Progression to type 2 diabetes in women with a known history of gestational diabetes: systematic review and meta-analysis
BMJ 2020; 369 doi: https://doi.org/10.1136/bmj.m1361 (Published 13 May 2020) Cite this as: BMJ 2020;369:m1361Linked Opinion
Gestational diabetes—missed opportunities in post-partum follow-up
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Dear Editor
The systematic review and meta-analysis is an important reminder of the need for early and long term support of women who have been diagnosed with gestational diabetes. Gestational diabetes mellitus (GDM) has been well documented as a risk factor for the development of type 2 diabetes mellitus (T2DM) with cumulative incidences markedly increasing in the first 5 years post-delivery (Kim, Newton, & Knopp, 2002). The call for programmes to prevent or delay the progression from GDM to T2DM is a timely one and should positively impact the prevalence of T2DM.
During the gestational period the immediate need for the woman is a healthy child and the return of blood sugar to a normal range in the postpartum period. Post-delivery however, the demands of motherhood and shifting priorities could result in the mother’s neglect of her own health. Though mothers with GDM are often aware of the long term dangers and have intent to make lifestyle changes, the barriers are multiple and complex (Nielsen, Kapur, Damm, de Courten & Bygbjerg, 2014). The question is how does one ensure screening and the necessary uninterrupted follow up post-partum in the first 5 years and beyond?
A diagnosis is usually made based on recommended criteria and the aim is to control blood sugar to ensure a healthy baby and prevent potential difficulties during childbirth such as macrosomia and shoulder dystocia (World Health Organization [WHO], 2018). Nurses and in particular those trained as diabetes educators play a pivotal role in the provision of education especially to the mother and by extension family in the area of insulin self-administration and nutritional therapy.
There is no doubt that post-delivery, the recommendation having the best chance of improving outcomes in the mother with GDM is ‘intensive lifestyle interventions and /or Metformin to prevent diabetes” (American Diabetes Association, 2020). A structured programme or approach at all levels would become necessary to facilitate lifestyle changes to delay or prevent the progression to T2DM. Additional recommendations are postnatal checks and three-yearly screening for pre-diabetes and or diabetes. Four of every five adults with undiagnosed diabetes live in low – and middle income countries (LMICs) (IDF Diabetes Atlas, 2019). Developing national databases of all mothers with GDM is therefore important to generate new evidence especially in the LIMCs.. Prevention or delay in the development of diabetes in the LMIC would certainly improve productivity and reduce physical disabilities and health care costs. Emotional aspects, in particular, diabetes distress and depression impacting on productivity are also of concern. The study protocol for the Face-it study which is an intervention study will utilize health visitors; that is, nurses with specialized training in maternal, postnatal and child care in the health promotion to reduce the risk of T2DM in patients who have had GDM (Nielsen et.al, 2020).
Emerging evidence links diabetes to other health issues, therefore early identification and treatment of women with GDM would be strategic in keeping with the Sustainable Development Goals (UN, 2019). Further research regarding health-system and patient-related barriers to post-partum follow up for GDM women in LMICs is needed to inform policy and programme decisions (Muhwava, Murphy, Zarowsky, & Levitt, 2018). Investment in nurses as diabetes educators, dedicated to support postpartum follow up of women with GDM, could make a significant difference in reducing the high burden of type 2 diabetes in LMICs.
Publication bias was insignificant for the studies included in the analysis. However, there was no indication that unpublished data was used and once valid could be significant for the research. Future research should solicit resources to exclude language bias as diabetes affects all ethnic groups and could provide invaluable data. Inability to compute ethnic risk, lack of incidence rate data and absence of individual patient level data (IPD) are areas that need to be addressed. Meta-analyses of IPD, if resources allow, would yield patient level characteristics.
Sincerely,
Andrea Norman McPherson
References
American Diabetes Association (2020). Classification and diagnosis of diabetes: Standards of medical care in diabetes. Diabetes Care, 43(Suppl. 1):S14–S31 https://care.diabetesjournals.org/content/43/Supplement_1/S14
International Diabetes Federation (2019). IDF Diabetes Atlas 9th ed. Brussels, Belgium. Available at: https://www.diabetesatlas.org
Kim C., Newton K.M. & Knopp R.H. (2002). Gestational diabetes and the incidence of
type 2 diabetes: A systematic review. Diabetes Care, 25(10):1862–8. https://doi.org/10.2337/diacare.25.10.1862.
