A B S T R A C T The glucose turnover rate in maturityonset diabetes in man has been variously reported as increased, normal, and decreased. The present experiments suggest that these discrepancies may have been due to methodology, and to nonrecognition of a circadian cycle in the glucose turnover rate that is present in health, and marked in diabetes.During the early morning hours the glucose turnover rate in maturity-onset diabetes is increased in proportion to the fasting blood glucose level. It may reach three to four times the rate found in health. During the evening hours the increments are about one-half as great.The glucose outflow rate constant, k, lower in diabetes than in health, is also lower in both groups in the evening than in the morning.An analysis of the relative contributions of glucose overproduction and underutilization to the development of hyperglycemia in maturity-onset diabetes indicates that overproduction is the greater factor. The relative role of underutilization appears to increase as the fasting blood glucose level increases.The circulating glucose oxidation rate in maturityonset diabetes is only slightly lower than in health, but the fraction oxidized is markedly lower, and only a small fraction is excreted.The principal conclusion is that in maturity-onset diabetes there is a hypertrophied flux of endogenous glucose, most of which is neither oxidized nor excreted. The precursors and the qualitative and quantitative metabolic fates of this excess glucose are unknown.

Alanine was selected for study as a representative circulating glucose precursor in relation to the question of the source of the excess circulating glucose in diabetes mellitus. U-14C alanine and U-14C glucose infusions were given to healthy subjects and to subjects with untreated mild maturity, severe maturity, and juvenile diabetes. Comparative studies after a 24-hour fast were made in healthy and in mildly diabetic subjects. The alanine production rate was unaltered by fasting or diabetes. The glucose production rate was unaltered by fasting but increased in diabetes in relation to the severity of the disease. The fractions of alanine-to-glucose and of glucose-from-alanine were increased by fasting. The effect of diabetes was different. The fraction of alanine-to-glucose was much less in mild maturity diabetes than in health, and it was increased only in juvenile diabetes. In all the diabetic groups the glucose-from-alanine fraction was much less than in health. In every group the change in the alanine oxidation rate was reciprocal to that in the alanine-derived glucogenesis rate. The results are consistent with the possibility that the principal source of the excess circulating glucose in diabetes is glycogen.

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