Publications by authors named "Matthew J Belanger"

12 Publications

  • Page 1 of 1

Novel Non-invasive Approaches to the Treatment of Obesity: From Pharmacotherapy to Gene Therapy.

Endocr Rev 2021 Oct 26. Epub 2021 Oct 26.

Section of Endocrinology, VA Boston Healthcare System, Harvard Medical School, Boston, USA.

Recent insights into the pathophysiologic underlying mechanisms of obesity have led to the discovery of several promising drug targets and novel therapeutic strategies to address the global obesity epidemic and its comorbidities. Current pharmacologic options for obesity management are largely limited in number and of modest efficacy/safety profile. Therefore, the need for safe and more efficacious new agents is urgent. Drugs which are currently under investigation modulate targets across a broad range of systems and tissues, including the central nervous system, gastrointestinal hormones, adipose tissue, kidney, liver, and skeletal muscle. Beyond pharmacotherapeutics, other potential antiobesity strategies are being explored, including novel drug delivery systems, vaccines, modulation of the gut microbiome, and gene therapy. The present review summarizes the pathophysiology of energy homeostasis, and highlights pathways being explored in the effort to develop novel antiobesity medications and interventions but does not cover devices and bariatric methods. Emerging pharmacologic agents and alternative approaches targeting these pathways and relevant research in both animals and humans are presented in detail. Special emphasis is given to treatment options at the end of the development pipeline and closer to the clinic, i.e., compounds that have a higher chance to be added to our therapeutic armamentarium in the near future. Ultimately, advancements in our understanding of the pathophysiology and interindividual variation of obesity may lead to multimodal and personalized approaches to obesity treatment that will result in safe, effective and sustainable weight loss until the root causes of the problem are identified and addressed.
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http://dx.doi.org/10.1210/endrev/bnab034DOI Listing
October 2021

Exercise, Physical Activity and Cardiometabolic Health: Pathophysiologic Insights.

Cardiol Rev 2021 Sep 15. Epub 2021 Sep 15.

Division of Medicine, Beth Israel Deaconess Medical Center, Boston, MA; Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, MA; Cardiovascular Research Center, Beth Israel Deaconess Medical Center, Boston, MA.

Physical activity and its sustained and purposeful performance - exercise - promote a broad and diverse set of metabolic and cardiovascular health benefits. Regular exercise is the most effective way to improve cardiorespiratory fitness, a measure of one's global cardiovascular, pulmonary and metabolic health and one of the strongest predictors of future health risk. Here, we describe how exercise affects individual organ systems related to cardiometabolic health, including the promotion of insulin and glucose homeostasis through improved efficiency in skeletal muscle glucose utilization and enhanced insulin sensitivity; beneficial changes in body composition and adiposity; and improved cardiac mechanics and vascular health. We subsequently identify knowledge gaps that remain in exercise science, including heterogeneity in exercise responsiveness. While the application of molecular profiling technologies in exercise science has begun to illuminate the biochemical pathways that govern exercise-induced health promotion, much of this work has focused on individual organ systems and applied single platforms. New insights into exercise-induced secreted small molecules and proteins that impart their effects in distant organs ("exerkines") highlight the need for an integrated approach towards the study of exercise and its global effects; efforts that are ongoing.
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http://dx.doi.org/10.1097/CRD.0000000000000417DOI Listing
September 2021

Exercise, Physical Activity, and Cardiometabolic Health: Insights into the Prevention and Treatment of Cardiometabolic Diseases.

Cardiol Rev 2021 Sep 15. Epub 2021 Sep 15.

Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, MA; Cardiovascular Research Center, Beth Israel Deaconess Medical Center, Boston, MA; Division of Medicine, Beth Israel Deaconess Medical Center, Boston, MA.