Muhwava, L. S., Murphy, K., Zarowsky, C., & Levitt, N. (2018). Policies and clinical practices relating to the management of gestational diabetes mellitus in the public health sector, South Africa - a qualitative study. BMC Health Services Research, 18(1), 349. https://doi.org/10.1186/s12913-018-3175-x
Nielsen, K. K., Kapur, A., Damm, P., de Courten, M., & Bygbjerg, I. C. (2014). From screening to postpartum follow-up - the determinants and barriers for gestational diabetes mellitus (GDM) services, a systematic review. BMC Pregnancy and Childbirth, 14, 41. https://doi.org/10.1186/1471-2393-14-41
Nielsen, K.K., Dahl-Petersen, I.K., Jensen, D.M., Ovesen, P., Damm, P., Jensen, N.H., Thøgersen, M., Timm, A., Hillersdal, L., Kampmann, U., Vinter, C. A., Mathiesen, E. R., Maindal, H.T. (2020). Protocol for a randomized controlled trial of a co-produced, complex, health promotional intervention for women with prior gestational diabetes and their families: The Face-it study.Trials 21, 146 (2020). https://doi.org/10.1186/s13063-020-4062-4
UN (2019). The Sustainable Development Goals Report 2019. UN, New York, https://doi.org/10.18356/55eb9109-en.
World Health Organization (2018). The WHO Reproductive Health Library. Geneva: WHO. Available from: www.who.int/rhl
Competing interests: No competing interests
Dear Editor,
Vounzoulaki and colleagues’ finding that women with a history of GDM are almost ten times more likely to develop T2DM, starkly underscores the importance of providing ongoing postnatal support for this high-risk group. However, postnatal and annual HbA1c screening alone is unlikely to achieve reduction in the risk of incident T2DM without access to interventions which support sustained lifestyle change in this population. There is currently a dearth of evidence regarding optimal timing, content, intensity and effectiveness of lifestyle change interventions in women who have had GDM.
Our patient and public engagement [1], and qualitative research [2] has found that while women with GDM are generally satisfied with their antenatal secondary care, they feel abandoned postnatally. They are uncertain what to expect from their GP in terms of follow-up, and experience significant barriers to optimising their diet and activity levels in the postnatal period [1].
These women feel postnatal care could be enhanced by peer support, multidisciplinary professional input, and subsidised exercise activities and facilities. Technology has the potential to act as an adjunct to this by providing access to tailored advice, enabling flexible and personalised self-management, and facilitating social support. Such interventions need to be based on sound behaviour change theory. Our more recent work has demonstrated the utility of the COM-B framework to code and the socio-ecological model to contextualise participant responses [3]. This has highlighted that a multi-level approach needs to be taken in the development of interventions for women with GDM. A top-down intervention approach is likely to be less effective than one which involves collaboration at the family and community level to ensure sustained
behaviour change [3].
One in twenty pregnant women in the UK develop GDM, and prevalence is increasing. The reduction of associated T2DM postnatally is an urgent public and primary healthcare priority. It is critical to intervene at both the antenatal and postnatal stage to reduce the likelihood that those with GDM will then go on to develop T2DM.
Sincerely,
Brian McMillan, Jen Boyd, Caroline Mitchell
References
1. McMillan, B., Easton, K., Goyder, E., Delaney, B., Madhuvrata, P., Abdelgalil, R., & Mitchell, C., (2018). Reducing risk of type 2 diabetes after gestational diabetes: a qualitative study to explore the potential of technology in primary care British Journal of General Practice, 68 (669): e260-e267. DOI: https://doi.org/10.3399/bjgp18X695297
2. McMillan B, Easton K, Delaney B, Mitchell C. Patient and public involvement research report. Reducing the risk of progression from Gestational Diabetes to Type 2 Diabetes Mellitus: women’s perspectives on the content, research development and evaluation of a mobile health technology lifestyle intervention to support postnatal dietary and activity lifestyle change. https://dx.doi.org/10.15131/shef.data.4509590
3. Mitchell, C., Boyd, J., McMillan, B., Easton, K., Delaney, B. What is the utility of the COM-B model in identifying facilitators and barriers to maintaining a healthy postnatal lifestyle following a diagnosis of gestational diabetes: a qualitative study. Proceedings of the SAPC Annual Scientific Conference, 15-17 July 2020 https://sapc.ac.uk/conference/2020/abstract/what-utility-of-com-b-model-...
Competing interests: No competing interests
Re: Progression to type 2 diabetes in women with a known history of gestational diabetes: systematic review and meta-analysis
Dear Editor
Vounzoulaki et al. conducted a meta-analysis to estimate the progression to type 2 diabetes mellitus (T2DM) in women with gestational diabetes mellitus (GDM) (1). The pooled relative risk (95% confidence interval [CI]) of GDM for T2DM was 9.51 (7.14 to 12.67). There was a racial difference in the cumulative incidence of T2DM in populations of women with previous GDM. The authors pointed out the importance of intervening to prevent the onset of T2DM in the early years after pregnancy of women with GDM.
