The relationship between zonulin level and indicators of carbohydrate metabolism in patients with metabolic-associated fatty liver disease combined with type 2 diabetes mellitus

This is the authors' abstract. We don't add key points for this paper.

Background. The purpose of the study was to determine the relationship between serum zonulin level and indicators of carbohydrate metabolism in patients with metabolic-associated fatty liver disease (MAFLD) combined with type 2 diabetes mellitus (DM). Materials and methods. The study involved 78 patients with MAFLD and type 2 DM, who were examined and divided into 2 groups. The first group consisted of 42 patients with МAFLD and type 2 DM without small intestinal bacterial overgrowth (SIBO). The second group included 36 patients with МAFLD and type 2 DM in combination with SIBO. The control group consisted of 20 practically healthy persons. The content of serum zonulin was determined by the enzyme-linked immunosorbent assay (ELISA) using the IDK Zonulin ELISA test systems, KR5601 (Immundiagnostik AG, Germany). Results. The study of the content of serum zonulin revealed its significant increase in patients with MAFLD combined with type 2 DM without SIBO — (70.78 ± 2.09) ng/ml and with SIBO — (82.64 ± 2.71) ng/ml compared to the control group — (13.26 ± 1.53) ng/ml (p < 0.001). When comparing the parameters of carbohydrate metabolism, a significant increase was found in fasting blood glucose — (10.25 ± 0.30) mmol/l and (10.43 ± 0.33) mmol/l, insulin — (22.66 ± 0.64 mU/l) and (22.96 ± 0.70) mU/l, НOMA-IR — 10.4 ± 0.4 and 10.87 ± 0.66, HbA1c — 8.89 (8.03–9.95) % and 8.61 (8.02–10.34) %, C-peptide — (5.44 ± 0.06) ng/ml and (5.95 ± 0.10) ng/ml in patients with MAFLD combined with type 2 diabetes without and with SIBO, respectively, as compared to the control group (p < 0.001). Indicators of fasting plasma glucose, insulin, HbA1c and the НOMA-IR in patients of the first and second groups did not differ significantly (p > 0.05), and the level of C-peptide was increased significantly in patients of the second group compared to the first one (p < 0.001). Correlation analysis between serum zonulin level and indicators of carbohydrate metabolism in patients with MAFLD combined with type 2 DM without and with SIBO found a moderate positive correlation with levels of glucose, insulin and HOMA-IR, and a weak correlation was found between serum zonulin level with HbA1c and C-peptide. Conclusions. An increase in serum zonulin was found in patients with MAFLD combined with type 2 DM without and with SIBO, which indicated an increase in the intestinal permeability. The content of serum zonulin was associated with hyperglycemia and hyperinsulinemia. Thus, impaired intestinal permeability is pathogenetically associated with the development of insulin resistance.

Serum zonulin was associated with hyperglycemia and insulin resistance in MAFLD with T2DM; leaves open whether permeability-targeted interventions alter outcomes.