Five-hour glucose tolerance (GTT), serum insulin (IRI) response to glucose, glucose tolerance after cortisone (CGTT), tolbutamide tolerance (TTT) with insulin response, free fatty acids (FFA) after fasting and after glucose, blood ketones after fasting, and fractional serum lipids after cortisone were determined in most or all of twenty-five subjects with a strong predisposition to diabetes, twenty-one of them being the offspring of pairs of diabetic parents. Twenty-four healthy subjects with no family history of diabetes served as controls. Although all results except those of the CGTT were within accepted limits of normal, “prediabetics” differed significantly from controls in having higher one-half-hour, one-hour and two-hour blood sugar values and higher IRI levels at one and two hours during GTT, higher blood sugar values at one-half hour, one hour and two hours during CGTT, and smaller and slower depression of blood sugar despite normal insulin response during TTT. No differences in lipid metabolism between the two groups were found except that, surprisingly, the controls had higher FFA after twenty-four-hour fasting than the “prediabetics.” Small but definite deviation in glucose metabolism, and possibly in insulin reponse glucose, remain the most sensitive biochemical indicators to the “prediabetic state,” but their predictive reliability has yet to be ascertained.

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