Association Between Markers of Glucose Metabolism and Risk of Colorectal Adenoma

doi:10.1053/j.gastro.2014.03.006

Gastroenterology

Volume 147, Issue 1, July 2014, Pages 78-87.e3

https://doi.org/10.1053/j.gastro.2014.03.006 Get rights and content

Background & Aims

Diabetes is a risk factor for colorectal cancer. We studied the association between markers of glucose metabolism and metabolic syndrome and the presence of colorectal adenomas in a large number of asymptomatic men and women attending a health screening program in South Korea. We also investigated whether these associations depend on adenoma location.

Methods

In a cross-sectional study, we measured fasting levels of glucose, insulin, hemoglobin A_1c, and C-peptide and calculated homeostatic model assessment (HOMA) values (used to quantify insulin resistance) for 19,361 asymptomatic South Korean subjects who underwent colonoscopy examinations from January 2006 to June 2009. Participants completed a standardized self-administered health questionnaire and a validated semiquantitative food frequency questionnaire. Blood samples were collected on the day of the colonoscopy; fasting blood samples were also collected. Robust Poisson regression was used to model the associations of glucose markers with the prevalence of any adenoma.

Results

Using detailed multivariable-adjusted dose-response models, the prevalence ratios (aPR, 95% confidence interval [CI]) for any adenoma, comparing the 90th with the 10th percentile, were 1.08 (1.00–1.16; P = .04) for fasting glucose, 1.07 (0.99–1.15; P = .10) for insulin, 1.09 (1.02–1.18, P = .02) for HOMA, 1.09 (1.01–1.17; P = .02) for hemoglobin A_1c, and 1.14 (1.05–1.24; P = .002) for C-peptide. The corresponding ratios for nonadvanced adenomas were 1.11 (0.99–1.25; P = .08), 1.10 (0.98–1.24; P = .12), 1.15 (1.02–1.29; P = .02), 1.14 (1.01–1.28; P = .03), and 1.20 (1.05–1.37; P = .007), respectively. The corresponding ratios for advanced adenomas were 1.32 (0.94–1.84; P = .11), 1.23 (0.87–1.75; P = .24), 1.30 (0.92–1.85; P = .14), 1.13 (0.79–1.61; P = .50), and 1.67 (1.15–2.42; P = .007), respectively. Metabolic syndrome was associated with the prevalence of any adenoma (aPR, 1.18; 95% CI, 1.13–1.24; P < .001), nonadvanced adenoma (aPR, 1.30; 95% CI, 1.20–1.40; P < .001), and advanced adenoma (aPR, 1.42; 95% CI, 1.14–1.78; P = .002). Associations were similar for adenomas located in the distal versus proximal colon.

Conclusions

Increasing levels of glucose, HOMA values, levels of hemoglobin A_1c and C-peptide, and metabolic syndrome are significantly associated with the prevalence of adenomas. Adenomas should be added to the list of consequences of altered glucose metabolism.

Section snippets

Study Population

We conducted a cross-sectional study of 21,688 consecutive routine colonoscopies performed during health screening examinations at the Center for Health Promotion of the Samsung Medical Center (Seoul, South Korea) between January 2006 and June 2009.²⁰ The Center for Health Promotion provides regular health checkups that include screening colonoscopy examinations for adults. We excluded 2327 colonoscopies for one or more of the following reasons: repeated colonoscopy (n = 1188), diagnostic or

Results

The average ± SD age of the study participants was 52.1 ± 8.3 years, and the average BMI was 24.1 ± 2.8 kg/m² (Table 1). A total of 5967 participants (30.8%) had prevalent adenomas, and 458 participants (2.4%) had prevalent advanced adenomas. The prevalence of adenomas was higher among participants who were older, male, and current smokers and alcohol consumers; who did not exercise regularly; who had a history of colorectal polyps, hypertension, or diabetes; who were currently using aspirin;

Discussion

In this large cross-sectional study of asymptomatic men and women undergoing screening colonoscopies, we found a progressive and statistically significant association between fasting glucose, HOMA-IR, HbA_1c, and C-peptide levels and the overall prevalence of colorectal adenomas. Levels of HOMA-IR, HbA_1c, and C-peptide were significantly associated with an increased prevalence of nonadvanced adenomas. C-peptide levels were significantly associated with an increased prevalence of advanced

