We have characterized the abnormalities of glucose metabolism associated with Friedreich's ataxia (FA) by studying plasma glucose, insulin, growth hormone (GH), and glucagon before and after an oral glucose tolerance test (OGTT), an IV glucose load, and an IV arginine load, in 21 patients and in controls. Twelve patients were normotolerant (NT) to glucose, five glucose-intolerant (IT), and four diabetic (DM). Insulin secretion of IT patients was increased and delayed during OGTT. Interestingly, the insulin release during arginine load was significantly decreased in NT and IT as well as in DM patients. The GH response to OGTT was altered in IT patients. Plasma glucagon after an arginine load was significantly higher in patients than in controls. The results indicate that FA is associated with insulin resistance, beta-cell deficiency, and type I diabetes. These alterations might be genetically linked or metabolically related to the primary defect in FA. Their interplay or independent effects are responsible for abnormalities of glucose metabolism in FA.

Cognitive processes in a group of neurologically asymptomatic patients with relatively severe but uncomplicated insulin-dependent diabetes mellitus (IDDM) were studied. In comparison with a homogeneous group of normoglycemic controls, the diabetic group performed significantly worse in global memory, abstract reasoning, and eye-hand coordination tests. The two groups scored similarly in intelligence, concentration and attention, spatial, visual, and psychomotor tests. The neuropsychological deficits did not correlate with the duration or the severity of the disease. Whether these mild neuropsychological deficits are transient or stable or whether they are caused by central nervous system vascular or metabolic dysfunctions or by the emotional influence of the chronic illness on the intellectual and educational development of patients remains unclear. Our findings need to be cautiously interpreted and perhaps could not be extended to diabetic patients with better metabolic control.

The present experiments were performed to investigate the possible role of histamine and its receptors, H1 and H2, in the control of PRL and LH release in normal adult humans of both sexes. Histamine infusion (200 microgram, iv, in 15 min) induced PRL and LH release in men; in women, histamine inhibited LH release without affecting PRL release. Two H1 antagonists, dexchlorpheniramine (10 mg, iv) and promethazine (50 mg, im), reduced PRL release in both sexes, stimulated LH release in men, and inhibited LH release in women. Cimetidine, an H2 antagonist (400 mg, iv), elicited PRL release in both sexes, more consistently in females than in males, and was without effect on LH release in either sex. These data suggest that in humans, the effect of histamine on PRL release is linked to H1 and H2 receptors, which respectively stimulate and inhibit PRL release independently of sex. The effect of histamine on LH release appears to depend on sex and to be mediated only by H1 receptors. To rule out the possibility that the effects of histamine are merely due to a nonspecific stress reaction, we have evaluated PRL and LH release in otherwise normal men and women undergoing surgery for gallstones. Surgery was accompanied by PRL release in both sexes, more evident in women, and by LH release only in men. These results indicate that the effect of histamine on PRL and LH release in humans is linked to sex and H1 and H2 receptors and is not due to stress; further studies are required to clarify the possible mechanism and site of action of histamine in modifying PRL and LH release in humans.

To evaluate the possible involvement of endogenous opioid peptides in the responses of PRL, LH, and cortisol to surgical stress, we have studied the effect of naloxone on these hormones in otherwise normal subjects of both sexes undergoing cholecystectomy for gallstones. In 24 subjects (12 males and 12 females), premedication consisted of atropine sulfate (0.007 mg/kg BW); general anesthesia (30 min later) was induced by thiopental (7 mg/kg) and maintained constant by 1% ethrane in a 70%:30% nitrous oxide-oxygen mixture. In 6 males and 6 females, naloxone (0.4 mg) was injected iv before anesthesia induction. After skin incision, a clear PRL release was observed in all subjects; this was more evident in females than in males. PRL release was significantly lower in naloxone-pretreated subjects. LH release was observed only in males and was significantly higher in naloxone-pretreated subjects. Cortisol release occurred in both sexes in a similar way and was not significantly different in naloxone-pretreated subjects. Cortisol release occurred in both sexes in a similar way and was not significantly different in naloxone-pretreated subjects. These results indicate that endogenous opioid peptides are involved in stress-induced PRL and LH release in humans.

Indirect evidence suggests that sulfonylureas, in addition to stimulating insulin release, exert additional effects at extrapancreatic levels which are of value in the management of type 2 diabetes. In order to characterize in vivo some of these effects, insulin sensitivity was studied in 9 type 1 diabetics with no residual insulin secretory activity, during treatment with chlorpropamide (250 mg b.i.d. for 8 days) and with glipizide (5 mg t.i.d. for 8 days). Employing the glucose clamp technique with the aid of an artificial pancreas (Biostator), glucose disposal during insulin infusion (0.1 U/kg in 60 min) was calculated by the amount of glucose required to keep the blood glucose at preinfusion levels. Chlorpropamide and glipizide administration was accompanied by a significant increase of the amount of glucose required to clamp blood glucose levels, while serum (free) insulin levels were superimposable during the different clamping studies. In the absence of endogenous insulin release, these data strongly suggest that the two sulfonylureas employed enhance in vivo the peripheral sensitivity to insulin. Further studies are required to indicate a preferential site of action (liver, muscle, adipose tissue) of sulfonylureas.