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Mao X, Cheung KS, Tan JT, Mak LY, Lee CH, Chiang CL, Cheng HM, Hui RWH, Yuen MF, Leung WK, Seto WK. Optimal glycaemic control and the reduced risk of colorectal adenoma and cancer in patients with diabetes: a population-based cohort study. Gut 2024; 73:1313-1320. [PMID: 38569845 DOI: 10.1136/gutjnl-2023-331701] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2024] [Accepted: 03/22/2024] [Indexed: 04/05/2024]
Abstract
OBJECTIVE Whether varying degrees of glycaemic control impact colonic neoplasm risk in patients with diabetes mellitus (DM) remains uncertain. DESIGN Patients with newly diagnosed DM were retrieved from 2005 to 2013. Optimal glycaemic control at baseline was defined as mean haemoglobin A1c (HbA1c)<7%. Outcomes of interest included colorectal cancer (CRC) and colonic adenoma development. We used propensity score (PS) matching with competing risk models to estimate subdistribution HRs (SHRs). We further analysed the combined effect of baseline and postbaseline glycaemic control based on time-weighted mean HbA1c during follow-up. RESULTS Of 88 468 PS-matched patients with DM (mean (SD) age: 61.5 (±11.7) years; male: 47 127 (53.3%)), 1229 (1.4%) patients developed CRC during a median follow-up of 7.2 (IQR: 5.5-9.4) years. Optimal glycaemic control was associated with lower CRC risk (SHR 0.72; 95% CI 0.65 to 0.81). The beneficial effect was limited to left-sided colon (SHR 0.71; 95% CI 0.59 to 0.85) and rectum (SHR 0.71; 95% CI 0.57 to 0.89), but not right-sided colon (SHR 0.86; 95% CI 0.67 to 1.10). Setting suboptimal glycaemic control at baseline/postbaseline as a reference, a decreased CRC risk was found in optimal control at postbaseline (SHR 0.79), baseline (SHR 0.71) and both time periods (SHR 0.61). Similar associations were demonstrated using glycaemic control as a time-varying covariate (HR 0.75). A stepwise greater risk of CRC was found (Ptrend<0.001) with increasing HbA1c (SHRs 1.34, 1.30, 1.44, 1.58 for HbA1c 7.0% to <7.5%, 7.5% to <8.0%, 8.0% to <8.5% and ≥8.5%, respectively). Optimal glycaemic control was associated with a lower risk of any, non-advanced and advanced colonic adenoma (SHRs 0.73-0.87). CONCLUSION Glycaemic control in patients with DM was independently associated with the risk of colonic adenoma and CRC development with a biological gradient.
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Affiliation(s)
- Xianhua Mao
- Department of Medicine, The University of Hong Kong, Hong Kong, Hong Kong
| | - Ka Shing Cheung
- Department of Medicine, The University of Hong Kong, Hong Kong, Hong Kong
- Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
| | - Jing-Tong Tan
- Department of Medicine, The University of Hong Kong, Hong Kong, Hong Kong
| | - Lung-Yi Mak
- Department of Medicine, The University of Hong Kong, Hong Kong, Hong Kong
| | - Chi-Ho Lee
- Department of Medicine, The University of Hong Kong, Hong Kong, Hong Kong
| | - Chi-Leung Chiang
- Department of Clinical Oncology, The University of Hong Kong, Hong Kong, Hong Kong
| | - Ho Ming Cheng
- Department of Medicine, The University of Hong Kong, Hong Kong, Hong Kong
| | - Rex Wan-Hin Hui
- Department of Medicine, The University of Hong Kong, Hong Kong, Hong Kong
| | - Man Fung Yuen
- Department of Medicine, The University of Hong Kong, Hong Kong, Hong Kong
| | - Wai Keung Leung
- Department of Medicine, The University of Hong Kong, Hong Kong, Hong Kong
| | - Wai-Kay Seto
- Department of Medicine, The University of Hong Kong, Hong Kong, Hong Kong
- Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
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Jung SY. Genetic Signatures of Glucose Homeostasis: Synergistic Interplay With Long-Term Exposure to Cigarette Smoking in Development of Primary Colorectal Cancer Among African American Women. Clin Transl Gastroenterol 2021; 12:e00412. [PMID: 34608882 PMCID: PMC8500576 DOI: 10.14309/ctg.0000000000000412] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2021] [Accepted: 08/22/2021] [Indexed: 11/17/2022] Open
Abstract
