EUROPEAN ASSOCIATION FOR THE STUDY OF DIABETES OFFICIAL HIGHLIGHTS

EUROPEAN ASSOCIATION FOR THE STUDY OF DIABETES

Conference summaries


NAFLD & DIABETES

EASD/EASL Symposium: is NAFLD a risk for health in the context of diabetes?

Presented by: Michael Roden, MD
German Diabetes Center, Leibniz Institute at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
Stefano Romeo, MD
Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden
Elisabetta Bugianesi, MD, PhD
Division of Gastroenterology and Hepatology, University of Turin, Italy
  • Nonalcoholic fatty liver disease (NAFLD) is common in patients with type 2 diabetes.
  • Lifestyle intervention is the most effective treatment for NAFLD.

NAFLD and diabetes are common metabolic disorders that are often comorbid. Proper dietary and pharmacological treatment is essential for preventing NAFLD progression. Among many proposed treatments, weight reduction is the only approved option for NAFLD to date. However, it is not easy to maintain weight loss by lifestyle modification alone, and pharmacological treatments are helpful in this regard. Attention should be paid to the management of NAFLD and diabetes: efforts should be made to intervene early and individualise treatment of NAFLD in patients with diabetes.

  • NAFLD comprises a spectrum of liver disease spanning non-alcoholic fatty liver (NAFL)/fatty liver steatosis and non-alcoholic steatohepatitis (NASH), which are a cause of cirrhosis and hepatocellular carcinoma.
  • NAFLD and NASH are becoming increasingly prevalent as the epidemics of obesity and diabetes continue to increase.
  • NAFLD is also associated with metabolic risk factors, including increased waist circumference, arterial blood pressure, fasting glucose, serum triacylglycerols and HDL cholesterol.
  • Patients with type 2 diabetes have increased risk for NAFLD that is more than 5 times higher than that of the general population: more than half of patients with type 2 diabetes have NAFLD, over a third have NASH and almost 20% have advanced fibrosis.
  • As expected, mortality is increased in patients with both diabetes and NAFLD.
  • Recently, several clusters of diabetes phenotypes have been identified and, of note, those in the insulin-resistant clusters are at higher risk for NAFLD.
  • This highlights that the liver is a key organ in systemic metabolism, contributing substantially to the development of insulin resistance and type 2 diabetes.
  • The mechanisms underlying these processes are not entirely understood, but involve hepatic fat accumulation, alterations of energy metabolism and inflammatory signals derived from various cell types including immune cells.
  • Lipotoxins, mitochondrial function, cytokines and adipocytokines have also been proposed to play a major part in both NAFLD and type 2 diabetes.
  • Moreover, saturated fat ingestion rapidly increases hepatic lipid storage, energy metabolism and insulin resistance, which is accompanied by regulation of hepatic gene expression and signaling that may contribute to development of NAFLD.
  • In terms of treatment of NAFLD, lifestyle intervention can be effective: weight reductions of ≥10% can induce a near universal NASH resolution and fibrosis improvement by at least one stage.
  • Following a Mediterranean diet can reduce liver fat even without weight loss and is the most recommended dietary pattern for NAFLD.
  • Treatment of NAFLD includes aggressive management of diabetes and cardiovascular risk factors, although the role of controlling hyperglycaemia per se in patients with type 2 diabetes in improving NAFLD has not been confirmed; there is some evidence that thiazolidinediones may be of benefit, but there are no drugs approved to treat NAFLD.
  • NAFLD is known to have a strong genetic component.
  • Despite the tight association between NAFLD and insulin resistance, genome-wide association studies have identified genetic variants associated with NAFLD severity that do not correlate with insulin resistance.
  • Among these, the most widely studied gene is patatin-like phospholipase domain-containing protein 3 (PNPLA3).
  • Notably, the I148M PNPLA3 variant has been identified as the major common genetic determinant of NAFLD, and variants with moderate effect size in TM6SF2, MBOAT7 and GCKR have also been shown to have a significant contribution.
  • These genetic studies are thus offering new tools for targeted screening of high-risk individuals, and may aid in patient stratification, as well as prognostication.
  • Some of these newly identified genes, such as PNPLA3, may also represent viable therapeutic targets for NAFLD.
  • Considering the impact of NAFLD, screening has been advocated by some management guidelines in selected patients, but there is still some debate on the need for screening due to the high direct and indirect costs of testing, low predictive value of non-invasive tests, risks of liver biopsy and lack of effective treatments.
  • However, there appears to be general consensus that routine screening should not be employed in all patients.
  • According to the EASD-EASL (European Association for the Study of the Liver)-EASO (European Association for the Study of Obesity) joint guidelines, clinicians need to find common ground where all the major players in the metabolic field can cooperate, and share resources and clinical data, in order to translate ‘disease mongering’ into an effective way forward for patients and healthcare systems.
  • NAFLD can be diagnosed using clinical data, even if they are both non-specific and inaccurate.
  • Diagnostic exams include clinical/lab tests, imaging (ultrasound, MRI, spectroscopy, CT), biomarkers (e.g. FIBROSpect) and liver biopsy, with the latter being the most sensitive and specific.
  • In NAFLD, fibrosis is the most important predictor of long-term outcomes.
  • Although liver biopsy is the current imperfect gold standard for NASH diagnosis, a number of non-invasive tests are being developed.
  • Considering imaging biomarkers, fibrosis has no molecular signature that is detectable by current imaging techniques, and as such imaging attempts to detect fibrosis indirectly.
  • Many biomarkers have been proposed: stiffness, diffusion, perfusion, metabolites, and image texture.
  • The leading biomarker is likely “liver stiffness measurement or LSM” (elasticity) and related parameters with the rationale that fibrotic collagen deposition imparts parenchymal rigidity.
  • LSM can be used as a non-invasive marker to predict survival.
  • Regardless, patients with NASH, and especially those with fibrosis, will urgently need treatment and should be identified.
  • It seems apparent that the future use of combination tools (fibrosis scores, LSM and serum fibrosis tests) may improve the clinical utility in a cost-effective manner.
  • Lastly, it is clear that future management of NASH will require multidisciplinary care.
  • Management of NAFLD merits a call to action considering that there are several barriers to therapy and lack of unequivocal treatment targets.
  • Pioglitazone is the only agent that has been definitely shown to improve liver histology in patients with and without diabetes with biopsy-proven NASH, to date.
  • There are several new agents in the pipeline, and combination therapy will likely be the standard of care in the future.
  • Fibrosis is the most important predictor of long-term outcomes.
  • Some genes associated with NAFLD have been identified and may represent potential therapeutic targets.
  • Pioglitazone and vitamin E appear to be valid therapies for NAFLD, together with lifestyle intervention.

