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Diabetic Emergencies: Hypoglycemia Caused by Insulin Secretagogues, Part 2

Jan 14, 2013

Nikolaos Tentolouris, Nikolaos Katsilambros







Symptoms and signs of hypoglycemia in Type 2 diabetes 


The symptoms of hypoglycemia do not differ between people with Type 1 and Type 2 diabetes.

In addition, the agent inducing hypoglycemia (sulfonylurea or insulin) induces identical symptoms in patients with Type 2 diabetes whenever blood glucose is lowered in the same individual to the same level. 22,23 However, in elderly people who have diabetes, symptoms of hypoglycemia may differ from those observed in younger individuals.24 Generalized malaise, hypothermia, and a group of neurological symptoms including unsteadiness, sleepiness, poor coordination, blurred and/or double vision, slurred speech, and other focal neurological deficits have been identified in patients with Type 2 diabetes.13,24 These neurological symptoms and signs may be confused with other conditions such as stroke or vaso-vagal syncope. In addition, elderly people usually report lower symptom scores of hypoglycemia and limited perception of symptoms than younger individuals, with autonomic and neuroglycopenic symptoms being affecting equally.3 Two studies suggested that the attenuation in symptom intensity is a feature of increasing age, independent of any effects of diabetes. 25,26

Previous data confirmed that the glycemic threshold at which symptomatic responses to hypoglycemia are generated is altered with age.27,28 Thus, in younger people with Type 2 diabetes, symptoms are evoked at a blood glucose level of 65 mg/dl (3.6 mmol/L), which is on average 18 mg/dl (1.0 mmol/L) higher than the level at which cognitive function becomes impaired. This allows for action for correction of low blood glucose levels and prevention of neuroglycopenia. In older people, however, the glycemic threshold of symptomatic responses and that of the reaction time is close to 54 mg/dl (around 3.0 mmol/L), eliminating the time available for correction and prevention of severe hypoglycemia 27 (Figure 5.3 ).  
Summary box

  • In elderly people with Type 2 diabetes hypoglycemia may manifest with neurological symptoms and signs including unsteadiness, poor coordination, blurred and/or double vision, slurred speech, and other focal neurological deficits
  • The intensity of classic hypoglycemic symptoms may be lower in elderly people with Type 2 diabetes
  • Elderly people may not have enough time to take action to correct hypoglycemia because symptoms occur late after the onset of neuroglycopenia



Thus, in older people with diabetes, differences in symptoms, lower symptom intensity, and altered glycemic thresholds can predispose to severe hypoglycemia.


In general, it is a good rule to regard all insulin secretagogues as having the potential to cause hypoglycemia and to inform patients and their families accordingly. The best way to prevent hypoglycemia is by frequent self-monitoring of blood glucose after initiation of a new therapy with insulin secretagogues and during periods of illness and reduced food intake. In case of doubt at home, it is always better for the patient to be treated for hypoglycemia than to ignore the possibility.

In elderly people and in those living alone, alternative treatment modalities should be considered such as dipeptidyl-peptidase inhibitors, glucagon-like 1 agonists, or insulin secretagogues with a low risk of hypoglycemia, instead of long-lasting sulfonylureas. 29 Particular attention should be paid to the concomitant medications the patients receive. Health care professionals should keep in mind that patients treated with sulfonylureas may not present with the classic symptoms of hypoglycemia and that concomitant treatments may mask symptoms.

Mild hypoglycemic episodes due to sulfonylureas may be treated with simple carbohydrates, as described in Chapter 4, and a meal if it is close to that time, but the patient/carers should be aware of the possibility of repeated hypoglycemia over the next hours. Frequent self-monitoring of blood glucose is the key to treatment (Figure 5.4 ). 


Hypoglycemic coma caused by insulin secretagogues is not uncommon. Virtually every unconscious diabetic patient should be considered to be hypoglycemic until immediate estimation of the blood glucose levels has ruled it out. 5,22

When hypoglycemia occurs due to the use of sulfonylureas it can be potentially prolonged and require hospitalization. Intravenous bolus administration of 20-50 ml of 50% glucose solution or 50 ml of 35% glucose solution followed by infusion of 10-20% glucose solution should begin immediately and continued uninterrupted for one or more days. Blood glucose levels should be monitored frequently (see Figure 5.4 ). In the case of refractory hypoglycemia, addition of glucagon, hydrocortisone sodium, or diazoxide may be needed until the effects of the sulfonylurea have worn off. The duration of hospitalization depends on the sulfonylurea used and its duration of action. Thus, hospitalization and frequent glucose monitoring for 24-72 hours may be needed. 22

Data from the ACCORD trial showed that patients with Type 2 diabetes who experience symptomatic, severe hypoglycemia are at increased risk of death, regardless of the intensity of glucose control. 30 Thus, hypoglycemia may be an important cause or contributing factor for death in 3-6% of patients with diabetes. The cause of death during hypoglycemia may be related to development of arrhythmia (frequent supraventricular and ventricular ectopic beats, prolongation of the QT interval and development of ventricular tachycardia, atrial fibrillation), silent myocardial ischemia, myocardial infarction, cerebral damage from glucopenia, and cerebral ischemia from acute thrombotic occlusion of the cerebral arteries. 21 In one series, among 102 patients hospitalized for hypoglycemic coma, 92 patients had Type 2 diabetes and 50 of these patients had been treated with glibenclamide (glyburide) alone, 15 with the combination of glibenclamide (glyburide) and insulin, and 10 with glibenclamide (glyburide) and metformin.31 Sixty-two patients responded to treatment with intravenous glucose infusion during the first 12 hours, while 40 patients had protracted hypoglycemia of 12-72 hours’ duration. Of note, severe head trauma and bone fractures were found in 8 patients, while transient asymptomatic myocardial ischemia was noticed in 2 patients; death occurred in 5 patients. 30 Because of increasing physical frailty and osteoporosis, elderly patients are more susceptible to physical injury during hypoglycemia, and bone fractures, joint dislocations, soft tissue injuries, and head injuries are not uncommon. 21


Summary box

  • Regard all insulin secretagogues as having the potential for hypoglycemia and inform patients and their families accordingly
  • Medications with a low risk of hypoglycemia should be preferred in older people with Type 2 diabetes
  • Manage every unconscious diabetic patient as hypoglycemic until immediate estimation of blood glucose levels rules it out
  • Hypoglycemia due to sulfonylurea may be prolonged and needs continuous intravenous glucose infusion and hospitalization for 24-72 hours

Next Excerpt: Hypoglycemia caused by insulin secretagogues Case Studies, Part 3


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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.

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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.

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