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.

The impact of age on quality of life and frailty outcomes after parathyroidectomy in patients with primary hyperparathyroidism.

OBJECTIVE: Parathyroidectomy (PTx) improves quality of life (QoL) in patients with primary hyperparathyroidism (PHPT). Whether this effect is modified according to the patients' age is unknown. The aim of this study was to evaluate the impact of age on the effect of PTx on QoL and frailty in patients with PHPT, six months post-PTx. METHODS: This was a prospective cohort study, including patients with PHPT, admitted from January 2016 to December 2019, divided into two categories: younger (≤ 65 years old) and older (> 65 years old). QoL was assessed with the Pasieka questionnaire (PAS-Q) two days pre- and six months post-operatively. Frailty was also assessed at the same time intervals, with the Frailty Index (FI). RESULTS: One hundred and thirty-four patients (younger group: 96 patients, mean age 50.4 ± 9.8 years; older group: 38 patients, mean age 72.1 ± 4.9 years) were included. PTx resulted in a significant reduction in PAS-Q score in both groups. Notably, a greater reduction in "mood swings", "irritability", "itchy skin" and "feeling thirsty" PAS-Q domains was observed in the younger group. In contrast, a greater decrease in "bone pain", "tiredness", "weakness", "joint pain", "getting off chair" and "headaches" items was observed in the older group. Moreover, PTx led to a decrease in FI only in this group. CONCLUSIONS: PTx leads to an improvement in QoL both in older (> 65 years) and younger (≤ 65 years) patients with PHPT, attributed to a differential effect on PAS-Q items. Frailty improves only in the older group.

Oral antidiabetes agents for the management of inpatient hyperglycaemia: so far, yet so close.

BACKGROUND: Hyperglycaemia is an ongoing challenge in hospital settings and is associated with poor outcomes. Current recommendations for the management of inpatient hyperglycaemia suggest insulin as the main glucose-lowering treatment choice and limit the administration of oral antidiabetes agents to a small proportion of cases because of safety concerns. AIM: To present and critically appraise the available evidence on the use of oral antidiabetes agents in the hospital setting and the risk-benefit balance of such an approach in the era of cardiovascular outcomes trials. METHODS: PubMed, Embase and Google Scholar databases were searched to identify relevant published work. Available evidence on the efficacy and the safety profile of oral agents in the context of their use in hospitalized individuals are summarized and discussed in this narrative review. RESULTS: There is no robust evidence to suggest the use of metformin, thiazolidinediones, sulfonylureas and sodium-glucose co-transporter-2 inhibitors in the hospital setting, although some of their effects on acute outcomes deserve further evaluation in future studies. However, the use of dipeptidyl peptidase-4 inhibitors in inpatients with type 2 diabetes is supported by a few, well-designed, randomized controlled trials. These trials have demonstrated good safety and tolerability profiles, comparable to insulin glucose-lowering efficacy, and a reduction in insulin dose when dipeptidyl peptidase-4 inhibitors are co-administered with insulin, in individuals with mild to moderate hyperglycaemia and a stable clinical condition. CONCLUSION: The administration of dipeptidyl peptidase-4 inhibitors to specific groups of inpatients might be a safe and effective alternative to insulin.

Training, detraining, and retraining effects on glycemic control and physical fitness in women with type 2 diabetes.

