Фармакоикономически анализ на лечението на захарния диабет през периода на бременност



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І.38 K. Todorova, N Jekova, M. Guenova. Oxidative stress and preeclampsia in pregnant women with type 1 diabetes. 4 –th International Symposium Diabetes and Pregnancy. Istanbul; Turkey. March 29-31; 2007. Program and Abstracts, p. 66.


The aim is to study the significance of the anlioxydants for reducing the frequency of preeclampsia (PRE) in pregnant women wuh type I diabetes (T1D).

Methods: 31 pregnant women with T1D were devided into two groups: group I (n1 =18) - treated with antioxidants and group 2 (n2= l3) -untreated with antioxidants. A multivitamin preparation, containing vitamin A-15000U. vitamin E-3000U, vitamin C-100 mg and selenium-25 mg was administered. Blood levels of preprandial and postprandial glucose, glycosylated hemoglobin (HbAlc), plasma selenium and glulathione-peroxydase (Gl-I'.x) were measured before and after treatment.

Results: The frequency of PRE in group I was 61.1% 111/18) vs. 55,5% (9/13) in group 2. The mean levels of selenium before treatment were 0,12 (± 0.06) pmol/'l in group 1 and 0,12 (±0.04) pmol/'l in group 2; (p=0.7). The values of selenium after the treatment were 0.1 (±0.09) pmol/l and 0.12 (±0,04) pmol/l; (p<0.06). Thc plasma selenium’ levels were lower between the two groups pregnant, but with no significant difference. The levels of Gl-Px before treatment were 39.l (±1.7) U/g Hb in group I and 47,8 (±1,8) U/g Hb in group 2, also without significantly differencecs (P=0,07). After treatment the mean values of GL-Px were similar [group 1= 41,9 (±1 .9) U/g Hb and group 2= 39.2 (±l,4) U/g Hb ; (P=0.06)]. The frequency of PRE rises from 3,2% to 16.1% with the increase of HbA1 from 8% to over 10%.

Conclusions: The treatment with antioxidants does not decrease the risk of PRE. Only normal glycemia during pregnancy may reduce the risk of PRE in diabetic women.

І.39 N Jekova, K. Todorova. Arterial thrombosis in utero causing arm gangrene in infant of diabetic mother. 4 –th International Symposium Diabetes and Pregnancy. Istanbul; Turkey. 2007; March 29-31. Program and Abstracts; p.110.


We present a rare case of infant of diabetic mother with in utero developed brachial artery thrombosis. The diagnosis - artery thrombosis was made postnatality using Doppler sonography flowmeter and its was confirmed with autopsy. An amputation of the upper limb was done in the early neonatal period and several days after that the newborn died. The death was caused by cardiovascular failure due to intoxication and secondary septic shock.

The mother has suffered of type 1 diabetes mellitus since one year. The metabolic glycaemic control was good before and during pregnancy. The levels of Ha1c in early pregnancy were 6.6% and 7.1% in the late pregnancy. No changes in coagulation were found either in mother or in the newborn. There were no data of hereditary or autoimmune trombopfillia of the mother.

The gangrene of a limb presenting at birth is an extremely rare disease. Approximately twenty two percent of the newborn infants are born from diabetic mothers. The maternal hypeglycemia and the changes in the coagulation factors may cause venous or arterial thrombosis in utero. In these cases maternal diabetes has been in good glycemic control and no increase in cloting factors was found.

Do the metabolic change influence indirectly on the processes of fetal clotting and fibrinolysis is still unknown.



І.40 Todorova-Ananieva K., M. Guenova, K. Petcova, K. Tzatcev, M. Stamenova, E. Konova. Analyses of Carbohydrate Metabolism of Women with High Diabetes Risk. A case control study. XVI Meeting of Balkan Clinical Laboratory Federation. Athens. Greece. 16-18 October; 2008.

The Aim of study is to analyze the changes in carbohydrate metabolism during pregnancy in women with high risk for developing of gestational diabetes (GDM) during pregnancy.

Design of study: A comparative, parallel group, prospective case-control study have been done by the risk evaluation for the development of GDM among pregnant women with high diabetic risk. A 75 grams OGTT have been performed on 66 pregnant women with previous diagnosed polycystic ovary syndrome (PCOS). The levels of blood glucose, C petide, proinsulin and insulin have been evaluated at 12 g.w. and 36 g.w. The autoimmune disturbances have been analyzed by determinantion of anti-GAD65 and anti-insulin autoantibodies.

