Foydalanuvchi:MD.Wikie/qumloq

Somatotropinlar tipik vakili somatotrop boʻlgan oqsillar guruhi hisoblanadi, shuningdek, organizm oʻsishida muhim rol oʻynaydigan o`sish gormoni sifatida tanilgan. Bu guruhning boshqa aʼzolariga laktogen va uning yoʻldosh analogi -prolaktin (yoʻldoshda prolaktinga bogʻliq boʻlgan oqsillarni va sut bezida laktatsiyani ragʻbatlantiradi), proliferin, proliferinga bogʻliq boʻlgan oqsillar va turli xil baliqlarda uchraydigan somatolaktin kiradi. Qoramol somatotropining 3D tuzilishi energiyani kamaytirish usullarining kombinatsiyasi yordamida bashorat qilingan.

Bu guruhdan odamda uchraydigan peptidlar

CSH1, CSH2, CSHL1, OʻG1; OʻG2, PRL

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Qandli diabet va homiladorlik

Bu sahifa avvaldan mavjud bo`lgan diabetning homiladorlik vaqtida ta`siri haqidadir. homiladorlikda vaqtinchalik rivojlangan diabet belgilari uchun Gestatsion diabet sahifasiga qarang.

Qandli diabetli homilador ayollarda ham bola ham ona uchun bir nechta qiyinchiliklar mavjud. Agar homilador ayolda avvaldan mavjud boʻlgan diabet boʻlsa, bu bolaning chala tug`ilishiga, tug`ma nuqsonlarga yoki homilaning katta tugʻilishiga olib kelishi mumkin. Shuning uchun mutaxassislar homiladorlikning rejalashtirishdan 3 oy avval qondagi shakar miqdorini normallashtirishni maslahat beradi.

Homilador boʻlishni rejalashtirgan ayolda birinchi tip qandli diabet yoki ikkinchi tip qandli diabet avvaldan mavjud boʻlsa, homilador boʻlishdan avval qondagi glyukoza miqdorini qatʼiy nazorat qilish kerak .

Fiziologiyasi

Pregestatsion diabet fiziologik mexanizmiga qarab birinchi tip yoki ikkinchi tip sifatida klassifikatsiyalanadi. Birinchi tip bu autoimmun kasalliklar boʻlib, oshqozon osti bezidagi betta hujayralarning funksiyasini buzilishiga olib keladi. Ikkinchi tip semizlik bilan bogʻliq boʻlib, insulin ishlab chiqarishning yetarli emasligi natijasida rivojlanadi. Homilador boʻlish vaqtida yo`ldosh qonda glyukoza miqdorini oshirib yuboradigan laktogen ishlab chiqaradi. Oldindan mavjud boʻlgan diabetli homilador onalardagi fiziologik oʻzgarishlar qonda glyukozaning xavfli darajada oshishiga olib keladi. Bu oʻzgarishlar muhim, chunki qandli diabet asoratlari homilador boʻlmagan holatlarga qaraganda homiladorlik paytida ogʻirroq boʻladi.

Homila uchun xavf omillari

Pregestatsion diabetning salbiy taʼsiri asosan homiladorlikning birinchi trimestrida (gestatsion diabetdan farqli ravishda) qondagi qand va insulin darajasining yuqoriligi bilan bogʻliq boʻlib, bu ikkinchi va uchinchi trimestrda homilada ogʻir holatlarga olib keladi. Bu davrlar homilaning koʻplab asosiy ichki aʼzo va toʻqimalari rivojlanadigan davr boʻlganligi sababli, oldindan mavjud boʻlgan diabet tugʻma nuqsonlarga olib kelishi mumkin. Bularga yurak va markaziy asab tizimining notoʻgʻri rivojlanishlari kiradi. Markaziy asab tizimining notoʻgʻri rivojlanishi chanoq ageniziyasi (chanoq suyagining gipoplaziyasi), xoloprosensefaliya (miya zararlanishiga oid)ga olib kelsa, yurakning notoʻgʻri rivojlanishi arteriya trunkusning notoʻgʻri rivojlanishiga, atrioventrikulyar blokadaga olib keladi. Bu asoratlarni qondagi qand miqdorini qattiq nazorat qilish orqali oldini olish mumkin. Bolalardagi yengil nevrologik va aqliy yetishmovchiliklar, jumladan, DEGS simptomlarining kuchayishi, harakatning maʼlum darajada cheklanishi va xotira pasayishi homiladorlikdan oldingi birinchi toifa diabet va gestatsion diabet bilan bogʻliq. Oldindan mavjud boʻlgan diabet, shuningdek, bolada tugʻruqdan keyingi asoratlarga, jumladan, fiziologik boʻlmagan sariqligi, gipoglikemiya va makrosomiya (homilaning kattalashib ketishi)ga olib kelishi mumkin. Biroq, homiladorlikdan oldingi diabet xromosoma oʻzgarishlari (masalan, Daun sindromi) tufayli paydo boʻladigan kasalliklar ehtimolini oshirmaydi. Bundan tashqari, homiladorlikning dastlabki bosqichlarida anormal rivojlanish tufayli homila tushish holatlari ham koʻpayadi, qonda glyukoza miqdorini nazorat qilmaslik bola tugʻilishidan qisqa vaqt oʻtib, uning oʻpkasi respirator kasalliklarga duch kelishiga olib keladi. Agar onaning qonidagi qand miqdori tugʻruq vaqtiga yaqin yuqori boʻlsa, gipoglikemiyali bola tugʻiladi, bu esa bolaning oʻzidan qoʻshimcha insulin ishlab chiqarilishiga olib keladi. Bunday bolalarda semirish, 2-toifa qandli diabet va metabolik sindrom kabi holatlar kuzatilishi xavfi yuqori boʻladi.

