Olympia Anastasiou

Role of vitamin D treatment in glucose metabolism in polycystic ovary syndrome

OBJECTIVE To determine the effect of treatment with vitamin D(3) analogue in the parameters of glucose metabolism in obese women with polycystic ovary syndrome (PCOS). DESIGN Observational study. SETTING Obese women with PCOS in an academic research environment. PATIENT(S) Fifteen obese women (mean age 28 +/- 1.3 years, mean body mass index 32.55 +/- 0.43) with documented chronic anovulation and hyperandrogenism were recruited into the study. INTERVENTION(S) Alphacalcidol (1-alpha-hydroxyvitamin D(3)) was administered orally 1 microg/day for 3 months. All subjects underwent a frequently sampled IV glucose tolerance test after a 10- to 12-hour overnight fast during a spontaneous bleeding episode before and after treatment with alphacalcidol. MAIN OUTCOME MEASURE(S) Peripheral insulin resistance and insulin effectiveness were estimated with minimal model. RESULT(S) The first phase of insulin secretion was significantly increased after treatment with alphacalcidol. A favorable statistically significant change also was observed in the lipid profile. CONCLUSION(S) Treatment with the vitamin D(3) analogue (alphacalcidol) could be of value in the management of PCOS.

Genetic variation in the visfatin (PBEF1/NAMPT) gene and type 2 diabetes in the Greek population

Visfatin (NAMPT formerly known as PBEF1) is an adipokine that is strongly expressed in visceral fat and has caused much debate among researchers, regarding its involvement in glucose homeostasis and insulin resistance. It was initially isolated from bone marrow cells, and its involvement in inflammatory procedures such as sepsis and acute lung inflammation is now evident. Several studies have also reported an association of plasma visfatin levels with obesity. We undertook an evaluation of the involvement of the NAMPT gene in the development of type 2 diabetes (T2DM) in the Greek population. We studied 178 patients with T2DM and 177 controls that were matched for sex, age and body mass index. We genotyped three tagging SNPs selected from the HapMap II CEPH European population as reference for the Greek population. These three SNPs tag another 12 SNPs over the entire NAMPT gene with a mean r(2) of 0.92. No indications of association with disease status were found with any of the tested variants or the inferred haplotypes. Results were also negative when the quantitative traits of weight and BMI were tested. Although our study covers common variants across the NAMPT gene, the possible involvement of rare variants in T2DM etiology cannot be ruled out and will require the investigation of very large numbers of cases and controls.

Response of biochemical markers of bone turnover to oral glucose load in diseases that affect bone metabolism

OBJECTIVE Postprandial suppression of bone resorption is considered one of the main contributors in the circadian rhythm of bone turnover markers. The aim of this study was to investigate this physiological response of bone tissue in diseases that affect bone metabolism. PATIENTS AND METHODS In this study, 118 patients (45 hypothyroid, 40 hyperthyroid, and 33 β-thalassemic patients) and 78 healthy individuals matched for age and body mass index were included. An oral glucose test (75 g glucose) was performed after overnight fasting. Serum levels of procollagen type-I N-terminal propeptide (P1NP), β-C-terminal telopeptide of type I collagen (β-CTX), and osteocalcin were assayed at 0, 60, and 120 min. RESULTS Baseline values of bone turnover markers were significantly elevated in hyperthyroid and β-thalassemic patients but not in hypothyroid patients compared with the control group. After oral glucose, the levels of β-CTX but not P1NP or osteocalcin were significantly suppressed in all groups (mean change from baseline is 46.9% for β-CTX, 7.9% for P1NP, and 8% for osteocalcin). The percentage change from baseline for β-CTX was significantly augmented in hypothyroidism (52 vs 42%, P=0.009). CONCLUSION The preservation or even augmentation of postprandial suppression of bone resorption in diseases that affect bone metabolism through distinct pathogenetic mechanisms suggests the importance of this physiological response to nutrients for the general homeostasis and functional integrity of the skeleton.

Intracerebroventricular infusion of neuropeptide Y increases glucose dependent-insulinotropic peptide secretion in the fasting conscious dog.

