RT Journal Article
SR Electronic
T1 Liver ATP Synthesis Is Lower and Relates to Insulin Sensitivity in Patients With Type 2 Diabetes
JF Diabetes Care
JO Diabetes Care
FD American Diabetes Association
SP 448
OP 453
DO 10.2337/dc10-1076
VO 34
IS 2
A1 Schmid, Albrecht Ingo
A1 Szendroedi, Julia
A1 Chmelik, Marek
A1 Krššák, Martin
A1 Moser, Ewald
A1 Roden, Michael
YR 2011
UL http://care.diabetesjournals.org/content/34/2/448.abstract
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.