Morey W. Haymond, MD Hypoglycemia in Infants and Children a Practical Approach Slide 1
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Hepatic Glycogen Storage Diseases: Pathogenesis, Clinical Symptoms and Therapeutic Management
State of the art paper Hepatology Hepatic glycogen storage diseases: pathogenesis, clinical symptoms and therapeutic management Edyta Szymańska1, Dominika A. Jóźwiak-Dzięcielewska2, Joanna Gronek2, Marta Niewczas3, Wojciech Czarny4, Dariusz Rokicki1, Piotr Gronek2 1Department of Gastroenterology, Hepatology, Feeding Disorders and Pediatrics, Corresponding author: The Children’s Memorial Health Institute, Warsaw, Poland Edyta Szymańska MD, PhD 2Laboratory of Genetics, Department of Gymnastics and Dance, University School Department of Physical Education, Poznan, Poland of Gastroenterology, 3Department of Sport, Faculty of Physical Education, University of Rzeszow, Rzeszow, Hepatology, Feeding Poland Disorders and 4Department of Human Sciences, Faculty of Physical Education, University of Rzeszow, Pediatrics Rzeszow, Poland The Children’s Memorial Health Institute Submitted: 13 October 2017; Accepted: 8 December 2017; Al. Dzieci Polskich 20 Online publication: 18 February 2019 Warsaw, Poland Phone: +48 22 815 74 94 Arch Med Sci 2021; 17 (2): 304–313 E-mail: edyta.szymanska@ DOI: https://doi.org/10.5114/aoms.2019.83063 ipczd.pl Copyright © 2019 Termedia & Banach Abstract Glycogen storage diseases (GSDs) are genetically determined metabolic diseases that cause disorders of glycogen metabolism in the body. Due to the enzymatic defect at some stage of glycogenolysis/glycogenesis, excess glycogen or its pathologic forms are stored in the body tissues. The first symptoms of the disease usually appear during the first months of life and are thus the domain of pediatricians. Due to the fairly wide access of the authors to unpublished materials and research, as well as direct contact with the GSD patients, the article addresses the problem of actual diag- nostic procedures for patients with the suspected diseases. -
What Is Ketotic Hypoglycemia?
KETOTICHYPOGLYCEMIA.ORGv Ketotic Hypoglycemia International Who we are, what we do and why Ketotic Hypoglycemia INTERNATIONAL What is ketotic hypoglycemia? “Ketotic hypoglycemia may be unexplained, or idiopathic (IKH). This is a challenge and should urge for more research” For the patients In a normal person, fuel for the brain and the general cell metabolism primarily comes from the burning of sugar deposits (glycogen). When the glycogen stores are depleted, the body will switch to burn fat deposits. The fat burn lead to two fuels for the brain, both glucose (sugar) and ketone bodies. However, ketones in the blood will lead to nausea and eventually vomiting. This will lead to a vicious circle, where you cannot eat or drink sugar-rich items, which again leads to further fat burn and production of ketone bodies. In a KH-patient, the glycogen stores are somehow insufficient. This leads to For the doctors decreased fasting tolerance with earlier Ketotic hypoglycemia can be seen in children Emergency treatment constitutes of oral onset of fat burn and hence ketone bodies. In because of growth hormone deficiency, cortisol or i.v. glucose, eventually i.m. glucagon, to most patients, the hypoglycemia is relatively deficiency, metabolic diseases with intact fatty raise the plasma glucose, which will prevent mild, and the ketone bodies helps to provide acid consumption, including glycogen storage further lipolysis. However, the ketones can fuel to the brain, which prevents loss of diseases (glycogenosis; GSD) type 0, III, VI, and take hours to be eliminated. In more severely consciousness and convulsions. However, in IX, or disturbances in transport or metabolism affected patients, the ketone production relatively few patients, the condition is more of ketone bodies. -
Recurrent Severe Hypoglycemia Due to Isolated Growth Hormone
