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
Citations
More filters
Journal ArticleDOI
The Evolution of Severe Steatosis After Bariatric Surgery Is Related to Insulin Resistance
Philippe Mathurin,Florent Gonzalez,Olivier Kerdraon,Emmanuelle Leteurtre,Laurent Arnalsteen,Antoine Hollebecque,Alexandre Louvet,Sébastien Dharancy,Perrine Cocq,T. Jany,J. Boitard,Pierre Deltenre,Monique Romon,François Pattou +13 more
TL;DR: It is demonstrated that severe steatosis and its evolution after surgery are intimately connected with IR and the amelioration of IR after surgery is associated with a decrease in the amount of fat.
Journal ArticleDOI
Iron Depletion by Deferoxamine Up-Regulates Glucose Uptake and Insulin Signaling in Hepatoma Cells and in Rat Liver
Paola Dongiovanni,Luca Valenti,Anna Ludovica Fracanzani,Stefano Gatti,Gaetano Cairo,Silvia Fargion +5 more
TL;DR: Investigation of the effect of iron depletion by deferoxamine on insulin signaling and glucose uptake in HepG2 hepatocytes and in rat liver found it up-regulates glucose uptake, and increases insulin receptor activity and signaling in hepatocytes in vitro and in vivo.
Journal ArticleDOI
Increased expression and activity of the transcription factor FOXO1 in nonalcoholic steatohepatitis.
Luca Valenti,Raffaela Rametta,Paola Dongiovanni,Marco Maggioni,Anna Ludovica Fracanzani,Marco Zappa,Enzo Lattuada,Giancarlo Roviaro,Silvia Fargion +8 more
TL;DR: FoxO1 expression and activity are increased in patients with steatohepatitis, and mRNA levels are correlated with hepatic insulin resistance, and FOXO1 mRNA levels correlated with nonalcoholic steato hepatitis activity score.
Journal ArticleDOI
Atorvastatin decreases serum levels of advanced glycation endproducts (AGEs) in nonalcoholic steatohepatitis (NASH) patients with dyslipidemia: clinical usefulness of AGEs as a biomarker for the attenuation of NASH
Yuki Kimura,Hideyuki Hyogo,Sho-ichi Yamagishi,Masayoshi Takeuchi,Tomokazu Ishitobi,Yoshitaka Nabeshima,Koji Arihiro,Kazuaki Chayama +7 more
TL;DR: It is demonstrated that atorvastatin decreased the serum levels of AGEs in NASH patients with dyslipidemia and suggested the usefulness of A GEs as a biomarker for the attenuation of NASH is suggested.
Journal ArticleDOI
Antiobesity effect of eicosapentaenoic acid in high-fat/high-sucrose diet-induced obesity: importance of hepatic lipogenesis.
Ayumi Sato,Hiroyuki Kawano,Tatsuto Notsu,Masahiko Ohta,Masanori Nakakuki,Kiyoshi Mizuguchi,Michiko Itoh,Takayoshi Suganami,Yoshihiro Ogawa +8 more
TL;DR: This study is the first demonstration that the anti-obesity effect of EPA in HF/HS-induced obesity is associated with the suppression of hepatic lipogenesis and steatosis, and the data suggest that EPA is suited for treatment of the metabolic syndrome.
References
More filters
Journal ArticleDOI
Homeostasis model assessment : insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man
TL;DR: The correlation of the model's estimates with patient data accords with the hypothesis that basal glucose and insulin interactions are largely determined by a simple feed back loop.
Journal ArticleDOI
Role of Insulin Resistance in Human Disease
TL;DR: The possibility is raised that resistance to insulin-stimulated glucose uptake and hyperinsulinemia are involved in the etiology and clinical course of three major related diseases— NIDDM, hypertension, and CAD.
Journal ArticleDOI
Report of the expert committee on the diagnosis and classification of diabetes mellitus
James R. Gavin,K. G M M Alberti,Mayer B. Davidson,Ralph A. DeFronzo,Allan Drash,Steven G. Gabbe,Saul M. Genuth,Maureen I. Harris,Richard Kahn,Harry Keen,William C. Knowler,Harold E. Lebovitz,Noel K. Maclaren,Jerry P. Palmer,Philip Raskin,Robert A. Rizza,Michael P. Stern +16 more
TL;DR: It was deemed essential to develop an appropriate, uniform terminology and a functional, working classification of diabetes that reflects the current knowledge about the disease.
Journal ArticleDOI
Glucose clamp technique: a method for quantifying insulin secretion and resistance.
TL;DR: Methods for the quantification of beta-cell sensitivity to glucose (hyperglycemic clamp technique) and of tissue sensitivity to insulin (euglycemic insulin clamp technique] are described.
Journal ArticleDOI
Insulin Resistance: A Multifaceted Syndrome Responsible for NIDDM, Obesity, Hypertension, Dyslipidemia, and Atherosclerotic Cardiovascular Disease
TL;DR: In summary, insulin resistance appears to be a syndrome that is associated with a clustering of metabolic disorders, including non-insulin-dependent diabetes mellitus, obesity, hypertension, lipid abnormalities, and atherosclerotic cardiovascular disease.