Methods: The levels of the immunoreactive insulin and С-peptide have been determined by ECLIA. The proinsulin has been measured by ELISA. For the quantitative determination of antibodies to glutamic acid decarboxylase (GAD65) in serums will be used Glutamic Acid Decarboxylase Antibody (GADAb) ELISA kit.

Results: In the case of healthy women, have shown that the basal and the stimulated insulin secretion progressively increase, without pathological change in the blood glucose level. There have been not found significantly difference in basal insulin secretion in early pregnancy between women with normal and pathological OGTT (11.5 ± versus 15.8 ± mU/ml, P. >0.5), but the stimulated insulin secretion after the firs hour glucose loading have been significantly higher in pregnant with GDM (56.9 ± versus 74.8 ± mU/ml, P <0.5). The basal insulin levels measuring at the end of pregnancy have been significantly higher in pregnant with normal OGTT than those insulin levels of pregnant with GDM (20.2 ± versus 14.9 ± mU/ml, P <0.5). The stimulated insulin secretion after the first hour during glucose loading of pregnant with normal OGTT have been also significantly higher (88.4 ± versus 69.1 ± mU/ml, P <0.5). The C-peptide and proinsulin concentrations of women with normal OGTT have increased progressively during the course of pregnancy. The women with GDM have non had synchronic changes in C-peptide and proinsulin secretion with progression of pregnancy. Only 0.6% of the women with GDM had show pathological values of anti-GAD65 and anti-insulin autoantibodies.

Conclusions: We confirm that the women with PCOS have different types of metabolic disturbances during pregnancy.

І.41 Todorova – Ananieva K., M.Guenova Pregnancy Outcomes in Women with Type 1 Diabetes Treated with Long Acting Insulin Analogs. A Case Control Study. The European Association for the Study of Diabetes. 44 Annual Meeting, Rome, Italy. 8-11 Sep. 2008. Diabetologia; Vol 51; Supl. p 456.

The aim was to evaluate and compare the pregnancy outcome in women with type1 diabetes (T1D) intensively treated with long acting insulin or insulin analogs.

Materials and methods: A prospective two years case control study in ninety pregnant women with T1D. The intensified treatment consisted of insulin aspart as bolus insulin and long acting insulin as basal. Women were divided into tree groups according to the basal insulin: n1=30 treated with NPH insulin, n2=30 treated with insulin detemir and n3=30 treated with insulin glargine. Participants were matched for age, duration of diabetes, BMI, HbA1c before pregnancy parity, number of previous pregnancies and abortions. Metabolic control, diabetic complications, severe hypoglycemic episodes and pregnancy induced hypertension and preeclampsia were registered. Perinatal mortality, stillbirth, macrosomia, weeks and route of delivery and neonatal complications were also recorded. Statistical methods: ANOVA - with multiple comparison and chi square test have been used.

Results: No statistically significant difference in mean values for age, diabetes duration, BMI, parity, and number of previous pregnancies. No differences were observed in pre-prandial, postprandial glucose and HbA1c levels in early pregnancy (HbA1c n1 = 7.3±0.8%, n2 = 6.9±0.9%, n3 = 7.1±0.8%, P=0.7) No difference were observed in postprandial glucose and Hba1c in late pregnancy (HbA1c n1 = 7.8±0.3%, n2 = 7.3±0.6%, n3 = 7.7±0.7%, P=0.06) as well. The level of preprandial glucose in late pregnancy was lowest in first group (n1=4.5±1.4 mmol/l, n2 = 6.6±1.1mmol/l, n3=6.9±0.8 mmol/l, P=0.0001). The dose of short acting insulin were significantly higher in the first group in early (n1 = 25.9 ± 34.5 U/kg, n2 = 17.0 ± 25.3 U/kg, n3 = 19.6 ± 26.7%, P=0.004) and in late pregnancy (n1 = 41.1±20.0 U/kg n2 = 26.1±12.9 U/kg, n3 = 21.9±10.1 U/kg, P=0.0001). There were no differences in the dose of long acting insulin in early pregnancy between the groups, but in late pregnancy the dose in n1 group was statistically lower in comparison to the others two groups (n1 = 16.0±6.8 U/kg n2 = 21.4±8.2 U/kg, n3 = 29.7±6.6 U/kg, P=0.001). Severe hypoglycemic episodes in the first group were observed at rate 16% (P=0.03). There were no differences in frequency of hypoglycemic episodes between groups n2 and n3. Caesarean section was the main choice in all groups. There was statistically significant difference in the time of delivery in the third group compared to the other groups (n1 = 36.7±1.1 week n2 = 36.2±1.2 week, n3 = 37.5±0.7 week, P=0.001). The newborns body weight in third group was statistically higher than the others two groups (n3 =3623.9±527.8 gr. ; n1 = 3364.3±662.4 gr.;, n2 = 3076.7±798.7 gr.; P=0.02). The incidence of Respiratory Distress Syndrome (RDS) was higher in the first group (P=0.04). The frequency of neonatal hypoglycemia was higher in the third group (P=0.003). The frequency of spontaneous abortion and stillbirths were higher in the third group, but without statistical significance. The evaluations of risk factors could not established relationship between the observed fetal complications and the insulin treatment.

