GLP-1R gene polymorphisms and metabolic traits during childhood and adolescence: The EPOCH study.

Aims/hypothesis: This is the first study to examine the association between variants of the glucagon-like-peptide-1 receptor gene (GLP-1R) and metabolic characteristics among youth. We explored separate associations of three GLP-1R polymorphisms (rs10305420, rs6923761, and rs1042044) with BMI trajectories and markers of glucose-insulin homeostasis.

Methods: Mixed models examined associations between GLP-1R polymorphisms and trajectories of BMI.

Fasting intact insulin by mass spectrometry is associated with metabolic dysfunction-associated steatotic liver disease in youth.

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.

Muscle mitochondrial function is impaired in adults with type 1 diabetes.

Aims: Type 1 diabetes has been associated with mitochondrial dysfunction. However, the mechanism of this dysfunction in adults remains unclear.

Methods: A secondary analysis was conducted using data from several clinical trials measuring in-vivo and ex-vivo mitochondrial function in adults with type 1 diabetes (n = 34, age 38.

Insulin sensitivity, body composition and bone mineral density after testosterone treatment in transgender youth with and without prior GnRH agonist therapy.

Background: 1.8% of youth identify as transgender; a growing proportion are transgender male (female sex, male gender identity). Many receive gonadotropin releasing hormone agonist (GnRHa) therapy to suppress endogenous puberty and/or will start testosterone to induce secondary sex characteristics that align with gender identity.

Diagnostic Accuracy of Transient Elastography in Hepatosteatosis in Youth With Obesity.

Context: Steatotic liver disease is common but overlooked in childhood obesity; diagnostic methods are invasive or expensive.

Objective: We sought to determine the diagnostic accuracy of vibration-controlled transient elastography (VCTE) compared with magnetic resonance imaging (MRI) in adolescents with obesity and high risk for hepatosteatosis.

Methods: Baseline data in 3 clinical trials enrolling adolescents with obesity were included (NCT03919929, NCT03717935, NCT04342390).

Prediction of resting energy expenditure for adolescents with severe obesity: A multi-centre analysis.

Background And Objectives: Resting energy expenditure (REE) assessments can help inform clinical treatment decisions in adolescents with elevated body mass index (BMI), but current equations are suboptimal for severe obesity. We developed a predictive REE equation for youth with severe obesity and obesity-related comorbidities and compared results to previously published predictive equations.

Methods: Data from indirect calorimetry, clinical measures, and body composition per Dual x-ray absorptiometry (DXA) were collected from five sites.

Comprehensive transition of care for polycystic ovary syndrome from adolescence to adulthood.

Polycystic ovary syndrome (PCOS) is a lifelong chronic condition that affects one in ten females and can be diagnosed in adolescence. As adolescents with PCOS transition to adulthood, counselling for lifestyle management and mental health concerns often transition from involving the family unit to increasingly individual-focused approaches. PCOS is associated with a large range of comorbidities affecting reproductive, metabolic, dermatological, and psychological health.

Metabolic effects of an essential amino acid supplement in adolescents with PCOS and obesity.

Objective: Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism, insulin resistance, and hepatic steatosis (HS). Because dietary essential amino acid (EAA) supplementation has been shown to decrease HS in various populations, this study's objective was to determine whether supplementation would decrease HS in PCOS.

Methods: A randomized, double-blind, crossover, placebo-controlled trial was conducted in 21 adolescents with PCOS (BMI 37.

Distinct Reproductive Phenotypes Segregate With Differences in Body Weight in Adolescent Polycystic Ovary Syndrome.

Introduction: Polycystic ovary syndrome (PCOS) is a heterogenous clinical syndrome defined by hyperandrogenism and irregular menses. In adult women with PCOS, discrete metabolic and reproductive subgroups have been identified. We hypothesize that distinct phenotypes can be distinguished between adolescent girls who are lean (LN-G) and girls with obesity (OB-G) at the time of PCOS diagnosis.

Estimating insulin sensitivity and β-cell function from the oral glucose tolerance test: validation of a new insulin sensitivity and secretion (ISS) model.

Efficient and accurate methods to estimate insulin sensitivity () and β-cell function (BCF) are of great importance for studying the pathogenesis and treatment effectiveness of type 2 diabetes (T2D). Existing methods range in sensitivity, input data, and technical requirements. Oral glucose tolerance tests (OGTTs) are preferred because they are simpler and more physiological than intravenous methods.

Estimating Insulin Sensitivity and Beta-Cell Function from the Oral Glucose Tolerance Test: Validation of a new Insulin Sensitivity and Secretion (ISS) Model.

Efficient and accurate methods to estimate insulin sensitivity (S) and beta-cell function (BCF) are of great importance for studying the pathogenesis and treatment effectiveness of type 2 diabetes. Many methods exist, ranging in input data and technical requirements. Oral glucose tolerance tests (OGTTs) are preferred because they are simpler and more physiological.

Glycerol as a precursor for hepatic de novo glutathione synthesis in human liver.

Background: Glycerol is a substrate for gluconeogenesis and fatty acid esterification in the liver, processes which are upregulated in obesity and may contribute to excess fat accumulation. Glycine and glutamate, in addition to cysteine, are components of glutathione, the major antioxidant in the liver. In principle, glycerol could be incorporated into glutathione via the TCA cycle or 3-phosphoglycerate, but it is unknown whether glycerol contributes to hepatic de novo glutathione biosynthesis.

Impaired glucose tolerance in pediatric burn patients at discharge from the acute hospital stay.

