Bone mineral density in diabetes mellitus.

In the present study bone mineral content (BMC) was measured at 1/3 and 1/10 the length of the radius from the distal end in 100 adult diabetic subjects (55 females, 45 males, 54 insulin-dependent [IDD], 46 non-insulin-dependent [NIDD]), using single photon absorptiometry. Each individual BMC value in the diabetics was first compared to normal BMC values for age obtained in our laboratory from 500 non-diabetic subjects. BMC in the diabetics was within the normal range (M +/- 2 SD) with respect to sex and age. Data from IDD and NIDD males, under and over 50 years of age, and of IDD and NIDD females, pre- and postmenopausal, were compared with the respective control group data after matching each diabetic subject to a non-diabetic one of identical age and menstrual history and of comparable body mass index. In each group BMC in the diabetic subjects was found not to be statistically different from BMC in the control ones. Correlation analysis was carried out between BMC and endocrine or metabolic parameters obtained in 52 of the diabetic patients. BMC in diabetic subjects was not correlated with plasma levels of hormones (thyroid hormones, cortisol, 17-beta-estradiol, testosterone), Ca, P or alkaline phosphatase activity. It was inversely correlated with urinary Ca and P in NIDD women and with urinary Ca in NIDD men. No relationship was found between BMC and the metabolic control of diabetes (evaluated by basal glycemia, 2h-post-prandial glycemia and glycosylated hemoglobin).

Basal and norepinephrine-stimulated lipolysis in differently sized human isolated adipocytes: comparison of three modalities for results expression.

Lipolytic rate in basal conditions and after adrenergic stimulation with norepinephrine (NE, 8.87 microM) from suspensions of differently sized human adipocytes has been tested. Adipocytes were intra surgically provide for obese (OB) and normal-weight (NW) individuals. Total volume of cells was constant in all samples, being 4% in the incubation system. Glycerol released in the buffer at the end of one hour incubation was measured and results expressed by three different features, i.e. related to: A) total volume of cells (nmol glycerol/40 microliters/h); B) cell number (nmol/cell x 10(4)/h), or C) cell surface unit (nmol/mm2/h). No statistically significant differences between OB and NW have been found, nor between histometrical parameters or between lipolytic rates. A positive, significant correlation between lipolytic rate B and Mean Cell Volume (MCV) or total Cell Surface (TCS 10(4)) has been found (rs from 0.90 to 0.94, p less than 0.01) both in basal conditions and after stimulation. A significant, positive correlation between stimulated lipolytic rate C and MCV (r = 0.67, p less than 0.05) has also been observed. Our results suggest that lipolytic rate appears to be correlated to cell volume. While the expression of lipolytic rate with relation to total volume of cells in the sample (rate A) may be more convenient to minimize the effect of different size of cells in different samples, data expressed as glycerol released per number of cells (rate B) or per surface unit (rate C) appears however to be more suitable form main experimental purposes in metabolic studies of adipocytes.

Influence of short-term lithium carbonate administration on stimulated insulin secretion in normal man.

We have studied the effects of short-term treatment with lithium carbonate (900-1,200 mg/day for 4 days) on insulin secretion and blood glucose levels of 28 healthy volunteers (8 females and 20 males, aged 23-29 years) who underwent the following stimulations: two intravenous glucose loads of 25 and 5 g (IVGTT25; IVGTT5); arginine infusion (25 g over 30 min); tolbutamide test (0.25 g i.v.). Seven subjects for each group were tested. A placebo treatment was also performed. Short-term lithium treatment significantly reduced the insulin response to IVGTT25, arginine and tolbutamide. No differences were observed in blood glucose levels during all stimuli. Serum electrolyte levels and thyroid function were not affected by the treatment. In conclusion, these findings suggest, in healthy subjects, a good peripheral glucose utilization after brief-term lithium administration, in spite of impaired insulin response to various stimuli.

Long-term administration of acetylsalicylic acid in impaired glucose tolerance in addition to the diet: effects and limits.

