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Published in: BMC Endocrine Disorders 1/2020

Open Access 01-12-2020 | Insulins | Research article

Triglyceride–glucose index (TyG index) is a predictor of incident colorectal cancer: a population-based longitudinal study

Authors: Takuro Okamura, Yoshitaka Hashimoto, Masahide Hamaguchi, Akihiro Obora, Takao Kojima, Michiaki Fukui

Published in: BMC Endocrine Disorders | Issue 1/2020

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Abstract

Background

Colorectal cancer (CRC), which is related with insulin resistance, is a one of the most common cancers. Triglyceride-glucose index (TyG index) was made for a marker of insulin resistance. We conducted the investigation of association between TyG index and incident CRC.

Methods

We examined the affect of TyG index on incident CRC in this historical cohort study of 27,944 (16,454 men and 11,490 women) participants. TyG index was calculated as ln [fasting triglycerides (mg/dL) × fasting plasma glucose (mg/dL)/2]. The impact of TyG index on incident CRC was investigated using Cox proportional hazard models, adjusting for sex, age, body mass index, smoking status, alcohol consumption, exercise, systolic blood pressure and creatinine. The covariate-adjusted receiver operating characteristic (ROC) curve calculated the area under the curve (AUC) and cut-off value of TyG index for the incidence of CRC.

Results

During the median 4.4-year follow-up, 116 participants were diagnosed as CRC. The cumulative incidence rate of CRC were 0.4%. In Cox proportional hazard model, the HRs of TyG index were 1.38 (95% Confidence interval (CI), 1.00–1.91, p = 0.049) after adjusting for covariates. In the covariate-adjusted ROC curve analysis, the cut-off value of TyG index for incident CRC was 8.272 (AUC 0.687 (95%CI, 0.637–737, sensitivity = 0.620, specificity = 0.668, p < 0.001)).

