Journal of Lipid Research, Vol 25, 1184-1194, Copyright © 1984 by Lipid Research, Inc.
Ketone body kinetics in humans: the effects of insulin-dependent diabetes, obesity, and starvation
SE Hall, ME Wastney, TM Bolton, JT Braaten and M Berman
The kinetics of acetoacetate (A) and beta-hydroxybutyrate (B) have been
studied following the injection as a pulse or continued infusion of [3-
14C]acetoacetate (A*) or [14C]beta-hydroxybutyrate (B*) into six newly
diagnosed, untreated, ketotic diabetic patients, ten obese subjects in the
postabsorptive state, and the ten obese subjects after 1-2 weeks starvation
(50 cal per day). Employing a compartmental model of acetoacetate and
beta-hydroxybutyrate kinetics developed using CONSAM for normal subjects,
the rate coefficients (Lij), rates of release of newly synthesized
acetoacetate and beta-hydroxybutyrate into the blood (UA, UB), and
fractional removal of each compound (FCRA and FCRB) were calculated. Ketone
body release into blood (UA + UB) in diabetic subjects was threefold higher
than normal (mean +/- SD, 208 +/- 118 versus 81 +/- 66 mumol min-1 m-2) and
in obese subjects the rate increased on starvation from 171 +/- 70 to 569
+/- 286 mumol min-1 m-2. In each case most of the increase was in
beta-hydroxybutyrate. The major change in diabetes and on starvation of the
obese subjects was in the rate coefficient for removal of ketone bodies.
Normally 0.168 +/- 0.109 min-1, it was 0.055 +/- 0.040 min-1 in the
diabetic patients and fell from 0.066 +/- 0.040 to 0.027 +/- 0.019 min-1 in
the obese subjects on starvation. In normal subjects, FCRA was similar to
FCRB (0.226 +/- 0.142 versus 0.188 +/- 0.124 min-1). However, in diabetics,
FCRA was 0.074 +/- 0.044 and FCRB was 0.050 +/- 0.034 min-1 and both were
lower than normal. On starvation of obese subjects, FCRA fell from 0.199
+/- 0.047 to 0.089 +/- 0.035 min-1, whereas FCRB fell from 0.141 +/- 0.040
to 0.033 +/- 0.012 min-1. Therefore, the removal of beta- hydroxybutyrate
was impaired more than that of acetoacetate in all patients. Our results
confirm previous observations that ketosis is associated with high rates of
ketogenesis and a decrease in fractional clearance. In addition, we found
that in diabetes, obesity, and in obese subjects following starvation, most
of the increased synthesis was in beta-hydroxybutyrate and that the
clearance of beta- hydroxybutyrate decreased more than that of
acetoacetate.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
