Effect of metabolic control on parathyroid hormone secretion in diabetic patients

The metabolic derangement caused by diabetes mellitus may potentially affect bone mineral metabolism. In the present study we evaluated the effect of diabetes metabolic control on parathyroid hormone (PTH) secretion during stimulation with EDTA infusion. The study was conducted on 24 individuals, 8 of them normal subjects (group N: glycated hemoglobin - HbA1C = 4.2 + or - 0.2 percent; range = 3.5-5.0 percent), 8 patients with good and regular metabolic control (group G-R: HbA1C = 7.3 + or - 0.4 percent; range = 6.0-8.5 percent), and 8 patients with poor metabolic control (group P: HbA1C = 12.5 + or - 1.0 percent; range: 10.0-18.8 percent). Blood samples were collected at 10-min intervals throughout the study (a basal period of 30 min and a 2-h period of EDTA infusion, 30 mg/kg body weight) and used for the determination of ionized calcium, magnesium, glucose and intact PTH. Basal ionized calcium levels were slightly lower in group P (1.19 + or - 0.01 mmol/l) than in group N (1.21 + or - 0.01 mmol/l) and group G-R (1.22 + or - 0.01 mmol/l). After EDTA infusion, the three groups presented a significant fall in calcium, but with no significant difference among them at any time. Basal magnesium levels and levels determined during EDTA infusion were significantly lower (P<0.01) in group P than in group N. The induction of hypocalcemia caused an elevation in PTH which was similar in groups N and G-R but significantly higher than in group P throughout the infusion period (+110 min, N = 11.9 + or - 2.1 vs G-R = 13.7 + or - 1.6 vs P = 7.5 + or - 0.7 pmol/l; P<0.05 for P vs N and G-R). The present results show that PTH secretion is impaired in patients with poorly controlled diabetes

Effect of metabolic control on parathyroid hormone secretion in diabetic patients.

The metabolic derangement caused by diabetes mellitus may potentially affect bone mineral metabolism. In the present study we evaluated the effect of diabetes metabolic control on parathyroid hormone (PTH) secretion during stimulation with EDTA infusion. The study was conducted on 24 individuals, 8 of them normal subjects (group N: glycated hemoglobin - HbA1C = 4.2 +/- 0.2%; range = 3.5-5.0%), 8 patients with good and regular metabolic control (group G-R: HbA1C = 7.3 +/- 0.4%; range = 6.0-8.5%), and 8 patients with poor metabolic control (group P: HbA1C = 12.5 +/- 1.0%; range: 10.0-18.8%). Blood samples were collected at 10-min intervals throughout the study (a basal period of 30 min and a 2-h period of EDTA infusion, 30 mg/kg body weight) and used for the determination of ionized calcium, magnesium, glucose and intact PTH. Basal ionized calcium levels were slightly lower in group P (1.19 +/- 0.01 mmol/l) than in group N (1.21 +/- 0.01 mmol/l) and group G-R (1.22 +/- 0.01 mmol/l). After EDTA infusion, the three groups presented a significant fall in calcium, but with no significant difference among them at any time. Basal magnesium levels and levels determined during EDTA infusion were significantly lower (P<0.01) in group P than in group N. The induction of hypocalcemia caused an elevation in PTH which was similar in groups N and G-R but significantly higher than in group P throughout the infusion period (+110 min, N = 11.9 +/- 2.1 vs G-R = 13.7 +/- 1.6 vs P = 7.5 +/- 0.7 pmol/l; P<0.05 for P vs N and G-R). The present results show that PTH secretion is impaired in patients with poorly controlled diabetes.

Renal handling of zinc in insulin-dependent diabetes mellitus patients.

