Gestational diabetes

Gestational diabetes mellitus (GDM) is defined as carbohydrate intolerance first presenting in pregnancy, a definition that includes women with pre-existing diabetes first recognised in pregnancy and women who manifest glucose abnormalities for the first time during pregnancy. The prevalence of GDM varies according to diagnostic criteria, ethnicity and environment but may affect up to 20% of all pregnancies. GDM predisposes to obstetric complications associated with big babies such as shoulder dystocia and an increased need for assisted delivery, and may also lead to fetal complications such as birth trauma and neonatal hypoglycaemia. The risk of a wide range of adverse outcomes rises linearly and in parallel with glucose levels from within the "normal" range, thus complicating determination of a cut-off point for diagnosing GDM. The risks of macrosomia, shoulder dystocia and caesarean section can however be reduced considerably by glucose-lowering therapies. This has prompted a determined attempt to develop a international criteria for diagnosis and screening, although the cut-off for intervention is still subject to some dispute. GDM typically remits following pregnancy but confers a 7-fold risk of subsequent type 2 diabetes, and long-term follow up is indicated.

History of GDM

A newborn infant with typical diabetic macrosomia.
A newborn infant with typical diabetic macrosomia.
It has long been known that women with pregestational diabetes have complicated pregnancies with big babies and a greatly increased risk of fetal death. In 1930s it was suggested (and later confirmed) that non-diabetic women with big babies were more likely to develop diabetes later in life. This was initially thought to be a manifestation of an inherited trait, but was later seen to be due to a combination of maternal overweight and asymptomatic hyperglycemia in pregnancy.

Decades have since passed in the attempt to define the glycemic threshold for fetal and maternal risk in pregnancy, the underlying pathophysiology, and the best way of screening and managing the condition.

Mothers with GDM typically revert to normal glucose tolerance following pregnancy, but are very likely to develop type 2 diabetes in later life. They have accordingly often been studied as a model for the development of this condition.

Diagnosis of GDM

Gestational diabetes mellitus (GDM) is defined as carbohydrate intolerance resulting in hyperglycemia, with onset or first recognition during pregnancy[1], and is one of the most common medical complications of pregnancy. The prevalence of GDM is 1-20%, depending on ethnicity and classification, and this number is increasing[2]. The condition has important health implications for mother and child.

The definition of GDM includes women with undiagnosed glucose intolerance/pregestational diabetes, and those who develop glucose intolerance/diabetes during their pregnancy. The definition applies regardless of whether or not insulin is used for treatment or if the condition persists after pregnancy.

The HAPO study has clearly documented that increasing maternal glucose levels even in the non-diabetic range increase the risk of preeclampsia, preterm delivery, caesarean section, macrosomia, shoulder dystocia, neonatal hyperglycemia, admittance to neonatal intensive care unit (NICU) and jaundice in a linear way without infliction point[3].

Screening

Lack of consensus and uniformity for screening and diagnosis of GDM has been a problem ever since the existence of GDM was recognized. Since most women with GDM have no symptoms screening is necessary. Different screening approaches are used globally; some screen women with so-called risk factors, while others use universal screening. In general the diagnosis is made by an OGTT (75 or 100 g) performed at 24-28 weeks. The internationally used diagnostic criteria are also very different. Therefore the outcome based IADPSG criteria were proposed in 2010[4] in an attempt to obtain one set of internationally accepted criteria.

Pathogenesis of gestational DM

The second half of pregnancy is an insulin resistant state, where insulin secretion has to increase a few times to keep glucose tolerance normal. Most pregnant women are able to fulfil this increased demand of insulin but some are not. These women develop glucose intolerance – also called GDM.[5]

The majority of women with GDM are overweight or obese, and many have latent metabolic syndrome, a genetic predisposition to type 2 diabetes, a physically inactive lifestyle and unhealthy eating habits prior to pregnancy.

The risk factors for GDM are similar to those of type 2 diabetes: increased waist circumference, dyslipidemia, hypertension, polycystic ovary syndrome, increasing age, family history of diabetes and ethnicity (Asian, Hispanic).

Prenatal programming may also contribute to GDM whereby nutritional stress induced by both maternal undernutrition and overnutrition or maternal hyperglycemia during pregnancy persistently alter metabolism of the offspring.

A minority of women develop type 1 diabetes in pregnancy, and clinicians should be alert to this possibility, but GDM may in general be regarded as pre-type 2 diabetes.

Maternal complications of GDM

Maternal consequences include increased rate of operative and caesarean delivery, hypertensive disorders during pregnancy and future risk for type 2 diabetes mellitus as well as other aspects of the metabolic syndrome, such as obesity, cardiovascular morbidities and recurrent GDM. There are also maternal implications secondary to a delivery of a macrosomic or a large for gestational age fetus, such as an increased rate of caesarean delivery, postpartum hemorrhage, birth trauma and shoulder dystocia.

