Hypoglycemia

Hypoglycemia unrelated to exogenous insulin administration is an uncommon clinical syndrome characterized by low plasma glucose, symptomatic sympathetic stimulation, and CNS dysfunction. Hypoglycemia is caused by many drugs and diseases. Diagnosis requires blood tests during the presence of symptoms or during a 72-hour fast. Treatment of hypoglycemia involves providing glucose in combination with treatment of the underlying cause.

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Causes hypoglycemia

Symptomatic hypoglycemia unrelated to diabetes treatment is relatively rare, partly because of counterregulatory mechanisms to compensate for low blood glucose levels. Glucagon and epinephrine levels rise in response to acute hypoglycemia and are the first line of defense. Cortisol and growth hormone levels also rise acutely and play a significant role in recovery from prolonged hypoglycemia. The threshold for the release of these hormones is usually higher than for symptomatic hypoglycemia.

Causes of physiological hypoglycemia can be classified as reactive (postprandial) or fasting, insulin-mediated or non-insulin-mediated, drug-induced or non-drug-induced. Insulin-mediated causes include exogenous administration of insulin or insulin secretagogues, or insulin-producing tumors (insulinomas).

A useful practical classification is based on the clinical condition: the occurrence of hypoglycemia in apparently healthy or ill patients. Within these categories, causes of hypoglycemia may be divided into drug-induced and other causes. Pseudohypoglycemia occurs when blood samples are processed slowly in unprepared tubes and glucose is taken up by cells such as red blood cells and white blood cells (especially when their numbers are increased, as in leukemia or polycythemia). Factitious hypoglycemia is true hypoglycemia caused by nontherapeutic administration of insulin or sulfonylureas.

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Symptoms hypoglycemia

Stimulation of autonomic activity in response to low plasma glucose causes increased sweating, nausea, fear, anxiety, increased heart rate, possibly hunger, and paresthesia. Insufficient glucose supply to the brain causes headache, blurred or double vision, impaired consciousness, limited speech, seizures, and coma.

Under controlled conditions, they begin at plasma glucose levels of 60 mg/dL (3.33 mmol/L) or lower, and CNS symptoms occur at levels of 50 mg/dL (2.78 mmol/L) or lower. However, hypoglycemia, the symptoms of which have obvious signs, is much more common than the condition itself. Many people with these glucose levels do not have symptoms, while many people with normal glucose levels have symptoms characteristic of hypoglycemia.

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Diagnostics hypoglycemia

In principle, the diagnosis of hypoglycemia requires the determination of a low glucose level [< 50 mg/dL (< 2.78 mmol/L)] during the occurrence of hypoglycemic symptoms and the response of symptoms to glucose administration. If the physician is present when symptoms develop, a blood glucose test should be taken. If the glucose level is within the normal range, hypoglycemia is excluded and no further testing is required. If the glucose level is very low, serum insulin, C-peptide, and proinsulin measured in the same tube may help differentiate insulin-mediated from non-insulin-dependent, factitious from physiologic hypoglycemia and may obviate the need for further testing. Insulin-like growth factor-2 (IGF-2) levels may help identify non-islet cell tumors (IGF-2 secreting tumors), a rare cause of hypoglycemia.

However, physicians are rarely present when patients develop symptoms suggestive of hypoglycemia. Home glucometers do not reliably detect hypoglycemia, and there are no clear cutoff HbA1c levels that differentiate prolonged hypoglycemia from normoglycemia. Thus, the need for more expensive diagnostic testing is based on the likelihood of underlying disorders causing hypoglycemia, with the patient's clinical manifestations and comorbidity.

The diagnostic standard is a 72-hour fast under controlled conditions. Patients drink only nonalcoholic, noncaffeinated beverages, and plasma glucose is measured at baseline when symptoms develop and every 4 to 6 hours or 1 to 2 hours if glucose falls below 60 mg/dL (3.3 mmol/L). Serum insulin, C-peptide, and proinsulin should be measured during periods of hypoglycemia to differentiate endogenous from exogenous (factitious) hypoglycemia. The fast is stopped after 72 hours if the patient has remained asymptomatic and glucose levels have remained within the normal range, or earlier if glucose levels have been below 45 mg/dL (2.5 mmol/L) and symptoms of hypoglycemia have occurred.

At the end of the fast, β-hydroxybutyrate is measured (its level should be low in insulinoma), serum sulfonylureas are measured to detect drug-induced hypoglycemia, and plasma glucose levels are measured after intravenous glucagon administration to detect an increase, which is typical of insulinoma. There are no data on the sensitivity, specificity, and predictive value of determining hypoglycemia using this scheme. There is no specific low glucose value that would unambiguously establish pathological hypoglycemia during a 72-hour fast; women have lower fasting glucose levels compared with men, and glucose levels up to 30 mg/dL can be observed without the development of characteristic symptoms. If symptomatic glycemia has not been observed for 72 hours, the patient should exercise for 30 minutes. If hypoglycemia does not develop after this, the probability of insulinoma is completely excluded, and further testing is not indicated.

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Treatment hypoglycemia

Immediate treatment of hypoglycemia includes provision of glucose. Patients who are able to eat may drink juices, sugar water, or glucose solutions; eat candy or other sweets; or chew glucose tablets if symptoms develop. Infants and young children may be given 10% dextrose solution by intravenous infusion at a rate of 2-5 mg/kg bolus. Adults and older children who are unable to drink or eat may be given glucagon 0.5 (< 20 kg) or 1 mg subcutaneously or intramuscularly or 50% dextrose solution 50-100 ml intravenously by bolus, with or without ongoing infusion of 5-10% dextrose solution in an amount sufficient to relieve symptoms. The effectiveness of glucagon administration depends on the glycogen stores in the liver; Glucagon has little effect on plasma glucose levels in fasting patients or during prolonged periods of hypoglycemia.

Underlying causes of hypoglycemia should also be treated. Islet and nonislet cell tumors should first be localized and then removed by enucleation or partial pancreatectomy; there is a 10-year recurrence rate of about 6%. Diazoxide and octreotide can be used to control symptoms while the patient is being prepared for surgery or when surgery is refused or impossible. The diagnosis of islet cell hypertrophy is most often made by exclusion, when an islet cell tumor has been sought but is not found. Drugs that cause hypoglycemia and alcohol should be stopped. Hereditary and endocrine disorders, liver, kidney, and heart failure, sepsis, and shock should also be treated.