Abstract
Background
Whether type 2 diabetes is cause or consequence, or both, of pancreatic cancer (PaC) remains unresolved. Leveraging repeated measurements of fasting blood glucose (FBG), we examined the temporal relationship between hyperglycemia and PaC incidence.
Methods
We conducted a nested case–control study of 278 cases and 826 matched-controls from the Korean National Health Insurance Service-Health Screening Cohort. Over 11 years before index date (date of PaC diagnosis for cases), all participants had at least one FBG measurement in each of the three time windows: − 11 to − 8, − 7 to − 4, and − 3 to 0 years. Using conditional logistic regression, we estimated odds ratios(ORs) of PaC and 95% confidence intervals (CIs) for hyperglycemia in the overall period and at each interval; for major long-term patterns of FBG across the three intervals (recent-onset, medium-term, and long-standing hyperglycemia).
Results
Higher FBG over the past 11 years was associated with an increased odds of PaC (p trend < .0001), with recent FBG more predictive of PaC than distant FBG. By FBG assessed in the − 3 to 0 interval, OR was 1.97 (95% CI 1.32–2.93) for 110–125 mg/dL and 3.17 (95% CI 2.09–4.80) for ≥ 126 mg/dL. By long-term patterns of FBG, compared to consistent normoglycemia, OR was 2.02 (95% CI 1.24–3.31) for long-standing hyperglycemia and 3.38 (95% CI 1.87–6.13) for recent-onset hyperglycemia. These associations were more pronounced among never-smokers than ever-smokers (p interaction = .06).
Conclusion
Recent-onset hyperglycemia may be an early manifestation of undetected PaC, while long-lasting hyperglycemia may serve as a moderate etiologic factor for PaC.
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References
Siegel RL, Miller KD, Jemal A (2016) Cancer statistics, 2016. CA Cancer J Clin 66:7–30
International Agency for Research on Cancer. Globocan 2012: Estimated Cancer Incidence, Mortality and Prevalence Worldwide in 2012. http://globocan.iarc.fr/Pages/fact_sheets_population.aspx. Accessed 21 Feb 2017
The US National Cancer Institute. Cancer Stat Facts: Pancreas Cancer. https://seer.cancer.gov/statfacts/html/pancreas.html. Accessed 21 Feb 2017
Yachida S, Iacobuzio-Donahue CA (2013) Evolution and dynamics of pancreatic cancer progression. Oncogene 32:5253–5260
Muniraj T, Chari ST (2012) Diabetes and pancreatic cancer. Minerva gastroenterologica e dietologica 58:331–345
Pannala R, Basu A, Petersen GM, Chari ST (2009) New-onset diabetes: a potential clue to the early diagnosis of pancreatic cancer. Lancet Oncol 10:88–95
Han L, Ma Q, Li J et al (2011) High glucose promotes pancreatic cancer cell proliferation via the induction of EGF expression and transactivation of EGFR. PLoS ONE 6:e27074
Giovannucci E, Harlan DM, Archer MC et al (2010) Diabetes and cancer: a consensus report. Diabetes Care 33:1674–1685
Sah RP, Nagpal SJS, Mukhopadhyay D, Chari ST. (2013) New insights into pancreatic cancer-induced paraneoplastic diabetes. Nat Rev Gastrol Hepatol 10:423–433
Pang JX, Hsu JP, Yeo TW, Leo YS, Lye DC (2017) Diabetes, cardiac disorders and asthma as risk factors for severe organ involvement among adult dengue patients: a matched case–control study. Sci Rep 7:39872
Fisher-Hoch SP, Vatcheva KP, Rahbar MH, McCormick JB (2015) Undiagnosed diabetes and pre-diabetes in health disparities. PLoS ONE 10:e0133135
Chari ST, Leibson CL, Rabe KG et al (2008) Pancreatic cancer-associated diabetes mellitus: prevalence and temporal association with diagnosis of cancer. Gastroenterology 134:95–101
Quan H, Sundararajan V, Halfon P et al (2005) Coding algorithms for defining comorbidities in ICD-9-CM and ICD-10 administrative data. Medical Care 43:1130–1139
American Diabetes Association (2010) Diagnosis and classification of diabetes mellitus. Diabetes Care 33(Suppl 1):S62–S69
Ardisson Korat AV, Willett WC, Hu FB (2014) Diet, lifestyle, and genetic risk factors for type 2 diabetes: a review from the Nurses’ Health Study, Nurses’ Health Study 2, and Health Professionals’ follow-up study. Curr Nutr Rep 3:345–354