Conclusions

TyG index can predict the onset of CRC. For early detection of CRC, we should encourage people with high TyG index to undergo screening for CRC.
Literature
2.
go back to reference Ahmed RL, Schmitz KH, Anderson KE, Rosamond WD, Folsom AR. The metabolic syndrome and risk of incident colorectal cancer. Cancer. 2006;107:28–36.PubMedCrossRef Ahmed RL, Schmitz KH, Anderson KE, Rosamond WD, Folsom AR. The metabolic syndrome and risk of incident colorectal cancer. Cancer. 2006;107:28–36.PubMedCrossRef
3.
go back to reference Russo A, Autelitano M, Bisanti L. Metabolic syndrome and cancer risk. Eur J Cancer. 2008;44:293–7.PubMedCrossRef Russo A, Autelitano M, Bisanti L. Metabolic syndrome and cancer risk. Eur J Cancer. 2008;44:293–7.PubMedCrossRef
4.
go back to reference Stocks T, Lukanova A, Johansson M, et al. Components of the metabolic syndrome and colorectal cancer risk; a prospective study. Int J Obes. 2008;32:304–14.CrossRef Stocks T, Lukanova A, Johansson M, et al. Components of the metabolic syndrome and colorectal cancer risk; a prospective study. Int J Obes. 2008;32:304–14.CrossRef
5.
go back to reference Inoue M, Noda M, Kurahashi N, et al. Impact of metabolic factors on subsequent cancer risk: results from a large-scale population-based cohort study in Japan. Eur J Cancer Prev. 2009;18:240–7.PubMedCrossRef Inoue M, Noda M, Kurahashi N, et al. Impact of metabolic factors on subsequent cancer risk: results from a large-scale population-based cohort study in Japan. Eur J Cancer Prev. 2009;18:240–7.PubMedCrossRef
6.
go back to reference Aleksandrova K, Boeing H, Jenab M, et al. Metabolic syndrome and risks of colon and Rectal cancer: the European prospective investigation into cancer and nutrition study. Cancer Prev Res. 2011;4:1873–83.CrossRef Aleksandrova K, Boeing H, Jenab M, et al. Metabolic syndrome and risks of colon and Rectal cancer: the European prospective investigation into cancer and nutrition study. Cancer Prev Res. 2011;4:1873–83.CrossRef
7.
go back to reference McKeown-Eyssen G. Epidemiology of colorectal cancer revisited: are serum triglycerides and/or plasma glucose associated with risk? Cancer Epidemiol Biomark Prev. 1994;3:687–95. McKeown-Eyssen G. Epidemiology of colorectal cancer revisited: are serum triglycerides and/or plasma glucose associated with risk? Cancer Epidemiol Biomark Prev. 1994;3:687–95.
8.
go back to reference Palmqvist R, Hallmans G, Rinaldi S, et al. Plasma insulin-like growth factor 1, insulin-like growth factor binding protein 3, and risk of colorectal cancer: a prospective study in northern Sweden. Gut. 2002;50:642–6.PubMedPubMedCentralCrossRef Palmqvist R, Hallmans G, Rinaldi S, et al. Plasma insulin-like growth factor 1, insulin-like growth factor binding protein 3, and risk of colorectal cancer: a prospective study in northern Sweden. Gut. 2002;50:642–6.PubMedPubMedCentralCrossRef
9.
go back to reference Giovannucci E. Insulin, insulin-like growth factors and colon cancer: a review of the evidence. J Nutr. 2001;131:3109–20.CrossRef Giovannucci E. Insulin, insulin-like growth factors and colon cancer: a review of the evidence. J Nutr. 2001;131:3109–20.CrossRef
10.
go back to reference Friedrich N, Thuesen B, Jorgensen T, et al. The association between IGF-I and insulin resistance: a general population study in Danish adults. Diabetes Care. 2012;35:768–73.PubMedPubMedCentralCrossRef Friedrich N, Thuesen B, Jorgensen T, et al. The association between IGF-I and insulin resistance: a general population study in Danish adults. Diabetes Care. 2012;35:768–73.PubMedPubMedCentralCrossRef
11.
go back to reference Saldeen J, Welsh N. p38 MAPK inhibits JNK2 and mediates cytokine-activated iNOS induction and apoptosis independently of NF-KB translocation in insulin-producing cells. Eur Cytokine Netw. 2004;15:47–52.PubMed Saldeen J, Welsh N. p38 MAPK inhibits JNK2 and mediates cytokine-activated iNOS induction and apoptosis independently of NF-KB translocation in insulin-producing cells. Eur Cytokine Netw. 2004;15:47–52.PubMed
12.
go back to reference Bogazzi F, Ultimieri F, Raggi F, et al. PPARgamma inhibits GH synthesis and secretion and increases apoptosis of pituitary GH-secreting adenomas. Eur J Endocrinol. 2004;150:863–75.PubMedCrossRef Bogazzi F, Ultimieri F, Raggi F, et al. PPARgamma inhibits GH synthesis and secretion and increases apoptosis of pituitary GH-secreting adenomas. Eur J Endocrinol. 2004;150:863–75.PubMedCrossRef
