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Department of Clinical Chemistry, Amsterdam Gastroenterology & Metabolism, Amsterdam UMC, University of Amsterdam, Endocrine Laboratory, Amsterdam, Netherlands
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Objective
PTH can be oxidised in vivo, rendering it biologically inactive. Non-oxidised PTH (n-oxPTH) may therefore give a better image of the hormonal status of the patient. While vitamin D supplementation decreases total PTH (tPTH) concentration, the effect on n-oxPTH concentration is unexplored. We investigated the effect of vitamin D on n-oxPTH concentration in comparison to tPTH and compared the correlations between parameters of calcium, bone and lipid metabolism with n-oxPTH and tPTH.
Methods
N-oxPTH was measured in 108 vitamin D-insufficient (25(OH)D <75 nmol/L) hypertensive patients, treated with vitamin D (2800 IE daily) or placebo for 8 weeks in the Styrian Vitamin D Hypertension Trial (NCT02136771). We calculated the treatment effect and performed correlation analyses of n-oxPTH and tPTH with parameters of calcium, bone and lipid metabolism and oxidative stress.
Results
After treatment, compared to placebo, 25(OH)D concentrations increased, tPTH decreased by 9% (P < 0.001), n-oxPTH by 7% (P = 0.025) and the ratio of n-oxPTH/tPTH increased (P = 0.027). Changes in phosphate and HDL concentration correlated with changes in n-oxPTH, but not tPTH.
Conclusions
tPTH and n-oxPTH decrease upon vitamin D supplementation. Our study suggests that vitamin D supplementation reduces the oxidation of PTH, as we observed a small but significant increase in the non-oxidised proportion of PTH upon treatment. In addition, we found that changes in phosphate and HDL concentration showed a relationship with changes in n-oxPTH, but not tPTH. This may be explained by the biological activity of n-oxPTH. Further research should be carried out to establish the clinical relevance of n-oxPTH.
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Background
Macrophage activation determined by levels of soluble sCD163 is associated with obesity, insulin resistance, diabetes mellitus type 2 (DM2) and non-alcoholic fatty liver disease (NAFLD). This suggests that macrophage activation is involved in the pathogenesis of conditions is characterised by adaptions in the lipid metabolism. Since sCD163 is shed to serum by inflammatory signals including lipopolysaccharides (LPS, endotoxin), we investigated sCD163 and correlations with lipid metabolism following LPS exposure.
Methods
Eight healthy male subjects were investigated on two separate occasions: (i) following an LPS exposure and (ii) following saline exposure. Each study day consisted of a four-hour non-insulin-stimulated period followed by a two-hour hyperinsulinemic euglycemic clamp period. A 3H-palmitate tracer was used to calculate the rate of appearance (Rapalmitate). Blood samples were consecutively obtained throughout each study day. Abdominal subcutaneous adipose tissue was obtained for western blotting.
Results
We observed a significant two-fold increase in plasma sCD163 levels following LPS exposure (P < 0.001), and sCD163 concentrations correlated positively with the plasma concentration of free fatty acids, Rapalmitate, lipid oxidation rates and phosphorylation of the hormone-sensitive lipase at serine 660 in adipose tissue (P < 0.05, all). Furthermore, sCD163 concentrations correlated positively with plasma concentrations of cortisol, glucagon, tumour necrosis factor (TNF)-α, interleukin (IL)-6 and IL-10 (P < 0.05, all).
Conclusion
We observed a strong correlation between sCD163 and stimulation of lipolysis and fat oxidation following LPS exposure. These findings support preexisting theory that inflammation and macrophage activation play a significant role in lipid metabolic adaptions under conditions such as obesity, DM2 and NAFLD.
