Short-Term Hyperinsulinemia and Hyperglycemia Increase Myocardial Lipid Content in Normal Subjects
- Yvonne Winhofer1,
- Martin Krššák1,
- Draženka Janković1,
- Christian-Heinz Anderwald1,2,3,
- Gert Reiter4,
- Astrid Hofer1,
- Siegfried Trattnig5,
- Anton Luger1 and
- Michael Krebs1⇓
- 1Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- 2Metabolic Unit, Institute of Biomedical Engineering-National Research Council, Padova, Italy
- 3Medical Direction, Agathenhof, Specialized Hospital for Metabolic Diseases, Micheldorf, Austria
- 4Siemens Healthcare, Vienna, Austria
- 5Department of Radiodiagnostics, Centre of Excellence High-Field Magnetic Resonance, Medical University of Vienna, Vienna, Austria
- Corresponding author: Michael Krebs, .
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.
- © 2012 by the American Diabetes Association.
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