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Prevalence of hepatic steatosis in patients with type 2 diabetes and response to glucose-lowering treatments. A multicenter retrospective study in Italian specialist care

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Abstract

Aim

Type 2 diabetes (T2D) is a risk factor for metabolic dysfunction-associated fatty liver disease (MAFLD), which is becoming the commonest cause of chronic liver disease worldwide. We estimated MAFLD prevalence among patients with T2D using the hepatic steatosis index (HSI) and validated it against liver ultrasound. We also examined whether glucose-lowering medications (GLM) beneficially affected HSI.

Methods

We collected data from 46 diabetes clinics (n = 281,381 T2D patients), extracted data to calculate HSI and validated it against ultrasound-detected hepatic steatosis. We then examined changes in HSI among patients with a follow-up visit within 1 year after initiating newer GLMs.

Results

MAFLD (defined by HSI > 36, i.e., a high probability of steatosis) was present in 76.3% of the 78,895 included patients, while only 2.7% had HSI < 30 (low probability of steatosis). After age- and sex-adjusting, higher HSI was associated with higher prevalence of chronic kidney disease (odds ratio 1.35; 95%CI 1.22–1.51) and macroangiopathy (odds ratio 1.18; 95%CI 1.07–1.30). Among 2,179 subjects in the validation cohort, the prevalence of MAFLD was 67.8% and was greater in those with high HSI. Performance of HSI for ultrasound-detected MAFLD was moderate (AUROC 0.70), yet steatosis prevalence was > threefold higher among subjects with HSI > 36 than among those with HSI < 30. Notably, HSI declined significantly ~ 6 months after initiation of dapagliflozin or incretin-based therapies, but not gliclazide.

Conclusion

About three quarters of patients with T2D have HSI values suggestive of MAFLD, a condition associated with macroangiopathy and nephropathy. Treatment with dapagliflozin or incretin therapies might improve MAFLD in T2D.

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Data availability

Original data are available from the corresponding author at a reasonable request.

References

  1. Targher G et al (2007) Prevalence of nonalcoholic fatty liver disease and its association with cardiovascular disease among type 2 diabetic patients. Diabetes Care 30(5):1212–1218

    Article  Google Scholar 

  2. Rodríguez-Tajes S, Pocurull A, Castillo J, Casanova G, Vega L, Lens S, Mariño Z, Londoño MC, Forner A, Torres F, Forns X (2020) Hepatitis C-related cirrhosis will be a marginal cause of hospital admissions in the near future. J Hepatol 73(6):1360–1367

    Article  Google Scholar 

  3. Targher G et al (2005) Nonalcoholic fatty liver disease and risk of future cardiovascular events among type 2 diabetic patients. Diabetes 54(12):3541–3546

    Article  CAS  Google Scholar 

  4. Targher G et al (2008) Non-alcoholic fatty liver disease is independently associated with an increased prevalence of chronic kidney disease and proliferative/laser-treated retinopathy in type 2 diabetic patients. Diabetologia 51(3):444–450

    Article  CAS  Google Scholar 

  5. Anstee QM, Targher G, Day CP (2013) Progression of NAFLD to diabetes mellitus, cardiovascular disease or cirrhosis. Nat Rev Gastroenterol Hepatol 10(6):330–344

    Article  CAS  Google Scholar 

  6. Dougherty JA, Guirguis E, Thornby KA (2020) A systematic review of newer antidiabetic agents in the treatment of nonalcoholic fatty liver disease. Ann Pharmacother 55:65–79

    Article  Google Scholar 

  7. Byrne CD, Targher G (2015) NAFLD: a multisystem disease. J Hepatol 62(1 Suppl):S47-64

    Article  Google Scholar 

  8. EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. J Hepatol 2016. 64(6): 1388–402.

  9. Ciardullo S, Sala I, Perseghin G (2020) Screening strategies for nonalcoholic fatty liver disease in type 2 diabetes: Insights from NHANES 2005–2016. Diabetes Res Clin Pract 167:108358

    Article  CAS  Google Scholar 

  10. Fedchuk L et al (2014) Performance and limitations of steatosis biomarkers in patients with nonalcoholic fatty liver disease. Aliment Pharmacol Ther 40(10):1209–1222

    Article  CAS  Google Scholar 

  11. Lee JH et al (2010) Hepatic steatosis index: a simple screening tool reflecting nonalcoholic fatty liver disease. Dig Liver Dis 42(7):503–508

    Article  CAS  Google Scholar 

  12. Guiu B et al (2012) Prediction for steatosis in type-2 diabetes: clinico-biological markers versus 1H-MR spectroscopy. Eur Radiol 22(4):855–863