INTRODUCTION Insulin resistance (IR)/glucose intolerance is a critical biologic mechanism for the development of colorectal cancer (CRC) in postmenopausal women. Whereas IR and excessive adiposity are more prevalent in African American (AA) women than in White women, AA women are underrepresented in genome-wide studies for systemic regulation of IR and the association with CRC risk. METHODS With 780 genome-wide IR single-nucleotide polymorphisms (SNPs) among 4,692 AA women, we tested for a causal inference between genetically elevated IR and CRC risk. Furthermore, by incorporating CRC-associated lifestyle factors, we established a prediction model on the basis of gene-environment interactions to generate risk profiles for CRC with the most influential genetic and lifestyle factors. RESUTLS In the pooled Mendelian randomization analysis, the genetically elevated IR was associated with 9 times increased risk of CRC, but with lack of analytic power. By addressing the variation of individual SNPs in CRC in the prediction model, we detected 4 fasting glucose-specific SNPs in GCK, PCSK1, and MTNR1B and 4 lifestyles, including smoking, aging, prolonged lifetime exposure to endogenous estrogen, and high fat intake, as the most predictive markers of CRC risk. Our joint test for those risk genotypes and lifestyles with smoking revealed the synergistically increased CRC risk, more substantially in women with longer-term exposure to cigarette smoking. DISCUSSION Our findings may improve CRC prediction ability among medically underrepresented AA women and highlight genetically informed preventive interventions (e.g., smoking cessation; CRC screening to longer-term smokers) for those women at high risk with risk genotypes and behavioral patterns.
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Affiliation(s)
- Su Yon Jung
- Translational Sciences Section, School of Nursing, University of California, Los Angeles, Los Angeles, California, USA; and
- Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, California, USA.
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Yu X, Chen C, Song X, Guo Y, Tong Y, Zhao Y, Song Z. Glycosylated Hemoglobin as an Age-Specific Predictor and Risk Marker of Colorectal Adenomas in Non-Diabetic Adults. Front Endocrinol (Lausanne) 2021; 12:774519. [PMID: 34803930 PMCID: PMC8595137 DOI: 10.3389/fendo.2021.774519] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2021] [Accepted: 10/14/2021] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND Diabetes is a risk factor for colorectal neoplasms. The association between the level of glycosylated hemoglobin (HbA1c) and the risk of colorectal adenomas (CRAs) in non-diabetic adults needs to be investigated. METHODS A cross-sectional study was performed on non-diabetic adults with normal HbA1c level who underwent colonoscopy between January 2010 and December 2016 during health check-ups in our hospital in China. The association between HbA1c level and CRAs was assessed by multiple logistic regression models stratified by age group (<40, ≥40 and <50, and ≥50 years old). The age group-specified thresholds for HbA1c on elevated risk of CRAs were estimated using the piecewise logistic regression. RESULTS Among the 2,764 subjects, 445 (16.1%) had CRA. The prevalence of CRA varied across the three age groups. A higher HbA1c level was found to be significantly associated with increased CRA risk in the 40-50 years group (odds ratio [OR]=1.70, 95% confidence interval [CI] 1.04-2.78, p=0.035) after adjusting for other related factors, while this association was borderline significant among the 50 years and older group (OR=1.57, 95% CI 0.97-2.54, p=0.067). Based on the piecewise logistic regression analysis results, the thresholds for HbA1c on elevated risk of CRA were 5.44% for the 40-50 years group and 4.81% for the 50 years and older group, respectively. CONCLUSIONS Higher levels of HbA1c, even within the normal range, were associated with elevated CRA risk among non-diabetic adults. The threshold effects of HbA1c on the risk of CRA varied across different age groups, and early screening colonoscopy might be needed for individuals in their 40s and with HbA1c levels ≥5.44%.
