How Hypoglycemia is investigated ?

A venous plasma glucose concentration below 50 mg/dl is called hypoglycaemia. The diagnosis of hypoglycemia necessitates the presence of Whipple’s triad. This consists of:

Fig. Whipple's Triad

1)   Symptoms of hypoglycemia

2)   Low plasma glucose concentration and

3)   Symptoms relieved by glucose administration.

Fig. Classical Signs and symptoms of Hypoglycemia

The classic signs and symptoms of hypoglycemia are trembling, sweating, nausea, rapid pulse, lightheadedness, hunger and epigastric discomfort. Neuroglycopenia can be seen in severe cases (headache, confusion, blurred vision, dizziness, and seizures).

The most common cause of hypoglycemia are drugs like propranolol, salicylate, oral hypoglycemic drugs with long half life like chlorpropamide, insulin secreting sulfonylureas, glycogen storage disease, alcoholism, septicemia, hepatic failure, Addison’s disease etc. 

REGULATORY RESPONSE TO HYPOGLYCEMIA

In hypoglycemia, the shortage of glucose in neurons activates hypothalamus, and an autonomic response to restore and maintain glucose supply initiates which has many effects like:

ACTIVATION OF SYMPATHETIC NERVOUS SYSTEM

 α-ADRENERGIC EFFECTS

• Inhibition of endogenous insulin release
• Increased cerebral blood flow (peripheral vasoconstriction)

 β-ADRENERGIC EFFECTS:

• Stimulation of glycogenolysis
• Stimulation of glucagon release (also α cells can sense directly)
• Stimulation of lipolysis
• Inhibition of muscle glucose uptake
• Increased cerebral blood flow (by increasing cardiac output)

CATECHOLAMINE RELEASE FROM ADRENAL MEDULLA

• Potentiates the α and β adrenergic effects

ACTIVATION OF PARASYMPATHETIC NERVOUS SYSTEM

• Stimulates vagus nerve
• Stimulation of gastric acid secretion
• Stimulation of parotid salivary secretion. 

There is hierarchy of response of counter-regulatory hormones; glucagon, epinephrine, cortisol and GH. Glucagon and epinephrine are rapidly acting hormones whereas latter two are slow acting and are active at late phase of hypoglycemia. During fast state the first mechanism is inhibition of endogenous insulin secretion and followed by release of counter regulatory hormones in hierarchy.

Decreased endogenous insulin occurs at glucose level 80 mg/dl; increase glucagon, adrenaline, cortisol and GH secretion at 60 mg/dl and development of hypoglycaemic symptoms occurs at 50 mg/dl and impairment of cognitive function at 40 mg/dl. 

INVESTIGATION OF HYPOGLYCEMIA

First is demonstration of hypoglycemia and second to identify the cause of hypoglycemia.

DEMONSTRAITON OF HYPOGLYCEMIA

MEASUREMENT OF BLOOD GLUCOSE

Measurement of blood glucose (insulin, C-peptide) during acute neuroglycopenia (characterized by sweating, anxiety, hunger, palpitation and weakness) is the best test for the diagnosis of hypoglycemia.

PROVOCATION TEST:

Prolonged fast:

This is the single most useful test to evaluate suspected hypoglycemia. The aim of this test is to demonstrate spontaneous hypoglycemia in the presence of neuroglycopenic symptoms during prolonged fasting for 48 h, and that the symptoms resolve on glucose administration.

During the fasting period blood glucose, insulin, C-peptide is measured at every 4-6 hours. But as glucose level falls below 50 mg/dl frequent sample must be taken. About 95% of patient will develop hypoglycaemia within 48 h. Measurement of β-hydroxybutyrate and its raising presence indicates suppression of insulin release and fast can be terminated by giving glucose when FBS becomes <45 mg/dL and patient exhibit signs or symptoms of hypoglycemia.

Mixed meal test:

This is used to investigate patients who experience postprandial symptoms, for the possibility of reactive hypoglycemia. Meal is ingested and plasma glucose measured every 30 min for 6h and at any time during symptomatic phase. Patients developing neuroglycopenia symptoms during hypoglycemia, but not at other times during the test, are considered to have postprandial hypoglycemia.