Down regulation of the inverse relationship between parathyroid hormone and irisin in male vitamin D-sufficient HIV patients.

PURPOSE: Infection with the human immunodeficiency virus (HIV) predisposes to endocrine disorders, manifesting as a metabolic phenotype that affects the entire adipose-musculoskeletal unit (AMS). The present cross-sectional study aimed to investigate differences in irisin and adiponectin concentrations between people living with HIV and healthy controls, as well as to explore potential correlations between the levels of the aforementioned adipokines and markers of calcium homeostasis. METHODS: 46 HIV-infected individuals and 39 healthy controls (all men) were included in the study. Anthropometric data, adipokine levels, 25-hydroxyvitamin D [(25(OH)D)] and parathyroid hormone (PTH) concentrations were evaluated in the two groups. Correlations for the relationship between adiponectin, irisin, and PTH levels were examined. The results were adjusted for several confounders, including 25(OH)D levels, anthropometry, physical activity, bone mineral density, testosterone levels, and exposure to ultraviolet B radiation. RESULTS: Mean adiponectin concentrations were significantly lower in the HIV group compared to the control group: 5868 ± 3668 vs 9068 ± 4277 ng/mL, p = 0.011. The same was applicable to irisin concentrations: 8.31 ± 8.17 (HIV) vs 29.27 ± 27.23 (controls) ng/mL, p = 0.013. A statistically significant and negative correlation was observed between irisin and PTH in the control group (r = - 0.591; p = 0.033). In contrast, no significant correlation was observed between PTH and irisin in the HIV group (p = 0.898). CONCLUSION: Our results are the first to suggest a possible down regulation of the inverse relationship between PTH and irisin in HIV patients and to highlight that AMS dyshomeostasis could be involved in the development of skeletal and adipose HIV-related morbidities.

Health benefits and consequences of the Eastern Orthodox fasting in monks of Mount Athos: a cross-sectional study.

BACKGROUND/OBJECTIVES: Greek Orthodox fasting (OF), which involves 180-200 days of fasting per year, is dictated by the Christian Orthodox religion. For the first time, this cross-sectional study examines the characteristics and the effects of OF on anthropometry, cardiometabolic markers and calcium homeostasis in Athonian monks (AMs). SUBJECTS/METHODS: Daily intakes of energy, macro- and micronutrients of a day during a weekend of Nativity Fast, defined as non-restrictive day (NRD), and a weekday during Great Lent, labeled as restrictive day (RD) were recorded. RESULTS: The daily energy intake of 70 AM (age=38.8±9.7 years) was low during both RD and NRD (1265.9±84.5 vs 1660±81 kcal, respectively, P<0.001). Paired samples t-test showed statistically significant difference between daily intakes in RD and NRD: carbohydrates (159.6±21.8 vs 294.3±23.4 g, P<0.0001) and saturated fat (12.7±0.0 vs 16.4±0.0 g, P<0.0001) were lower, whereas protein (89.2±1.3 vs 72.35±1.3 g, P<0.001) was higher during RD. A subsample of 50 monks (age=38.7±10.6 years) formed a study cohort for cardiometabolic and calcium homeostasis assessment. Body weight (74.3±12.9 kg) and body mass index (BMI; 23.8±4.1 kg/m2) were independent of level of physical activity. Optimal profiles for lipid and glucose parameters (total cholesterol: 183.4±41.7 mg/dl, LDL: 120.6±37.6 mg/dl, triglycerides: 72.2±31.3 mg/dl, HDL: 48.5±14.2 mg/dl and homeostasis model assessment of insulin resistance (HOMA-IR) 1.02±0.40) were found. Profound hypovitaminosis D (8.8±6.2 ng/ml), high parathyroid hormone (PTH): 115.5±48.0 pg/ml with normal serum calcium levels (8.9±3.2 mg/dl) was observed. CONCLUSIONS: Unaffected by variation in lifestyle factors, the results of this unique study offers clear evidence for the health benefits of the strict Athonian OF through optimal lipid and glucose homeostasis.

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 ß-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.

Ultraviolet radiation and effects on humans: the paradigm of maternal vitamin D production during pregnancy.

Current evidence indicates that neonates born of mothers with vitamin D deficiency during pregnancy have greater risk for developing hypocalcemia, rickets and extra-skeletal disorders. Despite the classic knowledge that ultraviolet-B (UVB) exposure is the most efficient way for a future mother to obtain optimal vitamin D concentrations, no current consensus or clinical recommendations exist regarding the duration and timing of UVB exposure for pregnant women. This article offers a narrative review of available data regarding how UVB exposure affects maternal vitamin D production during pregnancy, along with a discourse on clinical implications of this public health issue. Future studies would benefit from adopting UVB exposure estimates to recommend appropriate UVB exposure to pregnant women. Doing so could provide a more holistic and practical approach in managing maternal hypovitaminosis D during pregnancy.

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

UNLABELLED: 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.

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

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.

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

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.

Vitamin D during pregnancy: why observational studies suggest deficiency and interventional studies show no improvement in clinical outcomes? A narrative review.

