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In Reply

Research Institute for National Cancer Control and Evaluation, National Cancer Center, Goyang, Gyeonggi, Korea

We read with great interest the letter from Drs Farooki and Schneider, and we agree with their insightful comment that increased fasting serum glucose levels could be antiangiogenic as well as proinflammatory.

In our report on male cancer patients in Korea, we suggested that prediagnosis insulin resistance might contribute to poor survival through the selective growth advantage of cancer cells.¹ As Drs Farooki and Schneider suggest, inflammation could be a mechanism for that. Many studies have shown that elevation of proinflammatory markers such as C-reactive protein, interleukin 6, and tumor necrosis factor- are associated with insulin resistance.^2,3 Inflammation has been invoked as a potential contributory factor in the development of several cancers and other chronic disease.^4-6 Moreover, some proinflammatory cytokines and C-reactive protein are factors for poor prognosis in cancer patients.^7-10 In our cohort, unfortunately, inflammation data were not collected, but previous findings raise the possibility that reducing insulin resistance in cancer patients might improve outcome by decreasing both cancer cell growth and inflammation.^1,4-6

In addition, insulin resistance could increase angiogenesis in cancer.^1,11 Insulin-like growth factor-1 stimulates angiogenesis by increasing vascular endothelial growth factor production in cancer cells.^11,12 In our study, we assessed fasting blood glucose level before cancer diagnosis rather than at the same time. This unique feature of our study suggested that groups at high risk of cancer need to be educated about how to improve their health behavior and reduce insulin resistance—not only to prevent cancer, but also to improve prognosis.

We also agree with Drs Farooki and Schneider that diabetic patients may have a subclinical reduction in major organ system function, thereby blurring the precise cause of death. We considered that concurrent adverse health conditions or comorbidities could increase overall mortality among cancer patients.¹ When we confined our analysis to cancer-related deaths and adjusted for other comorbidities, the results were similar to those for overall mortality. Thus, we did not conclude that strict or aggressive control of insulin resistance is likely to improve morbidity or mortality in cancer patients but suggested, instead, that reducing it might improve survival.

In conclusion, we agree with Drs Farooki and Schneider that research on the effects of strict control of the insulin-resistant, hyperglycemic state in cancer patients is needed. Together with advances in treatment, this could lead to increased survival for cancer patients with diabetic conditions and organ function loss.

AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

The authors indicated no potential conflicts of interest.

REFERENCES

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2. Festa A, Hanley AJ, Tracy RP, et al: Inflammation in the prediabetic state is related to increased insulin resistance rather than decreased insulin secretion. Circulation 108:1822-1830, 2003[CrossRef][Medline]
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8. Martin F, Santolaria F, Batista N, et al: Cytokine levels (IL-6 and IFN-gamma), acute phase response and nutritional status as prognostic factors in lung cancer. Cytokine 11:80-86, 1999[CrossRef][Medline]
9. Chung YC, Chang YF: Significance of inflammatory cytokines in the progression of colorectal cancer. Hepatogastroenterology 50:1910-1913, 2003[Medline]
10. Ramsey S, Lamb GW, Aitchison M, et al: Evaluation of an inflammation-based prognostic score in patients with metastatic renal cancer. Cancer 109:205-212, 2007[CrossRef][Medline]
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