Journal
HEPATOLOGY
Volume 67, Issue 5, Pages 1797-1806Publisher
WILEY
DOI: 10.1002/hep.29660
Keywords
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Categories
Funding
- Nurses' Health Study infrastructure grant [UM1 CA186107]
- Nurses' Health Study program grant for cancer research [P01 CA87969]
- Health Professionals Follow Up Study infrastructure grant [UM1 CA167552]
- NIH [K24 DK078772, K23 DK099422, K23 DK099681, T32 CA009001, K24 DK098311, K07 CA188126]
- Career development award, American Gastroenterological Association
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Type 2 diabetes (T2D) is a risk factor for hepatocellular carcinoma (HCC). However, it is unknown whether T2D duration or additional metabolic comorbidities further contribute to HCC risk. From the Nurses' Health Study (NHS), 120,826 women were enrolled in 1980, and from the Health Professionals Follow-up Study (HPFS), 50,284 men were enrolled in 1986 and followed through 2012. Physician-diagnosed T2D was ascertained at baseline and updated biennially. Cox proportional hazards regression models were used to calculate age- and multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for incident HCC. Over 32 years of follow-up (4,488,410 person-years), we documented 112 cases of HCC (69 women, 43 men). T2D was associated 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). Compared to nondiabetics, the multivariable HRs for HCC were 2.96 (95% CI, 1.57-5.60) for 0-<2 years; 6.08 (95% CI, 2.96-12.50) for 2-<10 years; and 7.52 (95% CI, 3.88-14.58) for 10 years. Increasing number of metabolic comorbidities (T2D, obesity, hypertension, and dyslipidemia) was associated with increased HCC risk (P-trend<0.001); compared to individuals without metabolic comorbidity, those with four metabolic comorbidities had an 8.1-fold increased HCC risk (95% CI, 2.48-26.7). In T2D, neither insulin use nor oral hypoglycemic use was significantly associated with HCC risk (HR, 2.04 [95% CI, 0.69-6.09] and HR, 1.45 [95% CI, 0.69-3.07], respectively). Conclusion: T2D is independently associated with increased risk for HCC in two prospective cohorts of U.S. men and women. This risk is enhanced with prolonged diabetes duration and with comorbid metabolic conditions, suggesting the importance of insulin resistance in the pathogenesis of HCC. (Hepatology 2018;67:1797-1806)
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