Metformin improves diastolic dysfunction of non-diabetic patients with metabolic syndrome: the MET-DIME randomized trial

Background Metabolic syndrome (MetS) is a cluster of cardiovascular risk factors, including abdominal obesity, dyslipidaemia, arterial hypertension and abnormal glucose homeostasis, which occur together more frequently than by chance. Diastolic dysfunction (DD) is one of the most frequent manifestations of subclinical cardiac involvement of MetS, ultimately leading to heart failure with preserved ejection fraction. Metformin's new potential therapeutic actions include prevention of cardiac remodeling and fibrosis. Purpose We aimed to evaluate if metformin improves diastolic function (DF) in non-diabetic patients with MetS. Methods A prospective, randomized, open-label, blinded-endpoint trial was conducted over 24 months. Fifty-four non-diabetic adults with MetS and DD (defined as mean e'<10.2cm/s or <7.2cm/s for individuals 40–59 and 60–65 years old, respectively) were randomized to lifestyle counseling (control arm) or lifestyle counseling plus metformin (intervention arm) on a target dose of 1000 mg bid (figure 1). The primary endpoint was the change in mean e' velocity, assessed at 6, 12 and 24 months. Secondary endpoints included improvements in insulin resistance (HOMA-IR), functional capacity (peak oxygen uptake – VO2) and QoL (SF-36 score). Linear mixed effects modelling was used for longitudinal data analysis based on modified intention-to-treat (mITT) and per-protocol (PP) approaches. Results Forty-nine patients (mean age=51.8±6.4; 55% males) were included in the mITT analysis. Metformin use, on top of lifestyle counseling, led to an increase in mean e' velocity during follow-up (figure 2), with results at 24 months of +0.67±1.90cm/s (vs. −0.33±1.50cm/s in the control group, p=0.056), which reached statistical significance in PP analysis (+0.80±1.99cm/s vs. −0.37±1.52cm/s, p=0.039). In a random intercept linear mixed model adjusting for age, gender, treatment with drugs targeting the renin-angiotensin-aldosterone axis, presence of heart failure and baseline degree of DD, both mITT and PP analysis showed a statistically significant improvement of DF with metformin over time (β-coefficient=0.28, standard error (SE)=0.13, p=0.034, and β-coefficient=0.35, SE=0.14, p=0.011, respectively). This effect was independent of the observed reduction in insulin resistance. There were no differences regarding peak VO2 nor SF-36 score. Conclusions Treatment with metformin of non-diabetic MetS patients with DD, on top of lifestyle counseling, was associated with improved diastolic function. FUNDunding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Merck Study algorithm Primary endpoint results

Medical Student Perception of Lifestyle Medicine and Willingness to Engage in Lifestyle Counseling: A Pilot Study of Allopathic and Osteopathic Medical Students

Introduction. This study assessed medical students’ perception of lifestyle medicine and readiness to engage in lifestyle counseling. Methods. All medical students in one allopathic and one osteopathic medical school received a survey involving items designed to measure their awareness and interest in lifestyle medicine, perception of physicians serving as lifestyle role models for patients, and intent to practice lifestyle counseling. Results. Two hundred and eight-nine subjects (145 allopathic and 144 osteopathic students) responded to the survey. A total of 24.1% of responding allopathic students had heard about lifestyle medicine compared with 53.9% of responding osteopathic students ( P < .01). A total of 90.5% of allopathic students rated their current knowledge of lifestyle medicine as inadequate or poor compared with 78.7% of osteopathic students ( P < .01). Ninety-two percent of all respondents wanted to learn more about lifestyle medicine, while 95.2% believed they would provide more effective counseling if they were trained sufficiently to serve as a healthy lifestyle role model for their patients. Conclusions. Both cohorts favored learning more about lifestyle medicine and believed physicians should provide lifestyle counseling to patients with chronic diseases. Given these findings, and the demonstrated benefits of lifestyle medicine–based health care, the authors suggest that training in lifestyle medicine be increased in undergraduate medical education.