Hyperglycemia, secondary to the hypermetabolic stress response, is a common occurrence after thermal injury. This stress response has been documented to persist up to 9 months postburn. The purpose of this study was to measure insulin sensitivity in severely burned children before discharge when wounds are 95% healed.

Metabolic profiling of muscle contraction in lean compared with obese rodents.

Interest in the pathophysiological relevance of intramuscular triacylglycerol (IMTG) accumulation has grown from numerous studies reporting that abnormally high glycerolipid levels in tissues of obese and diabetic subjects correlate negatively with glucose tolerance. Here, we used a hindlimb perfusion model to examine the impact of obesity and elevated IMTG levels on contraction-induced changes in skeletal muscle fuel metabolism. Comprehensive lipid profiling was performed on gastrocnemius muscles harvested from lean and obese Zucker rats immediately and 25 min after 15 min of one-legged electrically stimulated contraction compared with the contralateral control (rested) limbs.

Intensive insulin therapy improves insulin sensitivity and mitochondrial function in severely burned children.

Objective: To institute intensive insulin therapy protocol in an acute pediatric burn unit and study the mechanisms underlying its benefits.

Design: Prospective, randomized study.

Setting: An acute pediatric burn unit in a tertiary teaching hospital.

Twenty-eight-day bed rest with hypercortisolemia induces peripheral insulin resistance and increases intramuscular triglycerides.

Spaceflight represents a unique physiologic challenge to humans, altering hormonal profiles and tissue insulin sensitivity. Among these hormonal alterations, hypercortisolemia and insulin insensitivity are thought to negatively affect muscle mass and function with spaceflight. As insulin sensitivity influences the accumulation of muscle triglycerides, we examined this relationship during hypercortisolemia and inactivity.

Muscle protein synthesis and balance responsiveness to essential amino acids ingestion in the presence of elevated plasma free fatty acid concentrations.

Context: Elevated plasma free fatty acid (FFA) concentrations are observed under various clinical circumstances and are associated with impaired glucose disposal in skeletal muscle.

Objective: The aim of the study was to determine the effects of elevated plasma FFA concentrations on the response of protein synthesis and balance in muscle after essential amino acids (EAAs) ingestion.

Design: Leg protein kinetics were determined in young healthy individuals before and after the ingestion of EAAs at 10 h after the initiation of either lipid (Liposyn/heparin+EAA) or saline (saline+EAA) infusions.

Amino acid supplementation decreases plasma and liver triacylglycerols in elderly.

Objective: Hypertriglyceridemia is a risk factor for coronary heart disease. The aim of this study was to determine the effect of amino acid (AA) supplementation on plasma, liver, and muscle lipid concentrations and insulin sensitivity in the elderly.

Methods: Twelve impaired glucose tolerant elderly (mean +/- SD 67.

Insulin resistance, secretion and breakdown are increased 9 months following severe burn injury.

Insulin resistance in the acute burn period has been well described, however, it is unknown if alterations in glucose metabolism persist beyond discharge from the acute injury. To measure the duration of insulin resistance following recovery from the acute burn injury, we performed a prospective cross-sectional study with a standard 2-h oral glucose tolerance test in 46 severely burned children at 6, 9 or 12 months following initial injury. Glucose uptake and insulin secretion were assessed following the glucose load.

Human mitochondrial oxidative capacity is acutely impaired after burn trauma.

Background: Mitochondrial proteins and genes are damaged after burn injury in animals and are assessed in human burn patients in this study.

Methods: The rates of maximal muscle mitochondrial oxidative capacity (adenosine triphosphate production) and uncoupled oxidation (heat production) for both palmitate and pyruvate were measured in muscle biopsies from 40 children sustaining burns on more than 40% of their body surface area and from 13 healthy children controls.

Results: Maximal mitochondrial oxidation of pyruvate and palmitate were reduced in burn patients compared with controls (4.

Insulin sensitivity is related to fat oxidation and protein kinase C activity in children with acute burn injury.

Impaired fatty acid oxidation occurs with type 2 diabetes and is associated with accumulations of intracellular lipids, which may increase diacylglycerol (DAG), stimulate protein kinase C activity, and inactivate insulin signaling. Glucose and fat metabolism are altered in burn patients, but have never been related to intracellular lipids or insulin signaling. Thirty children sustaining >40% total body surface area burns were studied acutely with glucose and palmitate tracer infusions and a hyper-insulinemic euglycemic clamp.

Postburn trauma insulin resistance and fat metabolism.

Hyperglycemia and insulin resistance have long been recognized in severe burn patients. More recently, it has been observed that controlling hyperglycemia, or alleviating insulin resistance, is associated with improved outcomes. This has led to a renewed interest in the etiology of insulin resistance in this population.

Plasma triglycerides are not related to tissue lipids and insulin sensitivity in elderly following PPAR-alpha agonist treatment.

Increases in plasma lipids, tissue triglycerides and decreases in mitochondrial function have been linked to insulin resistance and aging. In animals, peroxisome proliferator-activated receptor-alpha (PPAR-alpha) agonists decrease plasma lipids, intramyocellular fat (IMCL) and liver fat (LFAT) and improve mitochondrial beta-oxidative function and insulin sensitivity, but the effects in elderly were not known. Insulin sensitivity was assessed with a 2-h oral glucose tolerance test, magnetic resonance spectroscopy was used to asses IMCL, LFAT and plasma lipids were measured before and after 6, 11 and 61 days of PPAR-alpha agonist (fenofibrate) administration in 19 elderly (age 70+/-1 years) volunteers.