Plasma C‐peptide and glycated albumin and subsequent risk of cancer: From a large prospective case‐cohort study in Japan

Abstract

To elucidate the individual impacts of insulin and blood glucose on cancer risk, we investigated the association of plasma C-peptide, a surrogated marker of insulin and glycated albumin (GA), a more stable marker of blood glucose, with all-site and site-specific cancer risk by mutually accounting for their confounding effects. The study was prospectively conducted with nearly 4,000 cancer cases arising in our population-based cohort of 33,736 subjects who answered the baseline questionnaire and supplied blood samples. After exclusion of subjects with apparent DM, analysis was done in 3,036 cancer cases and 3,667 subcohort subjects. Among men and women combined, highest levels of C-peptide were statistically significantly associated with an increased risk of all-site [Hazard ratio (HR): 1.21; 95% confidence interval: 1.02-1.42], colon [1.73; 1.20-2.47], liver [3.23; 1.76-5.91], kidney, renal pelvis and ureter cancers [2.47; 1.07-5.69], compared to the respective lowest levels, after adjustment for GA levels. Among these C-peptide-related cancers, colon and liver cancers also showed an increased risk associated with elevated GA levels independently of C-peptide levels. The corresponding HRs for colon and liver cancers compared to the highest and lowest GA levels were 1.43 [1.02-2.00] and 2.02 [1.15-3.55], respectively. Effect modification by gender was only evident for the association between C-peptide and colon cancer (p for interaction = 0.04). Higher insulin levels, independently of higher blood glucose levels, may be relevant to DM-related carcinogenesis for several cancer sites. Examination of circulating insulin levels is a plausible option in evaluating cancer risk even in individuals who have not developed DM.

Associations of metabolic syndrome and metabolically unhealthy obesity with cancer mortality: The Japan Multi-Institutional Collaborative Cohort (J-MICC) study

“…In a case-cohort study performed in Japan, plasma C-peptide concentrations were associated with significantly increased risks of all-cancers and cancers of five sites [21]. Obesity-associated oxidative stress and inflammation are also involved in the development/progression of various cancers [22].…”

Frequency of Increased Plasma C-Peptide Levels in Colorectal Cancer Patients

“…Investigation of insulin concentration flowing in the blood is an acceptable option in assessing the risk of malignancy or cancer, even in cases who do not have diabetes mellitus. 25…”

Beneficial Roles of Histone Deacetylase Inhibitor Butyrate to Multiple Myeloma, Acute Leukemia and Acute Myeloid Leukemia: Case Reports

“…The author proposed bacterial species producing SCFAs, butyrate, associated with enhancement immune checkpoint inhibitor therapy in human. Hidaka et al [14] investigated the association of plasma C-peptide, a surrogated marker of insulin and glycated albumin (GA), a more stable marker of blood glucose, with all-site and site-specific cancer risk by mutually according for their confounding effects. The study was prospectively conducted with nearly 4,000 cancer cases arising in the population-based cohort of 33,736 subjects who answered the baseline questionnaire and supplied blood samples.…”