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Department of Cardiology, Department of Research, Institute of Clinical Studies, Clinical Research Unit, Department of Paediatrics, Department of Medicine, Department of Physiology and Nuclear Medicine, Institute of Clinical Medicine, Nephrology and Endocrinology
Department of Cardiology, Department of Research, Institute of Clinical Studies, Clinical Research Unit, Department of Paediatrics, Department of Medicine, Department of Physiology and Nuclear Medicine, Institute of Clinical Medicine, Nephrology and Endocrinology
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Department of Cardiology, Department of Research, Institute of Clinical Studies, Clinical Research Unit, Department of Paediatrics, Department of Medicine, Department of Physiology and Nuclear Medicine, Institute of Clinical Medicine, Nephrology and Endocrinology
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Department of Cardiology, Department of Research, Institute of Clinical Studies, Clinical Research Unit, Department of Paediatrics, Department of Medicine, Department of Physiology and Nuclear Medicine, Institute of Clinical Medicine, Nephrology and Endocrinology
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Department of Cardiology, Department of Research, Institute of Clinical Studies, Clinical Research Unit, Department of Paediatrics, Department of Medicine, Department of Physiology and Nuclear Medicine, Institute of Clinical Medicine, Nephrology and Endocrinology
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relationship between 25(OH)D, risk of CVD (measured as carotid IMT, carotid artery DC and YEM) and bone health (measured as BMD and trabecular bone score (TBS)) in a Danish cohort of patients with T2D participating in a randomised clinical trial (The Copenhagen
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Objective
The effect of combined oral contraceptives (COCs) on female sexuality has long been a matter of discussion, but placebo-controlled studies are lacking. Thus, the aim of the present study was to investigate if an oestradiol-containing COC influences sexual function.
Design
Investigator-initiated, randomised, double-blinded, placebo-controlled clinical trial where 202 healthy women were randomised to a combined oral contraceptive (1.5 mg oestradiol and 2.5 mg nomegestrol acetate) or placebo for three treatment cycles.
Methods
Sexual function at baseline and during the last week of the final treatment cycle was evaluated by the McCoy Female Sexuality Questionnaire. Serum and hair testosterone levels were assessed at the same time points.
Results
Compared to placebo, COC use was associated with a small decrease in sexual interest (COC median change score: −2.0; interquartile range (IQR): −5.0 to 0.5 vs placebo: −1.0; IQR: −3.0 to 2.0, P = 0.019), which remained following adjustment for change in self-rated depressive symptoms (B = −0.80 ± 0.30, Wald = 7.08, P = 0.008). However, the proportion of women who reported a clinically relevant deterioration in sexual interest did not differ between COC or placebo users (COC 18 (22.2%) vs placebo 16 (17.8%), P = 0.47). Change in other measured aspects of sexual function as well as total score of sexual function did not differ between the two treatments.
Conclusions
This study suggests that use of oestradiol-based COCs is associated with reduced sexual interest. However, the changes are minute, and probably not of clinical relevance.
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Imperial College Healthcare NHS Trust, London, UK
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correction of hormonal deficiencies. The potential for surgical management to improve recovery from neurological deficits remains a subject of conjecture in the absence of large randomised clinical trials ( 6 , 15 , 16 ). Thus, variability in the clinical
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of the Look AHEAD randomised clinical trial . Lancet: Diabetes and Endocrinology 2016 4 913 – 921 . ( https://doi.org/10.1016/S2213-8587(1630162-0 ) 11 Strelitz J Ahern AL Long GH Hare MJL Irving G Boothby CE Wareham NJ Griffin
The Clatterbridge Cancer Centre, Wirral, UK
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Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK
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hypothyroidism and de novo development of hypothyroidism. We also showed an association with gender and variable presence of autoantibodies. A recent systematic review of 38 randomised clinical trials showed that the risk of thyroid dysfunction was highest with
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strategy with liraglutide in patients with type 2 diabetes mellitus inadequately controlled on metformin: a randomised clinical trial . Diabtologia 2013 56 1503 – 1511 . ( doi:10.1007/s00125-013-2905-1 ) 11 Nauck M Weinstock RS Umpierrez
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glycaemic control in patients hospitalised in a mixed medical and surgical intensive care unit: a randomised clinical trial . Critical Care 2008 12 R120 . ( https://doi.org/10.1186/cc7017 ) 36 Brunkhorst FM Engel C Bloos F Meier-Hellmann A Ragaller
Department of Oncology and Metabolism, The Medical School, The University of Sheffield, Sheffield, UK
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the retrospective observational design which makes it susceptible to selection bias and confounding. Our findings are, however, important for hypothesis generation and confirmation in prospective randomised clinical trials. Also, while our cohort is