Little is known about the detraining and retraining effects of exercise in patients with diabetes. The purpose of the present study was to investigate the effects of training, detraining, and retraining, using a combined strength and aerobic exercise program on glycemic control in women with type 2 diabetes. Thirteen postmenopausal women with type 2 diabetes (n = 13, age: 55.8 ± 5.1 years) followed a supervised aerobic and strength training program for 9 months, which was interrupted for 3 months (detraining) and resumed again for a period of 9 months (retraining). Anthropometric characteristics, glycemic control, and physical fitness were determined at baseline and after 9, 12, and 21 months. Training induced a small reduction in body mass index (BMI: -3.3%, 95% CI -5.1 to -1.5%), a moderate decrease in fasting plasma glucose (FPG: -12.0%, 95% CI -20.70 to -3.2%), glycosylated hemoglobin (HbA1c: -4.7%, 95% CI -12.1 to 2.7%), and a large decrease in postprandial glucose (PPG: - 12.1%, 95% CI -20.2 to -4.1%). In addition, there was an increase in power output (20.2%, 95% CI 6.9 to 33.6%) and total muscle strength (33.8%, 95% CI 21.4 to 46.1%). Detraining reversed PPG, HbA1c, and physical fitness. Resumption of training, however, led to a moderate decrease in BMI (-5.4%, 95% CI -8.1 to -2.7%), PPG (-9.5%, 95% CI -19.4 to 0.3%), and HbA1c (-6.8%, 95% CI -14.1 to 0.5%), and to large changes in FPG (-20.9%, 95% CI -31.9 to -9.9%), power output (33.1%, 95% CI 17.9 to 48.4%) and total muscle strength (48.2%, 95% CI 34.0 to 62.4%) compared to baseline. Thus, systematic training improves body composition, glycemic control and physical fitness in patients with type 2 diabetes. The cessation of exercise brings about negative alterations, while retraining restores all beneficial adaptations and improves them even more. Therefore, diabetic patients should follow a regular and an uninterrupted exercise program throughout life in order to control glucose metabolism and improve health.

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.

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.

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 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.

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.

Efficacy and tolerability of vildagliptin as first line treatment in patients with diabetes type 2 in an outpatient setting.

BACKGROUND: Inhibitors of dipeptidyl-peptidase IV are recommended as second-line therapy in type 2 diabetes (DT2), but data, as a first-line treatment in everyday clinical practice are scarce. To address this issue we conducted a 12-month, clinical study in an outpatient setting, using vildagliptin as the first-line treatment. METHODS: Ninety-one drug naïve patients with DT2 started with vildagliptin monotherapy (100 mg daily) for 4 months and were scheduled to regular 4-monthly visits for 1 year. Patients received add-on treatment with metformin or metformin and glimepiride according to their glycosylated hemoglobin (HbA1c) at each study-visit. RESULTS: HbA1c was significantly decreased with vildagliptin monotherapy from 8.16 % ± 1.60 to 7.52 % ± 1.60, p < 0.001. Only 39 % of the patients achieved the target of HbA1c ≤ 7.0 % at the end of the 4th month. Mean change in HbA1c was significantly correlated with baseline HbA1c values (r = -0.51, p < 0.001). At the end of the study only 35 % of the patients remained on vildagliptin monotherapy while the rest required add-on treatment with metformin or metformin and sulfonylurea. CONCLUSIONS: Vildagliptin is well tolerated either as monotherapy or in combination but the majority of patients require add-on therapy shortly after the beginning of treatment.

No association between a thyrotropin receptor gene polymorphism and Graves' disease in the female population.

A polymorphism in codon 52 of the human thyrotropin receptor results in a proline to threonine substitution in the extracellular domain of the receptor, and it has been suggested that the rarer, 52Thr, allele is associated with susceptibility to Graves' disease in the female population. To investigate this association we analyzed the distribution of TSH-R alleles in male (n = 60) and female (n = 120) Graves' patients, and control subjects (male n = 160 and female n = 85), using a PCR amplification and mismatch oligonucleotide hybridization technique. The variant allele was present in 8.3% of patients and 7.3% of control subjects. The frequencies in male and female patients were 6.7 and 9.2% respectively, and the allele distribution did not differ significantly from that observed in controls. No association was found between this TSH-R polymorphism and the occurrence of Graves' disease in the male or female population.

Extramedullary haematopoiesis in thalassaemia: results of radiotherapy: a report of three patients.

