Diabetes with hypoglycemia
Introduction
Introduction to diabetes with hypoglycemia Under normal circumstances, the body maintains blood glucose in a relatively narrow range through a complex, systematic and precise regulation mechanism. Once the individual causes glucose utilization for more than glucose supply, the stability of the blood glucose environment is broken. Concentrations begin to decrease, such as: increased insulin or insulin analogues in the blood; insufficient glycosaminoglycans such as cortisol, glucagon, growth hormone, and adrenaline; severely inadequate sugar intake and/or absorption; glycogen stores Insufficient and/or decomposition disorders; tissue consumption of excess glucose and reduced gluconeogenesis, etc., is generally considered to be the standard for hypoglycemia: plasma glucose concentration is less than 2.8mmol / L (50mg / dl). basic knowledge The proportion of illness: 0.005%, the incidence of diabetes patients is as high as 3% Susceptible people: no specific population Mode of infection: non-infectious Complications: diabetic ketoacidosis
Cause
Diabetes associated with hypoglycemia
(1) Causes of the disease
1. Common causes and classification of hypoglycemia There are many reasons for clinically leading hypoglycemia, and there are many classification methods. For example, it can be divided into organic hypoglycemia and functional hypoglycemia according to the etiology. According to the pathogenesis, it can be divided into blood glucose utilization. Excessive and insufficient blood glucose production, the clinically commonly used method of classification of hypoglycemia is combined with the pathogenesis of hypoglycemia and the clinical features of hypoglycemia episodes, which are more practical and useful for finding the cause.
2. Common causes and causes of diabetes hypoglycemia Diabetes is a syndrome characterized by hyperglycemia, but during its long-term treatment, especially during the treatment with insulin and insulin secretagogues, hypoglycemia It is a relatively common adverse reaction and one of the common emergencies in diabetic patients.
(1) Insulin: In insulin-treated diabetic patients, hypoglycemia associated with insulin application is mainly found in:
1 insulin dose is too large: this is common in the early stage of diabetes treatment and intensive treatment of diabetes, occasionally visible calculation errors of patients or medical staff, such as 100u / ml human insulin error 40u / ml of animal or human insulin caused by insulin dose Excessive withdrawal; some patients may also cause dose extraction errors due to visual impairment;
2 Exercise: In non-diabetic individuals, exercise can significantly increase glucose uptake in muscle tissue (20 to 30 times higher than the baseline value), but the increase in glucose utilization can be compensated by increased glucose production in the liver and kidneys. At the same time, accompanied by inhibition of B cell insulin secretion (multiple secondary to exercise-induced increase in catecholamine secretion), it is generally not hypoglycemic, but this situation does not exist in insulin-treated diabetic patients, such as excessive exercise is not timely Adjusting insulin can often lead to hypoglycemia after exercise, especially when insulin is injected in the vicinity of exercise-related muscles, and insulin absorption can be significantly promoted. Therefore, it is better to prepare the injection site for insulin before exercise.
3 inappropriate food intake: patients who do not eat or eat on time after insulin injection is one of the most common causes of hypoglycemia in insulin-treated diabetic patients, which can occur when patients go out to eat or travel outside, at this time the patient can Carry some dry food with you to prevent hypoglycemia; if you have a bad appetite when you are sick, you should reduce the insulin dose properly. If you can't eat it, you should take intravenous rehydration, glucose and insulin.
4 other:
A. Local environmental changes at the injection site: hot water bath after insulin injection can promote insulin absorption, insulin injection too deep into muscle tissue, insulin absorption accelerates;
B. Combined renal insufficiency: When renal function deteriorates, insulin inactivation and clearance are reduced, renal gluconeogenesis is reduced, and food intake may be reduced, and insulin dose should be reduced in time;
C. Diabetic stomach cramps: due to diabetic autonomic neuropathy, delayed gastric emptying, often cause repeated hypoglycemia in patients treated with insulin;
D. Stress: Under various stress states, such as infection, surgery, trauma, etc. or mental stress, the insulin requirement is often increased to control hyperglycemia. Once the stress state is relieved or eliminated, the insulin dose should be restored to the time. Pre-excitation dose, otherwise it is easy to cause hypoglycemia;
E. Concomitant hypocortisolemia: Patients with type 1 diabetes may have a combination of primary adrenal insufficiency or concurrent pituitary dysfunction leading to a decrease in blood cortisol levels, increased sensitivity to insulin and prone to hypoglycemia. The amount of insulin needed should be reduced.
