Gestational Diabetes

 

Overview

Gestational diabetes mellitus (GDM) can be defined as glucose intolerance diagnosed in the second or third trimester of pregnancy with no previous diagnosis of diabetes before pregnancy (Joy A Dugan, 2019). Many studies found that gestational diabetes occurs in 2.2–8.8% of pregnancies (Cheung, 2009). gestational diabetes is seen in up to 14% of the population worldwide (José Alberto Laredo-Aguilera, 2020). In some countries, the frequency may reach as much as around 25.5% of pregnancies affected by gestational diabetes based on the International Association of Diabetes and Pregnancy Study Groups criteria (Irma Silva-Zolezzi, 2017).

A degree of intolerance of glucose developed during pregnancy is associated with a risk of future complications such as hypertension, high blood pressure, urinary tract infection, diabetes in the future, excess amniotic fluid building up during pregnancy, or increased operative intervention (Begum, 2016).

To determine the glucose level in the blood to be hyperglycemia, the International Association of Diabetes in Pregnancy Study Groups (IADPSG) derived a value by a Hyperglycaemia Adverse Pregnancy Outcome (HAPO) study data for pregnant women without known diabetes should have a 75 g on oral glucose tolerance test at 24–28 weeks gestation (Ryan, 2011).

The presence of high glucose levels in the blood may result in a short-term or long-term negative impact on the mother and the infant such as the increased risk of obesity in the infant and the mother leading to the development of type 2 diabetes mellitus in the future (Irma Silva-Zolezzi, 2017)

The increasing trend on increase in gestational diabetes may be due to suboptimal lifestyle and nutrition (Irma Silva-Zolezzi, 2017). The major risk factors for gestational diabetes are maternal age, ethnicity, family history of type 2 diabetes mellitus, history of gestational diabetes in a prior pregnancy, high-risk ethnicity, history of Polycystic ovary syndrome (PCOS), less physical activity, hypercholesterolemia, poor pregnancy outcome, pre-existing hypertension or cardiovascular disease, or a prior large baby ≥4000 g (Michelle Lende, 2020; Cheung, 2009; Begum, 2016; Caitlin MacGregor, 2020).

Diabetes mellitus is the most prevalent disease worldwide, affecting almost 370 million people and 4.8 million deaths annually (Irma Silva-Zolezzi, 2017).

Many studies have observed that maternal obesity is the root cause of gestational diabetes (Sarah R Murray, 2020; Emma C Johns, 2018; Michelle Lende, 2020). Obesity is defined as a body mass index of ≥30 Kg/m^{2 (Michelle Lende, 2020; Begum, 2016; Caitlin MacGregor, 2020)}.

Gestational diabetes (GDM) can be classified into two types, which are A1GDM and A2GDM. Management of gestational diabetes with nutritional therapy and without medications known as A1GDM (diet-controlled gestational diabetes). If diabetes needs medication to control glucose and cannot be controlled by diet is called A2GDM (Bryan S Quintanilla Rodriguez, 2022).

Majority of the gestational diabetes is asymptomatic and unsuspected for women weeks of pregnancy. Hence asymptomatic pregnant women need to be screened at 24-28 weeks' gestation (Dugan & Ma-Crawford, 2019; Mayo, 2019). The other signs or symptoms observed during gestational diabetes are more frequent urination and increased thirst (Mayo, 2019).

Pathophysiology of Gestational Diabetes

In pregnant women, there is a 60% reduction in insulin sensitivity. A study on rats was conducted to know the pathophysiology of gestational diabetes (Michelle Lende, 2020).

