Diabetes, Plasma Glucose, and Incidence of Fatty Liver, Cirrhosis, and Liver Cancer: A Prospective Study of 0.5 Million People

Abstract

The prevalence of diabetes is increasing rapidly in China. However, evidence is limited about its effects on chronic liver diseases and liver cancer. We examined the associations of diabetes with chronic liver diseases and liver cancer and of random plasma glucose (RPG) with these liver diseases among participants without diabetes in Chinese adults and the possible interaction by hepatitis B virus (HBV) infection. The prospective China Kadoorie Biobank recruited 512,891 adults. During 10 years of follow-up, 2,568 liver cancer, 2,082 cirrhosis, 1,298 hospitalized nonalcoholic fatty liver disease (NAFLD), and 244 hospitalized alcoholic liver disease (ALD) cases were recorded among 503,993 participants without prior history of cancer or chronic liver diseases at baseline. Cox regression was used to estimate hazard ratios (HRs) for each disease by diabetes status (previously diagnosed or screen-detected) and, among those without previously diagnosed diabetes, by levels of RPG. Overall 5.8% of participants had diabetes at baseline. Compared to those without diabetes, individuals with diabetes had adjusted HRs of 1.49 (95% confidence interval 1.30-1.70) for liver cancer, 1.81 (1.57-2.09) for cirrhosis, 1.76 (1.47-2.16) for NAFLD, and 2.24 (1.42-3.54) for ALD. The excess risks decreased but remained elevated in those with longer duration. Among those without previously diagnosed diabetes, RPG was positively associated with liver diseases, with adjusted HRs per 1 mmol/L higher RPG of 1.04 (1.03-1.06) for liver cancer, 1.07 (1.05-1.09) for cirrhosis, 1.07 (1.05-1.10) for NAFLD, and 1.10 (1.05-1.15) for ALD. These associations did not differ by HBV infection.

Conclusion: In Chinese adults, diabetes and higher blood glucose levels among those without known diabetes are associated with higher risks of liver cancer and major chronic liver diseases.

Figure 1

Adjusted HRs for liver cancer (A) and chronic liver diseases (B, C, D) by levels of RPG. Black boxes represent the HRs for RPG among participants without previously diagnosed diabetes, and the open box represents previously diagnosed diabetes. RPG levels for participants without previously diagnosed diabetes at baseline were classified as ≤5.5 (reference), 5.6‐6.7, 6.8‐7.7, and ≥7.8 mmol/L. HRs were plotted against the mean RPG level in each group. The size of the points is proportional to the inverse of the variance of the log HRs. Analyses were stratified by sex, region, and HBsAg and adjusted for age at baseline, education, smoking, alcohol, total physical activity, and fasting time. 1 mmol/L = 18 mg/dL. Number of participants: ≤5.5, n = 239,518; 5.6‐6.7, n = 156,602; 6.8‐7.7, n = 50,537; ≥7.8 mmol/L, n = 33,647. Abbreviation: CI, confidence interval.