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This article originally posted 17 December, 2012 and appeared in  Diabetes Clinical Mastery Series Issue 115

Diabetic Emergencies, Diagnosis and Clinical Management: Hypoglycemia Caused By Insulin, Part 4

Stavros Liatis, Nikolaos Katsilambros

Diabetic_Emergencies

Case 4.1

A 65-year-old man with history of Type 2 diabetes presented to the emergency department at 10.30 pm.

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He claimed he had mistakenly injected himself about half an hour earlier with 75 IU of insulin lispro, a rapid-acting insulin analog, instead of insulin glargine, a long-acting insulin analog. The patient had had Type 2 diabetes for 17 years and had been receiving basal insulin (glargine) for the last 3 years. Four months earlier, due to his poor glycemic control, prandial insulin (lispro) was introduced at a dosage of 8 units before each meal, and was gradually increased to 12 IU. His glargine dosage was 75 IU every evening at bedtime. One month earlier his HbA1c was 7.3%.

The patient reported a myocardial infarction eight years ago and a history of hypertension for the last 20 years. As well as insulin, he was taking low-dose aspirin, atorvastatin, carvedilol, ramipril, hydrochlorothiazide, amlodipine, and metformin.

The patient had realized his mistake only a few minutes after injection. He subsequently measured his capillary blood glucose and found it to be 132 mg/dl (7.3 mmol/L). He decided to "eat something sweet" and consumed 350 ml of sweetened fruit juice and one bar of dark chocolate, but he was still "too afraid" and decided to contact the nearest hospital. He arrived at the emergency room driving his own car.

Upon arrival, his capillary blood glucose was 91 mg/dl (6.7 mmol/L). He felt well, although "quite scared." His vital signs were normal except for a mild sinus tachycardia (102 beats/min). His self-reported weight was 92 kg and his height 1.72 m (BMI 31.1 kg/m 2).

How should this patient be managed?

This patient is in great danger of serious hypoglycemia. Despite his plasma glucose levels being still within the normal range, it could be estimated that the very high dose of rapid-acting insulin he had injected by mistake had just started to be absorbed at the injection site. Insulin lispro has a time-action profile similar to the other two rapid-acting insulin analogs available in most European countries and the United States (aspart and glulisine). Its onset of action is 20-30 minutes after subcutaneous injection, the peak is at 90-120 minutes, and its action lasts 3-4 hours. As with any type of insulin, however, action duration is strongly positively related to the injected dose. There is actually one case reported in the literature of an attempted suicide with 300 IU of insulin lispro injected subcutaneously, which resulted in protracted severe hypoglycemia for more than 11 hours.43

The patient was admitted to the hospital due to impending severe hypoglycemia. Serum potassium at admission was 4.2 mEq/L. A continuous infusion of 20% glucose solution was immediately initiated at a rate of 100 ml/h, providing 20 g of glucose per hour. A mixed meal, rich in carbohydrates, was also administered to the patient. Capillary blood glucose was closely monitored (every 30 minutes). One hour after admission, capillary blood glucose was 75 mg/dl (4.2 mmol/L). Glucose infusion was increased to 150 ml/h. At 01.30 am (about 3 hours after admission), a plasma glucose value of 48 mg/dl (2.7 mmol/L) was measured and 50 ml of 35% glucose solution were administered (providing 17.5 g of glucose) as a bolus IV and the 20% glucose infusion rate was increased to 200 ml/h. Serum potassium was 3.7 mEq/L and potassium chloride was added to the glucose infusion. During the rest of the night, plasma glucose values ranged between 95 and 155 mg/dl (5.3-8.6 mmol/L) with a mild tendency to increase over time. At 07.00 am (10 hours after the wrong insulin injection), capillary blood glucose was 181 mg/dl (10 mmol/L). The infusion rate was decreased to 100 ml/h and the patient was given his breakfast. One hour after breakfast, plasma glucose was 235 mg/dl (13.05 mmol/L) and the glucose infusion was stopped. The patient was further observed for 3 hours and then discharged, since he exhibited no further signs of blood glucose decline. He was instructed to continue his typical insulin program and inject insulin glargine at 10.00 pm. He was advised to keep different insulins in different places (e.g., prandial insulin in the kitchen and basal insulin in the bedroom). His diabetologist was contacted and informed about his hospitalization.

