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Was bedeuten die neuen Diabetessubgruppen für Menschen mit Fettlebererkrankung?

What do the new diabetes subgroups mean for people with nonalcoholic fatty liver disease?

  • Leitthema
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Der Diabetologe Aims and scope

Zusammenfassung

Hintergrund

Die nichtalkoholische Fettlebererkrankung (NAFLD) ist die häufigste Lebererkrankung bei Erwachsenen in den westlichen Ländern und mit Diabetes mellitus Typ 2 assoziiert. Beide Erkrankungen stellen eine zunehmende Belastung der Gesundheitssysteme dar.

Ziel der Arbeit

Der rezente Vorschlag einer neuen Einteilung des Diabetes in 5 Diabetessubgruppen („Cluster“) wirft die Frage auf, ob sich diese Subgruppen auch bezüglich des Risikos für NAFLD unterscheiden.

Methoden

Es erfolgten eine Literaturrecherche der Originalarbeiten, Übersichtsartikel und Leitlinienempfehlungen zu Diabetessubgruppen und Analyse bezüglich NAFLD.

Ergebnisse

Unter allen Subgruppen des Diabetes haben Menschen mit dem schwer insulinresistenten Diabetes (SIRD) bereits innerhalb des ersten Jahres nach Diagnose einen erhöhten Leberfettgehalt sowie innerhalb von 5 Jahren anhand des Fibrosis-4-Indexes (FIB-4) Hinweise auf eine Progression der NAFLD zur Fibrose. Die SIRD-Subgruppe weist zudem eine komplexe Beziehung zum „Patatin-like phospholipase domain-containing 3“(PNPLA3)-Gentyp auf, der an sich mit erhöhtem Risiko für NAFLD und Fibrose, aber auch Insulinresistenz des Fettgewebes assoziiert ist. Diese Daten unterstreichen die Bedeutung der Insulinresistenz für NAFLD.

Diskussion

Das Wissen um neue Subgruppen des Diabetes und deren unterschiedliches Risiko für Diabetes-bedingte Komorbiditäten wie NAFLD erlaubt derzeit noch keine Empfehlungen für eine gezielte Therapie, erfordert aber kontrollierte Interventionsstudien zur Beurteilung der Bedeutung einer subgruppenspezifischen Behandlung für Menschen mit Diabetes mellitus und NAFLD.

Abstract

Background

Nonalcoholic fatty liver disease (NAFLD) is the most frequent liver disease in adults in Western countries and is associated with type 2 diabetes mellitus. Both diseases represent a growing burden on the healthcare systems.

Objective

The recent proposal of a novel classification of diabetes into five diabetes subgroups (clusters) raises the question whether these subgroups also differ with respect to the risk of NAFLD.

Methods

A literature search was performed for original articles, reviews and guideline recommendations referring to diabetes subgroups and an analysis regarding NAFLD.

Results

Among all diabetes subgroups, persons in the severe insulin-resistant diabetes (SIRD) cluster already exhibit increased hepatic lipid content within the first year after diagnosis as well as evidence for NAFLD progression to fibrosis within the following 5 years according to the fibrosis‑4 index (FIB-4). Furthermore, the SIRD subgroup shows a complex relationship with the patatin-like phospholipase domain-containing 3 (PNPLA3) genotype, which in turn is related to an increased risk of NAFLD and fibrosis, but also to adipose tissue insulin resistance. These data underline the relevance of insulin resistance for NAFLD.

Discussion

Knowledge of the new diabetes subgroups and their different risk of diabetes-related comorbidities, such as NAFLD, does not currently enable recommendations for a targeted therapy but necessitates controlled interventional trials to assess the relevance of a subgroup-specific treatment for people with diabetes mellitus and NAFLD.

