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An ounce of prevention…

Published:February 24, 2017DOI:https://doi.org/10.1016/j.ajog.2017.01.024
      Related article, page 340.
      A number of factors have contributed to the estimated 16% prevalence of gestational diabetes mellitus (GDM) in diverse populations around the world.
      • Guariguata L.
      • Linnenkamp U.
      • Beagley J.
      • Whiting D.R.
      • Cho N.H.
      Global estimates of the prevalence of hyperglycaemia in pregnancy.
      As of 2014, 39% of the world’s adults were overweight, and 13% were obese.

      World Health Organization. Obesity and overweight. Available at: http://www.who.int/mediacentre/factsheets/fs311/en/. Accessed December 10, 2016.

      In the United States in that same year, 70% of adults were overweight or obese

      Centers for Disease Control and Prevention. Health, United States, 2015. Available at: https://www.cdc.gov/nchs/data/hus/hus15.pdf#053. Accessed December 16, 2016.

      ; 40% were obese, and 10% had a body mass index of >40 kg/m2 (class 3 obesity).
      • Flegal K.M.
      • Kruszon-Moran D.
      • Carroll M.D.
      • Fryar C.
      • Ogden C.L.
      Trends in obesity among adults in the United States, 2005-2014.
      Among adolescent girls aged 12–19 years, 21% were obese and 8% were extremely obese (≥120% of the 95th percentile for age).
      • Ogden C.L.
      • Carroll M.D.
      • Lawman H.G.
      • et al.
      Trends in obesity prevalence among children and adolescents in the United States, 1988-1994 through 2013-2014.
      This epidemic of overweight and obesity has been associated with a simultaneous increased prevalence of type 2 diabetes mellitus.

      World Health Organization. Diabetes. Available at: http://www.who.int/mediacentre/factsheets/fs312/en/. Accessed December 10, 2016.

      Various conditions associated with insulin resistance have also become more common in the United States
      • Aguilar M.
      • Bhuket T.
      • Torres S.
      • Liu B.
      • Wong R.J.
      Prevalence of the metabolic syndrome in the United States, 2003-2012.
      and presumably throughout the world. In some populations, childbearing has been postponed well into adulthood so that increasing maternal age is also likely a contributor.

      Centers for Disease Control and Prevention. Mean Age of Mothers is on the Rise: United States, 2000–2014. Available at: http://www.cdc.gov/nchs/products/databriefs/db232.htm. Accessed December 10, 2016.