(2) Oral hypoglycemic drugs: All oral hypoglycemic drugs that promote insulin secretion (including sulfonylureas and non-sulfonylurea insulin secretagogues) can cause hypoglycemia, of which glibenclamide and chlorsulfuron Urea (half-life up to 35h, domestically discontinued) leads to the highest and most serious risk of hypoglycemia, and the longest duration, especially when applied, starting from small doses, especially in elderly patients. In contrast, D860, mepyrazine, gliclazone, glimepiride (such as yamoli) and some non-sulfonylurea insulin secretagogues such as repaglinide and nateglinide The rate is lower and lighter, and clinical use of biguanide, -glucosidase inhibitor, thiazolidinedione derivative (insulin sensitizer) and pure Chinese medicine preparation generally does not cause clinical hypoglycemia, but If combined with insulin or sulfonylureas, it may increase the chance of hypoglycemia. Some Chinese patent medicines (such as Xiaoke Pills) may be mixed with sulfonylureas, and should be used to avoid hypoglycemia. .
(3) Combined use of certain drugs: Many other drugs combined with insulin or sulfonylurea-treated diabetic patients may enhance hypoglycemia induced by insulin or sulfonylureas. Common drugs include:
1 Ethanol: Ethanol can inhibit the gluconeogenesis of the liver. The maintenance of blood glucose on fasting depends mainly on the effect of hepatic gluconeogenesis. In addition, drinking can mask the symptoms of hypoglycemia. Therefore, diabetics should avoid drinking alcohol as much as possible. Drinking on an empty stomach should be avoided.
2 Salicylate: Salicylic acid has a certain hypoglycemic effect. It was once used as a blood sugar lowering drug, but it has a large dose (such as aspirin 4-6g/d) and its High-dose-related adverse reactions have been discontinued as hypoglycemic drugs. The mechanism of hypoglycemia of such drugs is not well defined, and may be related to high-dose stimulation of insulin secretion and inhibition of renal excretion; in addition, they can replace protein-bound sulfonate Amidoureas can increase the chance of hypoglycemia in diabetic patients treated with sulfonylureas. For example, patients with diabetes should be treated with salicylic drugs such as aspirin for antipyretic and analgesic. Start with a small dose and monitor blood sugar. .
3 blockers: Diabetic patients treated with beta blockers, especially non-selective beta blockers, may have an increased chance of hypoglycemia and may cause severe hypoglycemia in some patients, beta The mechanism of hypoglycemia caused by body blockers may be mainly due to inhibition of sympathetic stimulation or adrenaline output, thereby inhibiting the output of glycogen, which blocks the adrenaline reversal during hypoglycemia. Regulatory effects often delay the recovery of hypoglycemia. Another important issue is that beta blockers inhibit the important signs and symptoms of adrenaline-mediated tachycardia and palpitations during hypoglycemia. Patients are alert to hypoglycemia, therefore, appropriate attention should be paid to diabetic patients treated with beta blockers, reports from UKPDS and JNC-VI suggest that although beta blockers have some such as lowering peripherals Vascular blood flow, prolonging the recovery time of hypoglycemia and masking the symptoms of hypoglycemia, but the use of beta blockers in diabetic patients can be similar to or greater than non-diabetic patients The results of reduced cardiovascular events.
4 Others: Some drugs such as angiotensin converting enzyme inhibitors, monoamine oxidase inhibitors, phenytoin, tricyclic antidepressants, sulfa drugs and tetracycline combined with hypoglycemic drugs may also lead to hypoglycemia in diabetic patients increase.
(4) Intentional overdose of insulin or sulfonylureas: It is rare that some people with diabetes (especially those with some mental disorders or for the attention of others around them or for some other reason) may be over-applied. Insulin or sulfonylureas cause artificial hypoglycemia. If it is caused by exogenous insulin, patients often show hyperinsulinemia, and the immunological activity of plasma C-peptide is significantly inhibited.
(5) Type 2 diabetes: early type 2 diabetes patients have early perception of glucose stimulation by B cells, early insulin release disorder, leading to early postprandial hyperglycemia, delayed peak release of insulin and increased insulin release response, often Reactive hypoglycemia occurred 3 to 5 hours after a meal, also known as delayed hypoglycemia after a meal.
(two) pathogenesis
1. The response of hormones to hypoglycemia
Hormones play an important role in regulating blood sugar concentration and glucose metabolism. Insulin is the only hypoglycemic hormone in the body, and there are many types of glycosaminoglycans. The mechanism of action and the effect of glycemic action are different. The intensity and order of the reaction are also different. The glycosaminoglycans mainly include glucagon, adrenaline, norepinephrine, growth hormone and glucocorticoid. When the blood sugar is low, the release of the above-mentioned glucosamines increases, and the blood glucose concentration increases rapidly. Play a counteracting effect on hypoglycemia.
