NMR spectroscopy derived plasma biomarkers of inflammation in human populations: Influences of age, sex and adiposity.

Understanding the distribution and variation in inflammatory markers is crucial for advancing our knowledge of inflammatory processes and evaluating their clinical utility in diagnosing and monitoring acute and chronic disease. 1H NMR spectroscopy of blood plasma and serum was applied to measure a composite panel of inflammatory markers based on acute phase glycoprotein signals (GlycA and GlycB) and sub-regions of the lipoprotein derived Supramolecular Phospholipid Composite signals (SPC1, SPC2 and SPC3) to establish normal ranges in two healthy, predominantly white cohorts from Australia (n = 398) and Spain (n = 80; ages 20-70 years). GlycA, GlycB, SPC1 and SPC3 were not significantly impacted by age or sex, but SPC2 (an HDL-related biomarker) was significantly higher in women across all age ranges by an average of 33.

Predicting type 2 diabetes and testosterone effects in high-risk Australian men: development and external validation of a 2-year risk model.

Objective: We have shown that men aged 50 years+ at high risk of type 2 diabetes treated with testosterone together with a lifestyle program reduced the risk of type 2 diabetes at 2 years by 40% compared to a lifestyle program alone. To develop a personalized approach to treatment, we aimed to explore a prognostic model for incident type 2 diabetes at 2 years and investigate biomarkers predictive of the testosterone effect.

Design: Model development in 783 men with impaired glucose tolerance but not type 2 diabetes from Testosterone for Prevention of Type 2 Diabetes; a multicenter, 2-year trial of Testosterone vs placebo.

Comparison of cardiovascular risk prediction in type 1 diabetes: an Australian viewpoint.

Cardiovascular disease (CVD) is a significant burden in individuals with type 1 diabetes mellitus (T1DM). Yet the optimal method of CVD risk stratification remains uncertain. We found that the new Australian CVD risk calculator could overestimate risk category compared with the Steno Type 1 Risk Engine and underestimate risk category compared with the new Swedish/Scottish prediction tool, both of which were validated for T1DM.

Associations between subclinical thyroid dysfunction and cardiovascular risk factors according to age and sex.

Context: Subclinical thyroid dysfunction (ScTD) comprising subclinical hypothyroidism (SHypo) and subclinical hyperthyroidism (SHyper) has been associated with increased risk for cardiovascular events.

Objective: To assess associations between ScTD and cardiovascular risk factors (cvRFs) according to age and sex.

Design And Setting: Pooled individual participant data analysis of large prospective cohort studies from the Thyroid Studies Collaboration.

Sociodemographic, lifestyle, and medical factors associated with calculated free testosterone concentrations in men: individual participant data meta-analyses.

Objective: Sociodemographic, lifestyle, and medical variables influence total testosterone (T) and sex hormone-binding globulin (SHBG) concentrations. The relationship between these factors and "free" T remains unclear. We examined 21 sociodemographic, lifestyle, and medical predictors influencing calculated free T (cFT) in community-dwelling men across ages.

Associations of Serum Testosterone and Sex Hormone-Binding Globulin with Incident Fractures in Middle-Aged to Older Men.

Context: As men age, circulating testosterone (T) decreases, circulating sex-hormone binding globulin (SHBG) increases, and risk of fracture increases. It is unclear if circulating T, independently of comorbidities, is associated with fracture risk in men.

Objectives: To determine associations for T and SHBG with incident fractures in men.

Beyond T-Trials, T4DM and TRAVERSE: the next large testosterone randomized controlled trial.

Purpose Of Review: Lower testosterone concentrations have been associated with poorer health outcomes in ageing men, but proving causality and demonstrating potential for therapeutic benefit requires randomized clinical trials (RCTs). This review discusses recent observational findings and results of major testosterone RCTs, to explore the need for another, larger trial.

Recent Findings: Evidence of Leydig cell impairment emerges in men above the age of 70 years.

The role of bone in energy metabolism: A focus on osteocalcin.

Understanding the mechanisms involved in whole body glucose regulation is key for the discovery of new treatments for type 2 diabetes (T2D). Historically, glucose regulation was largely focused on responses to insulin and glucagon. Impacts of incretin-based therapies, and importance of muscle mass, are also highly relevant.

Distribution of Serum Testosterone Concentrations in IBD Males and Associations With Inflammatory Bowel Disease Activity.