Comment

Mistakes in insulin administration are not rare in clinical practice and involve errors in prescription, interpretation of prescriptions, preparation, and injection technique. Patients on basal-bolus therapy use two types of insulin, usually one or two injections of basal insulin (long-acting) and multiple injections of prandial insulin (short-acting). Meticulous education of the insulin-treated patient is mandatory for the success of every insulin regimen, especially for a basal-bolus scheme. Confusing short- with long-acting insulins might be extremely dangerous (as shown in this and other cases44) and although insulin manufacturers fabricate vials and pens using different colors, depending on the type of insulin, special attention should be always paid.

Case 4.2

A 28-year-old male was admitted at the emergency room at 4.00 am after a hypoglycemic event, having failed to recover despite the administration of glucagon. The patient was accompanied by his wife who described that one hour before admission she had realized that her husband had fallen unconscious during his night's sleep.

The patient had been diagnosed with Type 1 diabetes two years earlier. No other health problems were reported. His insulin regimen included NPH insulin injected twice a day (24 IU in the morning and 18 IU at bedtime) and regular insulin injected before each meal. He had frequent episodes of hypoglycemia, especially during the last 2 weeks, when he started exercising at a gym. Nevertheless, he had not been brought to the hospital on any previous occasion.

His wife was often the first one to notice him becoming hypoglycemic, as he would often become aggressive and exhibit signs of bizarre attitude. The patient had suffered from another episode of complete loss of consciousness one week earlier, but he had responded promptly after his wife administered 1 mg of glucagon injection subcutaneously. During the current episode his first capillary blood glucose, as measured by his wife, was "low" as indicated by the portable meter, which was not able to read a glucose level lower than 25 mg/dl (1.4 mmol/L). The patient did not respond to a glucagon injection (1 mg) that his wife had administered to him. She subsequently repeated the dose and a few minutes later he showed some signs of regaining consciousness but then vomited twice. His blood sugar was measured at that time to be 26 mg/dl (1.4 mmol/L) but he was too confused and aggressive to accept any food. The evening before this event occurred, he had injected his usual 18 IU of insulin NPH at 11.00 pm. He and his wife had had a light dinner but also consumed a whole bottle of red wine. His wife reported that she "only had one or two glasses" out of the whole bottle, while the rest was consumed by her husband. His wife insisted, however, that her husband was not a regular heavy drinker.

At the emergency room the patient was confused, disoriented, and very negative toward any intervention. His capillary blood glucose was 30 mg/dl (1.7 mmol/L). The department's staff managed to calm him down and he immediately responded to the administration of 50 ml 35% glucose solution given as an intravenous bolus infusion. He had nausea but did not vomit. A 10% continuous glucose infusion was started at a rate of 100 ml/h. Fifteen minutes later his capillary blood glucose was 121 mg/dl (6.7 mmol/L) and he was able to eat a sandwich and drink some orange juice. One hour after admission his capillary blood glucose was 249 mg/dl (13.8 mmol/L).

After his recovery the patient reported that the afternoon before the event had occurred he exercised "really hard" but his capillary blood glucose was normal after exercise and before dinner. He remembered feeling "quite dizzy" before falling asleep but thought this was probably due to the wine. He did not measure his blood glucose at that time.

Comment

This patient became a high risk for severe hypoglycemia that evening. Heavy exercise increases hypoglycemic risk, not only during or immediately following exercise, but several hours later as well, due to depletion of liver and muscle glycogen and the subsequent demand of these tissues for glucose to restore these pools. Furthermore, heavy alcohol consumption inhibits gluconeogenesis, further predisposing to, or even causing, hypoglycemia. The behavior-altering effects of alcohol can also cloud the recognition of hypoglycemia by the patient and those around him (family, colleagues, etc.), leading to delays in prompt treatment.