    Article  Google Scholar 

  13. Fadini GP et al (2017) Rationale and design of the DARWIN-T2D (DApagliflozin Real World evIdeNce in Type 2 Diabetes): a multicenter retrospective nationwide Italian study and crowdsourcing opportunity. Nutr Metab Cardiovasc Dis 27(12):1089–1097

    Article  CAS  Google Scholar 

  14. Fadini GP et al (2018) Use and effectiveness of dapagliflozin in routine clinical practice: An Italian multicentre retrospective study. Diabetes Obes Metab 20(7):1781–1786

    Article  CAS  Google Scholar 

  15. Levey AS et al (2009) A new equation to estimate glomerular filtration rate. Ann Intern Med 150(9):604–612

    Article  Google Scholar 

  16. Fadini GP et al (2019) Effectiveness of dapagliflozin versus comparators on renal endpoints in the real world: a multicentre retrospective study. Diabetes Obes Metab 21(2):252–260

    Article  CAS  Google Scholar 

  17. Eslam M et al (2020) A new definition for metabolic dysfunction-associated fatty liver disease: An international expert consensus statement. J Hepatol 73(1):202–209

    Article  Google Scholar 

  18. Ciardullo S et al (2020) Screening for non-alcoholic fatty liver disease in type 2 diabetes using non-invasive scores and association with diabetic complications. BMJ Open Diabetes Res Care 8(1):e000904. https://doi.org/10.1136/bmjdrc-2019-000904

    Article  PubMed  PubMed Central  Google Scholar 

  19. Singh A et al (2018) The utility of noninvasive scores in assessing the prevalence of nonalcoholic fatty liver disease and advanced fibrosis in type 2 diabetic patients. J Clin Gastroenterol 52(3):268–272

    Article  Google Scholar 

  20. Grecian SM et al (2020) Non-invasive risk scores do not reliably identify future cirrhosis or hepatocellular carcinoma in Type 2 diabetes: The Edinburgh type 2 diabetes study. Liver Int

  21. Mantovani A et al (2020) Efficacy and safety of anti-hyperglycaemic drugs in patients with non-alcoholic fatty liver disease with or without diabetes: An updated systematic review of randomized controlled trials. Diabetes Metab 46:427–441

    Article  CAS  Google Scholar 

  22. Tang W et al (2016) Comparative efficacy of anti-diabetic agents on nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized and non-randomized studies. Diabetes Metab Res Rev 32(2):200–216

    Article  Google Scholar 

  23. Latva-Rasku A et al (2019) The SGLT2 inhibitor dapagliflozin reduces liver fat but does not affect tissue insulin sensitivity: a randomized, double-blind, placebo-controlled study with 8-week treatment in type 2 diabetes patients. Diabetes Care 42(5):931–937

    Article  CAS  Google Scholar 

  24. Kuchay MS et al (2018) Effect of empagliflozin on liver fat in patients with type 2 diabetes and nonalcoholic fatty liver disease: a randomized controlled trial (E-LIFT Trial). Diabetes Care 41(8):1801–1808

    Article  CAS  Google Scholar 

  25. Kinoshita T et al (2020) Comparison of the effects of three kinds of glucose-lowering drugs on non-alcoholic fatty liver disease in patients with type 2 diabetes: a randomized, open-label, three-arm, active control study. J Diabetes Investig 11(6):1612–1622

    Article  CAS  Google Scholar 

  26. Johansson L et al (2020) Dapagliflozin plus saxagliptin add-on to metformin reduces liver fat and adipose tissue volume in patients with type 2 diabetes. Diabetes Obes Metab 22(7):1094–1101

    Article  CAS  Google Scholar 

  27. Gastaldelli A et al (2020) Exenatide and dapagliflozin combination improves markers of liver steatosis and fibrosis in patients with type 2 diabetes. Diabetes Obes Metab 22(3):393–403

    Article  CAS  Google Scholar 

  28. Mittag-Roussou V et al (2020) Noninvasive monitoring of liver fat during treatment with GLP-1 analogues and SGLT-2 inhibitors in a real-world setting. Endocrinol Diabetes Metab 3(3):e00131

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank Alessia Russo, Italian Diabetes Society, for the invaluable technical support.