Homiladorlikda diabetni davolash

Homiladorlikda glyukoza miqdori iloji boricha qatʼiy nazorat qilinishi kerak. Homiladorlikning birinchi haftasida qondagi qand miqdorini qattiq nazorat qilish, shuningdek, homilaning rivojlanishi uchun zarur boʻlgan qoʻshimcha glyukoza tufayli insulin bilan davolash kamroq talab qilinadi. Qondagi qand miqdorini nazorat qilib turish uchun tez-tez tekshirib turiladi. Homila oʻsishi va vazni ortishi sababli organizm koʻproq gormonlar ishlab chiqaradi, bu esa insulinga rezistentlik va koʻproq insulinga boʻlgan ehtiyojni keltirib chiqarishi mumkin. Bu vaqtda qondagi qand miqdori normada boʻlishi muhim, chunki bola onasining qonidagi yuqori qand miqdorini kamaytirish uchun oʻz insulinini koʻproq ishlab chiqaradi, bu esa homila makrosomiyasi (katta tugʻilishi)ga olib keladi. Tugʻruq paytida insulin miqdori kamaytirilishi kerak, yoʻqsa giperglikemiya paydo boʻlishi mumkin. Chaqaloq tugʻilgandan soʻng va keyingi kunlarda yoʻldoshdan koʻproq insulin talab qiladigan gormonlar boʻlmaydi, shuning uchun insulin talabi kamayadi va asta-sekin normal koʻrsatkichlarga qaytadi.

Qandli diabetni ovqatlanishni toʻgʻri rejalashtirish, jismoniy faollikni oshirish va insulin bilan davolash orqali samarali davolash mumkin. Homiladorlik davrida qandli diabetni nazorat qilish uchun baʼzi maslahatlar:

• Shirinliklarni kamaytiring, kuniga uch marta kam-kamdan taom isteʼmol qiling, ovqatlanish vaqtlarini toʻgʻri nazorat qiling va meva- sabzavot va toʻliq donli ekinlardan tayyorlangan taomlarni isteʼmol qiling.
• Jismoniy harakatlarni oshiring – yurish, suzish va boshqalar.
• Qondagi shakar miqdorini doim tekshirtirib turing.
• Ertalab uyqudan turganda qondagi qand miqdori 95 mg/dL (5.3 mmol/L), ovqatdan bir soat keyin 140 mg/dL (7.8 mmol/L) va ovqatdan ikki soat keyin 120 mg/dL (6.7 mmol/L) dan past boʻlishi kerak.
• Har safar qondagi qand miqdorini tekshirayotganda natijalarni tegishli tarzda qayd qilib boring va davolashni baholash va oʻzgartirish uchun shifokoringgizga taqdim eting. Agar qondagi qand miqdori belgilangan miqdordan yuqori boʻlsa, davolash usullari oʻzgartiriladi.
• Koʻpchilik homiladorlikda qondagi qand miqdorini kamaytirish uchun qoʻshimcha insulinga muhtoj boʻlishi mumkin. Insulin chaqaloq uchun zararli emas.

Sogʻliqni saqlash milliy instituti endi homilador yoki homiladorlikni rejalashtirayotgan 1-toifa diabet bilan ogʻrigan barcha ayollar uchun yopiq siklli insulin tizimlarini variant sifatida tavsiya qiladi.

Koʻkrak suti bilan boqish

Koʻp hollarda hattoki ona diabet bilan kasallangan boʻlsa ham koʻkrak suti bilan boqish bola uchun yaxshi boʻladi. Misol uchun, agar bola koʻkrak suti bilan boqilgan boʻlsa, bolada ikkinchi tip qandli diabet rivojlanish xavfi kamroq boʻladi. Shuningdek emizish, goʻdaklik davrida bolaning normal vaznini saqlashga yordam beradi. Biroq, qandli diabet bilan ogʻrigan onalarning koʻkrak suti qandli diabet boʻlmagan onalarnikidan farqli tarkibga ega ekanligi aniqlangan, ularning suti tarkibida glyukoza va insulin darajasining oshishi va politoʻyinmagan yogʻ kislotalarining pasayishi kabi holatlar kuzatiladi. Qandli diabet bilan ogʻrigan onalarning bolalari uchun ona suti bilan oziqlantirishning afzalliklari boʻlsa-da, diabetik koʻkrak sutini isteʼmol qilish ham dozaga bogʻliq ravishda bolaning soʻzlashuvi rivojlanishining kechikishiga olib kelishi mumkin. Baʼzi holatlarda, ayol homiladorlik vaqtida qonida qand miqdori juda past koʻrsatkichlarga ega boʻlganda, bola tugʻilgandan keyin unga og`iz suti berish tavsiya etilmaydi. Diabetli homilador ayollarda uning steril va foydali ekanligiga aniq dalillar yoʻq.