Fetal complications of GDM

Untreated, moderate or severe gestational diabetes mellitus (GDM) increases the risk of fetal and neonatal complications, and the risk of congenital malformations is slightly increased in infants of mothers with GDM compared to the general population. This increased risk of congenital malformations is found in the minority of GDM women entering pregnancy with increased glucose levels. Maternal obesity increases the risk of gestational diabetes and is an independent risk factor for perinatal complications. There is a positive correlation between maternal blood glucose levels and increased birth weight, and the risk of macrosomia can be reduced by treating glucose levels during pregnancy.[5][6]

Medical management of GDM

Two large RCT’s have documented that treatment of GDM is possible and effective[7][8] e.g. macrosomia can be reduced by 50%, preeclampsia by 30-50%, rate of Caesarean section by 0-20% and shoulder dystocia by 50%. The basic treatment is diet, but for some women (around 25%) medical treatment with e.g. insulin is needed. No preventive measure against GDM has been documented.

Obstetric management of GDM

There is no evidence to justify increased obstetric surveillance during pregnancy in women with diet-treated gestational diabetes who have no other risk factors. Nevertheless, most centres perform a few extra ultrasound scans to diagnose increased fetal growth. Pregnancy management in women with poorly controlled GDM, previously undiagnosed type 2 diabetes, and those whose fetuses have accelerated growth is similar to that in women with preexisting diabetes. Women with hypertension or whose fetuses are growth restricted should be monitored in the same manner as other pregnancies with such complications.

Prognosis for the mother

Although maternal glucose in general normalizes within days after delivery, women with previous GDM have a 7-fold increased risk [9] of developing diabetes in the years after pregnancy. The risk is primarily for type 2 diabetes but in some populations also for type 1 diabetes. In fact GDM is the best known predictor of type 2 diabetes. Furthermore these women have a markedly increased risk of the metabolic syndrome and cardiovascular disease[10] . Thus women with previous GDM are recommended to continue a healthy lifestyle after pregnancy and to loose weight if overweight. Their glucose tolerance should be checked by 1-3 years interval with an oral glucose tolerance test (OGTT), fasting plasma glucose or HbA1c to diagnose diabetes at an early stage.

Prognosis for the child

The offspring are also at increased risk of developing metabolic disease. A Danish study has e.g. shown a 8-fold increased risk of prediabetes/diabetes, a 2-fold risk for overweight and a 4-fold risk for the metabolic syndrome in young adult offspring of women with GDM[11].

References

  1. ^ Metzger BE. Summary and recommendations of the Fourth International Workshop-Conference on Gestational Diabetes Mellitus. Diabetes Care. 1998; 21(2): B161-B167.

  2. ^ Dabelea D, Snell-Bergeon JK, Hartsfield CL, Bischoff KJ, Hamman RF, McDuffie RS. Increasing prevalence of gestational diabetes mellitus (GDM) over time and by birth cohort: Kaiser Permanente of Colorado GDM Screening Program. Diabetes care. 2005;28(3):579-84.

  3. ^ HAPO Study Cooperative Research Group, Metzger BE, Lynn PL, Dyer AR, Trimble ER, Chaovarindr U, Coustan DR. Hyperglycemia and adverse pregnancy outcomes. N Engl J Med. 2008 May 8; 358(19): 1991-2002.

  4. ^ International Association of Diabetes and Pregnancy Study Groups consensus panel – Metzger BE, Gabbe SG, Persson B, Buchanan TA, Catalano PA, Damm P, Dyer AR, Leiva A, Hod M, Kitzmiler JL, Lowe LP, McIntyre HD, Oats JJ, Omori Y, Schmidt MI. International Association of Diabetes and Pregnancy Study Groups Recommendations on the Diagnosis and Classification of Hyperglycemia in Pregnancy. Diabetes Care 2010;33:676-682.

  5. ^ Buchanan TA, Xiang AH, Page KA. Gestational diabetes risks and management during and after pregnancy. Nat Rev Endocrinol. 2012 Nov; 8(11): 639-49.

  6. ^ H. E. Fadl, I. K. M. Ostlund, A. F. K. Magnuson and U. S. B. Hanson. Maternal and neonatal outcomes and time trends of gestational diabetes mellitus in Sweden from 1991 to 2003.Diabet. Med. 2010; 27, 436–441.

  7. ^ Crowther CA, Hiller JE, Moss JR, McPhee AJ, Jeffries WS, Robinson JS for the Australian Carbohydrate Intolerance Study in Pregnant Women (ACHOIS) Trial Group. Effect of Treatment of gestational diabetes mellitus on pregnancy outcomes. N Engl J Med. 2005; 352:2477-86.

  8. ^ Landon MB, Spong CY, Thom E, Carpenter MW, Ramin SM, Casey B et al. For the Eunice Kenedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. A multicenter, randomized trial of treatment for mild gestational diabetes. N Engl J Med. 2009; 361:1339-48.

  9. ^ Bellamy L, Casas JP, Hingorani AD, Williams D. Type 2 diabetes mellitus after gestational diabetes: a systematic review and meta-analysis. Lancet 2009;373(9677):1773-9.

  10. ^ Lauenborg L, Mathiesen E, Hansen T, Glümer C, Jørgensen T, Borch-Johnsen K, Hornnes P, Pedersen O, Damm P. The prevalence of the metabolic syndrome in a Danish population of women with previous GDM is 3-fold higher than in the general population. JCEM 2005;90:4004-10.

  11. ^ Clausen TD, Mahiesen ER, Hansen T, Pedersen O, Jensen DM, Lauenborg J, Schmidt L, Damm P. Overweight and the metabolic syndrome in adult offspring of women with diet-treated gestational diabetes mellitus or type 1 diabetes. JCEM 2009;94:2464-70.

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