Showing papers by "Spyridon N. Karras published in 2016"

Do studies reporting ‘U’-shaped serum 25-hydroxyvitamin D–health outcome relationships reflect adverse effects?

Abstract: Several reports describe U-shaped 25-hydroxyvitamin D [25(OH)D] concentration-health outcomes, including musculo-skeletal disorders such as falls and fractures, several cancers, cardiovascular disease (CVD), cognitive function, all-cause mortality rates, birth outcomes, allergic reactions, frailty, and some other disorders. This paper reviews reports of U-shaped outcome associations with vitamin D status for evidence of underlying pathophysiological processes, or of confounding, finding that some U-shaped associations appear to be biologically meaningful, but that many could well reflect confounding by factors such as lifestyle, or hypovitaminosis D-related disease onset being masked by self-supplementation that was begun too late to correct developing health problems but before baseline vitamin D status assessment. However, the various U-shaped associations for allergic reactions may be due to vitamin D modulation of the phenotype of the immune response, shifting the Th1-Th2 balance toward Th2 formation. For prostate cancer, there seems to be little effect of 25(OH)D concentration on incidence; however, there is an inverse correlation between 25(OH)D concentration and mortality rates. Future observational studies, and randomized controlled trial data analyses, should include adjustment for data collected on prior long-term vitamin D supplementation and solar UVB exposure, as well as other potential confounders.

Hypovitaminosis D in pregnancy in the Mediterranean region: a systematic review.

Abstract: Despite high levels of sunshine, maternal hypovitaminosis D during pregnancy is prevalent in the Mediterranean region. The aim of this study is to systematically review trials that investigated vitamin D concentrations during pregnancy in this region, in order to determine predictors of hypovitaminosis D and explain this phenomenon. After applying inclusion/exclusion criteria, 15 studies were entered into the systematic review involving 2649 pregnant women and 820 neonates. The main outcome was maternal vitamin D status, assessed by serum 25-hydroxy-vitamin D (25(OH)D) concentrations. Possible predictors of the outcome included maternal age, body mass index (BMI), race, socioeconomic status, skin type, gestational age, sun exposure, calcium and vitamin D intake and supplementation, smoking status, parity and season of delivery. Studies differed widely in vitamin D deficiency criteria, method of measurement and outcomes. The prevalence of vitamin D insufficiency ranges from 9.3 to 41.4%, whereas that of vitamin D deficiency from 22.7 to 90.3%. A positive association with 25(OH)D concentrations exists for light skin color, white race, uncovered dressing pattern, maternal vitamin D supplementation and season of gestation (spring/summer). An inverse association exists for BMI and gestational age, whereas data for smoking and socioeconomic status are controversial. We concluded that vitamin D deficiency in pregnancy seems to be quite common, even in the Mediterranean region. Racial, social and cultural habits, as well as the absence of preventive supplementation/dietary strategies, seem to negate the benefits of sun exposure.

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

Abstract: 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.

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

Abstract: 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.

Lipoprotein(a) in postmenopausal women: assessment of cardiovascular risk and therapeutic options.

Abstract: Introduction Lipoprotein(a) [Lp(a)], a low-density lipoprotein (LDL)-like particle, has been independently associated with increased cardiovascular disease (CVD) risk in various populations, such as postmenopausal women. The purpose of this narrative review is to present current data on the role of Lp(a) in augmenting CVD risk in postmenopausal women and focus on the available therapeutic strategies. Methods PubMed was searched for English language publications until November 2015 under the following terms: "therapy" OR "treatment" AND ["lipoprotein (a)" OR "Lp(a)"] AND ("postmenopausal women" OR "menopausal women" OR "menopause"). Results Only hormone replacement therapy (mainly oral estrogens) and tibolone have been specifically studied in postmenopausal women and can reduce Lp(a) concentrations by up to 44%, although evidence indicating a concomitant reduction in CVD risk associated with Lp(a) is lacking. As alternative treatments for women who cannot, or will not, take hormonal therapies, niacin and the upcoming proprotein convertase subtilisin / kexin type 9 (PCSK-9) inhibitors are effective in reducing Lp(a) concentrations by up to 30%. Statins have minimal or no effect on Lp(a). However, data for these and other promising Lp(a)-lowering therapies including mipomersen, lomitapide, cholesterol-ester-transfer protein inhibitors and eprotirome are derived from studies in the general, mainly high CVD risk, population, and include only subpopulations of postmenopausal women. Conclusions Past, present and emerging therapies can reduce Lp(a) concentrations to a varying extent. Overall, it remains to be proven whether the aforementioned reductions in Lp(a) by these therapeutic options are translated into CVD risk reduction in postmenopausal women.

