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Referee Comments: Referee 1

Posted by PLOS_ONE_Group on 22 Nov 2007 at 10:03 GMT

Reviewer 1's Review

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The authors have used magnetoencephalography during hyperinsulinemic clamping in 10 overweight volunteers to seek a differential effect of insulin detemir on human brain function compared to human soluble insulin. The glucose required to offset the insulin infusions was less in the detemir arm, despite the very high (~40 fold excess over human insulin) measured plasma insulin levels, suggesting that the amount of active insulin in the periphery was less with the detemir insulin. Beta activity increased with the detemir but not with the human insulin and the authors conclude that the detemir overcame an inherent cerebral insulin resistance of their obese subjects.

The data are of interest but there are significant problems, including a lack of discussion of the clinical correlates of the findings, the apparently extreme effect on the brain's response to human insulin of what seems a very minor degree of insulin resistance/overweight and the assumption that the effects of detemir will be of clinical benefit.

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N.B. These are the general comments made by the reviewer when reviewing this paper in light of which the manuscript was revised. Specific points addressed during revision of the paper are not shown.