Conclusion: The treatment with long acting insulin analogs during pregnancy has similar maternal efficacy and safety. In terms of fetal complications and safety the conduct of more long treatment trials in larger group are needed.

І.42 K. Todorova - Ananieva, E. Konova, A. Emin. Pregnancy Outcomes in Normoglycaemic Women with Hyperinsulinemia Treated with Metformin before and during Pregnancy. A Case Control Study. The European Association for the Study of Diabetes. 45 Annual Meeting Vienna, Austria. 29-02 Oct. 2009; Abstract Vol. p. 47.

Background and Aims: The purpose was to evaluate the effects of metformin on maternal and neonatal outcome of pregnancy among pregnant women with hyperinsulinemia with normal and pathologic glucose tolerance .

Materials and methods: A prospective one year case control study among sixty six pregnant women with one unsuccessful pregnancy without previous glucose intolerance has been done. A 75 grams OGTT were performed in all pregnant women during the second pregnancy at 12 g.w. and 36 g.w. in all pregnant women. The levels of blood glucose and immunoreactive insulin were measured at 0min.; 60 min. and 120 min. Women were divided into tree groups according to results of initial OGTT: n1=21 with normal OGTT without hyprinsulinemia, n2=24 with impaired OGTT (IGT) with hyprinsulinemia and n3=21 with gestational diabetes mellitus (GDM) with hyprinsulinemia. Women with IGT and GDM were placed on metformin ( 0.75 -1.5 g/day) according to levels of immunoreactive insulin after glucose loading. Participants were matched for age, BMI, number of previous pregnancies with abortions. Metabolic evaluation were performed before the initiation of metformin therapy and then on regular basis. Maternal and neonatal complications were recorded. Statistical methods: ANOVA - with multiple comparison and chi square test have been used.

Results: No statistically significant difference in mean values for age and BMI. The blood glucose levels in early pregnancy measuring before and during glucose loading were significantly higher in pregnant with GDM [(basal: n1 = 5.3 ± 0.6mmol/l, n2 = 5.2 ± 0.6mmol/l, n3 = 6.5 ±1.3mmol/l, P=0.04); ( 60 min. n1 = 7.1 ± 1.1mmol/l, n2 = 7.4 ± 1.2mmol/l, n3 = 9.6 ± 2.3mmol/l, P=0.03); ( 120 min. n1 = 6.4 ± 1.2mmol/l, n2 = 6.2 ± 1.2mmol/l, n3 = 8.5 ± 2.1mmol/l, P=0.01)]. No difference were observed in initial levels of insulin in early pregnancy (0 min. n1 = 11.4 ± 8.5 mUI/ml, n2 = 13.6 ± 4.5 mUI/ml, n3 = 15.8 ± 9.8 mUI/ml, P=0.06), but stimulated insulin levels after glucose loading were higher in second and third groups (60 min. n1 = 56.8 ± 20.8 mUI/ml, n2 = 70.1 ± 41.9 mUI/ml, n3 = 74.8 ± 44.1 mUI/ml, P=0.04). BMI in late pregnancy was statistically lower in pregnant with normal OGTT (BMI n1 = 26.8 ± 3.6 kg/m2 n2 = 28. 3± 3.6 kg/m2, n3 = 29.5 ± 4.2 kg/m2, P=0.001). There were statistically differences in mean levels of BMI compared in early and late pregnancy in all groups. The level of blood glucose in late pregnancy was lowest in second group [(basal: (n1 = 5.9 ± 0.5mmol/l, n2 = 5.6 ± 0.4mmol/l, n3 = 5.8 ± 0.4mmol/l, P=0.04; ( 60 min. n1 = 8.1 ± 0.8mmol/l, n2 = 7.3 ± 0.7mmol/l, n3 = 7.4 ± 0.7mmol/l, P=0.01); ( 120 min. n1 = 7.4 ± 0.9mmol/l, n2 = 6.5 ± 0.3mmol/l, n3 = 6.7± 0.7mmol/l, P=0.01)]. The both initial and stimulated levels of insulin were highest in the first group [(0 min. n1 = 20.2 ±11.5 mUI/ml, n2 = 17.4 ± 5.8 mUI/ml, n3 = 14.9 ± 6.1 mUI/ml, P=0.03); ( 60 min. n1 = 88.4 ± 11.5 mUI/ml, n2 = 66.2 ± 34.7 mUI/ml, n3 = 69.6 ± 24.0 mUI/ml, P=0.01)] in late pregnancy. The levels of insulin in late pregnancy were statistically lower in n2 and n3 groups comparison to same insulin levels the early pregnancy. There were no maternal complications attributed to metformin, and there were no birth defects. The newborns body weight was similar in all groups (n1 =3500.9 ± 443.5 g, n2 = 3560.3 ± 408.9 g, n3 = 3381.7 ± 267.2 g, P=0.6). The rate of spontaneous abortion was 13.6% (9/66). The frequency of miscarriages was highest in first group 28.5% (6/21). The evaluations of risk factors established relationship between the high insulin levels in early pregnancy and abortions.