The rapid increase of incretins glucose-dependent insulinotropic peptide (GIP) and glucagon like peptide-1 (GLP-1), within 5-15 min, after food ingestion, suggests that a neural mechanism might be involved in the regulation of their secretion. The aim of this study is to determine whether intracerebroventricular (i.c.v) administration of neuropeptide Y (NPY), a widely distributed neurotransmmiter, can mediate this neural regulation of GIP secretion after food consumption. Six healthy mongrel dogs were utilized for this study. A prototype epicranial apparatus was placed surgically, allowing easy and exact localization of the third ventricle for infusions or sampling. Simultaneous blood sampling was obtained from cannulation of a hind limb vein. Plasma insulin, and GIP concentrations were measured after i.c.v infusion of 5, 10 and 25 microg of NPY dissolved in 0.5 ml of artificial cerebrospinal fluid (a CSF). The secretion of GIP and insulin were increased after the injection of NPY in a different pattern. Our data indicate that NPY might be involved in a possible neural control mechanism of GIP secretion after food consumption.

Intracerebroventricular infusion of bombesin modulates GIP secretion in conscious dogs

UNLABELLED Glucose-dependent insulinotropic polypeptide (GIP) is an incretin with important role in glucose homeostasis and energy conservation. Thus far, the neural mechanisms involved in the regulation of GIP secretion, have not yet been fully elucidated. The aim of this study was to evaluate a possible effect of intracerebroventricular administration of Bombesin in the regulation of GIP secretion. METHODS Thirty-two adult dogs were used in this study. In group 1 the animals received a bolus icv infusion of 200 ng bombesin or an equivalent amount of artificial cerebrospinal fluid (aCSF). In group 2 the animals received a continuous icv infusion of bombesin or aCSF over a 3-h period. In group 3 the experiment of group 2 was repeated with a simultaneous intraduodenal infusion of a glucose load through the Mann-Bollman fistula. Blood samples were taken from cannulation of a hind limb and plasma levels of glucose, insulin and GIP were assayed. RESULTS Bolus icv infusion of bombesin produced an increase in glucose and GIP levels without a respective increase in plasma insulin levels. Continuous icv infusion and the simultaneous infusion of glucose intraduodenally increased significantly GIP, glucose and insulin levels. CONCLUSIONS Intracerebroventricular levels of bombesin seems to involve in the neural regulation of GIP secretion independently of the presence of nutrients and to potentiate GIP secretion during a glucose load.

Effect of intracerebroventricular infusion of insulin on glucose-dependent insulinotropic peptide in dogs.

UNLABELLED Glucose-dependent insulinotropic polypeptide (GIP), is an incretin with important role in glucose homeostasis and energy conservation. Thus far, the neural/hormonal mechanisms involved in the regulation of GIP secretion, have not yet been fully elucidated. The aim of this study was to evaluate a possible effect of intracerebroventricular administration of insulin in a centrally mediated regulation of GIP. METHODS Twenty-four adult dogs were used in this study. In group 1 the animals received a bolus icv infusion of regular insulin in a total volume of 50 microl or an equivalent amount of artificial cerebrospinal fluid (aCSF). In group 2 the animals received a continuous icv infusion of insulin or aCSF over a 3-h period. In group 3 the experiment of group 2 was repeated with a simultaneous intraduodenal infusion of a glucose load through the Mann-Bollman fistula. Blood samples were taken from cannulation of a hind limb vein at -15, 0, 5, 10, 15, 30, 45, 60, 90, 120, 150 and 180 min after infusions. Plasma levels of glucose, insulin and GIP were assayed. RESULTS Insulin levels were increased significantly in group 2 and 3 while GIP secretion was partly inhibited after icv administration of insulin and intraduodenal administration of glucose in the 3rd group. CONCLUSIONS It is suggested that the hypothalamic insulin signaling contributes to plasma insulin levels and possibly exerts a negative regulation of GIP secretion after glucose load.