Composition of the DARWIN-T2D network: Agostino Consoli and Gloria Formoso (Dipartimento di Medicina e Scienze dell’Invecchiamento—Università Degli studi G. D’Annunzio di Chieti-Pescara); Giovanni Grossi (Ospedale San Francesco di Paola—Azienda Sanitaria Provinciale di Cosenza); Achiropita Pucci (Azienda Sanitaria Provinciale di Cosenza); Giorgio Sesti and Francesco Andreozzi (Azienda Ospedaliero Universitaria di Catanzaro); Giuseppe Capobianco (Azienda Sanitaria Locale Napoli 2 Nord); Adriano Gatti (Ospedale San Gennaro dei Poveri—Azienda Sanitaria Locale Napoli 1 Centro); Riccardo Bonadonna, Ivana Zavaroni and Alessandra Dei Cas (Azienda Ospedaliero Universitaria di Parma); Giuseppe Felace (Ospedale di Spilimbergo—Azienda per l’Assistenza Sanitaria n.5 Friuli Occidentale); Patrizia Li Volsi (Ospedale di Pordenone—Azienda per l’Assistenza Sanitaria n.5 Friuli Occidentale); Raffaella Buzzetti and Gaetano Leto (Ospedale Santa Maria Goretti—Azienda Sanitaria Locale di Latina); Gian Pio Sorice (Fondazione Policlinico Universitario A. Gemelli, Roma); Paola D’Angelo (Ospedale Sandro Pertini—Azienda Sanitaria Locale Roma 2); Susanna Morano (Azienda Ospedaliera Universitaria Policlinico Umberto I, Roma); Antonio Carlo Bossi (Ospedale di Treviglio—Azienda Socio Sanitaria Territoriale Bergamo Ovest); Edoardo Duratorre (Ospedale Luini Confalonieri di Luino—Azienda Socio Sanitaria Territoriale Sette Laghi); Ivano Franzetti (Ospedale Sant’Antonio Abate di Gallarate—Azienda Socio Sanitaria Territoriale Valle Olona); Paola Silvia Morpurgo (Ospedale Fatebenefratelli—Azienda Socio Sanitaria Territoriale Fatebenefratelli Sacco); Emanuela Orsi (Fondazione IRCCS Ca’ Granda—Ospedale Maggiore Policlinico di Milano); Fabrizio Querci (Ospedale Pesenti Fenaroli di Alzano Lombardo—Azienda Socio Sanitaria Territoriale Bergamo Est); Massimo Boemi† and Federica D’Angelo (Presidio Ospedaliero di Ricerca INRCA-IRCCS di Ancona); Massimiliano Petrelli (Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona); Gianluca Aimaretti and Ioannis Karamouzis (Azienda Ospedaliero Universitaria Maggiore della Carità di Novara); Franco Cavalot (Azienda Ospedaliero Universitaria San Luigi Gonzaga, Orbassano); Giuseppe Saglietti† (Ospedale Madonna del Popolo di Omegna—Azienda Sanitaria Locale Verbano Cusio Ossola); Giuliana Cazzetta (Casa della Salute, Ugento—Distretto Socio Sanitario Gagliano del Capo—Azienda Sanitaria Locale di Lecce); Silvestre Cervone (Presidio ospedaliero San Marco in Lamis—Distretto Socio Sanitario San Marco in Lamis—Azienda Sanitaria Locale di Foggia); Eleonora Devangelio (Distretto Socio Sanitario di Massafra—Azienda Sanitaria Locale di Taranto); Olga Lamacchia (Azienda Ospedaliero Universitaria Ospedali Riuniti di Foggia); Salvatore Arena (Ospedale Umberto I—Azienda Sanitaria Provinciale di Siracusa); Antonino Di Benedetto (Azienda Ospedaliera Universitaria Policlinico G. Martino di Messina); Lucia Frittitta (Azienda Ospedaliera di Rilievo Nazionale e di Alta Specializzazione Garibaldi di Catania); Carla Giordano (Azienda Universitaria Policlinico Paolo Giaccone di Palermo); Salvatore Piro (Azienda Ospedaliera di Rilievo Nazionale e di Alta Specializzazione Garibaldi di Catania); Manfredi Rizzo, Roberta Chianetta and Carlo Mannina (Azienda Universitaria Policlinico Paolo Giaccone di Palermo); Roberto Anichini (Ospedale San Jacopo di Pistoia—Azienda USL Toscana Centro); Giuseppe Penno (Azienda Ospedaliero Universitaria Pisana); Anna Solini (Azienda Ospedaliera Universitaria Pisana); Bruno Fattor (Comprensorio Sanitario di Bolzano—Azienda Sanitaria della Provincia Autonoma di Bolzano); Enzo Bonora and Massimo Cigolini (Azienda Ospedaliero Universitaria Integrata di Verona); Annunziata Lapolla and Nino Cristiano Chilelli (Complesso Socio Sanitario Ai Colli—Azienda ULSS n.6 Euganea); Maurizio Poli (Ospedale Girolamo Fracastoro di San Bonifacio—Azienda ULSS n.9 Scaligera); Natalino Simioni and Vera Frison (Ospedale di Cittadella—Azienda ULSS n.6 Euganea); Carmela Vinci (Azienda ULSS n.4 Veneto Orientale).

