Showing papers by "Spyridon N. Karras published in 2019"

The Effects of High Altitude on Glucose Homeostasis, Metabolic Control, and Other Diabetes-Related Parameters: From Animal Studies to Real Life.

Abstract: Exposure to high altitude activates several complex and adaptive mechanisms aiming to protect human homeostasis from extreme environmental conditions, such as hypoxia and low temperatures. Short-term exposure is followed by transient hyperglycemia, mainly triggered by the activation of the sympathetic system, whereas long-term exposure results in lower plasma glucose concentrations, mediated by improved insulin sensitivity and augmented peripheral glucose disposal. An inverse relationship between altitude, diabetes, and obesity has been well documented. This is the result of genetic and physiological adaptations principally to hypoxia that favorably affect glucose metabolism; however, the contribution of financial, dietary, and other life-style parameters may also be important. According to existing evidence, people with diabetes are capable of undertaking demanding physical challenges even at extreme altitudes. Still, a number of issues should be taken into account, including the increased physical activity leading to changes in insulin demands and resistance, the performance of measurement systems under extreme weather conditions and the potential deterioration of metabolic control during climbing expeditions. The aim of this review is to present available evidence in the field in a comprehensive way, beginning from the physiology of glucose homeostasis adaptation mechanisms to high altitudes and ending to what real life experience has taught us.

Variations in 25-Hydroxyvitamin D in Countries from the Middle East and Europe: The Roles of UVB Exposure and Diet

Abstract: Serum 25-hydroxyvitamin D (25(OH)D) has been largely associated with latitude and sunshine exposure across several regions. According to previous results, 25(OH)D concentrations are, on average, relatively low in countries with abundant sunshine, including those of the Middle East and North Africa region, as well as lower-latitude Europe. The standard explanation for this phenomenon is that people wear concealing clothing because of cultural and religious practices and that high temperatures in summer limit direct sun exposure. However, the role of diet in the development of profound hypovitaminosis D has not been adequately explored in those countries. To examine how diet affects vitamin D status in the Middle Eastern and European countries, a search was conducted for papers from that region reporting 25(OH)D concentrations. Papers were sought that reported summertime and wintertime 25(OH)D concentrations for healthy nonpregnant adults representative of the entire population. Data from 15 Middle Eastern and European countries were found through this search. Data for postmenopausal women from 19 European countries were also obtained. Dietary supply data for animal products containing vitamin D (animal fat, eggs, ocean fish, animal meat, and milk) were obtained from the Food and Agriculture Organization of the United Nations. Latitude and a solar UVB dose index also were obtained for each country. For the 15-country study, energy from dietary factors was highly correlated with latitude, making it difficult to separate the effects of UVB exposure and dietary factors. However, for the 19-country study, dietary factors were only weakly correlated with latitude. In that study, ocean fish was the most important single dietary factor affecting serum 25(OH)D concentration for postmenopausal women in various European countries, but animal fat and meat also contributed. Because this is an ecological study, further research is encouraged to evaluate and extend the findings.

First Report of Diabetes Phenotype due to a Loss-of-Function ABCC8 Mutation Previously Known to Cause Congenital Hyperinsulinism.

Abstract: Monogenic Diabetes is relatively rare, representing only 1-2% of total diabetes cases; nevertheless, it is often misdiagnosed primarily as type 1 diabetes, leading to unnecessary insulin therapy and delayed recognition of affected family members. In the present article, we describe a case of a young, male patient who presented with hyperglycemia in the absence of ketosis and following genetic testing; he proved to harbor the loss-of-function p.Arg1353His (c.4058G>A) mutation in the ABCC8 gene, inherited from his mother. This mutation has been previously described in patients with Congenital Hyperinsulinism. Furthermore, different mutations in the ABCC8 gene have been linked with MODY 12, type 2, and gestational diabetes; however, to the best of our knowledge, this is the first report that associates this specific mutation with diabetes phenotype. ABCC8-related diabetes is characterized by remarkable heterogeneity in terms of clinical presentation and therapeutic approach. Early diagnosis and individualized treatment are essential to achieving metabolic targets and avoiding long-term diabetes complications.

Pharmacologic adjunctive to insulin therapies in type 1 diabetes: The journey has just begun.

Abstract: Treatment of type 1 diabetes (T1D) is currently based exclusively on insulin replacement therapy. However, there is a need for better glycemic control, lower hypoglycemia rates, more effective weight management, and further reduction of cardiovascular risk in people with T1D. In this context, agents from the pharmaceutical quiver of type 2 diabetes are being tested in clinical trials, as adjunctive to insulin therapies for T1D patients. Despite the limited amount of relevant evidence and the inter-class variability, it can be said that these agents have a role in optimizing metabolic control, assisting weight management and reducing glycemic variability in people with T1D. Specific safety issues, including the increased risk of hypoglycemia and diabetic ketoacidosis, as well as the effects of these treatments on major cardiovascular outcomes should be further assessed by future studies, before these therapeutic choices become widely available for T1D management.

Unbalanced X;9 translocation in an infertile male with de novo duplication Xp22.31p22.33.