      Furthermore, there is credible evidence in some ethnic groups that exposure to maternal hyperglycemia while in utero places the offspring at increased risk for childhood and adult obesity and type 2 diabetes mellitus later in life.
      • Pettit D.J.
      • Aleck K.A.
      • Baird H.R.
      • Carraher M.J.
      • Bennett P.H.
      • Knowler W.C.
      Congenital susceptibility to NIDDM: role of intrauterine environment.
      • Clausen T.D.
      • Mathiesen E.R.
      • Hansen T.
      • et al.
      High prevalence of type 2 diabetes and pre-diabetes in adult offspring of women with gestational diabetes mellitus or type 1 diabetes the role of intrauterine hyperglycemia.
      This would suggest the potential for a runaway “feedback loop” with more GDM predisposing the offspring to obesity and insulin resistance, leading to more GDM in each successive generation.
      Observational studies have demonstrated a continuous relationship between maternal oral glucose tolerance test (OGTT) glucose levels and various adverse pregnancy outcomes in the offspring, such as macrosomia and hyperinsulinemia with associated neonatal adiposity.
      HAPO Study Cooperative Research Group
      Hyperglycemia and adverse pregnancy outcomes.
      Adverse outcomes in the mother such as increasing cesarean delivery rates and hypertensive disorders of pregnancy have also been documented.
      HAPO Study Cooperative Research Group
      Hyperglycemia and adverse pregnancy outcomes.
      Randomized controlled trials (RCTs) have demonstrated that identification and treatment of even mild degrees of glucose intolerance can decrease the likelihood of adverse pregnancy outcomes.
      • Landon M.B.
      • Spong C.Y.
      • Thom E.
      • et al.
      A multicenter, randomized trial of treatment for mild gestational diabetes.
      • Crowther C.A.
      • Hiller J.E.
      • Moss J.R.
      • et al.
      Effect of treatment of gestational diabetes mellitus on pregnancy outcomes.
      The International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria for the diagnosis of GDM,
      International Association of Diabetes and Pregnancy Study Groups
      Recommendations on the diagnosis and classification of hyperglycemia in pregnancy.
      the only thresholds that are based on pregnancy outcomes, are being adopted increasingly around the world.
      • Hod M.
      • Kapur A.
      • Sacks D.A.
      • et al.
      The International Federation of Gynecology and Obstetrics (FIGO) Initiative on gestational diabetes mellitus: a pragmatic guide for diagnosis, management and care.
      World Health Organization
      Report of a WHO consultation: diagnostic criteria and classification of hyperglycaemia first detected in pregnancy: a World Health Organization guideline.
      They use a 75-g, 2-hr OGTT rather than the traditional (in the United States) 100-g, 3-hr OGTT and require only 1 (or more) elevated value(s) to diagnose GDM. Pregnant women meeting the IADPSG criteria, but not the traditional GDM criteria, have been shown to be at significantly increased risk of adverse outcomes.
      • Waters T.P.
      • Dyer A.R.
      • Scholtens D.M.
      • et al.
      Maternal and neonatal morbidity for women who would be added to the diagnosis of GDM Using IADPSG criteria: a secondary analysis of the Hyperglycemia and Adverse Pregnancy Outcome study.
      The use of these criteria will allow more at-risk gravid women to receive interventions that, it is hoped, will prevent some of the adverse outcomes and dampen the aforementioned cycle of mother-to-child transmission. However, use of the IADPSG criteria will further increase the proportion of gravid women with GDM who require such interventions, placing added stress on already limited healthcare resources. For these reasons, novel approaches to prevention of GDM, and innovative models for lower resource use in treatment when GDM is present, are critically important.
      The RCT by Wang et al
      • Wang C.
      • Wei Y.
      • Zhang X.
      • et al.
      A randomized clinical trial of exercise during pregnancy to prevent gestational diabetes mellitus and improve pregnancy outcome in overweight and obese pregnant women.
      published in this issue of the Journal tests an approach to the prevention of GDM in high-risk women in Beijing. One-half of 300 overweight or obese gravid women were assigned randomly to a supervised fairly intensive exercise program throughout the second and third trimesters; the other one-half of the women received routine prenatal care. RCTs are extremely labor intensive for the investigators and, in this case, for the subjects as well. The recruitment rate of 44% of eligible participants is extremely impressive for a study that involved overweight or obese, presumably sedentary, individuals committing to a supervised 30-minute stationary cycle exercise session 3 times weekly for approximately 23 weeks! Only 25% of each group (exercise and control) dropped out over the course of the trial, and 90% of those in the exercise group who continued attended ≥80% e of scheduled sessions. The study used the IADPSG criteria for GDM that used a 75-g 2-hr OGTT, which were adopted in China in August 2014. In the control group 41% of the women experienced GDM. This very high rate may be attributed to the high-risk nature of the subjects (all overweight or obese) as well as the use of the less stringent IADPSG diagnostic criteria. The rate of GDM was decreased by almost one-half to 22% in the group that was assigned to the exercise regimen. Such a reduction in GDM is a remarkable achievement and offers great promise as an approach to ameliorating the increasing GDM epidemic described earlier.