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The requirement for informed consent was waived because only de-identified data routinely collected during health screening visits were used. The comprehensive health-screening program included demographic characteristics, anthropometric measurements, detailed physical examination, and a self-administered health questionnaire on smoking, alcohol intake, current medication use, family history of CRC, and personal medical history including malignancy, previous colorectal polyps, and surgical history.28 Smoking status was categorized as light smoker (<20 pack-years) and heavy smoker (≥20 pack-years).
In individuals with either no or 1 to 2 nonadvanced adenomas, future risks of advanced colorectal neoplasia (AN) vary according to clinical risk factors. However, little is known about the association between the adenoma detection rate (ADR) and the risk for metachronous AN in patients with low-risk adenomas.
We identified 7171 participants with no or 1 to 2 nonadvanced adenomas at first-time screening colonoscopy. The risk of metachronous AN was investigated at surveillance colonoscopy, according to clinical characteristics and the ADR.
In multivariate analysis the risk for metachronous AN was strongly associated with increasing age, male sex, increasing number of adenomas, and the ADR of the endoscopist. With the ADR modeled as a continuous variable, each 1.0% increase in the rate of ADR predicted a 3.0% decrease in the risk of metachronous AN (adjusted odds ratio [OR], .97; 95% confidence interval [CI], .95-.99). With the ADR modeled using a binary cut-off (32%), the risk of metachronous AN was reduced in patients of endoscopists with an ADR ≥32% (adjusted OR, .53; 95% CI, .35-.83). Moreover, the risk of metachronous AN was reduced (adjusted OR, .66; 95% CI, .46-.95) in patients of endoscopists with an ADR in the highest tertile, compared with patients of endoscopists with ADRs in the lowest tertile. The impact of ADR on metachronous AN was significant for patients with low-risk adenomas rather than patients with no adenoma.
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We aimed to summarize the association between hyperinsulinemia/insulin resistance and risk of CRA, including whether the association is independent of adiposity.
Pubmed and Embase were searched through April, 2015 to identify observational studies investigating the associations between insulin, C-peptide and HOMA-IR and CRA risk. Using the highest versus lowest category meta-analysis and dose–response meta-analysis based on a random-effects model, we estimated summary odds ratio (OR) and the corresponding 95% confidence interval (95% CI).
A total of 27 studies (insulin: 16 studies including 14,007 cases; C-peptide: 11 studies including 8639 cases; HOMA-IR: 8 studies including 11,619 cases) were included in this meta-analysis. The summary ORs of CRA comparing the highest with the lowest quantile were 1.33 for insulin (95% CI = 1.12–1.58, I² = 73.9%, P_{heterogeneity} < 0.001), 1.44 for C-peptide (95% CI = 1.13–1.83, I² = 63.5%, P_{heterogeneity} = 0.003), and 1.33 for HOMA-IR (95% CI = 1.10–1.60, I² = 69.1%, P_{heterogeneity} = 0.004). Upon stratification by ethnicity, higher levels of insulin and C-peptide were significantly associated with increased risk of CRA in non-Asian ethnicity (summary OR for insulin = 1.67 [95% CI = 1.28–2.17], I² = 34.9%, P_{heterogeneity} = 0.16; summary OR for C-peptide = 1.59 [95% CI = 1.22–2.08], I² = 21.5%, P_{heterogeneity} = 0.27) but not in Asians (summary OR for insulin = 1.10 [95% CI = 0.92–1.33], I² = 76.6%, P_{heterogeneity} = 0.001; summary OR for C-peptide = 1.27 [95% CI = 0.84–1.91], I² = 72.6, P_{heterogeneity} = 0.01). We observed evidence for the existence of publication bias for insulin (P = 0.01 by Egger test) and HOMA-IR (P = 0.05 by Egger test). The results were confirmed in linear dose–response meta-analysis. These significant positive associations generally persisted even after adjustment for adiposity, although the effect size was substantially attenuated.
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Original ResearchFull Report: Clinical—Alimentary TractAssociation Between Markers of Glucose Metabolism and Risk of Colorectal Adenoma

Background & Aims

Methods

Results

Conclusions

Section snippets

Study Population

Results

Discussion

Diabetes Res Clin Pract

Diabetes Res Clin Pract

Am J Med Sci

Am J Pathol

Diabetes and cancer I: risk, survival, and implications for screening

Cancer Causes Control

Diabetes mellitus and the incidence of colorectal cancer: an updated systematic review and meta-analysis

Dig Dis Sci

Is diabetes mellitus an independent risk factor for colon cancer and rectal cancer?

Am J Gastroenterol

Diabetes mellitus and incidence and mortality of colorectal cancer: a systematic review and meta-analysis of cohort studies

Eur J Epidemiol

Diabetes mellitus and risk of colorectal cancer: a meta-analysis

J Natl Cancer Inst

Diabetes mellitus and the incidence and mortality of colorectal cancer: a meta-analysis of 24 cohort studies

Colorectal Dis

Diabetes mellitus and cancer risk: review of the epidemiological evidence

Cancer Sci

Diabetes and cancer II: role of diabetes medications and influence of shared risk factors

Cancer Causes Control

Association of colorectal adenoma with components of metabolic syndrome

Cancer Causes Control

Association between adenomas of rectosigmoid colon and metabolic syndrome features in a Chinese population

J Gastroenterol Hepatol

Relation of serum total cholesterol, serum triglycerides and fasting plasma glucose to colorectal carcinoma in situ

Int J Epidemiol

Serum fructosamine and colorectal adenomas

Eur J Epidemiol

Glycosylated hemoglobin and risk of colorectal cancer and adenoma (United States)

Cancer Causes Control

Metabolic syndrome components and colorectal adenoma in the CLUE II cohort

Cancer Causes Control

Associations of plasma C-peptide and IGFBP-1 levels with risk of colorectal adenoma in a multiethnic population

Cancer Epidemiol Biomarkers Prev

Insulin resistance, central obesity, and risk of colorectal adenomas

Cancer

Elevated C-peptide and insulin predict increased risk of colorectal adenomas in normal mucosa

BMC Cancer

Original Research
Full Report: Clinical—Alimentary Tract
Association Between Markers of Glucose Metabolism and Risk of Colorectal Adenoma