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Last reviewed: 25.06.2018

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Hypoglycemia not associated with exogenous administration of insulin is an infrequent clinical syndrome characterized by low plasma glucose, symptomatic stimulation of the sympathetic nervous system, and dysfunction of the central nervous system. Hypoglycemia is caused by many drugs and diseases. Diagnosis requires blood tests during the presence of symptoms or within 72-hour fasting. Treatment of hypoglycemia is to provide glucose in combination with the treatment of the cause.

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Causes of the hypoglycemia

Symptomatic hypoglycemia, not associated with the treatment  of diabetes, is relatively rare, in part because of the presence of counterregulatory mechanisms to compensate for low blood glucose levels. The levels of glucagon and epinephrine increase in response to acute hypoglycemia and are the first line of defense. The levels of cortisol and growth hormone also increase sharply and play a significant role in recovery after prolonged hypoglycemia. The threshold for the production of these hormones is usually higher than for the symptoms of hypoglycemia.

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

A convenient practical classification is based on the clinical state: the appearance of hypoglycemia in externally healthy or sick patients. Within these categories, the causes of hypoglycemia can be subdivided into drug-induced and other causes. Pseudohyglycaemia is observed when processing blood samples in unprepared vials and absorbing glucose by cells such as red blood cells and leukocytes (especially if their number increases, for example, in leukemia or polycythaemia). Artificial hypoglycemia is a true hypoglycemia caused by the non-therapeutic use of insulin or sulfonylurea preparations.

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Symptoms of the hypoglycemia

Stimulation of autonomic activity in response to low plasma glucose causes increased sweating, nausea, a sense of fear, anxiety, heart palpitations, perhaps hunger and paresthesia. Insufficient intake of glucose into the brain causes headache, fuzzy vision or double vision, impaired consciousness, speech limitation, seizures and to whom.

Under controlled conditions, begin with a plasma glucose level of 60 mg / dL (3.33 mmol / L) or lower, and symptomatology from the CNS is observed at a level of 50 mg / dL (2.78 mmol / L) or lower. However, hypoglycemia, the symptoms that have obvious signs are observed much more often than the condition itself. Many people at the indicated levels of glucose do not have the presence of the corresponding symptomatology, while at the same time many people with normal glucose concentrations have symptoms characteristic of hypoglycemia.

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Diagnostics of the hypoglycemia

In principle, the diagnosis of "hypoglycemia" requires the determination of a low level of glucose [<50 mg / dl (<2.78 mmol / l)] during the presence of symptoms of hypoglycemia, as well as the response of symptoms to the introduction of glucose. If the doctor is present with the development of symptoms, you need to take a blood test to determine the level of glucose. If the level of glycemia is within normal limits, hypoglycemia is excluded and no further analysis is required. If the glucose level is very low, the determination of serum insulin, C-peptide, proinsulin, carried out in the same tube, can help differentiate insulin-mediated from insulin-independent, artificial from physiological hypoglycemia and can eliminate the need for further testing. Determining the level of insulin-like growth factor-2 (IGF-2) can help to identify tumors of non-islet cells (secreting IGF-2), a rare cause of hypoglycemia.

However, doctors are rarely present when patients develop symptoms suggestive of hypoglycemia. Home glucometers do not reliably determine hypoglycemia, there are no clear threshold levels of HbA1c, which differentiate prolonged hypoglycemia from normoglycemia. Thus, the need for more expensive diagnostic testing is based on the likelihood of having underlying abnormalities that cause hypoglycemia, with the patient having clinical manifestations and a concomitant disease.

The standard of diagnosis is 72-hour fasting under controlled conditions. Patients drink only non-alcoholic, non-caffeinated beverages, the plasma glucose level is determined at baseline with symptom development and every 4 to 6 hours or 1-2 hours if the glucose level falls below 60 mg / dL (3.3 mmol / L) . Serum insulin, C-peptide and proinsulin should be determined during periods of hypoglycemia for the differential diagnosis of endogenous and exogenous (artificial) hypoglycemia. Fasting stops after 72 hours, if the patient has no symptoms, and the glucose level is within normal limits, or earlier, if the glucose level was below 45 mg / dl (2.5 mmol / l), hypoglycaemia symptoms were observed.

At the end of fasting, the determination of B-hydroxybutyrate (its level should be low with insulin), serum sulfonylureas for the detection of drug-induced hypoglycemia, plasma glucose level after intravenous glucagon injection to detect an increase that is characteristic of insulinoma is performed. There is no data on the sensitivity, specificity, and prognostic value of determining hypoglycemia according to this scheme. There is no specific low glucose value, which would unambiguously establish pathological hypoglycemia during 72-hour fasting; women have lower fasting glucose levels than men, glucose levels can be observed up to 30 mg / dL without developing characteristic symptoms. If symptomatic glycemia was not observed within 72 hours, the patient should be exercising for 30 minutes. If after this hypoglycemia does not develop, the probability of insulinoma is completely excluded, further research is not shown.

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Treatment of the hypoglycemia

Immediate treatment of hypoglycemia involves providing glucose. Patients who are able to consume food can drink juices, sweet water, glucose solutions; eat sweets or other sweets; chew tableted glucose with the development of symptoms. Newborns and young children may be given an intravenous infusion of 10% dextrose solution at a dose of 2-5 mg / kg bolus. Adults and older children who can not drink or eat glucagon 0.5 (<20 kg) or 1 mg subcutaneously or intramuscularly or 50% dextrose solution 50-100 ml intravenously bolus, with or without continued administration of 5-10% a solution of dextrose in an amount sufficient to stop the symptoms. The effectiveness of glucagon administration depends on glycogen stores in the liver; glucagon does not have a big effect on plasma glucose in patients who are starving, or with a prolonged period of hypoglycemia.

It is also necessary to treat the initial causes of hypoglycemia. Tumor of islet and neostrovkovyh cells must first be localized, and then removed by enucleation or partial pancreatectomy; about 6% of relapses occur within 10 years. Diazoxide and octreotide can be used to control symptoms while the patient is preparing for surgery, or when the surgery is refused or impossible. The diagnosis of islet cell hypertrophy is most often an exception, when an islet cell tumor was searched, but it was not detected. Taking medications that cause a condition such as hypoglycemia, as well as alcohol, should be discontinued. It is also necessary to treat hereditary and endocrine disorders, hepatic, renal and heart failure, sepsis and shock.

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