Elevated Liver Enzymes and Comorbidities in Type 2 Diabetes: A Population-Based Multicenter Analysis of 51,645 Patients of the DPV Database

Background: Awareness of fatty liver disease in people with diabetes is low and reliable epidemiological data on diabetes and liver enzymes are scarce. This population-based analysis of the DPV database assessed the prevalence of elevated liver enzymes and associated diabetes related comorbidities in type 2 diabetes (T2D).  Methods: This analysis comprises 281,245 patients with T2D between the age of 18 and 75 years from 501 diabetes centers from January 2010 until December 2019. Among these, complete demographic and concomitant data on liver enzymes were available in a total of 51,645 patients. Findings: Elevated liver enzymes were found in 40·2% of all patients. In contrast, only 8·6% of these patients were ICD-10 coded as nonalcoholic fatty liver disease (NAFLD) and/or nonalcoholic steatohepatitis (NASH), respectively. After adjustment for age, sex, diabetes duration, BMI, and HbA1c, a higher prevalence of arterial hypertension (p<·0001), dyslipidemia (p<·0001), peripheral artery disease (PAD) (p=·0029), myocardial infarction (p=·0003), coronary artery disease (CAD) (p=·0001), microalbuminuria (p<·0001), and chronic kidney disease (CKD) (p<·0001), respectively, was seen in patients with elevated versus normal liver enzymes. The prevalence of elevated liver enzymes was lowest in patients receiving SGLT2 inhibitors (SGLT2i) or a combination therapy of SGLT2i and GLP-1 receptor agonists (GLP-1RA).  Interpretation: Elevated liver enzymes are common in patients with T2D and clearly correlate with a higher prevalence of clinically relevant comorbidities. Assessing liver enzymes should be part of standard clinical routine in T2D to identify liver disease due to its predictive role for comorbidities and complications. Funding: This study was supported by the German Federal Ministry for Education, research within the German Center for Diabetes Research (DZD, 82DZD14A02), the German Robert Koch Institute (RKI), and the German Diabetes Association (DDG). Sponsors were not involved in data acquisition or analysis. Declaration of Interests: MR reports personal fees from Eli Lilly, Poxel S.A. Societe, Boehringer-Ingelheim, Terra Firma, Sanofi, Servier Labatories, Novo Nordisk, Fishawack Group, Novartis, Target Pharmasolutions, Gilead Sciences, Kenes Group, Bristol-Myers Squibb, Intercept Pharma, Inventiva, AstraZeneca, Pfizer, all outside the submitted work. SMS reports personal fees from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Daichii-Sanyo, Gilead, Ipsen, Lilly, MSD, Novartis, Novo Nordisk, Pfizer, Sandoz, Sanofi, and a grant from the German Diabetes Center (funded by the German Federal Ministry of Education and Research) for Diabetes research, all outside the submitted work. S.M., A.J.E., M.H., M.L., S.K., J.S., M.R., S.M.S. and R.W.H. declare no competing interest. Ethics Approval Statement: Analysis of anonymized routine data within the DPV initiative has been approved by the Ethics Committee of the Medical Faculty of the University of Ulm, Germany.