Hypoglycemia < 4 mmol/L (70 mg/dL)


THE CALL

Overview

  • Hypoglycemia is most commonly iatrogenic.
  • Hypoglycemia: < 4 mmol/L (70 mg/dL)
  • At approximately mean serum glucose concentration of ≤ 55 mg/dL (3.0 mmol/L), normal hunger drive usually induce ingestion of food
    • Normal physiological insulin secretion is suppressed below this level (non-diabetic)
  • Hypoglycemia and symptoms may develop once plasma-glucose utilization > plasma-glucose production/delivery into the circulation (i.e. gluconeogenesis, food digestion)
  • Glucose is brain’s sole energy source.
  • Symptoms may mimic CVA/TIA, epilepsy, MS, psychosis and depend on glucose level and rate of drop.
  • Glycogen released from liver by glucagon and epinephrine.

Etiology

  • Oral antihyperglycemics: sulfonylurea (e.g. glyburide)
    • the half-life of glyburide is 10h; therefore, close glucose monitoring can be indicated for a day after last dose. Metformin, although less prone to induce hypoglycemia, still requires monitoring of glucose levels.
  • Insulin incorrectly prescribed (inadequate sliding scale, too much long-acting insulin, etc.) It is often helpful to simply ask the patient about his insulin regimen.
  • The patient is receiving his insulin or oral antihyperglycemics but is not eating.
  • Acute alcohol Intoxication
  • Medications: Pentamidine, Bactrim, Quinine
  • Liver failure
  • Renal failure
  • Sepsis/Critically ill
  • Hypopituitarism
  • Adrenal Insufficiency
  • Myxedema
  • Insulinoma  (Pancreatic B Cell tumor)
    • Increased C-peptide level
  • Extrapancreatic neoplasm (Rare)
    • hepatocellular carcinoma, retroperitoneal sarcoma, adrenal carcinoma
  • Anti-insulin antibodies or antibodies to insulin receptors (Rare)
  • Counter-regulatory hormone deficiency
  • Hypothermia
  • Dumping syndrome

History/Symptoms

  • < 3.3 mmol/L or 60 mg/dL: sweating, palpitation, hunger, tremor
  • < 2.8 mmol/L or 50 mg/dL: lethargy and obtundation: ABCs!
     
  • Symptoms are variable
    • Diaphoresis, pallor, shakiness, hunger, nausea, dizziness, malaise, headache
    • Tingling around mouth, fingers, AMS, possible seizures (severe)
  • Hypoglycemia without DM
    • History of discrete spells (neurogenic symptoms probably do not have hypoglycemia since no documented low blood-glucose level)
       

Physical Exam/Signs

  • Generally not well in appearance, confusion
  • Cardiac
    • Tachycardia
    • Possible hypotension (i.e. orthostatic)
  • Nervous/Musculoskeletal
    • Tremors
    • Hypersensitivity, especially in extremities and face
    • Weakness
       

Workup

  • Labs/Tests
    • In any suspected hypoglycemic patient, STAT finger-stick blood-glucose level
      • Treatment should be start BEFORE finger stick if warranted (physician discretion)
      • Once patient has been stabilized, in a non-diabetic patient, labs can be collected to determine possible cause of hypoglycemia
    • Non-diabetic
      • Serum insulin levels, C-peptide, pro-insulin, beta-hydroxybutyrate levels
        • Key feature: endogenous hyperinsulinism has high serum insulin levels despite very low serum glucose concentrations (low glucose production vs high glucose utilization)
      • CBC (rule out infection, sepsis)
      • Oral hypoglycemic agent screen
      • Drug screen
         
  • Imaging
    • MRI/CT head if suspect tumor
    • If suspect insulinoma
      • MRI/CT
      • Transabdominal and/or endoscopic ultrasound
         
  • Other Tests/Criteria
    • 1.0 mg glucagon test (edogenous vs exogenous etiology)
    • Insulin antibodies
    • If suspect insulinoma: Hepatic venous insulin levels post-selective pancreatic arterial calcium injections
    • Test to be expected by primary care/internist: 72 hour fast eval and/or post-mixed-meal eval with IV glucagon challenge test
    • Classification of Hypoglycemia in non-diabetics
      • Traditional classification of Post-absorptive (fasting) vs Post-prandial (reactive) is challenged because of overlapping etiologies (i.e. insulinomas, factitious hypoglycemia)
      • More useful categorization determined by establishing wellness vs burden of disease/treatment
        • All hypoglycemic patients should be evaluated for medication etiology
    • Classification of Hypoglycemia in diabetics
      • Severe hypoglycemia: an event requiring assistance of another person to actively administer carbohydrates, glucagon, or resuscitation
      • Symptomatic hypoglycemia: blood glucose (BG) ≤ 70 mg/dL (≤ 3.9 mmol/L) with symptoms
        • Probable hypoglycemia: symptoms without BG determination
      • Relative hypoglycemia: symptoms with BG > 70 mg/dL (> 3.9 mmol/L)
         

