EASD 2020 Highlights

Conference summaries


DIABETES & PREGNANCY

20 years HAPO Study: What have we learned so far?

Presented by:

Patrick M. Catalano, MD


  • Maternal GDM is related to postpartum disorders of glucose metabolism.
  • Maternal BMI has significant associations with childhood adiposity.
  • Maternal glucose has a significant positive association with childhood glucose levels.

What do we already know about this topic?

  • At the time of the original HAPO study, it was controversial whether maternal hyperglycaemia less severe than that in diabetes mellitus is associated with increased risks of adverse pregnancy outcomes.
  • In HAPO, 25,505 pregnant women underwent 75-g oral glucose-tolerance testing at 24 to 32 weeks of gestation.1
  • Data remained blinded if the fasting plasma glucose was 105 mg/dL or less and the 2-hour plasma glucose level was 200 mg/dL or less.1
  • The results indicated that strong, continuous associations of maternal glucose levels below those diagnostics of diabetes with increased birth weight and increased cord-blood serum C-peptide levels.1

How was this study conducted?

  • The HAPO follow-up study aimed to determine associations of maternal glucose levels during pregnancy with measures of adiposity in offspring at 10-14 years of age, and to determine associations of maternal glucose levels during pregnancy and maternal metabolic disorders 10-14 years later.
  • A total of 4697 mothers and 4832 children were followed.

What does this study add?

  • Among mothers with a diagnosis of gestational diabetes mellitus (GDM) at study start, 52.2% had disorders of glucose metabolism compared to 20.0% of mothers without a diagnosis of GDM, with a significant association.
  • The frequency of overweight and obesity in children was 39.5% in those whose mothers had a diagnosis of GDM vs. 28.6% for those whose mothers did not.
  • In fully adjusted models controlling for child age, sex and maternal characteristics, maternal BMI had significant, positive associations with all childhood adiposity outcomes, while maternal glycemia had significant, positive associations with childhood adiposity outcomes except BMI.

Perspectives

How does this study impact clinical practice?

  • There was a continuous relationship between maternal glycaemia in pregnancy and adverse pregnancy outcomes.
  • Maternal GDM/increasing glycaemia was associated with increased postpartum disorders of glucose metabolism.
  • Maternal BMI along the continuum had significant associations with all measures of childhood adiposity: BMI, body fat %, sum of skinfolds and waist circumference, even when adjusted for GDM.
  • Maternal glucose across the continuum had a significant positive association with childhood glucose concentrations and an inverse correlation with insulin sensitivity and disposition index, even when adjusted for childhood obesity.


References

References


  1. HAPO Study Cooperative Research Group, Metzger BE, Lowe LP, et al. Hyperglycemia and adverse pregnancy outcomes. N Engl J Med. 2008;358(19):1991-2002.

 

Related content



Expert commentary by Elizabeth O. Buschur, MD

Expert commentary by Elizabeth O. Buschur, MD

 

Elizabeth O. Buschur, MD
Ohio State University Medical Center
Columbus, OH, USA

 

This presentation provides an excellent summary of the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study and highlights the importance of the HAPO Follow-up study showing that maternal hyperglycemia can affect long-term metabolic health of mothers and their offspring. The original study showed that mild hyperglycemia in pregnancy below the diagnostic criteria for gestational diabetes (GDM) at that time had adverse neonatal outcomes including increased birth weight and cord blood c-peptide levels.1 The HAPO Follow-up study has shown that hyperglycemia in pregnancy below the threshold for previous GDM diagnosis is related to adverse maternal, neonatal, and childhood outcomes;2 other studies have shown that treatment of mild GDM with dietary modification or insulin when needed improved maternal and neonatal outcomes.3,4 These studies helped shape the International Association of Diabetes and Pregnancy Study Groups (IADPSG) guidelines for diagnosis of GDM in 2010.5 This resulted in a significant increase in prevalence of GDM around the globe.6-8

The HAPO Follow-up study evaluated long-term outcomes in the mothers and offspring based on untreated GDM (identified post hoc using the IADPSG criteria). Data from the HAPO Follow-up study showed that untreated maternal hyperglycemia and GDM strongly correlated with maternal glucose abnormalities 10-14 years postpartum including prediabetes and type 2 diabetes.9 Maternal glycaemia in pregnancy was also associated with childhood adiposity measures at 10-14 years of age except body mass index (BMI).10 Furthermore, maternal obesity and GDM were independently associated with childhood adiposity and BMI at 10-14 years of age .10 Increasing hyperglycemia and untreated maternal GDM were significantly associated with childhood impaired glucose tolerance and insulin resistance compared to offspring of mothers without GDM2,11 in the HAPO Follow-up study.

Obesity is a burgeoning epidemic worldwide among adults and children12 that will drastically affect the future of healthcare for the next generation. The HAPO Follow-up study highlights the necessity of diagnosing and treating GDM with the goal of improving offspring metabolic health. Maternal prepregnancy or early pregnancy BMI is independently associated with childhood obesity,13 and higher gestational weight gain is associated with increased obesity in offspring.14 Intervention trials are needed to reduce maternal BMI before and during pregnancy and decrease gestational weight gain. Counseling reproductive aged women on achieving a normal weight and BMI before and after pregnancy is of paramount importance in decreasing obesity and hyperglycemia as well as health care expenditure during pregnancy and postpartum for mothers and their children.