Conclusion: Metformin use during pregnancy improved metabolic markers and reduced spontaneous miscarried rates in women with hyperinsulinemia and impaired OGTT.

І.43 Zacharieva S., K. Todorova – Ananieva, E. Konova, V. Petkova, S. Guerguiev, Z. Dimitrova. Pharmacoeconomic Analyses for the Future Treatment of Diabetes mellitus after Gestational Diabetes. The European Association for the Study of Diabetes. 45 Annual Meeting. Vienna, Austria. 29-02 Oct. 2009; Abstract Vol. p. 409.

The research aims to outline the risk of developing Diabetes Mellitus (DM) during the first year after giving birth for women with previous Gestational Diabetes Mellitus (GDM), as well as to estimate the social efficiency value of the applied prophylactic method.

Tools and Methods A study has been performed among 50 women, whit GDM for one year after delivery. During that period a prophylactic program has been applied for DM prevention. The social efficiency of the applied prophylactic method is presented using the “decision tree” model. All indirect costs for future DM treatment are presented, as well as calculations are given for the added years of life with invalidity (DALY).

Results: DM has been observed at 13 (or 26%) out of 50 women with previous GDM in the first year after birth delivery. The total cost per women for the applied prevantive programme have been calculated at 12.1€. The total annual expenses for treatment and control of a women with Т2 DM and good metabolic control is 98.9€, for satisfying metabolic control- 122.1€ and for bad metabolic control - 241.8€. The total annual expenses for treatment and control of one women with Т1 DM and good metabolic control is 241.8€, for satisfying metabolic control - 303.7€, and for bad metabolic control. The social cost of late diagnosed or complicated Т2 ДM is 10,994.80 €. The cost for the complicated Т1 DM treatment is 20,979.38 € at 5% discount. The rate of DALY also varies according to the rate of diabetic complications. The calculated DALY for women with DM at stage of disability are: - 10.1 year for women with DM with no complications, 12.1 years for women with DM and a mild rate of complications, 13.6. г. - years for women with DM and with moderate complications and 15.1 years for women with DM and a severe rate of complications.

Conclusions: Future DM treatment costs depend entirely on the extent of metabolic compensation, probability for later complications and the method of treatment. However, the prophylactic screening the women with previous GDM can considerably save these costs.

І.44 K. Todorova, K. Petkova, E. Konova, M. Stamenova. Changes in Hummoral Autoimmunity in Pregnant Women with Abnormal Glucose Tolerance. The European Association for the Study of Diabetes. 46 Annual Meeting. Stockholm, Sweden. Sep. 20-24, 2010; Abstract Vol. p.441.

Introduction: Autoantibodies (AAs) against pancreatic ß-cell antigens are found more frequently in women with gestational diabetes mellitus (GDM) requiring insulin treatment during pregnancy than those women without need of insulin medication. AAs are causing pancreatic β cells destruction and autoimmune β cell dysfunction. Arising hyperglycemia is results from tissue resistance to the glucose loading effects of insulin and inadequate β cell compensation for this resistance. The presence of autoimmune markers in pregnant women is the potential increased risk for the future development of type 1 diabetes (T1DM).

