Gestational diabetes (diabetes of pregnant women)

Description:

The Gestational Diabetes Mellitus (GDM) (WHO, 1999) — the hyperglycemia belonging to the categories the diabetes mellitus (DM) or the broken tolerance to glucose which arose or for the first time revealed during pregnancy, and is not excluded a possibility that disturbance of carbohydrate metabolism could precede pregnancy, but it was not established.
According to large-scale epidemiological researches GSD it is diagnosed approximately for 4% of pregnant women of kavkazoidny race. Prevalence of GSD can vary from 1 to 14% (on average 7%) that depends on the analyzed population of women and frequency of use of the oral glyukozotolerantny test (OGTT) applied to diagnosis of a disease. Prevalence and incidence of GSD in our country is not known as epidemiological researches according to the international standards of studying of this problem were not conducted. The program of screening and diagnosis of GSD is also badly organized. At the same time according to WHO data in the populations similar in number to Russia, namely in the European Union countries and the USA in 2009 230.000 cases of GSD were recorded.

Reasons of gestational diabetes (diabetes of pregnant women):

During pregnancy, in process of maturing of a placenta, insulin resistance gradually increases. The main role in this process is played by fetoplacental hormones (placental lactogen and прогрестерон) and mother's hormones (cortisol, estrogen, prolactin) which concentration also increases in blood with increase in durations of gestation. This process is compensated by increase in products and decrease in clearance of endogenous insulin of mother. Insulin resistance is aggravated with increase in caloric content by the accepted mother of food, decrease in physical activity, and a weight increase.

In the presence of internal causes, such as genetic predisposition to type SD2, obesity, etc., secretion of insulin becomes insufficient for overcoming insulin resistance, as leads to emergence of a hyperglycemia.

The pathogeny of SD1 of type, other SD types which can debut for the first time during pregnancy and also belong to the category GSD, differs in nothing from that at nonpregnant women.

Symptoms of gestational diabetes (diabetes of pregnant women):

The gestational diabetes mellitus has no the clinical manifestations connected with a hyperglycemia more often such as polyuria, polydipsia, weight reduction, itch Therefore it is necessary to carry out active screening of this disease.

Obstetric and perinatal complications.
The hyperglycemia at mother leads to development of a diabetic fetopathy. Risk of development of inborn malformations and misbirths at GSD same as in the general population it is also not connected with SD decompensation as often GSD develops after end of an organogenesis at a fruit.

The decompensation of GSD can be the reason of approach of perinatal death. At GSD the preeclampsia and an eclampsia develops more often that quite often demands the emergency delivery by operation of Cesarean section.

The diabetic fetopathy is one of the main reasons for perinatal losses at women with GSD. It quite often causes premature births, asphyxia at the birth, metabolic and other disturbances of adaptation of newborns to an extrauterine life and are the most frequent reasons of naonatalny diseases and mortality.

The main substrate for fetation is glucose which the fruit receives from mother as it cannot independently synthesize it. Glucose gets to a fruit by means of the facilitated diffusion. A transplacental carrier of glucose at the person is GLUT-1. Also freely get through a placenta and whale bodies. The hyperglycemia and a ketonemiya are the main trigger substances in start of the mechanism of development of a diabetic fetopathy.

The hyperglycemia in itself leads to morphological changes of the forming placenta. At a chronic decompensation of SD at mother in a placenta the thickening of walls of vessels comes to light, by the end of pregnancy even atherosclerotic damage of spiral arteries, focal necroses of a sintitsiotrofoblast takes place. The placenta increases in sizes, due to proliferation of a cytotrophoblast, hypostasis and fibrosis of a stroma ворсин, branchings and increases in their general surface. Decrease in volume of intervillous space, leads to decrease in a blood-groove in a fetoplacental complex and to a chronic hypoxia of a fruit which already develops at the high HbA1c level at mother, having high affinity to oxygen.