(1) catecholamine: sympathetic nerve excitement during hypoglycemia, increased release of catecholamines, promotion of mobilization and decomposition of muscle tissue glycogen; increased decomposition of adipose tissue triglycerides, increased plasma free fatty acid concentration, increased gluconeogenesis in liver and kidney; Directly stimulates the breakdown of hepatic glycogen and the gluconeogenesis of the adrenal cortex. In addition, cardiovascular and other manifestations of sympathetic excitation during hypoglycemia are important manifestations of hypoglycemia, such as diabetic patients with cardiovascular autonomic neuropathy and At the same time, the -blocker is used, and the sympathetic response is weakened.
(2) Glucagon: The increase of plasma catecholamine concentration in hypoglycemia and hypoglycemia can stimulate the release of glucagon from islet A cells. The increase of blood glucagon concentration can promote the decomposition of liver glycogen and liver. The output of sugar and enhance the activity of hepatic gluconeogenesis enzyme. Glucagon is a key hormone that affects the recovery of blood sugar during acute hypoglycemia. If hypoglycemia occurs slowly, the effect of glucagon is reduced. Diabetes mellitus In patients with hypoglycemia, there is a defect in the glucagon secretion reaction.
(3) Glucocorticoid: When central nervous tissue hypoglycemia, the release of pituitary ACTH increases, further leading to an increase in plasma glucocorticoid levels, which promotes the decomposition of adipose tissue, promotes protein catabolism, enhances liver and The kidneys convert amino acids into glucose.
(4) Growth hormone: When hypoglycemia, the release of pituitary growth hormone is also increased, its role in antagonizing hypoglycemia is relatively weak, but growth hormone can antagonize the utilization of glucose by insulin, promote lipolysis, and provide liver and adrenal cortex. A substrate of gluconeogenesis.
(5) Insulin: When hypoglycemia is relieved by the stimulation of B cells by glucose and the concentration of circulating catecholamines, the endogenous insulin secreted by B cells is significantly reduced, which is beneficial for the recovery of hypoglycemia, because of hypoglycemia: sugar Pro- and lipolysis increased; hepatic gluconeogenesis and ketogenic effects increased; adrenal cortex gluconeogenesis increased enzyme activity; and it reduced tissue utilization of glucose, but hypoinsulinemia in insulin and sulfonylureas The resulting hypoglycemia does not exist.
(6) Cholinergic neurotransmitters: Acetylcholine is released from parasympathetic nerve endings during hypoglycemia, and the vagus nerve is associated with hunger in hypoglycemia. In addition, the sympathetic postganglionic fibers that support the sweat glands also release acetylcholine during hypoglycemia ( This is in contrast to all other sympathetic postganglionic fibers), which is associated with hyperhidrosis during hypoglycemia.
(7) Threshold of hormone response to hypoglycemia: In normal people, when the blood glucose level is 3.6-3.9mmol/L (65-70mg/dl), the response of glycemic hormone is activated, and the symptoms of hypoglycemia are often as low as 2.8. ~3.0mmol / L (50 ~ 55mg / dl) appeared, normal people's blood sugar is rarely as low as 2.8mmoL / L, but sometimes in the long-term fasting state, some normal women's blood sugar can be as low as 1.7mmol / L (30mg /dl) and asymptomatic, this may be due to the increased production of ketone bodies to meet the energy requirements of the nervous system.
2. Central nervous hypoglycemia
The brain is one of the main organs that consume glucose in the body. Its metabolic glucose rate is about 1.0mg/(kg·min), which is equivalent to a normal adult consumes 100g of glucose for 24h, while the central nervous system itself has very limited energy reserves (2.5-3.0). mol/g brain tissue), the energy required is almost entirely dependent on the provision of blood sugar. In the case of chronic starvation and intravenous infusion of ketone bodies, the brain can also use ketone bodies for energy metabolism, but in the case of acute hypoglycemia, Ketone bodies can not compensate for the lack of glucose, and neurohypoglycemia (neuroglycopenia), the order of central nervous system damage is related to the degree of brain development and evolution, the more evolutionary cell development, the more sensitive to hypoglycemia, generally starting from the cerebral cortex, Subsequently, the subcortical center and brainstem are involved successively, and finally the medulla oblongata causes changes in respiratory and circulatory function. If hypoglycemia persists or can not be corrected for a long time (generally considered to be more than 6 hours), irreversible morphological changes may occur in brain cells. Congestion, multiple punctiform hemorrhage, cerebral edema, ischemic spot necrosis and brain softening, etc., even if blood sugar is corrected, It also often leaves the sequela of brain dysfunction.