The aim of study was to evaluate the changes in hummoral autoimmunity in high risk’s for T1DM pregnant women with normal and pathological glucose tolerance.

Subjects and Methods: An one year prospective study among 96 pregnant women has been done for period March 2008 - March 2009. A 75 grams Oral Glucose Tolerance Test (OGTT) have performed between 24 - 26 gestational weeks. The levels of blood glucose (BG) and immunoreactive insulin (IRI) have measured at 0 min.; 60 min. and 120 min. According to the results of OGTT the patients have been divided into two groups: pregnant with normal carbohydrate tolerance (g1= 53) and pregnant with impaired carbohydrate tolerance (g2 = 43). The presence of antibodies against insulin (AIA), glutamic acid decarboxylase (GAD65) and one of the heat stress shock protein (AHspA) have examined in sera using indirect ELISA (AIA and AHspA) and EIA (GAD65) methods. All statistic analyses have been done with statistic panel - SPSS for Windows version 11.0.1. The difference between groups are compares by two tailed Student,s t test.

Results: Seven sera from the g1 (13.2%) and five sera from the g2 (11.6%) were positive for AIA (P>0.05). GAD65 autoantibodies are found in one serum from the g1 (1.8%) and seven sera from the g2 (16.2%); (P<0.001). Sequent analysis for AHspA has found two positive sera in g1 (3.8%) and four positive sera in g2 (9.3%); (P>0.05). There were statistically significant difference in total percentage of presence of autoantibodies between g1 and g2 groups (18.8% vs. 37.2%; P<0.03). We have fond positive correlation between BG levels during OGTT and presence of AHspA in g2 (P<0.04). There were positive correlation between basal IRI levels at 0 min. and presence of AIA (P<0.02) in group 2. Four pregnant positive for IAI of g1 (51.7%) and three pregnant positive for IAI of g2 (60.0%) have first and second degree relatives with T2DM. Five pregnant of GAD65 positive of g2 (71.4%) have first and second degree relatives with T1DM.

Conclusion: These data support that autoimmune markers for the pancreatic β cell destruction were elevated in pregnant women with abnormal OGTT. In the absence of effective methods of preventions of T1DM measuring of immunologic markers in pregnant with high hereditary risk should be important tool for studying the progress of β cell dysfunction.
ІІ. ДОКУМЕНТИ, СВЪРЗАНИ С НАУЧНАТА АКТИВНОСТ



  1. СПИСЪК НА НАУЧНИТЕ ОБЗОРИ


ІІ. 1 Тодорова К. Профилактично приложение на цинк при бременни – или да се лекува рискът, а не болестта. Акуш. и гинекол.; 2003; (42); 6; 41-43.

Цинкът е микроелемент с доказана значимост за поддържане на нормалната физиологична активност на човешкия организъм. Аспектите на неговата клетъчна активност се свързват с участието му в процесите на тъканна регенерация, регулация на глюкозната хомеостаза, регулация на менструалния цикъл и съзряването на половите клетки, правилното развите на плода и нормалното протичане на бременноста, имунопротекция, имуномодулация, антиоксидация и др. Хроничният дефицит на цинк причинява повишена чувствителност към оксидативния стрес с необратими последици от пост-исхемично тъканно увреждане. Редовният прием на цинк през бременността намалява риска от спонтанни аборти, конгенитални аномалии, възпалителни заболявания и подобрява метаболитната хомеостаза.

В настоящият обзор се обсъжда биологичната значимост на цинка за поддържане на майчината хомеостаза през бременността, нормален фетален растеж и развитие и възможностите за неговата суплементация.

ІІ. 2 Тодорова К., В. Мазнейкова, Ст. Иванов. Лечение с нискомолекулярен хепарин при бременни жени с висок тромбозен риск. Акуш. и гинекол.; 2004; (43); 4; 46-52.

Промените в циркулиращият кръвен обем и хемостатичните механизми, заедно с подтисната фибринолиза при нормална бременност, спомагат да се намали рискът от кървене при раждане, но превръщат бременността в хиперкоагулитетно състояние.

Дълбокият венозен тромбоемболизъм (ДВТЕ) е най–честото и най–сериознота усложнение на нормално протичащата бременност и представлява сериозен медицински и социален проблем. Белодробният тромбо-емболизъм продължава да бъде първостепенна причина за майчина смърт, на фона на общото понижение на майчината смъртност, дължаща се на акушерски усложнения през последните 30 г.