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Affiliation(s)
- Xinyan Yu
- Department of General Practice and Health Management Center, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Chen Chen
- Department of Big Data in Health Science, School of Public Health, Zhejiang University, Hangzhou, China
- Center for Biostatistics, Bioinformatics, and Big Data, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Xiaoxiao Song
- Department of Endocrinology, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Yi Guo
- Department of General Practice and Health Management Center, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Yuling Tong
- Department of General Practice and Health Management Center, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Yi Zhao
- Department of General Practice and Health Management Center, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Zhenya Song
- Department of General Practice and Health Management Center, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- *Correspondence: Zhenya Song,
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HbA1c: High in acute cerebral infarction and low in brain trauma. PROGRESS IN MOLECULAR BIOLOGY AND TRANSLATIONAL SCIENCE 2019; 162:293-306. [DOI: 10.1016/bs.pmbts.2019.01.008] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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Kim JY, Lee YS, Jo G, Shin MJ. Glycated Hemoglobin and Cancer Risk in Korean Adults: Results from Korean Genome and Epidemiology Study. Clin Nutr Res 2018; 7:170-177. [PMID: 30079315 PMCID: PMC6073170 DOI: 10.7762/cnr.2018.7.3.170] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2018] [Revised: 04/09/2018] [Accepted: 04/09/2018] [Indexed: 01/05/2023] Open
Abstract
The purpose of this study was to test whether elevated glycated hemoglobin A1c (HbA1c) levels are associated with cancer incidence in the Korean population. In cohorts of the Korea Genome and Epidemiology Study (KoGES) consortium, we tested whether plasma levels of HbA1c were associated with all-site cancer incidence in 7,822 participants without any known history of cancer or diabetes. Cancer developed in 117 participants during the follow-up period. Subjects were subdivided into 3 categories according observed levels of HbA1c (< 5.7%, low; ≥ 5.7% and < 6.5%, mid; and ≥ 6.5%, high). The adjusted hazard ratio for all-site cancer was 3.03 (95% confidence intervals, 1.54–5.96) for the high HbA1c group relative to the low HbA1c group after adjusting for covariates. Higher circulating HbA1c levels were associated with an increased risk of all-site cancer in Korean population.
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Affiliation(s)
- Ji Young Kim
- Department of Public Health Sciences, Graduate School, Korea University, Seoul 02841, Korea
| | - Youn Sue Lee
- Korea National Enterprise for Clinical Trials, Seoul 04143, Korea
| | - Garam Jo
- Department of Public Health Sciences, Graduate School, Korea University, Seoul 02841, Korea
| | - Min-Jeong Shin
- Department of Public Health Sciences, Graduate School, Korea University, Seoul 02841, Korea
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Chang LC, Shun CT, Hsu WF, Tu CH, Tsai PY, Lin BR, Liang JT, Wu MS, Chiu HM. Fecal Immunochemical Test Detects Sessile Serrated Adenomas and Polyps With a Low Level of Sensitivity. Clin Gastroenterol Hepatol 2017; 15:872-879.e1. [PMID: 27498176 DOI: 10.1016/j.cgh.2016.07.029] [Citation(s) in RCA: 103] [Impact Index Per Article: 12.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2016] [Revised: 07/28/2016] [Accepted: 07/31/2016] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS The serrated pathway is a distinct pathway of colorectal carcinogenesis that has been implicated in development of a substantial proportion of interval colorectal cancers. The fecal immunochemical test (FIT) detects early neoplasms with a higher level of sensitivity than the guaiac test. We investigated the sensitivity of the FIT in detection of sessile serrated adenomas/polyps (SSA/Ps). METHODS We performed a prospective study of 6198 asymptomatic subjects (mean age, 59.0 ± 7.0 years) who received concurrent screening colonoscopies and FITs at the Health Management Center of National Taiwan University Hospital from August 2010 through November 2014. The sensitivity of FIT for conventional adenoma, advanced adenoma, and SSA/P at different cutoffs was calculated, and results were compared by using multivariate analysis adjusted for potential confounders. RESULTS Prevalence values of SSA/P, adenoma, and advanced adenoma were 1.4%, 20.2%, and 5.5%, respectively. At cutoffs of 10, 15, and 20 μg hemoglobin/g feces, the FIT detected all SSA/Ps with 12.3%, 6.2%, and 6.2% sensitivity, large SSA/Ps with 18.4%, 10.5%, and 10.5% sensitivity, and advanced adenomas with 32.4%, 24.5%, and 20.9% sensitivity, respectively. Multivariate analysis revealed that positive results from the FIT did not differ significantly between individuals with SSA/P and those with non-advanced adenoma or those with negative findings from colonoscopy. Patients with large SSA/Ps were less likely to have positive results from the FIT than patients with advanced adenoma, with odds ratios of 0.44 (95% confidence interval [CI], 0.18-1.05), 0.30 (95% CI, 0.10-0.90), and 0.37 (95% CI, 0.12-1.12) at cutoffs of 10, 15, and 20 μg hemoglobin/g feces, respectively, after adjusting for lesion size, even with synchronous conventional adenoma. CONCLUSIONS In a prospective study of 6198 subjects receiving the FIT and colonoscopy, we found that the FIT detected SSA/Ps with significantly lower levels of sensitivity than conventional adenoma. Further studies are needed to determine the effects of these findings on the effectiveness of FIT-based colorectal cancer screening program.
