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- Abnormally low concentration of glucose in circulating blood of a patient with diabetes mellitus (DM); often referred to as an insulin reaction
- Classification includes the following (1)[A]:
- Severe hypoglycemia: an event requiring assistance of another person to actively administer treatment
- Documented symptomatic hypoglycemia: an event during which typical symptoms are accompanied by a measured plasma glucose of <70 mg/dL (3.9 mmol/L)
- Asymptomatic hypoglycemia: an event not accompanied by symptoms but a measured glucose of <70 mg/dL (3.9 mmol/L)
- Probable symptomatic hypoglycemia: event with symptoms but glucose not tested
- Pseudohypoglycemia: an event with typical symptoms but glucose ≥70 mg/dL (3.9 mmol/L)
- Hypoglycemia is the leading limiting factor in the glycemic management of type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Severe or frequent hypoglycemia requires modification of treatment regimens, including higher treatment goals.
- Major risk factor for severe hypoglycemic reactions
- Most commonly found in patients with long-standing T1DM and children age <7 years
- From the Accord Study, the annual incidence of hypoglycemia was the following (2)[A]:
- 3.14% in the intensive treatment group
- 1.03% in the standard group
- Increased risk among women, African Americans, those with less than high school education, aged participants, and those who used insulin at trial entry
- From the RECAP-DM study (3)[A]: Hypoglycemia was reported in 35.8% of patients with T2DM who added a sulfonylurea or thiazolidinedione to metformin therapy during the past year.
Etiology and Pathophysiology
- Loss of hormonal counterregulatory mechanism in glucose metabolism
- Diet: too little food (skipping or delaying meals), decreased carbohydrate (CHO) intake
- Medication: too much insulin or oral hypoglycemic agent (improper dose, timing, or erratic absorption)
- Exercise/physical activity: unplanned or excessive
- Alcohol consumption
- Vomiting or diarrhea
- Nearly 3/4 of severe hypoglycemic episodes occur during sleep.
- Autonomic neuropathy
- Illness, stress, and unplanned life events
- Duration of DM >5 years, advanced age, renal/liver disease, congestive heart failure (CHF), hypothyroidism, hypoadrenalism, gastroenteritis, gastroparesis (unpredictable CHO delivery)
- Starvation or prolonged fasting
- Alcoholism: Alcohol consumption may increase risk of delayed hypoglycemia, 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.
- Current smokers with T1DM
- Insulin secretagogues: Sulfonylureas (glyburide, glimepiride, glipizide, etc.) and glinide derivatives (repaglinide, nateglinide) stimulate insulin secretion.
- Hypoglycemia is rare in diabetics not treated with insulin or insulin secretagogues.
- Other antidiabetes medications such as glucagon-like peptide-1 (GLP-1) agonist and sodium-glucose contransporter-2 (SGLT-2) agents carry a lower but present risk of hypoglycemia.
- Severe hypoglycemia is associated with comorbid conditions in patients aged ≥65 years and in users of a long-acting sulfonylurea.
- Intensive insulin therapy (further lowering A1C from 7% to 6%) is associated with higher rate of hypoglycemia.
American Geriatric Society Beers criteria recommend avoiding glyburide and chlorpropamide due to their prolonged half-life in older adults and risk for prolonged hypoglycemic episodes. Medications should be dosed for age and renal function.
Children may not realize when they have hypoglycemia, needing increased supervision during times of higher activity. Children may have higher glycemic goals for this reason. Caregivers should be instructed in use of glucagon (1,4)[A].
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.
- Maintain routine schedule of diet (consistent CHO intake), medication, and exercise (4)[A].
- Regular self-monitoring of blood glucose (SMBG), if taking insulin or secretagogue
- ≥3 times daily testing if multiple injections of insulin, insulin pump therapy, or pregnant diabetic; frequency and timing dictated by needs and treatment goals
- Particularly helpful for asymptomatic hypoglycemia
- 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 prevented with use of insulin analogs, continuous SC insulin infusion (CSII) pumps, and continuous glucose monitoring (CGM) systems.
- If preexercise glucose is <100 mg/dL and taking insulin or secretagogue, then CHO consumption or reduction in medication may prevent hypoglycemia.
Commonly Associated Conditions
- Autonomic dysfunction
- Older type 2 diabetics with severe hypoglycemia have a higher risk of dementia.