Abstract: Male carriers of an X-autosome translocation are generally infertile, regardless of the position of the breakpoint on the X chromosome while the pathogenicity of Xp22.3 subtelomeric duplications is under debate. To shed light into this controversy, we present a rare case, of an azoospermic male with no other significant clinical findings, in whom classical cytogenetics revealed additional unbalanced chromosomal material, at the telomere of the long arm of one homolog of chromosome 9. In peripheral blood specimens of the index case and his parents, we performed GBanding, Inverted-DAPI Banding, AgNOR staining, Telomere specific Fluorescence in Situ Hybridization (FISH), Molecular karyotyping by Multi-color FISH, whole genome SNP microarrays, sub-telomeric MLPA, and transcription analysis of the expression of KAL1 gene by RT-PCR. Multi-color FISH revealed an unbalanced translocation involving the short arm of chromosome X. SNP microarray analysis combined to classical cytogenetics and MLPA demonstrated a de novo 8.796 Mb duplication of Xp22.31-p22.33. Compared to three control specimens, the patient presented significantly elevated expression levels of KAL1 mRNA in peripheral blood, suggesting transcriptional functionality of the duplicated segment. The duplicated segment contains the pseudo-autosomal region PAR1 and more than 30 genes including SHOX, ARSE, STS, KAL1, and FAM9A and is not listed as polymorphic. Our data advocate that duplications of the Xp22.3 region may not be associated with a clinical consequence.

Anti-incretin effect: The other face of Janus in human glucose homeostasis.

Abstract: The provocative idea that type 2 diabetes (T2D) may be a surgically treated disorder is based on accumulating evidence suggesting impressive remission rates of obesity and diabetes following bariatric surgery interventions. According to the "anti-incretin" theory, ingestion of food in the gastrointestinal (GI) tract, apart from activating the well-described incretin effect, also results in the parallel stimulation of a series of negative feedback mechanisms (anti-incretin effect). The primary goal of these regulations is to counteract the effects of incretins and other postprandial glucose-lowering adaptive mechanisms. Disruption of the equilibrium between incretins and anti-incretins could be an additional pathway leading to the development of insulin resistance and hyperglycemia. This theory provides an alternative theoretical framework to explain the mechanisms behind the optimal effects of metabolic surgery on T2D and underlines the importance of the GI tract in the homeostatic regulation of energy balance in humans. The anti-incretin concept is currently based on a limited amount of evidence and certainly requires further validation by additional studies. The aim of the present review is to discuss and critically evaluate recent evidence on the anti-incretin theory, providing an insight into current state and future perspectives.

Reviews based on 1st Mediterranean Experts Meeting on the topic "Vitamin D in the prevention of health disparities during adult life".

Abstract: Vitamin D has traditionally been considered a key player in skeletal health preservation [1]. During the past few decades, there has been increasing interest in vitamin D biology, as it has also been associated with the pathogenesis of several human diseases. Research in the vitamin D field, which is intense and booming, has established that this vitamin is actually a molecule that resembles a hormone more than a vitamin, with actions that extend well beyond its established musculoskeletal role. Its biological functions are thought to be exerted by interaction of the activated form 1,25(OH)2D (either D2 or D3) mainly with an intracellular receptor [2]. Most studies have focused on the association between 25-hydroxyvitamin D (as it is considered to best reflect vitamin D stores and availability), or the activated 1,25(OH)2D, and disease processes. However, vitamin D biology is complex and, on the way to the formation of the final and prevailing metabolites, several intermediate molecules are generated that are no longer considered by-products or inactive [3]. Moreover, the BMediterranean paradox^ of vitamin D deficiency found to be prevalent in large parts of the population of countries with, nevertheless, abundant sunshine renders collaboration among scientists of these countries a necessity. The need to join forces to understand the magnitude of the above phenomenon and the magnitude of the disorders that may relate to this problem inspired us to set up a scientific workshop, named the Mediterranean Experts Meeting on Vitamin D, to date held two years running in Thessaloniki, Greece, to which we invited a large number of experts in the field who wished to contribute to vitamin D research by sharing knowledge, ideas, and proposals. Thus, two extremely successful Mediterranean Experts Meetings on BVitamin D in the prevention of health disparities during adult life^ were held in this Northern Greek city in 2017 and 2018. What started as an inspirational proposal among friends and colleagues became a friendly and highly professional exchange of scientific ideas and experience and has, meanwhile, evolved into a world-class scientific event (it will be hosted in Abu-Dhabi in 2019) thanks to the generous scientific input of all the distinguished participants. This issue of Hormones gives its readers a brief overview of the scientific work presented mostly during the 2017 meeting. Professor Salvatore Minisola and colleagues deal with the issue of vitamin D supplementation [4], while Professors Erdinc Dursun and Duygu Gezen-Ak present their original work on vitamin D and neurodegeneration, with an emphasis on preclinical and clinical data on Alzheimer’s disease [5, 6]. Professor William Grant scrutinizes the Mediterranean region, with particular focus on the potential association of vitamin D with disease status [7]. Finally, Maria Grammatiki, Spiros Karras, and Kalliopi Kotsa summarize preclinical and clinical data on vitamin D action on the pathogenesis of diabetes mellitus and complications [8]. By the end of both symposia, several important conclusions had been drawn on where we stand as regards the epidemiology and pathogenesis of vitamin D-related conditions as this pertains mostly to the Mediterranean region. * Kalliopi Kotsa kalmanthou@yahoo.gr

Adiponectin and vitamin D-binding protein concentrations are independently associated in apparently healthy women but not men: a validation cohort.

Abstract: Vitamin D-binding protein (VDBP) is one of the key factors regulating vitamin D homeostasis [1, 2]. Adiponectin is secreted mainly from visceral adipose tissue and affects energy homeostasis [3]. A possible interaction between vitamin D and adiponectin [4], especially in profound hypovitaminosis D, has been reported. Adipokine profile at birth has been associated with fat mass in late childhood [5]. We recently reported an independent positive association between VDBP and adiponectin in both mothers and neonates at birth [6]. This independent association raised a hypothesis regarding a potential role of VDBP as a regulator of biological activity of adiponectin. However, as VDBP concentrations are known to increase in pregnancy [1], our observation could be limited only to pregnancy. The aim of this study was to validate the association between adiponectin and VDBP levels in apparently healthy men and women. Patients and methods