Diagnosis of diabetes mellitus

In accordance with the definition of diabetes as a syndrome of chronic hyperglycaemia, proposed by WHO in the year 981, the main diagnostic test is the determination of the level of glucose in the blood.

The level of glycemia in healthy people reflects the condition of the insulin apparatus of the pancreas and depends on the method of studying blood sugar, the nature of the blood sample taken for the study (capillary, venous), the age preceding the diet, the time of food intake before the study, and the influence of certain hormonal and medicinal preparations.

To study sugar in the blood, Somogy-Nelson's method, orthotoluidine, glucose-oxidase, allows to determine the true glucose content in blood without reducing substances. The normal parameters of glycemia in this case are 3.33-5.55 mmol / l (60-100 mg%). (For the conversion of the blood sugar value, expressed in mg% or in mmol / l, the following formulas are used: mg% 0.055551 = mmol / L mmol / L x 18.02 = mg%.)

The level of basal glycemia is influenced by eating at night or just before the test; Some increase in blood sugar levels can be promoted by a diet rich in fats, intake of glucocorticoids, contraceptives, estrogens, dihlothiazide diuretics, salicylates, adrenaline, morphine, nicotinic acid, dilantine.

Hyperglycemia can be detected on the background of hypokalemia, acromegaly, Icenko-Cushing's disease, glucosteromas, aldosteromas, pheochromocytomas, glucagonomas, somatostatinomas, toxic goiter, traumas and brain tumors, fever, chronic liver and kidney failure.

For the mass detection of hyperglycemia, indicator paper impregnated with glucose oxidase, peroxidase and glucose-dye compounds is used. Using a portable device - a glucometer that operates on the principle of a photolarometer, and the test paper described, it is possible to determine the glucose content in the blood in the range from 50 to 800 mg%.

Reduction of blood glucose relative to normal is observed in diseases caused by absolute or relative hyperinsulinism, prolonged starvation and severe "physical stress, alcoholism.

[1], [2], [3], [4], [5], [6], [7],

Oral tests used to determine glucose tolerance

The most widely used oral standard glucose tolerance test with a load of 75 g of glucose and its modification, as well as a test with test breakfast (postprandial hyperglycemia).

The standard glucose tolerance test (SPT), in accordance with the WHO recommendation (1980), is a study of fasting glycemia and every hour for 2 hours after a single oral load of 75 g of glucose. For the examined children, glucose loading is recommended, based on 1.75 g per 1 kg of body weight (but not more than 75 g).

A prerequisite for the test is the acceptance of not less than 150-200 grams of carbohydrates per day for patients with food for several days on the eve of it, since a significant reduction in the amount of carbohydrates (including easily digestible) helps normalize the sugar curve, which complicates the diagnosis.

The change in blood indices in healthy individuals, patients with impaired glucose tolerance, as well as questionable results when using the standard glucose tolerance test are presented in the table.

Blood glucose in the oral (75 g) glucose tolerance test, mmol / l

Research conditions	Whole Blood		Plasma of venous blood
	venous	capillary
Healthy
On an empty stomach	<5.55	<5.55	<6.38
2 hours after the load	<6.70	<7.80	<7.80
Impaired glucose tolerance
On an empty stomach	<6.7	<6.7	<7.8
2 hours after the load	> 6.7 <10.0	> 7.8 - <11.1	> 7.8 - <11.1
Diabetes
On an empty stomach	> 6.7	> 6.7	> 7.8
2 hours after the load	> 10.0	> 11.1	> 11.1

Since the highest value in assessing glycemic parameters during the oral glucose tolerance test has a blood sugar level 2 hours after the glucose load, the WHO Expert Committee on Diabetes Mellitus has proposed its short version for mass studies. It is performed similarly to the usual, but the study of sugar in the blood is done only once every 2 hours after loading with glucose.

For the study of glucose tolerance in clinic and ambulatory conditions, a carbohydrate load test can be used. In this case, the subject should eat a test breakfast containing not less than 120 g of carbohydrates, 30 g of which should be easily digestible (sugar, jam, jam). The study of blood sugar is carried out 2 hours after breakfast. The test indicates a violation of glucose tolerance in the event that the glycemia exceeds 8.33 mmol / l (pure glucose).

Other tests with a glucose load of diagnostic benefits, according to WHO experts, do not have.

In diseases of the gastrointestinal tract, accompanied by a violation of glucose absorption (postrezektsionny gastric syndrome, malabsorption), a test is used with intravenous glucose.

