RESUMEN
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/m2; hemoglobin A1c 11.3%±1.9%, were studied during an admission with DKA and following its resolution. Solid and liquid GE were measured using scintigraphy. Solid emptying was assessed via the percentage intragastric retention at 100 min and that of liquid by the 50% emptying time. RESULTS: There was no difference in either solid or liquid GE at the initial study compared with the follow-up. Median (IQR) solid retention was 47±20 versus 38%±33%, respectively; p=0.31, and time to empty 50% of liquid was 37±25 min versus 35±15 min, p=0.31, at the initial and follow-up GE study, respectively. CONCLUSIONS: GE of solids and liquids is not affected by moderate DKA, inferring that earlier reintroduction of oral intake may be appropriate.
Asunto(s)
Diabetes Mellitus Tipo 1 , Cetoacidosis Diabética , Gastroparesia , Humanos , Adolescente , Adulto Joven , Adulto , Vaciamiento Gástrico , Diabetes Mellitus Tipo 1/complicaciones , Hemoglobina GlucadaRESUMEN
This cohort study examines the natural history and response to treatment of sodium glucose cotransporter 2 (SGLT2) inhibitorassociated ketoacidosis compared with that of type 1 diabetesassociated ketoacidosis.
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Diabetes Mellitus Tipo 1 , Cetoacidosis Diabética , Cetosis , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversos , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Cetoacidosis Diabética/inducido químicamente , Cetosis/inducido químicamenteRESUMEN
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. The major differential diagnosis of reninoma is renovascular hypertension. Fewer than 200 cases of reninoma have been described. Reninomas have been reported across a broad demographic but have a 2:1 predilection for women, often of childbearing age. Aldosterone receptor blockade, angiotensin-converting enzyme inhibitors, or angiotensin receptor blockers offer effective medical management but are contraindicated in pregnancy, so surgical curative resection is ideal. The current optimal imaging and biochemical workup of reninoma and management approach (ideally, tumor excision with subtotal renal resection) are described.
Asunto(s)
Adenoma , Hiperaldosteronismo , Hipertensión , Neoplasias Renales , Humanos , Femenino , Renina , Neoplasias Renales/diagnóstico , Neoplasias Renales/terapia , Riñón/metabolismo , Sistema Renina-Angiotensina , Hiperaldosteronismo/complicaciones , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/terapia , Adenoma/complicaciones , Aldosterona , Hipertensión/etiologíaRESUMEN
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. RESEARCH DESIGN AND METHODS: We describe the first two case reports of severe nondiabetic ketoacidosis after initiation of an SGLT2i for the treatment of heart failure with reduced ejection fraction, and we describe the management strategies employed and implication for the pathophysiology of SGLT2i-associated ketoacidosis. RESULTS: Each individual presented with ketoacidosis triggered by reduced oral nutrition intake. For both individuals, ketoacidosis resolved with intravenous glucose administration, encouragement of consumption of oral glucose-containing fluid, and minimal insulin administration. CONCLUSIONS: These two cases demonstrate that SGLT2i-associated ketoacidosis is possible in individuals without diabetes.
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Diabetes Mellitus Tipo 2 , Cetoacidosis Diabética , Insuficiencia Cardíaca , Cetosis , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/efectos adversos , Cetoacidosis Diabética/inducido químicamente , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversos , Volumen Sistólico , Insulina/efectos adversos , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/complicaciones , Glucosa/uso terapéutico , Sodio/efectos adversosRESUMEN
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 (PAM), as well as Pam-knockout mice, display increased resistance to GLP-1 in vivo. Pam 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. Meta-analysis of human data from studies examining GLP-1R agonist response (including RCTs) reveals a relative loss of 44% and 20% of glucose lowering (measured by glycated hemoglobin) in individuals with hypomorphic PAM alleles p.S539W and p.D536G treated with GLP-1R agonist. Genetic variation in PAM has effects on incretin signaling that alters response to medication used commonly for treatment of T2D.
RESUMEN
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. In this work, we outline the pathophysiology of the interaction between colonoscopy and SGLT2i use, the evidence regarding SGLT2i use in the periprocedural setting and Australian Diabetes Society guidelines.
