Plasma levels of 13,14-dihydro-15-keto-PGE2, a stable derivative of PGE2, are elevated in rats with diabetic ketoacidosis (DKA) and decrease in response to insulin therapy. In patients with insulin-dependent diabetes mellitus type I (IDDM) the plasma levels of this derivative also rise in response to insulin withdrawal and then fall in response to insulin replacement. We wished to determine whether the level of this substance is elevated acutely when patients present with DKA and to determine whether the levels fall during treatment. We also wished to identify the origin of the circulating 13,14-dihydro-15-keto-PGE2 in patients with DKA and in normal fasting subjects. We measured the plasma level of 13,14-dihydro-15-keto-PGE2 in five patients with DKA and in six normal subjects during a 24-h fast. In the patients with DKA before treatment, the plasma 13,14-dihydro-15-keto-PGE2 level was threefold above normal. During therapy, the 13,14-dihydro-15-keto-PGE2 level fell toward normal. There was a significant direct correlation between the plasma free fatty acid (FFA) level and the plasma 13,14-dihydro-15-keto-PGE2 level before and during treatment. In addition, the inverse correlation between the plasma free-insulin level and the plasma 13,14-dihydro-15-keto-PGE2 level approached significance (P = .06). In contrast, in the normal fasting subjects the plasma FFA level rose to values comparable to those observed in the patients with DKA, but there was no significant increase in the plasma 13,14-dihydro-15-keto-PGE2 level. There was no quantitatively important correlation between the plasma FFA level and the plasma 13,14-dihydro-15-keto-PGE2 level. We conclude that 1) the plasma level of 13,14-dihydro-15-keto-PGE2 is elevated in DKA and decreases during treatment, 2) the adipocyte is an important source of the circulating 13,14-dihydro-15-keto-PGE2 in this disorder, and 3) insulin inhibits the production of PGE2 by the adipocyte and perhaps other cells in patients with DKA. The increased production of PGE2, a potent antilipolytic substance, may moderate the accelerated lipolysis that occurs in DKA but is probably not of sufficient magnitude to produce systemic effects. The rise in the plasma FFA level without a concomitant rise in the plasma 13,14-dihydro-15-keto-PGE2 level in normal fasting subjects suggests that cells other than the adipocyte may be the source of the circulating 13,14-dihydro-15-keto-PGE2 in normal subjects.

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