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Affiliation(s)
- Li-Chun Chang
- Department of Internal Medicine, National Taiwan University Hospital, Bei-Hu Branch, Taipei, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Chia-Tung Shun
- Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan
| | - Weng-Feng Hsu
- Department of Internal Medicine, National Taiwan University Hospital, Hsin-Chu Branch, Hsin-Chu, Taiwan
| | - Chia-Hong Tu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Health Management Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Pei-Yu Tsai
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Been-Ren Lin
- Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan
| | - Jin-Tung Liang
- Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan
| | - Ming-Shiang Wu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Health Management Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Han-Mo Chiu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Health Management Center, National Taiwan University Hospital, Taipei, Taiwan.
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Kim NH, Suh JY, Park JH, Park DI, Cho YK, Sohn CI, Choi K, Jung YS. Parameters of Glucose and Lipid Metabolism Affect the Occurrence of Colorectal Adenomas Detected by Surveillance Colonoscopies. Yonsei Med J 2017; 58:347-354. [PMID: 28120565 PMCID: PMC5290014 DOI: 10.3349/ymj.2017.58.2.347] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2016] [Revised: 10/29/2016] [Accepted: 11/11/2016] [Indexed: 11/27/2022] Open
Abstract
PURPOSE Limited data are available regarding the associations between parameters of glucose and lipid metabolism and the occurrence of metachronous adenomas. We investigated whether these parameters affect the occurrence of adenomas detected on surveillance colonoscopy. MATERIALS AND METHODS This longitudinal study was performed on 5289 subjects who underwent follow-up colonoscopy between 2012 and 2013 among 62171 asymptomatic subjects who underwent an initial colonoscopy for a health check-up between 2010 and 2011. The risk of adenoma occurrence was assessed using Cox proportional hazards modeling. RESULTS The mean interval between the initial and follow-up colonoscopy was 2.2±0.6 years. The occurrence of adenomas detected by the follow-up colonoscopy increased linearly with the increasing quartiles of fasting glucose, hemoglobin A1c (HbA1c), insulin, homeostasis model assessment of insulin resistance (HOMA-IR), and triglycerides measured at the initial colonoscopy. These associations persisted after adjusting for confounding factors. The adjusted hazard ratios for adenoma occurrence comparing the fourth with the first quartiles of fasting glucose, HbA1c, insulin, HOMA-IR, and triglycerides were 1.50 [95% confidence interval (CI), 1.26-1.77; p(trend)<0.001], 1.22 (95% CI, 1.04-1.43; p(trend)=0.024), 1.22 (95% CI, 1.02-1.46; p(trend)=0.046), 1.36 (95% CI, 1.14-1.63; p(trend)=0.004), and 1.19 (95% CI, 0.99-1.42; p(trend)=0.041), respectively. In addition, increasing quartiles of low-density lipoprotein-cholesterol and apolipoprotein B were associated with an increasing occurrence of adenomas. CONCLUSION The levels of parameters of glucose and lipid metabolism were significantly associated with the occurrence of adenomas detected on surveillance colonoscopy. Improving the parameters of glucose and lipid metabolism through lifestyle changes or medications may be helpful in preventing metachronous adenomas.
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Affiliation(s)
- Nam Hee Kim
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jung Yul Suh
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jung Ho Park
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Dong Il Park
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Yong Kyun Cho
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Chong Il Sohn
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Kyuyong Choi
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Yoon Suk Jung
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
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Ferroni P, Formica V, Della-Morte D, Lucchetti J, Spila A, D'Alessandro R, Riondino S, Guadagni F, Roselli M. Prognostic value of glycated hemoglobin in colorectal cancer. World J Gastroenterol 2016; 22:9984-9993. [PMID: 28018105 PMCID: PMC5143765 DOI: 10.3748/wjg.v22.i45.9984] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2016] [Revised: 10/18/2016] [Accepted: 11/16/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the clinical significance of routinely used glycemic parameters in a cohort of colorectal cancer (CRC) patients.