Methods for diagnosing glucosuria

Urine of healthy people contains very small amounts of glucose - 0.001-0.015%, which is 0.01-0.15 g / l.

With most laboratory methods, the above amount of glucose in urine is not determined. A slight increase in glucosuria, reaching 0.025-0.070% (0.25-0.7 g / l), is observed in newborns during wool 2 weeks and elderly people over 60 years. The release of glucose in the urine of healthy people depends little on the amount of carbohydrates in the diet, but it can increase by 2-3 times compared to the norm against a background of a high-carbohydrate diet after a prolonged fasting or a glucose tolerance test.

In a massive population survey for the purpose of identifying clinical diabetes use methods that quickly detect glucosuria. The indicator paper Glucotest (production of Reagent, Riga) has a high specificity and sensitivity. Similar test paper is produced by foreign companies called test-taip, clinicix, glucotest, biofan, etc. The indicator paper is impregnated with a composition consisting of glucose oxidase, peroxidase and ortholidine. A strip of paper (yellow) is lowered into the urine; in the presence of glucose, the paper changes color from light blue to blue after 10 seconds due to the oxidation of ortholidine in the presence of glucose. The sensitivity of the above types of test paper ranges from 0.015 to 0.1% (0.15-1 g / l), while urine is determined only by glucose without reducing substances. To detect glucosuria, you must use 24-hour urine or collected for 2-3 hours after a test meal.

The glucosuria found by one of the above methods is not always a sign of the clinical form of diabetes mellitus. Glucosuria can be a consequence of renal diabetes, pregnancy, kidney disease (pyelonephritis, acute and chronic nephritis, nephrosis), Fanconi syndrome.

Glycosylated hemoglobin

The methods allowing to reveal transient hyperglycemia include the definition of glycosylated proteins, the period of their presence in the body varies from 2 to 12 weeks. Linking to glucose, they seem to cumulate it, representing a kind of memory device that stores information about the blood glucose level "Blood glucose memory"). Hemoglobin A in healthy people contains a small fraction of hemoglobin A _1c, which includes glucose. The percentage (glycosylated hemoglobin (HbA _1c ) is 4-6% of the total hemoglobin .In patients with diabetes mellitus with constant hyperglycemia and with a tolerated glucose tolerance (with transient hyperglycemia), the process of switching glucose into the hemoglobin molecule increases, which is accompanied by an increase in the fraction of HbA _1c. Recently discovered and other small fraction of hemoglobin - a _1a and a _1b, which also have the ability to bind to glucose in diabetic patients total content of heme. A globin ₁ in blood exceeds 9.10% -. A value typical for healthy individuals Transient hyperglycaemia is accompanied by increased hemoglobin levels A ₁ and A _1c for 2-3 months (during the period of life of an erythrocyte) and after normalization of blood sugar level. Methods of column chromatography or calorimetry are used to determine glycosylated hemoglobin.

Determination of fructosamine in serum

Fructosamines belong to the group of glycosylated proteins of blood and tissues. They arise in the process of nonenzymatic glycosylation of proteins during the formation of aldimine, and then ketoamine. An increase in fructosamine (ketoamine) in the blood serum reflects a constant or transient increase in blood glucose levels for 1-3 weeks. The final reaction product is a formazan, the level of which is determined spectrographically. In the blood serum of healthy people, 2-2.8 mmol / l of fructosamine is contained, and if there is a violation of glucose tolerance - more.

[8], [9], [10], [11], [12], [13], [14], [15]

Determination of C-peptide

Its level in the blood serum allows to assess the functional state of the P-cell apparatus of the pancreas. Determine the C-peptide by radioimmunoassay test kits. Its normal content in healthy individuals is 0.1-1.79 nmol / L, according to the test set by Hoechst, or 0.17-0.99 nmol / l, according to Byk-Mallin-crodt (1 nmol / L = 1 ng / mlx0.33). In patients with type 1 diabetes mellitus, the level of C-peptide is lowered, in type II diabetes mellitus it is normal or elevated, and in patients with insulinoma it is increased. By the level of C-peptide, it is possible to judge endogenous secretion of insulin, including against the background of insulin therapy.

[16], [17], [18], [19]

Determination of immunoreactive insulin

The study of immunoreactive insulin (IRI) makes it possible to judge the secretion of endogenous insulin only in patients who have not received insulin preparations and have not received them before, since antibodies that distort the result of the determination of immunoreactive insulin are formed to exogenous insulin. The content of immunoreactive insulin in healthy people in the serum is 0-0.29 μED / ml. I type of diabetes mellitus is characterized by a decreased, and type II - normal or increased basal insulin level.