Excess intake of glucose to a fruit after the 13th week of pregnancy leads to a hypertrophy and a hyperplasia of its β-cells. According to experimental and clinical observations it leads to a fetalis giperinsulinemiya, than generally and the further pathological changes developing at a fruit are caused. So in plasma of an umbilical cord and amniotic liquid of fruits with a macrosomia high levels of the general and connected insulin, S-peptide, insulinopodobny factors rosta1 and 2 were found.

The decompensation of carbohydrate metabolism at mother during the first 2 trimeters of pregnancy can lead on the contrary to exhaustion of β-cells of a fruit, to a gipoinsulinemiya and afterwards to development of a syndrome of a delay of pre-natal growth of a fruit.

After the 28th week of pregnancy when the fruit has an opportunity independently to synthesize triglycerides and to create a hypodermic fatty tissue, the fetalis giperinsulinemiya is the main reason for development of a syndrome of an advancing of pre-natal fetation owing to stimulated activation of a lipogenesis at a fruit. At dynamic ultrasonography (ultrasonography) increase in the main sizes of a fruit in comparison with the real term of a gestation more than for 2 weeks, or> the 90th percentile comes to light according to tables of dynamics of pre-natal growth of a fruit. Others of BONDS signs of the beginning diabetic fetopathy are the hydramnion, a disproportion of the sizes of a fruit, puffiness of fabrics and a hypodermic fatty tissue that is also caused by a giperinsulinemiya at a fruit owing to a decompensation of SD of mother. Separate article of the Horde V. F is devoted to ultrasonic signs of a fetopathy.

Against the background of a chronic hypoxia synthesis of fetalis hemoglobin (HbF) having bigger affinity to oxygen and glucose in comparison with HbA that promotes aggravation of a hypoxia increases. The last is the reason of increase in an erythrogenesis at a fruit because of considerable activation of synthesis of fetalis erythropoetin.

The organomegaliya, generally at the expense of a liver and a spleen develops. The considerable delay of formation and development of pulmonary fabric in a fruit against the background of SD decompensation at mother takes place.

The decompensation in itself of SD during the 3rd trimester can be the reason of perinatal losses. Tranzitorny rises in level of a glycemia at mother on 36 – 38 week of pregnancy during the day before meals can lead of more than 7,8 mmol/l (whole capillary blood) to antenatal death of a fruit.

Diabetic fetopatiyayavlyatsya by the main reason for neonatal diseases of the children born from mothers with GSD. Even at the full-term pregnancy doctors to neonatologa should deal with functionally and morphologically unripe newborns who are often demanding stage treatment.

At the birth of the child treat phenotypical signs of a diabetic fetopathy: the macrosomia, dysplastic obesity, a crescent-shaped face, a short neck which swam away eyes, a hypertrichosis, pastosity, hypostases standing, a waist, the expressed shoulder girdle, a long trunk, short extremities, a cardiomyopathy, a hepatomegalia, a splenomegaly. Such child is externally very similar to the patient with a hypercorticoidism syndrome.

Macrosomia. It is accepted to understand the birth of the child weighing more than 4000 g at the full-term pregnancy as a macrosomia or> the 90th percentile according to tables of intrauterine growth of a fruit at premature pregnancy. The macrosomia against the background of GSD occurs at mother in 25-42% of cases in comparison with 8-14% in the general population. The macrosomia is the reason of more frequent delivery by Cesarean section, and also patrimonial traumatism. The clavicle fracture, paralysis of a phrenic nerve, shoulder dislocation, paralysis of Erba, pheumothorax, injuries of the head, a neck and internals, fruit asphyxia in labor belong to birth trauma which are often connected with the birth of the large child in natural patrimonial ways. Asphyxia can lead to acute fatal changes of the newborn: insufficiency of function of lungs, kidneys and central nervous system.