C O R R E S P O N D E N C E Recurrent Severe Hypoglycemia hyperinsulinism, ketotic hypoglycemia and hormonal deficiencies such as cortisol, GH and thyroxine [1]. GH due to Isolated Growth Hormone deficiency may occasionally manifest as recurrent Deficiency hypoglycemia as seen in our patient. The mechanisms of hypoglycemia in GH deficiency are increased insulin sensitivity and hypoglycemia unawareness [2]. Additionally, GH deficiency impairs carbohydrate meta- A 6-year-old boy presented to us with repeated episodes bolism resulting in deceased basal insulin level, impaired of seizures since early infancy. He was born small for insulin secretion and carbohydrate intolerance with gestational age to non-consanguineous parents at term. reactive hypoglycemia [1,2]. Although hypoglycemia is During neonatal period, he suffered multiple episodes of described in GH deficiency, severe symptomatic hypoglycemia requiring intravenous dextrose but no hypoglycemia is extremely rare and usually occurs in etiological investigations were done. Three of the four association with another causative factor such as hypoglycemic events beyond neonatal age were glycogen storage disorder [3,4]. Children with even associated with seizures. There were no precipitating complete GH deficiency do not usually manifest factors for hypoglycemia such as prolonged fasting, an hypoglycemia [5]. Our patient unusually developed intercurrent illness or intake of medications. There was recurrent episodes of severe symptomatic hypoglycemia no family history of similar illness, metabolic disorders or due to an isolated GH deficiency. an unexplained death. DEVI DAYAL AND JAIVINDER Y ADAV* On examination, he was short (106 cm, -2.02 z-score) Department of Pediatrics, and underweight (13.8 kg, -3.15 z-score) and had normal PGIMER, Chandigarh, India. -
Acid-Base Disorders in Critical Care
Update in Anaesthesia Acid-base disorders in critical care Alex Grice Correspondence Email: [email protected] INTRODUCTION assess severity (and likely outcome) and allow the Metabolic acidosis is a common component of critical clinician to determine whether current treatments are cid-base disorders illness. Evaluation of this component can aid diagnosis, working. A CASE EXAMPLES was dehydrated and hypotensive. Admission bloods revealed Na+ 134, K+ 2.5, Cl- 122, urea 15.4, creatinine Case 1 280, and blood gas analysis revealed: Summary A known diabetic patient presented with severe diabetic ketoacidosis. He was drowsy, exhibited pH 7.21 Disorders in acid-base balance are commonly classical Kussmaul respiration and proceeded to PaCO 2.9 kPa have a respiratory arrest whilst being admitted to 2 found in critically ill patients. Clinicians responsible for the ICU. After immediate intubation the trainee PaO 19.5 kPa 2 these patients need a clear ventilated the patient with the ventilator’s default HCO - 6.4mmol.L-1 understanding of acid-base settings (rate 12, tidal volume 500ml, PEEP 5, FiO 0.5) 3 2 pathophysiology in order to and attempted to secure arterial and central venous • Describe the acid-base disorder present. What provide effective treatment access. Shortly after intubation the patient became is the likely cause? for these disorders. This asystolic and could not be resuscitated. • Is her compensation adequate? article concentrates on • Why did this patient have a respiratory arrest? aspects of metabolic acidosis often seen in intensive care, Case 4 • Why did he deteriorate after intubation? including poisoning with the A man was brought in to the emergency room heavily alcohols (ethanol, methanol Case 2 intoxicated. -
First Do No Harm…Hypoglycemia Or Hyperglycemia? Dr
First do no harm…Hypoglycemia or hyperglycemia? Dr. Van den Berghe has received a research grant from Novo Nordisk to the University of Leuven. Copyright © 2006 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins DOI: 10.1097/01.CCM.0000242913.88721.6E 2843 Crit Care Med 2006 Vol. 34, No. 11 Hyperglycemia is common in intensive care unit (ICU) patients, and severity of hyperglycemia has been repeatedly associated with adverse outcome of a variety of illnesses including critical illness (1). Traditionally, insulin was not administered until blood glucose exceeded 180–200 mg/dL based on the rationale that such mild increases were not deleterious and tighter control might be complicated by life- threatening hypoglycemia. In 2001, our large, randomized, controlled study revealed that intensive insulin therapy to maintain normal blood glucose levels (<110 mg/dL) saves lives and prevents debilitating and expensive complications in a predominantly surgical ICU population (2). The level of blood glucose control rather than the insulin dose explained the benefits (3). This study was followed by a publication by Krinsley (4), who reported that when intensive insulin therapy is implemented in real life intensive care, the benefits on morbidity and mortality can be largely reproduced. Our subsequent randomized, controlled study of intensive insulin therapy in a very ill medical ICU population, with a high co-morbidity and a high risk of death, confirmed the morbidity benefits and, when blood glucose control is continued for at least a third day, also the reduced mortality (5). Furthermore, analysis of healthcare resource utilization clearly revealed substantial cost savings (6, 7). -