Healthy Lifestyle Counseling by Healthcare Practitioners: A Time to Event Analysis

Introduction Medical societies have heavily prioritized preventive care, as evidenced by numerous best practice guidelines supporting counseling patients on lifestyle factors. This report examines preventive counseling by healthcare providers in a rural healthcare system. We utilized electronic medical records to determine whether patient characteristics and chronic conditions were predictors of preventive counseling, and what the average time-interval was before a patient received this counseling. Methods Medical records from a cohort of 395 subjects participating in the 1999 Bassett Health Census Survey were reviewed for documented counseling with respect to smoking cessation, weight management, physical activity, and health condition-related diets (anti-hypertensive and diabetic diets). Results Our analyses revealed extensive delays in counseling for smoking cessation among smokers (median time to counseling = 4.2 years), for weight management among the obese (median time = 4.8 years), and for physical activity for all subjects (median time = 10.9 years). For those with diabetes, a median time of 7.5 years passed before being counseled on a diabetic diet. Hypertensive diet counseling did not occur for more than 50% of hypertensives. Conclusion In this population, we did not find documentation of lifestyle counseling that was in compliance with current guidelines for any of the lifestyle factors. The measurement of actual delay times provides further support for the position that preventive efforts of health care providers need to be improved.

Metformin in non-diabetic patients with metabolic syndrome and diastolic dysfunction: the MET-DIME randomized trial

Funding Acknowledgements Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Merck Background Metabolic syndrome (MetS) affects one out of 3 adults in the western world and is associated with preclinical diastolic dysfunction that impairs functional capacity and quality of life (QoL). Purpose This randomized trial was designed to evaluate if the addition of metformin to the standard treatment of non-diabetic patients with MetS improves diastolic dysfunction. Methods Prospective, randomized, open-label, blinded-endpoint trial. Fifty-four non-diabetic adults with MetS and diastolic dysfunction were randomized to lifestyle counseling or lifestyle counseling plus metformin (target dose 1000 mg bid). The primary endpoint was the change in mean e’ velocity (assessed at baseline, 6, 12 and 24 months). Secondary endpoints were improvements in insulin resistance, functional capacity and QoL. Linear mixed effects modelling was used for longitudinal data analysis using modified intention-to-treat (mITT) and per-protocol (PP) approaches. Results Forty-nine patients were included in the mITT analysis (mean age = 51.8 ± 6.4; 55% males). Metformin treatment was associated with a significant decrease in HOMA-IR. There was a significantly different mean change in e’ velocity during the study period between trial arms, both in the mITT (at 24 months, change of +0.67 ± 1.90cm/s in metformin arm vs. -0.33 ± 1.50cm/s in control arm) and PP populations (+0.80 ± 1.99cm/s in metformin arm vs. -0.37 ± 1.52cm/s in control arm), using a random intercept linear mixed model. There were no significant differences in peak oxygen uptake and SF-36 scores between trial arms. Conclusion Treatment with metformin of non-diabetic MetS patients with diastolic dysfunction, on top of lifestyle counseling, is associated with improved diastolic function. Abstract Figure.

Lifestyle Risk Factors, Quality of Life, and Intervention Preferences of Barrett’s Esophagus Patients: A Prospective Cohort Study

Background and Aims Lifestyle counseling to achieve a healthy weight, quit smoking, and reduce alcohol is a cornerstone in the management of Barrett’s Esophagus (BE). However, little is known about whether patients make these recommended lifestyle changes or the impact of non-adherence on their quality of life (QOL). This study characterized the lifestyle risk factors, QOL, and intervention preferences of BE patients as a first step toward developing lifestyle change interventions for this population. Methods Patients with a confirmed BE diagnosis (N = 106) completed surveys at a surveillance endoscopy visit (baseline) and at 3- and 6-month follow-ups. Patients reported on lifestyle risk factors, adherence determinants (e.g., perceived benefits/barriers, risk, intentions), QOL, and intervention preferences. Results Most patients (56%) had uncontrolled reflux, were overweight/obese (65.1%), and had low dietary fiber intake (91%). Many (45%) reported poor QOL. Patients’ perceived risk of developing esophageal cancer was high, but their behavior change intentions were low. Despite receiving lifestyle counseling from physicians, there were no significant changes in patients’ QOL or lifestyle risk factors over time. Nonetheless, patients indicated strong interest in internet (62.6%) and multimedia programs (57.9%) addressing acid reflux and weight control. Conclusion BE patients reported uncontrolled reflux, poor QOL, and multiple lifestyle risk factors that did not change over time. Despite low levels of intention for making lifestyle changes, patients were interested receiving more information about controlling acid reflux, suggesting a potential teachable moment and opportunity for web-based and multimedia multiple behavior interventions that seek to control acid reflux symptoms through weight loss and a high fiber diet.