 

Elizabeth O. Buschur, MD, FACE
The Ohio State Wexner Medical Center, Columbus, Ohio, USA

Elizabeth Buschur is an Assistant Clinical Professor at the Ohio State University Wexner Medical Center. Dr. Buschur graduated magna cum laude from Washington and Lee University in Virginia with a bachelor of science degree in neuroscience. She then attended the University of Texas Health Science Center in San Antonio for medical school and graduated AOA. She completed internal medicine residency and endocrinology fellowship at the University of Michigan. She also completed a women’s health fellowship at the University of Michigan and served as a clinical lecturer following completion of her fellowship. She has been an Assistant Clinical Professor at the Ohio State University Wexner Medical Center since 2014 and is active in the Gold Humanism Honor Society. She is the director of the Transition Clinic for emerging adults with type 1 diabetes at the Nationwide Children’s Hospital. In addition, she created an Endocrine Disorders in Pregnancy Clinic where she sees patients with diabetes, thyroid disease, and other endocrine problems during pregnancy and postpartum. She is the site Principal Investigator for the JDRF sponsored two-site clinical trial Pregnancy Intervention with a Closed Loop System (PICLS) study with the Barbara Davis Center and is actively recruiting subjects for this exciting research.

 

References

  1. Group HSCR, Metzger BE, Lowe LP, et al. Hyperglycemia and adverse pregnancy outcomes. N Engl J Med. 2008;358(19):1991-2002.
  2. Lowe WL, Jr., Scholtens DM, Kuang A, et al. Hyperglycemia and Adverse Pregnancy Outcome Follow-up Study (HAPO FUS): Maternal Gestational Diabetes Mellitus and Childhood Glucose Metabolism. Diabetes Care. 2019;42(3):372-80. 
  3. Landon MB, Spong CY, Thom E, et al. A multicenter, randomized trial of treatment for mild gestational diabetes. N Engl J Med. 2009;361(14):1339-48.
  4. Crowther CA, Hiller JE, Moss JR, et al. Effect of treatment of gestational diabetes mellitus on pregnancy outcomes. N Engl J Med. 2005;352(24):2477-86. 
  5. International Association of D, Pregnancy Study Groups Consensus P, Metzger BE, Gabbe SG, Persson B, et al. International association of diabetes and pregnancy study groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy. Diabetes Care. 2010;33(3):676-82.
  6. Sacks DA, Hadden DR, Maresh M, et al. Frequency of gestational diabetes mellitus at collaborating centers based on IADPSG consensus panel-recommended criteria: the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study. Diabetes Care. 2012;35(3):526-8.
  7. Kong JM, Lim K, Thompson DM. Evaluation of the International Association of the Diabetes In Pregnancy Study Group new criteria: gestational diabetes project. Can J Diabetes. 2015;39(2):128-32. 
  8. Duran A, Saenz S, Torrejon MJ, et al. Introduction of IADPSG criteria for the screening and diagnosis of gestational diabetes mellitus results in improved pregnancy outcomes at a lower cost in a large cohort of pregnant women: the St. Carlos Gestational Diabetes Study. Diabetes Care. 2014;37(9):2442-50.
  9. Lowe WL, Jr., Scholtens DM, Lowe LP, et al. Association of Gestational Diabetes With Maternal Disorders of Glucose Metabolism and Childhood Adiposity. JAMA. 2018;320(10):1005-16.
  10. Josefson JL, Catalano PM, Lowe WL, et al. The Joint Associations of Maternal BMI and Glycemia with Childhood Adiposity. J Clin Endocrinol Metab. 2020;105(7):2177-88.
  11. Scholtens DM, Kuang A, Lowe LP, et al. Hyperglycemia and Adverse Pregnancy Outcome Follow-up Study (HAPO FUS): Maternal Glycemia and Childhood Glucose Metabolism. Diabetes Care. 2019;42(3):381-92.
  12. Collaboration NCDRF. Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measurement studies in 128.9 million children, adolescents, and adults. Lancet. 2017;390(10113):2627-42.
  13. Patro Golab B, Santos S, Voerman E, et al. Influence of maternal obesity on the association between common pregnancy complications and risk of childhood obesity: an individual participant data meta-analysis. Lancet Child Adolesc Health. 2018;2(11):812-21.
  14. Voerman E, Santos S, Patro Golab B, et al. Maternal body mass index, gestational weight gain, and the risk of overweight and obesity across childhood: An individual participant data meta-analysis. PLoS Med. 2019;16(2):e1002744.

Acknowledgements

This is a highlights summary of an oral session given at the EASD 2020 Virtual Meeting and presented by:

Patrick M. Catalano, MD
Mother Infant Research Institute, Friedman School of Nutrition and Policy, Tufts University School of Medicine, Boston, USA

The presenting authors of the original session had no part in the creation of this conference highlights summary. 

The content is produced by Infomedica. The summary text was drafted by Patrick Moore, PhD, and reviewed by Marco Gallo, MD, an independent external expert, and approved by Florian Toti, MD, the scientific editor of the program.


DIABETES & PREGNANCY

20 years HAPO Study: What have we learned so far?

Presented by: Patrick M. Catalano, MD
Expert commentary by Elizabeth O. Buschur, MD

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