Publications by authors named "Michael J McPhaul"

Article Synopsis
  • High-dose testosterone replacement therapy (TRT) combined with finasteride offers benefits such as improved body composition, muscle strength, and bone density in older men, while mitigating the risk of prostate enlargement.
  • A pilot study involved 12 men with spinal cord injuries, demonstrating that TRT with finasteride significantly increased lean body mass and muscle size, alongside enhancing bone mineral density compared to a placebo.
  • Results suggest TRT + finasteride reduced fat mass and improved muscular strength, with measurable benefits observed as early as 6 months into the treatment, indicating its potential effectiveness for men with low testosterone post-injury.
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Objectives: Limited data are available on the hormonal response of children to venepuncture or intravenous cannulation (IVC). Catecholamines [epinephrine (E) and norepinephrine (NE)] have been traditionally recognized as stress hormones. Copeptin, the carboxyl-terminus of the arginine vasopressin (AVP) precursor peptide, is also a known marker for stressful stimuli, including myocardial infarction, critical illness, and sepsis.

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Background: Fasting intact insulin concentrations can predict metabolic dysfunction-associated steatotic liver disease (MASLD) in adults without diabetes; however, research in youth is limited. We sought to determine whether fasting intact insulin, measured by liquid chromatography-tandem mass spectrometry, is associated with MASLD in children.

Methods: This retrospective cross-sectional analysis used data and samples from children who participated in studies across 3 universities between 2014 and 2022.

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Background: Dysglycemia and insulin resistance increase type 2 diabetes (T2D) and cardiovascular disease (CVD) risk, yet associations with specific glucose-insulin homeostatic biomarkers have been inconsistent. Vitamin D and marine omega-3 fatty acids (n-3 FA) may improve insulin resistance. We sought to examine the association between baseline levels of insulin, C-peptide, HbA1c, and a novel insulin resistance score (IRS) with incident cardiometabolic diseases, and whether randomized vitamin D or n-3 FA modify these associations.

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Background: In many practices, the screening for primary aldosteronism relies on a single-blood draw for plasma aldosterone concentration (PAC) and plasma renin activity (PRA) to establish an aldosterone-to-renin ratio (ARR). ARR levels vary between expert centers and repeated assays in the same individual, emphasizing the potential variability of this screening approach. A suppressed PRA to <1 ng/mL per h has been proposed as an alternative test to the ARR.

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Article Synopsis
  • Statin drugs, which help lower cholesterol and prevent cardiovascular disease, may cause adverse effects in women, especially new-onset diabetes and muscle weakness.
  • Research in female mice shows that these negative effects are linked to lower levels of the omega-3 fatty acid DHA, as well as issues with cellular function and energy production.
  • Administering fish oil to provide DHA can mitigate these adverse effects, and the study suggests that genetic factors related to the X chromosome may increase women's risk, highlighting the potential of DHA supplementation as a helpful therapy.
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Background And Aims: Previous studies have derived and validated an HDL apolipoproteomic score (pCAD) that predicts coronary artery disease (CAD) risk. However, the associations between pCAD and markers of cardiometabolic health in healthy adults are not known, nor are the effects of regular exercise on pCAD.

Methods: A total of 641 physically inactive adults free of cardiovascular disease from the HERITAGE Family Study completed 20 weeks of exercise training.

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Introduction: Stimulated copeptin may provide an alternative to water deprivation testing (WDT) in the evaluation of polyuria-polydipsia syndrome (PPS). Though best studied, arginine stimulation alone produces a modest copeptin response in children. We investigated the effectiveness of the arginine + LevoDopa/Carbidopa stimulation test (ALD-ST) for copeptin.

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Oral calorie intake causes an acute and transient decline in serum testosterone concentrations. It is not known whether this decline occurs in men on testosterone therapy. In this study, we evaluated the change in testosterone concentrations following oral glucose ingestion in hypogonadal men before and after treatment with testosterone therapy.

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Background: Professional guidelines recommend an HbA1c < 7% for most people with diabetes and < 8.5% for those with relaxed glycemic goals. However, many people with type 2 diabetes mellitus (T2DM) are unable to achieve the desired HbA1c goal.

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Objectives: Although AVP and its surrogate, copeptin, are mainly regulated by osmotic and volume stimuli, their secretion is also elicited by stress and growth hormone (GH) stimulating agents. The aim of this report is to describe unusual patterns of copeptin response in a subset of children undergoing GH stimulation tests (GH-ST).

