Hypoglycemia

GENERAL PRINCIPLES

Classification

Iatrogenic factors usually account for hypoglycemia in the setting of diabetes, complicating therapy with insulin or SFUs and limiting achievement of glycemic control during intensive therapy in patients with diabetes.³⁸ Hypoglycemia is uncommon in patients not treated for diabetes and can be classified as fasting or postprandial hypoglycemia.

Risk Factors

Hypoglycemia resulting from too intensive diabetes management with insulin or SFU may increase the risk of mortality in older patients with CV risk factors and should be avoided.

• Risk factors for hypoglycemia during insulin or SFU treatment include skipped or insufficient meals, unaccustomed physical exertion, misguided therapy, alcohol ingestion, and drug overdose.

• Recurrent episodes of hypoglycemia impair recognition of hypoglycemic symptoms, thereby increasing the risk for severe hypoglycemia (hypoglycemia unawareness).

• Hypoglycemia unawareness results from defective glucose counterregulation with blunting of autonomic symptoms and counterregulatory hormone secretion during hypoglycemia. Seizures or coma may develop in such patients without the usual warning symptoms of hypoglycemia.

DIAGNOSIS

Clinical Presentation

• Hypoglycemia is a clinical syndrome in which low serum (or plasma) glucose levels lead to symptoms of sympathetic-adrenal activation (sweating, anxiety, tremor, nausea, palpitations, and tachycardia) from increased secretion of counterregulatory hormones (e.g., epinephrine).

• Neuroglycopenia occurs as the glucose levels decrease further (fatigue, dizziness, headache, visual disturbances, drowsiness, difficulty speaking, inability to concentrate, abnormal behavior, confusion, and ultimately loss of consciousness or seizures).

Differential Diagnosis

Plasma or capillary BG values should be obtained, whenever feasible, to confirm hypoglycemia.

• Hypoglycemia in persons with diabetes

î Classified as level 1 (BG lt;70 mg/dL or 3.9 mmol/L), level 2 (BG lt;54 mg/dL or 3 mmol/L), or severe hypoglycemia (altered mental status, needing assistance for recovery).

î Mitigation strategies for iatrogenic hypoglycemia include diabetes education to determine the cause of mismatched insulin doses with food intake; reduction in insulin or SFU doses; increased monitoring using SMBG; or use of CGM with alarms.

• Evaluation of hypoglycemia in persons without diabetes

î In persons without diabetes, a serum glucose concentration of lt;60 mg/dL (3.3 mmol/L) is concerning for a hypoglycemic disorder, and further evaluation is required if the value is lt;55 mg/dL (3.0 mmol/L).

î These levels are usually accompanied by symptoms of hypoglycemia. Absence of symptoms suggests the possibility of artifactual hypoglycemia. Whipple's triad includes symptoms and/or signs of hypoglycemia, a documented low plasma glucose, and resolution of symptoms with an increase in plasma glucose.

î Detailed evaluation is usually required in a healthy appearing patient without diabetes, whereas hypoglycemia may be readily recognized as part of the underlying illness in a sick patient.

° Fasting hypoglycemia in persons without diabetes can be caused by inappropriate insulin secretion (e.g., insulinoma), alcohol abuse, severe hepatic or renal insufficiency, hypopituitarism, glucocorticoid deficiency, or surreptitious injection of insulin or ingestion of an SFU.

î These patients present with neuroglycopenic symptoms, but episodic autonomic symptoms may be present.

î Definitive diagnosis of fasting hypoglycemia requires hourly BG monitoring during a supervised fast lasting up to 72 hours, and measurement of plasma insulin, C-peptide, proinsulin, beta­hydroxybutyrate, and SFU metabolites if hypoglycemia (lt;55 mg/dL [3.0 mmol/L]) is documented on a plasma glucose sample. Patients who develop hypoglycemia and have measurable plasma insulin and C-peptide levels without SFU metabolites require further evaluation for an insulinoma.

î Postprandial hypoglycemia occurs 1 or more hours after meals.

î This should be considered in patients with a history of partial gastrectomy or intestinal resection in whom recurrent symptoms develop 1-2 hours after eating. The mechanism is thought to be related to too rapid glucose absorption, resulting in a robust insulin response and altered incretin response. These symptoms should be distinguished from dumping syndrome, which is not associated with hypoglycemia and occurs in the first hour after food intake. Frequent small meals with reduced carbohydrate content may ameliorate symptoms.

TREATMENT

Isolated episodes of mild hypoglycemia may not require specific intervention in persons with diabetes. Recurrent episodes require a review of lifestyle factors; adjustments may be indicated in the content, timing, and distribution of meals, as well as medication dosage and timing. Severe hypoglycemia is an indication for supervised treatment.

• Readily absorbable carbohydrates (e.g., glucose and sugar-containing beverages) can be administered orally to conscious patients for rapid effect. Alternatively, milk, candy bars, fruit, cheese, and crackers may be used in some patients with mild hypoglycemia. Glucose tablets and carbohydrate supplies should be readily available to patients with DM at all times.

• IV dextrose is indicated for severe hypoglycemia, in patients with altered consciousness, and during restriction of oral intake. An initial bolus, 20-50 mL of 50% dextrose, should be given immediately, followed by infusion of 5% dextrose in water (D5W) (or D10W) to maintain BG levels above 100 mg/dL (5.6 mmol/L). Prolonged IV dextrose infusion and close observation are warranted in SFU overdose, in the elderly, and in patients with defective counterregulation.

• Glucagon, 1 mg IM (or SC), is an effective initial therapy for severe hypoglycemia in patients unable to receive oral intake or in whom an IV access cannot be secured immediately. Vbmiting is a frequent side effect, and therefore, care should be taken to prevent the risk of aspiration.

Patient Education

• Education regarding etiologies of hypoglycemia, preventive measures, and appropriate adjustments to medication, diet, and exercise regimens is an essential task to be addressed during hospitalization for severe hypoglycemia.

• Hypoglycemia unawareness can develop in patients who are undergoing intensive diabetes therapy. These patients should be encouraged to monitor their BG levels frequently and take timely measures to correct low values (lt;70 mg/dL [3.9 mmol/L]). Continuous glucose monitor technology with low alert alarms helps prevent severe hypoglycemia. In patients with very tightly controlled diabetes, slight relaxation in glycemic control and scrupulous avoidance of hypoglycemia may restore the lost warning symptoms.