A considerable number of studies have examined vitamin D status during pregnancy. Although data from observational studies denote vitamin D hypovitaminosis (deficiency or insufficiency) during pregnancy is associated with a plethora of adverse maternal and neonatal outcomes, data from interventional (supplementation) trials fail to reveal a significant impact on maternal and offspring health. The aim of this narrative review was to critically appraise the methodology of the most representative published randomized controlled trials in an attempt to explain the difference between observational and supplementation results. We found that this difference could be attributed to a variety of factors, namely: (i) study design (lack of a specific outcome in conjunction with timing of supplementation, enrolment of participants with heterogeneous vitamin D status); (ii) pitfalls in the interpretation of vitamin D equilibrium (lack of determination of plasma half-life); (iii) supplementation regimen (administration of a wide range of regimens, in terms of dose, bolus and form); (iv) geographical characteristics (vitamin D needs could vary significantly within a country, particularly in areas with a wide range of latitude gradient); (v) adaptations of vitamin D metabolism during pregnancy (vitamin D and calcium equilibrium are changed during pregnancy compared with the non-pregnant state) and (vi) supplementation of populations with low baseline 25(OH)D values would likely manifest beneficial effects. All these parameters should be taken into consideration in the design of future vitamin D supplementation trials.

Vitamin D status during pregnancy: time for a more unified approach beyond borders?

Maternal hypovitaminosis D during pregnancy has been associated with a plethora of adverse health effects on the offspring. Maternal vitamin D status during pregnancy is affected by local climatic conditions. The aim of this article was to report on difficulties related to the heterogeneity of studies available in current literature on vitamin D status during pregnancy and discuss the incorporation of geophysical data in future studies, in an attempt to optimize their design and facilitate their interpretation. We focused on current vitamin D trials during pregnancy and their association with local regional climatic condition in geographical regions such as the Mediterranean basin based on our perspective on the field. Conduction of studies from areas with similar geophysical conditions is necessary, in order to extend our knowledge with respect to the question of which populations and under which circumstances would benefit most from vitamin D supplementation. Future vitamin D studies could benefit from the adoption of a unified concept minimizing these variations by selecting populations residing in areas with similar geophysical conditions adjusting also for their social and dietary habits.

Bone disease in patients with haemophilia A and B--where are we now?

It is evident that haemophilia A and B are associated with decreased bone mass in both adults and children. Decreased physical activity and vitamin D deficiency are some of the major factors leading to bone loss. Hepatitis C virus (HCV) infection may also contribute to low bone mineral density (BMD). However, definite conclusions regarding the exact prevalence and pathogenesis of osteoporosis cannot be conducted yet, due to the small sample size and significant heterogeneity among studies. Discordant findings with regard to the skeletal site of low BMD have also been reported. Furthermore, data on fracture risk are sparse. The use of the Fracture Risk Assessment Tool (FRAX) for assessing fracture risk, regular BMD assessment at the age of 25 and thereafter, careful evaluation of risk factors associated with bone loss and optimal calcium and vitamin D intake are recommended. Long-term prophylactic factor replacement therapy, resistance exercise and bisphosphonates, in severe cases of increased fracture risk, can prevent bone loss.

Bone mineral density in men and children with haemophilia A and B: a systematic review and meta-analysis.

SUMMARY: Although haemophilia is not considered among the classic causes of secondary osteoporosis, the present meta-analysis provides strong evidence that men with haemophilia have a significant reduction in both lumbar spine and femoral bone mineral density, which appears to begin in childhood. INTRODUCTION: Haemophilia is not considered among the classic causes of secondary osteoporosis. The aim of this study was to systematically review the literature for case-control trials that have studied bone mass in males with haemophilia and to meta-analyze the best evidence available. METHODS: Electronic databases MEDLINE, EMBASE and CENTRAL were systematically searched for case-control trials that have studied bone mass in men or boys with haemophilia. Standardized mean difference (SMD) for bone mineral density (BMD) in the lumbar spine was the main study outcome and SMD in femoral neck and total hip BMD the secondary ones. Patient and control characteristics, such as age, body mass index (BMI), level of physical activity and blood-borne infections were recorded as possible predictors of the main outcome. RESULTS: Thirteen studies were included in the systematic review and ten in the main outcome meta-analysis. Men with haemophilia demonstrated reduced lumbar spine [random effects SMD [95 % confidence interval (CI)] = -0.56 (-0.84, -0.28), between-study heterogeneity (I (2)) = 51 %] and femoral neck BMD [random effects SMD (95 % CI) = -0.82 (-1.21, -0.44), I (2) = 63 %] compared with controls, which indicated a large and clinically significant association. Similar results were obtained for children [random effects SMD (95 % CI) = -0.92 (-1.77, -0.07), I (2) = 92 %]. No evidence of publication bias was detected. There was no evidence that age, BMI, level of physical activity or presence of blood-borne infections predicted lumbar spine BMD. CONCLUSIONS: This meta-analysis shows that men with haemophilia present a significant reduction in both lumbar spine and hip BMD, which appears to begin in childhood.

Maternal vitamin D status during pregnancy: the Mediterranean reality.

