Short-Term Hyperinsulinemia and Hyperglycemia Increase Myocardial Lipid Content in Normal Subjects

  1. Michael Krebs1
  1. 1Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
  2. 2Metabolic Unit, Institute of Biomedical Engineering-National Research Council, Padova, Italy
  3. 3Medical Direction, Agathenhof, Specialized Hospital for Metabolic Diseases, Micheldorf, Austria
  4. 4Siemens Healthcare, Vienna, Austria
  5. 5Department of Radiodiagnostics, Centre of Excellence High-Field Magnetic Resonance, Medical University of Vienna, Vienna, Austria
  1. Corresponding author: Michael Krebs, michael.krebs{at}meduniwien.ac.at.

Abstract

Increased myocardial lipid content (MYCL) recently has been linked to the development of cardiomyopathy in diabetes. In contrast to steatosis in skeletal muscle and liver, previous investigations could not confirm a link between MYCL and insulin resistance. Thus, we hypothesized that cardiac steatosis might develop against the background of the metabolic environment typical for prediabetes and early type 2 diabetes: combined hyperglycemia and hyperinsulinemia. Therefore, we aimed to prove the principle that acute hyperglycemia (during a 6-h clamp) affects MYCL and function (assessed by 1H magnetic resonance spectroscopy and imaging) in healthy subjects (female subjects: n = 8, male subjects: n = 10; aged 28 ± 5 years; BMI 22.4 ± 2.6 kg/m2). Combined hyperglycemia (202.0 ± 10.6 mg/dL) and hyperinsulinemia (110.6 ± 59.0 μU/mL) were, despite insulin-mediated suppression of free fatty acids, associated with a 34.4% increase in MYCL (baseline: 0.20 ± 0.17%, clamp: 0.26 ± 0.22% of water signal; P = 0.0009), which was positively correlated with the area under the curve of insulin (R = 0.59, P = 0.009) and C-peptide (R = 0.81, P < 0.0001) during the clamp. Furthermore, an increase in ejection fraction (P < 0.0001) and a decrease in end-systolic volume (P = 0.0002) were observed, which also were correlated with hyperinsulinemia. Based on our findings, we conclude that combined hyperglycemia and hyperinsulinemia induce short-term myocardial lipid accumulation and alterations in myocardial function in normal subjects, indicating that these alterations might be directly responsible for cardiac steatosis in metabolic diseases.

  • Received September 11, 2011.
  • Accepted January 9, 2012.

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  1. Diabetes vol. 61 no. 5 1210-1216
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