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Gestational Diabetes Mellitus – Causes, Risk factors, and Treatment.

Introduction

Gestational diabetes mellitus defined as “carbohydrate intolerance of variable severity with onset or first recognition during pregnancy”. Diabetes is a common condition in which the body’s cells are unable to effectively obtain glucose from the bloodstream. Glucose is required to provide the body with energy for day-to-day activities. The hormone insulin moves glucose from the blood into the body’s cells, where it can be used for energy.

 

Pathophysiology of gestational diabetes mellitus

During pregnancy, the maternal tissues become insensitive to insulin. It occurs due to the placental lactogen hormone and other hormones, such as progesterone, cortisol and growth hormone. When the pancreas is unable to offer an appropriate response of insulin to compensate normal insulin resistance, GDM is present.

 

The resistance to insulin leads to maternal hyperglycemia, and this stimulates the fetal hyperinsulinemia. Insulin secretion increases at the beginning of pregnancy, whereas the sensitivity to insulin remains unchanged. At around 20 weeks of pregnancy, insulin sensitivity reduces progressively and it is even lower in the third trimester. However, after birth, the GMD disappears almost immediately

History behind GDM

The first documented evidence of the effects of hyperglycaemia in pregnancy in the modern era was in 1824, when Bennewitz recorded a case of severe fetal macrosomia and stillbirth in a 22 year old multigravida woman in Berlin. She had symptoms of severe hyperglycaemia, but he was only able to estimate this by boiling the urine to dryness.

Until the discovery of insulin in 1923 there was no effective treatment for this condition, and the outcome of pregnancy for both mother and fetus was usually disastrous. The first attempt to define the concept of ‘hyperglycaemia in pregnancy’ was over 50 years ago in Boston USA.

A sub-committee of the World Health Organisation subsequently decided that the results of a two hour 75g oral glucose tolerance test derived from non-pregnant men and women could be used in pregnancy, with a cut-off point decided by consensus. These two different sets of criteria have continued to be used in various parts of the world to the present day.

The term ‘Gestational Diabetes Mellitus’ (GDM) was not universally used until popularised by Freinkel in Chicago in a major paper in 1980. In this wide ranging presentation ‘Of Pregnancy and Progeny’ , incorporating several important insights into the pathophysiology of glucose metabolism in both mother and fetus, he developed his concepts of more subtle consequences of faulty maternal insulinisation. This led to an American Diabetes Association sponsored workshop, and a definition of gestational diabetes as ‘glucose intolerance with onset or first recognition during pregnancy’

Epidemic view of gestational diabetes

The prevalence of GDM in India varied from 3.8 to 21% in different parts of the country, depending on the geographical locations and diagnostic methods used. GDM has been found to be more prevalent in urban areas than in rural areas. For a given population and ethnicity, the prevalence of GDM corresponds to the prevalence of impaired glucose tolerance (IGT) (in non-pregnant adult) within that given population.

What causes gestational diabetes mellitus?

  1. Growth hormones
  2. Cortisol (a stress hormone)
  3. Estrogen and progesterone
  4. Human placental lactogen (a hormone produced in the placenta that helps break down fat from the mother to provide energy for the fetus)
  5. Placental insulinase (another hormone from the placenta that inactivates insulin)

Who is at increased risk of gestational diabetes?

  1. South Asian
  2. Vietnamese
  3. Chinese
  4. Middle Eastern
  5. Polynesian/Melanesian

Complications associated with GDM

Symptoms

Usually there are no symptoms, or the symptoms are mild and not life threatening to the pregnant woman. The blood sugar (glucose) level usually returns to normal after delivery. Symptoms may include:

Diagnosis and Testing of GDM

Gestational diabetes usually starts halfway through the pregnancy. GDM is diagnosed if the woman has either:

Oral glucose tolerance test

All pregnant women should receive an oral glucose tolerance test between the 24th and 28th week of pregnancy to screen for the condition. Women who have risk factors for gestational diabetes may have this test earlier in the pregnancy.

Criteria for Diagnosis of GDM with a 2-hour Pregnancy Oral GTT

Diagnosis Fasting plasma glucose

(mmol/l)

1-hour glucose (mmol/l)

following 75g oral

glucose load

2-hour glucose

(mmol/l) following

75g oral glucose

load

Normal < 5.1 < 10.0 < 8.5
GDM 5.1 – 6.9 > 10.0 8.5 – 11.0

Glycosylated hemoglobin, or hemoglobin A1c test

Glycosylated hemoglobin, or hemoglobin A1c, is another test that may be performed. This test is used to monitor long-term blood glucose levels in people with diabetes. The hemoglobin A1c level offers a measure of the average blood glucose level over the past few months.

Treatment of gestational diabetes mellitus

The goals of treatment are to keep blood sugar (glucose) levels within normal limits during the pregnancy, and to make sure that the growing baby is healthy.

Watching your baby

Your health care provider should closely check both you and your baby throughout the pregnancy. Fetal monitoring will check the size and health of the fetus. A nonstress test is a very simple, painless test for you and your baby.

Medical Nutrition Therapy (MNT)

All women with GDM should receive nutritional counseling. The meal pattern should provide adequate calories and nutrients to meet the needs of pregnancy. The expected weight gain during pregnancy is 300–400 g per week and total weight gain is 10–12 kg by term.

The best way to improve your diet is by eating a variety of healthy foods. You should learn how to read food labels, and check them when making food decisions. Talk to your doctor or dietitian if you are a vegetarian or on some other special diet. In general, when you have gestational diabetes your diet should:

If managing your diet does not control blood sugar (glucose) levels, you may be prescribed diabetes medicine by mouth or insulin therapy.

Insulin therapy

Once diagnosis is made, medical nutritional therapy (MNT) is advised initially for 2 weeks. If MNT fails to achieve control, i.e. FPG ~90 mg/dL and/or post-meal glucose ~120 mg/dL, insulin may be initiated.

  1. Preferable to start with Premix insulin 30/70 of any brand. Starting dose: 4 units before breakfast

Every 4th day increase 2 units till 10 units

If FPG remains > 90 mg/dL advise → 6 units before breakfast and 4 units before dinner

Review with blood sugar test Adjust dose further

Total insulin dose per day can be divided as two-thirds in the morning and one-third in the evening.

Initially if post-breakfast plasma glucose is high → Start Premix 50/50

  1. If GDM is diagnosed in the third trimester; MNT is advised for a week. Insulin is initiated if MNT fails.
  2. If 2-hour PG > 200 mg/dL at diagnosis, a starting dose of 8 units of premixed insulin could be administered straightaway before breakfast and the dose has to be titrated on follow-up. Along with insulin therapy, MNT is also advised.

There are different types of premixed insulin.

Locations of insulin injection

Prevention of gestational diabetes mellitus

There are no guarantees when it comes to preventing gestational diabetes — but the more healthy habits you can adopt before pregnancy, the better. If you’ve had gestational diabetes, these healthy choices may also reduce your risk of having it in future pregnancies or developing type 2 diabetes down the road.

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