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Colonoscopía , Diabetes Mellitus Tipo 2 , Cetoacidosis Diabética , Hipoglucemiantes , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Australia , Glucemia/análisis , Colonoscopía/efectos adversos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/complicaciones , Cetoacidosis Diabética/sangre , Cetoacidosis Diabética/etiología , Cetoacidosis Diabética/fisiopatología , Cetoacidosis Diabética/prevención & control , Glucosa , Hipoglucemiantes/efectos adversos , Hipoglucemiantes/uso terapéutico , Sodio , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversos , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Catárticos/administración & dosificación , Catárticos/efectos adversos , Cetonas/metabolismoRESUMEN
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. Adrenal vein sampling (AVS) is required to biochemically lateralise aldosterone secretion prior to adrenalectomy. However, diagnostic success of AVS is variable and can be poor even at tertiary centres; failure is largely due to unsuccessful adrenal vein cannulation. Intra-procedural rapid semiquantitative cortisol testing (RCT) identifies correct catheter placement in real time. We compared diagnostic success rates of AVS before and after the introduction of intraprocedural cortisol testing at the Royal Adelaide Hospital-a medium throughput tertiary centre (average 6.2 procedures a year over the last 8 years). We observed an increase in success rate from 63% to 94%. Intraprocedural cortisol testing also led to a net financial saving of ~$100 AUD per procedure. RCT is likely to be cost effective if pre-RCT success rate is less than 78%. Procedure time and number of samples collected, however, were increased with RCT. This suggests that intraprocedural cortisol testing will improve success in low to medium throughput centres and may make AVS feasible in less specialised centres.
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Hidrocortisona , Hiperaldosteronismo , Humanos , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/cirugía , Aldosterona , Venas , Glándulas Suprarrenales/irrigación sanguínea , Cateterismo , Estudios RetrospectivosRESUMEN
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 1.7 mmol/L. There was no history of sulphonylurea use prompting anatomical insulinoma studies to locate an insulinoma. However, a routine plasma insulinoma screen-detected glimepiride. Directed history implicated a medication taken for erectile dysfunction prior to disturbed consciousness, with alcohol. The tablets, obtained online, were analysed by mass spectrometry and contained tadalafil and dapoxetine as advertised but also contained glimepiride. Learning points: Symptomatic unexplained hypoglycaemia requires investigation with plasma glucose level, c-peptide, insulin level, pro-insulin, beta-hydroxybutyrate, and a sulphonylurea screen regardless of known exposure to sulphonylureas. Consider contamination of alternative or undisclosed medication, including PDE-5 inhibitor erectile dysfunction drugs. Concomitant alcohol may impair glycogenolysis and gluconeogenesis, exacerbating hypoglycaemia.
RESUMEN
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. PAM deficiency results in reduced insulin content and altered dynamics of insulin secretion in a human ß-cell model and primary islets from cadaveric donors. Thus, our results demonstrate a role for PAM in ß-cell function, and establish molecular mechanisms for T2D risk alleles at this locus.
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Amidina-Liasas/genética , Diabetes Mellitus Tipo 2/genética , Secreción de Insulina/genética , Células Secretoras de Insulina/patología , Oxigenasas de Función Mixta/genética , Alelos , Animales , Línea Celular , Predisposición Genética a la Enfermedad , Células HEK293 , Humanos , Insulina/genética , Ratones , Polimorfismo de Nucleótido SimpleRESUMEN
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. Ten healthy men received intravenous saline (placebo) or GLP-1 (0.8 pmol/kg â min), as a continuous 24-h infusion ("prolonged"), two 4.5-h infusions separated by 20 h ("intermittent"), and a 4.5-h infusion ("acute") in a randomized, double-blind, crossover fashion. Gastric emptying of a radiolabeled mashed potato meal was measured using scintigraphy. Acute GLP-1 markedly slowed gastric emptying. The magnitude of the slowing was attenuated with prolonged but maintained with intermittent infusions. GLP-1 potently diminished postprandial glycemia during acute and intermittent regimens. These observations suggest that short-acting GLP-1 agonists may be superior to long-acting agonists when aiming specifically to reduce postprandial glycemic excursions in the treatment of type 2 diabetes.
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Glucemia/efectos de los fármacos , Vaciamiento Gástrico/fisiología , Péptido 1 Similar al Glucagón/administración & dosificación , Péptido 1 Similar al Glucagón/farmacología , Receptores de Glucagón/metabolismo , Área Bajo la Curva , Estudios Cruzados , Método Doble Ciego , Receptor del Péptido 1 Similar al Glucagón , Glucosa/metabolismo , Humanos , Insulina/sangre , Masculino , Adulto JovenRESUMEN
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. Between T0 and T420 minutes, GLP-1 (1.2 pmol/kg·min(-1)) was infused intravenously with either GIP (2 pmol/kg·min(-1)) or 0.9% saline. Between T60 and T420 minutes, nutrient liquid was infused into the small intestine at 1.5 kcal/min. RESULTS: Adding GIP did not alter blood glucose or insulin responses to small intestinal nutrient. GIP increased glucagon concentrations slightly before nutrient delivery (P=0.03), but not thereafter. CONCLUSIONS: The addition of GIP to GLP-1 does not result in additional glucose-lowering or insulinotropic effects in critically ill patients with acute-onset hyperglycemia.