Associations between serum glucose, insulin, insulin resistance and the risk of incident primary liver cancer or chronic liver disease mortality: a nested case–control study

Background To evaluate the associations between pre-diagnostic levels of serum insulin, glucose and insulin resistance (HOMA-IR) and future risk of incident primary liver cancer (PLC) or chronic liver disease (CLD)-related mortality. Methods We used a nested case-control design to evaluate subjects over 22 years of follow-up. Glucose, insulin, and three markers of hepatitis B virus (HBV) and hepatitis C virus were measured in fasting baseline serum from 119 incident PLCs, 157 CLD-death cases and 512 matched controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression to estimate the associations between insulin, glucose, HOMA-IR and the risk of PLC or CLD death. Results Compared with the lowest quartile of insulin, multivariable adjusted models showed that subjects in the highest quartile had elevated odds of developing PLC (OR Q4/Q1 = 2.42, 95% CI = 1.26–4.75, P trend = 0.007), particularly in HBV-positive subjects ( P interaction = 0.040), and of CLD death (OR Q4/Q1 = 1.80, 95% CI = 1.02–3.21, P trend = 0.018). For glucose, in the HBV-positive group, subjects in the fourth quartile had an increased risk of PLC (OR Q4/Q1 = 2.18, 95% CI = 1.07–4.60, P trend = 0.009), and of CLD mortality (OR Q4/Q1 = 1.75, 95% CI = 0.95–3.28, P trend = 0.019). Subjects with the highest HOMA-IR values had a threefold risk of developing PLC (OR Q4/Q1 = 2.94, 95% CI = 1.54–5.87, P trend = 0.001), and a twofold risk of CLD death (OR Q4/Q1 = 2.20, 95% CI = 1.25–3.94, P trend = 0.005). Conclusions We found that serum insulin and HOMA-IR could potentially be risk factors for PLC or CLD death.