Glucose Turnover and Disposal in Maturity-onset Diabetes

The glucose turnover rate in maturity-onset 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 maturity-onset 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.