Prognosis for the mother
Gestational diabetes is one of the best predictors of type 2 diabetes, and the level of risk is modulated by factors affecting both the pregnancy and postpartum period. In most instances the diabetic state will resolve soon after delivery. In the longer term, however, these women are at risk of developing diabetes or glucose intolerance. Diabetes and prediabetes apart, the increased morbidity observed in women with a history of gestational diabetes typically relates to the associated disorders of hypertension, hyperlipidemia and insulin resistance. No large scale intervention study has been performed in women with previous gestational diabetes following delivery, and the cost and benefit of regular follow-up screening for hyperglycemia is unknown.
The pathophysiology of gestational diabetes (GDM) is similar to that of type 2 diabetes (T2DM) with a defect in insulin resistance or secretion, or both. Furthermore the two entities share common type 2 diabetes risk gene variants. T2DM is also what the majority of women will develop if they develop diabetes following a pregnancy complicated by GDM, a risk that has been estimated to be more than 70% in cohorts followed up to 28 years. This makes GDM one of the best predictors for T2DM. A minority of the women will have type 1 diabetes or a monogenic diabetes such as maturity onset diabetes of the young (MODY).
Risk factors for manifest diabetes
The risk of developing overt diabetes depends on several factors. One important factor is the diagnostic test applied in pregnancy for diagnosing GDM. Unlike the oral glucose tolerance test (OGTT) used for diagnosing T2DM, no universal test exists for diagnosing GDM. The different tests are developed at different locations in different populations, and the diagnostic criteria are based on different outcome. They use different glucose loads, different cut off levels and different time measurement points.
Recently The International Association of the Diabetes and Pregnancy Study Group (IADPSG) has proposed a new set of recommendations for diagnosing hyperglycemia in pregnancy. The recommendations are based on the results from a large multicenter study (The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study) on neonatal outcome according to blood glucose levels during a 2 hour oral glucose tolerance test with 75 g glucose. The new criteria are not as yet adopted worldwide. One major concern is that lowering the cut-off level will markedly increase the prevalence of GDM. Another criticism is based around the absence of evidence that treating milder cases of GDM is beneficial.
Leaving to one side the issue of the best diagnostic test to use in pregnancy, several other pregnancy-associated factors confer an increased risk of progression to diabetes. These include:
- gestational age at diagnosis of GDM,
- blood glucose level at diagnosis,
- the need for insulin to treat GDM
- the gestational stage at which insulin becomes necessary. Use of insulin does however vary markedly between centres.
- ethnicity, body mass index and physical activity are also associated with a higher risk of diabetes.
- a test diagnostic for diabetes 2-3 months after pregnancy is also highly predictive for the development of diabetes within a few years.
Table 1: Possible risk factors of type 2 diabetes in women with a history of gestational diabetes
|Pregestational BMI||Hyperglycemia within 2-6 months after delivery||Ethnicity|
|Blood glucose levels at diagnosis||BMI at follow up||Previous GDM|
|Gestational age at diagnosis||Age/length of follow up|
|Insulin treatment||Physical activity|
For postpartum testing and later follow up, screening with a 75g OGTT, evaluated according to WHO criteria is recommended. Half of the cases with prediabetes will have impaired glucose tolerance and testing with fasting blood glucose alone will deprive subjects at high risk of the possible benefit of intervention and/or treatment. The same is in evidence for random blood glucose or glycated haemoglobin (HbA1c).
With regular testing for diabetes after a pregnancy complicated by GDM, the cumulative incidence of T2DM increases rapidly over the first five years after pregnancy and more slowly after 10 years. GDM is one of the best predictors of future diabetes and the women should be advised to go for regular testing of glucose tolerance with the first testing a few months after delivery and thereafter yearly or every second year. However, no large scale study exists regarding intervention in women with previous gestational diabetes and normal glucose tolerance and the benefit of early diagnosis of hyperglycaemia is unknown.
The metabolic syndrome
Women with a history of GDM are more insulin resistant and more often diagnosed with the metabolic syndrome, which may be detected even in normal weight, glucose tolerant women. The metabolic syndrome with central obesity and hypertension, dyslipidimia or hyperglycaemia, helps predicting individuals at high risk of type 2 diabetes and cardiovascular disease. The definition of the metabolic syndrome has changed through the years and between nationalities. In the early years, the definition included insulin resistance that can be difficult to estimate. Today, we know that visceral fat results in insulin resistance and visceral fat is easily measured as waist circumference.
Lifestyle intervention is known to reduce the risk of progression to T2DM in subjects with impaired glucose tolerance, and intervention and/or metformin treatment in women with a history of GDM and impaired glucose tolerance may reduce the risk of progression to T2DM. Based on studies in subjects with prediabetes and due to the increased risk of T2DM compared with women without a history of GDM, lifestyle intervention, even in glucose tolerant women, should be recommended. However, it has not been demonstrated that regular testing and early intervention in glucose intolerant women can reduce morbidity and prolong life. Neither do we know if maintaining a continuous healthy lifestyle after a pregnancy complicated by GDM has any positive effect. The advice to keep a healthy lifestyle is based solely upon data from intervention studies in people with impaired glucose tolerance.
|Recommendation for women with a history of GDM|
|Regular testing for glucose tolerance|
|Regular control of body weight, waist circumference, blood pressure and lipid profile|
|Healthy lifestyle including healthy, but not diabetes, diet|
|Daily physical activity|
^ Kim C, Newton KM, Knopp RH. Gestational Diabetes and the Incidence of Type 2 Diabetes: A systematic review. Diabetes Care 2002 Oct;25(10):1862-8.
^ Lauenborg J, Hansen T, Jensen DM, Vestergaard H, Mølsted-Pedersen L, Hornnes P, et al. Increasing incidence of diabetes after gestational diabetes mellitus – A long-term follow-up in a Danish population. Diabetes Care 2004 May;27(5):1194-9.
^ Metzger BE, Gabbe SG, Persson B, Buchanan TA, Catalano PA, Damm P, et al. International association of diabetes and pregnancy study groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy. Diabetes Care 2010 Mar;33(3):676-82.
^ The diagnosis of gestational diabetes mellitus: new paradigms or status quo? J Matern Fetal Neonatal Med 2012 Dec;25(12):2564-9.
^ Committee opinion no. 504: screening and diagnosis of gestational diabetes mellitus. Obstet Gynecol 2011 Sep;118(3):751-3.
^ Dornhorst A, Rossi M. Risk and prevention of type 2 diabetes in women with gestational diabetes. Diabetes Care 1998 Aug;21 suppl.2:B43-B49.
^ Lauenborg J, Mathiesen E, Hansen T, Glumer C, Jorgensen T, Borch-Johnsen K, et al. The prevalence of the metabolic syndrome in a danish population of women with previous gestational diabetes mellitus is three-fold higher than in the general population. J Clin Endocrinol Metab 2005 Jul;90(7):4004-10.
^ Alberti KG, Zimmet P, Shaw J. Metabolic syndrome--a new world-wide definition. A Consensus Statement from the International Diabetes Federation. Diabet Med 2006 May;23(5):469-80.
^ Ratner RE, Christophi CA, Metzger BE, Dabelea D, Bennett PH, Pi-Sunyer X, et al. Prevention of diabetes in women with a history of gestational diabetes: effects of metformin and lifestyle interventions. J Clin Endocrinol Metab 2008 Dec;93(12):4774-9.
^ Tuomilehto J, Lindstrom J, Eriksson JG, Valle TT, Hamalainen H, Ilanne-Parikka P, et al. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med 2001 May 3;344(18):1343-50.