The combination of vigorous exercise with heavy alcohol consumption may lead to dramatic effects in insulin-treated patients if insulin dose is not reduced and frequent glucose monitoring is not performed. An additional danger derives from the fact that glucagon may be less effective in reversing hypoglycemia in the absence of adequate glycogen stores. In the case presented, inadequate response to glucagon was probably caused by incomplete replenishment of glycogen stores after exercise due to alcohol consumption.

It should also be noted that the use of NPH insulin as a substitute for basal insulin has been associated with increased risk of hypoglycemia 4-6 hours after its subcutaneous injection, corresponding to the peak of action of this insulin preparation. The use of basal insulin analogs (glargine and detemir) has been associated with a small but significant, in clinical trial terms, reduction of nocturnal hypoglycemia in patients with Type 1 diabetes, compared to insulin NPH.45

Most importantly, this patient has hypoglycemia unawareness. Both previous episodes of hypoglycemia and sleep are associated with hypoglycemia-associated autonomic failure, a condition leading to unawareness of hypoglycemic episodes. Since HAAF substantially increases the risk of severe hypoglycemia, it is mandatory to reconsider the insulin plan for this patient in order to strictly avoid low blood glucose values in the next 15-20 days and consequently restore autonomic symptoms elicited by hypoglycemic glucose levels.

References

43. Brvar M, Mozina M, Bunc M. Prolonged hypoglycaemia after insulin lispro overdose. Eur J Emerg Med 2005; 12: 234-5.

44. Adlersberg MA, Fernando S, Spollett GR, et al. Glargine and lispro: two cases of mistaken identity. Diabetes Care 2002; 25: 404-5.

45. DeWitt DE, Hirsch IB. Outpatient insulin therapy in type 1 and type 2 diabetes mellitus: Scientifi c review. JAMA 2003; 289: 2254-64.

Next Excerpt: Hypoglycemia caused by insulin secretagogues

Nikolaos Katsilambros, MD, PhD, FACP
SCOPE Founding Fellow
Professor of Internal Medicine
Athens University Medical School
Evgenideion Hospital and Research Laboratory 'Christeas Hall'
Athens, Greece

Christina Kanaka-Gantenbein, MD, PhD
Associate Professor of Pediatric Endocrinology and Diabetology
First Department of Pediatrics, University of Athens
Agia Sofia Children's Hospital
Athens, Greece

Stavros Liatis, MD
Consultant in Internal Medicine and Diabetology
Laiko General Hospital

Konstantinos Makrilakis, MD, MPH, PhD
Assistant Professor of Internal Medicine and Diabetology
Athens University Medical School
Laiko General Hospital
Athens, Greece

Nikolaos Tentolouris, MD, PhD
Assistant Professor of Internal Medicine and Diabetology
University of Athens
Laiko General Hospital
Athens, Greece

A John Wiley & Sons, Ltd., Publication This edition first published 2011 © 2011 by John Wiley & Sons, Ltd.

All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, except as permitted by the UK Copyright, Designs and Patents Act 1988, without the prior permission of the publisher. This publication is designed to provide accurate and authoritative information in regard to the subject matter covered. It is sold on the understanding that the publisher is not engaged in rendering professional services. If professional advice or other expert assistance is required, the services of a competent professional should be sought. The contents of this work are intended to further general scientific research, understanding, and discussion only and are not intended and should not be relied upon as recommending or promoting a specific method, diagnosis, or treatment by physicians for any particular patient.

Diabetic Emergencies: Diagnosis and Clinical Management provides emergency room staff, diabetes specialists and endocrinologists with highly practical, clear-cut clinical guidance on both the presentation of serious diabetic emergencies like ketoacidosis, hyperosmolar coma and severe hyper- and hypoglycemia, and the best methods of both managing the emergencies and administering appropriate follow-up care.

For more information and to purchase this book, just follow this link: Diabetic Emergencies: Diagnosis and Clinical Management 

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This article originally posted 17 December, 2012 and appeared in  Diabetes Clinical Mastery Series Issue 115

Past five issues: Diabetes Clinical Mastery Series Issue 199 | Issue 739 | GLP-1 Special Editions July 2014 | Diabetes Clinical Mastery Series Issue 198 | Issue 738 |

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