Physical activity (PA) and exercise are widely recognized as essential components of primary and secondary cardiovascular disease (CVD) prevention efforts and are emphasized in the health promotion guidelines of numerous professional societies and committees. The protean benefits of PA and exercise extend across the spectrum of CVD, and include the improvement and reduction of risk factors and events for atherosclerotic CVD (ASCVD), cardiometabolic disease, heart failure, and atrial fibrillation, respectively. Here, we highlight recent insights into the salutary effects of PA and exercise on the primary and secondary prevention of ASCVD, including their beneficial effects on both traditional and non-traditional risk mediators; exercise "prescriptions" for ASCVD; the role of PA regular exercise in the prevention and treatment of heart failure; and the relationships between, PA, exercise and atrial fibrillation. While our understanding of the relationship between exercise and CVD has evolved considerably, several key questions remain including the association between extreme volumes of exercise and subclinical ASCVD and its risk; high-intensity exercise and resistance (strength) training as complementary modalities to continuous aerobic exercise; and dose- and intensity-dependent associations between exercise and atrial fibrillation. Recent advances in molecular profiling technologies (i.e., genomics, transcriptomics, proteomics, and metabolomics) have begun to shed light on inter-individual variation in cardiometabolic responses to PA and exercise and may provide new opportunities for clinical prediction in addition to mechanistic insights.
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http://dx.doi.org/10.1097/CRD.0000000000000416DOI Listing
September 2021

Postural hypotension.

BMJ 2021 04 23;373:n922. Epub 2021 Apr 23.

UCL Research Department of Primary Care and Population Health, University College London Medical School (Royal Free Hospital Campus), London NW3 2PF, UK.

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http://dx.doi.org/10.1136/bmj.n922DOI Listing
April 2021

Model-Based and Model-Free Control Predicts Alcohol Consumption Developmental Trajectory in Young Adults: A 3-Year Prospective Study.

Biol Psychiatry 2021 05 27;89(10):980-989. Epub 2021 Jan 27.

Department of Psychiatry, Technische Universität Dresden, Dresden, Germany; Neuroimaging Center, Technische Universität Dresden, Dresden, Germany. Electronic address:

Background: A shift from goal-directed toward habitual control has been associated with alcohol dependence. Whether such a shift predisposes to risky drinking is not yet clear. We investigated how goal-directed and habitual control at age 18 predict alcohol use trajectories over the course of 3 years.

Methods: Goal-directed and habitual control, as informed by model-based (MB) and model-free (MF) learning, were assessed with a two-step sequential decision-making task during functional magnetic resonance imaging in 146 healthy 18-year-old men. Three-year alcohol use developmental trajectories were based on either a consumption score from the self-reported Alcohol Use Disorders Identification Test (assessed every 6 months) or an interview-based binge drinking score (grams of alcohol/occasion; assessed every year). We applied a latent growth curve model to examine how MB and MF control predicted the drinking trajectory.

Results: Drinking behavior was best characterized by a linear trajectory. MB behavioral control was negatively associated with the development of the binge drinking score; MF reward prediction error blood oxygen level-dependent signals in the ventromedial prefrontal cortex and the ventral striatum predicted a higher starting point and steeper increase of the Alcohol Use Disorders Identification Test consumption score over time, respectively.

Conclusions: We found that MB behavioral control was associated with the binge drinking trajectory, while the MF reward prediction error signal was closely linked to the consumption score development. These findings support the idea that unbalanced MB and MF control might be an important individual vulnerability in predisposing to risky drinking behavior.
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http://dx.doi.org/10.1016/j.biopsych.2021.01.009DOI Listing
May 2021

Genetic Risk Assessment for Atherosclerotic Cardiovascular Disease: A Guide for the General Cardiologist.

Cardiol Rev 2021 Mar 19. Epub 2021 Mar 19.

Department of Medicine Division of Cardiovascular Medicine Cardiovascular Institute, Beth Israel Deaconess Medical Center, Boston, MA.

Genetic testing for cardiovascular (CV) disease has had a profound impact on the diagnosis and evaluation of monogenic causes of CV disease, such as hypertrophic and familial cardiomyopathies, long QT syndrome, and familial hypercholesterolemia (FH). The success in genetic testing for monogenic diseases has prompted special interest in utilizing genetic information in the risk assessment of more common diseases such as atherosclerotic cardiovascular disease (ASCVD). Polygenic risk scores (PRS) have been developed to assess the risk of coronary artery disease (CAD) that now include millions of single-nucleotide polymorphisms (SNPs) that have been identified through genome-wide association studies (GWAS). While these PRS have demonstrated a strong association with CAD in large cross-sectional population studies, there remains intense debate regarding the added value that PRS contribute to existing clinical risk prediction models such as the pooled cohort equations (PCEs). In this review, we provide a brief background of genetic testing for monogenic drivers of CV disease and then focus on the recent developments in genetic risk assessment of ASCVD, including the use of PRS. We outline the genetic testing that is currently available to all cardiologists in the clinic and discuss the evolving sphere of specialized cardiovascular genetics programs (CVGPs) that integrate the expertise of cardiologists, geneticists, and genetic counselors. Finally, we review the possible implications that PRS and pharmacogenomic data may soon have on clinical practice in the care for patients with or at risk of developing ASCVD.
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http://dx.doi.org/10.1097/CRD.0000000000000384DOI Listing
March 2021

Vitamin D Status Is Associated With In-Hospital Mortality and Mechanical Ventilation: A Cohort of COVID-19 Hospitalized Patients.

