title: Inverse association between liver fat content and hepatic glucose uptake in patients with type 2 diabetes mellitus.
abstract: The objective of this research was to study (1) the mutual relationship between liver fat content (LFC) and hepatic glucose uptake (HGU) in patients with type 2 diabetes mellitus and (2) the relationship between changes in LFC and HGU uptake induced by rosiglitazone in these patients. Liver fat was measured with proton magnetic resonance spectroscopy and insulin-stimulated HGU with [(18)F]-labeled 2-fluoro-2-deoxyglucose positron emission tomography in 54 patients with type 2 diabetes mellitus and 8 healthy subjects. Measurements were repeated in diabetic patients after a 16-week intervention period with rosiglitazone (n = 27) or placebo (n = 27). Patients with diabetes had lower HGU (24.5 +/- 14.2 vs 35.6 +/- 9.7 micromol/[kg min], P < .01) and higher LFC (10.9% +/- 9.2% vs 2.5% +/- 1.4%, P < .001) compared with healthy subjects. Liver fat was inversely associated with HGU (r = -0.31, P < .05), but more strongly with whole-body insulin sensitivity and adiponectin levels. Rosiglitazone treatment reduced liver fat by 24.8% (P = .01 vs placebo) and increased HGU by 29.2% (P = .013 vs placebo). This decrease in LFC was best explained by the increment in suppression of nonesterified fatty acid levels during hyperinsulinemia (P < .001) and improved glycemic control (P = .034), but not by changes in HGU. A significant inverse relationship between LFC and HGU was observed, but changes were not related. This suggests that the beneficial effects of rosiglitazone on liver metabolism are indirect and can be partly explained by increased suppression of nonesterified fatty acid levels, leading to reduced liver fat.
authors.affiliation: Medical Imaging Centre of Southwest Finland, Turku University Hospital, FIN-20521 Turku, Finland.
authors.forename: Ronald
authors.initials: R
authors.lastname: Borra
authors.forename: Riika
authors.initials: R
authors.lastname: Lautamäki
authors.forename: Riita
authors.initials: R
authors.lastname: Parkkola
authors.forename: Markku
authors.initials: M
authors.lastname: Komu
authors.forename: Paul E
authors.initials: PE
authors.lastname: Sijens
authors.forename: Kirsti
authors.initials: K
authors.lastname: Hällsten
authors.forename: Jörgen
authors.initials: J
authors.lastname: Bergman
authors.forename: Patricia
authors.initials: P
authors.lastname: Iozzo
authors.forename: Pirjo
authors.initials: P
authors.lastname: Nuutila
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism*; D005234:Fatty Liver / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D019788:Fluorodeoxyglucose F18; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D000077154:Rosiglitazone; D018709:Statistics, Nonparametric; D045162:Thiazolidinediones / Q000494:pharmacology
chemical_list: D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D019788:Fluorodeoxyglucose F18; D005947:Glucose