title: Higher Glucose and Insulin Levels Are Associated with Risk of Liver Cancer and Chronic Liver Disease Mortality among Men without a History of Diabetes.
abstract: Insulin resistance likely increases the risk of chronic liver disease (CLD) and liver cancer, but long-term prospective studies with measured fasting glucose and insulin are lacking. We evaluated the associations of prediagnostic fasting glucose, insulin, and the homeostasis model assessment of insulin resistance (HOMA-IR) with liver cancer and CLD mortality in a prospective study of Finnish male smokers with extended follow-up time (≤22 years) and information on known risk factors using data from 138 incident primary liver cancer cases, 216 CLD deaths, and 681 matched controls. Fasting glucose and insulin were measured in baseline serum. We used unconditional logistic regression to estimate ORs and 95% confidence intervals adjusted for age, alcohol, education, smoking, body mass index, and hepatitis B and C viral status. Among those without self-reported diabetes, glucose was positively associated with liver cancer [quartile 3 vs. quartile 1 (Q3/Q1): OR = 1.88; 1.03-3.49; Q4/Q1: OR = 2.40; 1.33-4.35; Ptrend= 0.002], and undiagnosed, biochemically defined, diabetes was associated with higher risk of liver cancer (OR = 2.95; 1.46-5.96) and CLD mortality (OR = 1.88; 1.00-3.56). Serum insulin and HOMA-IR were also positively associated with liver cancer (Q4/Q1: OR = 3.41; 1.74-6.66; Ptrend< 0.0001; OR = 3.72; 1.89-7.32, Ptrend< 0.0001, respectively) and CLD (OR = 2.51; 1.44-4.37; Ptrend= 0.0002; OR = 2.31; 1.34-3.97; Ptrend= 0.001, respectively), with stronger associations observed for liver cancer diagnosed >10 years after baseline. In conclusion, elevated fasting glucose and insulin and insulin resistance were independently associated with risk of liver cancer and CLD mortality, suggesting a potentially important etiologic role for insulin and glucose dysregulation even in the absence of diagnosed diabetes. Cancer Prev Res; 9(11); 866-74. ©2016 AACR.
authors: Division of Cancer Epidemiology and Genetics, NCI, NIH, Rockville, Maryland. erikka.loftfield@nih.gov.
authors: Erikka
authors: E
authors: Loftfield
authors: Division of Cancer Epidemiology and Genetics, NCI, NIH, Rockville, Maryland.
authors: Neal D
authors: ND
authors: Freedman
authors: Division of Cancer Epidemiology and Genetics, NCI, NIH, Rockville, Maryland.
authors: Gabriel Y
authors: GY
authors: Lai
authors: Division of Cancer Epidemiology and Genetics, NCI, NIH, Rockville, Maryland.
authors: Stephanie J
authors: SJ
authors: Weinstein
authors: Division of Cancer Epidemiology and Genetics, NCI, NIH, Rockville, Maryland.
authors: Katherine A
authors: KA
authors: McGlynn
authors: Division of Cancer Epidemiology and Genetics, NCI, NIH, Rockville, Maryland.
authors: Philip R
authors: PR
authors: Taylor
authors: National Institute for Health and Welfare, Helsinki, Finland.
authors: Satu
authors: S
authors: Männistö
authors: Division of Cancer Epidemiology and Genetics, NCI, NIH, Rockville, Maryland.
authors: Demetrius
authors: D
authors: Albanes
authors: Division of Cancer Epidemiology and Genetics, NCI, NIH, Rockville, Maryland.
authors: Rachael Z
authors: RZ
authors: Stolzenberg-Solomon
mesh_terms: D000368:Aged; D001786:Blood Glucose; D002908:Chronic Disease; D004032:Diet; D004311:Double-Blind Method; D005387:Finland; D006801:Humans; D015994:Incidence; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance; D008107:Liver Diseases / Q000401:mortality*; D008113:Liver Neoplasms / Q000453:epidemiology*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000453:epidemiology / Q000517:prevention & control; D011446:Prospective Studies; D012307:Risk Factors; D012907:Smoking; D024502:alpha-Tocopherol / Q000627:therapeutic use; D019207:beta Carotene / Q000627:therapeutic use
chemical_list: D001786:Blood Glucose; D007328:Insulin; D019207:beta Carotene; D024502:alpha-Tocopherol