title: Short-term hyperinsulinemia and hyperglycemia increase myocardial lipid content in normal subjects.
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 (1)H 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/m(2)). 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.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Winhofer
authors.forename: Martin
authors.initials: M
authors.lastname: Krssák
authors.forename: Drazenka
authors.initials: D
authors.lastname: Jankovic
authors.forename: Christian-Heinz
authors.initials: CH
authors.lastname: Anderwald
authors.forename: Gert
authors.initials: G
authors.lastname: Reiter
authors.forename: Astrid
authors.initials: A
authors.lastname: Hofer
authors.forename: Siegfried
authors.initials: S
authors.lastname: Trattnig
authors.forename: Anton
authors.initials: A
authors.lastname: Luger
authors.forename: Michael
authors.initials: M
authors.lastname: Krebs
mesh_terms: D000328:Adult; D001786:Blood Glucose; D004334:Drug Administration Schedule; D005260:Female; D005947:Glucose / Q000008:administration & dosage / Q000494:pharmacology; D015309:Glucose Clamp Technique; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism*; D006946:Hyperinsulinism / Q000378:metabolism*; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology; D050356:Lipid Metabolism / Q000187:drug effects*; D008055:Lipids / Q000737:chemistry; D008297:Male; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism*; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D007328:Insulin; D008055:Lipids; D005947:Glucose