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Hyperglycemia, Insulin Resistance, and the Risk of Pancreatic Cancer

; Atlanta Vol. 35, Iss. 19,  (Oct 2013).

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Dr. Ershler reports no financial relationships relevant to this field of study. This article originally appeared in the August 2013 issue of Clinical Oncology Alert.

Source: Wolpin BM, et al. Hyperglycemia, insulin resistance, imparired pancreatic ß-cell function, and risk of pancreatic cancer. J Natl Cancer Inst 2013;105:1027-1035.

Pancreatic cancer remains both a challenge to diagnose and an even greater challenge to effectively treat. In fact, only patients discovered early and with resectable disease have a chance for long-term survival. Unfortunately, the majority of patients (> 85%) have unresectable disease by the time disease-associated symptoms occur and a diagnosis is made. 1 Patients who have the greatest chance for curative resection are those who have their tumors diagnosed when under evaluation for other problems and the pancreatic mass is discovered before symptoms occur. The timeline for progression of pancreatic cancer from resectable to unresectable is unknown. Glucose intolerance is known to occur in a substantial percentage of pancreatic cancer patients and it may occur earlier than other signs or symptoms of disease. 2-5 Yet the relationship between glucose metabolism and pancreatic cancer remains unclear, and an observed associated risk could be secondary to consequences of peripheral insulin resistance, pancreatic ß-cell dysfunction, or hyperglycemia itself. Hemoglobin A1c (HbA1c) is a measure of hyperglycemia, whereas plasma insulin and proinsulin are markers of peripheral insulin resistance, 6 and the proinsulin to insulin ratio marks pancreatic ß-cell dysfunction. 7

Capitalizing on data from five prospective U.S. cohorts followed through 2008, Wolpin and colleagues performed a nested, case-control study of 449 pancreatic cancer patients and 982 control subjects, all of whom had prediagnostic blood samples but no prior diagnosis of diabetes. Two or three control subjects were matched to each case patient by year of birth, cohort, smoking, and fasting status. Pancreatic cancer risk was assessed by...