Prevention
Diabetes combined with hypoglycemia prevention
1. Extensively carry out publicity and education to enable diabetic patients and their families to understand the causes and symptoms of hypoglycemia. Mild hypoglycemia should be treated in time to prevent hypoglycemia from developing from mild to low blood sugar to coma.
2. Diabetic people should regularly check blood sugar, urine sugar, and find a low blood sugar tendency to work closely with the physician to determine the cause of hypoglycemia, or timely oral syrup or prescribed medical treatment.
3. Inject insulin or oral hypoglycemic agents to avoid large doses or increase the dose by yourself to prevent hypoglycemia.
4. After the insulin injection, it is necessary to eat according to the regulations, and it is forbidden to eat fasting after the insulin injection.
5. The diet should be reasonable to prevent partial eclipse from eating only protein and fat. This is a wrong diet and should be avoided.
6. Frequent hypoglycemia often occurs before breakfast to exclude islet B cell tumor. Islet B cell tumor can be surgically removed. If the tumor cannot be surgically removed, diazoxide 0.4g can be taken to prevent hypoglycemia. / times, 3 times / d, the drug's adverse reactions are sodium retention, gastrointestinal discomfort, long-term use can occur skin pigmentation, can also take the growth inhibitory octreotide (Octreotide) trade name Sandostatin (Sandostatin) .
Complication
Diabetes complicated with hypoglycemia complications Complications, diabetic ketoacidosis
It is more common in clinical practice. Because diabetes is a complex disease, it can coexist with several diseases. Before or during treatment, when the condition worsens, it is necessary to think of hyperglycemia, and also think of the development of some comorbidities. Or hypoglycemia caused by improper treatment.
1. Diabetes is basically stable or general treatment, if it is repeated hypoglycemia, consider having pituitary, thyroid, adrenal gland and other hypofunction or liver and kidney dysfunction; or with some tumors with insulin enhancement.
2. Severe diabetic acidosis. When insulin is used, blood sugar is increased, which indicates that there is reactive hyperglycemia (Somogyi effect) or acidosis after hypoglycemia. After treatment is improved, respiratory balance, blood pressure rise and other conditions are stable. Excessive skin sweating, irritability, and rapid heart rate should consider the possibility of hypoglycemia.
Symptom
Diabetes with hypoglycemia symptoms Common symptoms Hypoglycemia Anxiety Diabetes coma convulsions Drowsiness Nervousness Disorders Diplopia Attention deficit
The clinical manifestations of hypoglycemia are affected by the decline in blood glucose (lower blood glucose, the more severe the symptoms), the rate of hypoglycemia (the faster the sympathetic symptoms, the slower the speed, the more obvious the symptoms of brain dysfunction) , the frequency of attacks (recurrent hypoglycemia, decreased ability of patients to respond to hypoglycemia), the age of the patient (the older, the worse the sympathetic response to hypoglycemia), with or without autonomic neuropathy (especially with diabetes) Cardiovascular autonomic neuropathy, the performance of sympathetic nerve excitation may not be obvious) and the combination of certain drugs (such as beta blockers) and other factors.
1. Symptoms and signs of sympathetic excitation: The body releases a large amount of catecholamines due to hypoglycemia, which can be clinically characterized by sweating, palpitations (increased heart rate), hunger, anxiety, nervousness, paleness, limb tremors, and mildly elevated blood pressure. The faster the blood sugar declines [the rate of blood glucose decline > 1mg / (dl · min) or > 0.06mmol / (L · min)], the more obvious the symptoms of sympathetic excitation, clinically, some patients with diabetes are obviously Symptoms of sympathetic excitation during hypoglycemia, and blood glucose measurement is not low, may be related to the rapid decline in blood glucose, this group of symptoms is not specific for hypoglycemia.
2. Neuropathic hypoglycemia symptoms: Symptoms of dysfunction due to lack of glucose energy supply in the central nervous system, especially brain cells, initially impaired mental and mental activity, manifested as inattention and unresponsiveness And confusion of thought, followed by a series of neuropsychiatric symptoms dominated by central nervous function inhibition, the affected part begins from the cerebral cortex, clinical manifestations of blurred vision, diplopia, hearing loss, lethargy, confusion, behavioral weird, exercise Disorders, ambiguous language, headache and stupor, some patients may show atypical symptoms such as convulsions or epileptic seizures or limb hemiplegia. In the end, coma and respiratory and circulatory failure may occur in severe cases. The lower the blood sugar and the slower the blood sugar declines. The more obvious the manifestation of brain dysfunction, if it is not aware of the warning symptoms of sympathetic excitation during hypoglycemia or the symptoms of sympathetic excitation before neurohypoglycemia, it is called hypoglycemia unawareness.