Respiratory frustration. The Respiratory Distress Syndrome (RDS), or a disease of hyaline membranes as its main manifestation, is connected with immaturity of lungs and is the main reason for approach of post-natal death of newborns from mother with GSD. The risk of development of RDS in such children is 5,6 times higher, than in the general population. Development of a syndrome directly correlates with extent of compensation of SD at mother. The hyperglycemia at mother and developing thereof a giperinsulinemiya of a fruit result in deficit of surfactant and increase risk of RDS at newborns. The risk of RDS increases by 5 times at delivery of the pregnant woman before the 38th week of pre-natal fetation. Heart diseases, phrenic hernia, aspiration, a pneumomediastinum, pheumothorax and tranzitorny a tachypnea are meconium other reasons of respiratory frustration at newborns from mother with GSD.

Newborn's hypoglycemia. The hyperglycemia of mother is the main reason for a fetalis hyperglycemia, a fetalis giperinsulinemiya and a neonatal hypoglycemia. At such newborns glikogensintetichesky function of a liver, a gluconeogenesis, and also secretion of a glucagon are reduced. A hypoglycemia of newborns glucose level in whole capillary blood < 1 7 ммоль л у недоношенных и 2 2 ммоль л у доношенных детей. Этот диагноз является лабораторным. Так как HbF имеет еще большее сродство к глюкозе по сравнению с HbA лабораторное оборудование должно находиться непосредственно в операционной и отделении реанимации новорожденных. Средства самоконтроля для констатации a target="_blank" href="index-2169.htm" tppabs="medicalmeds.eu/endokrinologiya/gipoglikimija/">of a hypoglycemia is considered cannot be used. Portable laboratory express analyzers of HemoCue (Sweden) - a classical sample of the diagnostic equipment "point-of-care" – diagnosis in the place of observation of the patient, allowing the doctor in real time, if necessary repeatedly to conduct researches, to quickly make decisions.  The HemoCue system consists of two parts: specially developed a microditch disposable, containing a dry reactant and the analyzer calibrated industrially. In comparison with the international reference method (ICSH method) the accuracy of the HemoCue systems makes ±1,5%. Numerous researches also showed excellent comparability to various laboratory systems. As parties precisely correspond each other, there is no need for repeated calibration or regulation of devices between parties a microditch. Including, in the HemoCue systems the two-wave method of measurement allowing to avoid influence of a turbidity of blood on result of the analysis is used: HemoCue analyzers have the built-in electronic system of self-checking. Every time at inclusion of a photometer this system automatically checks functioning of the optical device. At constantly included photometer this check is carried out each two hours. Everyone a ditch is made according to the strict requirements corresponding or exceeding requirements of the managements (GMP) for Practice of good production Fda.Fotometr HemoCue Glucose 201+ is two-wave (660 nanometers for measurement of glucose and 840 nanometers for compensation of a turbidity). Can be kept up to 600 results with the indication of date and time in memory. It is necessary for the analysis of level of glucose only 5 мкл for capillary blood.

Clinical manifestations of a hypoglycemia of newborns are: unusual crying, apathy, apnoea, cardiac standstill, spasms, cyanosis, hypothermia, hypotonia, excitement, lethargy, tremor, tachypnea.

Glycemia level at mother at the time of delivery> 6,9 mmol/l often is complicated by the newborn's hypoglycemia which can develop in 30 minutes after bandaging of an umbilical cord, persistirovat within 48 hours after the birth or develop in 24 hours after the birth. Frequency of a hypoglycemia of newborns varies from 21 to 60% while clinical symptoms of a hypoglycemia are present only at 25-30% of newborns.

The complications developing in pregnancy time at mother with GSD.
Some complications of pregnancy, being characteristic not only for GSD, nevertheless, are more often observed at women with this disease. The preeclampsia (PE) is noted 4 times more often even in the absence of the previous vascular complications. More often infections of uric ways, a premature rupture of fetal membranes and premature births develop. The last complications, perhaps, are connected with existence of a hydramnion and an infection. The macrosomia of a fruit, PE and disturbance of a functional condition of a fruit are indications to delivery of pregnant women with GSD by operation of Cesarean section. Also puerperal bleeding is more often noted that can be connected with uterus restretching at a hydramnion and the large sizes of a fruit.

