AJP - Regulatory, Integrative and Comparative Physiology, Vol 248, Issue 5 611-R620, Copyright © 1985 by American Physiological Society
Acetoacetate and 3-hydroxybutyrate kinetics in obese and insulin-dependent diabetic humans
R. Nosadini, A. Avogaro, R. Trevisan, E. Duner, C. Marescotti, E. Iori, C. Cobelli and G. Toffolo
[3-14C]acetoacetate (AcAc) and beta-[3-14C]hydroxybutyrate (beta-OHB)
administration, measurements of labeled AcAc and beta-OHB in blood, and
kinetic modeling have been used to investigate ketone body (KB) metabolism
in five normal, five obese, and eight insulin-withdrawn diabetic subjects.
Diabetic subjects were divided in mildly ketotic (MKD) and highly ketotic
(HKD) patients according to beta-OHB blood level. A four-compartmental
model successfully described the tracer kinetic data in obese and normal
subjects, whereas in diabetic patients a five-compartmental model was
necessary. Obese subjects showed a significantly lower (P less than 0.05)
KB de novo synthesis (R30 = 159 +/- 54 (SD) mumol X min-1 X m-2) in
comparison with normal subjects (282 +/- 93), but the clearance rates of
AcAc (PCR1) and beta-OHB (PCR2) were similar in the two groups. R30 was 596
+/- 534 in MKD and 1,278 +/- 445 (P less than 0.01) in HKD. PCR1 was not
significantly different both in MKD and HKD in comparison with normal
subjects. In contrast PCR2 was markedly reduced in HKD (0 +/- 0 ml X min-1
X m-2) in comparison with MKD (1,031 +/- 615) and normal subjects (782 +/-
278). The percentage distribution of KB among various tissues inside the
organism of diabetic subjects is abnormal. Both AcAc and beta-OHB recycling
and mean residence time are not normal in HKD. A significant correlation
was found between C-peptide and KB production in diabetes. These results
suggest that a selective defect of beta-OHB peripheral utilization is
important in determining and maintaining severe diabetic ketoacidosis.
