TABLE 87-1 Drugs and Toxins Associated with Hypoglycemia | ||||||||
|---|---|---|---|---|---|---|---|---|
|
Hypoglycemia
Hypoglycemia
John P. Mordes
Samir Malkani
I. GENERAL PRINCIPLES
A. Hypoglycemia is common and must be excluded in every patient with stupor or coma.
B. Cases of refractory, prolonged hypoglycemia of unknown etiology require ICU admission.
C. Severe hypoglycemia can lead to permanent neurologic damage.
D. No specific blood glucose concentration uniformly defines hypoglycemia.
1. Typically <50 mg/dL (2.8 mM).
2. Physiologic definition: blood glucose low enough to cause release of counterregulatory hormones and impair mental status.
E. “Whipple triad” defines hypoglycemia best.
1. Documentation of a low glucose concentration.
2. Concurrent symptoms of hypoglycemia.
3. Resolution of symptoms after administration of glucose.
II. PATHOPHYSIOLOGY
A. Hypoglycemia can be divided into fasting and nonfasting categories.
1. “Nonfasting,” “postprandial,” “reactive” hypoglycemic states are, with one exception, not usually life threatening and can be managed on an outpatient basis.
2. Exception: postprandial hypoglycemia after gastric bypass surgery.
B. Hypoglycemia has several etiologies.
1. Excess insulin.
a. Insulin overdose.
i. The commonest cause of hypoglycemia.
ii. In most cases, the overdose is inadvertent, due to a missed meal or intense exercise.
iii. Suspect intentional medication overdose in anyone with access to insulin or oral hypoglycemic agents who has unexplained hypoglycemia.
iv. Long-standing diabetes causes increased sensitivity to shortacting insulins, defective counterregulatory responses, and more severe hypoglycemia.
v. When counterregulation is impaired, adrenergic symptoms (e.g., tremor, diaphoresis, tachycardia) may not occur and neuroglycopenic symptoms (e.g., confusion, combativeness, seizure, coma) can develop rapidly.
vi. Inadequate counterregulation also delays recovery from hypoglycemia.
2. Intensive insulin therapy.
a. Efforts to achieve near-normal glucose in the ICU and in some ambulatory patients are associated with high rates of hypoglycemia and no improvement in outcome.
3. Hypoglycemia due to oral medications.
a. “Hypoglycemic agents” augment insulin secretion.
i. The sulfonylurea-class oral hypoglycemic agents are the leading cause of hypoglycemia in persons over 60, usually in the setting of starvation superimposed on liver or kidney impairment.
ii. Overdoses of sulfonylureas also cause hypoglycemia in younger persons. Oral hypoglycemic agent pharmacy errors (e.g., chlorpropamide for chlorpromazine) have been reported.
iii. The meglitinides also cause hypoglycemia. Surreptitious abuse of repaglinide has been reported.
iv. The incretins and DPP-4 inhibitors enhance insulin secretion, but only in response to oral glucose ingestion, so they rarely cause hypoglycemia when used as monotherapy. Combined with insulin or oral agents they increase the risk of hypoglycemia.
b. “Antidiabetic agents” promote normoglycemia via other mechanisms. These include metformin, thiazolidinediones, and alpha-glucosidase inhibitors.
i. When given as monotherapy they seldom cause hypoglycemia.
ii. They increase the likelihood of hypoglycemia when used in combination with insulin or oral hypoglycemic drugs.
iii. Metformin is sold in fixed-ratio tablets in combination with other drugs such as sulfonylureas and thiazolidinediones; overdosage with a combination drug can cause severe hypoglycemia.
iv. Because alpha-glucosidase inhibitors interfere with the digestion of carbohydrates, hypoglycemic patients treated taking these drugs plus insulin or sulfonylureas may not respond to therapy with oral complex sugars.
4. Several medications not used to treat diabetes can increase circulating insulin concentration and cause hypoglycemia. Some are listed in Table 87-1.
5. Insulinomas and other causes of hyperinsulinemia.
a. Insulin-secreting pancreatic islet cell tumors are rare and usually cause fasting hypoglycemia.
b. Paraneoplastic hypoglycemia may be caused by tumors that secrete insulin-like growth factors.
c. An unusual cause of hypoglycemia in children is nesidioblastosis (nonmalignant islet cell adenomatosis).
d. Gastric bypass surgery leads to postprandial hypoglycemia in some patients years after surgery. Some cases are due to dumping syndrome and are self-limiting; others are associated with hyperinsulinemia, possibly as a result of nesidioblastosis, though this is disputed.
e. Autoimmune or antibody-mediated hypoglycemia is a rare condition in which autoantibodies activate the insulin receptor.