Diagnosis:

Women with high risk have development of GSD in the presence of two and more of above-mentioned signs (SD at the immediate family, obesity, disturbance of carbohydrate metabolism in the anamnesis, a glucosuria) at the first address OGTT from 75 g of glucose is carried out. If GSD does not come to light, then the test repeats between 24 and 28 weeks of pregnancy.

To all women with average risk of development of GSD oral тестс 75 g of glucose are carried out between 24 and 28 weeks of pregnancy.

To women with low risk of development of GSD the oral test from 75 g of glucose is not carried out.

Technique of carrying out OGTT from 75 g of glucose. Before test the patient within 3 days has to be on a usual diet, carbohydrate-rich (more than 150 g of carbohydrates a day) and to adhere to physical activity, usual for herself. In the evening before test it is necessary to eat food containing 30-50 g of carbohydrates. OGTT needs to be carried out in the morning after night starvation within 8-14 hours during which it is possible to drink only water. During test it is not allowed to smoke, go. It is necessary to consider all factors which can affect test results. So, for example, some medicines (glucocorticoids and tokolitik), and also intercurrent infections can reduce tolerance to carbohydrates. After a fence of the first test of plasma of a venous blood on an empty stomach the level of a glycemia is measured immediately as when obtaining the results characteristic of the diagnosis of GSD, the test stops. At identification of a normoglikemiya or the broken glycemia on an empty stomach, the patient within 5 minutes has to drink the solution prepared from 75 g of glucose in the form of dry matter and 250-300 ml of water. The beginning of reception of solution of glucose is considered the beginning of the test. In 2 hours to be carried out repeated sampling of plasma of a venous blood.

At a glycemia level research in venous plasma blood samples are taken in a test tube with sodium fluoride (6 mg on 1 ml of whole blood) and EDTA. Then immediately (within the next 30 minutes) are centrifuged for prevention of spontaneous glycolysis. It is known that even in the presence of preservatives glycemia level in whole blood at the room temperature can decrease by 10% and more. If right after centrifuging not to be carried out definitions of a glycemia, then plasma should be frozen. Patients with a normal hematocrit have a concentration of glucose in whole blood ~ 15% lower, than in plasma, and in an arterial blood ~ is 7% higher, than in plasma.

The diagnosis of GSD is made to pregnant women at whom glycemia indicators under WHO recommendations correspond to criteria of diagnosis of SD or the broken tolerance to glucose. Value of the broken glycemia on an empty stomach during pregnancy is not established yet (WHO, 1999). To all the pregnant woman with NGN recommends carrying out OGTT from 75 g of glucose. If results of a research meet standard, then repeatedly the test is surely carried out on 24-28 weeks of pregnancy. On earlier terms of GSD often does not come to light, and establishment of the diagnosis after 28 weeks not always prevents development of a diabetic fetopathy. To all women having risk factors of development of GSD, even at a normoglikemiya OGTT from 75 g of glucose is carried out.

Accidental determination of level of a glycemia by a laboratory method (WHO, 1999)> 11,1 mmol/l (> 200 mg/dl) in whole capillary blood or in plasma of a venous blood during the day, or a glycemia on an empty stomach> 7,0 mmol/l (> 126 mg/dl) in plasma of a venous blood and> 6,0 mmol/l in whole capillary blood enough for diagnosis of GSD also does not demand further confirmation.

