Neue Marker für NASH bei Typ-2-Diabetes und Adipositas

N. Stefan; H.-U. Häring

doi:10.1055/s-0037-1618700

Adipositas - Ursachen, Folgeerkrankungen, Therapie, Table of Contents

Adipositas - Ursachen, Folgeerkrankungen, Therapie 2010; 04(02): 65-69
DOI: 10.1055/s-0037-1618700

NAFLD/NASH bei Adipositas

Schattauer GmbH

Neue Marker für NASH bei Typ-2-Diabetes und Adipositas

Novel markers for NASH in patients with type 2 diabetes and obesity

N. Stefan^*

¹Innere Medizin, Abteilung für Endokrinologie, Diabetologie, Vaskuläre Medizin, Nephrologie und Klinische Chemie, Universitätsklinik Tübingen, Mitglied des Deutschen Zentrums für Diabetesforschung

,

H.-U. Häring

¹Innere Medizin, Abteilung für Endokrinologie, Diabetologie, Vaskuläre Medizin, Nephrologie und Klinische Chemie, Universitätsklinik Tübingen, Mitglied des Deutschen Zentrums für Diabetesforschung

› Author Affiliations

Abstract

Zusammenfassung

Die nichtalkoholische Fettleber (NAFL) und nichtalkoholische Steatohepatitis (NASH) sind nicht nur Risikofaktoren für Leberfibrose, Leberzirrhose und das hepatozelluläre Karzinom, sondern sie sind auch stark mit Insulinresistenz, Typ-2-Diabetes und Atherosklerose assoziiert. Darüber hinaus sagt eine Fettleber die Erkrankungswahrscheinlichkeit für Typ-2-Diabetes und Atherosklerose voraus, was eine kausale Rolle der Fettleber in der Pathogenese dieser Erkrankungen impliziert. Folgerichtig zielen Strategien zur Prävention und Therapie der Fettleber darauf hin, frühzeitig zu handeln. Dabei ist zu beachten, dass nicht nur eine genaue und frühzeitige Diagnose einer Fettleber gestellt wird, wie sie es zur Zeit nichtinvasiv mittels der Protonen-Magnetresonz-Spektroskopie möglich ist, sondern auch der NASH, der malignen Form der Fettleber.

Summary

Nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH) are not only risc factors for liver fibrosis, liver cirrhosis and hepatocellular carcinoma, but are also strongly associated with insulin resistance, type 2 diabetes, and atherosclerosis. In addition fatty liver predicts incident type 2 diabetes and atherosclerosis, indicating a causal role of fatty liver in the pathogenesis of these diseases. Consequently strategies aiming at early preventing and treating fatty liver, need to be implemented. In this respect it is important not only to early and precisely diagnose fatty liver, as can be done using non-invasive protone magnetic resonance spectroscopy, but also to diagnose NASH, the malignant form of fatty liver.

Schlüsselwörter

Nichtalkoholische Fettleber (NAFL) - nichtalkoholische Steatohepatitis (NASH) - Typ-2-Diabetes - Atherosklerose - Fetuin-A - Sex Hormone-Binding Globuline

Keywords

Nonalcoholic fatty liver (NAFL) - nonalcoholic steatohepatitis (NASH) - type 2 diabetes - atherosclerosis - Fetuin-A - Sex Hormone-Binding Globuline