Turlari

Vait klassifikatsiyasi (fizik olim Preskella Vait) onada va homilada xavf omillarini baholash uchun keng qoʻllaniladi. Bu homiladorlikdagi gestatsion diabet va homiladorlikdan avval mavjud boʻlgan pregestatsion diabetlarni farqlash imkonini beradi. Bu ikki guruh kasallik xavf omillari va davolashga koʻra turlarga ajratilgan. Homiladorlik davrida boshlangan gestatsion diabetning 2 ta turi bor:

• A₁ sinf: parhez orqali nazorat qilinadigan gestatsion diabet;
• A₂ sinf: dorilar yordamida nazorat qilinadigan gestatsion diabet.

Pregestatsion diabetni quyidagi turlarga ajratishimiz mumkin:

• B sinf: 20 va undan katta yoshda yoki 10 yildan kam davom etadigan;
• C sinf: 10-19 yoshda boshlanishi yoki davomiyligi 10-19 yil;
• D sinf: 10 yoshdan oldin yoki 20 yildan ortiq davom etishi;
• E sinf: tos tomirlari kalsiylashgan qandli diabet;
• F sinf: diabetli nefropatiya;
• R sinf: proliferativ retinopatiya;
• RF sinf: retinopatiya and nefropatiya;
• H sinf: koronar arteriya kasalligi;
• T sinf: buyrak transplantatsiyasi.

Kasallikning erta boshlanishi yoki uzoq davom etishi katta xavf tugʻdiradi.

Yana qarang

• Qandli diabet
• Gestatsion diabet
• Homiladorlik

Havolalar

• CDC’s National Center on Birth Defects and Developmental Disabilities

[[Turkum:Qandli diabet [[Turkum:Homiladorlikda patologiyalar

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Gestatsion diabet

Gestatsion diabet
Belgilari	bir nechta belgilari
Mutaxassislik	akusherlik va endokrinologiya
Asoratlari	preeklampsiya, o‘lik tug‘ilishi, depressiya, kesarcha kesish xavfini oshiradi
Sabablari	insulin yetishmovchiligi
Xavf omillari	ortiqcha vazn, avvalgi homiladorlikda ham gestatsion diabet bo`lganligi, naslida 2-tip qandli diabet borligi, tuxumdon polikistoz sindromi
Tashxis usullari	qon tahlili
Davolash	parhez, jismoniy mashqlar, insulin inyeksiyasi

Gestatsion diabet diabetsiz ayollarning homiladorlik davrida qonda shakar miqdori ortib ketadigan (giperglikemiya) holati. Gestatsion diabet odatda bir nechta asoratlarga olib keladi, jumladan, preeklampsiya xavfini oshiradi, depressiyaga olib keladi, tug`ruq kesarcha kesish orqali o`tkaziladi. Homiladorlik davrida yaxshi davolanmagan gestatsion qandli diabet bilan tug‘ilgan chaqaloqlarda makrosomiya, tug‘ilgandan keyin gipoglikemiya va sariqlik xavfi yuqori bo‘ladi. Shuningdek, davolanmasa bolaning o`lik tug`ilishiga olib keladi. Kelajakda bolalarda ortiqcha vazn va qandli diabetning 2-turi rivojlanishiga moyilligi yuqori bo‘ladi.

Sabablari va tashxis qo`yish

Gestatsion diabet homiladorlik davrida insulin yetishmovchiligi natijasida kelib chiqadi. Xavf omillariga ortiqcha vaznlilik, avvalgi homiladorlikda ham gestatsion diabet bo`lganligi, naslida 2-tip qandli diabet borligi, tuxumdon polikistoz sindromi kabilar kiradi. Tashxis qo`yish uchun qon tahlili olinadi.Xavf omillari kam bo`lganda gestatsiyaning 24-28-haftalari orasida tekshirilish tavsiya qilinadi. Kasallik og`ir darajada bo`lganda birinchi prenatal davrdanoq tekshirtirish kerak.

Profilaktika va davolash

Homiladorlikdan avval jismoniy mashqlar bilan muntazam shug`ullanish, vazn saqlash kasallikni oldini olishga yordam beradi. Gestatsion diabet parhez, jismoniy mashqlar, dori vositalari (masalan, metformin), va insulin inyeksiyalari yordamida davolanadi. Ko`p bemorlar qonidagi shakar miqdorini mashqlar va parhez bilan nazorat qiladi. Qondagi qand miqdorini tekshirish kuniga to`rt marta tavsiya etiladi. Bola tug`ilganidan keyin tezroq emizish (koʻkrak suti bilan boqish) tavsiya etiladi.

Epidemiologiyasi va prognozi

Gestatsion diabet 3-9% homiladorlarda uchraydi. Bu ayniqsa uchinchi trimesterda keng tarqalgan. Ularning 1%i 20 yoshdan past va 1-3%i 44 yoshdan baland bo`ladi. Bir qator etnik guruhlar, jumladan osiyoliklar, amerikalik hindular, Avstraliyaning tub aholisi va Tinch okeani orollari aholisida bu kasallik uchrash ehtimoli yuqori. 90% hollarda gestatsion diabet chaqaloq tug‘ilgandan keyin o`tib ketadi. Ba`zan 2-tip qandli diabetni rivojlantiradi.

