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Managing gestational diabetes

Siva Sivappriyan
MBBS MRCP (UK)
Specialist Registrar in Diabetes and Endocrinology

Stephanie E Baldeweg
MD FRCPI FRCP
Consultant Physician in Diabetes and Endocrinology

Department of Diabetes and Endocrinology
University College London Hospital NHS Foundation Trust

Gestational diabetes mellitus (GDM) occurs during pregnancy. Currently, the average estimated prevalence of GDM is roughly about 1-6% of pregnancies. It is important that healthcare professionals recognise GDM and initiate appropriate management early to prevent adverse prenatal outcomes

Diabetes mellitus is a metabolic disorder resulting from either a defect in the insulin secretion by pancreatic b-cell, insulin action or both. Gestational diabetes mellitus (GDM) occurs during pregnancy. Currently, the average estimated prevalence of GDM is roughly about 1-6% of pregnancies in different study populations.

It is estimated that global prevalence of diabetes is to rise from 308 million in 2007 to 380 million in 2025, of which 95% will be with type 2 diabetes. It is important that healthcare professionals recognise GDM and initiate appropriate management early to prevent adverse prenatal outcome.

What is GDM?
GDM is defined by the American Diabetes Association (ADA) and the World Health Organization (WHO) as, ''Any degree of glucose intolerance with onset or first recognition during pregnancy". These diagnostic criteria will include the women with pre-existing type 1 or type 2 diabetes diagnosed during pregnancy and women with impaired glucose tolerance or new development of diabetes during pregnancy. This diagnostic criterion does not include women who have already been diagnosed with diabetes before their pregnancy. GDM typically resolves following birth.

Women with GDM often lack any symptoms of hyperglycaemia. Symptoms of GDM are non-specific and include increased fatigue, excessive thirst, frequency of urination and nocturia. Obstetric investigations can show increased liquor volume or large for date baby.
 
During pregnancy there will be production of anti-insulin hormones like cortisol, human chorionic gonadotropin, placental growth hormone and human placental lactogen. This creates an insulin resistance state. This insulin resistance is greatest in the third trimester. GDM usually develops going into this period.

Why GDM is important?
Gestational diabetes can result in adverse foetal and maternal outcome. This risk can be reduced by improving glycaemic control during pregnancy. Also it has been increasingly recognised that a hyperglycaemic intrauterine environment appears to be involved in the pathogenesis of type 2 diabetes or pre-diabetes status in adult offspring.3

How do we diagnose GDM?
Various diagnostic criteria are used to diagnose GDM during pregnancy. The most commonly used criteria are shown in Table 1. A National Institute for Health and Clinical Excellence (NICE) expert panel has recommended a one-step approach with a two-hour 75 g oral glucose tolerance test (OGTT) to diagnose GDM using the criteria defined by WHO.2 This will be usually done at 24-28 weeks for at-risk pregnant mothers. If they had GDM during their previous pregnancy they should be offered self-glucose monitoring and OGTT at 16-18 weeks and if normal a repeat at 28 weeks' gestation. The ADA has adopted a two-step approach for the diagnosis of GDM.

[[Tab 1 GDM]]

Returning to our patients (Box 1), if we use the ADA recommendations for our first patient she meets the criteria for GDM. Our second patient has clear symptoms of diabetes and her random blood sugar clearly indicates that she has diabetes.

[[Box 1 GDM]]

It is not essential for her to undergo an OGTT to diagnose GDM. Each patient should be carefully assessed on an individual basis for any suspicion of GDM during pregnancy. NICE has also recommended the following groups as high risk for developing GDM.

High risk factors for GDM2

  • Body mass index (BMI) above 30 kg/m2.
  • Previous macrosomic baby weighing 4.5 kg or above.
  • Previous gestational diabetes.
  • Family history of diabetes (first-degree relative with diabetes).
  • Family origin with a high prevalence of diabetes:
        - South Asian (specifically, women whose country of
    family origin is India, Pakistan or Bangladesh)
        - Black Caribbean
        - Middle Eastern (specifically women whose country of family origin is Saudi Arabia, United Arab Emirates, Iraq, Jordan, Syria, Oman, Qatar, Kuwait, Lebanon or Egypt).

