Effects of Insulin Therapy on Myocardial Lipid Content and Cardiac Geometry in Patients with Type-2 Diabetes Mellitus

Abstract

Aims/HypothesisRecent evidence suggests a link between myocardial steatosis and diabetic cardiomyopathy. Insulin, as a lipogenic and growth-promoting hormone, might stimulate intramyocardial lipid (MYCL) deposition and hypertrophy. Therefore, the aim of the present study was to investigate the short-term effects of insulin therapy (IT) on myocardial lipid content and morphology in patients with T2DM.MethodsEighteen patients with T2DM were recruited (age 56±2 years; HbA1c: 10.5±0.4%). In 10 patients with insufficient glucose control under oral medication IT was initiated due to secondary failure of oral glucose lowering therapy (IT-group), while 8 individuals did not require additional insulin substitution (OT-group). In order to assess MYCL and intrahepatic lipid (IHLC) content as well as cardiac geometry and function magnetic resonance spectroscopy (MRS) and imaging (MRI) examinations were performed at baseline (IT and OT) and 10 days after initiation of IT. Follow up measurements took place 181±49 days after IT.ResultsInterestingly, basal MYCLs were 50% lower in IT- compared to OT-group (0.41±0.12 vs. 0.80±0.11% of water signal; p = 0.034). After 10 days of IT, an acute 80%-rise in MYCL (p = 0.008) was observed, while IHLC did not change. Likewise, myocardial mass (+13%; p = 0.004), wall thickness in end-diastole (+13%; p = 0.030) and concentricity, an index of cardiac remodeling, increased (+28%; p = 0.026). In the long-term MYCL returned to baseline, while IHCL significantly decreased (−31%; p = 0.000). No acute changes in systolic left ventricular function were observed.Conclusions/InterpretationThe initiation of IT in patients with T2DM was followed by an acute rise in MYCL concentration and myocardial mass.

Effects of Insulin Glargine and Liraglutide Therapy on Liver Fat as Measured by Magnetic Resonance in Patients With Type 2 Diabetes: A Randomized Trial

“…The reduction in the liver fat fraction with insulin therapy is consistent with the findings of previous studies that have used MRS (6)(7)(8) or computed tomography (9) for quantification and monitoring of fractional liver fat. In parallel to liver fat fraction reduction, our study revealed an average concomitant liver volume decrease of 152 mL in the insulin-treated group.…”

“…Yet, prior studies that have used imaging techniques for fat quantification have shown a reduction in liver fat with insulin therapy (6)(7)(8)(9). The mechanisms by which insulin therapy may reduce liver fat include inhibition of lipolysis, which may reduce free fatty acid flux to the liver (7), and decreased production of endogenous insulin passing through the liver to stimulate hepatic lipogenesis (6).…”

Insulin Resistance as a Physiological Defense Against Metabolic Stress: Implications for the Management of Subsets of Type 2 Diabetes

“…1). In support of this concept, treatment of patients with T2D with 10 days of exogenous insulin increased the myocardial lipid content by 80%, the level of which was positively associated with the initial mean glucose concentration (18). Even in normal subjects, short-term hyperinsulinemia and hyperglycemia caused an increase in myocardial lipid content, indicative of how hyperinsulinemia together with hyperglycemia can contribute to cardiac lipid accumulation (19).…”

Pericardial- Rather than Intramyocardial Fat Is Independently Associated with Left Ventricular Systolic Heart Function in Metabolically Healthy Humans

“…Our recent studies suggest that MYCL accumulation is not directly related to insulin resistance [ 6 ] and is highly dynamic, quickly responding to changes in the metabolic and hormonal milieu [ 12 – 14 ]. Furthermore, sufficient MYCL stores might be prerequisite to stimulated systolic function in response to catecholamine-induced stress [ 14 ].…”