Turlari

Gestatsion diabet "homiladorlikning boshlanishida glyukozananing har qanday darajada oshib ketishi" deya izohlanadi. Bu ta`rif ayolda avvaldan mavjud bo`lgan tashxislanmagan diabet yoki homiladorlikda vaqtincha paydo bo`lgan diabetligini tan oladi. Homiladorlikdan keyin simptomlarning yo`qolishi tashxis qo`yishda ahamiyatsiz. Ayolga gestatsion diabet tashxisi homiladorlikning 24-28-haftalari oralig`ida qondagi glyukozaning miqdori oshib ketganda qo`yiladi. Vait klassifikatsiyasi (fizik olim Preskella Vait) onada va homilada xavf omillarini baholash uchun keng qoʻllaniladi. Bu homiladorlikdagi gestatsion diabet va homiladorlikdan avval mavjud boʻlgan pregestatsion diabetlarni farqlash imkonini beradi. Bu ikki guruh kasallik xavf omillari va davolashga koʻra turlarga ajratilgan. Homiladorlik davrida boshlangan gestatsion diabetning 2 ta turi bor:

• A₁ sinf: parhez orqali nazorat qilinadigan gestatsion diabet;
• A₂ sinf: dorilar yordamida nazorat qilinadigan gestatsion diabet.

Pregestatsion diabetni quyidagi turlarga ajratishimiz mumkin:

• B sinf: 20 va undan katta yoshda yoki 10 yildan kam davom etadigan;
• C sinf: 10-19 yoshda boshlanishi yoki davomiyligi 10-19 yil;
• D sinf: 10 yoshdan oldin yoki 20 yildan ortiq davom etishi;
• E sinf: tos tomirlari kalsiylashgan qandli diabet;
• F sinf: diabetli nefropatiya;
• R sinf: proliferativ retinopatiya;
• RF sinf: retinopatiya and nefropatiya;
• H sinf: koronar arteriya kasalligi;
• T sinf: buyrak transplantatsiyasi.

Kasallikning erta boshlanishi yoki uzoq davom etishi katta xavf tugʻdiradi.

Gestatsion qandli diabetni tashxislash uchun qondagi qand miqdoriga qarab yana ikkita mezon to‘plami mavjud.

Carpanter va Coustan bo‘yicha 100 gramm glyukozaga tolerantlik testi yordamida gestatsion diabetni tashxislash mezonlari:

• Ochlik 95 mg/dl
• 1 soatda 180 mg/dl
• 2 soatda 155 mg/dl
• 3 soatda 140 mg/dl

Diabet bo‘yicha Milliy Ma’lumotlar guruhiga ko`ra gestatsion diabet tashxisi mezonlari:

• Ochlik 105 mg/dl
• 1 soatda 190 mg/dl
• 2 soatda 165 mg/dl
• 3 soatda 145 mg/dl

Xavf omillari

Gestatsion diabetni rivojlanishidagi xavf omillari quyidagilardan iborat:

• Polycystic ovary syndrome
• A previous diagnosis of gestational diabetes or prediabetes, impaired glucose tolerance, or impaired fasting glycaemia
• A family history revealing a first-degree relative with type 2 diabetes
• Maternal age – a woman's risk factor increases as she gets older (especially for women over 35 years of age).
• Paternal age – one study found that a father's age over 55 years was associated with GD
• Ethnicity (those with higher risk factors include African-Americans, Afro-Caribbeans, Native Americans, Hispanics, Pacific Islanders, and people originating from South Asia)
• Being overweight, obese or severely obese increases the risk by a factor 2.1, 3.6 and 8.6, respectively.
• A previous pregnancy which resulted in a child with a macrosomia (high birth weight: >90th centile or >4000 g (8 lbs 12.8 oz))
• Previous poor obstetric history
• Other genetic risk factors: There are at least 10 genes where certain polymorphism are associated with an increased risk of gestational diabetes, most notably TCF7L2. The MTNR1B gene is a common gene that is associated with how the body handles insulin and glucose. When this gene is not working properly, it can lead to less insulin production and higher blood glucose levels.

In addition to this, statistics show a double risk of GDM in smokers. Some studies have looked at more controversial potential risk factors, such as short stature.

About 40–60% of women with GDM have no demonstrable risk factor; for this reason many advocate to screen all women. Typically, women with GDM exhibit no symptoms (another reason for universal screening), but some women may demonstrate increased thirst, increased urination, fatigue, nausea and vomiting, bladder infection, yeast infections and blurred vision.

Pregnant women with these risk factors may need to undergo an early screening in addition to the routine screening.

Pathophysiology

Effect of insulin on glucose uptake and metabolism. Insulin binds to its receptor (1) on the cell membrane which in turn starts many protein activation cascades (2). These include: translocation of Glut-4 transporter to the plasma membrane and influx of glucose (3), glycogen synthesis (4), glycolysis (5) and fatty acid synthesis (6).

The precise mechanisms underlying gestational diabetes remain unknown. The hallmark of GDM is increased insulin resistance. Pregnancy hormones and other factors are thought to interfere with the action of insulin as it binds to the insulin receptor. The interference probably occurs at the level of the cell signaling pathway beyond the insulin receptor. Since insulin promotes the entry of glucose into most cells, insulin resistance prevents glucose from entering the cells properly. As a result, glucose remains in the bloodstream, where glucose levels rise. More insulin is needed to overcome this resistance; about 1.5–2.5 times more insulin is produced than in a normal pregnancy.