During pregnancy, maternal glucose is transported across the placenta to the fetus due to the concentration gradient formed between the fetus and the maternal glucose level. The fetus diverts a large amount of glucose towards itself causing demand in the maternal glucose level. This demand increases the production of glucose in the mother and results in glucose build-up in the blood. This in turn increases the demand for insulin production by pancreatic β-cell mass. When the β-cell expansion fails a relatively inadequate rise in insulin secretion leads to GDM (Michelle Lende, 2020). In women with normal functions during pregnancy, the pancreas compensates for the secretion of insulin for physiologic insulin resistance. But when the maternal pancreas fails to respond to the increased insulin requirements from the pancreatic beta cells causes gestational diabetes (Dugan & Ma-Crawford, 2019).

This is similar to patients with type 2 diabetes. However, in a majority of the cases, the post-partum maternal insulin sensitivity quickly returns to normal (Chloe A Zera, 2021; Begum, 2016).

Prevention

Effective and safe exercise and increased intake of fresh fruits have proven that it has reduced the risk of gestational diabetes. In addition, they should consume a limited quantity of dry fruits and sausages. Below are the preventive measures that can be taken to prevent gestational diabetes.

·        Health food: high fibre but low fat and calories contained fruits, vegetables, and whole grains

·        Physically active: a brisk daily walk, a short walk, and 30 minutes of moderate activity

·        Initiate pregnancy at a healthy weight: weights lost before or during planning to get pregnant

·        Keeping track of weight gain: maintain a reasonable level of weight gain during the gestational period (Irma Silva-Zolezzi, 2017; Polina Viktorovna Popova, 2017; Bryan S Quintanilla Rodriguez, 2022)

Diagnosis

In 1973 a study was conducted to describe the screening test for gestational diabetes of 50 g, 1-hour oral glucose tolerance test. This was considered the most reliable method to determine if one has gestational diabetes. The normal range during pregnancy is 130 mg/dL (7.22 mmol/L). Any value ≥140 mg/dL (7.77 mmol/L) is considered to be GDM (Bryan S Quintanilla Rodriguez, 2022).

In 1985, a routine screening test for pregnant women was conducted considering the high risk for gestational diabetes (Michelle Lende, 2020). Standards of Medical Care in Diabetes, the American Diabetes Association (ADA) recommends single-step and two-step processes to determine GDM (Dugan & Ma-Crawford, 2019).

·        One-step fasting test includes a 75 g oral glucose tolerance test at 1 hour and 2 hours. Any values ≥92 mg/dL at fasting or ≥180 mg/dL after 1 hour or ≥153 mg/dL after 2 hours will be diagnostic for gestational diabetes (Dugan & Ma-Crawford, 2019)

·        A confirmatory test is necessary by 100 g, 3-hour oral glucose tolerance test, and the normal values are at 1 hour: ≤180 mg/dL, 2 hours: ≤155 mg/dL, and 3 hours: ≤140 mg/dL. The presence of two or more abnormal results establishes the diagnosis of gestational diabetes (Bryan S Quintanilla Rodriguez, 2022; Chloe A Zera, 2021)

Glycosuria is another method to determine glucose intolerance in blood. This is a urine test conducted using a reagent strip. The test needs to be done 2 or more times at a single incidence or more than one time on many occasions (Begum, 2016). It is recommended that the initial test be conducted before 24 weeks gestation, known as early blood glucose screening (Watson, 1990).

Effect of gestational diabetes

Perinatal and offspring are affected by long-term gestational diabetes mellitus (Emily D Szmuilowicz, 2019). Gestational diabetes mellitus confers lifelong risks to both women and their children (Chloe A Zera, 2021). Potential adverse outcomes seen in offspring exposed to gestational diabetes mellitus are listed below (Emily D Szmuilowicz, 2019).

There are a few short-term effects of gestational diabetes mellites, which include excessive birth weight (>4 kg), hypoglycemia, and respiratory distress (Sarah R Murray, 2020).

The increase in glucose in the fetus results in the increased production of fetal insulin. This causes fetal hyperinsulinemia, which leads to excessive fetal growth resulting in forming of a big baby. There are possibilities of birth complications including a high risk of cesarean, slow or difficult labour or birth, or birth injury due to a large baby (Emily D Szmuilowicz, 2019).

