Somogyi pointed out that conventional tests for insulin tolerance are not adequate for determining sensitivity or responsiveness to insulin, since blood glucose below the fasting level rapidly initiates counter-regulatory mechanisms which promptly mask the degree of response to insulin.

The uncertainty of the period of action of the hyperglycemic factor existing in presently available crystalline insulin makes it quite impossible to appraise satisfactorily the primary influence of the administered insulin on blood glucose in respect to the promptness of initiation of action (“latent period” of Himsworth) and in respect to the unhampered degree of fall in blood glucose. It is essential, therefore, that for a good test of responsiveness these latter two factors be registered before any extensive fall in glucose has had an opportunity to excite the body's counter-effort at homeostatic readjustment. Such time would fall well within the first few minutes after injection of insulin.

The valid criticisms of tests now in vogue for sensitivity to insulin can be obviated by careful timing, using an insulin which is free of the hyperglycemic-glycogenolytic factor (HGF or glucagon). The suggested responsiveness test with glucagon-free insulin records blood glucose readings in a time period before marked reactive compensatory phenomena have come into play, namely within the first six minutes after administration of the insulin. Under such conditions, only factors already residing in the individual and actively functioning at the very time of the injection of insulin could prevent the initiation of a fall in blood glucose. These are antiinsulin factors peculiarly inherent in the individual and possibly actually creating the diabetic state in the obese adult.

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