Background: An inverse relationship exists between inflammation and testosterone concentrations in non-inflammatory bowel disease (IBD) immune conditions but has not been objectively explored in the IBD male population. We aimed to characterize the distribution of testosterone concentrations in a cohort of males with IBD and identify any relationship between testosterone levels and disease activity.

Methods: We conducted a prospective cross-sectional study of male IBD patients.

Testosterone therapy in older men: clinical implications of recent landmark trials.

Testosterone therapy for men with hypogonadism due to identifiable hypothalamic-pituitary-testicular (HPT) pathology is uncontroversial. However, the risks and benefits of testosterone for men with clinical features of hypogonadism in the absence of identifiable HPT axis pathology have been uncertain. Recent landmark placebo-controlled trials assessed the benefits and risks of testosterone therapy (≤3 years) for middle-aged and older men with symptoms and possible signs of hypogonadism or end-organ androgen deficiency, low or low-normal serum testosterone concentrations, but no HPT pathology: Testosterone therapy (1) had modest-but clinically significant-benefits on average self-reported energy and mood, sexual function, and satisfaction; (2) in conjunction with a lifestyle programme, reversed or reduced incident type 2 diabetes mellitus (T2D) in men at high risk of or newly diagnosed with T2D; (3) modestly improved objectively assessed muscle strength and timed walking distance; (4) increased bone density and strength, but did not reduce falls or typical osteoporotic fractures and surprisingly increased the risk of fractures typically attributable to trauma; and (5) did not significantly increase the risk of myocardial infarction, stroke, or prostate cancer.

Correction: Testosterone treatment combined with exercise to improve muscle strength, physical function and quality of life in men affected by inclusion body myositis: A randomised, double-blind, placebo-controlled, crossover trial.

[This corrects the article DOI: 10.1371/journal.pone.

Associations of Diabetes and Hyperglycaemia with Extent and Outcomes of Acute Burn Injuries.

Background: Severe burns may induce hyperglycaemia in the absence of diabetes, but how glucose trajectories relate to burns outcomes is unclear.

Aim: To assess incidence of hyperglycaemia following acute burn injury, and associations with diabetes history and length of stay (LOS).

Methods: Retrospective cohort study of adults admitted with acute burns to tertiary centres.

Associations of Testosterone and Related Hormones With All-Cause and Cardiovascular Mortality and Incident Cardiovascular Disease in Men : Individual Participant Data Meta-analyses.

Background: Whether circulating sex hormones modulate mortality and cardiovascular disease (CVD) risk in aging men is controversial.

Purpose: To clarify associations of sex hormones with these outcomes.

Data Sources: Systematic literature review to July 2019, with bridge searches to March 2024.

Testosterone and the risk of incident atrial fibrillation in older men: further analysis of the ASPREE study.

Background: A cardiovascular safety trial of testosterone in men with cardiovascular risk factors or disease found no difference in rates of major adverse cardiovascular events (MACE) or death but noted more atrial fibrillation (AF) events in testosterone-treated men. We investigated the relationship between endogenous testosterone concentrations with risk of developing AF in healthy older men.

Methods: Post-hoc analysis of 4570 male participants in the ASPirin in Reducing Events in the Elderly (ASPREE) study.

Incretin-Based Weight Loss Pharmacotherapy: Can Resistance Exercise Optimize Changes in Body Composition?

This narrative review highlights the degree to which new antiobesity medications based on gut-derived nutrient-stimulated hormones (incretins) cause loss of lean mass, and the importance of resistance exercise to preserve muscle. Glucagon-like peptide 1 receptor agonists (GLP-1RA) induce substantial weight loss in randomized trials, effects that may be enhanced in combination with glucose-dependent insulinotropic polypeptide (GIP) receptor agonists. Liraglutide and semaglutide (GLP-1RA), tirzepatide (GLP-1 and GIP receptor dual agonist), and retatrutide (GLP-1, GIP, and glucagon receptor triple agonist) are peptides with incretin agonist activity that induce ∼15-24% weight loss in adults with overweight and obesity, alongside beneficial impacts on blood pressure, cholesterol, blood glucose, and insulin.

Comparing the Impacts of Testosterone and Exercise on Lean Body Mass, Strength and Aerobic Fitness in Aging Men.

Background: Based on the largely untested premise that it is a restorative hormone that may reverse the detrimental impacts of aging, prescription of testosterone (T) has increased in recent decades despite no new clinical indications. It is apparent that middle-aged and older men with low-normal serum T levels are considering T supplementation as an anti-aging strategy. At the same time, there is evidence that physical activity (PA) is at historical lows in the Western world.