Mayo Clin Proc 2021 04 9;96(4):875-886. Epub 2021 Jan 9.

Department of Medicine, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, MA; Section of Endocrinology, VA Boston Healthcare System, Harvard Medical School, Boston, MA. Electronic address:

Objective: To explore the possible associations of serum 25-hydroxyvitamin D [25(OH)D] concentration with coronavirus disease 2019 (COVID-19) in-hospital mortality and need for invasive mechanical ventilation.

Patients And Methods: A retrospective, observational, cohort study was conducted at 2 tertiary academic medical centers in Boston and New York. Eligible participants were hospitalized adult patients with laboratory-confirmed COVID-19 between February 1, 2020, and May 15, 2020. Demographic and clinical characteristics, comorbidities, medications, and disease-related outcomes were extracted from electronic medical records.

Results: The final analysis included 144 patients with confirmed COVID-19 (median age, 66 years; 64 [44.4%] male). Overall mortality was 18%, whereas patients with 25(OH)D levels of 30 ng/mL (to convert to nmol/L, multiply by 2.496) and higher had lower rates of mortality compared with those with 25(OH)D levels below 30 ng/mL (9.2% vs 25.3%; P=.02). In the adjusted multivariable analyses, 25(OH)D as a continuous variable was independently significantly associated with lower in-hospital mortality (odds ratio, 0.94; 95% CI, 0.90 to 0.98; P=.007) and need for invasive mechanical ventilation (odds ratio, 0.96; 95% CI, 0.93 to 0.99; P=.01). Similar data were obtained when 25(OH)D was studied as a continuous variable after logarithm transformation and as a dichotomous (<30 ng/mL vs ≥30 ng/mL) or ordinal variable (quintiles) in the multivariable analyses.

Conclusion: Among patients admitted with laboratory-confirmed COVID-19, 25(OH)D levels were inversely associated with in-hospital mortality and the need for invasive mechanical ventilation. Further observational studies are needed to confirm these findings, and randomized clinical trials must be conducted to assess the role of vitamin D administration in improving the morbidity and mortality of COVID-19.
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http://dx.doi.org/10.1016/j.mayocp.2021.01.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834253PMC
April 2021

Effects of dietary macronutrients on serum urate: results from the OmniHeart trial.

Am J Clin Nutr 2021 06;113(6):1593-1599

Division of General Medicine, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, MA, USA.

Background: Dietary recommendations to prevent gout emphasize a low-purine diet. Recent evidence suggests that the Dietary Approaches to Stop Hypertension (DASH) diet reduces serum urate while also improving blood pressure and lipids.

Objective: To compare the effects of DASH-style diets emphasizing different macronutrient proportions on serum urate reduction.

Methods: We conducted a secondary analysis of the Optimal Macronutrient Intake Trial to Prevent Heart Disease feeding study, a 3-period, crossover design, randomized trial of adults with prehypertension or hypertension. Participants were provided with 3 DASH-style diets in random order, each for 6 wk. Each DASH-style diet emphasized different macronutrient proportions: a carbohydrate-rich (CARB) diet, a protein-rich (PROT) diet, and an unsaturated fat-rich (UNSAT) diet. In the PROT diet, approximately half of the protein came from plant sources. We compared the effects of these diets on serum urate at weeks 4 and 6 of each feeding period.

Results: Of the 163 individuals included in the final analysis, the mean serum urate at baseline was 5.1 mg/dL. Only the PROT diet reduced serum urate from baseline at the end of the 6-wk feeding period (-0.16 mg/dL; 95% CI: -0.28, -0.04; P = 0.007). Neither the CARB diet (-0.03 mg/dL; 95% CI: -0.14, 0.09; P = 0.66) nor the UNSAT diet (-0.01 mg/dL; 95% CI: -0.12, 0.09; P = 0.78) reduced serum urate from baseline. The PROT diet lowered serum urate by 0.12 mg/dL (95% CI: -0.20, -0.03; P = 0.006) compared with CARB and by 0.12 mg/dL (95% CI: -0.20, -0.05; P = 0.002) compared with UNSAT.