Measurement of level of a glycemia is taken in laboratory by means of fermental methods (glyukozo-oksidazny, hexokinase or glyukozo-degidrogenazny). Means of self-checking are not used for screening and diagnosis of GSD. The analysis of the HbA1c level also did not prove as sensitive diagnostic test for identification of GSD. Glikirovaniye of proteins is not fermental process which depends on hyperglycemia duration. In this regard there are several problems in use of determination of level of glycated proteins as diagnostic tests:
at pregnant women the level of a glycemia is on an empty stomach lower, than at nonpregnant;
during pregnancy постпрандиальныйуровень glucose is higher;
in connection with acceleration of an erythrogenesis during pregnancy the HbA1c level is lower than normative indicators for 20%;
during screening GSD, duration of any potential disturbance of tolerance to glucose can be too short.

The glucosuria is not diagnostic criterion of GSD as many pregnant women several times during the day can have a glucosuria. It is connected with increase in a glomerular filtration rate, decrease in a renal threshold for glucose and a canalicular reabsorption of glucose during pregnancy. However existence of a glucosuria demands measurement of level of a glycemia, and with risk factors carrying out OGTT from 75 g of glucose.

Clinical recommendations and assessment of efficiency of treatment
Protocol of maintaining women of SGSD
Starting with the first address and further during all pregnancy, the patients entering into risk group on GSD and the woman with the revealed GSD are observed on an outpatient basis in the specialized center "Pregnancy and Diabetes Mellitus". Observation assumes:
training at Gestational Diabetes Mellitus school;
till 29th week of pregnancy visits to the center are carried out by patients each 2 weeks, and from 29th week – 1raz in a week;
reception is conducted at the same time by the endocrinologist and the obstetrician-gynecologist;
in need of the patient actively are caused on additional visits by phone by the nurse;
patients keep the diary of self-checking where they daily fix indicators of self-checking (table 5). Diary entries are discussed during each planned and additional visit to the center or consultations by phone;
for the emergency consultations access to the doctor-endocrinologist on mobile telephone communication is provided;
after identification of GSD to all patients the corresponding treatment is selected, recommendations about a diet, exercise stresses are made, if necessary the insulin therapy mode is selected.

Recommendations about a dietotherapy have to be aimed at restriction of the use with food of digestible carbohydrates for achievement and stable maintenance of the target objectives of a glycemia. Daily caloric content of food of 30 kcal/kg is recommended to women with normal body weight, and at excess body weight – 25 kcal/kg weighing 120-150% from ideal body weight, 12-15 kcal/kg with a weight> 150% of ideal body weight. Consumption of carbohydrates with a high glycemic index is excluded. Carbohydrates with the high content of food fibers have to make no more than 38-45% of the daily caloric content of food, proteins – 20-25% (1,3 g/kg), fats – do30%. The products containing carbohydrates evenly are distributed during the day on 3 main meals and 2-3 having a snack, with their minimum contents in a breakfast diet.
Women carry out self-checking of a glycemia not less than 4 times a day – natoshchak in 1-2 hours after the main meals. The patients who are on an insulin therapy in addition to a postprandialny glycemia control a glycemia before food, for the night and at 3 o'clock in the morning.
The pregnant women who are on a hypocaloric diet daily on an empty stomach in a morning portion of urine or whole capillary blood need to control ketonic bodies for identification of the insufficient use of carbohydrates or calories with food.
If against the background of a dietotherapy within 1 week it is not possible to reach target indicators of a glycemia, then an insulin therapy is appointed. During pregnancy only genetically engineered insulin of the person or analogs of insulin of ultrashort action (Aspart, Lizpro) are appointed. Use of peroral glucose-lowering drugs during pregnancy is not authorized. The mode of reusable injections of insulin is applied: a combination of insulin of short or ultrashort action before each meal, containing carbohydrates, depending on carbohydrate coefficient, and for the purpose of correction of a hyperglycemia taking into account coefficient of sensitivity and insulin izofanovogochelovechesky in the 2nd or 3rd injections. Use of the fixed mixes of in of the person or the above-stated analogs is possible. Insulin is entered subcutaneously by means of insulin syringes or insulin dosers (handles). At a daily dose of insulin> 100 Pieces transfer of the pregnant woman into continuous pozhkozhny infusion of insulin by means of an insulin pomp is possible. Schemes and doses of an insulin therapy are revised during each visit depending on data of self-checking, dynamics of growth of a fruit, the HbA1c level.
Emergence of ultrasonic signs of a diabetic fetopatiiila of increase in level of insulin in amniotic liquid at the established diagnosis of GSD at the women who are on a dietotherapy also is the indication to purpose of an insulin therapy even if the target objectives of a glycemia are supported.
For each woman the program of physical exercises, according to its opportunities individually is selected.
Necessary dynamic inspections of the patient take place either in the "Pregnancy and Diabetes Mellitus" center or in clinic for women at the place of residence.