Differential Diagnosis

  • DM
  • Surreptitious Insulin injection
  • Alcoholism
  • Sepsis
  • Drug-induced
  • Insulinoma
  • Tumor

Treatment

Hold or adjust insulin.

Depending on symptoms, aiming for > 5 mmol/L (90 mg/dL)

  1. Initial/Prep
    • Therapy should be individualized to patient's specific underlying etiology, the following is a recommended protocol
    • If severe symptomatic hypoglycemia suspected, treat BEFORE finger stick test
    • If patient on subcutaneous insulin drip (insulin pump)
      • Suspend until blood-glucose (BG) > 60 mg/dL (> 3.3 mmol/L), if unconsciousness pull out infusion site if unable to suspend pump
      • Initiate seizure precautions
    • If patient on fluid restrictions or renal restrictions recommended glucose gel
      • Renal restrictions avoid juice or dairy
    • If swallowing restrictions or puree diet (level 1) recommended 4 oz juice with 2 tablespoon thickener (physician discretion)
    • If patient on acarbose recommended use of glucose gel only (sucrose ineffective)
       
  2. Medical/Pharmaceutical Alorgithm
    • Mild
      • Glucose tabs PO, fruit juices, etc.
         
    • BG < 70 mg/dL (< 3.9 mmol/L) and OBTUNDED/uncooperative/NPO
      • DO NOT WAIT TO TREAT
      • If IV access: 50 ml (25 grams) D50 IVP over 2-5 minutes
      • If no IV access with BG < 60 mg/dL (3.3 mmol/L): one dose of 1 mg Glucagon SC, then STAT IV access
        • Glucagon may be ineffective if inadequate glycogen stores
      • Patient turned on side to prevent aspiration
      • Repeat BG measures every 15 minutes, retreat until BG > 70-80 mg/dL (> 3.9-4.4 mmol/L) and no symptoms
        • Glucagon should only be repeated once
      • Feed patient to avoid recurrent episode (if not NPO and able to swallow)
        • If > 1 hour until next meal, give 15-20 grams carbohydrates (i.e. 3 graham crackers)
        • If > 2 hours until next meal, add protein (i.e. 1/2 sandwich)
      • If NPO or still unconscious/uncooperative check IV access and make sure 5% dextrose, recheck BG in 1 hour
         
    • BG > 60 mg/dL (> 3.3 mmol/L) and no symptoms, alert, able to swallow
      • No treatment required if next meal is in < 30 min
      • If > 30 min until next meal, give 15-20 grams carbohydrate (i.e. 4 oz juice, 1 tube dextrose gel, or 1 tablespoon jelly)
      • Check BG every 15 minutes and retreat until BG > 100 mg/dL (> 5.6 mmol/L)
      • Feed patient to avoid recurrent episode (if not NPO and able to swallow)
        • If > 1 hour until next meal, give 15-20 grams carbohydrates (i.e. 3 graham crackers)
        • If > 2 hours until next meal, add protein (i.e. 1/2 sandwich)
       
    • BG is 60-100 mg/dL (3.3-5.6 mmol/L) and SYMPTOMATIC but conscious, cooperative, able to swallow
      • Give 15-20 grams carbohydrate (i.e. 4 oz juice, 1 tube dextrose gel, or 1 tablespoon jelly)
      • Check BG every 15 minutes and retreat until BG > 100 mg/dL (> 5.6 mmol/L) or symptoms resolve
      • If the patient is not NPO, provide food, juices, etc. Otherwise, consider starting a maintenance IV D5W or D10W, especially if the hypoglycemia is 2nd to oral antihyperglycemics or long-acting insulin. Be careful with CHF patients.
      • Hydrocortisone if adrenal insufficiency.
      • Octreotide for sulfonylurea induced hypoglycemia
        • Inhibits pancreatic insulin secretion
      • Feed patient to avoid recurrent episode (if not NPO and able to swallow)
        • If > 1 hour until next meal, give 15-20 grams carbohydrates (i.e. 3 graham crackers)
        • If > 2 hours until next meal, add protein (i.e. 1/2 sandwich)
           
