Liver ATP synthesis is lower and relates to insulin sensitivity in patients with type 2 diabetes

AI Schmid, J Szendroedi, M Chmelik, M Krššák… - Diabetes …, 2011 - Am Diabetes Assoc
AI Schmid, J Szendroedi, M Chmelik, M Krššák, E Moser, M Roden
Diabetes care, 2011Am Diabetes Assoc
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 …
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.
Am Diabetes Assoc