Circadian plasma citrate rhythms in juvenile diabetics

Postabsorptive plasma concentrations of citrate, glucose, lactate, free fatty acids (FFA), ketone bodies and free insulin were measured once weekly for 5 weeks in 18 male juvenile diabetics. The circadian rhythms of the same substances were followed in 12 male diabetics. In 8 of them, daily rhythms were measured twice, before and after plasma glucose was lowered by increasing insulin doses. In the postabsorptive state, the mean plasma citrate concentration of the diabetics, 117 mumol/l (range 65--160), did not differ from that of non-diabetics despite two- to threefold higher levels of plasma glucose, FFA and ketone bodies in diabetics. Daily plasma citrate profile in diabetics showed peak concentrations in the morning and late afternoon. Citrate level throughout the day fell after increased insulin administration, whereas the diurnal pattern remained unchanged. Both the week-to-week coefficient of variation (mean 10%) and the diurnal coefficient of variation (mean 17%) of plasma citrate were below those of any other substances measured (p less than 0.001). Postabsorptive citrate concentration correlated negatively to the diurnal variation of plasma glucose whether diabetic control was apparently good or poor. The results support the idea that plasma citrate level reflects intracellular citrate regulation of glucose utilization. In spite of an interindividual range of 100%, individual citrate level was remarkably constant. Postabsorptive plasma citrate concentration is proposed as a control marker of lability of circulating glucose in insulin-treated diabetics.