Immunogenetic susceptibility to diabetes mellitus in patients with liver disease

Genetic, environmental, metabolic and infectious influences, such as hepatitis C virus (HCV) infection, are thought to impact on the development of diabetes in patients with liver disease. As specific human leucocyte antigen (HLA) alleles provide the major genetic risk factors for type 1 diabetes, our aim was to investigate whether HLA class I and II alleles constitute additional risk factors for diabetes in patients with liver disease.

We evaluated two independent databases of 193 and 728 adult patients with chronic liver disease for the diagnosis of diabetes and the presence of specific HLA subtypes.

In each database, 24 and 19% of patients met criteria for diabetes. In the first database, specific class I and II alleles were observed more frequently in diabetics compared with non-diabetics: Cw7 (50 vs. 32%, P=0.04), DR51 (17 vs. 3%P=0.003) and DQ6 (37 vs. 18%, P=0.02). In the second database, DQ6 was observed in 16% of diabetics vs. 8% of non-diabetics (P=0.04). The DR2-DR51-DQ6 haplotype was higher in patients with diabetes in both databases (22 vs.7%, P=0.02 and 12 vs. 5%, P=0.02). In a subgroup analysis of patients with HCV infection, increased frequencies of Cw7, DR2/DR51, DQ6 and DR2-DR51-DQ6 were also observed to be higher in subjects with diabetes compared with those without diabetes.

Patients with chronic liver disease, especially those with HCV infection, have an immunogenetic risk for diabetes characterized by the presence of Cw7, DR51, DQ6 and DR2-DR51-DQ6.