Full Text

References

Literatur
1 Campos GM, Bambha K, Vittinghoff E. et al. A clinical scoring system for predicting nonalcoholic steatohepatitis in morbidly obese patients. Hepatology 2008; 47: 1916-1923.
2 Ding EL, Song Y, Manson JE. et al. Sex hormone-binding globulin and risk of type 2 diabetes in women and men. N Engl J Med 2009; 361: 1152-1163.
3 Feldstein AE, Wieckowska A, Lopez AR. et al. Cytokeratin-18 fragment levels as noninvasive biomarkers for nonalcoholic steatohepatitis: a multicenter validation study. Hepatology 2009; 50: 1072-1078.
4 Fisher E, Stefan N, Saar K. et al. Association of AHSG gene polymorphisms with fetuin-A plasma levels and cardiovascular diseases in the EPIC-Potsdam study. Circ Cardiovasc Genet 2009; 02: 607-613.
5 Hennige AM, Staiger H, Wicke C. et al. Fetuin-A induces cytokine expression and suppresses adiponectin production. PLoS ONE 2008; 03: e1765.
6 Kantartzis K, Machann J, Schick F. et al. The impact of liver fat vs visceral fat in determining categories of prediabetes. Diabetologia. 2010 Jan 23 [Epub ahead of print] DOI 10.1007/s00125-010-1663-6.
7 Kantartzis K, Machicao F, Machann J. et al. The DGAT2 gene is a candidate for the dissociation between fatty liver and insulin resistance in humans. Clin Sci (Lond) 2009; 116: 531-537.
8 Kantartzis K, Peter A, Machicao F. et al. Dissociation between fatty liver and insulin resistance in humans carrying a variant of the patatin-like phospholipase 3 gene. Diabetes 2009; 58: 2616-2623.
9 Kantartzis K, Thamer C, Peter A. et al. High cardiorespiratory fitness is an independent predictor of the reduction in liver fat during a lifestyle intervention in non-alcoholic fatty liver disease. Gut 2009; 58: 1281-1288.
10 Patton HM, Lavine JE, Van Natta ML. et al. Nonalcoholic Steatohepatitis Clinical Research Network. Clinical correlates of histopathology in pediatric nonalcoholic steatohepatitis. Gastroenterology 2008; 135: 1961-1971 e2.
11 Poynard T, Ratziu V, Charlotte F. LIDO Study Group; CYTOL study group. et al. Diagnostic value of biochemical markers (NashTest) for the prediction of non alcoholo steato hepatitis in patients with non-alcoholic fatty liver disease. BMC Gastroenterol 2006; 06: 34.
12 Roden M. Mechanisms of Disease: hepatic steatosis in type 2 diabetes--pathogenesis and clinical relevance. Nat Clin Pract Endocrinol Metab 2006; 02: 335-348.
13 Solga SF, Alkhuraishe A, Cope K. et al. Breath biomarkers and non-alcoholic fatty liver disease: preliminary observations. Biomarkers 2006; 11: 174-183.
14 Sookoian S, Castaño G, Burgueño AL. A diagnostic model to differentiate simple steatosis from nonalcoholic steatohepatitis based on the likelihood ratio form of Bayes theorem. Clin Biochem 2009; 42: 624-629.
15 Stefan N, Fritsche N, Weikert C. et al. Plasma Fetuin-A Levels and the Risk of Type 2 Diabetes. Diabetes 2008; 57: 2762-2767.
16 Stefan N, Häring HU, Schulze MB. Association of Fetuin-A Level and Diabetes Risk. JAMA 2008; 300: 2247.
17 Stefan N, Hennige AM, Staiger H. et al. Alpha2-Heremans-Schmid Glycoprotein/Fetuin-A is associated with Insulin Resistance and Fat Accumulation in the Liver in Humans. Diabetes Care 2006; 29: 853-857.
18 Stefan N, Hennige AM, Staiger H. et al. High circulating retinol-binding protein 4 is associated with elevated liver fat but not with total, subcutaneous, visceral, or intramyocellular fat in humans. Diabetes Care 2007; 30: 1173-1178.
19 Stefan N, Kantartzis K, Häring HU. Causes and Metabolic Consequences of Fatty Liver. Endocr Rev 2008; 29: 939-960.
20 Stefan N, Kantartzis K, Machann J. et al. Identification and Characterization of Metabolically Benign Obesity in Humans. Arch Intern Med 2008; 168: 1609-1616.
21 Stefan N, Schick F, Häring HU. Sex hormone-binding globulin and risk of type 2 diabetes. N Engl J Med 2009; 361: 2675-2676.
22 Stefan N, Thamer C, Staiger H. et al. Genetic variations in PPARD and PPARGC1A determine mitochondrial function and change in aerobic physical fitness and insulin sensitivity during lifestyle intervention. J Clin Endocrinol Metab 2007; 92: 1827-1833.
23 Sumida Y, Nakashima T, Yoh T. et al. Serum thioredoxin levels as a predictor of steatohepatitis in patients with nonalcoholic fatty liver disease. J Hepatol 2003; 38: 32-38.
24 Szendroedi J, Chmelik M, Schmid AI. et al. Abnormal hepatic energy homeostasis in type 2 diabetes. Hepatology 2009; 50 (04) 1079-1086.
25 Thamer C, Machann J, Stefan N. et al. Variations in PPARD Determine the Change in Body Composition during Lifestyle Intervention: A Whole-Body Magnetic Resonance Study. J Clin Endocrinol Metab 2008; 93: 1497-1500.
26 Weikert C, Stefan N, Schulze MB. et al. Plasma Fetuin-A Levels and the Risk of Myocardial Infarction and Ischemic Stroke. Circulation 2008; 118: 2555-2562.