Hyperzincuria is a common feature in diabetic patients, which is still not understood. Based on the above consideration, the aim of the present study was to investigate the renal handling of zinc in insulin-dependent diabetes mellitus (IDDM) patients. The glomerular filtration rate, urinary zinc excretion, zinc clearance, zinc clearance/creatinine clearance ratio, zinc tubular reabsorption, glycosuria, plasma glucose, C-peptide, glucagon, and cortisol were investigated in 10 normal individuals (Group C1 and Group C2, respectively) and 10 IDDM patients (Group E1: hyperglycemic and glycosuric and Group E2: normoglycemic and aglycosuric) during placebo or venous zinc tolerance test. The results showed that urinary zinc excretion and renal zinc clearance were increased after zinc injection in normal individuals (Group C2) and IDDM patients (Groups E1 and E2) when compared with normal individuals-placebo (Group C1). However, these renal parameters were statistically more significant in the hyperglycemic and glycosuric diabetics (Group E1). Because patients in Group E1 had the lowest plasma C-peptide levels and showed a strong negative correlation between CZn++/Ccr ratio and this hormone, we suggest that in this setting insulin inhibits urinary zinc excretion.

Zinc kinetics in insulin-dependent diabetes mellitus patients.

Zinc has an important role in the control of carbohydrate metabolism, and diabetic patients are at risk for zinc deficiency. However, there are conflicting data concerning nutritional zinc status. In order to investigate this topic, 10 normal and 10 insulin-dependent diabetic patients were studied following venous zinc tolerance test. Our results found no evidence of zinc deficiency or of changes on the kinetic parameters of zinc in patients with insulin-dependent diabetes mellitus following a venous zinc tolerance test.

Effects of a single venous dose of zinc on thyroid status in healthy individuals and patients with graves' disease.

Zinc metabolism may regulate thyroid function acting at TRH (thyrotropin-releasing hormone) synthesis, peripheral deiodination of T4 (tetraiodothyronine), and binding of thyroid hormones to nuclear receptors. The aim of this study was to investigate the effect of acute zinc administration on TSH (thyroid-stimulating hormone), FT3 (free triiodothyronine), and FT4 (free tetraiodothyronine) in 10 healthy individuals and 12 hyperthyroid patients with Graves' disease. All these individuals were studied following 25 mg Zn(++) administered intravenously, at 7:00 a.m. after 12 h fast. Blood samples collected at 0, 3, 30, 60, 90, and 120 min after zinc administration showed no significant alteration in the plasma levels of TSH, FT3, and FT4 in hyperthyroid patients. There were no changes in the plasma levels of FT3 and FT4 in the control subjects, but TSH levels were acutely depressed by zinc administration. This study suggests that zinc given acutely and in pharmacological doses does not affect thyroid function in hyperthyroid subjects, but affect plasma TSH levels in healthy individuals.

Lack of acute zinc effects in glucose metabolism in healthy and insulin-dependent diabetes mellitus patients.

Acute or chronic zinc administration may cause hyperglycemia in experimental animals. These findings are attributed to permissive actions of glucocorticoids and glucagon upon hepatic gluconeogenesis and glycogenolysis. The effect of Zn(+)+ on plasma glucose, C-peptide, glucagon, and cortisol was investigated in healthy and insulin-dependent diabetes mellitus (IDDM) patients. Ten normal individuals (5 of each sex, aged 24.10 +/- 1.96) and 10 IDDM (5 of each sex, aged 25.20 +/- 8.10) were tested at 7:00 AM after 12-h fast. Twenty-five mg of Zn(+)+ were administered intravenously during 1 min, and blood samples were collected from the contralateral arm at 0, 3, 30, 60, 90 and 120 min after Zn(+)+ injection. The plasma levels of glucose, C-peptide, and glucagon remained constant throughout the experimental period in both groups studied. Plasma cortisol levels decreased significantly, which is consistent with our previous findings. These results suggest that, in contrast to experimental animals, acute Zn(+)+ administration, despite decreasing cortisol levels, does not change carbohydrate metabolism in human beings.

Effect of zinc administration on thyrotropin releasing hormone-stimulated prolactinemia in healthy men.