Relatively, the oxygen availability to the fetus is disturbed due to the hyperinsulinemia that changes lung surfactant synthesis. This in turn causes distress to the respiratory system causing unavailability of oxygen to the fetus resulting in stillbirth and admission to the neonatal intensive care unit (Emily D Szmuilowicz, 2019; Mayo, 2019).

As gestational diabetes causes increased glucose levels in the blood that is passed to the fetus. This causes increased production of insulin in the fetus. During delivery, the supply of glucose is abruptly stopped. This makes the insulin utilize the available neonatal glucose, resulting in neonatal hypoglycemia (Emily D Szmuilowicz, 2019).

The other complication observed in gestation diabetes mellitus in the fetus and neonatal are malformations, serious infection, preterm birth, jaundice, cardiometabolic risk in both childhood and adulthood, neurodevelopmental impairments, increased adiposity, insulin resistance, and high glucose levels (less than diagnosis range for diabetes) (Cheung, 2009; Sarah R Murray, 2020; Dugan & Ma-Crawford, 2019; Emily D Szmuilowicz, 2019).

The other long-term effect on adults is obesity, insulin resistance, cesarean delivery, high glucose levels (less than the diagnosis range for diabetes), and type 2 diabetes mellitus (Ryan, 2011).

Intervention

Initial diagnosis and prevention are the best practice to keep the glucose level in control. Hence one should have enough knowledge of the various precautions to be taken to prevent getting gestational diabetes (Cheung, 2009; Dugan & Ma-Crawford, 2019).

Dietary and physical activity

As per Aguilera et al., the performance of physical activity and maintenance of gestational diabetes have positive relationships. There is up to 70–85% of gestational diabetes can be managed with adequate physical activity, and dietary, and lifestyle changes (Michelle Lende, 2020; José Alberto Laredo-Aguilera, 2020).

Approximately 80-90% of women’s gestational diabetes can be managed by medical nutritional therapy. The therapy includes the following diet and activities:

·        3 small to moderate-sized meals

·        2 to 3 snacks

·        balanced diet including whole-grain carbohydrates, protein, and unsaturated fats

·        moderate physical activity: 30 mins of moderate-intensity aerobic exercise for at least 5 days per week or a minimum of 150 mins per week (Emily D Szmuilowicz, 2019)

Pharmaceutical intervention

Insulin

In case gestational diabetes is not controlled using diet and physical exercise, then they are recommended to use insulin as first-line therapy. Insulin does not cross the placenta at a significant level. The different types of insulin used are:

·        Fasting hyperglycemia: basal insulin (long or intermediate-acting)

·        Postprandial hyperglycemia: prandial insulin (rapid-acting)

Oral agents

1.      Glyburide (glibenclamide)

This medication has a risk of macrosomia and neonatal hypoglycemia as they are suspected to cross the placenta.

2.      Metformin 

Metformin also freely crosses over the placenta and is determined to have an equal or larger fetal metformin concentration than maternal concentration. It has a mixed outcome of less maternal weight gain, lower postprandial glucose, and less pregnancy-induced hypertension, but higher rates of preterm birth.

 

The ACOG, ADA, and Diabetes Canada insist on to use of insulin as the first-line agent for the treatment of gestational diabetes. Other societies recommend metformin to the patient only when they are unable or unwilling to take insulin (Chloe A Zera, 2021). The list of preferred medications for gestational diabetes mellites by each society is listed in Table 1.

