title: Type 2 diabetes, smoking, insulin use, and mortality from hepatocellular carcinoma: a 12-year follow-up of a national cohort in Taiwan.
abstract: BACKGROUND
  The effect of smoking and insulin use in the association between diabetes and hepatocellular carcinoma (HCC) is not known.
  
  
  METHODS
  Age-standardized HCC mortality trends during 1995-2006 in the general population were calculated. A total of 88,694 type 2 diabetic patients aged ≥25 years recruited in 1995-1998 were followed till 2006. Age- and sex-specific mortality rates and the mortality rate ratios (vs. the average mortality rates in the general population) were calculated. Risk factors were evaluated by Cox regression.
  
  
  RESULTS
  The age-standardized mortality trend slightly increased significantly in women but was steady in men. For diabetic patients aged ≥25 years, 830 men and 515 women died of HCC during 1995-2006. Mortality rate ratios (95 % confidence interval) were larger with the decreasing age: 7.36 (6.52, 8.31), 2.48 (2.22, 2.78), 1.79 (1.59, 2.02), and 1.87 (1.51, 2.32) for age 25-54, 55-64, 65-74, and ≥75 years for men, respectively, 10.12 (7.73, 13.25), 4.08 (3.57, 4.67), 2.45 (2.15, 2.78), and 1.71 (1.34, 2.19) for women. Age, male sex, lower BMI, smoking, and insulin use were associated with HCC mortality, but diabetes duration was not. Smoking and insulin use carried a significantly higher risk of 22-29 % and 37-58 %, respectively, without interaction. A dose-responsive pattern between the duration of insulin use and HCC mortality was noted, with a relative risk of 1.5-1.7 in those who used insulin for ≥10 years.
  
  
  CONCLUSIONS
  Diabetic patients have a higher risk of HCC mortality, which is more remarkable in the younger age. Smoking and insulin are potentially modifiable risk factors.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan. ccktsh@ms6.hinet.net.|Department of Internal Medicine, National Taiwan University Hospital, No. 7 Chung-Shan South Road, Taipei, Taiwan. ccktsh@ms6.hinet.net.
authors.forename: Chin-Hsiao
authors.initials: CH
authors.lastname: Tseng
keywords: Diabetes; Hepatocellular carcinoma; Insulin; Mortality; Smoking