(Idiopathic) Ketotic Hypoglycemia in Children
(Idiopathic) Ketotic hypoglycemia in children *Leena Priyambada, **Srinivas Raghavan *E-mail: [email protected] **Department of Pediatrics, Jawaharlal Institute of Medical Education and Research, Puducherry, India Abstract Idiopathic Ketotic Hypoglycemia is the most common non-iatrogenic cause of hypoglycemia in children beyond infancy. It improves with age and is rare after puberty. Early morning hypoglycemia, responding promptly to glucose, is a typical presentation. Etiology of hypoglycemia is unclear; deficiency of gluconeogenic substrate (hypoalaninemia) has been widely proposed. Idiopathic Ketotic Hypoglycemia is a diagnosis of exclusion. Rule out specific etiologies first. Ketonuria precedes hypoglycemia by several hours, testing for ketonuria helps in early detection. For prevention, avoiding fasting states and bedtime snacks are helpful. Keywords: Ketotic hypoglycemia, children, hypoalaninemia Introduction classic presentation is the appearance of ‘G, a 4 yr old developmentally normal girl, recurrent episodes of hypoglycemia and ketosis presented with recurrent seizures (3 episodes) provoked by fasting for 12 to 24 hours. Early for the past three months. The seizures were morning hypoglycemia before breakfast generalised tonic clonic in nature, preceded by especially when associated with strenuous vomiting early in the morning and responding physical activity the previous evening or during immediately to glucose. There was no suggestive intercurrent illnesses is a classic presentation. past, neonatal or family history. Clinical These episodes respond promptly to glucose examination, baseline biochemical, neurological administration and neurological sequelae are investigations in the interictal period when the rare. child was referred to us was normal. Fasting IKH usually presents between 18 months and test resulted in blood sugar of 26 mg/dl with five years of age. -
Effect of Ketone Bodies on Glucose Production and Utilization in the Miniature Pig
Effect of ketone bodies on glucose production and utilization in the miniature pig. M J Müller, … , U Paschen, H J Seitz J Clin Invest. 1984;74(1):249-261. https://doi.org/10.1172/JCI111408. Research Article The effect of ketone bodies on glucose production (Ra) and utilization (Rd) was investigated in the 24-h starved, conscious unrestrained miniature pig. Infusing Na-DL-beta-OH-butyrate (Na-DL-beta-OHB) and thus shifting the blood pH from 7.40 to 7.56 resulted in a decrease of Ra by 52% and of Rd by 45%, as determined by the isotope dilution technique. Simultaneously, the concentrations of arterial insulin and glucagon were slightly enhanced, whereas the plasma levels of glucose, lactate, pyruvate, alanine, alpha-amino-N, and free fatty acids (FFA) were all reduced. Infusion of Na- bicarbonate, which yielded a similar shift in blood pH, did not mimick these effects. Infusion of equimolar amounts of the ketoacid, yielding a blood pH of 7.35, induced similar metabolic alterations with respect to plasma glucose, Ra, Rd, and insulin; however, plasma alanine and alpha-amino-N increased. Infusing different amounts of Na-DL-beta-OHB resulting in plasma steady state levels of ketones from 0.25 to 1.5 mM had similar effects on arterial insulin and glucose kinetics. No dose dependency was observed. Prevention of the Na-DL-beta-OHB-induced hypoalaninemia by simultaneous infusion of alanine (1 mumol/kg X min) did not prevent hypoglycemia. Infusion of Na-DL-beta-OHB plus insulin (0.4 mU/kg X min) showed no additive effect on the inhibition of Ra. -
Syncope and Hypoglycemia