Key messages/Clinical Perspectives

  • Patients with NAFLD, especially those with fibrosis, need urgent treatment and should be identified.


References

References


  1. Zaharia OP, Strassburger K, Strom A, et al. Risk of diabetes-associated diseases in subgroups of patients with recent-onset diabetes: a 5-year follow-up study. Lancet Diabetes Endocrinol 2019 Sep;7(9):684-94

Presenter disclosure: The presenters has reported the follow relationships: M. Roden: Boehringer Ingelheim GmbH. Research Support; Self; Boehringer Ingelheim GmbH. Consultant; Self; Poxel SA. Research Support; Self; Danone Nutricia Early Life Nutrition, GlaxoSmithKline plc., Nutricia Advanced Medical Nutrition, Sanofi. S. Romeo: GSK, Amgen, Pfizer, Sanofi, Akcea Therapeutics, Ionis, Celgene, Camp4, AstraZeneca, MedaCorp., Forsitel Lab. E. Bugianesi: Boehringer Ingelheim, Genfit, Intercept, Ibsa, Innova, Sanofi, Janssen.

Medical writer: Patrick Moore, PhD

Reviewer: Marco Gallo, MD

Local reviewers: Marco Gallo, MD (Italia); Anna Novials Sardá, MD, PhD (España); Eric Renard, MD, PhD (France); Peter Schwarz, MD, PhD (Deutschland) 

Scientific Editor: Florian Toti, MD


CLINICAL TRIALS

T2D & NEPHROPATY

CREDENCE – Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy

Presented by: Carol Pollock, MBBS, PhD, FRACP, AAHMS; Hiddo Lambers Heerspink, PharmD, PhD; Kenneth W. Mahaffey, MD

PREVENTION

Results from the Anti-CD3 mAb (teplizumab) prevention trial

Presented by: Kevan Herold, MD; Peter S. Linsley, PhD

DIABETES & CVD

DECLARE study: call for action

Presented by: Itamar Raz, MD; Ofri Mosenzon, MD, MSc; Avivit Cahn, MD

T2D TREATMENT

VERIFY – Vildagliptin Efficacy in combination with metfoRmIn For earlY treatment of type 2 diabetes

Presented by: Chantal Mathieu, MD; Michael Stumvoli, MD; David R. Matthews, MD; Stefano del Prato, MD

DIABETES & HF

DAPA-HF: dapagliflozin and prevention of adverse-outcomes in heart failure

Presented by: Mikhail Kosiborod, MD; Silvio Inzucchi, MD

CV SAFETY

Results and implications of CAROLINA (CARdiOvascular Safety of LINAgliptin) comparing linagliptin vs glimepiride

Presented by: Julio Rosenstock, MD; Mark A. Espeland, MD; Steven E. Kahn, MD; Nikolaus Marx, MD; Bernard Zinman, MD; Darren McGuire, MD

T2D & CV PREVENTION

T1D DETERMINANTS

The Environmental Determinants of Diabetes in the Young (TEDDY) study

Presented by: Anette-Gabriele Ziegler, MD; Heikki Hyöty, MD, PhD
 

SYMPOSIA

NAFLD & DIABETES

EASD/EASL Symposium: is NAFLD a risk for health in the context of diabetes?

Presented by: Michael Roden, MD; Stefano Romeo, MD; Elisabetta Bugianesi, MD, PhD

HF & T2D

EASD/ESC Symposium: heart failure in type 2 diabetes

Presented by: M. Louis Handoko, MD; Javed Butler, MD, MPH, MBA

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