PT  - JOURNAL ARTICLE
AU  - Schmid, Albrecht Ingo
AU  - Szendroedi, Julia
AU  - Chmelik, Marek
AU  - Krššák, Martin
AU  - Moser, Ewald
AU  - Roden, Michael
TI  - Liver ATP Synthesis Is Lower and Relates to Insulin Sensitivity in Patients With Type 2 Diabetes
AID  - 10.2337/dc10-1076
DP  - 2011 Feb 01
TA  - Diabetes Care
PG  - 448--453
VI  - 34
IP  - 2
4099  - http://care.diabetesjournals.org/content/34/2/448.short
4100  - http://care.diabetesjournals.org/content/34/2/448.full
SO  - Diabetes Care2011 Feb 01; 34
AB  - 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.