Gestational Diabetes (Diabetes During Pregnancy) — Signs and Therapy

Definition of Gestational Diabetes

Gestational diabetes is defined as the first manifestation/recognition of a disruption of the glucose tolerance levels, which occurs during a pregnancy and ends within 6 weeks post-partum. It is triggered by an increased insulin resistance, which is caused by the pregnancy. The transition from so-called normal glucose tolerance levels during pregnancy and gestational diabetes are smooth; such a thing as a threshold value does not exist.

Epidemiology of Gestational Diabetes

About 2% of all pregnant women have gestational diabetes. The frequency differs between the various ethnic population groups: Asian and Latin American women are more likely to be affected by it than Caucasian women.

At the moment of birth, the GDM-prevalence in Germany has relatively increased by 2.52 times between 2002 and 2010. (AWMF guidelines.)

Etiology and Pathogenesis of Gestational Diabetes

The pathophysiology of gestational diabetes and diabetes type 2 are identical, for the most part. During the pregnancy, the carbohydrate metabolism changes. In the first trimester, increased estrogen and progesterone levels are associated with decrease in fasting blood sugar until 12 weeks of gestation.

From the second trimester on, there is a risk for a peripheral insulin resistance due to release of anti-insulin signals from the placenta. This triggers a rise in fasting and postprandial glucose leading to the transplacental transfers of glucose into the bloodstream of the fetus. Lowered transfer of maternal amino acids and increase carbohydrate mobilization to supply fetal demands follows this. Maternal carbohydrate metabolism is diverted into fat and this increases insulin resistance. Aside from the hormonal changes during the pregnancy, cytokine and adipokine may be released by the adipose tissue and the placenta.

Image: “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).” by User Meiquer. License: CC BY-SA 3.0

Risk factors for developing gestational diabetes

Certain risk factors facilitate the development of gestational diabetes.

• Record of diabetes mellitus within the family
• Age > 30 years
• Overweight (BMI > 27 kg/m²)
• Previous pregnancies with an overweight fetus (> 4.500 g)
• Arterial hypertonia, dyslipidemia prior to conception
• Polycystic Ovarian syndrome (PCO-syndrome)
• Anamnesis of CHD, PAOD
• Ingestion of medication against insulin (i.e. glucocorticoids)

Symptoms and Clinic of Gestational Diabetes

Case study

A case study about gestational diabetes could look like this.

A 36-year-old woman in the ninth week of pregnancy is carrying her second child. Her first pregnancy was unproblematic and the healthy child, who was born seven days after the due date, had a birth weight of 4280 g.

The values of the blood sugar tests in the second trimester were “marginal.“ During that first pregnancy, she gained a total weight of 18 kg and, despite occasional sports and “more vegetables and fruit,“ she was not able to lose the additional weight entirely. Her metabolism was not monitored during the pregnancy since she has moved in the meantime and has not found a family doctor yet.

With gestational diabetes, there is mostly not any of the initial discomforts due to the increased blood sugar levels; therefore, it does not cause the typical clinical picture of diabetes type 1. Polydipsia, glucosuria, changes in the quantity of amniotic fluids and arterial hypertension may occur. However, the possible disruption of the development of the fetus and the increased maternal risk for secondary diseases, are deciding factors. Infantile malformations (Fetopathia diabetica) are more common.

Complications of Gestational Diabetes

Complications for the mother

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  Image: “Measurement of the blood pressure of a pregnant woman.”  by nih.gov – http://www.nih.gov/researchmatters/november2009/images/preeclampsia_l.jpg. License: Public Domain

  Increased risk of urinary tract infections

• Development of a hypertensive disease with preeclampsia
• Excessive weight gain during the pregnancy
• Deterioration of an existing retinopathy and diabetic nephropathy that regresses 6 weeks after delivery
• Derailment of the metabolism (hyperglycemia)

Complications for the fetus

The organ that is most commonly affected by fetopathica diabetica is the heart leading to development of anomalies such as atrial and ventral septal defects, transposition of great arteries and tetralogy of Fallot. Other systems involved include the nervous system, renal and formation of abdominal wall defects. The risk of malformations increases with the level of HBA_1c.

Growth restriction and disturbances of the blood circulation in the placenta are also common. The resulting under-supply can lead to an intrauterine death.

Growth acceleration and fetal obesity are seen in 15-45% of cases.

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  Image: “Diabetes and High Blood Sugar.” by BruceBlaus. License: CC BY 3.0

  Hyperglycemia → polyuria (polyhydramnios), excessive insulin production and macrosomia of the child → increased size and weight of the fetus can cause problems at birth. (Example: shoulder dystocia.)

• Pulmonary malfunctions through premature lungs.
• Malfunctions of the liver (hyperbilirubinemia).
• Fetal beta cells of the pancreas adapt to the mother’s high glucose levels and react with hyperplasia and more secretion of insulin → this state suspends for a short amount of time, even after the placenta has been detached. It is the cause of hypoglycemia for a newborn child.
• Polycythemia triggered by hyperglycemia induced release of fetal erythropoietin. It may also be the cause of hyperbilirubinemia.
• Caudal regression syndrome (rare): malformation of the lower body half.
• Fetal programming: increased risk of developing adiposis, diabetes type 2.

Diagnosis of Gestational Diabetes

To diagnose gestational diabetes, an oral glucose tolerance test will be performed (oGTT), first a screening, then as a 75 g-oGTT.

1. Screening: pour 50 g of glucose into 200 ml of water, not dependent on the time of day or sobriety, measure the glucose level of the blood in venous plasma.
2. 75 g-oGTT: blood glucose level according to the screening > 135 mg/dl. 75 g of glucose in 300 ml of water within 3 – 5 minutes. Diagnostical threshold values in venous plasma are as follows.

Screening for gestational diabetes

All pregnant women should be screened for gestational diabetes between 24 – 28 weeks gestational age. Women that are at high-risk should be screened in the first trimester and again at 24 – 28 weeks if negative in the first trimester.

If a patient screens positive, a 3 h GTT is performed to diagnose gestational diabetes.

3 h GTT involves:

• A fasting blood sugar
• A 100 g glucose drink
• A 1 h, 2 h, and 3 h blood draw

Management of Gestational Diabetes

Dietary modification is the first line method of management of diabetes. If not controlled by diet, then oral hypoglycemic or insulin are needed.

Women with gestational diabetes have 15 – 50% lifetime risk of developing diabetes.

Blood glucose level target values

For the first two weeks, the target values will be aspired to be achieved by diet (switch to carbohydrates that are slowly absorbed, renunciation of industrial sugars, products made of superfine flour, etc). In case this approach fails, medicinal therapy with human insulin is possible.

Development of Gestational Diabetes

There is approximately a 50% risk for the mother to develop gestational diabetes again in case of another pregnancy. Additionally, the risk of developing diabetes mellitus type 2 is increased as well.

If the blood glucose levels are well adjusted, a premature induction of labor or C-section is unlikely.

Review Questions

The correct answers can be found below the references.

1. Which is no possible manifestation of gestational diabetes of the fetus?

1. Macrosomia
2. Hyperbilirubinemia
3. Pulmonary malfunctions
4. Polyhydramnios
5. Caudal regression syndrome

2. Medicinal therapy of gestational diabetes is carried out with

1. Metformin
2. Insulin analogues
3. Human insulin
4. Glucagon
5. Metoprolol

3. During therapy for gestational diabetes, what is the blood sugar target value in a state of sobriety?

1. 70 mg/dl
2. 100 mg/dl
3. 80 mg/dl
4. 90 mg/dl
5. 110 mg/dl