International Journal of Clinical Medicine, 2011, 2, 129-132 doi:10.4236/ijcm.2011.22023 Published Online May 2011 (http://www.SciRP.org/journal/ijcm) Syncope and Hypoglycemia Alfonso Lagi Emergency Department, Ospedale Santa Maria Nuova, Florence, Italy. Email: [email protected] Received February 8th, 2011; revised March 10th, 2011; accepted March 28th, 2011. ABSTRACT Objective: This review focuses on syncope in diabetic patients who suffer from hypoglycemia. Clinically, transient loss of consciousness during hypoglycemia appears similar to vasovagal syncope. Research Design and Methods: Current understanding of this problem is based on physicians’ personal experiences as well as on published case reports. It is difficult to explain a temporary loss of consciousness as a result of hypoglycemia. Demonstration that hypoglycemia can be transient, with the patient suffering from neuroglycopenia without autonomic symptoms due to delayed counter- regulation, might be a first step in confirming that a diabetic patient suffered from a transient loss of consciousness with spontaneous recovery. Results: Hypoglycemic syncope is uncommon, affecting 1.9% of diabetic patients using insulin therapy. It is characterized clinically by brief periods of unconsciousness with slow recovery and without loss of postural muscle tone. The difficulty in correlating loss of consciousness to hypoglycemia arises from mismatching symptoms, that is, there may be mental symptoms such as confusion, loss of memory or consciousness, in the absence of autonomic manifestations such as sweating or blurred vision. There are currently no established glucose values that define the level of hypoglycemia that causes loss of consciousness. Conclusion: Hypoglycemic syncope should be sus- pected in older diabetic patients with preserved postural tone, usually but not always using insulin therapy, who show a slow recovery from transient loss of consciousness with persisting neurological impairment and low blood glucose lev- els. -
Hypoglycemia Unawareness in the Geriatric Patient: a Safety Concern
7/28/17 Hypoglycemia Unawareness in the Geriatric Patient: A Safety Concern 29TH ANNUAL TNP CONFERENCE TRANSFORMING HEALTHCARE IN TEXAS SEPTEMBER 8, 2017 AUSTIN, TEXAS Kenneth Lowrance, DNP, APRN, CNS, FNP-BC, NEA-BC, FAANP Associate Professor of Professional Practice Director, Post-Master’s DNP and CNS Programs Texas Christian University Disclaimer: The presenter has no conflicts of interest to declare. Objectives: • Describe the concept of hypoglycemia unawareness • Articulate and identify physiologic, sensory, and cognitive changes associated with aging that contribute to hypoglycemia unawareness • Analyze the relationship of hypoglycemia to frailty and dementia • Formulate implementation strategies to mitigate hypoglycemic episodes in the elderly 1 7/28/17 Definition of Hypoglycemia Unawareness Onset of neuroglycopenia before the appearance of autonomic warning symptoms (palpitations, sweating, hunger, anxiety, tremors, etc.) Impairment or inability of an individual to recognize the presence of hypoglycemia (Elliott & Heller, 2011) Definition of Neuroglycopenia Neuroglycopenia refers to a shortage of glucose in the brain. (Martin-Timon & Canizo-Gomez, 2015) The brain uses glucose as an exclusive energy source, using up to 25% of the total glucose in the body. (Cryer, 2012) Diabetes Facts: • 29.1 million people in the US have diabetes (1 of 11 people) • 1 of 4 do not know they have it • 86 million people have prediabetes • 9 of 10 do not know they have it • 5% of people with diabetes have Type 1; 95% have Type 2 • Annual cost of care -
Paroxysmal Dyskinesia Associated with Hypoglycemia
LE JOURNAL CANADIEN DES SCIENCES NEUROLOGIQUES Paroxysmal Dyskinesia Associated with Hypoglycemia Brian J. Schmidt and Neelan Pillay ABSTRACT: The association of movement disorders with hypoglycemia has been rarely noted in the past. We recently observed 2 patients with documented hypoglycemia and paroxysmal dyskinesias. One patient had evidence of an insulin-secreting tumor. The other patient had insulin-dependent diabetes, and also experienced recurrent episodes of hypoglycemic hemiparesis. Classical adrenergic symptoms of hypoglycemia were absent in both patients. Our observa tions support the concept that the development of neuroglycopenie symptoms cannot be predicted from blood glucose measurements alone, but must depend on other factors controlling the availability or metabolism of glucose in the brain. RESUME: Dyskinesies paroxystiques associees a I'hypoglycemic L'association de desordres du mouvement avec I'hypoglycemie a rarement ete notee dans le passe. Nous avons recemment observe 2 patients avec une hypoglycemic documented et des dyskinesies paroxistiques. Un patient avait des manifestations cliniques associees a une tumeur secretant de l'insuline. L'autre patient avait un diabete insulino-dependant accompagne d'episodes recurrents d'hemi- paresie hypoglycemique. Les symptomes adrenergiques classiques d'hypoglycemie etaient absents chez ces deux patients. Nos observations appuient la notion que I'apparition de symptomes de neuroglycopenie ne peut etre predite sur la base de la glycemie seulement mais depend d'autres facteurs controlant la disponibilite ou le metabolisme du glucose dans le cerveau. Can../. Neurol. Sci. 1993; 20:151-153 In 1937 Golden described the occurrence of a variety of movements. The attacks usually began with a sudden "restless sensa involuntary movements in psychiatric patients undergoing tion" in his lower limbs, followed by chaotic thrashing of his legs and insulin-induced hypoglycemic shock treatment.1 During deeper sometimes arms. -
