hypoglycaemia

Last edited 08/2021 and last reviewed 11/2023

Hypoglycaemia describes the situation of an abnormally low plasma glucose concentration.

It may be defined biochemically as a plasma glucose of less than 2.5 mmol/l (although the threshold for symptoms is variable); note that a BM stix estimation may be subject to user error and it is always wiser to obtain a lab estimation.

The Diabetes Audit and Research in Tayside, Scotland (DARTS) study of 367,501 people, 8655 of whom had diabetes, identified a total of 244 episodes of severe hypoglycemia in 160 patients (1)

• overall prevalence was 7.1% in patients with type 1 diabetes and 7.3% in patients with type 2 diabetes treated with insulin, compared with 0.8% in patients with type 2 diabetes treated with an oral sulfonylurea

Notes:

• as plasma glucose levels decrease in people without diabetes, various physiological consequences occur. At levels of 4.2 mmol/L,endogenous insulin secretion is suppressed (2)
  • at approximate levels of 3.7 mmol/L, increased glucagon, adrenaline, cortisol and growth hormone secretion occur
  • when levels of 3.1 mmol/L are reached, autonomic symptoms appear. Cognitive dysfunction occurs at levels of approximately 2.5 mmol/L
  • levels vary greatly between individuals and can be affected by the antecedent glucose control in any individual
    
    
• people with diabetes, the severity of hypoglycemia is defined based on the clinical manifestations of the episodes
  
  • a level of less than 4.0 mmol/L is suggested for definition of hypoglycemia in patients treated with insulin or an insulin secretagogue (2)
    • mild hypoglycemia
      • with a mild episode of hypoglycemia, autonomic mediated symptoms are present and the patient is able to self-treat
    • moderate hypoglycemia
      • with a moderate episode, autonomic and neuroglycopenic mediated symptoms occur and the patient is able to self-treat
    • severe hypoglycemia
      • with severe hypoglycemia, the patient requires the assistance of another person, unconsciousness may occur and the plasma glucose is typically less than 2.8 mmol/L

    • Neurogenic (Autonomic) (approximate percentage that symptoms occur)	Neuroglycopenic
      Trembling (32-78%)	Difficulty concentrating (31-75%)
      Palpitations (8-62%)	Confusion (13-53%)
      Sweating (47-84%)	Weakness (28-71%)
      Anxiety (10-44%)	Drowsiness (16-33%)
      Hunger (39-49%)	Vision changes (24-60%)
      Nausea (5-20%)	Difficulty speaking (7-41%)
      Tingling (10-39%)	Headache (24-36%)
      	Dizziness (11-41%)
      	Tiredness (38-46%)

  • hypoglycemia unawareness occurs when the threshold for autonomic warning symptoms to appear becomes lower than the threshold for the neuroglycopenic symptoms, so that the first signs of hypoglycemia will often be confusion or loss of consciousness
    • attenuated epinephrine response to hypoglycemia in type 1 diabetes is a marker of an attenuated autonomic, sympathetic neural as well as adrenomedullary, response that causes the clinical syndrome of hypoglycemia unawareness-loss of the warning, largely neurogenic symptoms of developing hypoglycemia (3)
      • because it compromises behavioral defenses against developing hypoglycemia (e.g., the ingestion of food), hypoglycemia unawareness is also associated with a high frequency of severe iatrogenic hypoglycemia
  • asymptomatic hypoglycemia is the presence of a biochemically low glucose level without any symptom
    
    
  • American Diabetes Association (4) classification of hypoglycemia:
    • Level 1 - glucose <70 mg/dL (3.9 mmol/L) and >= 54 mg/dL (3.0 mmol/L)
    • Level 2 - glucose <54 mg/dL (3.0 mmol/L)
    • Level 3 - a severe event characterized by altered mental and/or physical status requiring assistance for treatment of hypoglycemia

Reference:

• 1)Leese GP et al.Frequency of severe hypoglycemia requiring emergency treatment in type 1 and type 2 diabetes: a population-based study of health service resource use. Diabetes Care. 2003 Apr;26(4):1176-80.
• 2) Yale JF et al.Canadian Diabetes Association clinical practice guidelines for the prevention and management of hypoglycemia in diabetes. Canadian Journal of Diabetes Care 2001.
• 3) Cryer PE, Davis SN, Shamoon H. Hypoglycemia in diabetes. Diabetes Care. 2003 Jun;26(6):1902-12
• 4) American Diabetes Association (ADA). Glycemic Targets: Standards of Medical Care in Diabetes-2021. Diabetes Care 2021 Jan; 44(Supplement 1): S73-S84