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Literatur

  1. Ahlqvist E, Storm P, Käräjämäki A et al (2018) Novel subgroups of adult-onset diabetes and their association with outcomes: a data-driven cluster analysis of six variables. Lancet Diabetes Endocrinol 6:361–369

    Article  Google Scholar 

  2. Armstrong MJ, Gaunt P, Aithal GP et al (2016) Liraglutide safety and efficacy in patients with non-alcoholic steatohepatitis (LEAN): a multicentre, double-blind, randomised, placebo-controlled phase 2 study. Lancet 387:679–690

    Article  CAS  Google Scholar 

  3. Cassidy S, Hallsworth K, Thoma C et al (2015) Cardiac structure and function are altered in type 2 diabetes and non-alcoholic fatty liver disease and associate with glycemic control. Cardiovasc Diabetol 14:23

    Article  Google Scholar 

  4. Cusi K (2016) Treatment of patients with type 2 diabetes and non-alcoholic fatty liver disease: current approaches and future directions. Diabetologia 59:1112–1120

    Article  CAS  Google Scholar 

  5. Del Campo JA, Gallego-Duran R, Gallego P et al (2018) Genetic and epigenetic regulation in nonalcoholic fatty liver disease (NAFLD). Int J Mol Sci 19. https://doi.org/10.3390/ijms19030911

    Article  PubMed  PubMed Central  Google Scholar 

  6. Dennis JM, Shields BM, Henley WE et al (2019) Disease progression and treatment response in data-driven subgroups of type 2 diabetes compared with models based on simple clinical features: an analysis using clinical trial data. Lancet Diabetes Endocrinol 7:442–451

    Article  Google Scholar 

  7. Estes C, Anstee QM, Arias-Loste MT et al (2018) Modeling NAFLD disease burden in China, France, Germany, Italy, Japan, Spain, United Kingdom, and United States for the period 2016–2030. J Hepatol 69:896–904

    Article  Google Scholar 

  8. Estes C, Razavi H, Loomba R et al (2018) Modeling the epidemic of nonalcoholic fatty liver disease demonstrates an exponential increase in burden of disease. Hepatology 67:123–133

    Article  CAS  Google Scholar 

  9. European Association for the Study of The L, European Association for the Study Of D, European Association for the Study Of O (2016) EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. J Hepatol 64:1388–1402

    Google Scholar 

  10. Gerber L, Otgonsuren M, Mishra A et al (2012) Non-alcoholic fatty liver disease (NAFLD) is associated with low level of physical activity: a population-based study. Aliment Pharmacol Ther 36:772–781

    Article  CAS  Google Scholar 

  11. Kahl S, Gancheva S, Strassburger K et al (2020) Empagliflozin effectively lowers liver fat content in well-controlled type 2 diabetes: a randomized, double-blind, phase 4, placebo-controlled trial. Diabetes Care 43:298–305

    Article  CAS  Google Scholar 

  12. Kleiner DE, Brunt EM (2012) Nonalcoholic fatty liver disease: pathologic patterns and biopsy evaluation in clinical research. Semin Liver Dis 32:3–13

    Article  CAS  Google Scholar 

  13. Koehler EM, Plompen EP, Schouten JN et al (2016) Presence of diabetes mellitus and steatosis is associated with liver stiffness in a general population: The Rotterdam study. Hepatology 63:138–147

    Article  CAS  Google Scholar 

  14. Lee SS, Park SH, Kim HJ et al (2010) Non-invasive assessment of hepatic steatosis: prospective comparison of the accuracy of imaging examinations. J Hepatol 52:579–585

    Article  CAS  Google Scholar 

  15. Li L, Cheng WY, Glicksberg BS et al (2015) Identification of type 2 diabetes subgroups through topological analysis of patient similarity. Sci Transl Med 7:311r

    Google Scholar 

  16. Ratziu V (2017) Non-pharmacological interventions in non-alcoholic fatty liver disease patients. Liver Int 37(Suppl 1):90–96

    Article  Google Scholar 

  17. Roden M, Shulman GI (2019) The integrative biology of type 2 diabetes. Nature 576:51–60

    Article  CAS  Google Scholar 

  18. Roeb E, Steffen HM, Bantel H et al (2015) S2k Guideline non-alcoholic fatty liver disease. Z Gastroenterol 53:668–723

    Article  CAS  Google Scholar 

  19. Sanyal AJ, Chalasani N, Kowdley KV et al (2010) Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. N Engl J Med 362:1675–1685

