Diabetes Mellitus Following Pentamidine-induced Hypoglycemia in Humans

Four patients, treated with pentamidine because of Pneumocystis carinii pneumonitis, displayed severe fasting hypoglycemia during this treatment. Diabetes mellitus appeared later, requiring insulin therapy in the three of them who survived more than a few weeks. The metabolic study, performed in two cases during the hypoglycemic period, demonstrated inappropriately high insulin levels in the postaborptive state. 28 ± 1 μU/ml (blood glucose 41 ± 4 mg/dl) and 86 ± 5 μU/ml (blood glucose 15 ± 5 mg/dl) vs. 15 ± 3 μU/ml in 10 control subjects and 55 ± 3 μU/ml in 6 patients with a verified B-cell tumor, respectively. Poor B-cell secretory responses followed the stimulations by oral glucose (maximal increment over basal: +5 μU/ml vs. +40 μU/ml in control group and +77 μU/ml in the insulinoma group), by i.v. arginine (maximal increment +10 and +28 μU/ml, respectively, vs. +55 in the controls and +90 μU/ml in the insulinoma group) and by i.v. glucagon (+10 and +23 μU/ml, respectively) vs. +40 μU/ml in both the control and the insulinoma groups). Plasma cortisol and glucagon, and the A-cell response to arginine were higher than normal. These high, nonsuppressible, nonstimulable insulin levels and the sequence of hypoglycemia followed by insulin-dependent diabetes mellitus is consistent with the hypothesis of a selective toxicity turned towards the B-cells. In vitro incubation of islets with pentamidine 10−10 M produced a passive release of insulin, followed by a significant decrease in B-cell response to glucose + theophylline. It is suggested that pentamidine can induce hypoglycemia because of an early cytolytic release of insulin, and then diabetes mellitus because of B-cell destruction and insulin deficiency.</jats:p

Effects of antiglucocorticoids on glucocorticoid hypertension in the rat.

The early phase of hypertension induced in rats by a glucocorticoid agonist RU 26988 was studied. Systolic blood pressure increased by 35 mm Hg. Water and sodium urinary excretion increased transiently, and plasma volume decreased. Total and ouabain-sensitive sodium efflux, as well as rubidium efflux, were enhanced by glucocorticoid administration. Low salt intake did not prevent hypertension. Pretreatment with RU 38486, a steroid with antiglucocorticoid properties, largely prevented the rise in blood pressure (+10 mm Hg) and suppressed transient natriuresis and the decrease in plasma volume. Changes in total and ouabain-sensitive sodium efflux were completely prevented, whereas changes in rubidium efflux were only partly reversed. Similarly, administration of progesterone, a steroid with antiglucocorticoid effects, prevented glucocorticoid hypertension (+11 mm Hg) and vascular ionic changes. In contrast administration of RU 28318, an antimineralocorticoid agent, was without effect on glucocorticoid hypertension (+38 mm Hg). Progesterone or RU 38486 administered after glucocorticoid also decreased blood pressure. Present data indicate that glucocorticoid hypertension may be prevented or reversed in its early phase by steroid drugs with antiglucocorticoid properties. These drugs also appeared to prevent the sodium and rubidium flux abnormalities induced by glucocorticoid. We suggest that activation of the vascular glucocorticoid receptors may be involved in the pathophysiology of glucocorticoid hypertension.</jats:p