Интересите на изследователите през последните две декади се насочиха към жените, при които има повишен риск от загуба на бременността, поради тромбоза на плацентарните капиляри. Доказа се, че вродената или придобита тромбофилия е каузален фактор за възникване на артериални и венозни тромбози с последваща рекурентна загуба на плода, по механизми, които все още са не - добре проучени.

Намаление на майчината смъртност и заболеваемост от венозeн тромбоeмболизъм, може да бъде постигнато само след детайлно изясняване на предразполагащите фактори и селективно прилагана профилактика с ниско молекулярин хепарин при жените с висок тромбофиличен риск.

ІІ. 3 Тодорова К., Ст. Иванов. Приложение на нискомолекулярен хепарин при жени с рекурентна загуба на плода. Акуш. и гинекол.; 2004; доп.4 (43); 31-36.

Физиологично, бременността е хиперкоагулитетно състояние. Съществуват случаи при които, някои хемостатични фактори, свързани с бременността, могат да задълбочат състоянието на хиперкоагулация и да наклонят баланса в посока към тромбоза. Тромбозният процес се влияе също от редица биохимични майчини и фетални фактори, които могат да причинят запушване на плацентарните капиляри. Тромбозата на плацентарните капиляри най-често се причинява от вродена или придобита тромбофилия, която е каузален фактор за загуба на бременността в 40% от случаите със спонтанни аборти, интраутеринна смърт, изоставане във феталния растеж, прееклампсия или преждевременно раждане.

Подобрение на пернаталния изход може да бъде постигнато чрез изучаване нва механизмите, включени в процеса на плацентарна тромбогенеза. Приложението на ниско-молекулярен хепарин може ефективно да намали риска от плацентарна тромбоза и да подобри перинаталната прогноза на бременността.

Николов, А., А. Димитров, Г. Коларов, К. Тодорова, Ц. Механджиев. Контрацепция при жени със захарен диабет. Акуш. и гин.; 2005; (44); 5; 47-52.

Контрацепцията при жените, болни от захарен диабет е важен въпрос, тъй като е доказано, че изхода на бременността, както за майката, така и за плода, е свързан със степента на контрол на гликемията преди концепцията до раждането. Това прави планирането на бременността задължително за диабетно болните. Пациентките се съветват за предпазване от забременяване до оптимизиране на метаболитния контрол или до пълното и своевременно лечение на съпътстващите диабета усложнения. Неправилно подбрания контрацептивен метод може да задълбочи метаболитните нарушения и да окаже влияние върху развитието на съдовите усложнения на диабета. Изборът на контрацептивна терапия се определя от целта на контрацепцията: краткотрайна контрацепция с цел планиране на бъдеща бременност или продължителна контрацепция с цел семейно планиране. При жени със захарен диабет е особено важно да се вземат предвид такива фактори като, типа на диабета, неговата давност, степента на метаболитна компенсация, съпътстващи усложнения на диабета, индекс на телесната маса, наличие на рискови фактори за ССЗ и планиране на бъдеща бременност. При планиране на бременност да се предпочита локална контрацепция - презервативи, диафрагми. При нераждали жени или при жени с множество партньори - презервативи. При раждали жени ВМКС е средство на избор.

При жени със захарен диабет тип I е възможно използуването на хормонална контрацепция, по желание на пациентката или по медицински индикации в случай, че диабетът е с давност по-малка от 15 години и липсват микроангиопатични усложнения и други съдови рискови фактори. Комбинираните хормонални контрацептивни препарати трябва да съдържат по-малко от 30 pg. етинилестрадиол и гестаген от "трето" или "четвърто" поколение. Тази контрацепция следва да се предпише успоредно с коригирана инсулинова доза и изисква чест метаболитен контрол на диабета и контрол на телесното тегло. Когато комбинираните препарати са противопоказани, може да бъде предложена прогестагенна орална хормонална контрацепция, при липса на гинекологични контраиндикации и ако това не води до менструални смущения. При жени със захарен диабет тип II комбинираните хормонални контрацептиви не трябва да се прилагат защото могат да влошат клиничната изява и да утежнят клиничното протичане на диабета.


Каталог: procedures -> acad
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acad -> Конкурс за „Доцент (Заповед №892/31. 05. 2011г на Ректора на му плевен ) о т н о с н о
acad -> Конкурс за получаване на научно звание „Доцент по биология с шифър 01. 06. 00


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