ANALISI DEL METABOLISMO GLUCIDICO IN PAZIENTI CIRROTICI SOTTOPOSTI A TRAPIANTO EPATICO: RUOLO DELLA SECREZIONE BETA CELLULARE E DELL'INSULINORESISTENZA.

Impaired glucose metabolism is frequently described in cirrhotic patients. The pathogenesis of diabetes mellitus (DM) in this population is complex and not precisely known. Insulin resistance (IR) plays a central role in the glucose metabolism disturbance and it has been speculated that genetic and environmental factors and some etiologic agents in liver disease impair insulin secretion. Aim of the study: evaluate β cell secretion and insulin sensitivity in a cohort of cirrhotic patients undergoing liver transplantation (LT). 107 cirrhotic patients (31 female e 76 male) were evaluated before LT. The patients who underwent LT were evaluated 3, 6, 12 months after surgery. To evaluate insulin resistance HOMA-IR was used. To assess the β cell secretion, a state-of-art modelling of glucose/C-peptide curves during OGTT was used. Two outputs were provided: dynamic evaluation (1st phase) and proportional evaluation (2nd phase). Before LT the prevalence of DM and prediabetes (pre DM) were 50.5% and 31.8 % respectively. DM patients showed a lower insulin secretion (both 1st and 2nd phase) and tended to have higher HOMA-IR when compared to pre DM and non DM subjects. After LT glucose metabolism improved (impaired glucose metabolism: 6 months 61.1%, 12 months 65.6%). HOMA-IR was decreased (pre LT: 5.48±5.14, 3 months post LT: 2.17±1.62, 6 months post LT: 2.28±1.44, 12 months post LT: 2.36±1.73 P=0.0017). No differences in β cell secretion was found. When the population who underwent LT was divided in 2 groups according to the improvement or not of glucose metabolism, higher insulin secretion was found in improved subjects (2nd phase). No differences in HOMA-IR, age, duration of hepatic disease, family history of type 2 DM, immunosuppressive therapy were observed. In conclusion IR and reduced insulin secretion was observed in cirrhotic diabetic patients. After LT an improved glucose metabolism was observed. Insulin sensitivity was increased in all patients and higher β cell secretion was observed only in subjects with improved glucose metabolism.