Nonalcoholic fatty liver disease a feature of the metabolic syndrome
Giulio Marchesini,Mara Brizi,Giampaolo Bianchi,Sara Tomassetti,Elisabetta Bugianesi,Marco Lenzi,Arthur J. McCullough,S. Natale,Gabriele Forlani,Nazario Melchionda +9 more
TLDR
It is concluded that NAFLD, in the presence of normoglycemia and normal or moderately increased body weight, is characterized by clinical and laboratory data similar to those found in diabetes and obesity.Abstract:
Insulin sensitivity (euglycemic clamp, insulin infusion rate: 40 mU m(-2) min(-1)) was studied in 30 subjects with biopsy-proven nonalcoholic fatty liver disease (NAFLD), normal glucose tolerance, and a BMI <30 kg/m(2) Of those 30 subjects, 9 had pure fatty liver and 21 had evidence of steatohepatitis In addition, 10 patients with type 2 diabetes under good metabolic control and 10 healthy subjects were studied Most NAFLD patients had central fat accumulation, increased triglycerides and uric acid, and low HDL cholesterol, irrespective of BMI Glucose disposal during the clamp was reduced by nearly 50% in NAFLD patients, as well as in patients with normal body weight, to an extent similar to that of the type 2 diabetic patients Basal free fatty acids were increased, whereas insulin-mediated suppression of lipolysis was less effective (-69% in NAFLD vs -84% in control subjects; P = 0003) Postabsorptive hepatic glucose production (HGP), measured by [6,6-(2)H(2)]glucose, was normal In response to insulin infusion, HGP decreased by only 63% of basal in NAFLD vs 84% in control subjects (P = 0002) Compared with type 2 diabetic patients, NAFLD patients were characterized by lower basal HGP, but with similarly reduced insulin-mediated suppression of HGP There was laboratory evidence of iron overload in many NAFLD patients, but clinical, histological, and biochemical data (including insulin sensitivity) were not correlated with iron status Four subjects were heterozygous for mutation His63Asp of the HFE gene of familiar hemochromatosis We concluded that NAFLD, in the presence of normoglycemia and normal or moderately increased body weight, is characterized by clinical and laboratory data similar to those found in diabetes and obesity NAFLD may be considered an additional feature of the metabolic syndrome, with specific hepatic insulin resistanceread more
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Mechanisms of Disease: hepatic steatosis in type 2 diabetes--pathogenesis and clinical relevance.
TL;DR: Liver fat is a critical determinant of metabolic fluxes and inflammatory processes, thereby representing an important therapeutic target in insulin resistance and type 2 diabetes mellitus.
Journal ArticleDOI
Elevated alanine aminotransferase predicts new-onset type 2 diabetes independently of classical risk factors, metabolic syndrome, and C-reactive protein in the west of Scotland coronary prevention study.
Naveed Sattar,Olga Scherbakova,Ian Ford,Denis St. J. O’Reilly,Adrian J. Stanley,Ewan Forrest,Peter W. Macfarlane,Chris J. Packard,Stuart M. Cobbe,James Shepherd +9 more
TL;DR: Elevated ALT levels within the "normal" range predict incident diabetes, and the simplicity of ALT measurement and its availability in routine clinical practice suggest that this enzyme activity could be included in future diabetes prediction algorithms.
Journal ArticleDOI
Cardiovascular Risk Factors and the Metabolic Syndrome in Pediatric Nonalcoholic Fatty Liver Disease
TL;DR: NAFLD in overweight and obese children is strongly associated with multiple cardiovascular risk factors and should prompt global counseling to address nutrition, physical activity, and avoidance of smoking to prevent the development of cardiovascular disease and type 2 diabetes.
Journal ArticleDOI
Gene expression in human NAFLD.
Dario Greco,Anna Kotronen,Jukka Westerbacka,Oscar Puig,Perttu Arkkila,Tuula Kiviluoto,Saara Laitinen,Maria Kolak,Rachel M. Fisher,Anders Hamsten,Petri Auvinen,Hannele Yki-Järvinen +11 more
TL;DR: The data show that multiple changes in gene expression characterize simple steatosis, and genes involved in hepatic glucose and lipid metabolism, insulin signaling, inflammation, coagulation, and cell adhesion are found to be significantly associated with liver fat content.
Journal ArticleDOI
Histopathology of Nonalcoholic Fatty Liver Disease
Elizabeth M. Brunt,Dina Tiniakos +1 more
TL;DR: In this article, the rationale for liver biopsy, as well as the histopathological lesions, the microscopically observable patterns of injury, and the differential diagnoses of NAFLD and NASH are discussed.
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