Effects of combined calcium and vitamin D supplementation on insulin secretion, insulin sensitivity and β-cell function in multi-ethnic vitamin D-deficient adults at risk for type 2 diabetes: a pilot randomized, placebo-controlled trial

ObjectivesTo examine whether combined vitamin D and calcium supplementation improves insulin sensitivity, insulin secretion, &beta;-cell function, inflammation and metabolic markers.Design6-month randomized, placebo-controlled trial.ParticipantsNinety-five adults with serum 25-hydroxyvitamin D [25(OH)D] &le;55 nmol/L at risk of type 2 diabetes (with prediabetes or an AUSDRISK score &ge;15) were randomized. Analyses included participants who completed the baseline and final visits (treatment n = 35; placebo n = 45).InterventionDaily calcium carbonate (1,200 mg) and cholecalciferol [2,000&ndash;6,000 IU to target 25(OH)D &gt;75 nmol/L] or matching placebos for 6 months.MeasurementsInsulin sensitivity (HOMA2%S, Matsuda index), insulin secretion (insulinogenic index, area under the curve (AUC) for C-peptide) and &beta;-cell function (Matsuda index x AUC for C-peptide) derived from a 75 g 2-h OGTT; anthropometry; blood pressure; lipid profile; hs-CRP; TNF-&alpha;; IL-6; adiponectin; total and undercarboxylated osteocalcin.ResultsParticipants were middle-aged adults (mean age 54 years; 69% Europid) at risk of type 2 diabetes (48% with prediabetes). Compliance was &gt;80% for calcium and vitamin D. Mean serum 25(OH)D concentration increased from 48 to 95 nmol/L in the treatment group (91% achieved &gt;75 nmol/L), but remained unchanged in controls. There were no significant changes in insulin sensitivity, insulin secretion and &beta;-cell function, or in inflammatory and metabolic markers between or within the groups, before or after adjustment for potential confounders including waist circumference and season of recruitment. In a post hoc analysis restricted to participants with prediabetes, a significant beneficial effect of vitamin D and calcium supplementation on insulin sensitivity (HOMA%S and Matsuda) was observed.ConclusionsDaily vitamin D and calcium supplementation for 6 months may not change OGTT-derived measures of insulin sensitivity, insulin secretion and &beta;-cell function in multi-ethnic adults with low vitamin D status at risk of type 2 diabetes. However, in participants with prediabetes, supplementation with vitamin D and calcium may improve insulin sensitivity.<br /

Experience in Optimising Fertility Outcomes in Men with Congenital Adrenal Hyperplasia due to 21 Hydroxylase Deficiency.

OBJECTIVE: Men with congenital adrenal hyperplasia (CAH) have impaired fertility. We aimed to assess fertility outcomes and the importance of hypogonadotropic hypogonadism, testicular failure and the presence of testicular adrenal rest tumours (TART). DESIGN: Retrospective analysis of men attending an adult CAH clinic in a tertiary centre. PATIENTS: Fifty men with CAH due to 21 hydroxylase deficiency were identified of whom 35 were salt-wasting and 15 were non-salt-wasting. MEASUREMENTS: Review of fertility history and parameters including luteinising hormone (LH), follicle stimulating hormone (FSH), androstenedione, 17-hydroxyprogesterone (17-OHP), semen analysis and the presence of testicular adrenal rest tissue (TART) on ultrasound. RESULTS: TART were detected by ultrasound in 21 (47%) and their presence was associated with an elevated FSH (p=0.01). Severe oligospermia was present in 11/23 (48%), and this was associated with an elevated FSH (p=0.02), suppressed LH (p5 x 10(6) per ml. Of those that desired fertility, 10/17 (59%) required treatment intensification, and 4 underwent in vitro fertilisation. Intensification resulted in a rise in median LH (0.6 to 4.3 IU/L; p=0.01). Live birth rate was 15/17 (88%) with a median (range) time to conception of 8(0-38) months. CONCLUSIONS: Suppressed LH is a marker for subfertility and is often reversible. Testicular failure is closely associated with TART formation. If TART are detected, sperm cryopreservation should be offered given the risk of progression to irreversible testicular failure. Male fertility in CAH can be improved by intensified treatment and assisted reproductive technology. This article is protected by copyright. All rights reserved

Reference range determination for imaging biomarkers : Myocardial T1

Funding Information NHS‐Endowments. Grant Number: EA0537 University of Aberdeen Elphinstone scholarship We thank the Cardiovascular Medicine Research team at the University of Aberdeen for acquisition of healthy volunteer data.Peer reviewedPostprin