13.
go back to reference Schoen RE, Tangen CM, Kuller LH, et al. Increased blood glucose and insulin, body size, and incident colorectal cancer. J Natl Cancer Inst. 1999;91:1147–54.PubMedCrossRef Schoen RE, Tangen CM, Kuller LH, et al. Increased blood glucose and insulin, body size, and incident colorectal cancer. J Natl Cancer Inst. 1999;91:1147–54.PubMedCrossRef
14.
go back to reference Yamamoto S, Nakagawa T, Matsushita Y, et al. Visceral fat area and markers of insulin resistance in relation to colorectal neoplasia. Diabetes Care. 2010;33:184–9.PubMedCrossRef Yamamoto S, Nakagawa T, Matsushita Y, et al. Visceral fat area and markers of insulin resistance in relation to colorectal neoplasia. Diabetes Care. 2010;33:184–9.PubMedCrossRef
15.
go back to reference Limburg PJ, Stolzenberg-Solomon RZ, Vierkant RA, et al. Insulin, glucose, insulin resistance, and incident colorectal cancer in male smokers. Clin Gastroenterol Hepatol. 2006;4:1514–21.PubMedPubMedCentralCrossRef Limburg PJ, Stolzenberg-Solomon RZ, Vierkant RA, et al. Insulin, glucose, insulin resistance, and incident colorectal cancer in male smokers. Clin Gastroenterol Hepatol. 2006;4:1514–21.PubMedPubMedCentralCrossRef
16.
go back to reference Simental-Mendía LE, Rodríguez-Morán M, Guerrero-Romero F. The product of fasting glucose and triglycerides as surrogate for identifying insulin resistance in apparently healthy subjects. Metab Syndr Relat Disord. 2008;6:299–304.PubMedCrossRef Simental-Mendía LE, Rodríguez-Morán M, Guerrero-Romero F. The product of fasting glucose and triglycerides as surrogate for identifying insulin resistance in apparently healthy subjects. Metab Syndr Relat Disord. 2008;6:299–304.PubMedCrossRef
17.
go back to reference Du T, Yuan G, Zhang M, Zhou X, Sun X, Yu X. Clinical usefulness of lipid ratios, visceral adiposity indicators, and the triglycerides and glucose index as risk markers of insulin resistance. Cardiovasc Diabetol. 2014;13:146.PubMedPubMedCentralCrossRef Du T, Yuan G, Zhang M, Zhou X, Sun X, Yu X. Clinical usefulness of lipid ratios, visceral adiposity indicators, and the triglycerides and glucose index as risk markers of insulin resistance. Cardiovasc Diabetol. 2014;13:146.PubMedPubMedCentralCrossRef
18.
go back to reference Navarro-González D, Sánchez-Íñigo L, Pastrana-Delgado J, Fernández-Montero A, Martinez JA. Triglyceride–glucose index (TyG index) in comparison with fasting plasma glucose improved diabetes prediction in patients with normal fasting glucose: the vascular-metabolic CUN cohort. Prev Med (Baltim). 2016;86:99–105.CrossRef Navarro-González D, Sánchez-Íñigo L, Pastrana-Delgado J, Fernández-Montero A, Martinez JA. Triglyceride–glucose index (TyG index) in comparison with fasting plasma glucose improved diabetes prediction in patients with normal fasting glucose: the vascular-metabolic CUN cohort. Prev Med (Baltim). 2016;86:99–105.CrossRef
19.
go back to reference Low S, Chin Jonathon Khoo K, Irwan B, et al. The role of triglyceride glucose index in development of type 2 diabetes mellitus. Diabetes Res Clin Pract. 2018;143:43–9.PubMedCrossRef Low S, Chin Jonathon Khoo K, Irwan B, et al. The role of triglyceride glucose index in development of type 2 diabetes mellitus. Diabetes Res Clin Pract. 2018;143:43–9.PubMedCrossRef
20.
go back to reference Sánchez-Íñigo L, Navarro-González D, Fernández-Montero A, Pastrana-Delgado J, Martínez JA. The TyG index may predict the development of cardiovascular events. Eur J Clin Investig. 2016;46:189–97.CrossRef Sánchez-Íñigo L, Navarro-González D, Fernández-Montero A, Pastrana-Delgado J, Martínez JA. The TyG index may predict the development of cardiovascular events. Eur J Clin Investig. 2016;46:189–97.CrossRef
21.
go back to reference Hamaguchi M, Kojima T, Takeda N, et al. The metabolic syndrome as a predictor of nonalcoholic fatty liver disease. Ann Intern Med. 2005;143:722–8.PubMedCrossRef Hamaguchi M, Kojima T, Takeda N, et al. The metabolic syndrome as a predictor of nonalcoholic fatty liver disease. Ann Intern Med. 2005;143:722–8.PubMedCrossRef
22.