Regarding the progress to T2D in women with GDM, Lai et al. conducted a 8-years postpartum follow-up study with special reference to lipidomics profiling (2). They identified 311 lipids positively and 70 lipids negatively associated with T2D risk. Increased glycerolipid metabolism and decreased sphingolipid metabolism both activated lipid storage before diabetes onset. A lipid signature was also identified to predict future diabetes risk. They concluded that GDM women with dyslipidemia during the early postpartum might have a risk of progression to T2D. I want to present information on lipid profiles in women with GDM.
Chodick et al. assessed the course of lipid levels over time in postpartum women with GDM (3). They adjusted potential confounders including comorbid conditions and body weight. Hazard ratios (95% CIs) of GDM for dyslipidemia defined by triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were 1.8 (1.73 to 1.88), 1.45 (1.38 to 1.52), and 1.44 (1.39 to 1.50), respectively. O'Malley et al. also examined the association between GDM and maternal dyslipidemia with special reference to obesity (4). Odds ratios (95% CIs) of women with GDM for increased TG, lower HDL-C, and increased TG/HDL-C were 3.2 (1.4 to 6.9), 2.2 (1.1 to 4.7), and 2.3 (1.1 to 4.9), respectively. These significant increases were only observed if women had obesity. I suppose that obesity control might be effective to prevent dyslipidemia in women with GDM. In addition, risk of increased TG was largest in their study, which was in concordance with data by Chodick et al. To verify the association between GDM and dyslipidemia, nutritional status and physical activity should also be checked for the analysis.
Regarding the risk of hyperlipidemia for GDM, Ryckman et al. conducted a meta-analysis on the relationship between lipid profiles during pregnancy and GDM (5). They confirmed that TG was predominantly elevated among women with GDM, and the finding persisted across all three trimesters of pregnancy. Although HDL-C level also significantly lowered among women with GDM, there was no significant difference in total cholesterol or LDL-C level between women with GDM and those without insulin resistance. This review also supports that TG is a most useful markers of dyslipidemia in women with GDM.
Prados et al. conducted a prospective study to evaluate the effect of GDM on atherogenic lipid profile during and after pregnancy (6). They clarified that women with previous GDM had a risk of postpartum dyslipidemia. They also presented a risk of postpartum T2DM caused by GDM, biological link between dyslipidemia and T2DM should be further explored in women with GDM.
Finally, Retnakaran et al. evaluated the relationship between GDM, gestational impaired glucose tolerance (GIGT) and lipid profile in pregnancy and the 3-month postpartum (7). By multiple linear regression analysis, they concluded that women with GDM had increased LDL-C and apolipoprotein B. In contrast, women with GIGT had increased total cholesterol to HDL ratio. According to the level of glucose intolerance during pregnancy, subsequent type of dyslipidemia might be changed.
References
1. Vounzoulaki E, Khunti K, Abner SC, et al. Progression to type 2 diabetes in women with a known history of gestational diabetes: systematic review and meta-analysis. BMJ 2020;369:m1361.
2. Lai M, Al Rijjal D, Röst HL, et al. Underlying dyslipidemia postpartum in women with a recent GDM pregnancy who develop type 2 diabetes. Elife 2020;9:e59153.
3. Chodick G, Tenne Y, Barer Y, et al. Gestational diabetes and long-term risk for dyslipidemia: a population-based historical cohort study. BMJ Open Diabetes Res Care 2020;8(1):e000870.
4. O'Malley EG, Reynolds CME, Killalea A, et al. Maternal obesity and dyslipidemia associated with gestational diabetes mellitus (GDM). Eur J Obstet Gynecol Reprod Biol 2020;246:67-71.
5. Ryckman KK, Spracklen CN, Smith CJ, et al. Maternal lipid levels during pregnancy and gestational diabetes: a systematic review and meta-analysis. BJOG 2015;122(5):643-51.
6. Prados M, Flores-Le Roux JA, Benaiges D, et al. Previous gestational diabetes increases atherogenic dyslipidemia in subsequent pregnancy and postpartum. Lipids 2018;53(4):387-392.
7. Retnakaran R, Qi Y, Connelly PW, Sermer M, Hanley AJ, Zinman B. The graded relationship between glucose tolerance status in pregnancy and postpartum levels of low-density-lipoprotein cholesterol and apolipoprotein B in young women: implications for future cardiovascular risk. J Clin Endocrinol Metab 2010;95(9):4345-53.
Competing interests: No competing interests