Kalliopi Kotsa

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.

Vitamin D administration during pregnancy as prevention for pregnancy, neonatal and postnatal complications

Pregnancy represents a time of rapid bodily change, which includes physical proportions, physiology and responsibility. At this context, maternal vitamin D stores have been the objective of extensive scientific research during the last decades, focusing on their potential effects on maternal an neonatal health. A growing body of observational studies indicated that maternal hypovitaminosis D (as defined by maternal 25-hydroxyvitamin D [25(OH)D] levels <20 ng/ml or <50 nmol/l) is a significant risk factor for adverse neonatal outcomes including asthma, multiple sclerosis and other neurological disorders. On that basis, this review aims to provide to the reader new insights into the vitamin D requirements and function during pregnancy supported by recent data and will not discuss the classical roles of vitamin D and skeletal function during pregnancy. In addition, we will focus on recent results that demonstrate that maternal vitamin D supplementation could reduce neonatal respiratory and neurological complications, suggesting that available guidelines should be updated, since it remains unclear why these recommendations are not updated according to recent results. Also, with regard to randomized controlled trials (RCT’s) for vitamin D, we consider that they are largely doomed to fail. The reasons for this are many and specific cases of this failure will be presented in this text.

Vitamin D and cardiovascular disease: From atherosclerosis to myocardial infarction and stroke

There continues to be interest in understanding the role of vitamin D in the pathogenesis, epidemiology and prevention of cardiovascular disease (CVD). In fact vitamin D deficiency has been associated to an increased risk of developing CVD given to the relationship between low vitamin D levels and obesity, diabetes mellitus, dyslipidaemia, endothelial dysfunction and hypertension. However, although vitamin D has been identified as a potentially important marker of CVD, the mechanisms through which vitamin D deficiency leads from endothelial dysfunction to myocardial infarction and stroke are not fully understood. Thus, the goal of this review is to provide an updated review of the literature on the basic science of how vitamin D may affect the cardiovascular system and in particular to analyze the role that vitamin D may have in the whole dynamic process from the initiation of endothelial dysfunction to the development of myocardial infarction and stroke.

Maternal vitamin D levels during pregnancy and neonatal health: evidence to date and clinical implications.

Low maternal vitamin D levels during pregnancy have been associated with a plethora of adverse neonatal outcomes, including small for gestational age and preterm births, detrimental effect on offspring bone and teeth development, and risk of infectious diseases. Although most observational studies indicate a significant linear relationship between maternal 25-hydroxyvitamin D and the above outcomes, some randomized controlled trials to date are inconclusive, mostly due to differences in study design and supplementation regimen. The currently available results indicate that vitamin D supplementation during pregnancy reduces the risk of preterm birth, low birth weight, dental caries of infancy, and neonatal infectious diseases such as respiratory infections and sepsis. This narrative review aims to summarize available trial results regarding the effect of low maternal vitamin D levels during pregnancy, in conjunction with neonatal outcomes on the field, with a discourse on the appropriate clinical approach of this important issue.

The Incretin Effect and Secretion in Obese and Lean Women with Polycystic Ovary Syndrome: A Pilot Study

BACKGROUND Insulin resistance is considered to play an important role in the pathogenesis of polycystic ovary syndrome (PCOS) and in the progression to type 2 diabetes. Recent reports concentrate on a possible relationship between incretin secretion and beta-cell function in PCOS. The aim of the present study is to investigate the incretin effect in obese and lean women with PCOS. METHODS Twenty women with PCOS and ten age-matched healthy women were recruited in the study. The oral glucose tolerance test (OGTT) and isoglycemic test were carried out on each participant after an overnight fast at 2-weeks interval. Plasma levels of insulin, glucose, C-peptide, glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1) were assayed. RESULTS Obese women with PCOS demonstrated lower GIP concentrations (area under the curve [AUC]) in response to OGTT compared to the control group. The incretin effect was found significantly augmented in the obese women with PCOS compared to controls. This finding remained robust in the subgroup analysis including only body mass index (BMI)-matched healthy women. CONCLUSIONS Increased insulinotropic effect could counteract the blunted GIP response to OGTT in obese women with PCOS. It is suggested that the pathology of PCOS may also include impaired activity of the enteroinsular axis.

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.

Vitamin D and diabetes mellitus: Causal or casual association?

The incidence of both type 2 and type 1 diabetes mellitus has been increasing worldwide. Vitamin D deficiency, or the awareness of its prevalence, has also been increasing. Vitamin D may have a role in the pathogenic mechanisms predisposing to type 2 diabetes by modulating insulin resistance and/or pancreatic β-cell function. Vitamin D status or elements involved in its activation or transport may also be involved in the development of type 1 diabetes mellitus through immunomodulatory role . Based on these observations a potential association between vitamin D and diabetes has been hypothesized. In this review we discuss up to date evidence linking vitamin D with the development of diabetes. Moreover, the role of vitamin D supplementation in the prevention of both types of diabetes is analysed together with its role in improving glycemic control in diabetic patients. We also address the potential role of vitamin D deficiency in the development of macro- and microvascular complications in diabetes. Finally, we provide recommendation for Vitamin D therapy in diabetes in view of current evidence and highlight areas for potential future research in this area.

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.

Vitamin D in Fibromyalgia: A Causative or Confounding Biological Interplay?

Fibromyalgia (FM) is a chronic syndrome with an increasing prevalence, characterized by widespread musculoskeletal pain in combination with a variety of cognitive symptoms and fatigue. A plethora of scientific evidence that has accumulated during the last decades, resulted in a significant improvement of the understanding of the pathophysiology of the disease. However, current therapeutic approaches in patients with FM remains a multidimensional approach including patient education, behavioral therapy, exercise, pain management, and relief of chronic symptoms, rather than the use drug therapies, based on the mechanisms of disease development. Vitamin D, a fat-soluble vitamin derived mainly from skin synthesis through ultraviolet radiation, has been recognized to manifest a plethora of extraskeletal actions, apart from its fundamental role in skeletal and calcium homeostasis, including modulation of cell growth, neuromuscular actions, and potential anti-inflammatory properties. Recent findings indicate that hypovitaminosis D to be highly prevalent in patients with FM. Supplementation studies are limited so far, indicating potential beneficial effects on pain and severity of the disease, however specific recommendations are lacking. This review aims to summarize and critically appraise data regarding the pathophysiological interplay between vitamin D and FM, available results from observational and supplementation studies so far, with a clinical discourse on current knowledge gaps and future research agenda.