Association between markers of glucose metabolism and risk of colorectal cancer

Abstract

Objectives: Independent epidemiological studies have evaluated the association between markers of glucose metabolism (including fasting glucose, fasting insulin, homeostasis model of risk assessment-insulin resistance (HOMA-IR), glycated haemoglobin (HbA1c) and C peptide) and the risk of colorectal cancer (CRC). However, such associations have not been systematically analysed and no clear conclusions have been drawn. Therefore, we addressed this issue using a meta-analysis approach.

Design: Systematic review and meta-analysis.

Data sources: PubMed and EMBASE were searched up to May 2015.

Primary and secondary outcome measures: Either a fixed-effects or random-effects model was adopted to estimate overall ORs for the association between markers of glucose metabolism and the risk of CRC. In addition, dose-response, meta-regression, subgroup and publication bias analyses were conducted.

Results: 35 studies involving 25 566 patients and 5 706 361 participants were included. Higher levels of fasting glucose, fasting insulin, HOMA-IR, HbA1c and C peptide were all significantly associated with increased risk of CRC (fasting glucose, pooled OR=1.12, 95% CI 1.06 to 1.18; fasting insulin, pooled OR=1.42, 95% CI 1.19 to 1.69; HOMA-IR, pooled OR=1.47, 95% CI 1.24 to 1.74; HbA1c, pooled OR=1.22, 95% CI 1.02 to 1.47 (with borderline significance); C peptide, pooled OR=1.27, 95% CI 1.08 to 1.49). Subgroup analysis suggested that a higher HOMA-IR value was significantly associated with CRC risk in all subgroups, including gender, study design and geographic region. For the relative long-term markers, the association was significant for HbA1c in case-control studies, while C peptide was significantly associated with CRC risk in both the male group and colon cancer.

Conclusions: The real-time composite index HOMA-IR is a better indicator for CRC risk than are fasting glucose and fasting insulin. The relative long-term markers, HbA1c and C peptide, are also valid predictors for CRC risk. Considering the included case-control studies in the current analysis, more cohort studies are warranted to enhance future analysis.

Keywords: C-peptide; HOMA-IR; HbA1c; colorectal cancer; fasting glucose; fasting insulin.

Figure 1

Flow diagram of study selection process.

Figure 2

The association between real-time markers of glucose metabolism and the risk of CRC. Pooled ORs of CRC for the highest versus lowest categories of (A) fasting glucose level; (B) fasting insulin level and (C) HOMA-IR value. A, advanced cancer; CC, colon cancer; CRC, colorectal cancer; E, early cancer; F, female; HOMA-IR, homeostasis model of risk assessment-insulin resistance; M, male; RC, rectal cancer; RR, relative risk.

Figure 3

Dose–response relationship between real-time markers of glucose metabolism and the risk of CRC. Dose–response relationship between (A) fasting glucose level and the risk of CRC; (B) fasting insulin level and the risk of CRC and (C) HOMA-IR value and the risk of CRC. The solid line represents the pooled RRs, and the dotted line represents the 95% CIs of the RRs. CRC, colorectal cancer; HOMA-IR, homeostasis model of risk assessment-insulin resistance; RR, relative risk.

Figure 4

The association between relative long-term markers of glucose metabolism and the risk of CRC. Pooled ORs of CRC for the highest versus lowest categories of (A) HbA1c level and (B) C peptide level. CC, colon cancer; CRC, colorectal cancer; F, female; HbA1c, glycated haemoglobin; M, male; RC, rectal cancer; RR, relative risk.

Figure 5

Dose–response relationship between long-term markers of glucose metabolism and the risk of CRC. Dose–response relationship between (A) HbA1c level and the risk of CRC and (B) C peptide level and the risk of CRC. The solid line represents the pooled RRs, and the dotted line represents the 95% CIs of the RRs. CRC, colorectal cancer; HbA1c, glycated haemoglobin; RR, relative risk.