1 Exponent Health Group, Washington, DC 20036
2 Division of Epidemiology, School of Public Health, University of Minnesota, Minneapolis, MN 55454
We appreciate Dr. Mutis letter (1) and his interest in our paper (2). We will address each of his points in turn. First, given that our paper was a brief report, we did not have space to describe the details of our highly standardized blood collection and processing protocol (see http://www.cscc.unc.edu/aric/visit/index.phtml?visit=1) and referred readers to previous reports from the Atherosclerosis Risk in Communities (ARIC) Study (3, 4). Venous blood was carefully drawn (serum separating tubes, for glucose and insulin) and processed within an hour. Serum and plasma aliquots were stored at 70°C until analysis at central research laboratories within 23 weeks. We reported the respectable short-term reliability coefficients for glucose (r = 0.84) and insulin (r = 0.81) in our paper, based on repeated sampling of individuals over several weeks, but Eckfeldt et al. (4) reported more detailed indices of laboratory variability.
Second, participants were asked to fast during the 12 hours prior to the clinic examination, and as not all did fast, compliance with this request was recorded. As described in the paper, we excluded women from the insulin analyses if they had not fasted for at least 8 hours prior to the blood draw. There was no need to do this for glucose, as a nonfasting level of at least 200 mg/dl is generally accepted to be in the diabetic range.
Third, we excluded diabetic women from the analyses of fasting insulin for several reasons. 1) Endogenous insulin levels are largely uninterpretable in the diabetic women taking exogenous insulin; in fact, exogenous insulin may interfere with the assay. 2) Among women taking oral hypoglycemic agents, fasting insulin levels may not reflect their natural state. 3) Finally, although we could have included untreated diabetic women in the analysis of insulin level and breast cancer, their levels may have fallen as a result of some degree of pancreatic beta-cell exhaustion. We therefore believed the most unbiased estimate of the association of insulin with breast cancer would come from the nondiabetic women, of whom many had high insulin levels.
Fourth, we agree with the author that menopausal status is an important effect modifier for several breast cancer risk factors. We reported no evidence of effect modification by age group. In addition, we found no evidence of effect modification when analyses were stratified by baseline menopausal status. However, less than 22 percent of the person-years in this analysis was among premenopausal women, and the relative risk estimates were unstable among these women.
In summary, Dr. Mutis concerns, which could not be addressed fully in our brief report, seem unlikely to have had an impact on our conclusions.
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