Extramedullary haematopoiesis is sometimes encountered in severe anaemia. Rarely, it may cause neurological symptoms, leading to spinal cord or cauda equina compression. Three patients with thalassaemia intermedia, who developed neurological complications, are described. The diagnoses were based on the clinical findings, computed tomography and magnetic resonance imaging. Small doses of radiotherapy (10-20 Gy in 5-10 fractions) relieved symptoms in all of these patients. Our experience supports the role of radiation therapy as a treatment for this complication.

Effects of intracerebroventricular infusion of somatostatin-14 on peripheral glucoregulation in dogs.

Somatostatin (SST) is an inhibitory hormone that regulates numerous biological processes and circulates in two bioactive isoforms: SST-14 and SST-28. SST-14 is the predominant form in the hypothalamus and regulates the secretion of growth hormone (GH) (directly) and of thyroid-stimulating hormone (indirectly). In the periphery, SST is a potent inhibitor of glucagon and insulin secretion. In the present study, we aimed to investigate the effect of i.c.v. administration of SST-14 on glucose metabolism. Twenty healthy adult dogs randomly received either a bolus i.c.v. infusion of 5, 25 or 50 µg of SST-14 or an equivalent amount of artificial cerebrospinal fluid through an epicranial apparatus during fasting. The same experiment was repeated during concomitant intraduodenal infusion of glucose solution through a Mann-Bollman fistula. Serum levels of glucose, insulin and glucose-dependent insulinotrophic peptide (GIP), plasma SST and serum GH levels were assayed. Circulating levels of SST and GH did not change significantly during i.c.v. infusions. Bolus infusion of 50 µg of SST-14 produced an increase in serum glucose levels at 10 min (94 ± 2.5 mg/dl at baseline versus 101 ± 3 mg/dl, P = 0.04) and significantly suppressed insulin levels, reaching maximal suppression at 60 min after infusion (9 ± 1.3 µIU/ml at baseline versus 4.6 ± 0.5 µIU/ml P = 0.04) in fasting animals. Similar results were obtained during intraduodenal infusion of glucose through a Mann-Bollman fistula. GIP levels did not change significantly during i.c.v. administration of SST-14. Intracerebroventricular infusion of SST-14 increases glucose and suppresses insulin levels in the periphery independently of circulating SST levels.

A CTLA-4 gene polymorphism is associated with both Graves disease and autoimmune hypothyroidism.

OBJECTIVE: The autoimmune thyroid diseases, Graves disease and autoimmune hypothyroidism, result from a complex interaction between genetic, environmental and endogenous factors. The genetic loci conferring susceptibility remain unclear. A recent report has demonstrated an association between a microsatellite polymorphism of the CTLA-4 gene (allele 106) on chromosome 2q33 and Graves' disease in Caucasian patients in the USA. The aim of the present study was to confirm this association in UK patients and to determine whether this polymorphism is also associated with autoimmune hypothyroidism. DESIGN: Analysis of Caucasian patients with autoimmune thyroid disease from a single clinic, compared to local Caucasian controls. PATIENTS: We studied 112 patients with Graves' disease, 44 with autoimmune hypothyroidism and 91 controls. MEASUREMENTS: CTLA-4 microsatellite gene polymorphisms were determined by polymerase chain reaction amplification of genomic DNA and resolution of the products on sequencing gels. RESULTS: As in previous studies, 21 alleles of the CTLA-4 microsatellite region were detected. Allele 106 was significantly increased in patients with Graves' disease (P = 0.006) and in those with autoimmune hypothyroidism (P = 0.02) when compared to controls. There was no significant difference between the groups in the distribution of the other alleles and no association between allele 106 and sex, HLA-DR or -DQ specificities or the presence of ophthalmopathy in the Graves' patients. CONCLUSIONS: These results confirm that the CTLA-4 gene, or one closely associated with it, confers susceptibility to Grave's disease but is not specific as the CTLA-4 106 allele is also associated with autoimmune hypothyroidism. This association seems to be with autoimmune thyroid disease in general.