Insulin resistance is a normal phenomenon emerging in the second trimester of pregnancy, which in cases of GDM progresses thereafter to levels seen in a non-pregnant woman with type 2 diabetes. It is thought to secure glucose supply to the growing fetus. Women with GDM have an insulin resistance that they cannot compensate for with increased production in the β-cells of the pancreas. Placental hormones, and, to a lesser extent, increased fat deposits during pregnancy, seem to mediate insulin resistance during pregnancy. Cortisol and progesterone are the main culprits, but human placental lactogen, prolactin and estradiol contribute, too. Multivariate stepwise regression analysis reveals that, in combination with other placental hormones, leptin, tumor necrosis factor alpha, and resistin are involved in the decrease in insulin sensitivity occurring during pregnancy, with tumor necrosis factor alpha named as the strongest independent predictor of insulin sensitivity in pregnancy. An inverse correlation with the changes in insulin sensitivity from the time before conception through late gestation accounts for about half of the variance in the decrease in insulin sensitivity during gestation: in other words, low levels or alteration of TNF alpha factors corresponds with a greater chance of, or predisposition to, insulin resistance or sensitivity.

It is unclear why some women are unable to balance insulin needs and develop GDM; however, a number of explanations have been given, similar to those in type 2 diabetes: autoimmunity, single gene mutations, obesity, along with other mechanisms.

Though the clinical presentation of gestational diabetes is well characterized, the biochemical mechanism behind the disease is not well known. One proposed biochemical mechanism involves insulin-producing β-cell adaptation controlled by the HGF/c-MET signaling pathway. β-cell adaption refers to the change that pancreatic islet cells undergo during pregnancy in response to maternal hormones in order to compensate for the increased physiological needs of mother and baby. These changes in the β-cells cause increased insulin secretion as a result of increased β-cell proliferation. HGF/c-MET has also been implicated in β-cell regeneration, which suggests that HGF/c-MET may help increase β-cell mass in order to compensate for insulin needs during pregnancy. Recent studies support that loss of HGF/c-MET signaling results in aberrant β-cell adaptation.

c-MET is a receptor tyrosine kinase (RTK) that is activated by its ligand, hepatocyte growth factor (HGF), and is involved in the activation of several cellular processes. When HGF binds c-MET, the receptor homodimerizes and self-phosphorylates to form an SH2 recognition domain. The downstream pathways activated include common signaling molecules such as RAS and MAPK, which affect cell motility, and cell cycle progression.

Studies have shown that HGF is an important signaling molecule in stress related situations where more insulin is needed. Pregnancy causes increased insulin resistance and so a higher insulin demand. The β-cells must compensate for this by either increasing insulin production or proliferating. If neither of the processes occur, then markers for gestational diabetes are observed. It has been observed that pregnancy increases HGF levels, showing a correlation that suggests a connection between the signaling pathway and increased insulin needs. In fact, when no signaling is present, gestational diabetes is more likely to occur.

The exact mechanism of HGF/c-MET regulated β-cell adaptation is not yet known but there are several hypotheses about how the signaling molecules contribute to insulin levels during pregnancy. c-MET may interact with FoxM1, a molecule important in the cell cycle, as FOXM1 levels decrease when c-MET is not present. Additionally, c-MET may interact with p27 as the protein levels increase with c-MET is not present. Another hypothesis says that c-MET may control β-cell apoptosis because a lack of c-MET causes increases cell death but the signaling mechanisms have not been elucidated.

Although the mechanism of HGF/c-MET control of gestational diabetes is not yet well understood, there is a strong correlation between the signaling pathway and the inability to produce an adequate amount of insulin during pregnancy and thus it may be the target for future diabetic therapies.

Because glucose travels across the placenta (through diffusion facilitated by GLUT1 carrier), which is located in the syncytiotrophoblast on both the microvillus and basal membranes, these membranes may be the rate-limiting step in placental glucose transport. There is a two- to three-fold increase in the expression of syncytiotrophoblast glucose transporters with advancing gestation. Finally, the role of GLUT3/GLUT4 transport remains speculative. If the untreated gestational diabetes fetus is exposed to consistently higher glucose levels, this leads to increased fetal levels of insulin (insulin itself cannot cross the placenta). The growth-stimulating effects of insulin can lead to excessive growth and a large body (macrosomia). After birth, the high glucose environment disappears, leaving these newborns with ongoing high insulin production and susceptibility to low blood glucose levels (hypoglycemia).

Screening

Tests for gestational diabetes

Non-challenge blood glucose test Fasting glucose test 2-hour postprandial (after a meal) glucose test Random glucose test

Screening glucose challenge test

Oral glucose tolerance test (OGTT)

A number of screening and diagnostic tests have been used to look for high levels of glucose in plasma or serum in defined circumstances. One method is a stepwise approach where a suspicious result on a screening test is followed by diagnostic test. Alternatively, a more involved diagnostic test can be used directly at the first prenatal visit for a woman with a high-risk pregnancy. (for example in those with polycystic ovarian syndrome or acanthosis nigricans).

Non-challenge blood glucose tests involve measuring glucose levels in blood samples without challenging the subject with glucose solutions. A blood glucose level is determined when fasting, two hours after a meal, or simply at any random time. In contrast, challenge tests involve drinking a glucose solution and measuring glucose concentration thereafter in the blood; in diabetes, they tend to remain high. The glucose solution has a very sweet taste which some women find unpleasant; sometimes, therefore, artificial flavours are added. Some women may experience nausea during the test, and more so with higher glucose levels.

There is currently not enough research to show which way is best at diagnosing gestational diabetes. Routine screening of women with a glucose challenge test may find more women with gestational diabetes than only screening women with risk factors. Hemoglobin A^1c (HbA1c) is not recommended for diagnosing gestational diabetes, as it's a less reliable marker of glycemia during pregnancy than oral glucose tolerance testing (OGTT).

