Physiology and Pharmacology of Effects of GLP-1-based Therapies on Gastric, Biliary and Intestinal Motility.

Glucagon-like peptide-1 (GLP-1) receptor agonists and the dual GLP-1- and glucose-dependent insulinotropic polypeptide receptor co-agonist tirzepatide (referred to here collectively as "GLP-1-based therapy") are incretin-based therapies being used increasingly in the management of both type 2 diabetes and obesity. They are now recognized to have beneficial effects beyond improved glycemic control and weight loss, including cardiovascular and renal protection. GLP-1-based therapy also slows gastric emptying, which has benefits (lowering postprandial glucose), but also potential risks (eg, hypoglycemia in individuals on insulin or sulphonylurea therapy).

Propofol-induced transient arginine vasopressin deficiency.

Summary: We describe and characterise the case of a 26-year-old female undergoing surgery for a right-sided sinonasal alveolar rhabdomyosarcoma who developed profound, transient arginine vasopressin deficiency (AVP-D, formerly central diabetes insipidus (DI)) associated with anaesthesia. In this case report, we characterise the development of AVP-D with serial copeptin and paired urine and serum osmolality measurements. Based on the anaesthetic agent's profile and the literature, we attribute this presentation to propofol exposure.

Testosterone and the prevention of type 2 diabetes mellitus: therapeutic implications from recent trials.

Purpose Of Review: Type 2 diabetes (T2D) is increasing to epidemic proportions and frequently associated with obesity and a low serum testosterone concentration in men. This review valuates recent randomized controlled trials (RCTs) investigating the effect of testosterone treatment on glycemic control and T2D prevention.

Recent Findings: The 2-year Testosterone for the Prevention of Type 2 diabetes Trial (T4DM) study showed that in men aged 50 years and over with visceral obesity and impaired glucose tolerance, testosterone treatment on the background of a lifestyle intervention reduced T2D risk by 40%.

Gastric emptying during and following resolution of moderate diabetic ketoacidosis in type 1 diabetes: a case series.

Introduction: To use the 'gold standard' technique of scintigraphy to quantify gastric emptying (GE) as soon as practicable during an admission with diabetic ketoacidosis (DKA) and following its resolution at least 7 days later.

Research Design And Methods: Five patients with type 1 diabetes, age 29±12 years; Body Mass Index 23±3 kg/m; hemoglobin A1c 11.3%±1.

Euglycemic Ketoacidosis in Two Patients Without Diabetes After Introduction of Sodium-Glucose Cotransporter 2 Inhibitor for Heart Failure With Reduced Ejection Fraction.

Objective: Ketoacidosis induced by sodium-glucose cotransporter 2 inhibitor (SGLT2i) treatment has been consistently observed in clinical practice in patients with type 2 diabetes despite minimal indication from the landmark cardiovascular outcome trials. It has been postulated that individuals without diabetes will not develop this complication due to an adequate insulin secretory capacity, which will protect against significant ketone formation. Cardiovascular outcome trials examining SGLT2i use in individuals with heart failure but not diabetes have not reported ketoacidosis.

Approach to the Patient: Reninoma.

A reninoma is a functional tumor of afferent arteriolar juxtaglomerular cells that secretes the enzyme renin, leading to hyperactivation of the renin-angiotensin-aldosterone system. Reninoma is a potentially curable cause of pathological secondary hyperaldosteronism that results in often severe hypertension and hypokalemia. The lack of suppression of plasma renin contrasts sharply with the much more common primary aldosteronism, but diagnosis is often prompted by screening for that condition.

Postprandial plasma GLP-1 levels are elevated in individuals with postprandial hypoglycaemia following Roux-en-Y gastric bypass - a systematic review.

Background And Aims: Bariatric surgery is the most effective treatment in individuals with obesity to achieve remission of type 2 diabetes. Post-bariatric surgery hypoglycaemia occurs frequently, and management remains suboptimal, because of a poor understanding of the underlying pathophysiology. The glucoregulatory hormone responses to nutrients in individuals with and without post-bariatric surgery hypoglycaemia have not been systematically examined.

Beware of little expenses: Low-value endocrinological blood tests in geriatric medical inpatients.