Serum 25-Hydroxyvitamin D, Calcium Intake, and Risk of Type 2 Diabetes After 5 Years: Results from a national, population-based prospective study (the Australian Diabetes, Obesity and Lifestyle study)

OBJECTIVE To examine whether serum 25-hydroxyvitamin D (25OHD) and dietary calcium predict incident type 2 diabetes and insulin sensitivity.RESEARCH DESIGN AND METHODS A total of 6,537 of the 11,247 adults evaluated in 1999&ndash;2000 in the Australian Diabetes, Obesity and Lifestyle (AusDiab) study, returned for oral glucose tolerance test (OGTT) in 2004&ndash;2005. We studied those without diabetes who had complete data at baseline (n = 5,200; mean age 51 years; 55% were women; 92% were Europids). Serum 25OHD and energy-adjusted calcium intake (food frequency questionnaire) were assessed at baseline. Logistic regression was used to evaluate associations between serum 25OHD and dietary calcium on 5-year incidence of diabetes (diagnosed by OGTT) and insulin sensitivity (homeostasis model assessment of insulin sensitivity [HOMA-S]), adjusted for multiple potential confounders, including fasting plasma glucose (FPG).RESULTS During the 5-year follow-up, 199 incident cases of diabetes were diagnosed. Those who developed diabetes had lower serum 25OHD (mean 58 vs. 65 nmol/L; P &lt; 0.001) and calcium intake (mean 881 vs. 923 mg/day; P = 0.03) compared with those who remained free of diabetes. Each 25 nmol/L increment in serum 25OHD was associated with a 24% reduced risk of diabetes (odds ratio 0.76 [95% CI 0.63&ndash;0.92]) after adjusting for age, waist circumference, ethnicity, season, latitude, smoking, physical activity, family history of diabetes, dietary magnesium, hypertension, serum triglycerides, and FPG. Dietary calcium intake was not associated with reduced diabetes risk. Only serum 25OHD was positively and independently associated with HOMA-S at 5 years.CONCLUSIONS Higher serum 25OHD levels, but not higher dietary calcium, were associated with a significantly reduced risk of diabetes in Australian adult men and women.<br /

Spectroscopic studies as a toolbox for biophysical and chemical characterization of lipid-based nanotherapeutics

The goal of this study is to provide tools to minimize trial-and-error in the development of novel lipid-based nanotherapeutics, in favor of a rational design process. For this purpose, we present case-study examples of biophysical assays that help addressing issues of lipid-based nanotherapeutics' profiling and assist in the design of lipid nanocarriers for therapeutic usage. The assays presented are rooted in spectroscopic methods (steady-state and time-resolved fluorescence; UV-Vis derivative spectroscopy; fluorescence anisotropy and fluorescence lifetime image microscopy) and allow accessing physical-chemical interactions between drugs and lipid nanocarriers, as well as studying interactions between lipid-based nanotherapeutics and membranes and/or proteins, as this is a key factor in predicting their therapeutic and off target effects. Derivative spectroscopy revealed Naproxen's high distribution (LogD ≈ 3) in different lipid-based nanocarriers (micelles and unilamellar or multilamellar vesicles) confirming the adequacy of such systems for encapsulating this anti-inflammatory drug. Fluorescence quenching studies revealed that the anti-inflammatory drugs Acemetacin and Indomethacin can reach an inner location at the lipid nanocarrier while being anchored with its carboxylic moiety at the polar headgroup. The least observed quenching effect suggested that Tolmetin is probably located at the polar headgroup region of the lipid nanocarriers and this superficial location may translate in a fast drug release from the nanocarriers. Fluorescent anisotropy measurements indicated that the drugs deeply buried within the lipid nanocarrier where the ones that had a greater fluidizing effect which can also translate in a faster drug release. The drug binding strength to serum albumin was also compared for a free drug (Clonixin) or for the same drug after encapsulation in a lipid nanocarrier DSPC:DODAP (2:1). Under both conditions there is a strong binding to serum albumin, at one binding site, suggesting the need to produce a stealth nanosystem. Finally the cellular uptake of lipid nanocarriers loaded with Daunorubicin was investigated in cancer cells using fluorescence lifetime imaging microscopy. From the images obtained it was possible to conclude that even at short incubation times (15 min) there was a distribution of the drug in the cytoplasm, whereas for longer incubation periods (4 h) the drug has reached the nucleus.This work was supported by the Portuguese Foundation for Science and Technology (FCT) in the framework of the Strategic Funding UID/FIS/04650/2013 and in the ambit of the project IF/00498/2012