Examine
Diabetes combined with hypoglycemia check
1. Blood sugar is lower than the lower limit of normal, <2.8mmol / L can diagnose hypoglycemia.
2. Glycated hemoglobin test >7%, may suggest an acute attack of hypoglycemia; <7% may have a longer period of chronic hypoglycemia.
3. Blood, urine ketone body examination: blood ketone body increased, urinary ketone body positive indicates increased fat catabolism, hunger ketosis.
4. Hunger test: Allow patients to completely fast, check blood sugar, insulin, and patient intolerance fasting hunger test at regular (starting every 4 hours), prone to hypoglycemia reaction, generally 85% positive after 24 hours of fasting, 95% positive after 48 hours, very few (about 2%) 72 hours and increased exercise to be positive, if fasting blood glucose <2.8mmol / L, insulin release index > 0.4 should be considered abnormal.
5. Drug challenge test:
(1) Tolbutamide (D860) test: 2g of tolbutamide (D860) was taken on a fasting stomach to avoid gastrointestinal reactions. At the same time, the same amount of sodium bicarbonate was taken orally, and blood was taken once every 1 hour for 3 times. Blood sugar and insulin, normal human blood glucose drops no more than 40% of the baseline value, as follows, the base value is 65%, and/or the blood glucose level after treatment is less than 1.7mmol / L (30mg / dl), lasting more than 3 hours, Or if the insulin level is higher than 120 U/ml, it is abnormal.
(2) Glucagon test: fasting intravenous injection of glucagon 0.03mg/kg body weight, the total amount does not exceed 1mg, measured 3h blood sugar and insulin, normal people's blood sugar rises more than 40% of the basic value, if hypoglycemia, An insulin level above 150 U/ml is abnormal.
(3) Leucine test: Calculate the dose of leucine at 150mg/kg body weight, and take it orally within 10min. Measure blood glucose and insulin levels for 3h. Normal blood sugar does not change. If there is hypoglycemia, blood insulin level is higher than 40U/ Ml, it is abnormal.
6.C peptide inhibition test: the subject is injected with exogenous insulin to inhibit endogenous insulin secretion, and normal human endogenous insulin is significantly inhibited, which is manifested by a significant decrease in blood C-peptide or insulin levels. U/kg is calculated by intravenous injection of human insulin on an empty stomach, and then the blood C-peptide level is directly measured. The blood C-peptide level of the normal person is decreased by more than 50% of the basic value, and the blood C-peptide level of the insulinoma patient is decreased by <50. %.
Diagnosis
Diagnostic diagnosis of diabetes complicated with hypoglycemia
diagnosis
The diagnosis of diabetic hypoglycemia includes the clinical symptoms of hypoglycemia; the laboratory blood glucose test standard <2.8mmol/L; the condition is rapidly improved after the application of glucose treatment; the diagnosis can be established.
At the same time of diagnosis, the cause of hypoglycemia should be ascertained, and the patient should prevent hypoglycemia from recurring. The differential diagnosis should exclude insulinoma (Insolinoma) hypoglycemia. The incidence of insulin cell tumor is one in a million, insulin cells in adults. 80% of the tumors are single benign tumors, 5% are single malignant tumors, 10% are multiple benign tumors, and the rest are multiple malignant tumors or islet B cell tumor hyperplasia.
Characteristics of insulin cell tumors or islet B cell tumors:
1. Insulin cell tumors have a Whipple triad:
(1) Fasting episodes of hypoglycemia.
(2) Blood sugar is lower than 2.8mmol/L at the onset of hypoglycemia.
(3) Immediately after the injection of glucose.
2. Hunger test: fasting for 48h, 90% of islet cell tumor patients were positive; fasting 72h, 98% of patients were positive.
3. Selective celiac angiography: the diagnostic accuracy is above 80%, and there are few false positives.
Differential diagnosis
The differential diagnosis of hypoglycemia is mainly based on sympathetic excitation symptoms, and it is easy to identify. Patients with brain dysfunction are easily misdiagnosed as neurosis, psychosis, epilepsy or cerebrovascular accident. They should be carefully asked about medical history and physical examination, and timely blood glucose. Measurement and related auxiliary examinations are helpful for identification.
