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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Obesity and liver disease
André Scheen,Françoise Luyckx +1 more
TL;DR: In this article, the authors considered NASH may be considered as another disease of affluence, as is the insulin resistance syndrome, and perhaps being part of it, especially in obese patients, and the identification of obese patients who may progress from steatosis to NASH and from NASH to fibrosis/cirrhosis is an important clinical challenge.
Journal ArticleDOI
Prevalence of Hepatic Steatosis After Islet Transplantation and Its Relation to Graft Function
Ravi Bhargava,Peter A. Senior,Thomas Ackerman,Edmond A. Ryan,Breay W. Paty,Jonathan R. T. Lakey,A. M. James Shapiro +6 more
TL;DR: Serum triglycerides and the use of exogenous insulin were associated with increased odds of steatosis in a logistic regression model (chi(2) [degrees freedom] = 13.6 [2]; P = 0.001).
Journal ArticleDOI
Silencing of Hepatic Fatty Acid Transporter Protein 5 in Vivo Reverses Diet-induced Non-alcoholic Fatty Liver Disease and Improves Hyperglycemia
Holger Doege,Holger Doege,Dirk Grimm,Alaric Falcon,Bernice Tsang,Theresa A. Storm,Hui Xu,Angelica M. Ortegon,Melissa Kazantzis,Mark A. Kay,Andreas Stahl +10 more
TL;DR: This work demonstrates the ability to achieve specific, non-toxic, and persistent knockdown of fatty acid transport protein 5 in mouse livers from a single adeno-associated virus injection, resulting in a marked reduction of hepatic dietary fatty acid uptake, reduced caloric uptake, and concomitant protection from diet-induced non-alcoholic fatty liver disease.
Journal ArticleDOI
Association of the rs738409 polymorphism in PNPLA3 with liver damage and the development of nonalcoholic fatty liver disease
Kikuko Hotta,Masato Yoneda,Hideyuki Hyogo,Hidenori Ochi,Seiho Mizusawa,Takato Ueno,Kazuaki Chayama,Atsushi Nakajima,Kazuwa Nakao,Akihiro Sekine +9 more
TL;DR: It is found that in the Japanese population, individuals harboring the G-allele of rs738409 were susceptible to NAFLD, and that the SNP was associated with plasma levels of ALT, AST, and ferritin, and the histological fibrosis stage.
Journal ArticleDOI
Trimethylamine-N-oxide (TMAO) as Novel Potential Biomarker of Early Predictors of Metabolic Syndrome
Luigi Barrea,Giuseppe Annunziata,Giovanna Muscogiuri,Carolina Di Somma,Daniela Laudisio,Maria Maisto,Giulia de Alteriis,Gian Carlo Tenore,Annamaria Colao,Silvia Savastano +9 more
TL;DR: Findings allow us to hypothesize a role of TMAO as an early biomarker of adipose dysfunction and NAFLD-FLI in all borderline conditions in which overt MetS is not present, and suggest that a specific cut-off of TmaO might help in identifying subjects at high risk ofNAFLD.
References
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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.