Vitamin D status during pregnancy is linked to bone mineralization of developing fetus, which justifies targeting sufficient levels of vitamin D in pregnant women. Despite high level of sunshine in the Mediterranean regions, maternal hypovitaminosis D remain common in these countries. The aim of this narrative review was to provide potential explanations for this phenomenon in an effort to guide future public health policies and vitamin D intakes during pregnancy. We searched Medline for publications regarding hypovitaminosis D during pregnancy in the Mediterranean region. Available studies confirmed the high prevalence of hypovitaminosis D among pregnant women in the Mediterranean regions (50-65% in most studies), resulting in severe skeletal and nonskeletal health events among the offspring. Reasons for this may rely on maternal darker skin pigmentation, poor dietary vitamin D intake, veiled clothing and reduced sunshine exposure, health policies and increased prevalence of obesity. Public health organizations should be aware of this phenomenon and develop specific policies to prevent hypovitaminosis D and its adverse outcomes in maternal and neonatal health.

The clinical utility of bone turnover markers in the evaluation of bone disease in patients with haemophilia A and B.

Haemophilia A and B have been associated with increased prevalence of low bone mineral density (BMD). However, the utility of bone turnover markers (BTM) remains unknown. The aim of this study was to evaluate bone metabolism in men with haemophilia and to investigate associations between BTM and bone disease. Serum N- (NTX-I), C-terminal telopeptide of type I collagen (CTX-I) and tartrate-resistant acid phosphatase band-5b (TRAP-5b), as bone resorption markers, and osteocalcin (OC) and bone-specific alkaline phosphatase (b-ALP), as bone formation markers, were assessed. Seventy men with haemophilia A (n = 59) or B (n = 11) were studied. Patients with low BMD had significantly higher b-ALP concentrations compared with those with normal BMD (12.8 ± 1.60 vs. 9.72 ± 0.58 µg/L, P = 0.009), without any differences in the other BTM. NTX-I and CTX-I concentrations were negatively associated with oestradiol levels and hip BMD and positively with human immunodeficiency virus infection, number of affected joints and arthropathy scores. B-ALP and OC concentrations were negatively associated with hip BMD, severity of haemophilia and fracture history, and positively with the number of affected joints and testosterone concentrations. After multivariate analysis, NTX-I levels remained negatively associated with oestradiol levels, whereas b-ALP concentrations negatively correlated with the level of physical activity and positively with the number of affected joints. Increased bone metabolism exists in men with haemophilia and low BMD. Increased b-ALP levels may identify patients at high risk for fracture. Increased number of target joints, low physical activity and low oestradiol concentrations are independently associated with increased bone metabolism.

Maternal vitamin D status in pregnancy and offspring bone development: the unmet needs of vitamin D era.

Data from animal and human studies implicate maternal vitamin D deficiency during pregnancy as a significant risk factor for several adverse outcomes affecting maternal, fetal, and child health. The possible associations of maternal vitamin D status and offspring bone development comprise a significant public health issue. Evidence from randomized trials regarding maternal vitamin D supplementation for optimization of offspring bone mass is lacking. In the same field, data from observational studies suggest that vitamin D supplementation is not indicated. Conversely, supplementation studies provided evidence that vitamin D has beneficial effects on neonatal calcium homeostasis. Nevertheless, a series of issues, such as technical difficulties of current vitamin D assays and functional interplay among vitamin D analytes, prohibit arrival at safe conclusions. Future studies would benefit from adoption of a gold standard assay, which would unravel the functions of vitamin D analytes. This narrative review summarizes and discusses data from both observational and supplementation studies regarding maternal vitamin D status during pregnancy and offspring bone development.

Long-term control of hypertension in dialysis patients by low dose atenolol.

Hypertension in dialysis patients is considered a major factor in cardiovascular mortality. We investigated long-term efficacy of intermittent atenolol (AT) administration in 10 (7M/3F) hypertensive dialysis patients, age 60.5 (38-72), on dialysis for 56.5 months (8-156) thrice per week (10.5-13.5 h/w) (A). A similar group of 11 normotensive patients served as controls (B). Hypertension was defined as BP> 140/90 (day) and >120/80 mmHg (night) by a 44-h ambulatory BP monitoring (ABPM) after the mid-week session. Dialysis ultrafiltration, hematology, biochemistry were similar in A and B. Atenolol was started on an alternate day, 37.5 mg/w and increased as needed. After 34 days (6-80) and a dose of 68.75 (37.5-450) mg/w, BP dropped (ABPM: MAP 104+/-11.5 to 95.6+/-10.4 mmHg, P=0.0025) similar to controls and daytime HR dropped: 84.6+/-9.2 to 69.3+/-8.2, P=0.0008 and at night: 79.5+/-7.6 to 68.6+/-8.6 b/1' becoming lower than in B: 83+/-10.8/69.3+/-8.2, P=0.009 and 80.5+/-11.7/68.6+/-8.6 b/1' (P=0. 02). Six months later ABPM in A as well as echocardiography in A and B remained unchanged. Moderate, volume independent hypertension in stable dialysis patients is easily controlled during the interdialytic period by small intermittent atenolol doses.