We read with interest the article by Cho et al. (1), which demonstrated that an elevated level of alanine aminotransferase (ALT) was associated with risk of type 2 diabetes in their community-based study of 10,038 participants. Excluding diabetic individuals and those with hepatitis B (HBV) or C (HCV) infection (15.1%), the authors concluded that the highest quartile of ALT activity carried a twofold increase in the risk of diabetes independently of conventional risk factors.

Between June 2002 and May 2004, we also conducted a large-scale community-based study of 9,932 residents aged 40–65 years in Taiwan, an HBV-hyperendemic country (2). The prevalence of anti-HCV+, HBV surface antigen positive (HBsAg+), and diabetic individuals was 6.5, 13.1, and 12.5%, respectively. This HBV- and HCV-endemic area thus provided a better scope of view to observe the association between viral hepatitis infections and diabetes. Setting the highest quartile of ALT activity (>31.0 IU/l) into analysis among both HBV- and HCV-negative subjects (n = 8,060), elevated ALT level ranked as the most significant factor (odds ratio [OR] 1.71 [95% CI 1.46–1.99]) (P < 0.001) associated with diabetes in multivariate analyses, followed by male sex, BMI, and age.

Intriguingly, based on multivariate analyses, HCV viremia (OR 2.01 [95% CI 1.15–3.52]) (P = 0.01) played a more significant role than the highest quartile of ALT activity (1.75 [1.53–2.01]) (P < 0.001) in the risk of diabetes among all 9,932 subjects. Thus, our study suggests that a significant link between HCV viremia and diabetes exists and also provides the epidemiological evidence addressing the diabetogenic role of HCV infection (3).

Type 2 diabetes is a common endocrine disorder encompassing multifactorial pathogenetic mechanisms. An abnormal liver function test in itself may be a biochemical manifestation of underlying metabolic disorders such as fatty liver disease and lipid and glucose abnormalities. Nonetheless, it may also be a direct clinical manifestation of a diabetogenic viral infection. Regarding type 2 diabetes prediction, our data imply that HCV contributes most highly to the risk of diabetes, followed by an HBV- and HCV-unrelated abnormal liver function test. These results also emphasize the importance of glucose abnormalities determination not only for subjects with abnormal liver function test but also for those with HCV infection.

Cho NH, Jang HC, Kim HR, Lee HK, Chan JCN, Lim S: Abnormal liver function test predicts type 2 diabetes: a community-based prospective study.
Diabetes Care
Huang JF, Dai CY, Hwang SJ, Ho CK, Hsiao PJ, Hsieh MY, Lee LP, Chen SC, Hsieh MY, Wang LY, Shin SJ, Chang WY, Chuang WL, Yu ML: Hepatitis C viremia increases the association with type 2 diabetes mellitus in a hepatitis B and C endemic area: an epidemiological link with virological implication.
Am J Gastroenterol
Lecube A, Hernández C, Genescà J, Esteban JI, Jard í R, Simó R: High prevalence of glucose abnormalities in patients with hepatitis C virus infection: a multivariate analysis considering the liver injury.
Diabetes Care