[20], [21], [22], [23], [24], [25], [26], [27],

A trial with tolbutamide (according to Unger and Madison)

After examining the blood sugar in the blood, an intravenous injection of 20 ml of a 5% solution of tolbutamide is administered to the patient on an empty stomach and after 30 minutes the sugar in the blood is re-examined. In healthy individuals, blood sugar is reduced by more than 30%, and in diabetics - less than 30% to the baseline. In patients with insulinoma, blood sugar drops by more than 50%.

[28], [29], [30], [31], [32]

Glucagon

The content of this hormone in the blood is determined by the radioimmunological method. The normal values are 0-60 ng / l. The level of glucagon in the blood increases with decompensated diabetes, glucagon, starvation, physical activity, chronic liver and kidney diseases.

If the disease has arisen in childhood or adolescence and for a long period was compensated by the introduction of insulin, then the question of the presence of type I diabetes is beyond doubt. A similar situation arises in the diagnosis of Type II diabetes, if the compensation of the disease is achieved by diet or sugar-lowering oral medications. Difficulties usually arise when the patient, who was previously classified as suffering from type II diabetes, needs to be transferred to insulin therapy. Approximately 10% of patients with type II diabetes have an autoimmune lesion of the islet apparatus of the pancreas, and the question of the type of diabetes is solved only with the help of a special examination. A method that allows in this case to establish the type of diabetes is the study of the C-peptide. Normal or elevated blood serum values confirm the diagnosis of type II, and significantly lower - type I.

Methods for detecting a potential violation of glucose tolerance (NTG)

To the contingent of persons with potential NTG, as is known, are children of two patients with diabetes of parents, a healthy twin of a pair of monogens, if the second is suffering from diabetes (especially type II), mothers who gave birth to children weighing 4 kg or more, as well as patients with a genetic marker of sugar type I diabetes. The presence of histocompatibility in diabetic HLA antigens in various combinations increases the risk of the incidence of type I diabetes mellitus. Predisposition to diabetes mellitus type II can be expressed in redness of the face after taking 40-50 ml of wine or vodka, if it is preceded (in 12 hours in the morning) by taking 0.25 g of chlorpropamide. It is believed that in people susceptible to diabetes, under the influence of chlorpropamide and alcohol, enkephalins and the expansion of the skin vessels are activated.

Potential violation of glucose tolerance should also be attributed to the syndrome of inadequate secretion of insulin, expressed in recurring clinical manifestations of spontaneous hypoglycemia, and also (an increase in the body weight of patients that may precede the development of NTG or clinical diabetes for several years. The parameters of GTT in the subjects at this stage are characterized by the hyperinsulinemic type of the sugar curve.

For the detection of diabetic microangiopathy, life biopsies of the skin, muscles, gums, stomach, intestines, kidneys. Light microscopy can detect proliferation of endothelium and perithelium, dystrophic changes in the elastic and argyrophilic walls of arterioles, venules and capillaries. With the help of electron microscopy, it is possible to detect and measure the thickening of the basement membrane of the capillaries.

To diagnose the pathology of the organ of vision, according to the methodological recommendations of the Ministry of Health of the RSFSR (1973), it is necessary to determine the severity and field of view. With the help of biomicroscopy of the anterior part of the eye, it is possible to detect vascular changes in the conjunctiva, limbus, iris. Direct ophthalmoscopy, fluorescent angiography allows to assess the state of the retinal vessels and to reveal the signs and severity of diabetic retinopathy.

Early diagnosis of diabetic nephropathy is achieved by identifying microalbuminuria and renal biopsy. Manifestations of diabetic nephropathy must be differentiated from chronic pyelonephritis. The most characteristic features of it are: leukocyturia in combination with bacteriuria, asymmetry and changes in the secretory segment of the renogram, an increase in the excretion of beta _2- microglobulin in the urine. For diabetic nephromicroangiopathy without pyelonephritis, the increase of the latter is not observed.

Diagnosis of diabetic neuropathy is based on the examination of the patient by a neurologist with the involvement of instrumental methods, including electromyography, if necessary. Autonomic neuropathy is diagnosed by measuring the variation in cardio intervals (which is reduced in patients) and performing an orthostatic test, examining the vegetative index, and others.