    • BG is 45-59 mg/dL (2.5-3.3 mmol/L) and symptomatic but conscious, cooperative, able to swallow
      • Give 20 grams carbohydrates (i.e. 6 oz juice, 1.5 tubes dextrose gel, or 1.5 tablespoons jelly)
      • Check BG every 15 minutes and retreat until BG > 70 mg/dL (> 3.9 mmol/L) and no symptoms or BG > 80 mg/dL (> 4.4 mmol/L)
      • If the patient is not NPO, provide food, juices, etc. Otherwise, consider starting a maintenance IV D5W or D10W, especially if the hypoglycemia is 2nd to oral antihyperglycemics or long-acting insulin. Be careful with CHF patients.
      • Hydrocortisone if adrenal insufficiency.
      • Octreotide for sulfonylurea induced hypoglycemia
        • Inhibits pancreatic insulin secretion
      • Feed patient to avoid recurrent episode (if not NPO and able to swallow)
        • If > 1 hour until next meal, give 15-20 grams carbohydrates (i.e. 3 graham crackers)
        • If > 2 hours until next meal, add protein (i.e. 1/2 sandwich)
           
    • BG < 45 mg/dL (< 2.5 mmol/L) and symptomatic but conscious, cooperative, able to swallow
      • Give 30 grams carbohydrates (i.e 8 oz juice, 2 tubes dextrose gel, or 2 tablespoons jelly)
      • Check BG every 15 minutes and retreat until BG > 70 mg/dL (> 3.9 mmol/L) and no symptoms or BG > 80 mg/dL (> 4.4 mmol/L)
      • If the patient is not NPO, provide food, juices, etc. Otherwise, consider starting a maintenance IV D5W or D10W, especially if the hypoglycemia is 2nd to oral antihyperglycemics or long-acting insulin. Be careful with CHF patients.
      • Hydrocortisone if adrenal insufficiency.
      • Octreotide for sulfonylurea induced hypoglycemia
        • Inhibits pancreatic insulin secretion
      • Feed patient to avoid recurrent episode (if not NPO and able to swallow)
        • If > 1 hour until next meal, give 15-20 grams carbohydrates (i.e. 3 graham crackers)
        • If > 2 hours until next meal, add protein (i.e. 1/2 sandwich)

     

  3. Surgical/Procedural
    • If hypoglycemia is caused by insulinoma, prep for surgical removal if feasible
       
  4. Prevention
    • Feed patient to avoid recurrent episode (if not NPO and able to swallow)
      • If > 1 hour until next meal, give 15-20 grams carbohydrates (i.e. 3 graham crackers)
      • If > 2 hours until next meal, add protein (i.e. 1/2 sandwich)

Disposition

  1. Admit patient if acute treatment does not resolve or surgical consult is required
  2. Consult PCP, endocrinologist, surgery, if required
  3. Discharge protocols and instructions for patient for preventing another episode if acute treatment resolves




ITE 2013, Q#111.
A 69-year-old male with type 2 diabetes mellitus comes to your office for a routine follow-up visit. He takes insulin glargine (Lantus) as a basal insulin, with meal-time boluses of insulin lispro (Humalog). He reports repeated episodes of hypoglycemia with blood glucose levels in the 40–50 mg/dL range. He treats them appropriately by consuming about 15 g of carbohydrates. He has a history of severe episodes of hypoglycemia requiring emergency services. In addition to insulin, his current medications include simvastatin (Zocor), lisinopril (Prinivil, Zestril), and aspirin. He has both diabetic autonomic neuropathy and retinopathy.

Which one of the following factors in this patient’s case is the most significant predictor of severe hypoglycemia?

A) His age
B) His sex
C) His medications
D) His previous episodes of severe hypoglycemia
E) His diabetic autonomic neuropathy

ANSWER: D

  • In patients with type 2 diabetes mellitus, the single most important predictor of severe hypoglycemia is a previous history of severe hypoglycemia that required external assistance. It is thought that hypoglycemia reduces the body’s protective responses (glucagon and epinephrine) to subsequent episodes of hypoglycemia.
  • Increased blood glucose level goals and increased self-monitoring of blood glucose are the most important measures for avoiding further episodes.
  • Less significant risk factors for hypoglycemia include:
    • Advanced age
    • Use of five or more medications
    • African-American ethnicity, and
    • Recent hospital discharge.
  • Diabetic autonomic neuropathy may be a risk factor but this has not been definitively established.