METHODS Pre-treatment fasting blood glucose, insulin, HbA1c and homeostasis model of risk assessment (HOMA-IR) were retrospectively evaluated in a case-control study of 224 CRC and 112 control subjects matched for sex, obesity and diabetes frequency and blood lipid profile. Furthermore, the prognostic value of routinely used glycemic parameters towards progression-free (PFS) and overall survival (OS) was prospectively evaluated.
RESULTS Fasting blood glucose, insulin, HOMA-IR and HbA1c (all P < 0.0001) levels were higher in non-diabetic CRC patients compared with obesity-matched controls. All parameters were associated with increased CRC risk at ROC analysis, but no relationship with clinical-pathological variables or survival outcomes was observed for glycemia, insulinemia or HOMA-IR. Conversely, advanced CRC stage (P = 0.018) was an independent predictor of increased HbA1c levels, which were also higher in patients who had disease progression compared with those who did not (P = 0.05). Elevated HbA1c levels showed a negative prognostic value both in terms of PFS (HR = 1.24) and OS (HR = 1.36) after adjustment for major confounders, which was further confirmed in a subgroup analysis performed after exclusion of diabetic patients.
CONCLUSION HbA1c might have a negative prognostic value in CRC, thus suggesting that glycemic metabolic markers should be carefully monitored in these patients, independently of overt diabetes.
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Abdelsatir AA, Husain NE, Hassan AT, Elmadhoun WM, Almobarak AO, Ahmed MH. Potential Benefit of Metformin as Treatment for Colon Cancer: the Evidence so Far. Asian Pac J Cancer Prev 2016; 16:8053-8. [PMID: 26745038 DOI: 10.7314/apjcp.2015.16.18.8053] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Metformin is known as a hypoglycaemic agent that regulates glucose homeostasis by inhibiting liver glucose production and increasing muscle glucose uptake. Colorectal cancer (CRC) is one of the most common cancers worldwide, with about a million new cases diagnosed each year. The risk factors for CRC include advanced age, smoking, black race, obesity, low fibre diet, insulin resistance, and the metabolic syndrome. We have searched Medline for the metabolic syndrome and its relation to CRC, and metformin as a potential treatment of colorectal cancer. Administration of metformin alone or in combination with chemotherapy has been shown to suppress CRC. The mechanism that explains how insulin resistance is associated with CRC is complex and not fully understood. In this review we have summarised studies which showed an association with the metabolic syndrome as well as studies which tackled metformin as a potential treatment of CRC. In addition, we have also provided a summary of how metformin at the cellular level can induce changes that suppress the activity of cancer cells.
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Hope C, Robertshaw A, Cheung KL, Idris I, English E. Relationship between HbA1c and cancer in people with or without diabetes: a systematic review. Diabet Med 2016; 33:1013-25. [PMID: 26577885 DOI: 10.1111/dme.13031] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/11/2015] [Indexed: 12/25/2022]
Abstract
AIM To identify the relationship between HbA1c and cancers in people with or without diabetes. BACKGROUND Cancer is a major public health problem, accounting for 8.2 million deaths worldwide in 2012. HbA1c level has been associated with the risk of developing certain cancers, although the existing evidence is conflicting. METHODS EMBASE, MEDLINE, CINAHL and the Cochrane Library were searched. Eligible articles included randomized controlled trials, cohort studies, case-control studies, systematic reviews and meta-analyses. Participants of either sex, with or without Type 1 or 2 diabetes, were included. The studies were assessed using the Scottish Intercollegiate Guidelines Network (SIGN) criteria by two independent assessors. No meta-analysis was performed because of the heterogeneity of results. RESULTS A total of 19 studies from 1006 met the inclusion criteria, of which 14 were cohort studies and five were nested case-control studies. Eight studies investigated outcomes for all cancer sites. Four of these studies reported that higher HbA1c levels were associated with higher incidence and/or mortality risk for all cancers. One study observed a U-shaped relationship between HbA1c and cancer incidence and mortality. Increasing HbA1c levels were associated with increasing risk of developing colorectal, pancreatic, respiratory and female genital tract cancers. No increased risk was observed for breast cancer, gastrointestinal or urological malignancies. CONCLUSION HbA1c appears to be associated with cancer incidence and/or cancer mortality, but further studies are needed to fully understand the complex relationship between HbA1c and cancer.
