New research sheds light on the impact of obesity and insulin resistance (IR) on heart abnormalities in patients with heart failure with preserved ejection fraction (HFpEF). The study, published in the Journal of the American College of Cardiology, challenges long standing beliefs that that these conditions have overlapping effects on the heart in this complex patient population. “Obesity and insulin resistance (IR) are strongly correlated with one another, such that patients with diabetes typically have greater adiposity, and vice versa,” says the paper’s authors, led by Yogesh N.V. Reddy, MBBS, from the Mayo Clinic in Rochester, Minnesota. “The independent roles of obesity and diabetes or IR in hemodynamic abnormalities in HFpEF remain unknown." Main findings Of 276 patients with HFpEF, 246 (89%) had increased waist/height ratio, and 166 (60%) had BMI ≥30 kg/m2, with 114 (69%) of the latter having IR and 75 (45%) having diabetes. Of 110 (40%) with HFpEF and BMI <30 kg/m2, 44 (40%) had IR and 27 (25%) had diabetes (both P < 0.0001 vs obesity phenotype). The presence of IR was not associated with worse left heart remodeling or pulmonary capillary wedge pressure (PCWP). In contrast, obesity (regardless of IR status) was associated with greater biventricular enlargement, worse exercise performance, poorer quality of life and higher rest and exercise PCWP (P < 0.01 for all). “Excess adiposity is present in most patients with HFpEF, even among those not considered obese according to BMI, calling for further study of cardiometabolic therapies among patients with HFpEF and excess adiposity with BMI <30 kg/m2,” said the paper’s authors. “Although excess body fat is associated with IR and diabetes, cardiac remodeling, hemodynamics, and functional impairment are independently correlated with body fat, but not IR. “These findings suggest that diabetes is primarily a marker of greater adiposity in HFpEF, with less direct impact on heart failure severity.” IR and T2D contribution While obesity is highly prevalent in HFpEF, an accompanying editorial questioned whether associated metabolic issues like IR and type 2 diabetes (T2D) independently contribute to the condition or were merely correlated. Recent clinical trials demonstrated the effectiveness of metabolic therapies regardless of T2D status and genetic studies linking obesity, but not T2D, to HFpEF underscored this uncertainty. The editorial, written by Jennifer E. Ho, MD, Zsu-Zsu Chen, MD and Emily S. Lau, MD, from Harvard Medical School in Boston, Massachusetts, highlighted the study’s aim to determine if IR and T2D directly contribute to HFpEF pathogenesis or were "simply bystanders, falsely implicated by the company they keep with obesity?" According to the commentators, the question underlined the importance of disentangling these interconnected factors to better understand and treat HFpEF, a condition affecting a large proportion of overweight or obese individuals. Sources: Reddy YNV, Frantz RP, Hemnes AR, et al. Disentangling the Impact of Adiposity From Insulin Resistance in Heart Failure With Preserved Ejection Fraction. J Am Coll Cardiol. 2025;85:1774-1788. Ho JE, Chen ZZ, Lau ES. Insulin Resistance and Diabetes in HFpEF: Bystander or Instigator? J Am Coll Cardiol. 2025;85:1789–1791. Image Credit: Halfpoint – stock.adobe.com