Because women diagnosed with Gestational Diabetes (GDM) during pregnancy are at an increased risk for developing Type 2 Diabetes Mellitus after pregnancy, post pregnancy glucose tolerance testing is needed. Based on the recent meta-analysis conducted by the Patient-Centered Outcomes Research Institute, research has shown that post pregnancy testing reminders are associated with greater adherence to oral glucose tolerance testing up to 1 year postpartum.

Pathways

Opinions differ about optimal screening and diagnostic measures, in part due to differences in population risks, cost-effectiveness considerations, and lack of an evidence base to support large national screening programs. The most elaborate regimen entails a random blood glucose test during a booking visit, a screening glucose challenge test around 24–28 weeks' gestation, followed by an OGTT if the tests are outside normal limits. If there is a high suspicion, a woman may be tested earlier.

In the United States, most obstetricians prefer universal screening with a screening glucose challenge test. In the United Kingdom, obstetric units often rely on risk factors and a random blood glucose test. The American Diabetes Association and the Society of Obstetricians and Gynaecologists of Canada recommend routine screening unless the woman is low risk (this means the woman must be younger than 25 years and have a body mass index less than 27, with no personal, ethnic or family risk factors) The Canadian Diabetes Association and the American College of Obstetricians and Gynecologists recommend universal screening. The U.S. Preventive Services Task Force found there is insufficient evidence to recommend for or against routine screening, and a 2017 a Cochrane review found that there is not evidence to determine which screening method is best for women and their babies.

Some pregnant women and careproviders choose to forgo routine screening due to the absence of risk factors, however this is not advised due to the large proportion of women who develop gestational diabetes despite having no risk factors present and the dangers to the mother and baby if gestational diabetes remains untreated.

Non-challenge blood glucose tests

When a plasma glucose level is found to be higher than 126 mg/dL (7.0 mmol/L) after fasting, or over 200 mg/dL (11.1 mmol/L) on any occasion, and if this is confirmed on a subsequent day, the diagnosis of GDM is made, and no further testing is required. These tests are typically performed at the first antenatal visit. They are simple to administer and inexpensive, but have a lower test performance compared to the other tests, with moderate sensitivity, low specificity and high false positive rates.

Screening glucose challenge test

The screening glucose challenge test (sometimes called the O'Sullivan test) is performed between 24 and 28 weeks, and can be seen as a simplified version of the oral glucose tolerance test (OGTT). No previous fasting is required for this screening test, in contrast to the OGTT. The O'Sullivan test involves drinking a solution containing 50 grams of glucose, and measuring blood levels one hour later.

If the cut-off point is set at 140 mg/dL (7.8 mmol/L), 80% of women with GDM will be detected. If this threshold for further testing is lowered to 130 mg/dL, 90% of GDM cases will be detected, but there will also be more women who will be subjected to a consequent OGTT unnecessarily.

Oral glucose tolerance test

A standardized oral glucose tolerance test (OGTT) should be done in the morning after an overnight fast of between 8 and 14 hours. During the three previous days the subject must have an unrestricted diet (containing at least 150 g carbohydrate per day) and unlimited physical activity. The subject should remain seated during the test and should not smoke throughout the test.

IADPSG (International Association of Diabetes and Pregnancy Study Groups) has developed diagnostic criteria for GDM, based on the results of adverse pregnancy outcomes in the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study. These were recommended by WHO 2013.

According to these gestational diabetes mellitus should be diagnosed at any time in pregnancy if one of the following criteria are met, using a 75 g glucose OGTT:

• Fasting blood glucose level ≥92 mg/dL (5.1 mmol/L)
• 1 hour blood glucose level ≥180 mg/dL (10 mmol/L)
• 2 hour blood glucose level ≥153 mg/dL (8.5 mmol/L)

Urinary glucose testing

Women with GDM may have high glucose levels in their urine (glucosuria). Although dipstick testing is widely practiced, it performs poorly, and discontinuing routine dipstick testing has not been shown to cause underdiagnosis where universal screening is performed. Increased glomerular filtration rates during pregnancy contribute to some 50% of women having glucose in their urine on dipstick tests at some point during their pregnancy. The sensitivity of glucosuria for GDM in the first two trimesters is only around 10% and the positive predictive value is around 20%.

Prevention

Vitamin D supplementation during pregnancy may help to prevent gestational diabetes. A 2015 review found that when done during pregnancy moderate physical exercise is effective for the prevention of gestational diabetes. A 2014 review however did not find a significant effect. It is uncertain if additional dietary advice interventions help to reduce the risk of gestational diabetes. However, data from the Nurses' Health Study shows that adherence to a healthy plant-based diet is associated with lower risk for GDM. Diet and physical activity interventions designed to prevent excessive gestational weight gain reduce the rates of gestational diabetes. However, the impact of these interventions varies with the body-mass index of the person as well as with the region in which the studies were performed.

Moderate-quality evidence suggest that there is a reduced risk of gestational diabetes mellitus and caesarean section with combined diet and exercise interventions during pregnancy as well as reductions in gestational weight gain, compared with standard care.

A 2023 review found that a plant-based diet (including fruits, vegetables, whole grains, nuts and seeds, and tea) rich in phytochemicals lowers the risk of GDM. A Cochrane review, updated 2023, stated that myo‐inositol has a potential beneficial effect of improving insulin sensitivity, which suggested that it may be useful for women in preventing gestational diabetes″.