The effect of controlled long-term oral trial with 2 g/die of acetylsalicylic acid (ASA) in addition to diet in 14 patients suffering from impaired glucose tolerance (according to WHO criteria) was compared to diet alone plus placebo (PL). All patients were randomly assigned to ASA or PL, and then submitted to cross-over scheduling procedure (30 + 30 days). Plasma glucose levels observed after an oral glucose tolerance test (OGTT, 100 g) became normal in patients receiving ASA for 30 days (p less than 0.01 at x2 analysis). No change of abnormal OGTT data was observed when patients were treated with PL. Insulin secretin after OGTT and after i.v. glucose tolerance test (IVGTT, 5 g) was unmodified by ASA. Basal glucose levels and plasma glucose disappearance rate after IVGTT also remained unchanged after ASA. Only two subjects had to stop ASA treatment because of gastric discomfort. The oral administration of 2 g of ASA might possibly interfere with intestinal glucose absorption. The well known influence of ASA on prostaglandin synthesis and on insulin secretion could not be relevant in our own pharmacological approach.

Pharmacological interaction between tolbutamide and acetylsalicylic acid: study on insulin secretion in man.

This study has been planned to investigate some aspects of the interaction between acetylsalicylic acid (ASA) and tolbutamide on insulin secretion. In healthy subjects, oral administration of 3.2 g daily of ASA for 3 days significantly enhanced a) basal insulin levels (p less than 0.01), b) arginine-stimulated insulin secretion (25 g i.v. over 30 min) (p less than 0.01) and c) tolbutamide-stimulated insulin secretion (1 g or 0.25 g i.v. as a bolus) (areas under curves: p less than 0.02). Corresponding decreases in glycemia were observed. Tolbutamide binding to serum proteins was significantly reduced after ASA treatment (p less than 0.02). We conclude that, in case of tolbutamide test, interferences between ASA and tolbutamide on insulin secretion might be dependent, at least in part, on enhancement of free-tolbutamide percentage in plasma and not only on a direct or synergic action of ASA on pancreatic B-cell. Therefore, acute stimulation of insulin secretion by tolbutamide appears not to be completely comparable to other traditional stimuli, when ASA effects are studied.

Sleep-related growth hormone secretion in human obesity: effect of dietary treatment.

Eight obese patients (4 male, 4 female; mean age = 35.9 years) before [mean body mass index (BMI) = 37.1] and after (mean BMI = 31.4) weight loss by means of a mixed hypocaloric diet were compared with 8 lean subjects (4 male, 4 female; mean age = 37.1 years, mean BMI = 22.3) in a study of their nocturnal sleep patterns and sleep-related growth hormone (GH) secretions. Although no sleep disorders (in particular, sleep apnea and hypersomnia) were observed, GH secretion was markedly altered in obese patients that showed no sleep-related GH peaks. After weight loss, the sleep architecture in obese subjects was unchanged. On the contrary, GH peak appeared to be only partially restored and delayed until after stage III-IV of non-REM sleep. Our study on obese subjects suggests that the altered nocturnal GH secretion, probably related to a hypothalamic dysfunction, may be the result of the obesity per se.

Alpha-adrenoceptors and insulin release from pancreatic islets of normal and diabetic rats.

The role of alpha-adrenoceptors in the regulation of glucose-induced insulin release (GIR) was investigated in islets of normal and neonatally streptozotocin-injected non-insulin-dependent diabetic rats (STZ). In normal islets GIR was suppressed to approximately 50% by 10(-8) M of the alpha 2-adrenergic agonist UK 14304, whereas 10(-9) M of the agonist induced a similar inhibition in STZ islets. In normal islets, suppression of GIR by UK 14304 (10(-8) M) was totally antagonized by 10(6) M idazoxan (alpha 2-antagonist) or 10(6) M phentolamine (alpha 1 + alpha 2-antagonist). In STZ islets, the inhibitory effect of UK 14304 (10(-9) M) was entirely reversed by 10(-5) M idazoxan or 10(-6) M phentolamine. The alpha 1-antagonist prazosin (10(-7)-10(-5) M) was without effect on insulin release suppressed by UK 14304 in normal and STZ islets. Insulin release at 3.3, 8.3, or 16.7 mM glucose was augmented by phentolamine but not by idazoxan. It is concluded that the inhibitory effect of catecholamines on insulin release is mediated by alpha 2-receptors in normal and STZ islets. Phentolamine augments basal and glucose-induced insulin release by a mechanism that does not involve alpha 2-adrenoceptors.

The effect of acetylsalicylic acid and diclofenac on stimulated growth hormone and prolactin secretion in humans.

