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Hypoglycemia is the most common biochemical emergency in pediatric patients. Therefore, the ability to efficiently evaluate and treat of this condition is essential for the general pediatrician. Four broad categories of problems contribute to the development of hypoglycemia: loss of homeostatic control, inadequate intake of food, intoxication with a substance that induces low blood sugar, and inborn errors in the utilization, production, or release of sugar. When all systems are operating, there is a balance of supply and demand to maintain normal blood sugar (euglycemia) over a broad range of physiologic settings.

Euglycemia is maintained by a balance of glucose intake and production and glucose consumption. In the immediate postprandial period, there is a transient increase in the blood glucose level from glucose provided by digested food. However, this rapidly corrects, primarily through the action of insulin, which promotes the consumption and storage of glucose. In all cells, glucose is consumed primarily through the glycolytic pathway, by which the breakdown of glucose produces energy in the form of adenosine triphosphate (ATP), as well as products that can be further used in the tricarboxylic acid cycle or for lipogenesis. Insulin also promotes the uptake of glucose into the liver, where it is stored in the form of glycogen.

In the typical fasting state, euglycemia is maintained by the provision of glucose. Initially, this is done by glycogenolysis—the fast release of free glucose via the breakdown of liver glycogen. In a long fast, after glycogen stores are exhausted, glucose is synthesized, largely from the breakdown of amino acids and triglycerides. This process is known as gluconeogenesis. As fasting time lengthens, although euglycemia is maintained, the glucose level is lower in comparison to the immediate postprandial level. The maintenance of euglycemia in the face of fasting is coordinated by several hormones, including glucagon, cortisol, epinephrine, and norepinephrine.

Different organ systems have distinct roles in glucose homeostasis. Different organs also have different energy demands and different avidities for glucose as an energy source. Of note is the brain, which preferentially consumes glucose and is responsible for 15% to 18% of glucose consumption. The liver is the most important buffer for blood glucose, storing glucose during times of excess and releasing it during times of fasting. Muscle produces glucose only for local use and cannot release it. Adipose tissue provides energy in the form of fatty acids that can be used during fasting, but it cannot synthesize glucose to be used by other tissues.

Ketogenesis is a key component of the normal physiological response to fasting. Ketones are produced by the breakdown of fatty acids. Ketones are a glucose-sparing energy source, as they can enter the tricarboxylic acid cycle to drive the production of ATP. Ketones are also important in the fasting period, as they provide the ATP needed for gluconeogenesis.


As hypoglycemia develops, ...

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