Delivery at gestational diabetes:

The gestational diabetes mellitus in itself is not the indication to Cesarean section or delivery till 38th week of pregnancy. Prolongation of pregnancy after the 38th week against the background of a decompensation of SD increases risk of development of a macrosomia of a fruit, without reducing probability of Cesarean section. Therefore delivery on the 38th week of pregnancy is recommended to a thicket at SD. Antihyperglycemic therapy at the time of delivery depends on features of treatment during pregnancy, a way and urgency of delivery. The target objective of a glycemia in whole capillary blood at the time of delivery does not exceed 4-6 mmol/l.
During independent childbirth control of a glycemia in whole capillary blood is carried out each 2 hours at achievement of the target objectives and hourly at tendencies of development hypo - or a hyperglycemia. To the patients who are earlier on an insulin therapy during independent childbirth insulin of short action is entered intravenously by means of an infuzomat. Intravenous infusion of glyukozo-potassium mix begins only at the remaining tendency to a hypoglycemia against the background of already reduced speed of infusion of insulin or its stop.
At GSD after department of an afterbirth an insulin therapy is cancelled, at a tendency to development of a hypoglycemia intravenous infusion of glyukozo-potassium mix is possible. The target objectives of a glycemia in whole capillary blood after delivery: on an empty stomach, before food, before going to bed 4,0-6,0 mmol/l, in 2 hours after food of 6,0-7,8 mmol/l, at night (at 3:00 o'clock) – not less than 5,5 mmol/l.
During operation of Cesarean section control of a glycemia is carried out before operation, before extraction of a fruit, after department of an afterbirth, further each 2 hours at achievement of the target objectives and hourly at a tendency to development hypo - or a hyperglycemia before resuming of a samostoyateny enteroalimentation.
To the women who are before childbirth on a dietotherapy in the perioperatsionny period insulin it is not entered. It is necessary to avoid in/in infusion of the solutions containing glucose and a lactate.
To women on an insulin therapy in the perioperatsionny period insulin of short action is entered intravenously by means of an infuzomat. Intravenous infusion of glyukozo-potassium mix begins only at the remaining tendency to development of a hypoglycemia against the background of already reduced speed of infusion of insulin or its stop. After department of an afterbirth infusion of insulin stops. If necessary intravenous infusion of glyukozo-potassium mix begins. The target objectives of a glycemia in whole capillary blood in the intraoperative period of 4,0-6,0 mmol/l, in the post-operational period: on an empty stomach, before food, before going to bed 4,0-6,0 mmol/l, in 2 hours after food of 6,0-7,8 mmol/l, at night (at 3:00 o'clock) not less than 5,5 mmol/l.

To the women who are on continuous hypodermic infusion of insulin by means of an insulin pomp administration of insulin with a standard basal speed at the time of delivery continues. After department of an afterbirth the speed of infusion decreases twice and intravenous infusion of glyukozo-potassium mix begins, full cancellation of insulin is possible.
If pregnancy at GSD proceeded against the background of compensation of carbohydrate metabolism, the patient was conducted and there was a rodorazreshena according to the protocol, then the forecast for mother and future fruit favorable.