go back to reference Hashimoto Y, Hamaguchi M, Kojima T, et al. Modest alcohol consumption reduces the incidence of fatty liver in men: a population-based large-scale cohort study. J Gastroenterol Hepatol. 2015;30:546–52.PubMedCrossRef Hashimoto Y, Hamaguchi M, Kojima T, et al. Modest alcohol consumption reduces the incidence of fatty liver in men: a population-based large-scale cohort study. J Gastroenterol Hepatol. 2015;30:546–52.PubMedCrossRef
23.
go back to reference Ryu S, Chang Y, Kim D-I, Kim WS, Suh B-S. Glutamyltransferase as a predictor of chronic kidney disease in nonhypertensive and nondiabetic Korean men. Clin Chem. 2006;53:71–7.PubMedCrossRef Ryu S, Chang Y, Kim D-I, Kim WS, Suh B-S. Glutamyltransferase as a predictor of chronic kidney disease in nonhypertensive and nondiabetic Korean men. Clin Chem. 2006;53:71–7.PubMedCrossRef
24.
go back to reference Wulaningsih W, Garmo H, Holmberg L, et al. Serum lipids and the risk of gastrointestinal malignancies in the Swedish AMORIS study. J Cancer Epidemiol. 2012;2012:792034.PubMedPubMedCentralCrossRef Wulaningsih W, Garmo H, Holmberg L, et al. Serum lipids and the risk of gastrointestinal malignancies in the Swedish AMORIS study. J Cancer Epidemiol. 2012;2012:792034.PubMedPubMedCentralCrossRef
25.
go back to reference Colditz GA, Atwood KA, Emmons K, et al. Harvard report on cancer prevention volume 4: Harvard cancer risk index. Risk index working group, Harvard center for cancer prevention. Cancer Causes Control. 2000;11:477–88.PubMedCrossRef Colditz GA, Atwood KA, Emmons K, et al. Harvard report on cancer prevention volume 4: Harvard cancer risk index. Risk index working group, Harvard center for cancer prevention. Cancer Causes Control. 2000;11:477–88.PubMedCrossRef
27.
go back to reference Sekine Y, Koike H, Nakano T, Nakajima K, Suzuki K. Remnant lipoproteins stimulate proliferation and activate MAPK and Akt signaling pathways via G protein-coupled receptor in PC-3 prostate cancer cells. Clin Chim Acta. 2007;383:78–84.PubMedCrossRef Sekine Y, Koike H, Nakano T, Nakajima K, Suzuki K. Remnant lipoproteins stimulate proliferation and activate MAPK and Akt signaling pathways via G protein-coupled receptor in PC-3 prostate cancer cells. Clin Chim Acta. 2007;383:78–84.PubMedCrossRef
28.
go back to reference Johnson SM, Gulhati P, Rampy BA, et al. Novel expression patterns of PI3K/Akt/mTOR signaling pathway components in colorectal cancer. J Am Coll Surg. 2010;210:767–78.PubMedPubMedCentralCrossRef Johnson SM, Gulhati P, Rampy BA, et al. Novel expression patterns of PI3K/Akt/mTOR signaling pathway components in colorectal cancer. J Am Coll Surg. 2010;210:767–78.PubMedPubMedCentralCrossRef
29.
30.
go back to reference Wang X, Häring M-F, Rathjen T, et al. Insulin resistance in vascular endothelial cells promotes intestinal tumour formation. Oncogene. 2017;36:4987–96.PubMedPubMedCentralCrossRef Wang X, Häring M-F, Rathjen T, et al. Insulin resistance in vascular endothelial cells promotes intestinal tumour formation. Oncogene. 2017;36:4987–96.PubMedPubMedCentralCrossRef
32.
go back to reference Warren RS, Yuan H, Matli MR, Ferrara N, Donner DB. Induction of vascular endothelial growth factor by insulin-like growth factor 1 in colorectal carcinoma. J Biol Chem. 1996;271:29483–8.PubMedCrossRef Warren RS, Yuan H, Matli MR, Ferrara N, Donner DB. Induction of vascular endothelial growth factor by insulin-like growth factor 1 in colorectal carcinoma. J Biol Chem. 1996;271:29483–8.PubMedCrossRef
33.
go back to reference Shiratsuchi I, Akagi Y, Kawahara A, et al. Expression of IGF-1 and IGF-1R and their relation to clinicopathological factors in colorectal cancer. Anticancer Res. 2011;31:2541–5.PubMed Shiratsuchi I, Akagi Y, Kawahara A, et al. Expression of IGF-1 and IGF-1R and their relation to clinicopathological factors in colorectal cancer. Anticancer Res. 2011;31:2541–5.PubMed
34.
go back to reference Maile LA, Capps BE, Ling Y, Xi G, Clemmons DR. Hyperglycemia alters the responsiveness of smooth muscle cells to insulin-like growth factor-I. Endocrinology. 2007;148:2435–43.PubMedCrossRef Maile LA, Capps BE, Ling Y, Xi G, Clemmons DR. Hyperglycemia alters the responsiveness of smooth muscle cells to insulin-like growth factor-I. Endocrinology. 2007;148:2435–43.PubMedCrossRef
35.