Table 1: Recommendation for treatment of gestational diabetes mellites

Organization	First line	Alternative first line	Second line	Third linear insulin
ADA	Insulin	–	Metformin or glyburide for women who cannot safely take insulin. Do not use in women with hypertension, pre-eclampsia, or at risk for intrauterine growth restriction	–
ACOG	Insulin	–	Metformin for women who decline, cannot safely take, or cannot afford insulin	Glyburide
SMFM	Metformin	Insulin	–	–
NICE	Metformin only if mild fasting hyperglycemia (glucose <108 mg/dL) and no complications	Insulin if fasting glucose ≥126 mg/dL; consider starting with insulin if fasting glucose is 108–125 mg/dL or obstetric complications	–	Glibenclamide
Diabetes Canada	Insulin	Metformin	–	Glyburide
ACOG = American College of Obstetricians and Gynecologists; ADA = America Diabetes Association; N/A = not applicable; NICE = National Institute for Health and Care Excellence; SMFM = Society for Maternal-Fetal Medicine Source: (Chloe A Zera, 2021)

Other oral hypoglycaemic agents for type 2 diabetes are not recommended during pregnancy (Chloe A Zera, 2021).

The treatment for gestational diabetes is preferred by altering lifestyle and pharmacological intervention based on the level of complication. After obtaining positive results on gestational diabetes mellites, one should consult a doctor.

References

Begum, P. R. R. a. J., 2016. Screening and Diagnosis of Gestational Diabetes Mellitus, Where Do We Stand. J Clin Diagn Res, p. 10(4): QE01–QE04.

Bryan S Quintanilla Rodriguez, H. M., 2022. Gestational Diabetes, Treasure Island (FL): StatPearls Publishing.

Caitlin MacGregor, A. F. L. K.-D. W. G. P. W. H. N. S. C. B. A. B., 2020. Maternal perceived discrimination and association with gestational diabetes. Am J Obstet Gynecol MFM, p. 2(4):100222.

Cheung, N. W., 2009. The management of gestational diabetes. Vasc Health Risk Manag, p. 5:153–164.

Chloe A Zera, E. W. S., 2021 . Controversies in Gestational Diabetes. touchREV Endocrinol, p. 17(2):102–107.

Emily D Szmuilowicz, J. L. J. a. B. E. M., 2019 . Gestational Diabetes Mellitus. Endocrinol Metab Clin North Am, p. 48(3):479–493.

Emma C Johns, F. C. D. J. E. N. R. M. R., 2018 . Gestational Diabetes Mellitus: Mechanisms, Treatment, and Complications. Trends Endocrinol Metab, pp. 29(11):743-754.

Irma Silva-Zolezzi, T. M. S. J. S., 2017 . Maternal nutrition: opportunities in the prevention of gestational diabetes. Nutr Rev, pp. 75(suppl 1):32-50.

José Alberto Laredo-Aguilera, M. G.-B. A. R.-S. A. I. C.-C. a. J. M. C.-T., 2020. Physical Activity Programs during Pregnancy Are Effective for the Control of Gestational Diabetes Mellitus. Int. J. Environ. Res. Public Health, pp. 17(17),6151.

Joy A Dugan, J. M. C., 2019 . Managing gestational diabetes. Journal of the American Academy of Physician Assistants, pp. 32:9;21-25.

Mayo, C., 2019. Gestational diabetes - Symptoms and causes. [Online]
Available at: https://www.mayoclinic.org/diseases-conditions/gestational-diabetes/symptoms-causes/syc-20355339

Michelle Lende, A. R., 2020 . Gestational Diabetes: Overview with Emphasis on Medical Management. Int J Environ Res Public Health, p. 21;17(24):9573.

Polina Viktorovna Popova, A. S. T. Y. A. B. A. S. G. K. A. D. E. A. P. L. V. K. E. N. G., 2017. Risk of gestational diabetes mellitus: Which lifestyle parameters should be changed?. Diabetes Mellitus, pp. 20(1),85-92.

Ryan, E. A., 2011. Diagnosing gestational diabetes. Diabetologia , pp. 54,480–486.

Sarah R Murray, R. M. R., 2020. Short- and long-term outcomes of gestational diabetes and its treatment on fetal development. Prenat Diagn, pp. 40(9):1085-1091.

Watson, W. J., 1990. Screening for glycosuria during pregnancy. South Med J, pp. 83(2):156-8.