Early SGLT2 inhibitor use is associated with improved left atrial strain following acute coronary syndrome.

Aim: Left atrial (LA) strain, a novel marker of LA function, reliably predicts diastolic dysfunction. SGLT2 inhibitors improve heart failure outcomes, but limited data exists regarding their use in the immediate aftermath of acute coronary syndrome (ACS). We studied the effect of empagliflozin on LA strain in patients with type 2 diabetes (T2D) and ACS.

Association of Serum Phosphate, Calcium and Alkaline Phosphatase With Risk of Incident Fractures in Healthy Older Adults.

Context: Aging increases fracture risk through bone loss and microarchitecture deterioration due to an age-related imbalance in bone resorption and formation during bone remodeling.

Objective: We examined the associations between levels of phosphate, calcium (Ca), and alkaline phosphatase (ALP), and fracture risk in initially healthy older individuals.

Methods: A post hoc analysis of the Aspirin in Reducing Events in the Elderly (ASPREE) trial recruited 16 703 Australian participants aged 70 years and older and 2411 US participants aged 65 years and older.

Testosterone Treatment, Weight Loss, and Health-related Quality of Life and Psychosocial Function in Men: A 2-year Randomized Controlled Trial.

Objective: To determine the effect of testosterone vs placebo treatment on health-related quality of life (HR-QOL) and psychosocial function in men without pathologic hypogonadism in the context of a lifestyle intervention.

Design, Setting, Participants: Secondary analysis of a 2-year randomized controlled testosterone therapy trial for prevention or reversal of newly diagnosed type 2 diabetes, enrolling men ≥ 50 years at high risk for type 2 diabetes from 6 Australian centers.

Interventions: Injectable testosterone undecanoate or matching placebo on the background of a community-based lifestyle program.

Group-based behaviour therapy improves self-care, glycaemic control and distress in adults with type 1 diabetes.

Aims: Psychological interventions have had modest effects on HbA1c in adults with Type 1 diabetes (T1D). We evaluated a novel behaviour therapy (BT) group program aiming to improve diabetes self-care and reduce HbA1c and distress. Core features were the application of a functional-analytic model, behavioural self-management training, and personally selected T1D self-care behaviours as treatment targets.

Changes in thyroid function and evolution of subclinical thyroid disease in older men.

Objective: Prevalence of subclinical thyroid disease increases with age, but optimal detection and surveillance strategies remain unclear particularly for older men. We aimed to assess thyroid stimulating hormone (TSH) and free thyroxine (FT4) concentrations and their longitudinal changes, to determine the prevalence and incidence of subclinical thyroid dysfunction in older men.

Design, Participants And Measurements: Longitudinal study of 994 community-dwelling men aged ≥70 years without known or current thyroid disease, with TSH and FT4 concentrations assessed at baseline and follow-up (after 8.

The optimal healthy ranges of thyroid function defined by the risk of cardiovascular disease and mortality: systematic review and individual participant data meta-analysis.

Background: Reference intervals of thyroid-stimulating hormone (TSH) and free thyroxine (FT) are statistically defined by the 2·5-97·5th percentiles, without accounting for potential risk of clinical outcomes. We aimed to define the optimal healthy ranges of TSH and FT based on the risk of cardiovascular disease and mortality.

Methods: This systematic review and individual participant data (IPD) meta-analysis identified eligible prospective cohorts through the Thyroid Studies Collaboration, supplemented with a systematic search via Embase, MEDLINE (Ovid), Web of science, the Cochrane Central Register of Controlled Trials, and Google Scholar from Jan 1, 2011, to Feb 12, 2017 with an updated search to Oct 13, 2022 (cohorts found in the second search were not included in the IPD).

Exposure to low-level ambient air pollution and the relationship with lung and bladder cancer in older men, in Perth, Western Australia.

Background: Air pollution is a cause of lung cancer and is associated with bladder cancer. However, the relationship between air pollution and these cancers in regions of low pollution is unclear. We investigated associations between fine particulate matter (PM), nitrogen dioxide, and black carbon (BC), and both these cancers in a low-pollution city.

Factors Associated With Circulating Sex Hormones in Men : Individual Participant Data Meta-analyses.

Background: Various factors modulate circulating testosterone in men, affecting interpretation of testosterone measurements.

Purpose: To clarify factors associated with variations in sex hormone concentrations.

Data Sources: Systematic literature searches (to July 2019).