Cardiac Steatosis in Diabetes Mellitus

TLDR

Heart failure risk in type 2 diabetes exceeds that explained by hypertension or coronary disease, and animal and post‑mortem human studies link cardiac lipid accumulation to cell death and cardiomyopathy. The study investigates whether cardiac steatosis precedes cardiomyopathy in individuals with impaired glucose tolerance or type 2 diabetes mellitus. Researchers stratified 134 participants into lean, obese, impaired glucose tolerance, and type 2 diabetes groups and quantified myocardial triglyceride content with 1H‑MRS and left ventricular function with CMR. Impaired glucose tolerance and type 2 diabetes subjects exhibited 2.3‑ and 2.1‑fold higher myocardial triglyceride content than lean controls, while ejection fraction remained normal, indicating early cardiac steatosis precedes systolic dysfunction.

Abstract

Background— The risk of heart failure in type 2 diabetes mellitus is greater than can be accounted for by hypertension and coronary artery disease. Rodent studies indicate that in obesity and type 2 diabetes mellitus, lipid overstorage in cardiac myocytes produces lipotoxic intermediates that cause apoptosis, which leads to heart failure. In humans with diabetes mellitus, cardiac steatosis previously has been demonstrated in explanted hearts of patients with end-stage nonischemic cardiomyopathy. Whether cardiac steatosis precedes the onset of cardiomyopathy in individuals with impaired glucose tolerance or in patients with type 2 diabetes mellitus is unknown. Methods and Results— To represent the progressive stages in the natural history of type 2 diabetes mellitus, we stratified 134 individuals (age 45±12 years) into 1 of 4 groups: (1) lean normoglycemic (lean), (2) overweight and obese normoglycemic (obese), (3) impaired glucose tolerance, and (4) type 2 diabetes mellitus. Localized 1 H magnetic resonance spectroscopy and cardiac magnetic resonance imaging were used to quantify myocardial triglyceride content and left ventricular function, respectively. Compared with lean subjects, myocardial triglyceride content was 2.3-fold higher in those with impaired glucose tolerance and 2.1-fold higher in those with type 2 diabetes mellitus ( P <0.05). Left ventricular ejection fraction was normal and comparable across all groups. Conclusions— In humans, impaired glucose tolerance is accompanied by cardiac steatosis, which precedes the onset of type 2 diabetes mellitus and left ventricular systolic dysfunction. Thus, lipid overstorage in human cardiac myocytes is an early manifestation in the pathogenesis of type 2 diabetes mellitus and is evident in the absence of heart failure.