Funding

The study was supported by the Italian Diabetes Society through a grant from Gilead Sciences.

Author information

Authors and Affiliations

  1. Department of Medicine, University of Padova, Via Giustiniani 2, 35128, Padova, Italy

    M. L. Morieri, N. Vitturi, A. Avogaro & G. P. Fadini

  2. Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Piazzale A. Stefani 1, 37126, Verona, Italy

    G. Targher

Authors
  1. M. L. Morieri
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  2. N. Vitturi
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  3. A. Avogaro
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  4. G. Targher
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  5. G. P. Fadini
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Consortia

DARWIN-T2D Network of the Italian Diabetes Society

  • Agostino Consoli
  • , Gloria Formoso
  • , Giovanni Grossi
  • , Achiropita Pucci
  • , Giorgio Sesti
  • , Francesco Andreozzi
  • , Giuseppe Capobianco
  • , Adriano Gatti
  • , Riccardo Bonadonna
  • , Ivana Zavaroni
  • , Alessandra DeiCas
  • , Giuseppe Felace
  • , Patrizia Li Volsi
  • , Raffaella Buzzetti
  • , Gaetano Leto
  • , Gian Pio Sorice
  • , Paola D’Angelo
  • , Susanna Morano
  • , Antonio Carlo Bossi
  • , Edoardo Duratorre
  • , Ivano Franzetti
  • , Paola Silvia Morpurgo
  • , Emanuela Orsi
  • , Fabrizio Querci
  • , Massimo Boemi
  • , Massimiliano Petrelli
  • , Gianluca Aimaretti
  • , Ioannis Karamouzis
  • , Franco Cavalot
  • , Giuseppe Saglietti
  • , Giuliana Cazzetta
  • , Silvestre Cervone
  • , Eleonora Devangelio
  • , Olga Lamacchia
  • , Salvatore Arena
  • , Antonino Di Benedetto
  • , Lucia Frittitta
  • , Carla Giordano
  • , Salvatore Piro
  • , Manfredi Rizzo
  • , Roberta Chianetta
  • , Carlo Mannina
  • , Roberto Anichini
  • , Giuseppe Penno
  • , Anna Solini
  • , Bruno Fattor
  • , Enzo Bonora
  • , Massimo Cigolini
  • , Annunziata Lapolla
  • , Nino Cristiano Chilelli
  • , Maurizio Poli
  • , Natalino Simioni
  • , Vera Frison
  •  & Carmela Vinci

Contributions

The work submitted for publication is original and has not been published other than as an abstract and has not been submitted elsewhere for print or electronic publication consideration. Each author participated in the work in a substantive manner, in accordance with ICMJE authorship guidelines. All authors approved the final version of the manuscript.

Corresponding author

Correspondence to G. P. Fadini.

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Conflict of interest

MLM received lecture or advisory fees or grant support from Mylan, SlaPharma, Amryt Pharma and Servier. AA received research grants, lecture or advisory board fees from Merck Sharp & Dome, AstraZeneca, Novartis, Boeringher-Ingelheim, Sanofi, Mediolanum, Janssen, Novo Nordisk, Lilly, Servier, and Takeda. GPF received lecture fees or grant support from Abbott, AstraZeneca, Boehringer, Lilly, Merck-Sharp-Dome, Mundipharma, Novartis, Novo Nordisk, Sanofi, Servier. GT does not have any competing interest to declare.

Ethical approval

The study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki and was approved by the Ethical Committees of all participating centers.

Informed consent

The study used anonymous data and, based on National and International regulations, a waiver was applied to the requirement for the patient’s informed consent.

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The members of the DARWIN-T2D Network of the Italian Diabetes Society are given in Acknowledgement section.

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Morieri, M.L., Vitturi, N., Avogaro, A. et al. Prevalence of hepatic steatosis in patients with type 2 diabetes and response to glucose-lowering treatments. A multicenter retrospective study in Italian specialist care. J Endocrinol Invest 44, 1879–1889 (2021). https://doi.org/10.1007/s40618-021-01501-y

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