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Abnormal hepatic energy homeostasis in type 2 diabetes
Author(s) -
Szendroedi Julia,
Chmelik Marek,
Schmid Albrecht Ingo,
Nowotny Peter,
Brehm Attila,
Krssak Martin,
Moser Ewald,
Roden Michael
Publication year - 2009
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.23093
Subject(s) - phosphomonoesters , medicine , endocrinology , steatosis , insulin resistance , type 2 diabetes mellitus , type 2 diabetes , homeostasis , diabetes mellitus , insulin , biology , chemistry , energy metabolism , phosphocreatine
Increased hepatocellular lipids relate to insulin resistance and are typical for individuals with type 2 diabetes mellitus (T2DM). Steatosis and T2DM have been further associated with impaired muscular adenosine triphosphate (ATP) turnover indicating reduced mitochondrial fitness. Thus, we tested the hypothesis that hepatic energy metabolism could be impaired even in metabolically well‐controlled T2DM. We measured hepatic lipid volume fraction (HLVF) and absolute concentrations of γATP, inorganic phosphate (Pi), phosphomonoesters and phosphodiesters using noninvasive 1 H/ 31 P magnetic resonance spectroscopy in individuals with T2DM (58 ± 6 years, 27 ± 3 kg/m 2 ), and age‐matched and body mass index–matched (mCON; 61 ± 4 years, 26 ± 4 kg/m 2 ) and young lean humans (yCON; 25 ± 3 years, 22 ± 2 kg/m 2 , P < 0.005, P < 0.05 versus T2DM and mCON). Insulin‐mediated whole‐body glucose disposal (M) and endogenous glucose production (iEGP) were assessed during euglycemic‐hyperinsulinemic clamps. Individuals with T2DM had 26% and 23% lower γATP (1.68 ± 0.11; 2.26 ± 0.20; 2.20 ± 0.09 mmol/L; P < 0.05) than mCON and yCON individuals, respectively. Further, they had 28% and 31% lower Pi than did individuals from the mCON and yCON groups (0.96 ± 0.06; 1.33 ± 0.13; 1.41 ± 0.07 mmol/L; P < 0.05). Phosphomonoesters, phosphodiesters, and liver aminotransferases did not differ between groups. HLVF was not different between those from the T2DM and mCON groups, but higher ( P = 0.002) than in those from the yCON group. T2DM had 13‐fold higher iEGP than mCON ( P < 0.05). Even after adjustment for HLVF, hepatic ATP and Pi related negatively to hepatic insulin sensitivity (iEGP) (r =‐0.665, P = 0.010, r =‐0.680, P = 0.007) but not to whole‐body insulin sensitivity. Conclusion: These data suggest that impaired hepatic energy metabolism and insulin resistance could precede the development of steatosis in individuals with T2DM. (H EPATOLOGY 2009.)