Methods: We conducted a secondary analysis of a cohort of 93 healthy short children with no polydipsia, polyuria or fluid/electrolyte abnormalities, undergoing GH-ST with intravenous arginine, insulin, oral clonidine, or L-Dopa/carbidopa in various combinations.

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High-density lipoproteins (HDLs) are promising targets for predicting and treating atherosclerotic cardiovascular disease (ASCVD), as they mediate removal of excess cholesterol from lipid-laden macrophages that accumulate in the vasculature. This functional property of HDLs, termed cholesterol efflux capacity (CEC), is inversely associated with ASCVD. HDLs are compositionally diverse, associating with >250 different proteins, but their relative contribution to CEC remains poorly understood.

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Article Synopsis
  • The study aimed to determine how common IGF-1 variants are in a clinical population and what implications these variants might have.
  • Out of over 243,000 patients screened, 1,099 were found to have IGF-1 variants, with the majority being mutations at the C-terminus; some new variants were also identified.
  • The research suggests that IGF-1 variants affect hormone activity and lifespan in the bloodstream, indicating potential pathogenicity for certain variants located near the C-domain.
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We found that individuals in the top tertile of HOMA-IR and with HbA1c-defined prediabetes have elevated risk of cardiometabolic outcomes.

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Background: Insulin resistance (IR) is associated with cardiovascular disease (CVD). However, insulin immunoassay variability and scarce research of the elderly have hindered the adoption of IR assessment for CVD prevention. We asked whether the probability of having IR [p(IR)]-derived from insulin and C-peptide mass-spectrometry assays-was associated with CVD in the elderly.

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Objective: Insulin resistance (IR) increases risk of type 2 diabetes and atherosclerotic cardiovascular disease and is associated with lipid and lipoprotein abnormalities including high triglycerides (TG) and low high-density lipoprotein cholesterol (HDL-C). Lipoprotein size and lipoprotein subfractions (LS) have also been used to assist in identifying persons with IR. Associations of LS and IR have not been validated using both direct measures of IR and direct measures of LS.

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Introduction: Copeptin, co-secreted with arginine vasopressin, is regulated by osmotic and volume stimuli but also responds to intravenous arginine and insulin-induced hypoglycemia. The serum copeptin response to the latter agents has been studied in adults but only to a limited extent in children. The objective of this study was to describe the copeptin response to combined arginine and insulin in children with normal posterior pituitary function.

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Context: The mechanisms leading to increased cardiovascular disease in patients with nonalcoholic fatty liver disease (NAFLD) and advanced liver fibrosis remain incompletely understood.

Objective: This study assessed HDL-bound proteins in patients with NAFLD with or without advanced fibrosis.

Methods: This cross-sectional study at a university hospital included 185 patients with or without type 2 diabetes (T2D).

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A method for free thyroxine measurement in human serum using equilibrium dialysis followed by liquid chromatography tandem mass spectrometry (LC-MS/MS) is described. Free thyroxine in serum is first separated from protein-bound thyroxine by equilibrium dialysis and then measured by LC-MS/MS.

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Article Synopsis
  • The study aimed to determine if an 8-year diabetes risk could be lowered within 2 years through a digital Diabetes Prevention Program (dDPP) in a workforce setting.
  • Participants with prediabetes and a BMI of 25 or more were evaluated for diabetes risk before and after the program using the Framingham diabetes risk score.
  • Results showed a significant 5.3% decrease in diabetes risk after the first year of dDPP, following a slight increase the year prior, with the reduced risk maintained into the second year.
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Objective: Obesity in adolescent males is associated with the lowering of total and free testosterone concentrations. Weight loss may increase testosterone concentrations.

Design And Methods: We evaluated the changes in sex hormones following bariatric surgery in 34 males (age range: 14.

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Article Synopsis
  • Vitamin D supplementation has been linked to reductions in total cholesterol, LDL cholesterol, and triglycerides in clinical trials, but does not affect HDL cholesterol levels.
  • A real-world cohort study analyzed over 18,000 individuals to determine the relationship between changes in vitamin D levels and shifts in lipid profiles over a year, revealing that increased vitamin D correlates with lower levels of TC, LDL-C, and TG.
  • The study showed significant differences in lipid level changes between those who increased and decreased vitamin D levels, while changes in vitamin D were not associated with HDL cholesterol levels, even after controlling for various health factors.
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Background: Chromogranin A (CgA) is a 48 kDa protein that serves as a diagnostically sensitive, but nonspecific, serum biomarker for neuroendocrine tumors. Immunoassays for CgA are not standardized and have a narrow dynamic range, which requires dilution of concentrated specimens. We developed and validated an antibody-free, liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based method for CgA without these limitations.

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