Eans of magnetic resonance spectroscopy in obese patients with T2DM and non-ischemic cardiomyopathy demonstrated increased intramyocardial lipid content (MYCL) [6?]. However, to date contradictive results have been published concerning the short term effects of MYCL accumulation (steatosis) on cardiac function [7,9]. Growing evidence indicates a potential relationship between chronic hyperinsulinemia in pre-diabetic patients and structuralInsulin Alters Myocardial Lipids and Morphologychanges of the heart leading to myocardial fibrosis [10,11]. A crucial role in the pathogenesis of myocardial hypertrophy has been identified for insulin-related cell signaling pathways including the insulin/PI3k/PKB/Akt axis [12]. Consistently, it was demonstrated that disturbances of this pathway induce a decrease in glucose uptake and glucose oxidation and an increase in fatty acid utilization [13]. In a recent study we observed that insulin acutely increases MYCL content and alters cardiac function in the presence of standardized hyperglycemia/hyperinsulinemia (clamp test) in healthy subjects [14]. Therefore we hypothesized that exogenous insulin supply promotes the development of myocardial steatosis and modifies left ventricular contractility in patients with T2DM.Methods Ethics StatementThe study was approved by the institutional medical ethical committee (Ethics Committee of the Medical University of Vienna) and written informed consent was obtained from all participants. 1313429 All clinical investigations have been conducted according to the principles expressed in the Declaration of Helsinki.glycemic control ameliorated in 8 out of 18 patients (OT-group, mean plasma glucose ,190 mg/dl). Thus, these patients did not require standardized IT corresponding to the study protocol and only baseline MR examinations were performed in this subgroup of patients. During the course of the study no adjustments of lipid lowering and/or anti-hypertensive medication were performed. During the first 10 days of the inpatient setting standardized frequent measurements of blood glucose order JW 74 concentrations (0 h, 3 h, 6 h, 9 h, 12 h, 15 h, 18 h, 21 h; Accu-Check Go Blood Glucose Monitor, Roche Diagnostics, Vienna, Austria) allowed to quickly titrate insulin doses and achieve pre-prandial glucose concentrations of 100?20 mg/dl. Insulin doses were adjusted twice daily by experienced buy Sudan I physicians. In addition a standardized diet with 1400 kilocalories per day (fat/carbohydrate/protein: 32 /48 /20 ) was administered during inpatient treatment. All patients were advised to adhere to the diet plan after 1407003 the discharge. Furthermore, structured inpatient diabetes training included recommendations for regular moderate physical activity. Ten days after the initiation of IT MRI and MRS studies were repeated. Patients were discharged on day 10. Clinical and MR follow up examinations were performed in 7 patients 181649 days after initiation of IT.Study ParticipantsEighteen patients with T2DM were recruited from the outpatient service of our department (Table 1). Inclusion criteria were insufficient metabolic control under oral anti-diabetic medication at the time point of clinical assessment (HbA1c .8 ) and resting blood pressure ,150/85 mmHg with or without antihypertensive medication. Patients with previous myocardial infarction, coronary artery disease and/or history of congestive heart failure were excluded. In addition, subjects, who received digitalis and/or thioazolidinediones did not part.Eans of magnetic resonance spectroscopy in obese patients with T2DM and non-ischemic cardiomyopathy demonstrated increased intramyocardial lipid content (MYCL) [6?]. However, to date contradictive results have been published concerning the short term effects of MYCL accumulation (steatosis) on cardiac function [7,9]. Growing evidence indicates a potential relationship between chronic hyperinsulinemia in pre-diabetic patients and structuralInsulin Alters Myocardial Lipids and Morphologychanges of the heart leading to myocardial fibrosis [10,11]. A crucial role in the pathogenesis of myocardial hypertrophy has been identified for insulin-related cell signaling pathways including the insulin/PI3k/PKB/Akt axis [12]. Consistently, it was demonstrated that disturbances of this pathway induce a decrease in glucose uptake and glucose oxidation and an increase in fatty acid utilization [13]. In a recent study we observed that insulin acutely increases MYCL content and alters cardiac function in the presence of standardized hyperglycemia/hyperinsulinemia (clamp test) in healthy subjects [14]. Therefore we hypothesized that exogenous insulin supply promotes the development of myocardial steatosis and modifies left ventricular contractility in patients with T2DM.Methods Ethics StatementThe study was approved by the institutional medical ethical committee (Ethics Committee of the Medical University of Vienna) and written informed consent was obtained from all participants. 1313429 All clinical investigations have been conducted according to the principles expressed in the Declaration of Helsinki.glycemic control ameliorated in 8 out of 18 patients (OT-group, mean plasma glucose ,190 mg/dl). Thus, these patients did not require standardized IT corresponding to the study protocol and only baseline MR examinations were performed in this subgroup of patients. During the course of the study no adjustments of lipid lowering and/or anti-hypertensive medication were performed. During the first 10 days of the inpatient setting standardized frequent measurements of blood glucose concentrations (0 h, 3 h, 6 h, 9 h, 12 h, 15 h, 18 h, 21 h; Accu-Check Go Blood Glucose Monitor, Roche Diagnostics, Vienna, Austria) allowed to quickly titrate insulin doses and achieve pre-prandial glucose concentrations of 100?20 mg/dl. Insulin doses were adjusted twice daily by experienced physicians. In addition a standardized diet with 1400 kilocalories per day (fat/carbohydrate/protein: 32 /48 /20 ) was administered during inpatient treatment. All patients were advised to adhere to the diet plan after 1407003 the discharge. Furthermore, structured inpatient diabetes training included recommendations for regular moderate physical activity. Ten days after the initiation of IT MRI and MRS studies were repeated. Patients were discharged on day 10. Clinical and MR follow up examinations were performed in 7 patients 181649 days after initiation of IT.Study ParticipantsEighteen patients with T2DM were recruited from the outpatient service of our department (Table 1). Inclusion criteria were insufficient metabolic control under oral anti-diabetic medication at the time point of clinical assessment (HbA1c .8 ) and resting blood pressure ,150/85 mmHg with or without antihypertensive medication. Patients with previous myocardial infarction, coronary artery disease and/or history of congestive heart failure were excluded. In addition, subjects, who received digitalis and/or thioazolidinediones did not part.
