Liver ATP Synthesis Is Lower and Relates to Insulin Sensitivity in Patients With Type 2 Diabetes

  1. Michael Roden, MD3,4
  1. 1MR Center of Excellence, Medical University of Vienna, Vienna, Austria
  2. 2Centre for Biomedical Engineering and Physics, Medical University of Vienna, Vienna, Austria
  3. 3Institute for Clinical Diabetology, German Diabetes Center, Department of Metabolic Diseases, Heinrich-Heine University, Düsseldorf, Germany
  4. 4Karl-Landsteiner Institute of Endocrinology and Metabolism, Vienna, Austria
  5. 5Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
  1. Corresponding author: Michael Roden, michael.roden{at}ddz.uni-duesseldorf.de.
  1. A.I.S. and J.S. contributed equally to this work.

Abstract

OBJECTIVE Steatosis associates with insulin resistance and may even predict type 2 diabetes and cardiovascular complications. Because muscular insulin resistance relates to myocellular fat deposition and disturbed energy metabolism, we hypothesized that reduced hepatic ATP turnover (fATP) underlies insulin resistance and elevated hepatocellular lipid (HCL) contents.

RESEARCH DESIGN AND METHODS We measured hepatic fATP using 31P magnetic resonance spectroscopy in patients with type 2 diabetes and age- and body mass–matched controls. Peripheral (M and M/I) and hepatic (suppression of endogenous glucose production) insulin sensitivity were assessed with euglycemic-hyperinsulinemic clamps.

RESULTS Diabetic individuals had 29% and 28% lower peripheral and hepatic insulin sensitivity as well as 42% reduced fATP than controls. After adjusting for HCL, fATP correlated positively with peripheral and hepatic insulin sensitivity but negatively with waist circumference, BMI, and fasting plasma glucose. Multiple regression analysis identified waist circumference as an independent predictor of fATP and inorganic phosphate (PI) concentrations, explaining 65% (P = 0.001) and 56% (P = 0.003) of the variations. Hepatocellular PI primarily determined the alterations in fATP.

CONCLUSIONS In patients with type 2 diabetes, insulin resistance relates to perturbed hepatic energy metabolism, which is at least partly accounted for by fat depots.

Footnotes

    • Received June 7, 2010.
    • Accepted October 26, 2010.

    Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

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    1. Diabetes Care vol. 34 no. 2 448-453
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