Relationships Between Hyperglycemia and Cognitive Performance Among Adults with Type 1 and Type 2 Diabetes
Epidemiology/Health Services/Psychosocial Research ORIGINAL ARTICLE Relationships Between Hyperglycemia and Cognitive Performance Among Adults With Type 1 and Type 2 Diabetes DANIEL J. COX, PHD ANTHONY MCCALL, MD, PHD test cognitive functioning at 14.5 and 16 BORIS P. KOVATCHEV, PHD KEVIN J. GRIMM, MA mmol/l in adults with type 2 diabetes. LINDA A. GONDER-FREDERICK, PHD WILLIAM L. CLARKE, MD During hyperglycemia, significant dis- KENT H. SUMMERS, PHD ruptions occurred in the performance of complex tests of cognitive functioning, such as four-choice reaction time. How- ever, other investigators (5,6) were un- OBJECTIVE — Hyperglycemia is a common event among patients with type 1 and type 2 able to detect decay in cognitive-motor diabetes. While the cognitive-motor slowing associated with hypoglycemia is well documented, the acute effects of hyperglycemia have not been studied extensively, despite patients’ reports of performance on selected neuropsycho- negative effects. This study prospectively and objectively assessed the effects of hyperglycemia on logical tests during hyperglycemia. cognitive-motor functioning in subjects’ natural environment. Contrary to hypoglycemia and its associated neuroglycopenia, a major RESEARCH DESIGN AND METHODS — Study 1 investigated 105 adults with type 1 barrier to the investigation of the effects of diabetes (mean age 37 years and mean duration of diabetes 20 years), study 2 investigated 36 hyperglycemia on cognitive-motor per- adults with type 2 diabetes (mean age 50 years and mean duration of diabetes 10 years), and formance is the absence of a clear physi- study 3 investigated 91 adults with type 1 diabetes (mean age 39 years and mean duration of ological mechanism that explains how diabetes 20 years). -
Danielle Drachmann. Denmark
Danielle Drachmann. Denmark Non-diabetic ketotic hypoglycemia Literature review provided by professor Henrik Thybo Christesen Hans Christian Andersen Children’s Hospital, Odense, Denmark Fact 1 Hypoglycemia is seen in 1-10% of newborns in Denmark. Lower after the introduction of a national prevention program The birth of a Shaking baby Noah Noah - Born shaking - 0.8 mmol/l (14 mg/dl) - An i.v glucose need of 12 mg/kg/min - indicate of hyperinsulinism - Diazoxide for 5 days, good effect - Spontaneous resolution → discharged - Nursed night and day until 12 months - Seizure at 17 months old - One year later, diagnosed with Idiopathic Ketotic Hypoglycemia Fact 2 A small group of children with neonatal hypoglycemia has prolonged or persistent hypoglycemia as consequence of congenital metabolic diseases or congenital hormone disorder The birth of a hyper-nursing baby Savannah Savannah - BG dropped to 2.2 mmol/l (39 mg/dL) but stabilized with nursing. Milk was running from day 1. - Nursed 24/7. Nursed all night, with short breaks in the daytime. 17 month old: BG 3.7 (66 mg/dl), ketones 3.3, admitted. - Doctors believed it was due to malnutrition - 2nd opinion from professor Christesen: Gave her a Dexcom CGM, cut down the nursing at night: Admitted and diagnosed with severe ketotic hypoglycemia. ADHD, bulimia and a bad memory Danielle Danielle ADHD - Extreme bad memory Bulimia - Low blood glucose after glucose tolerance test - Ice cream while giving birth - Suspected low blood glucose during both pregnancies - Diagnosed with non-diabetic ketotic hypoglycemia at 26-year-old - Dexcom and cornstarch - “Cured” from ADHD and bulimia Fact 3 Non-diabetic ketotic hypoglycemia can be seen in children without diabetes because of growth hormone deficiency, adrenocortical deficiency or fatty acid metabolism, and glycogen storage diseases Fact 4 When these diagnoses are ruled out, non-diabetic ketotic hypoglycemia can be categorised as unexplained or idiopathic (IKH), otherwise known as accelerated starvation.