group received an intensive lifestyle program; the UC group had routine care. Body weight was measured; further, eating behaviors (restraint, disinhibition), dietary intake (percentage fat intake, fruit and vegetable intake), physical activity, and weight- and health-related quality of life constructs were measured through questionnaires. Mediation analyses assessed whether questionnaire variables explained between-group variations in weight change during 2 periods: baseline to month 12 (n=779) and month 12 to month 24 (n=767). The ILI induced greater weight loss at month 12 compared with UC (between-group difference: -7.19kg; 95% CI: -8.43, -6.07kg). Improvements in disinhibition (-0.33kg; 95% CI: -0.55, -0.10kg), percentage fat intake (-0.25kg; 95% CI: -0.50, -0.01kg), physical activity (-0.26kg; 95% CI: -0.41, -0.09kg), and subjective fatigue (-0.28kg; 95% CI: -0.46, -0.10kg) at month 6 during the ILI partially explained this between-group difference. Greater weight loss occurred in the ILI at month 24, yet the ILI group gained 2.24kg (95% CI: 1.32, 3.26kg) compared with UC from month 12 to month 24. Change in fruit and vegetable intake (0.13kg; 95% CI: 0.05, 0.21kg) partially explained this response, and no variables attenuated the weight regain of the ILI group. In an underserved sample, weight change induced by an ILI compared with UC was mediated by several psychological and behavioral variables. These findings could help refine weight management regimens in underserved patients with obesity.This trial was registered at clinicaltrials.gov as NCT02561221.

Maximizing lifestyle changes to manage type 2 diabetes

Four dietary plans can reduce A1C levels but may differ in long-term outcomes. Intensive lifestyle interventions may even make remission possible.

Development of a novel clinical decision support tool for diabetes prevention and feasibility of its implementation in primary care

Prediabetes impacts 88 million U.S. adults, yet uptake of evidence-based treatment with intensive lifestyle interventions and metformin remains exceedingly low. After incorporating feedback from 15 primary care providers collected during semi-structured interviews, we developed a novel Prediabetes Clinical Decision Support (PreDM CDS) from August 2019 to February 2020. This tool included order options enabling prediabetes management in a single location within the electronic health record. We conducted a retrospective observational study examining the feasibility of implementing this tool at Erie Family Health Centers, a large community health center, examining its use and related outcomes among patients for whom it was used vs not. Overall, 7,424 eligible patients were seen during the implementation period (February 2020 to August 2021), and the PreDM CDS was used for 108 (1.5 %). Using the PreDM CDS was associated with higher rates of hemoglobin A1c orders (70.4 % vs 22.2 %; p < 0.001), lifestyle counseling (38.0 % vs 7.8 %; p < 0.001), and metformin prescription orders (5.6 % vs 2.6 %; p = 0.06). Exploratory analyses revealed small, nonsignificant weight loss among patients for whom the PreDM CDS was used. This study demonstrates the feasibility of developing and implementing the PreDM CDS in primary care. Its low use was likely related to not imposing an interruptive ‘pop-up’ alert, as well as major changes in workflows and clinical priorities during the Covid-19 pandemic. Use of the tool was associated with improved process outcomes. Future efforts with the PreDM CDS should follow standard CDS implementation processes that were not possible due to the Covid-19 pandemic.