Hypoglycemia

Glucose is an obligate metabolic fuel for the brain. Hypoglycemia should be

considered in any patient withconfusion, altered level of consciousness, or

seizures. Counterregulatory responses to hypoglycemia include insulin suppression

and the release of catecholamines, glucagon, growth hormone, and

cortisol.

The laboratory diagnosis of hypoglycemia is usually defined as a plasma

glucose level _2.5–2.8 mmol/L (_45–50 mg/dL), although the absolute glucose

level at which symptoms occur varies among individuals. For this reason, Whipple’s triad should be present: (1) symptoms consistent with hypoglycemia,

(2) a low plasma glucose concentration, and (3) relief of symptoms after the

plasma glucose level is raised.

Etiology

Hypoglycemia occurs most commonly as a result of treating patients withdiabetes

mellitus. However, a number of other disorders are also associated with

hypoglycemia, and it is useful to divide these into those associated with fasting

or the postprandial state.

1. Fasting:

a. Underproduction of glucose: hormone deficiencies (hypopituitarism

and adrenal insufficiency), inherited enzyme defects, hepatic failure,

renal failure, hypothermia, and drugs (ethanol, beta blockers, and rarely

salicylates).

b. Overutilization of glucose: hyperinsulinism (exogenous insulin, sulfonylureas,

insulin or insulin receptor antibodies, insulinoma, endotoxic

shock, renal failure, and use of pentamidine, quinine, or disopyramide)

and withappropriate insulin levels but increased levels of

insulin-like growthfactors suchas IGF-II (mesenchymal or other extrapancreatic

tumors and prolonged starvation).

2. Postprandial (reactive): after gastric surgery and in children with rare enzymatic

defects.

Clinical Features

Symptoms of hypoglycemia can be divided into autonomic (adrenergic: palpitations,

tremor, and anxiety; and cholinergic: sweating, hunger, and paresthesia)

and neuroglycopenic (behavioral changes, confusion, fatigue, seizure, loss of

consciousness, and, if hypoglycemia is severe and prolonged, death). Tachycardia,

elevated systolic blood pressure, pallor, and diaphoresis may be present

on physical examination.

Recurrent hypoglycemia shifts thresholds for the autonomic symptoms

and counterregulatory responses to lower glucose levels, leading to hypoglycemic

unawareness. Under these circumstances, the first manifestation of hypoglycemia

is neuroglycopenia, placing patients at risk of being unable treat

themselves.

Diagnosis

Diagnosis of the hypoglycemic mechanism is critical for choosing a treatment

that prevents recurrent hypoglycemia (Fig. 25-1). Urgent treatment is often necessary in patients with suspected hypoglycemia. Nevertheless, blood should be

drawn at the time of symptoms, whenever possible before the administration of

glucose, to allow documentation of the glucose level. If the glucose level is low

and the cause of hypoglycemia is unknown, additional assays should be performed

on blood obtained at the time of a low plasma glucose. These should

include insulin, C-peptide, sulfonylurea levels, cortisol, and ethanol. In the absence

of documented spontaneous hypoglycemia, overnight fasting or food deprivation

during observation in the outpatient setting will sometimes elicit hypoglycemia

and allow diagnostic evaluation. An extended (up to 72 h) fast under

careful supervision in the hospital may otherwise be required—the test should

be terminated if plasma glucose drops below 2.5 mmol/L (45 mg/dL) and the

patient has symptoms.

Interpretation of fasting test results is shown in Table 25-1.

TREATMENT

The syndrome of hypoglycemic unawareness in patients with diabetes mellitus is

reversible after as little as 2 weeks of scrupulous avoidance of hypoglycemia.

This involves a shift of glycemic thresholds back to higher glucose concentrations.

Acute therapy of hypoglycemia requires administration of oral glucose or

25 g of a 50% solution intravenously followed by a constant infusion of 5 or

10% dextrose if parenteral therapy is necessary. Hypoglycemia from sulfonylureas

is often prolonged, requiring treatment and monitoring for 24 hor

more. Subcutaneous or intramuscular glucagon can be used in diabetics. Prevention

of recurrent hypoglycemia requires treatment of the underlying cause

of hypoglycemia, including discontinuation or dose reduction of offending

drugs, replacement of hormonal deficiencies, treatment of critical illnesses,

and surgery of insulinomas or other tumors. Treatment of other forms of

hypoglycemia is dietary, with avoidance of fasting and ingestion of frequent

small meals.