Conclusions: A DASH-style diet emphasizing plant-based protein lowered serum urate compared with those emphasizing carbohydrates or unsaturated fat. Future trials should test the ability of a DASH-style diet emphasizing plant-based protein to lower serum urate and prevent gout flares in patients with gout. This trial was registered at clinicaltrials.gov as NCT00051350.
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http://dx.doi.org/10.1093/ajcn/nqaa424DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168362PMC
June 2021

A New Method to Estimate Dietary Sodium Intake From a Spot Urine Sample: Context and Caution.

Am J Hypertens 2021 08;34(7):686-688

Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.

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http://dx.doi.org/10.1093/ajh/hpab036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8351498PMC
August 2021

Characteristics and Significance of Tricuspid Valve Prolapse in a Large Multidecade Echocardiographic Study.

J Am Soc Echocardiogr 2021 01 16;34(1):30-37. Epub 2020 Oct 16.

Richard A. and Susan F. Smith Center for Outcomes Research in Cardiology, Boston, Massachusetts; Cardiovascular Division, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, Massachusetts. Electronic address:

Background: Characteristics of tricuspid valve prolapse (TVP) on transthoracic echocardiography are not well defined. As tricuspid valve interventions are increasingly considered, information on the definition and clinical significance of TVP is needed.

Methods: At the authors' institution, between January 26, 2000, and September 20, 2018, 410 patients (0.3%) were determined to have suspected TVP. These transthoracic echocardiograms and those of 97 age- and sex-matched normal control subjects were reviewed. Interrater agreement on TVP by visual inspection was assessed in a blinded subset. Leaflet atrial displacement (AD) > 2 SDs above the mean in normal control subjects was used to identify an empiric definition of TVP Features of patients meeting this definition were evaluated.

Results: Three hundred twelve transthoracic echocardiograms with available and interpretable images (76.1%) were included. Interrater agreement on TVP diagnosis by visual inspection was moderate. Normal values of AD were up to 4 mm in the right ventricular inflow view and 2 mm in all other views. AD > 2 mm in the parasternal short-axis view had the best accuracy against suspected TVP to identify TVP. Those with TVP by this definition more frequently had 3 to 4+ tricuspid regurgitation (22.2% vs 3.1%; P < .001), mitral valve prolapse (MVP; 75.0% vs 3.1%; P < .001), and more clinically significant MVP (greater prevalence of 3 to 4+ mitral regurgitation). No difference in mortality was observed in those with isolated TVP versus TVP and MVP (log-rank P = .93).

Conclusions: In the largest study of TVP to date, interrater agreement on TVP diagnosis by visual inspection was moderate. A cutoff of >2-mm AD in the parasternal short-axis view was optimal to define TVP. Those with TVP by this definition had more significant tricuspid regurgitation, larger right ventricles, and more clinically significant MVP. Overall, these results suggest an increased role for surveillance for TVP and the need for clear diagnostic criteria in updated guidelines.
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http://dx.doi.org/10.1016/j.echo.2020.09.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7796941PMC
January 2021

Covid-19 and Disparities in Nutrition and Obesity.

N Engl J Med 2020 Sep 15;383(11):e69. Epub 2020 Jul 15.

From the Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School (M.J.B., A.M.A., C.S.M.), and the Section of Endocrinology, VA Boston Healthcare System and Harvard Medical School (C.S.M.) - both in Boston; the Dalton Cardiovascular Research Center and the Department of Medical Pharmacology and Physiology (M.A.H., J.R.S.) and the Diabetes and Cardiovascular Research Center (J.R.S.), University of Missouri, Columbia; and the Department of Biologic Chemistry, School of Medicine, National and Kapodistrian University of Athens, Athens (M.D.).

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http://dx.doi.org/10.1056/NEJMp2021264DOI Listing
September 2020

Commentary: COVID-19 and diabetes mellitus: What we know, how our patients should be treated now, and what should happen next.

Metabolism 2020 06 19;107:154245. Epub 2020 Apr 19.

Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA; Section of Endocrinology, VA Boston Healthcare System, Harvard Medical School, Boston, MA 02115, USA. Electronic address:

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http://dx.doi.org/10.1016/j.metabol.2020.154245DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7167295PMC
June 2020
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