go back to reference Aljada A, Friedman J, Ghanim H, Mohanty P, Hofmeyer D, Chaudhuri A, et al. Glucose ingestion induces an increase in intranuclear nuclear factor κB, a fall in cellular inhibitor κB, and an increase in tumor necrosis factor α messenger RNA by mononuclear cells in healthy human subjects. Metabolism. 2006;55:1177–85.PubMedCrossRef Aljada A, Friedman J, Ghanim H, Mohanty P, Hofmeyer D, Chaudhuri A, et al. Glucose ingestion induces an increase in intranuclear nuclear factor κB, a fall in cellular inhibitor κB, and an increase in tumor necrosis factor α messenger RNA by mononuclear cells in healthy human subjects. Metabolism. 2006;55:1177–85.PubMedCrossRef
36.
go back to reference Chen C, Edelstein LC, Gélinas C. The Rel/NF-kappaB family directly activates expression of the apoptosis inhibitor Bcl-x (L). Mol Cell Biol. 2000;20:2687–95.PubMedPubMedCentralCrossRef Chen C, Edelstein LC, Gélinas C. The Rel/NF-kappaB family directly activates expression of the apoptosis inhibitor Bcl-x (L). Mol Cell Biol. 2000;20:2687–95.PubMedPubMedCentralCrossRef
37.
go back to reference Slattery ML, Mullany LE, Sakoda L, et al. The NF-κB signalling pathway in colorectal cancer: associations between dysregulated gene and miRNA expression. J Cancer Res Clin Oncol. 2018;144:269–83.PubMedCrossRef Slattery ML, Mullany LE, Sakoda L, et al. The NF-κB signalling pathway in colorectal cancer: associations between dysregulated gene and miRNA expression. J Cancer Res Clin Oncol. 2018;144:269–83.PubMedCrossRef
38.
go back to reference Sarraf P, Mueller E, Jones D, et al. Differentiation and reversal of malignant changes in colon cancer through PPARγ. Nat Med. 1998;4:1046–52.PubMedCrossRef Sarraf P, Mueller E, Jones D, et al. Differentiation and reversal of malignant changes in colon cancer through PPARγ. Nat Med. 1998;4:1046–52.PubMedCrossRef
39.
go back to reference Sarraf P, Mueller E, Smith WM, et al. Loss-of-function mutations in PPAR gamma associated with human colon cancer. Mol Cell. 1999;3:799–804.PubMedCrossRef Sarraf P, Mueller E, Smith WM, et al. Loss-of-function mutations in PPAR gamma associated with human colon cancer. Mol Cell. 1999;3:799–804.PubMedCrossRef
40.
go back to reference Gong Z, Xie D, Deng Z, et al. The PPAR Pro12Ala polymorphism and risk for incident sporadic colorectal adenomas. Carcinogenesis. 2004;26:579–85.PubMedCrossRef Gong Z, Xie D, Deng Z, et al. The PPAR Pro12Ala polymorphism and risk for incident sporadic colorectal adenomas. Carcinogenesis. 2004;26:579–85.PubMedCrossRef
41.
go back to reference Shimada T, Kojima K, Yoshiura K, Hiraishi H, Terano A. Characteristics of the peroxisome proliferator activated receptor gamma (PPARgamma) ligand induced apoptosis in colon cancer cells. Gut. 2002;50:658–64.PubMedPubMedCentralCrossRef Shimada T, Kojima K, Yoshiura K, Hiraishi H, Terano A. Characteristics of the peroxisome proliferator activated receptor gamma (PPARgamma) ligand induced apoptosis in colon cancer cells. Gut. 2002;50:658–64.PubMedPubMedCentralCrossRef
42.
go back to reference Kubota N, Terauchi Y, Miki H, et al. PPAR gamma mediates high-fat diet-induced adipocyte hypertrophy and insulin resistance. Mol Cell. 1999;4:597–609.PubMedCrossRef Kubota N, Terauchi Y, Miki H, et al. PPAR gamma mediates high-fat diet-induced adipocyte hypertrophy and insulin resistance. Mol Cell. 1999;4:597–609.PubMedCrossRef
43.
go back to reference Lefebvre AM, Chen I, Desreumaux P, et al. Activation of the peroxisome proliferator-activated receptor gamma promotes the development of colon tumors in C57BL/6J-APCMin/+ mice. Nat Med. 1998;4:1053–7.PubMedCrossRef Lefebvre AM, Chen I, Desreumaux P, et al. Activation of the peroxisome proliferator-activated receptor gamma promotes the development of colon tumors in C57BL/6J-APCMin/+ mice. Nat Med. 1998;4:1053–7.PubMedCrossRef
Metadata
Title
Triglyceride–glucose index (TyG index) is a predictor of incident colorectal cancer: a population-based longitudinal study
Authors
Takuro Okamura
Yoshitaka Hashimoto
Masahide Hamaguchi
Akihiro Obora
Takao Kojima
Michiaki Fukui
Publication date
01-12-2020
Publisher
BioMed Central
Published in
BMC Endocrine Disorders / Issue 1/2020
Electronic ISSN: 1472-6823
DOI
https://doi.org/10.1186/s12902-020-00581-w

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