It has been suggested that for women who have had gestational diabetes, diet, exercise, education, and lifestyle changes between pregnancies may lower their chances of having gestational diabetes again in future pregnancies. However, there is no research to show whether interventions between pregnancies lower the number of women who develop gestational diabetes again.

Management

Asosiy sahifa: Diabetes management

A kit with a glucose meter and diary used by a woman with gestational diabetes

Treatment of GDM with diet and insulin reduces health problems mother and child. Treatment of GDM is also accompanied by more inductions of labour.

A repeat OGTT should be carried out 6 weeks after delivery, to confirm the diabetes has disappeared. Afterwards, regular screening for type 2 diabetes is advised.

Lifestyle interventions include exercise, diet advice, behavioural interventions, relaxation, self-monitoring glucose, and combined interventions. Women with gestational diabetes who receive lifestyle interventions seem to have less postpartum depression, and were more likely to reach their weight loss targets after giving birth, than women who had no intervention. Their babies are also less likely to be large for their gestational age, and have less percentage of fat when they are born. More research is needed to find out which lifestyle interventions are best. Some women with GDM use probiotics but it is very uncertain if there are any benefits in terms of blood glucose levels, high blood pressure disorders or induction of labour.

If a diabetic diet or G.I. Diet, exercise, and oral medication are inadequate to control glucose levels, insulin therapy may become necessary.

The development of macrosomia can be evaluated during pregnancy by using sonography. Women who use insulin, with a history of stillbirth, or with hypertension are managed like women with overt diabetes.

Lifestyle

Counselling before pregnancy (for example, about preventive folic acid supplements) and multidisciplinary management are important for good pregnancy outcomes. Most women can manage their GDM with dietary changes and exercise. Self monitoring of blood glucose levels can guide therapy. Some women will need antidiabetic drugs, most commonly insulin therapy.

Any diet needs to provide sufficient calories for pregnancy, typically 2,000–2,500 kcal with the exclusion of simple carbohydrates. The main goal of dietary modifications is to avoid peaks in blood sugar levels. This can be done by spreading carbohydrate intake over meals and snacks throughout the day, and using slow-release carbohydrate sources—known as the G.I. Diet. Since insulin resistance is highest in mornings, breakfast carbohydrates need to be restricted more.

The Mediterranean diet may be associated with reduced incidence of gestational diabetes. However, there is not enough evidence to indicate if one type of dietary advice is better than another.

Regular moderately intense physical exercise is advised, although there is no consensus on the specific structure of exercise programs for GDM. Pregnant women who exercise have lower blood sugar levels when fasting and after meals compared to those who do not exercise. It is not clear which form of exercise is best when pregnant.

Self monitoring can be accomplished using a handheld capillary glucose dosage system. Compliance with these glucometer systems can be low. There is not a lot of research into what target blood sugar levels should be for women with gestational diabetes and targets recommended to women vary around the world. Target ranges advised by the Australasian Diabetes in Pregnancy Society are as follows:

• fasting capillary blood glucose levels <5.5 mmol/L
• 1 hour postprandial capillary blood glucose levels <8.0 mmol/L
• 2 hour postprandial blood glucose levels <6.7 mmol/L

Regular blood samples can be used to determine HbA1c levels, which give an idea of glucose control over a longer time period.

Research suggests a possible benefit of breastfeeding to reduce the risk of diabetes and related risks for both mother and child.

Medication

If monitoring reveals failing control of glucose levels with these measures, or if there is evidence of complications like excessive fetal growth, treatment with insulin might be necessary. This is most commonly fast-acting insulin given just before eating to blunt glucose rises after meals. Care needs to be taken to avoid low blood sugar levels due to excessive insulin. Insulin therapy can be normal or very tight; more injections can result in better control but requires more effort, and there is no consensus that it has large benefits. A 2016 Cochrane review (updated in 2023) concluded that quality evidence is not yet available to determine the best blood sugar range for improving health for pregnant women with GDM and their babies.

There is some evidence that certain medications by mouth might be safe in pregnancy, or at least, are less dangerous to the developing fetus than poorly controlled diabetes. When comparing which diabetes tablets (medication by mouth) work best and are safest, there is not enough quality research to support one medication over another. The medication metformin is better than glyburide. If blood glucose cannot be adequately controlled with a single agent, the combination of metformin and insulin may be better than insulin alone. Another review found good short term safety for both the mother and baby with metformin but unclear long term safety.

People may prefer metformin by mouth to insulin injections. Treatment of polycystic ovarian syndrome with metformin during pregnancy has been noted to decrease GDM levels.

Almost half of the women did not reach sufficient control with metformin alone and needed supplemental therapy with insulin; compared to those treated with insulin alone, they required less insulin, and they gained less weight. With no long-term studies into children of women treated with the drug, there remains a possibility of long-term complications from metformin therapy. Babies born to women treated with metformin have been found to develop less visceral fat, making them less prone to insulin resistance in later life.

Prognosis

Gestational diabetes generally resolves once the baby is born. Based on different studies, the chances of developing GDM in a second pregnancy, if a woman had GDM in her first pregnancy, are between 30 and 84%, depending on ethnic background. A second pregnancy within one year of the previous pregnancy has a large likelihood of GDM recurrence.