Comparison of IFCC-calibrated HbA1c from laboratory and point of care testing systems

Objective: WHO, IDF and ADA recommend HbA1c ≥6.5% (48 mmol/mol) for diagnosis of diabetes with pre-diabetes 6.0% (42 mmol/mol) [WHO] or 5.7% (39 mmol/mol) [ADA] to 6.4% (47 mmol/mol). We have compared HbA1c from several methods for research relating glycaemic markers.Research design and methods: HbA1c was measured in EDTA blood from 128 patients with diabetes on IE HPLC analysers (Bio-Rad Variant II NU, Menarini HA8160 and Tosoh G8), point of care systems, POCT, (A1cNow+ disposable cartridges and DCA 2000®+ analyser), affinity chromatography (Primus Ultra2) and the IFCC secondary reference method (Menarini HA8160 calibrated using IFCC SRM protocol).Results: median (IQ range) on IFCC SRM was 7.5% (6.8–8.4) (58(51–68) mmol/mol) HbA1c with minimum 5.3%(34 mmol/mol)/maximum 11.9%(107 mmol/mol). There were positive offsets between IFCC SRM and Bio-Rad Variant II NU, mean difference (1SD), +0.33%(0.17) (+3.6(1.9) mmol/mol), r2 = 0.984, p &lt; 0.001 and Tosoh G8, +0.22%(0.20) (2.4(2.2) mmol/mol), r2 = 0.976, p &lt; 0.001 with a very small negative difference −0.04%(0.11) (−0.4(1.2) mmol/mol), r2 = 0.992, p &lt; 0.001 for Menarini HA8160. POCT methods were less precise with negative offsets for DCA 2000®+ analyser −0.13%(0.28) (−1.4(3.1) mmol/mol), r2 = 0.955, p &lt; 0.001 and A1cNow+ cartridges −0.70%(0.67) (−7.7(7.3) mmol/mol), r2 = 0.699, p &lt; 0.001 (n = 113). Positive biases for Tosoh and Bio-Rad (compared with IFCC SRM) have been eliminated by subsequent revision of calibration.Conclusions: small differences observed between IFCC-calibrated and NGSP certified methods across a wide HbA1c range were confirmed by quality control and external quality assurance. As these offsets affect estimates of diabetes prevalence, the analyser (and calibrator) employed should be considered when evaluating diagnostic data.</p

Results of the first recorded evaluation of a national gestational diabetes mellitus register: challenges in screening, registration, and follow-up for diabetes risk

OBJECTIVE:Gestational Diabetes Mellitus (GDM) increases the risk of type 2 diabetes. A register can be used to follow-up high risk women for early intervention to prevent progression to type 2 diabetes. We evaluate the performance of the world's first national gestational diabetes register. RESEARCH DESIGN AND METHODS:Observational study that used data linkage to merge: (1) pathology data from the Australian states of Victoria (VIC) and South Australia (SA); (2) birth records from the Consultative Council on Obstetric and Paediatric Mortality and Morbidity (CCOPMM, VIC) and the South Australian Perinatal Statistics Collection (SAPSC, SA); (3) GDM and type 2 diabetes register data from the National Gestational Diabetes Register (NGDR). All pregnancies registered on CCOPMM and SAPSC for 2012 and 2013 were included-other data back to 2008 were used to support the analyses. Rates of screening for GDM, rates of registration on the NGDR, and rates of follow-up laboratory screening for type 2 diabetes are reported. RESULTS:Estimated GDM screening rates were 86% in SA and 97% in VIC. Rates of registration on the NGDR ranged from 73% in SA (2013) to 91% in VIC (2013). During the study period rates of screening at six weeks postpartum ranged from 43% in SA (2012) to 58% in VIC (2013). There was little evidence of recall letters resulting in screening 12 months follow-up. CONCLUSIONS:GDM Screening and NGDR registration was effective in Australia. Recall by mail-out to young mothers and their GP's for type 2 diabetes follow-up testing proved ineffective.Douglas I. R. Boyle, Vincent L. Versace, James A. Dunbar, Wendy Scheil, Edward Janus, Jeremy J. N. Oats, Timothy Skinner, Sophy Shih, Sharleen O'Reilly, Ken Sikaris, Liza Kelsall, Paddy A. Phillips, James D. Best, on behalf of MAGDA Study Grou