BASICS
- ADA defines hypoglycemia as blood glucose <70 mg/dL.
- Levels:
- Level 1: <70 mg/dL but ≥54 mg/dL (hypoglycemia alert value)
- Level 2: <54 mg/dL (clinically significant hypoglycemia)
- Level 3: severe hypoglycemia with cognitive impairment needing assistance
- Pseudohypoglycemia: symptoms without low glucose (<70 mg/dL).
EPIDEMIOLOGY
- Most common in long-standing type 1 DM and children <7 years.
- ACCORD study: 3.14% annual hypoglycemia incidence in intensive treatment group.
- RECAP-DM: 35.8% of T2DM patients on sulfonylurea or thiazolidinedione report hypoglycemia.
- Risk increased in women, African Americans, older adults, insulin users.
ETIOLOGY AND PATHOPHYSIOLOGY
- Loss of counterregulatory hormones (insulin, glucagon, epinephrine).
- Impaired glucose metabolism and hormonal responses.
RISK FACTORS
- Majority of severe episodes occur during sleep.
- Comorbidities: renal/liver disease, CHF, hypothyroidism, hypoadrenalism, gastroparesis, autonomic neuropathy, pregnancy, psychiatric illness.
- Insulin secretagogues (sulfonylureas, glinides).
- Alcohol intake, smoking.
- Duration of diabetes >5 years.
- Children and elderly at increased risk.
GENERAL PREVENTION
- Consistent diet, medication, and exercise schedule.
- Self-monitoring of blood glucose (SMBG) or continuous glucose monitoring (CGM), especially for insulin/secretagogue users.
- Diabetes treatment and teaching programs (DTTP) improve outcomes.
- Use of insulin analogs, CSII pumps, and CGM reduces hypoglycemia risk.
DIAGNOSIS
History
- Adrenergic symptoms: hunger, tremors, sweating, anxiety.
- Neurologic symptoms: confusion, dizziness, seizures.
- Behavioral: irritability, fatigue.
- Surgical history (e.g., bariatric surgery).
Physical Exam
- Confusion, lethargy, tremor.
- Tachycardia.
- Signs of end-organ damage.
Differential Diagnosis
- Non-diabetic causes: alcohol abuse, hormonal deficiencies, sepsis, insulinoma, factitious hypoglycemia.
Diagnostic Tests
- Blood glucose measurement (fingerstick, serum).
- SMBG/CGM for asymptomatic hypoglycemia.
- HbA1c may be low due to recurrent hypoglycemia.
- Confirm CGM low readings with fingerstick glucose.
TREATMENT
Acute
- Immediate administration of fast-acting carbohydrates (15-20 g glucose).
- “Rule of 15”: consume 15-20 g CHO, recheck glucose in 15 min, repeat if <70 mg/dL.
- Glucagon for unconscious or unable to swallow:
- IM/SC glucagon: 0.5 mg if <6 years or <20-25 kg; 1 mg if older/larger.
- Intranasal glucagon 3 mg for age ≥4 years.
- Hospital: IV 50% dextrose 25 g every 5-10 min until conscious, then maintain with oral/IV glucose.
Chronic
- Adjust glycemic goals to avoid recurrent episodes.
- Address medications causing hypoglycemia.
- Educate patients and caregivers.
ONGOING CARE
- Discuss prevention at every visit.
- Alcohol increases risk of delayed hypoglycemia.
- Avoid high-protein CHO for treatment.
- Food insecurity raises risk.
PATIENT EDUCATION
- Keep fast-acting CHO accessible.
- Adjust insulin/diet before exercise if pre-exercise glucose <100 mg/dL.
- Teach signs and symptoms recognition.
- Use SMBG and adjust therapy accordingly.
- Wear medical alert ID.
COMPLICATIONS
- Seizures, coma, MI, stroke.
- Possible permanent neurologic damage from prolonged/severe episodes.
- Children with T1DM more vulnerable neurologically.
ALERT
- Intensive glycemic control increases risk of mortality (ACCORD trial).
REFERENCES
- ElSayed NA, Aleppo G, Aroda VR, et al; ADA. Glycemic targets: standards of care in diabetes—2023. Diabetes Care. 2023;46(Suppl 1):S97-S110.
- Seaquist ER, Anderson J, Childs B, et al; ADA, Endocrine Society. Hypoglycemia and diabetes: a workgroup report. J Clin Endocrinol Metab. 2013;98(5):1845-1859.
- Cryer PE, Axelrod L, Grossman AB, et al; Endocrine Society. Evaluation and management of adult hypoglycemic disorders: clinical guideline. J Clin Endocrinol Metab. 2009;94(3):709-728.
Clinical Pearls
- Hypoglycemia often limits glycemic management in diabetes.
- Immediate treatment with fast-acting glucose or glucagon is essential.
- Frequent SMBG or CGM use helps prevent unrecognized hypoglycemia.
- Individualize glycemic targets balancing control and hypoglycemia risk.
- “Rule of 15” is simple and effective for home management of hypoglycemia.