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Affiliation(s)
- C Hope
- School of Medicine, University of Nottingham, Royal Derby Hospital, Derby, UK
| | - A Robertshaw
- School of Medicine, University of Nottingham, Royal Derby Hospital, Derby, UK
| | - K L Cheung
- School of Medicine, University of Nottingham, Royal Derby Hospital, Derby, UK
| | - I Idris
- School of Medicine, University of Nottingham, Royal Derby Hospital, Derby, UK
| | - E English
- School of Medicine, University of Nottingham, Royal Derby Hospital, Derby, UK
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Associations Between Parameters of Glucose and Lipid Metabolism and Risk of Colorectal Neoplasm. Dig Dis Sci 2015; 60:2996-3004. [PMID: 25986527 DOI: 10.1007/s10620-015-3713-x] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2015] [Accepted: 05/07/2015] [Indexed: 01/24/2023]
Abstract
BACKGROUND Diabetes and dyslipidemia have been linked to an increased risk of colorectal neoplasm (CRN). However, previous studies evaluating these associations have shown inconsistent results, and large-scale studies are few in number. AIM To investigate the associations between the parameters of glucose and lipid metabolism and the presence of CRN. METHODS A cross-sectional study was performed on 38,490 Korean adults aged ≥30 years undergoing their first colonoscopy as part of routine preventive health care between 2010 and 2011. RESULTS The prevalence of overall CRN increased with increasing levels of glucose, hemoglobin A1c (HbA1c), insulin, homeostasis model assessment of insulin resistance (HOMA-IR), triglycerides, total cholesterol, low-density lipoprotein cholesterol (LDL-C), and apolipoprotein B (ApoB) and with decreasing level of apolipoprotein A1 (ApoA1). The adjusted prevalence ratios for overall CRN comparing the fourth with the first quartiles of fasting glucose, HbA1c, insulin, HOMA-IR, triglycerides, total cholesterol, LDL-C, ApoB, and ApoA-1 were 1.83 (95% CI 1.62-2.06), 1.17 (95% CI 1.03-1.33), 1.09 (95% CI 0.97-1.23), 1.22 (95% CI 1.08-1.37), 1.31 (95% CI 1.16-1.48), 1.19 (95 % CI 1.07-1.33), 1.38 (95% CI 1.23-1.54), 1.30 (95% CI 1.14-1.47), and 0.85 (95% CI 0.76-0.95), respectively. There was also a significant association between higher levels of glucose, LDL-C, and ApoB with a higher prevalence of advanced CRN. Moreover, the risk of CRN increased further in cases in which the parameters of glucose metabolism and lipid metabolism worsened simultaneously. CONCLUSIONS The levels of parameters of glucose and lipid metabolism are significantly associated with the prevalence of CRN. Altered glucose and lipid metabolism may contribute to the development of CRN.
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Rampal S, Yang MH, Sung J, Son HJ, Choi YH, Lee JH, Kim YH, Chang DK, Rhee PL, Rhee JC, Guallar E, Cho J. Association between markers of glucose metabolism and risk of colorectal adenoma. Gastroenterology 2014; 147:78-87.e3. [PMID: 24632359 DOI: 10.1053/j.gastro.2014.03.006] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2013] [Revised: 02/27/2014] [Accepted: 03/05/2014] [Indexed: 01/02/2023]
Abstract
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 A1c, 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 A1c, 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 A1c 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.
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Affiliation(s)
- Sanjay Rampal
- Department of Social and Preventive Medicine, Julius Centre University of Malaya, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; Department of Epidemiology and Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland
| | - Moon Hee Yang
- Center for Health Promotion, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Jidong Sung
- Center for Health Promotion, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea; Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Hee Jung Son
- Center for Health Promotion, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea; Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
| | - Yoon-Ho Choi
- Center for Health Promotion, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea; Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Jun Haeng Lee
- Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Young-Ho Kim
- Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Dong Kyung Chang
- Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Poong-Lyul Rhee
- Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Jong Chul Rhee
- Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Eliseo Guallar
- Department of Epidemiology and Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland; Department of Medicine and Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, Maryland
| | - Juhee Cho
- Department of Epidemiology and Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland; Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, South Korea; Biostatistics and Clinical Epidemiology Center, Research Institute for Future Medicine, Samsung Medical Center Sungkyunkwan University School of Medicine, Seoul, South Korea.
