Simon TG, et al. - This study was performed to investigate whether type 2 diabetes (T2D), metabolic comorbidities were correlated with the risk of hepatocellular carcinoma (HCC). In 2 prospective cohorts of U.S. men and women, the clinicians found an independent association between T2D and increased risk for HCC. With prolonged diabetes duration and with comorbid metabolic conditions, this risk was enhanced, suggesting the importance of insulin resistance in the pathogenesis of HCC.

Methods

• The clinicians enrolled 120,826 women in 1980 from the Nurses' Health Study (NHS), and 50,284 men in 1986 from the Health Professionals Follow-up Study (HPFS), and followed through 2012.
• They ascertained physician-diagnosed T2D at baseline and updated biennially.
• They used Cox proportional hazards regression models to calculate age- and multivariable adjusted hazard ratios (HRs) and 95% confidence intervals (CI) for incident HCC.

Results

• The clinicians documented 112 cases of HCC (69 women, 43 men) over 32 years of follow-up (4,488,410 person-years).
• T2D was correlated with an increased HCC risk (multivariable HR 4.59, 95% CI 2.98-7.07), as was an increasing T2D duration (P_trend < 0.001).
• The multivariable HRs for HCC were 2.96 (95% CI 1.57-5.60) for 0 to <2 years; 6.08 (95% CI 2.96-12.50) for 2 to <10 years; and 7.52 (95% CI 3.88-14.58) for ≥10 years, compared to non-diabetics.
• Increasing number of metabolic comorbidities (T2D, obesity, hypertension, dyslipidemia) was correlated with increased HCC risk (P_trend < 0.001).
• Compared to individuals without metabolic comorbidity, those with 4 metabolic comorbidities had an 8.1-fold increased HCC risk (95% CI 2.48-26.7).
• Neither insulin use nor oral hypoglycemic use was significantly associated with HCC risk in T2D (HR 2.04 [95% CI 0.69-6.09], and HR 1.45 [95% CI 0.69-3.07] respectively).