      Metaanalyses of RCTs of exercise to prevent or treat GDM have reported mixed results
      • Hans S.
      • Middleton P.
      • Crowther C.A.
      Exercise for pregnant women for preventing gestational diabetes mellitus.
      • Sanabria-Martínez G.
      • García-Hermoso A.
      • Poyatos-León R.
      • Álvarez-Bueno C.
      • Sánchez-López M.
      • Martínez-Vizcaíno V.
      Effectiveness of physical activity interventions on preventing gestational diabetes mellitus and excessive maternal weight gain: a meta-analysis.
      ; in the current RCT, an important feature appears to be the early institution of regular exercise at the beginning of the second trimester. The exercising group gained significantly less weight than the control group during the second trimester (4.1 vs 5.9 kg). As the authors point out, the lack of weight gain difference between groups in the third trimester could be at least partially related to the fact that 40% of the women in the control group were diagnosed with GDM and that the interventions applied in these pregnancies might have limited their third-trimester weight gain.
      • Wang C.
      • Zhu W.
      • Wei Y.
      • Feng H.
      • Su R.
      • Yang H.
      Exercise intervention during pregnancy can be used to manage weight gain and improve pregnancy outcomes in women with gestational diabetes mellitus.
      The third-trimester weight gain in the 2 groups was so similar (4.6 kg in each group) that this explanation may not be adequate to explain the phenomenon. The finding that reductions in weight gain (compared with control group) were limited to the second trimester supports the role of early institution of the intervention.
      Some important questions remain to be answered about the generalizability of this strategy to other populations. Are there ethnic differences in the impact of exercise on carbohydrate metabolism? Similar trials in other ethnic groups will be helpful. It seems likely that there will be varying degrees of willingness or resistance to this approach in different populations and cultures. Will it be feasible to convince overweight and obese gravid women in other settings and circumstances to participate in a similar exercise regimen from early pregnancy? Although direct supervision of the exercise sessions was critical to the study design, such an approach may be quite costly and limit the applicability in underfunded healthcare systems. Will an exercise prescription be followed under nonexperimental, less closely supervised, conditions? It also remains to be determined whether other forms of exercise may be similarly effective in settings where the availability of cycle ergometry exercise equipment is limited. If most of these questions can be answered affirmatively, there will be a relatively low-tech intervention that can help to interrupt the cycle of ever increasing GDM.
      This report raises other intriguing possibilities. Women with a history of GDM are at increased risk for the development of type 2 diabetes mellitus as the years go by. In the Diabetes Prevention Program RCT, when women with a history of GDM who met the criteria for prediabetes were assigned randomly to lifestyle intervention, metformin or usual care, those in the control group experienced type 2 diabetes mellitus at a rate of 15% per year, although the rate in the 2 treatment groups was halved.
      • Ratner R.E.
      • Christophi C.A.
      • Metzger B.E.
      • et al.
      Prevention of diabetes in women with a history of gestational diabetes: effects of metformin and lifestyle interventions.
      This suggests potential long-term benefits to the program of exercise during pregnancy. Introducing sedentary overweight and obese women to a regimen of exercise performed at least 3 times weekly during pregnancy might influence them to continue in this healthy lifestyle subsequently. Will the decrease in weight gain over the course of pregnancy be carried over and result in less retained weight over time? A decision analysis demonstrated that the IADPSG recommendations for diagnosing GDM would be cost-effective only if women with GDM received intensive counseling and care after delivery to prevent type 2 diabetes mellitus.
      • Werner E.F.
      • Pettker C.M.
      • Zuckerwise L.
      • et al.
      Screening for gestational diabetes mellitus: are the criteria proposed by the International Association of Diabetes and Pregnancy Study Groups cost-effective?.
      If gravid women are willing to follow an intervention such as this and if it is effective in other populations, this could be an effective way to introduce overweight and obese women who are at risk for type 2 diabetes mellitus to the kind of lifestyle intervention needed for primary prevention!

