Impact of Non-Alcoholic Fatty Liver Disease on Metabolic Comorbidities in Type 2 Diabetes Mellitus

Abstract

Objective Type 2 Diabetes (T2D) is a major risk factor for the development and progression of non-alcoholic fatty liver disease (NAFLD). The published prevelance in epidemiological studies in this high risk population exceeds 70%. The aim of this analysis was to investigate the impact of NAFLD on T2D patients in Germany.

Methods Using the Disease Analyzer Database (IQVIA), T2D patients with NAFLD diagnosed in Germany were matched to a cohort without NAFLD controlling for age, sex, physician, index year and metabolic comorbidities and assessed for their risk of developing myocardial infarction, stroke, peripheral arterial disease (PAD) or chronic kidney disease, as well as the type of T2D treatment on NAFLD.

Results 2633 T2D patients with NAFLD were matched to 2633 T2D patients without liver disease. The ICD coded prevalence of NAFLD in patients with T2D in primary care in Germany was 7.8%. On regression analysis of patients with T2D , the presence of NAFLD was associated with a higher risk of renal failure during follow-up (HR 1.17, 95% CI 1.02–1.34, p=0.027). No association with the development of myocardial infarction, stroke, PAD or initiation of insulin therapy was observed. NAFLD patients were more frequently treated with DDP-4 inhibitors (+/-metformin) and less frequently with insulin within the first year of T2D diagnosis. The metabolic control (HbA1c range 6.5–7.5%) during follow-up did not differ between both groups.

Conclusion The coded prevalence of NAFLD in T2D patients is low, which is in contrast to published series. Enhancing disease awareness of NAFLD and screening recommendations in high risk populations will be beneficial for the active management of these patients.

Key words

liver disease - cirrhosis - metabolic comorbidities - disease burden - hyperglycemia

Publikationsverlauf

Eingereicht: 03. Dezember 2020
Eingereicht: 10. Januar 2021

Angenommen: 29. Januar 2021

Artikel online veröffentlicht:
18. Februar 2021

• References

• 1 Lazarus JV, Colombo M, Cortez-Pinto H. et al. NAFLD - sounding the alarm on a silent epidemic. Nat Rev Gastroenterol Hepatol 2020; 17: 377-379
• 2 Younossi ZM, Golabi P, de Avila L. et al. The global epidemiology of NAFLD and NASH in patients with type 2 diabetes: A systematic review and meta-analysis. J Hepatol 2019;
• 3 American Diabetes A. 4. Comprehensive Medical Evaluation and Assessment of Comorbidities: Standards of Medical Care in Diabetes-2020. Diabetes Care 2020; 43: S37-S47
• 4 Taylor RS, Taylor RJ, Bayliss S. et al. Association Between Fibrosis Stage and Outcomes of Patients With Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis. Gastroenterology 2020; 158: 1611-1625
• 5 Labenz C, Huber Y, Kalliga E. et al. Predictors of advanced fibrosis in non-cirrhotic non-alcoholic fatty liver disease in Germany. Aliment Pharmacol Ther 2018; 48: 1109-1116
• 6 Kaps L, Labenz C, Galle PR. et al. Non-alcoholic fatty liver disease increases the risk of incident chronic kidney disease. United European. Gastroenterol J 2020; 2050640620944098
• 7 Labenz C, Huber Y, Michel M. et al. Impact of NAFLD on the incidence of cardiovascular diseases in a primary care population in Germany. Dig Dis Sci 2020; 65: 2112-2119
• 8 Belfort R, Harrison SA, Brown K. et al. A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis. N Engl J Med 2006; 355: 2297-2307
• 9 Armstrong MJ, Gaunt P, Aithal GP. et al. Liraglutide safety and efficacy in patients with non-alcoholic steatohepatitis (LEAN): A multicentre, double-blind, randomised, placebo-controlled phase 2 study. Lancet 2016; 387: 679-690
• 10 Newsome PN, Buchholtz K, Cusi K. et al. A placebo-controlled trial of subcutaneous semaglutide in nonalcoholic steatohepatitis. N Engl J Med 2020;
• 11 Zhang H, Gao C, Fang L. et al. Metformin and reduced risk of hepatocellular carcinoma in diabetic patients: A meta-analysis. Scand J Gastroenterol 2013; 48: 78-87
• 12 Michel M, Kalliga E, Labenz C. et al. A young patient with type 2 diabetes associated non-alcoholic steatohepatitis, liver cirrhosis, and hepatocellular carcinoma. Z Gastroenterol 2020; 58: 57-62
• 13 Kogiso T, Sagawa T, Kodama K. et al. Long-term outcomes of non-alcoholic fatty liver disease and the risk factors for mortality and hepatocellular carcinoma in a Japanese population. J Gastroenterol Hepatol 2020;
• 14 Gehrke N, Schattenberg JM. Metabolic inflammation-a role for hepatic inflammatory pathways as drivers of comorbidities in nonalcoholic fatty liver disease?. Gastroenterology 2020; 158: 1929-1947
• 15 Rathmann W, Bongaerts B, Carius HJ. et al. Basic characteristics and representativeness of the German Disease Analyzer database. International Journal of Clinical Pharmacology and Therapeutics 2018; 56: 459-466
• 16 Alexander M, Loomis AK, van der Lei J. et al. Risks and clinical predictors of cirrhosis and hepatocellular carcinoma diagnoses in adults with diagnosed NAFLD: real-world study of 18 million patients in four European cohorts. BMC Med 2019; 17: 95
• 17 Dulai PS, Singh S, Patel J. et al. Increased risk of mortality by fibrosis stage in nonalcoholic fatty liver disease: Systematic review and meta-analysis. Hepatology 2017; 65: 1557-1565
• 18 Ekstedt M, Hagstrom H, Nasr P. et al. Fibrosis stage is the strongest predictor for disease-specific mortality in NAFLD after up to 33 years of follow-up. Hepatology 2015; 61: 1547-1554
• 19 Stepanova M, Younossi ZM. Independent association between nonalcoholic fatty liver disease and cardiovascular disease in the US population. Clin Gastroenterol Hepatol 2012; 10: 646-650
• 20 Sinn DH, Kang D, Chang Y. et al. Non-alcoholic fatty liver disease and the incidence of myocardial infarction: A cohort study. J Gastroenterol Hepatol 2019;
• 21 Targher G, Bertolini L, Poli F. et al. Nonalcoholic fatty liver disease and risk of future cardiovascular events among type 2 diabetic patients. Diabetes 2005; 54: 3541-3546
• 22 Newsome P, Francque S, Harrison S. et al. Effect of semaglutide on liver enzymes and markers of inflammation in subjects with type 2 diabetes and/or obesity. Aliment Pharmacol Ther 2019; 50: 193-203