Hypoglycemia

Glucose Supply

The brain needs glucose, but the CNS can neither make it nor store it – plasma glucose must remain 60-150mg/dL

Sources of Glucose – GI absorption, glycogenolysis, hepatic and renal gluconeogenesis

Glucose Homeostasis – varies tremendously depending upon fuel supply

Post absorptive state (2 hrs after eating) – glucose production = utilization (brain), using hepatic glycogen (100 g)

Prolonged fast (24 hrs) – glucose mainly from gluconeogenesis, but plasma glucose is only slightly decreased

little hepatic glycogen (10 g), so muscle and adipose tissue switch to FFA’s; ketones supply 50% of brain’s energy

Extended fast (20 days) –ketones supply 80-90% of brain’s energy; 50% blood glucose from renal gluconeogenesis

Hypoglycemia – ordinarily defined as a venous plasma glucose < 50 mg/dL, clinically when symptoms present

Triggering of Counter-regulation – most important antihypoglycemic hormone is glucagon; also Epi, cortisol, GH

threshold is 50 mg/dL – absolute glucose level is more important than change, although rate of fall is also important

Symptoms of Hypoglycemia – due to primary response (adregenic) or secondary effects (neuroglycopenic)

Adrenergic (Neurogenic) – mediated by Epi in response to ß blood glucose – usually 1^st signs ("warning signs" for diagnosis)

Neuroglyopenic – due to low brain glucose; signs that the cells of the body are starving for glucose

Two types of Hypoglycemia

(1) Fasting Hypoglycemia (postabsorptive) – >6hrs after eating, in general more medically significant – Etiologies:

(a) Drugs – exogenous insulin, antihyperglycemic drugs (sulfonylureas, etc.) – increase insulin amount or effect

EtOH – inhibits gluconeogenesis (Ý NADH), no effect on glycogenolysis – problems only after glycogen depleted

salicylates – aspirin overdose, especially in kids

propranolol and other anti-adrenergic drugs – block Epi, inhibiting body’s ability to counter low blood glucose

(b) Hyperinsulinism – frequently due to pancreatic b -cell adenoma or (rarely) carcinoma – other causes:

infants born to diabetic mothers – have Islet hyperplasia because of the glucose challenge in utero

Nesidioblastosis or Beckwith-Wiedemann Syndrome (overgrowth synd) – both involve Islet hyperplasia

(c) Defective Counter-regulation – many possibilities

hormone deficiencies – glucagon (rare), Epi, cortisol (Addison’s disease), growth hormone

enzyme deficiency – glycogen storage diseases, gluconeogenic enzyme deficiency, carnitine deficiency (can’t use FFA so use up glucose too fast)

diabetes – glucagon deficient so Epi is critical – and long standing diabetes leads to ß Epi so no warning signs

Somogyi phenomenon Þ blood sugar is low at night and body overcompensates Þ high sugar in morning

(d) Inadequate Glucose Production – anything that compromises the liver’s ability to make glucose

(2) Postprandial Hypoglycemia – "Reactive Hypoglycemia" occurring 2-4 hours after a big meal

1% from inhibition of glycogenolysis (galacosemia, fructose intolerance) or GI surgery (dumping syndrome)

99% of cases are idiopathic – possibly due to low counter-regulatory threshold (insulin is not increased)

overdiagnosed due to false positive Oral Glucose Tolerance Test (OGTT) – normal subjects can have 50 mg/dL

Diagnosis and Treatment

Diagnosis:

Whipple’s triad:

Gold standard for diagnosis is ß blood glucose, Ý C-peptide (=Ý insulin), and ß counter-regulatory proteins when symptoms appear

self glucose monitoring during symptoms may help to establish a pattern

Treatment:

Chronic Hypoglycemia – drugs that block insulin release (diazoxide) or insulin response (hydrocortisol)

Acute hypoglycemia – 10-20 g carbohydrates (, IM glucagon for diabetic individuals, IV glucose (response < 15 min)

giving glucose never hurts, so it should always be done if hypoglycemic coma is suspected