Overview Of Diabetes In Pregnancy

Diabetes mellitus has been an important topic worldwide as its incidence has been increasing for the past few decades which is concurrence with the increased of obesity trend. Even though most of us are aware of the consequences of being a diabetic, practising what is considered as healthy can be quite difficult especially if this particular lifestyle was not adopted early on. Diabetes mellitus can be classified into two types which are type I and type II, everyone knew that! However, do you know that pregnant women are predisposed to get diabetes which is neither of those types? It's called gestational diabetes or diabetes in pregnancy.

Like any type of diabetes, gestational diabetes is diagnosed among pregnant women who were found to have a deranged blood glucose reading or beyond a specified range as indicated by various guidelines such as RCOG, Malaysian Clinical Practice Guideline (CPG) and NICE. Each guideline might give a different set of reading but the discrepancy is not that significant. For example, in the NICE guideline (which has been reviewed in July 2018), the value for a deranged fasting blood glucose level is 5.6 mmol/L while in the Malaysian CPG for gestational diabetes, the value for a deranged fasting blood glucose reading is 5.1 mmol/L; this value was adopted from the Malaysian Endocrine & Metabolic Society (MEMS) and the Ministry of Health, Malaysia.

As a future clinician, when it comes to the different guidelines adopted by different hospitals, it's important for me to know, what is the normal clinical value for the fasting blood glucose adopted by the hospital in which I was working in to determine the next step of the patient's management. In hospitals which are governed by the Ministry of Health, a reading of fasting blood glucose of 5.4 mmol/L would require a referral to a dietitian for diet control as all of those hospitals are required to use Malaysian CPG as their primary guideline but in teaching hospitals in Malaysia which are governed by the ministry of high education, the value is within a normal range (provided they were using the NICE guideline) and the only thing in which we (clinicians) are required to do is to give them some advice regarding their diet and current lifestyle. No active management is required.

So why women who are pregnant are predisposed to get diabetes? Before I explain why is it common for people who pregnant to be affected by these pathophysiological changes, you should know that people who were tested positive for deranged blood glucose readings during pregnancy are those who were diagnosed as gestational diabetes. Those who have diabetes prior to conception are people who have pre-existing diabetes mellitus of either type, often called pre-gestational diabetes. It's important for people who have diabetes to stabilise their own blood glucose readings and level of glycosylated blood component (often called Hb1Ac) before planning for conception. This is due to the fact that most of the women with poor diabetic control have a higher chance of facing bad obstetric histories such as miscarriage, fetal organs' malformation and any other associated anomalies.

People with diabetes who were planning to get pregnant will be prescribed with 500 microgram folic acid tablets that have to be taken daily until 12th week period of gestation to prevent the incidence of neural tube defect (any associated anomalies related to the brain, spine and spinal cord). Instituting folic acid tablets as prophylaxis to neural tube defect would be able to reduce as high as 50% of the occurrences of the aforementioned defect which is a huge upgrade in the future quality of life of fetuses. This medication act by ensuring the methylation and DNA biosynthesis process were intact in the soon-to-be-born fetus so that they would have a proper neural tube closure. There are so much to be done for people who are diabetics and they are planning of getting pregnant.

In the hospital whereby I was posted, gestational diabetes is extremely common along with maternal obesity and pregnancy at advanced maternal age (more than 35 years old). It was established in the Manual of Obstetrics textbook which was published by Lippincott Williams and Wilkins that as high as 90% of all the total pregnancies are associated with gestational diabetes. Although it could be pathological for some, in others, gestational diabetes is caused by physiological changes that happen during pregnancy which alters maternal carbohydrate metabolism so that more of the macronutrient is available for the growing fetus.

Insulin is an important hormone which aids the entry of glucose into the cells so that it can be utilised as energy sources. Too much glucose in the blood circulation for a long period of time can cause dire consequences which manifest itself as macro and microvascular complications in people who were having diabetes. In pregnancy, various hormones (oestrogens, progesterone, human placental lactogen and prolactin) are released to aid the growth of the fetus and most (if not all of them) confer antagonistic effect to insulin action. We can say that people who were pregnant experienced a state of insulin resistance that would resolve as soon as the baby is out. This condition is further complicated by the existence of a hormone which is released by the placenta that degrades insulin called insulinase.

