LY2405310 : un analogue du FGF21 avec une efficacité métabolique partielle

Abstract

The purpose of this study was to investigate the relationship between hepatic triglyceride content and both myocardial function and metabolism in type 2 diabetes mellitus (T2DM).Heart disease is the leading cause of mortality in T2DM. Central obesity and hepatic steatosis, both hallmark abnormalities in T2DM, have been related to increased risk of heart disease.Sixty-one T2DM patients underwent myocardial perfusion and substrate metabolism measurements by positron emission tomography, using [15O]water, [11C]palmitate, and [18F]-2-fluoro-2-deoxy-d-glucose. In addition, whole-body insulin sensitivity (M/I) was determined. Myocardial left ventricular function and high-energy phosphate metabolism were measured using magnetic resonance imaging and [31P]-magnetic resonance spectroscopy, respectively. Hepatic triglyceride content was measured by proton magnetic resonance spectroscopy. Patients were divided according to hepatic triglyceride content (T2DM-low ≤5.56% vs. T2DM-high >5.56%).In addition to decreased M/I (p = 0.002), T2DM-high patients had reduced myocardial perfusion (p = 0.001), glucose uptake (p = 0.005), and phosphocreatine/adenosine triphosphate (PCr/ATP) ratio (p = 0.003), compared with T2DM-low patients, whereas cardiac fatty acid metabolism and left ventricular function were not different. Hepatic triglyceride content correlated inversely with M/I (Pearson's r = −0.620, p < 0.001), myocardial glucose uptake (r = −0.413, p = 0.001), and PCr/ATP (r = −0.442, p = 0.027). Insulin sensitivity correlated positively with myocardial glucose uptake (r = 0.528, p < 0.001) and borderline with myocardial PCr/ATP (r = 0.367, p = 0.072), whereas a positive association was found between cardiac glucose uptake and PCr/ATP (r = 0.481, p = 0.015).High liver triglyceride content in T2DM was associated with decreased myocardial perfusion, glucose uptake, and high-energy phosphate metabolism in conjunction with impaired M/I. The long-term clinical implications of hepatic steatosis with respect to cardiac metabolism and function in the course of T2DM require further study.