DESCRIPTION

• Abnormally low concentration of glucose in circulating blood of a patient with diabetes mellitus (DM); often referred to as an insulin reaction, as classified by the ADA
  • Level 1: hypoglycemia alert value; <70 mg/dL (3.9 mmol/L) but ≥54 mg/dL (≥3.0 mmol/L): may or may not be accompanied by symptoms; asymptomatic hypoglycemia if symptoms not present; should alert patients to ingest carbohydrates to prevent progressive hypoglycemia
  • Level 2: clinically significant hypoglycemia; <54 mg/dL (<3.0 mmol/L)
  • Level 3: severe hypoglycemia associated with severe cognitive impairment requiring external assistance for recovery
  • Pseudohypoglycemia: typical symptoms but glucose ≥70 mg/dL (≥3.9 mmol/L)
• Hypoglycemia is the leading limiting factor in the glycemic management of type 1 DM (T1DM) and type 2 DM (T2DM). Severe or frequent hypoglycemia requires modification of treatment regimens with higher treatment goals.

EPIDEMIOLOGY

ETIOLOGY AND PATHOPHYSIOLOGY

• Loss of hormonal counterregulatory mechanism in glucose metabolism
• Impaired insulin, glucagon, and epinephrine secretion

RISK FACTORS

• Taking medications known to cause hypoglycemia (e.g., insulin, insulin secretagogues: sulfonylureas [glyburide, glimepiride, glipizide, etc.] and glinide derivatives [repaglinide, nateglinide])
• Intensive insulin therapy (further lowering HbA1c from 7% to 6%)
• Comorbidities: renal/liver disease, congestive heart failure, hypothyroidism, hypoadrenalism, gastroenteritis, gastroparesis (unpredictable carbohydrate [CHO] delivery), autonomic neuropathy, pregnancy, anxiety, depression, disordered eating behavior, illness/stress, and unplanned life events
• Advance age
• Longer duration of DM (including those using insulin for >5 years)
• Young children with T1DM
• Reduced cognitive function (including dementia) and those with intellectual disability
• Irregular eating schedules, starvation, prolonged fasting, weight loss, or food insecurity
• Current smokers with T1DM
• Alcohol consumption, especially if on insulin or insulin secretagogues. Evening consumption of alcohol is associated with an increased risk of nocturnal and fasting hypoglycemia, especially in patients with T1DM.
• Individuals fasting for religious or cultural reasons
• History of severe hypoglycemia (especially recent within the past 3 to 6 months)
• Hypoglycemia is rare in diabetics not treated with insulin or insulin secretagogues.
• Other antidiabetes medications such as dipeptidyl peptidase 4 inhibitors (DPP-4), glucagon-like peptide-1 (GLP-1) agonists, and sodium-glucose cotransporter-2 (SGLT-2) agents carry a lower but present risk of hypoglycemia, which may increase when combining agents from different categories.

Geriatric Considerations

• American Geriatric Society Beers Criteria recommend avoiding long-acting sulfonylureas (SU) (e.g., glyburide) due to prolonged half-life in older adults and risk for prolonged hypoglycemic episodes. Medications should be dosed for age and renal function.
• Individualize pharmacologic therapy in older adults to reduce the risk of hypoglycemia, avoid overtreatment, and simplify complex regimens if possible while maintaining the HbA1c target.

Pediatric Considerations
Children may not realize when they have hypoglycemia, needing increased supervision during times of higher activity such as competitive sports. Children may have higher glycemic goals for this reason. Caregivers should be instructed in use of glucagon.Pregnancy Considerations
Hypoglycemia management and avoidance education should be reemphasized and blood glucose monitoring increased due to more stringent glycemic goals and increased risk in early pregnancy.

GENERAL PREVENTION

• Maintain routine schedule of diet (consistent CHO intake), medication, and exercise.
• Self-monitoring of blood glucose (SMBG) or continuous glucose monitoring (CGM) (1)[A]

  • Particularly helpful for asymptomatic hypoglycemia and if taking insulin or secretagogue.
  • Consider CGM rather than SMBG with T1DM or those requiring multiple injections of insulin, insulin pump therapy, or pregnant diabetic
• Diabetes treatment and teaching programs (DTTPs) especially for high-risk type 1 patients, which teach flexible insulin therapy to enable dietary freedom
• Hypoglycemia may be decreased with use of insulin analogs, continuous SC insulin infusion (CSII) pumps, and CGM systems.