Abstract
BackgroundKnown associations between diabetes and cancer could logically be attributed to hyperglycemia, hypersecretion of insulin, and/or insulin resistance. This study examined the relationship between initial glycemic biomarkers among men and women with impaired fasting glucose or undiagnosed diabetes and cancer mortality during follow up.MethodsThe cohort included subjects aged 40 years and above from the Third National Health and Nutrition Examination Survey (NHANES III) with fasted serum glucose >100 mg/dl without the aid of pharmaceutical intervention (insulin or oral hypoglycemics). Cancer mortality was obtained from the NHANES III-linked follow-up database (up to December 31, 2006). A Cox regression model was applied to test for the associations between cancer mortality and fasting serum glucose, insulin, glycosylated hemoglobin (HbA1c), C-peptide, insulin like growth factor (IGF-1), IGF binding protein 3 (IGFBP3) and estimated insulin resistance.ResultsA total of 158 and 100 cancer deaths were recorded respectively from 1,348 men and 1,161 women during the mean 134-month follow-up. After adjusting for the effect of age and smoking in women, all-cause cancer deaths (HR: 1.96 per pmol/ml, 95% CI: 1.02–3.77) and lung cancer deaths (HR: 2.65 per pmol/ml, 95% CI: 1.31–5.36) were specifically associated with serum C-peptide concentrations. Similar associations in men were not statistically significant. Serum glucose, HbA1c, IGF-1, IGFBP3 and HOMA were not independently related to long-term cancer mortality.ConclusionC-peptide analyses suggest a modest association with both all-cause and lung cancer mortality in women but not in men. Further studies will be required to explore the mechanisms.
Highlights
The association between type 2 diabetes and several types of cancer has been widely reported [1]
In support of this thesis, evidence suggests that the mechanisms underlying the association between pre-diabetes/metabolic syndrome and cancer incidence involves the influence of elevated insulin and IGF-1 [10]
impaired fasting glucose (IFG) was defined as a fasted serum glucose .100 mg/dl without insulin or oral hypoglycemic therapy and undiagnosed diabetes defined as fasted serum glucose .126 mg/ dl without pharmacologic intervention
Summary
The association between type 2 diabetes and several types of cancer has been widely reported [1]. Diabetes and cancer share many common risk factors such as age, sex, race, socioeconomic status, body mass index, insulin resistance, physical activity, smoking, and alcohol intake [2]. Within type 2 diabetic patients, aggressive versus standard glycemic control does not appear to reduce cancer risk [9]. These results indicate that elevated insulin secretion is perhaps the better mechanistic candidate than hyperglycemia. Specific associations between hyperglycemia, insulin, IGF-1, IGFBP3 and the risk of cancer among people with type 2 diabetes remain unclear. This study examined the relationship between initial glycemic biomarkers among men and women with impaired fasting glucose or undiagnosed diabetes and cancer mortality during follow up
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