    Article  CAS  Google Scholar 

  20. Tanabe H, Saito H, Kudo A et al (2020) Factors associated with risk of diabetic complications in novel cluster-based diabetes subgroups: a Japanese retrospective cohort study. J Clin Med 9. https://doi.org/10.3390/jcm9072083

    Article  PubMed  PubMed Central  Google Scholar 

  21. Tilg H, Moschen AR, Roden M (2017) NAFLD and diabetes mellitus. Nat Rev Gastroenterol Hepatol 14:32–42

    Article  CAS  Google Scholar 

  22. Tonnies T, Rockl S, Hoyer A et al (2019) Projected number of people with diagnosed Type 2 diabetes in Germany in 2040. Diabet Med 36:1217–1225

    Article  CAS  Google Scholar 

  23. Tovo CV, Villela-Nogueira CA, Leite NC et al (2019) Transient hepatic elastography has the best performance to evaluate liver fibrosis in non-alcoholic fatty liver disease (NAFLD). Ann Hepatol 18:445–449

    Article  CAS  Google Scholar 

  24. Udler MS, Kim J, Von Grotthuss M et al (2018) Type 2 diabetes genetic loci informed by multi-trait associations point to disease mechanisms and subtypes: A soft clustering analysis. PLoS Med 15:e1002654

    Article  Google Scholar 

  25. Williams CD, Stengel J, Asike MI et al (2011) Prevalence of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis among a largely middle-aged population utilizing ultrasound and liver biopsy: a prospective study. Gastroenterology 140:124–131

    Article  Google Scholar 

  26. Younes R, Bugianesi E (2018) Should we undertake surveillance for HCC in patients with NAFLD? J Hepatol 68:326–334

    Article  Google Scholar 

  27. Zaharia OP, Strassburger K, Knebel B et al (2020) Role of Patatin-like Phospholipase domain–containing 3 gene for hepatic lipid content and insulin resistance in diabetes. Diabetes Care. https://doi.org/10.2337/dc20-0329

    Article  PubMed  Google Scholar 

  28. Zaharia OP, Strassburger K, Strom A et al (2019) Risk of diabetes-associated diseases in subgroups of patients with recent-onset diabetes: a 5-year follow-up study. Lancet Diabetes Endocrinol 7:684–694

    Article  Google Scholar 

  29. Zein CO, Unalp A, Colvin R et al (2011) Smoking and severity of hepatic fibrosis in nonalcoholic fatty liver disease. J Hepatol 54:753–759

    Article  CAS  Google Scholar 

  30. Zou X, Zhou X, Zhu Z et al (2019) Novel subgroups of patients with adult-onset diabetes in Chinese and US populations. Lancet Diabetes Endocrinol 7:9–11

    Article  Google Scholar 

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Authors and Affiliations

  1. Institut für Klinische Diabetologie, Deutsches Diabetes-Zentrum (DDZ), Leibniz-Zentrum für Diabetes-Forschung, Heinrich-Heine-Universität Düsseldorf, Auf’m Hennekamp 65, 40225, Düsseldorf, Deutschland

    Benjamin Schröder &  Michael Roden

  2. Deutsches Zentrum für Diabetesforschung (DZD), Partner Düsseldorf, Düsseldorf, Deutschland

    Benjamin Schröder &  Michael Roden

  3. Univ. Klinik für Endokrinologie und Diabetologie, Medizinische Fakultät, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Deutschland

    Michael Roden

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  1. Benjamin Schröder
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Correspondence to Michael Roden.

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Interessenkonflikt

B. Schröder und M. Roden geben an, dass bezüglich dieses Beitrages kein Interessenkonflikt besteht.

Für diesen Beitrag wurden von den Autoren keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

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Schröder, B., Roden, M. Was bedeuten die neuen Diabetessubgruppen für Menschen mit Fettlebererkrankung?. Diabetologe 17, 20–25 (2021). https://doi.org/10.1007/s11428-020-00698-5

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  • DOI: https://doi.org/10.1007/s11428-020-00698-5

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