      References

        • Guariguata L.
        • Linnenkamp U.
        • Beagley J.
        • Whiting D.R.
        • Cho N.H.
        Global estimates of the prevalence of hyperglycaemia in pregnancy.
        Diabetes Res Clin Pract. 2014; 103: 176-185
      1. World Health Organization. Obesity and overweight. Available at: http://www.who.int/mediacentre/factsheets/fs311/en/. Accessed December 10, 2016.

      2. Centers for Disease Control and Prevention. Health, United States, 2015. Available at: https://www.cdc.gov/nchs/data/hus/hus15.pdf#053. Accessed December 16, 2016.

        • Flegal K.M.
        • Kruszon-Moran D.
        • Carroll M.D.
        • Fryar C.
        • Ogden C.L.
        Trends in obesity among adults in the United States, 2005-2014.
        JAMA. 2016; 315: 2284-2291
        • Ogden C.L.
        • Carroll M.D.
        • Lawman H.G.
        • et al.
        Trends in obesity prevalence among children and adolescents in the United States, 1988-1994 through 2013-2014.
        JAMA. 2016; 315: 2292-2299
      3. World Health Organization. Diabetes. Available at: http://www.who.int/mediacentre/factsheets/fs312/en/. Accessed December 10, 2016.

        • Aguilar M.
        • Bhuket T.
        • Torres S.
        • Liu B.
        • Wong R.J.
        Prevalence of the metabolic syndrome in the United States, 2003-2012.
        JAMA. 2015; 313: 1973-1974
      4. Centers for Disease Control and Prevention. Mean Age of Mothers is on the Rise: United States, 2000–2014. Available at: http://www.cdc.gov/nchs/products/databriefs/db232.htm. Accessed December 10, 2016.

        • Pettit D.J.
        • Aleck K.A.
        • Baird H.R.
        • Carraher M.J.
        • Bennett P.H.
        • Knowler W.C.
        Congenital susceptibility to NIDDM: role of intrauterine environment.
        Diabetes. 1988; 37: 622-628
        • Clausen T.D.
        • Mathiesen E.R.
        • Hansen T.
        • et al.
        High prevalence of type 2 diabetes and pre-diabetes in adult offspring of women with gestational diabetes mellitus or type 1 diabetes the role of intrauterine hyperglycemia.
        Diabetes Care. 2008; 31: 340-346
        • HAPO Study Cooperative Research Group
        Hyperglycemia and adverse pregnancy outcomes.
        N Engl J Med. 2008; 358: 1991-2002
        • Landon M.B.
        • Spong C.Y.
        • Thom E.
        • et al.
        A multicenter, randomized trial of treatment for mild gestational diabetes.
        N Engl J Med. 2009; 361: 1339-1348
        • Crowther C.A.
        • Hiller J.E.
        • Moss J.R.
        • et al.
        Effect of treatment of gestational diabetes mellitus on pregnancy outcomes.
        N Engl J Med. 2005; 352: 2477-2486
        • International Association of Diabetes and Pregnancy Study Groups
        Recommendations on the diagnosis and classification of hyperglycemia in pregnancy.
        Diabetes Care. 2010; 33: 676-682
        • Hod M.
        • Kapur A.
        • Sacks D.A.
        • et al.
        The International Federation of Gynecology and Obstetrics (FIGO) Initiative on gestational diabetes mellitus: a pragmatic guide for diagnosis, management and care.
        Int J Gynecol Obstet. 2015; 131: S173-S211
        • World Health Organization
        Report of a WHO consultation: diagnostic criteria and classification of hyperglycaemia first detected in pregnancy: a World Health Organization guideline.
        Diabetes Res Clin Pract. 2014; 103: 341-363
        • Waters T.P.
        • Dyer A.R.
        • Scholtens D.M.
        • et al.
        Maternal and neonatal morbidity for women who would be added to the diagnosis of GDM Using IADPSG criteria: a secondary analysis of the Hyperglycemia and Adverse Pregnancy Outcome study.
        Diabetes Care. 2016; 39: 2204-2210
        • Wang C.
        • Wei Y.
        • Zhang X.
        • et al.
        A randomized clinical trial of exercise during pregnancy to prevent gestational diabetes mellitus and improve pregnancy outcome in overweight and obese pregnant women.
        Am J Obstet Gynecol. 2017; 216: 340-351
        • Hans S.
        • Middleton P.
        • Crowther C.A.
        Exercise for pregnant women for preventing gestational diabetes mellitus.
        Cochrane Database Syst Rev. 2012; : CD009021
        • Sanabria-Martínez G.
        • García-Hermoso A.
        • Poyatos-León R.
        • Álvarez-Bueno C.
        • Sánchez-López M.
        • Martínez-Vizcaíno V.
        Effectiveness of physical activity interventions on preventing gestational diabetes mellitus and excessive maternal weight gain: a meta-analysis.
        BJOG. 2015; 122: 1167-1174
        • Wang C.
        • Zhu W.
        • Wei Y.
        • Feng H.
        • Su R.
        • Yang H.
        Exercise intervention during pregnancy can be used to manage weight gain and improve pregnancy outcomes in women with gestational diabetes mellitus.
        BMC Pregnancy Childbirth. 2015; 15: 255
        • Ratner R.E.
        • Christophi C.A.
        • Metzger B.E.
        • et al.
        Prevention of diabetes in women with a history of gestational diabetes: effects of metformin and lifestyle interventions.
        J Clin Endocrinol Metab. 2008; 93: 4774-4779
        • Werner E.F.
        • Pettker C.M.
        • Zuckerwise L.
        • et al.
        Screening for gestational diabetes mellitus: are the criteria proposed by the International Association of Diabetes and Pregnancy Study Groups cost-effective?.
        Diabetes Care. 2012; 35: 529-535

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