Patients with chronic liver diseases are at risk for diabetes even before development of cirrhosis
(2022) EASL International liver congress 2022 — Location: London (22.June.2022)
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- Background and Aims: The prevalence of insulin resistance (IR) and type 2 diabetes mellitus (T2DM) is higher in patients with cirrhosis, compared to control patients without liver disease. The exact mechanism for this is unknown but could include liver inflammation. In this study, we investigate whether cirrhosis is the primum movens of IR or if impaired insulin sensitivity is already present in non-cirrhotic patients with chronic liver diseases. Method: Patients were recruited and divided into three groups: control (CTL), active chronic liver disease without cirrhosis (CLD) and cirrhosis (CIR). In patients not taking pharmacological treatment for T2DM, IR was quantified using the homeostasis model assessment of insulin resistance (HOMA-IR). The proportion of patients treated for T2DM was recorded in each group. Additionally, HOMA-IR levels among different disease etiologies were compared. The study was approved by the local ethics committee. Results: 422 patients were included in our study, 16 were controls, 278 had a CLD and 128 were cirrhotic (CIR). The causes of liver disease were as follows: metabolic-dysfunction associated fatty liver disease (MAFLD, n=206), alcoholic liver disease (ALD, n=117), active chronic hepatitis C (HCV, n=59), other cause (n=24). IR, represented by a HOMA-IR value exceeding 2.5, is already present in patients with non-cirrhotic CLD (median HOMA-IR 4.0). HOMA-IR levels lie between those seen in CTL (median HOMA-IR 1.3) and CIR patients (median HOMA-IR 5.7), with a statistically significant difference between the three groups (p-value <0.001). Median glycemia in the CLD and CIR groups is the same (98 mg/dL and 99 mg/dL respectively) but insulinemia is different (101.5 pmol/L and 132.3 pmol/L respectively) resulting in distinct HOMA-IR values in CLD and CIR patients (p=0.018). Compared to CLD patients, patients in the CIR group are also characterised by a higher age, higher AST levels and a lower platelet count consistent with portal hypertension. The number of patients with T2DM is the same in the CLD and CIR groups (36.7 and 37.5 % respectively). Finally, HOMA-IR levels differ according to disease etiology (p-value <0.001): MAFLD and HCV associated liver disease are associated with higher levels of IR compared to ALD and other causes of CLD. Conclusion: Chronic liver disease is already a predisposing factor to T2DM, regardless of the presence of cirrhosis. Certain disease etiologies are associated with more severe IR. Cirrhosis is a factor which in itself elicits additional increase in insulin levels. The increased insulin levels in this group may be related to increased IR in this situation or to decreased insulin clearance due to portal hypertension.
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Bale, G. L., Clarembeau, F., Starkel, P., Dahlqvist, G., Horsmans, Y., & Lanthier, N. (2022). Patients with chronic liver diseases are at risk for diabetes even before development of cirrhosis. Journal of Hepatology, 7(Suppl 1), S736-7. https://hdl.handle.net/2078.5/165487 (Original work published 2022)