What is the approach to diagnosing and managing hypoglycemia (low blood sugar)?

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Last updated: May 14, 2025View editorial policy

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From the Guidelines

The workup for hypoglycemia should begin with confirming true hypoglycemia through Whipple's triad: symptoms of hypoglycemia, documented low blood glucose (typically <70 mg/dL), and resolution of symptoms after glucose administration. Initial evaluation includes a detailed history focusing on timing of symptoms relative to meals, medication use (especially insulin, sulfonylureas, and other diabetes medications), alcohol consumption, and recent changes in diet or exercise.

Key Components of the Workup

  • Laboratory tests should be obtained during a hypoglycemic episode and include plasma glucose, insulin, C-peptide, proinsulin, beta-hydroxybutyrate, and sulfonylurea screen 1.
  • A 72-hour supervised fast may be necessary to provoke hypoglycemia in suspected cases of endogenous hyperinsulinism.
  • Additional testing may include imaging studies such as CT, MRI, or endoscopic ultrasound of the pancreas if insulinoma is suspected.
  • For reactive hypoglycemia, a mixed-meal tolerance test is more appropriate than a glucose tolerance test.
  • Cortisol and growth hormone levels should be checked to rule out adrenal insufficiency and growth hormone deficiency. The workup aims to differentiate between exogenous causes (medication-induced), endogenous causes (insulinoma, nesidioblastosis), and non-islet cell tumors, as treatment approaches differ significantly based on the underlying cause 1.

Importance of Recent Guidelines

According to the most recent guidelines, individuals at risk for hypoglycemia should be asked about symptomatic and asymptomatic hypoglycemia at each encounter 1. Glucose (approximately 15–20 g) is the preferred treatment for the conscious individual with blood glucose <70 mg/dL, although any form of carbohydrate that contains glucose may be used 1.

Treatment and Prevention

Glucagon should be prescribed for all individuals at increased risk of level 2 or 3 hypoglycemia, so that it is available should it be needed 1. Hypoglycemia unawareness or one or more episodes of level 3 hypoglycemia should trigger hypoglycemia avoidance education and reevaluation and adjustment of the treatment plan to decrease hypoglycemia 1. Insulin-treated patients with hypoglycemia unawareness, one level 3 hypoglycemic event, or a pattern of unexplained level 2 hypoglycemia should be advised to raise their glycemic targets to strictly avoid hypoglycemia for at least several weeks in order to partially reverse hypoglycemia unawareness and reduce risk of future episodes 1. Ongoing assessment of cognitive function is suggested with increased vigilance for hypoglycemia by the clinician, patient, and caregivers if impaired or declining cognition is found 1.

From the FDA Drug Label

Instruct patients and their caregivers on the signs and symptoms of severe hypoglycemia Because severe hypoglycemia requires the help of others to recover, instruct the patient to inform those around them about Glucagon for Injection and its Instructions for Use. Administer Glucagon for Injection as soon as possible when severe hypoglycemia is recognized The recommended dosage is 1 mg (1 mL) injected subcutaneously or intramuscularly into the upper arm, thigh, or buttocks, or intravenously If there has been no response after 15 minutes, an additional 1 mg dose (1 mL) of Glucagon for Injection may be administered using a new kit while waiting for emergency assistance.

To work up hypoglycemia, administer glucagon as soon as possible when severe hypoglycemia is recognized. The recommended dosage is:

  • 1 mg (1 mL) for adults and pediatric patients weighing more than 25 kg or for pediatric patients with unknown weight 6 years and older
  • 0.5 mg (0.5 mL) for pediatric patients weighing less than 25 kg or for pediatric patients with unknown weight less than 6 years of age If there is no response after 15 minutes, an additional dose of glucagon may be administered using a new kit while waiting for emergency assistance. It is also important to instruct patients and their caregivers on the signs and symptoms of severe hypoglycemia and to inform those around them about glucagon and its instructions for use 2.

From the Research

Hypoglycemia Management

  • Hypoglycemia is a common occurrence in people with diabetes, and its management is crucial to prevent serious complications 3.
  • The American Diabetes Association recommends a management protocol for hypoglycemia, including a clear prevention and treatment plan 3.
  • For patients with type 1 diabetes and type 2 diabetes, optimizing insulin doses and carbohydrate intake, as well as a short warm-up before or after physical activity sessions, may help avoid hypoglycemia 3.

First Aid Glucose Administration

  • The best enteral route for glucose administration for suspected hypoglycemia in a first aid situation is unknown 4.
  • Sublingual glucose administration may result in a higher blood glucose concentration after 20 minutes compared to oral administration in children with hypoglycemia and symptoms of concomitant malaria or respiratory tract infection 4.
  • Oral glucose administration results in a higher blood glucose concentration after 20 minutes when compared to buccal administration of glucose 4.

Adrenal Insufficiency and Hypoglycemia

  • Adrenal insufficiency may be a cause of hypoglycemia, and its frequency is higher than anticipated 5.
  • Recognition of hypoglycemia as a symptom of adrenal insufficiency is important to prevent treatable causes of sudden deaths 6.
  • Cortisol has a key role in glucose homeostasis, particularly in the counter-regulatory mechanisms to prevent hypoglycemia in times of biological stress 6.

Emergency Treatment of Hypoglycemia

  • High-quality evidence for the management of hypoglycemia is lacking, limiting treatment recommendations 7.
  • Guidelines and studies recommend 15-20 g of oral glucose or sucrose, repeated after 10-15 min for treatment of the responsive adult, and 10% intravenous dextrose or 1 mg intramuscular glucagon for treatment of the unresponsive adult 7.
  • Further high-quality studies are required to inform the optimum management of hypoglycemia 7.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Hypoglycaemia and its management in primary care setting.

Diabetes/metabolism research and reviews, 2020

Research

First aid glucose administration routes for symptomatic hypoglycaemia.

The Cochrane database of systematic reviews, 2019

Research

Hypoglycaemia in adrenal insufficiency.

Frontiers in endocrinology, 2023

Research

Emergency treatment of hypoglycaemia: a guideline and evidence review.

Diabetic medicine : a journal of the British Diabetic Association, 2017

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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