Previous in vitro studies have demonstrated zinc (Zn++) inhibition of basal and of potassium (K+) or thyrotropin-releasing hormone (TRH)-stimulated prolactin (PRL) secretion, in a selective, reversible, and dose-dependent manner. Thus, Zn++ may regulate physiologically pituitary PRL secretion. Furthermore, studies with patients with uremia, cirrhosis or prolactinoma, have shown the coexistence of hypozincemia and hyperprolactinemia and zinc supplementation did not correct hyperprolactinemia in these patients. In normal individuals Zn++ administration produced controversial results on PRL secretion. Here, we investigated whether zinc administration affects TRH-stimulated PRL in healthy men. We found that Zn++ administration does not change the TRH-stimulated PRL. Therefore, in normal conditions, Zn++ does not inhibit TRH-stimulated prolactinemia. In addition, we found that acute increases of blood PRL and TRH do not alter blood Zn++ levels.

Interaction among zinc, glucose, and insulin in normal individuals during glucose and tolbutamid perfusion.

Reports in the literature have shown that acute or chronic zinc administration may cause hyperglycemia, with a fall in serum or insular insulin occurring in experimental animals. On the other hand, under conditions of both acute and chronic hyperglycemia, an increase, a decrease, or a normal level of blood zinc has been observed in studies conducted on humans. Thus, the objective of the investigation described here was to determine the relationship existing among zinc, glucose, and insulin under acute conditions. Thirty-six subjects of both sexes (mean age, 23 yr) were tested at 7:00 A.M. after a 12-h fast. Two antecubital veins of both forearms were punctured and maintained with physiological saline. Three experiments were performed in which zinc was administered orally, and hypertonic glucose and tolbutamid were administered intravenously. Blood samples were then collected over a period ranging from 93 to 240 min after the basal times of -30 and 0 min. Hyperzincemia did not cause changes in plasma glucose or insulin either in the absence of or during perfusion of glucose. Hyperglycemia, hypoglycemia, and hyperinsulinemia did not modify serum zinc levels. These results demonstrate that acute zinc administration did not change carbohydrate metabolism and that sudden variations in glucose and insulin levels did not modify the serum profile of zinc.

Zinc acutely and temporarily inhibits adrenal cortisol secretion in humans. A preliminary report.

Hypo- and hyperzincemia has been reported to cause alterations in the adrenal secretion. To determine the acute effect of zinc on cortisol levels, we studied 27 normal individuals of both sexes aged 20-27 y after a 12-h fast. The tests were initiated at 7:00 AM when an antecubital vein was punctured and a device for infusion was installed and maintained with physiological saline. Zinc was administered orally at 8:00 AM. Subjects were divided into an experimental group of 13 individuals who received doses of 25, 37.5, and 50 mg of zinc and a control group of 14 individual who received 20 mL of physiological saline. Serial blood samples were collected over a period of 240 min after basal samples (-30 and 0 min). We detected an acute inhibitory effect of zinc on cortisol secretion during 240 min of the study period in the experimental group.

Interrelationships of zinc with glucose and insulin metabolism in humans.

Hyperzincemia has been reported to cause alterations in the homeostasis of glycid metabolism. To determine this effect on plasma glucose and insulin levels, we studied 36 normal individuals of both sexes aged 22-26 y after a 12-h fast. The tests were initiated at 7:00 AM when an antecubital vein was punctured and a device for infusion was installed and maintained with physiological saline. Zinc was administered orally at 8:00 AM. Subjects were divided into an experimental group of 22 individuals who received doses of 25, 37.5, and 50 mg of zinc and a control group of 14 individuals. Blood samples were collected over a period of 240 min after the basal samples (-30 and 0 min). We did not detect any change in plasma glucose or insulin levels, a fact that we attribute either to the ineffectiveness of the 50 mg dose of zinc or to the lack of human response to the acute action of this trace element. The individuals who ingested zinc showed a significant fall in plasma cortisol, probably caused by the action of this trace element.