The effects of short-term oral treatments with prostaglandin (PG) synthesis inhibitors, acetylsalicylic acid (ASA), or diclofenac (DCF), on basal and stimulated growth hormone (GH) and prolactin (PRL) secretion were studied in 23 healthy volunteers. Before and after 4 days on ASA (3.2 g daily) or DCF (75 mg daily), subjects were given cimetidine or metoclopramide to evaluate PRL reserve. Arginine infusion test (for GH and PRL response) was performed only in ASA-treated subjects. Arginine-induced GH and PRL release was abolished and enhanced, respectively, by ASA pre-treatment. PRL response to cimetidine was greater than that observed in basal conditions when ASA was given, but remained unchanged after DCF administration. Neither ASA nor DCF was capable of modifying the PRL response to metoclopramide. Basal GH and PRL levels were not influenced by ASA or DCF. In conclusion, some PG may play an important role in the regulation of GH and PRL secretion, and some PG inhibitors (like ASA) may significantly interfere with some dynamic tests for pituitary reserve.

Early improvement of left ventricular function during caloric restriction in obesity.

Left ventricular function (LVF) was studied in 25 obese patients (four males and 21 females) by serial poligraphic measurements, namely systolic time intervals (STI), during a short period of dieting (2721 kJ/day (650 kcal/day) as single daily meal regimen). In the same period, all the patients underwent also three standardized exercise tests at the cycloergometer. At the end of the study (20th day), statistically significant differences were obtained in weight loss (P less than 0.001); two main parameters of STI, namely pre-ejection period index (PEPI) and PEP/LVET ratio were lowered (P less than 0.001): furthermore, peak and recovery systolic blood pressure (SBP) and heart rate (HR) during exercising, were also significantly reduced. These data suggest that an improvement of LVF and cardiac performance are present since the early phases of caloric restriction in obesity.

Food-related sensory stimuli are able to promote pancreatic polypeptide elevation without evident cephalic phase insulin secretion in human obesity.

The data concerning the cephalic phase of insulin secretion (CPIS) in human obesity are controversial. We investigated the effect of a variety of sensory challenges on CPIS in 17 non-diabetic obese patients (four males, 13 females, mean age 41.1 years, mean BMI 38.7). Water, saccharin, and lemon juice were used as oral stimuli, and a complete meal was simply presented as visual and olfactory stimulations. Twelve healthy normal-weight subjects (four men, eight women, mean age 39.9, mean BMI 22.5) also underwent oral stimulation as controls, and the patients who underwent the sight and smell stimulations were also tested for pancreatic polypeptide (PP) changes in order to verify the occurrence of truly cephalic reflex during the test. Insulin levels were measured before and after each stimulation (every min for the first 5 min, and then after 10, 20, and 30 min). None of the stimuli (saccharin, lemon juice or water retained in the mouth for 2 min and were then spat out; the combined and separate sight and smell of a meal for 2 min) led to a significant increase in insulin in the obese patients (except in the case of one woman after oral stimulation). The oral stimuli led to a variable CPIS in one female and three male controls. Despite the absence of CPIS, the five obese patients undergoing all three sensory stimulations related to the meal (combined sight and smell, sight alone and smell alone) showed an early and significant increase in plasma PP concentrations within the first 3 min; this was more pronounced after the combined than after the separate exposure. Although only preliminary, these results underline the variability but substantial lack of CPIS in obese patients, thus suggesting that it can be considered a relatively rare and unrelevant event even in the presence of a true brain-mediated reflex revealed by the rapid and consistent increase in PP found in our experiments.

Effects of long-term antiepileptic therapy on the hypothalamic-pituitary axis in man.

Effects of long-term antiepileptic therapy on the hypothalamic-pituitary axis were evaluated from the basal and stimulated plasma levels of growth hormone (GH) and prolactin (PRL) and from circadian adrenocorticotropic hormone (ACTH)/cortisol rhythms. Data for patients with well-controlled epilepsy of mild-to-moderate severity were compared with those for normal healthy volunteers. Analysis of the effects of each antiepileptic drug (AED) and of combined AEDs revealed minor abnormalities of stimulated GH secretion in all treated patients. In epileptic men, all individual AEDs (except valproate) and AED polytherapy increased both basal and stimulated plasma levels of PRL. In epileptic women, this effect was more variable and less marked, probably because of early depletion of PRL reserves. Each AED and combined AEDs did not significantly change circadian ACTH/cortisol rhythms in epileptic patients. The effects observed seem not to be related to epilepsy per se. Clinical implications, pathways, and neurotransmitters involved and possible mechanisms of the neuroendocrine effects of long-term AED therapy are discussed.