Objectives: Blood tests for endocrinological derangements are frequently requested in general medical inpatients, in particular those in the older age group. Interrogation of these tests may present opportunities for healthcare savings.

Methods: This multicentre retrospective study over a 2.

Type 2 Diabetes risk alleles in Peptidyl-glycine Alpha-amidating Monooxygenase influence GLP-1 levels and response to GLP-1 Receptor Agonists.

Patients with type 2 diabetes vary in their response to currently available therapeutic agents (including GLP-1 receptor agonists) leading to suboptimal glycemic control and increased risk of complications. We show that human carriers of hypomorphic T2D-risk alleles in the gene encoding peptidyl-glycine alpha-amidating monooxygenase as well as -knockout mice, display increased resistance to GLP-1 . inactivation in mice leads to reduced gastric GLP-1R expression and faster gastric emptying: this persists during GLP-1R agonist treatment and is rescued when GLP-1R activity is antagonized, indicating resistance to GLP-1's gastric slowing properties.

Peri-colonoscopy Implications of Sodium-Glucose Cotransporter-2 Inhibitor Therapy: A Mini-review of Available Evidence.

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are a class of oral glucose-lowering agents commonly used for the treatment of type 2 diabetes. With increased use, there has been an increase in the incidence of the rare but life-threatening complication of euglycemic diabetic ketoacidosis. A common but underappreciated precipitant is colonoscopy.

Intraprocedural cortisol testing improves adrenal vein cannulation success and diagnostic accuracy in assessment of primary aldosteronism, in a medium throughput centre.

Primary aldosteronism is the most common cause of secondary hypertension. Identifying individuals who have unilateral secretion from aldosterone secreting adenomas allows adrenalectomy. Surgical treatment when feasible may be superior to medical management with improved cardiovascular outcomes and reduced medication dependence.

Accidental exposure to glimepiride from adulterated medication resulting in severe hypoglycaemia.

Summary: Sulphonylureas are insulinotropic and are not only useful in patients with diabetes but also act in non-diabetic individuals where hypoglycaemia and hyperinsulinism mimic insulinoma. We present a 63-year-old man who presented with inadvertent sulphonylurea-induced life-threatening hypoglycaemia on two occasions, resulting in hazardous and invasive investigation. Biochemistry revealed endogenous hyperinsulinaemia, with elevated serum c-peptide and insulin concentrations during symptomatic hypoglycaemia, and plasma glucose of 1.

Effects of androgens on glucose metabolism.

Type 2 diabetes (T2D) and obesity are common and associated with increased morbidity and mortality. Cross-sectional and longitudinal studies have demonstrated a clear association between T2D, obesity and reduced total testosterone concentration. This relationship becomes less significant or absent with correction for changes in body composition, supporting the notion that changes in body composition are mediating these effects.

Type 2 diabetes risk alleles in PAM impact insulin release from human pancreatic β-cells.

The molecular mechanisms underpinning susceptibility loci for type 2 diabetes (T2D) remain poorly understood. Coding variants in peptidylglycine α-amidating monooxygenase (PAM) are associated with both T2D risk and insulinogenic index. Here, we demonstrate that the T2D risk alleles impact negatively on overall PAM activity via defects in expression and catalytic function.

Comparative effects of prolonged and intermittent stimulation of the glucagon-like peptide 1 receptor on gastric emptying and glycemia.

Acute administration of glucagon-like peptide 1 (GLP-1) and its agonists slows gastric emptying, which represents the major mechanism underlying their attenuation of postprandial glycemic excursions. However, this effect may diminish during prolonged use. We compared the effects of prolonged and intermittent stimulation of the GLP-1 receptor on gastric emptying and glycemia.

The effect of exogenous glucose-dependent insulinotropic polypeptide in combination with glucagon-like peptide-1 on glycemia in the critically ill.

Objective: Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) have additive insulinotropic effects when coadministered in health. We aimed to determine whether GIP confers additional glucose lowering to that of GLP-1 in the critically ill.

Research Design And Methods: Twenty mechanically ventilated critically ill patients without known diabetes were studied in a prospective, randomized, double-blind, crossover fashion on 2 consecutive days.