Hypoglycemia and the Central Nervous System

Hypoglycemia and the Central Nervous System

Fisher Simon J, Puente Erwin C, Tanoli Tariq
US Endocrinology - Volume 4 - Issue II
Published: April 2009
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The Diabetes Control and Complications Trial (DCCT) convincingly demonstrated that intensive insulin therapy reduces the microvascular complications associated with diabetes, including retinopathy, neuropathy, and nephropathy.1,2 However, intensive insulin therapy that lowers blood glucose towards normal levels also significantly increases the risk for hypoglycemia. Moderate hypoglycemia can acutely affect cognitive ability, leading to temporary stupor and confusion. Severe hypoglycemia can lead to seizures, coma, and even death. Therefore, hypoglycemia causes recurrent morbidity that can interfere with the ability of individuals to work, as well as to perform activities of daily living.3 The fear of a hypoglycemic reaction is also a barrier to intensive insulin therapy.

Hypoglycemia is not limited to patients with type 1 diabetes, but frequently occurs in patients with type 2 diabetes as well.4,5 As the ratelimiting step for insulin therapy in diabetes, hypoglycemia precludes the maintenance of long-term euglycemia and the long-term benefits associated with tight glucose control. Recognizing the impact of hypoglycemia and the development of novel therapies aimed at reducing iatrogenic hypoglycemia are all vital to improve blood sugar management and improve the lives of people with diabetes.

Physiological Defenses Against Hypoglycemia
Glucose is the major energy source for maintenance of brain metabolism and function; however, the brain has limited glucose reserves and needs a continuous supply of the monosaccharide.6 Therefore, the body has developed multiple systems to maintain glucose delivery to the brain and prevent hypoglycemia (see Table 1). First, a hierarchical hormonal response exists in response to decreasing blood glucose levels.7–9 As blood glucose drops below 80mg/dl, pancreatic β-cell insulin secretion is reduced. If blood glucose drops further, the pancreatic α-cell will secrete glucagon and the adrenal medulla will release epinephrine.7–9 Both glucagon and epinephrine act rapidly to increase glucose availability and therefore are the two major counter-regulatory hormones. Cortisol and growth hormone are also released, but they are unable to prevent prolonged hypoglycemia if glucagon and epinephrine responses are absent.10 In sensing hypoglycemia, the nutritionally deprived brain also stimulates the sympathetic nervous system, leading to neurogenic symptoms such as sweating, palpitations, tremulousness, anxiety, and hunger.11 These symptoms prompt individuals to ingest food to increase blood sugar levels. If these defenses are unable to restore blood sugar levels, inadequate glucose supply to the brain leads to neuroglycopenic symptoms such as confusion, difficulty speaking, ataxia, paresthesias, headaches, seizures, and coma.12

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