Women diagnosed with gestational diabetes have an increased risk of developing diabetes mellitus in the future. The risk is highest in women who needed insulin treatment, had antibodies associated with diabetes (such as antibodies against glutamate decarboxylase, islet cell antibodies and/or insulinoma antigen-2), women with more than two previous pregnancies, and women who were obese (in order of importance). Women requiring insulin to manage gestational diabetes have a 50% risk of developing diabetes within the next five years. Depending on the population studied, the diagnostic criteria and the length of follow-up, the risk can vary enormously. The risk appears to be highest in the first 5 years, reaching a plateau thereafter. One of the longest studies followed a group of women from Boston, Massachusetts; half of them developed diabetes after 6 years, and more than 70% had diabetes after 28 years. In a retrospective study in Navajo women, the risk of diabetes after GDM was estimated to be 50 to 70% after 11 years. Another study found a risk of diabetes after GDM of more than 25% after 15 years. In populations with a low risk for type 2 diabetes, in lean subjects and in women with auto-antibodies, there is a higher rate of women developing type 1 diabetes (LADA).

Children of women with GDM have an increased risk for childhood and adult obesity and an increased risk of glucose intolerance and type 2 diabetes later in life. This risk relates to increased maternal glucose values. It is currently unclear how much genetic susceptibility and environmental factors contribute to this risk, and whether treatment of GDM can influence this outcome.

Relative benefits and harms of different oral anti-diabetic medications are not yet well understood as of 2017.

There are scarce statistical data on the risk of other conditions in women with GDM; in the Jerusalem Perinatal study, 410 out of 37,962 women were reported to have GDM, and there was a tendency towards more breast and pancreatic cancer, but more research is needed to confirm this finding.

Research is being conducted to develop a web-based clinical decision support system for GDM prediction using machine learning techniques. Results so far demonstrated great potential in clinical practicality for automatic GDM prognosis.

Complications

GDM poses a risk to mother and child. This risk is largely related to uncontrolled blood glucose levels and its consequences. The risk increases with higher blood glucose levels. Treatment resulting in better control of these levels can reduce some of the risks of GDM considerably.

The two main risks GDM imposes on the baby are growth abnormalities and chemical imbalances after birth, which may require admission to a neonatal intensive care unit. Infants born to mothers with GDM are at risk of being both large for gestational age (macrosomic) in unmanaged GDM, and small for gestational age and Intrauterine growth retardation in managed GDM. Macrosomia in turn increases the risk of instrumental deliveries (e.g. forceps, ventouse and caesarean section) or problems during vaginal delivery (such as shoulder dystocia). Macrosomia may affect 12% of normal women compared to 20% of women with GDM. However, the evidence for each of these complications is not equally strong; in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study for example, there was an increased risk for babies to be large but not small for gestational age in women with uncontrolled GDM. In a recent birth cohot study of 5150 deliveries, a research group active at the University of Helsinki and Helsinki University Hospital, Finland demonstrated that the mother's GDM is an independent factor that increases the risk of fetal hypoxia, during labour. The study was published in the Acta Diabetologica in June 2021. Another finding was that GDM increased the susceptibility of the fetus to intrapartum hypoxia, regardless of the size of the fetus. The risk of hypoxia and the resulting risk of poor condition in newborn infants was nearly 7-fold in the fetuses of mothers with GDM compared to the fetuses of non-diabetic mothers. Furthermore, according to the findings, the risk of needing to perform resuscitation on the newborn after birth was 10-fold.

Another finding was that gestational diabetes increased the susceptibility of the fetus to intrapartal hypoxia, regardless of the size of the fetus.

"The risk of hypoxia and the resulting risk of poor condition in newborn infants was nearly seven-fold in the fetuses of mothers with gestational diabetes compared to the fetuses of non-diabetic mothers," says researcher Mikko Tarvonen. According to the findings, the risk of needing to perform resuscitation on the newborn was ten-fold.Research into complications for GDM is difficult because of the many confounding factors (such as obesity). Labelling a woman as having GDM may in itself increase the risk of having an unnecessary caesarean section.

Neonates born from women with consistently high blood sugar levels are also at an increased risk of low blood glucose (hypoglycemia), jaundice, high red blood cell mass (polycythemia) and low blood calcium (hypocalcemia) and magnesium (hypomagnesemia). Untreated GDM also interferes with maturation, causing dysmature babies prone to respiratory distress syndrome due to incomplete lung maturation and impaired surfactant synthesis.

Unlike pre-gestational diabetes, gestational diabetes has not been clearly shown to be an independent risk factor for birth defects. Birth defects usually originate sometime during the first trimester (before the 13th week) of pregnancy, whereas GDM gradually develops and is least pronounced during the first and early second trimester. Studies have shown that the offspring of women with GDM are at a higher risk for congenital malformations. A large case-control study found that gestational diabetes was linked with a limited group of birth defects, and that this association was generally limited to women with a higher body mass index (≥ 25 kg/m²). It is difficult to make sure that this is not partially due to the inclusion of women with pre-existent type 2 diabetes who were not diagnosed before pregnancy.

Because of conflicting studies, it is unclear at the moment whether women with GDM have a higher risk of preeclampsia. In the HAPO study, the risk of preeclampsia was between 13% and 37% higher, although not all possible confounding factors were corrected.

Epidemiology

Gestational diabetes affects 3–10% of pregnancies, depending on the population studied.

External links

• IDF Diabetes Atlas
• International Diabetes Federation
• National Institute of Child Health and Human Development – Am I at Risk for Gestational Diabetes?
• National Institute of Child Health and Human Development – Managing Gestational Diabetes: A Patient's Guide to a Healthy Pregnancy
• Gestational Diabetes Resource Guide – American Diabetes Association
• Diabetes.co.uk: Gestational Diabetes