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

[摘要]：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 H-1 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 mu U/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. Diabetes 61:1210-1216, 2012

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