What are the complications of gestational diabetes?
The results of the hyperglycaemia and adverse pregnancy outcome (HAPO) study demonstrated the linear relationship between increasing levels of fasting, one hour and two hour plasma glucose in a 75 g oral glucose tolerance test to several significant adverse outcome endpoints.1 The International Association of Diabetes and Pregnancy Study Group (IADPSG) was formed in 1998 to collaborate between international groups interested in pregnancy and diabetes.

GDM results in maternal and foetal complications, including high rates of miscarriage, stillbirth, congenital anomalies and macrosomia, which can also cause birth injuries. Common maternal complications of GDM include increased incidence of hypertension during pregnancy, preterm labour, polyhydramnios and operative delivery. Neonatal complications include increased incidence of hypoglycaemia, hypocalcaemia, polycythaemia, respiratory distress and high bilirubin levels in the serum.

How do we manage GDM during pregnancy?
Management of diabetes during pregnancy requires a multidisciplinary approach with diabetologists, obstetricians, diabetic specialist nurses, midwives and dietitians in a joint clinic. Regular obstetric assessment is needed to identify any related complications early. We can target management of GDM at three different stages of the pregnancy - preconception, antenatal and postnatal.

Preconception period
Preconception advice should be offered to mothers who had GDM during a previous pregnancy.

Antenatal
Initial management of GDM includes education, self-monitoring of glucose and exercise. Glycaemic control can be achieved by diet alone or pharmacological therapy with insulin or metformin.

Dietary advice
Dietary advice is the cornerstone in the management of GDM. This should be given by a dietitian with a special interest in GDM. The aim is to keep the glucose within target, without compromising nutrients to the mother and foetal growth. Dietary advice will help to limit the weight gain in obese pregnant women.

Self-glucose monitoring
Self-glucose monitoring is strongly recommended by NICE.2 Women should be taught how to monitor glucose with glucometers. The target glucose is fasting glucose of less than 5.5 mmol/l and 1 hour postprandial glucose of less than 7.5 mmol/l.

Exercise
Moderate exercise has been shown to improve glycaemic control in GDM.

Pharmacological therapy
If pregnant women fail to achieve glycaemic control with diet alone they should be offered pharmacotherapy with insulin or oral hypoglycaemic agents.

Insulin
The standard treatment for GDM is insulin. There are various types available, including short-acting insulin, such as insulin aspart and intermediate-acting insulin, such as insulin lispro. Insulin therapy should be initiated by a diabetes specialist nurse with a special interest in GDM. Follow-up is required to titrate the insulin requirements. Generally, the insulin requirements will increase with the advancement of the pregnancy due to the increasing levels of anti-insulin.

Oral hypoglycaemic agents
Oral antidiabetic agents are increasingly popular. They are easy to administer and cost effective. Metformin sensitises the action of the insulin and inhibits the production of glucose from the liver. In the Metformin in Gestational Diabetes (MiG) trial, metformin (alone or with supplemental insulin) is not associated with increased perinatal complications as compared with insulin. In this trial the women preferred metformin to insulin treatment.5 Other agents that are second-generation sulphonylureas, like glibenclemide and glyburide, can also be considered as alternatives to metformin.

Postnatal period and long-term management
GDM during pregnancy is a recognised risk factor for future development of type 2 diabetes with the incidence of 20-60% of affected women within five years. Women who had GDM during pregnancy should be offered a fasting blood sugar as per NICE guidelines or OGTT as per ADA during the postpartum period.

Appropriate lifestyle advice should be given to prevent them developing diabetes or GDM in the future. These include weight management, regular exercise and smoking cessation. Women should be tested regularly in the years following GDM to allow early detection of type 2 diabetes.

References
HAPO Study Cooperative Research Group. The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study. Int J Gynaecol Obstet 2002;78:69-77.
National Institute for Health and Clinical Excellence (NICE). Diabetes in pregnancy: management of diabetes and its complications from pre-conception to the postnatal period. London: NICE; 2008. Available from: www.nice.org.uk/CG63
Pettitt DJ, Knowler WC. Long-term effects of the intrauterine environment, birth weight, and breastfeeding in Pima Indians. Diabetes Care 1998;21(Suppl 2):B138-41.
Hadar M, Hod M. Establishing consensus criteria for the diagnosis of diabetes in pregnancy following the HAPO study. Ann N Y Acad Sci 2010;1205(1):88-93.
Rowan JA, Hague WM, Gao W, Battin MR, Moore MP; MiG Trial Investigators. Metformin versus insulin for the treatment of gestational diabetes. New Engl J Med 2008;358(19):2003-15.