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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

  1. 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.
  2. 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.
  3. 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.