Secretory Capacity of the Parathyroid Glands after Total Thyroidectomy in Normocalcemic Subjects

CONTEXT Hypocalcemia, transient or permanent, represents a common complication after total thyroidectomy, but data on the secretory capacity of the parathyroid glands in thyroidectomized patients without clinical or biochemical hypocalcemia are limited. STUDY DESIGN To address this issue, we studied the parathyroid response to acute hypocalcemia induced by iv infusion of sodium bicarbonate in normocalcemic patients submitted to total thyroidectomy at the early postoperative period and 3 months later. PATIENTS AND METHODS Sixty patients who underwent total thyroidectomy for benign thyroid disease and did not develop clinical or biochemical hypocalcemia and hypoparathyroidism postoperatively and 50 healthy volunteers were included in the study. Patients (at 48 h and 3 months after surgery) and controls (after overnight fast) were subjected to a sodium bicarbonate infusion test. RESULTS In healthy volunteers plasma intact PTH increased significantly at 3 min after infusion (4.42 ± 0.15 ng/ml vs. 11.22 ± 0.5 ng/ml, P < 0.001) and gradually returned to baseline values. In the thyroidectomized patients, mean PTH levels were also increased after sodium bicarbonate infusion but to a significantly lesser degree compared with healthy controls (1.77 mean fold increase vs. 2.57 mean fold increase, respectively, P < 0.001). Using as criterion the lowest fold increase of plasma PTH levels at 3 min after infusion observed in healthy volunteers, 38% of the thyroidectomized patients at 48 h after surgery and 6.6% of the patients at 3 months after surgery demonstrated a diminished PTH response to acute hypocalcemia induced by sodium bicarbonate infusion. CONCLUSION In thyroidectomized patients, normal postoperative calcium and PTH values do not exclude a reduced secretory response of the parathyroids to hypocalcemic stimuli.

Intracerebroventricular infusion of neuropeptide Y modulates VIP secretion in the fasting conscious dog.

Intracerebroventricular (icv) injection of neuropeptide Y (NPY), which is a widely-distributed neurotransmitter, into the paraventricular nuclear area has been shown previously to increase secretion of insulin and glucagon from the pancreatic islets. Vasoactive intestinal polypeptide (VIP) is a 28-amino-acid peptide that is associated with the mobilisation of energy during situations of energy depletion, such as fasting and exercise. VIP has also been reported to alter insulin and glucagon levels in a glucose-dependent manner. The aim of this study was to determine whether icv infusion of NPY affected VIP secretion in dogs. Intracerebroventricular injections (0.5 ml) were administered through a stereotactic apparatus to six healthy dogs. This prototype epicranial apparatus was positioned surgically to allow the easy and exact localisation of the third ventricle for infusion or sampling. Doses of 5, 10, and 25 microg NPY, dissolved in artificial cerebrospinal fluid (aCSF), were infused for a total of 30 min using a Harvard infusion pump. For control experiments, aCSF alone was injected. Blood samples were taken 15 min before icv injection (basal), immediately after injection, and at 5, 10, 15, 30, 45, 60, 90, and 120 min after, to determine the levels of glucose, insulin, glucagon, and VIP. Intracerebroventricular infusion of NPY resulted in a short-term increase in VIP secretion, followed by a more gradual and lengthier decrease in VIP levels. The secretion of insulin and glucagon increased significantly with all three doses of NPY. Intracerebroventricular infusion of NPY increased secretion of insulin and glucagon from the pancreas. The rapid change in the levels of VIP suggested the possibility of neural regulation by NPY.

Patterns in the Parathyroid Response to Sodium Bicarbonate Infusion Test in Healthy Volunteers

Background. The sodium bicarbonate infusion test evaluates the function of the parathyroid glands. The present study aims to evaluate the range of parathyroid response in healthy individuals and the potential influence of various factors. Methods. Fifty healthy volunteers were subjected to the test. Levels of vitamin D, calcium, albumin, and PTH were measured before infusion. PTH was measured at 3, 5, 10, 30, and 60 minutes after infusion. Results. A curve describing the response of parathyroids to the test was drawn. Twenty percent of the subjects had blunted PTH response. No significant difference was observed between normal and blunted responders concerning age, BMI, baseline PTH, or calcium levels. Nonetheless, there was a significant difference in vitamin D levels (P = 0.024). Interpretation. The test is easy to perform and may be used for everyday screening. It has to be clarified whether our observations are, at least partly, produced due to the presence of individuals with a constitutively blunted response or if low levels of vitamin D decrease the ability of the parathyroids to respond. Whichever the case, PTH response of normal individuals to sodium bicarbonate infusion test is more varied than previously thought and vitamin D levels influence it.