Combined treatment with sitagliptin and vitamin D in a patient with latent autoimmune diabetes in adults

Abstract: Latent autoimmune diabetes in adults (LADA) is a relatively new type of diabetes with a clinical phenotype of type 2 diabetes (T2D) and an immunological milieu characterized by high titers of islet autoantibodies, resembling the immunological profile of type 1 diabetes (T1D). Herein, we report a case of a young male, diagnosed with LADA based on both clinical presentation and positive anti-glutamic acid decarboxylase antibodies (GAD-abs), which were normalized after combined treatment with a dipeptidyl peptidase-4 inhibitor (DPP-4) (sitagliptin) and cholecalciferol. Learning points Anti-glutamic acid decarboxylase antibodies (GAD-abs) titers in young patients being previously diagnosed as type 2 diabetes (T2D) may help establish the diagnosis of latent autoimmune diabetes in adults (LADA). Sitagliptin administration in patients with LADA might prolong the insulin-free period. Vitamin D administration in patients with LADA might have a protective effect on the progression of the disease. Background Latent autoimmune diabetes in adults (LADA) is a slowly progressive form of autoimmune diabetes mellitus characterized by older age at diagnosis compared with type 1 diabetes (T1D) and the presence of pancreatic islet cell autoantibodies (1). This results in the development of glucose intolerance and overt clinical disease when the majority of pancreatic cells are not functional due to the chronic autoimmune inflammation. This pathophysiological process is characterized by the presence of circulating antibodies against pancreatic islet cells and islet cell infiltration by mononuclear lymphocytes. Commonly, patients with LADA present with a relatively preserved beta-cell function compared with patients with T1D, they manifest a progressive deterioration of beta-cell function necessitating basal and prandial insulin therapy early after diagnosis (1). Although, LADA is genetically associated with T1D, it shares some clinical features with type 2 diabetes (T2D). Usually, LADA patients are older than 30 years, have higher BMI in comparison with T1D patients, and because initially they maintain residual insulin production are often misdiagnosed as T2D. However, in clinical practice, LADA patients are younger at diagnosis than T2D, they tend to have worse glycemic control, lower BMI, and frequently insulin treatment is initiated much earlier than T2D (1). Hence, in rare instances, LADA patients present solely with diabetic ketoacidosis (2; Table 1). Table 1 Clinical presentation of T1D, T2D, and LADA. In this report, we describe the case of a young male diagnosed with LADA based on both clinical presentation and positive anti-glutamic acid decarboxylase antibodies (GAD-abs), which were normalized after combined treatment with a dipeptidyl peptidase-4 inhibitor (DPP-4) inhibitor (sitagliptin) and cholecalciferol.

Vitamin D and gonadal function in men: a potential inverse U-shaped association?

Abstract: Accumulating evidence from animal and human studies suggests that vitamin D, apart from its regulatory effects on musculoskeletal health, is involved in reproductive function in both genders. The basis of the interplay between vitamin D and reproduction lays on the presence of both vitamin D receptor (VDR) and 1α-hydroxylase (CYP27B1) enzyme in reproductive organs. In males, VDR are present in testis, epididymis, prostate, and seminal vesicles. In Sertoli cells, whose secretory activities are ion channel-dependent, vitamin D has been shown to stimulate calcium uptake through a nuclear receptor activity. Epidemiological studies support a positive association between serum 25-hydroxy-vitamin D [25(OH)D] concentrations and sperm motility in both fertile and infertile men In addition, large multi-center, cross-sectional studies from Europe and USA have shown positive, linear association between 25(OH)D and androgen concentrations. On the contrary, there are studies that support an inverse U-shaped association, that is, men with both low and high 25(OH)D concentrations demonstrate poorer gonadal function compared with those with intermediate concentrations. Given the rapid increase in over-the-counter use of vitamin D supplements by men that anticipate advantageous health outcomes, the aim of the present commentary is to provide an overview of the studies that present either U-shaped or linear association between 25(OH)D concentrations and male gonadal function.

Haemophilia and low bone mass. Ok, but what about fracture risk?

Abstract: Accumulative evidence during the last decade has established an association between haemophilia (A and B) and low bone mineral density (BMD), both in adults and children [1–3]. Despite the heterogeneity among studies, regarding sample size, population and definition criteria of low BMD, haemophilia leads to bone loss due to a variety of mechanisms. In brief, repeated bleeding episodes and concomitant arthropathy from childhood (‘haemophilic arthropathy’), lead to impaired mobility and avoidance of regular (mostly weight-bearing) exercise, which compromises optimal acquisition of peak bone mass [1–4]. Other factors also contribute to bone loss to a various extent, such as hepatitis C (HCV) and human immunodeficiency virus (HIV) infections, level of physical activity, 25-hydroxyvitamin D concentrations and the degree of haemophilic arthropathy [1,5–7]. Nonetheless, what matters most is whether these patients are indeed at increased risk of fracture, taking into account the increased morbidity and the difficulties in their fracture management. The purpose of this editorial is to focus on fracture risk in patients with haemophilia (PWH), regarding prevalence, potential pathogenetic mechanisms and future perspectives.