Both β-cell dysfunction and insulin resistance are primary determinants of diabetes mellitus in patients with liver cirrhosis candidate to organ transplant
V Grancini1, E Lunati1, L Boselli2, B Masserini1, D Zimbalatti1, F Agnelli3, R Bonadonna2, P Beck-Peccoz1 & E Orsi1
Background: Impaired glucose (G) regulation (IGR) and diabetes mellitus (DM) are common in patients with liver cirrhosis. DM development has been associated to advanced liver disease (LD) and HCV infection. The relative roles played by insulin secretion and action, advanced LD and HCV infection in DM are somewhat unclear.
Aim of the study: To assess in cirrhotic patients candidate to organ transplantation with no history of G abnormalities: i) prevalence of altered G homeostasis; ii) β-cell function (βF); and iii) insulin resistance.
Materials and methods: 104 patients, 33M/71F, age 53±9 years, with liver cirrhosis (HCV +/HCV−=44/60), with normal fasting G (5.2±0.11 mmol/l) and with HbA1c of 4.9±0.08%. βF was assessed by state-of-art modeling of G/C-peptide curves during a 180′ sampled OGTT, thereby providing the β-cell responses to the rate of G increase (derivative control: DC) and to G concentration (proportional control: PC). Insulin resistance was estimated by the HOMA index (HOMA-IR).
Results: 13 patients had normal G regulation (NGR), 35 had IGR, 56 had DM. HOMA-IR steadily increased with declining G tolerance (P=0.065), and it was higher in HCV+ than in HCV- patients (5.7±0.7 vs 4.5±0.5, P=0.023). Both DC and PC gradually declined from NGR to IGR to DM (P<0.01 for both). Child-Pugh score, HCV infection and alcoholic LD were neither related to alterations in G regulation (P=0.130.99) nor to βF (P=0.550.88). In a multivariate model, HOMA-IR (P=0.014) and betaF (P=0.017), but no LD related parameter (P=0.400.78), were independent predictors of DM.
Conclusions: In cirrhotic patients, altered G homeostasis, including DM, is due primarily to alterations in both βF and insulin action, neither of which apparently is influenced by alcohol or severity of LD. HCV infection might play a role in deteriorating G homeostasis via insulin resistance.
Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.