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de Beer JC, Liebenberg L. Does cancer risk increase with HbA1c, independent of diabetes? Br J Cancer 2014; 110:2361-8. [PMID: 24675382 PMCID: PMC4007234 DOI: 10.1038/bjc.2014.150] [Citation(s) in RCA: 80] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2013] [Revised: 02/24/2014] [Accepted: 02/26/2014] [Indexed: 12/31/2022] Open
Abstract
Background: The risks for several cancer types are increased in people with diabetes. Hyperglycaemia, hyperinsulinaemia, inflammation and altered hormonal concentrations are common characteristics between the two diseases and can all be linked to hyperglycaemia. Methods: Here, we use glycated haemoglobin (HbA1c) as a biomarker for chronic hyperglycaemia. We explore whether cancer risk increases with HbA1c, independent of diabetes, and, therefore, if risk is already increased below the diabetic HbA1c range, by analysing data from current studies linking HbA1c to risk of several cancer types. Results: The data reveal that chronic hyperglycaemia correlates with increased cancer risk for a number of cancers, except prostate cancer. Evidence is also provided that risk is already increased in the pre-diabetic and normal ranges for several cancers. Conclusions: These results merit urgent investigation into the risks and advantages of updating recommendations for stricter glycaemic control in diabetic and non-diabetic subjects, as this could help reduce the risk of cancer incidence and mortality.
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Affiliation(s)
- J C de Beer
- Center for Research and Continued Engineering Development, North-West University (Pretoria Campus), Suite No. 91, Private Bag X30, Lynnwood Ridge, Pretoria 0040, South Africa
| | - L Liebenberg
- 1] Center for Research and Continued Engineering Development, North-West University (Pretoria Campus), Suite No. 91, Private Bag X30, Lynnwood Ridge, Pretoria 0040, South Africa [2] TEMM International (Pty) Ltd, Pretoria, South Africa
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Muhidin SO, Magan AA, Osman KA, Syed S, Ahmed MH. The relationship between nonalcoholic fatty liver disease and colorectal cancer: the future challenges and outcomes of the metabolic syndrome. J Obes 2012; 2012:637538. [PMID: 23304464 PMCID: PMC3523590 DOI: 10.1155/2012/637538] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2012] [Accepted: 11/11/2012] [Indexed: 02/06/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is closely related to insulin resistance, metabolic syndrome, obesity, type 2 diabetes, and dyslipidaemia. Obesity and metabolic syndrome are associated with an increased cancer risk, and recent evidence demonstrated an association between NAFLD and colorectal cancer (CRC). The mechanism of how NAFLD can be associated with increased risk of CRC is not fully understood; however, NAFLD represents a condition of profound insulin resistance and a proinflammatory state. Insulin and insulin-like growth factors may promote the development of CRC through their proliferative and antiapoptotic effects. Patients with NAFLD have reduced expression of adiponectin, an adipokine with anti-inflammatory effects. Importantly, hypoadiponectinemia is associated with an increased risk of CRC. Decreased levels of adiponectin lead to increased insulin levels due to marked insulin resistance and in turn increased insulin growth factor-1 (IGF-1). Insulin binds to IGF-1 receptors and plays an important role in cell proliferation, apoptosis, and increased production of vascular endothelial growth factor, an angiogenic factor that supports cancer growth. Further studies are needed to establish (i) the pathophysiology of NAFLD with colorectal cancer, (ii) the benefit of early screening of CRC in NAFLD patients, and (iii) the impact of treatment of NAFLD in the modulation of the risk of colorectal cancer.
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Affiliation(s)
- Said O. Muhidin
- Department of Ophthalmology, Southampton University Hospitals, Southampton SO16 6YD, UK
| | - Ahmed A. Magan
- Department of Trauma & Orthopedics, Cambridge University Hospitals, Cambridge CB2 0QQ, UK
| | - Khalid A. Osman
- Department of Surgery, North Tyneside General Hospital, North Shields NE29 8NH, UK
| | - Shareef Syed
- Department of General Surgery, CMU Healthcare, Central Michigan University, Saginaw, MI 48602, USA
| | - Mohamed H. Ahmed
- Department of Medicine, Wexham Park Hospital, Slough, Berkshire SL2 4HL, UK
- *Mohamed H. Ahmed:
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