Zinc: an inhibitor of prolactin (PRL) secretion in humans.

The response of plasma prolactin (PRL) to oral administration of increasing doses of zinc (25.0, 37.5 and 50.0 mg) was studied in 17 normal adult men and women. Blood samples were collected at 10 and 30-min intervals over a period of 120 min after two basal times (-30 and 0 min). PRL concentrations significantly fell below basal levels in all subjects in response to the increase in plasma zinc levels, as compared to the controls. These results suggest that acute hyperzincemia can inhibit basal PRL secretion in normal individuals.

Effect of copper on the secretion of human growth hormone.

The response of human growth hormone to the oral administration of 5.0 mg copper was studied in plasma from 12 normal adults. Blood samples were collected at 30 min intervals over a period of 240 min after two basal measurements taken at time = -30 and time = 0 min. Six subjects responded to the stimulus with increased growth hormone secretion, revealing a positive correlation with plasma copper levels. The other six subjects presented a similar rise in plasma copper levels but no increase in plasma growth hormone levels. These results suggest that acute, high blood copper levels can increase basal growth hormone secretion in normal individuals, presumably by acting on the hypothalamic center.

Acute effects of human growth hormone on zinc, copper, calcium and magnesium metabolism in normal subjects.

The acute effects of human growth hormone (hGH) on the metabolism of zinc, copper, calcium and magnesium ions was studied. Seven normal subjects were perfused iv with doses of 0.2 or 1.0 mg hGH over a period of 60 min. An increase in plasma zinc, calcium and magnesium, and a decrease in plasma copper levels was noted for the 0.2 mg dose, and these effects were reversed for the 1.0 mg dose although no urine changes occurred. Plasma mobilization of these ions appears to be related to their roles as essential physiological modulators for the action of hGH.

Metabolic effects of glucagon on plasma and urine zinc, copper, calcium and magnesium levels.

The present study determines the effect of glucagon on the behavior of zinc, copper, calcium and magnesium ions in human plasma and urine. Five normal adults were submitted to intravenous infusion of 2.0 mg glucagon over a period of 120 min. A decrease in plasma magnesium and copper was observed with no significant change in urine ion concentrations. We related plasma magnesium mobilization to glucagon, and copper mobilization to plasma variation in free fatty acids and albumin.

[Zinc in protein-calorie malnutrition. I. Concentration in serum of children with the clinical types, kwashiorkor and marasmic kwashiorkor]. / Zinco na desnutrição protéico-calórica. I. Concentração no soro de crianças com os tipos clínicos kwashiorkor e kwashiorkor-marasmático.

Zinc concentration was measured in the serum of 10 children with protein-energy malnutrition (eight with clinical signs of kwashiorkor, and two with marasmic-kwashiorkor) on the first, 15th and 30th day after admission. The zinc levels were significantly lower for these patients on the first day than those observed for children with good nutritional status. No significant increase in zinc concentration occurred in the serum of these patients during initial period of recovery of nutritional status. The possibility of zinc supplementation for malnourished children during recovery is discussed.

Zinco na desnutricao proteico-calorica.I. Concentracao no soro de criancas com os tipos clinicos kwashiorkor e kwashiorkor-marasmatico. / Zinc in protein-calorie malnutrition. I. Concentration in serum of children with clinical features of kwashiorkor and marasmatic kwashiorkor

Foram determinadas as concentracoes sericas de zinco em 10 criancas com desnutricao proteico-calorica (oito com tipo clinico kwashiorkor e duas com o tipo kwashiorkor-marasmatico), no primeiro, decimo quinto e trigesimo dias de internaco. Nestes pacientes os niveis de zinco, no primeiro dia foram significativamente inferiores aqueles observados em criancas com bom estado nutricional. Durante o periodo inicial de recuperacao do estado nutricional, nao houve aumento significativo da concentracao deste oligoelemento no soro. E discutida a possibilidade de suplementacao deste cation durante a recuperacao de criancas desnutridas