Hypoglycemia

Abstract

Iatrogenic hypoglycemia often causes recurrent morbidity and precludes maintenance of lifelong euglycemia in people with diabetes mellitus. It causes an array of neurogenic (autonomic) and neuroglycopenic symptoms, cardiovascular responses, neurophysiological changes and cognitive impairments, and, if severe and prolonged, death. It is the result of the interplay of exogenous or endogenous insulin excess and compromised physiological and behavioral defenses against falling glucose levels in type 1 diabetes and advanced type 2 diabetes. Absolute or relative insulin excess occurs when (1) insulin (or insulin secretagogue) doses are excessive, ill‐timed, or of the wrong type; (2) the intake of exogenous carbohydrate is decreased as following a missed meal or snack or during an overnight fast; (3) endogenous glucose production is decreased as following alcohol ingestion; (4) insulin‐independent glucose utilization is increased as during exercise; (5) sensitivity to insulin is increased as following exercise, in the middle of the night, during effective glycemic therapy, or following weight loss; (6) insulin clearance is decreased as with progressive renal insufficiency. However, insulin excess alone explains only a minority of episodes of severe hypoglycemia. Compromised defenses include defective glucose counterregulation (absent glucagon responses and reduced adrenaline responses) and impaired awareness of hypoglycemia (partial or complete loss of the warning symptoms of developing hypoglycemia that previously prompted the patient to eat and abort the episode). The concept of hypoglycemia‐associated autonomic failure in diabetes posits that recent antecedent hypoglycemia causes both defective glucose counterregulation (by reducing the adrenaline response, in the setting of an absent glucagon response, to subsequent hypoglycemia) and impaired awareness of hypoglycemia (by reducing the autonomic response and the resultant symptomatic responses to subsequent hypoglycemia) and thus a vicious cycle of recurrent iatrogenic hypoglycemia. It has been supported by the discovery that as little as 2–3 weeks of scrupulous avoidance of hypoglycemia reverses impaired awareness and improves the adrenaline response in most affected patients. Risk factors for hypoglycemia‐associated autonomic failure include more marked insulin deficiency, a history of severe hypoglycemia, impaired awareness of hypoglycemia, or both and aggressive glycemic therapy per se as evidenced by lower mean glycemia (HbA 1c ), lower glycemic goals, or both. Prevention of iatrogenic hypoglycemia includes thorough patient education, partnership and ongoing professional support, regular self‐monitoring of blood glucose, individualized glycemic goals, and rational and flexible drug regimens. The latter include use of newer long‐acting and rapid‐acting insulin analogues in insulin‐deficient diabetes and perhaps of insulin sensitizers or relatively glucose‐dependent insulin secretagogues in those with sufficient residual endogenous insulin secretion. Oral carbohydrate or glucose is sufficient to treat most episodes, but parenteral glucagon or intravenous glucose is often necessary for severe episodes. Such short‐term treatments must be followed by regimen adjustments designed to prevent recurrent hypoglycemia, often including a period of scrupulous avoidance of iatrogenic hypoglycemia. Ultimately we need to learn to replace insulin in a much more physiological fashion, to prevent, correct, or compensate for compromised glucose counterregulation, or both if we are to achieve euglycemia safely over a lifetime of diabetes.

Exercise-Induced Hypoglycemic Hemiplegia in a Child with Type 1 Diabetes: A Rare Find with Multiple Potential Causative Mechanisms

“…In diabetic children these responses are more vigorous than in diabetic adults, but the neuroendocrine response to hypoglycemia is impaired, with reduced catecholamine, growth hormone, and glucagon surges [ 16 ]. Excellent glycemic control usually leads to intermittent hypoglycemia that, even if mild or transient, may further impair the neuroendocrine counterregulatory response, resulting in more severe hypoglycemia [ 17 , 18 ].…”

Impediments to and impact of checklists on performance of emergency interventions in primary care: an in situ simulation-based randomized controlled trial

“…Severe hypoglycemia can lead to seizures, pulmonary aspiration, malignant ventricular arrhythmias [ 3 ] and, if sustained, irreversible brain damage [ 4 ]. Immediate administration of intravenous glucose or intramuscular glucagon is recommended [ 5 ].…”

Economic burden of hypoglycemia for type II diabetes mellitus patients in Malaysia

“…Hypoglycemia is not an uncommon presentation at accident and emergency (A&E) departments. An estimated 2–4% of diabetes deaths are due to hypoglycemia [1]. Hypoglycemic episodes are inevitable in 90% of diabetics with insulin therapy [2]; those on certain anti-hyperglycemic medicine are also at risk.…”