Other hormones such as cortisol would worsen the insulin resistance which would stimulate the pancreas to produce more insulin but more does not necessarily correlate to effectiveness. If the pancreas can't provide enough insulin to compensate the increased glucose, those people would be diagnosed with gestational diabetes. This effect would often be exaggerated in people with pre-existing diabetes thus careful planning by multidisciplinary team combined with good patient's factors (disease awareness, adherence to insulin therapy, diet control) would increase the chances of them to successfully give birth to a healthy fetus.

According to the Malaysian CPG, there are a few risk factors which predisposed women to get gestational diabetes thus requiring them to be tested so that it can be identified and treated early:

• Body mass index (BMI) of more than 27 kg/m²
• Gestational diabetes in the previous pregnancy
• First degree relative with diabetes mellitus
• History of giving birth to a baby with more than 4 kg of birth weight (macrosomia)
• Any bad obstetric history (intrauterine death, neural tube defect, shoulder dystocia)
• Urine glucose of more than or equal to 2+ on two occasions
• Experiencing any obstetric problem (polyhydramnios, pregnancy-induced hypertension)

Previously, women are thought to have an increased risk of getting gestational diabetes if they conceive after 35 years old of age but based on the current evidence, any women who aged 25 years old and above are required to submit themselves to a universal screening test. If they have any other risk factor which has been listed above, they should be tested in between 12 to 16 weeks of pregnancy and if it is normal, the test should be repeated when they were at 26 to 28 weeks of pregnancy. A negative result after this point (26 to 28 weeks) would mean a high improbability of getting gestational diabetes, although there are some cases of late-onset gestational diabetes which have been recorded in the literature.

In Malaysia, almost all hospitals were well-equipped with whatever necessary to conduct gestational diabetes screening, so universal screening can be employed. Any people who don't have any of the aforementioned risk factors except maternal age factor, they should be tested in between 26 to 28 weeks. However, if there are some administrative issues (financials, equipment) then selective screening can be practised by testing people who have at least one of the aforementioned risk factors along with maternal age factor. However, it should be noted that if selective screening to be practised, particularly among the Asian population, then we can expect most of the women who have gestational diabetes would be missed as people who were presented with the above risk factors only constitute about 30-40% out of all of the women who have gestational diabetes. According to the Malaysia CPG, gestational diabetes would be diagnosed if:

• Fasting plasma glucose is more than or equal to 5.1 mmol/L
• 2-hours post meal glucose of more than 7.8 mmol/L

The level of acceptable fasting plasma glucose would depend on the type of guideline you were using. In NICE guideline, fasting plasma glucose of less than 5.6 mmol/L is still considered normal.

In terms of management, it usually executed in a specific arrangement. Pregnant women who were found to have a deranged blood glucose level (either fasting or 2 hours post meal) would be advised on diet control and given referrals to dietitians. Lifestyle modifications are important to reduce the need for further interventions. Gestational weight gain would be recorded and calories needed would be adjusted so that the total weight gain for the whole pregnancy would be appropriate to BMI of the pregnant woman. Gaining excessive weight would increase the risk of weight retention post delivery and eventually maternal obesity later in life. They would be monitored every two weeks and if blood glucose control is still suboptimal, then 500 mg metformin tablets would be prescribed. The last resort would be to prescribe insulin injection but the need for insulin therapy would depend on the following criteria:

• The optimal blood glucose level is not achieved despite proper diet control and metformin therapy
• The patient is contraindicated for metformin therapy
• Fasting plasma glucose of more than or equal to 7.0 mmol/L (even without metformin therapy)
• Fasting plasma glucose in between 6.0 to 6.9 mmol/L with evidence or suspicion of gestational diabetes complications (macrosomia, polyhydramnios etc.); even without metformin therapy.

Sounds simple yet it's difficult. Patients should be encouraged to participate actively so that blood glucose control can be optimised and any of the risk and complications related to gestational diabetes can be avoided. After delivery, ideally, 6 weeks, women who are diagnosed with gestational diabetes would be screened once again. If they were negative, then, it would be fine but if they were positive for deranged blood glucose, the diagnosis would be changed to diabetes mellitus type II. Pregnant women who were diagnosed with gestational diabetes would have a 50% risk of getting diabetes mellitus type II later in life.

References: [1], [2], [3]

All images were taken from Pixabay

Images: [1], [2], [3], [4], [5], [6]