Kahn SE, Prigeon RL, Schwartz RS et al (2001) Obesity, body fat distribution, insulin sensitivity and Islet beta-cell function as explanations for metabolic diversity. J Nutr 131:354S–360S
Lim U, Ernst T, Buchthal SD et al (2011) Asian women have greater abdominal and visceral adiposity than Caucasian women with similar body mass index. Nutr Diabetes 1:e6
Hu FB (2011) Globalization of diabetes: the role of diet, lifestyle, and genes. Diabetes Care 34:1249–1257
Liao WC, Tu YK, Wu MS, Lin JT, Wang HP, Chien KL. (2015) Blood glucose concentration and risk of pancreatic cancer: systematic review and dose-response meta-analysis. BMJ-Brit Med J 349:g7371
Ramlo-Halsted BA, Edelman SV (1999) The natural history of type 2 diabetes: implications for clinical practice. Primary Care 26:771–789
Wolpin BM, Bao Y, Qian ZR et al (2013) Hyperglycemia, insulin resistance, impaired pancreatic -cell function, and risk of pancreatic cancer. JNCI-J Natl Cancer Inst 105:1027–1035
Mayers JR, Wu C, Clish CB et al (2014) Elevation of circulating branched-chain amino acids is an early event in human pancreatic adenocarcinoma development. Nat Med 20:1193–1198
Cohen R, Neuzillet C, Tijeras-Raballand A, Faivre S, de Gramont A, Raymond E (2015) Targeting cancer cell metabolism in pancreatic adenocarcinoma. Oncotarget 6:16832–16847
Boroughs LK, DeBerardinis RJ (2015) Metabolic pathways promoting cancer cell survival and growth. Nat Cell Biol 17:351–359
Vincent A, Herman J, Schulick R, Hruban RH, Goggins M (2011) Pancreatic cancer. Lancet 378:607–620
Sinacore DR, Gulve EA. (1993) The role of skeletal muscle in glucose transport, glucose homeostasis, and insulin resistance: implications for physical therapy. Phys Ther 73:878–891
Chan JM, Rimm EB, Colditz GA, Stampfer MJ, Willett WC (1994) Obesity, fat distribution, and weight gain as risk factors for clinical diabetes in men. Diabetes Care 17:961–969
Hu Y, Bhupathiraju SN, de Koning L, Hu FB (2014) Duration of obesity and overweight and risk of type 2 diabetes among US women. Obesity 22:2267–2273
Hu FB, Leitzmann MF, Stampfer MJ, Colditz GA, Willett WC, Rimm EB (2001) Physical activity and television watching in relation to risk for type 2 diabetes mellitus in men. Arch Intern Med 161:1542–1548
Grontved A, Pan A, Mekary RA et al (2014) Muscle-strengthening and conditioning activities and risk of type 2 diabetes: a prospective study in two cohorts of US women. PLoS Med 11:e1001587
Munigala S, Singh A, Gelrud A, Agarwal B (2015) Predictors for pancreatic cancer diagnosis following new-onset diabetes mellitus. Clin Transl Gastroenterol 6:e118
Davidson MB, Schriger DL, Peters AL, Lorber B (1999) Relationship between fasting plasma glucose and glycosylated hemoglobin: potential for false-positive diagnoses of type 2 diabetes using new diagnostic criteria. JAMA 281:1203–1210
Pang Y, Kartsonaki C, Guo Y et al. (2017) Diabetes, plasma glucose and incidence of pancreatic cancer: a prospective study of 0.5 million Chinese adults and a meta-analysis of 22 cohort studies. Int J Cancer 140:1781
Acknowledgments
This study used NHIS-HealS data (NHIS-2017-2-304) made by National Health Insurance Service (NHIS).
Funding
This work was supported by a Grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (Grant Number: HI13C0715). Dr. Bao was supported by NIH Grants KL2 TR001100, U54CA155626 and P30 DK046200, and by Department of Defense Grant CA150357.
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10552_2017_988_MOESM1_ESM.jpg
Supplementary Fig. 1 Median Fasting Blood Glucose of Case and Control Groups across Time Windows before Index Date (JPG 31 KB)
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Keum, N., Ha, K.H., Bao, Y. et al. Long-term patterns of fasting blood glucose levels and pancreatic cancer incidence. Cancer Causes Control 29, 135–142 (2018). https://doi.org/10.1007/s10552-017-0988-6
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DOI: https://doi.org/10.1007/s10552-017-0988-6