Cited by 577Gestational Diabetes Research and ManagementBirth, Development, and HealthPancreatic function and diabetes

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Hyperglycemia and Adverse Pregnancy Outcome Follow-up Study (HAPO FUS): Maternal Gestational Diabetes Mellitus and Childhood Glucose Metabolism

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Lowe, William L., Scholtens, Denise M., Kuang, Alan, Linder, Barbara, Lawrence, Jean M., Lebenthal, Yael, McCance, David, Hamilton, Jill, Nodzenski, Michael, Talbot, Octavious, Brickman, Wendy J., Clayton, Peter, Ma, Ronald C., Tam, Wing Hung, Dyer, Alan R., Catalano, Patrick M., Lowe, Lynn P., Metzger, Boyd E., HAPO Follow-up Study Cooperative Research Group, Deerochanawong, Chaicharn, Tanaphonpoonsuk, Thadchanan, Chotigeat, Sukeeta Binratkaew Uraiwan, Manyam, Wanee, Forde, Martinette, Greenidge, Andre, Neblett, Kathleen, Lashley, Paula Michele, Walcott, Desiree, Corry, Katie, Francis, Loraine, Irwin, Jo-anne, Langan, Anne, McCance, David R., Mousavi, Maureen, Young, Ian, Gutierrez, Jennifer, Jimenez, Jennifer, Lawrence, Jean M., Sacks, David A., Takhar, Harpreet S., Tanton, Elizabeth, Brickman, Wendy J., Howard, Jennifer, Josefson, Jami L., Miller, Lauren, Bjaloncik, Jacqui, Catalano, Patrick M., Davis, Ajuah, Koontz, Michaela, Presley, Larraine, Smith, Shoi, Tyhulski, Amanda, Li, Albert Martin, Ma, Ronald C., Ozaki, Risa, Tam, Wing Hung, Wong, Michelle, Yuen, Cindy Siu Man, Clayton, Peter E., Khan, Aysha, Vyas, Avni, Maresh, Michael, Benzaquen, Hadasse, Glickman, Naama, Hamou, Alona, Hermon, Orna, Horesh, Orit, Keren, Yael, Lebenthal, Yael, Shalitin, Shlomit, Cordeiro, Kristina, Hamilton, Jill, Nguyen, Hahn Y., Steele, Shawna, Chen, Fei, Dyer, Alan R., Huang, Wenyu, Kuang, Alan, Jimenez, Maria, Lowe, Lynn P., Lowe, William L., Metzger, Boyd E., Nodzenski, Michael, Reisetter, Anna, Scholtens, Denise, Talbot, Octavious, Yim, Paul, Dunger, David, Thomas, Alicia, Horlick, Mary, Linder, Barbara, Unalp-Arida, Aynur, Grave, Gilman·2019·Diabetes Care

Abstract

OBJECTIVE: Whether hyperglycemia in utero less than overt diabetes is associated with altered childhood glucose metabolism is unknown. We examined associations of gestational diabetes mellitus (GDM) not confounded by treatment with childhood glycemia in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) cohort. RESEARCH DESIGN AND METHODS: HAPO Follow-up Study (FUS) included 4,160 children ages 10–14 years who completed all or part of an oral glucose tolerance test (OGTT) and whose mothers had a 75-g OGTT at ∼28 weeks of gestation with blinded glucose values. The primary predictor was GDM by World Health Organization criteria. Child outcomes were impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and type 2 diabetes. Additional measures included insulin sensitivity and secretion and oral disposition index. RESULTS: For mothers with GDM, 10.6% of children had IGT compared with 5.0% of children of mothers without GDM; IFG frequencies were 9.2% and 7.4%, respectively. Type 2 diabetes cases were too few for analysis. Odds ratios (95% CI) adjusted for family history of diabetes, maternal BMI, and child BMI z score were 1.09 (0.78–1.52) for IFG and 1.96 (1.41–2.73) for IGT. GDM was positively associated with child’s 30-min, 1-h, and 2-h but not fasting glucose and inversely associated with insulin sensitivity and oral disposition index (adjusted mean difference −76.3 [95% CI −130.3 to −22.4] and −0.12 [−0.17 to −0.064]), respectively, but not insulinogenic index. CONCLUSIONS: Offspring exposed to untreated GDM in utero are insulin resistant with limited β-cell compensation compared with offspring of mothers without GDM. GDM is significantly and independently associated with childhood IGT.

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Authors
Lowe, W. L., Scholtens, D. M., Kuang, A., Linder, B., Lawrence, J. M., Lebenthal, Y., McCance, D., Hamilton, J., Nodzenski, M., Talbot, O., Brickman, W. J., Clayton, P., Ma, R. C., Tam, W. H., Dyer, A. R., Catalano, P. M., Lowe, L. P., Metzger, B. E., HAPO Follow-up Study Cooperative Research Group, Deerochanawong, C., Tanaphonpoonsuk, T., Chotigeat, S. B. U., Manyam, W., Forde, M., Greenidge, A., Neblett, K., Lashley, P. M., Walcott, D., Corry, K., Francis, L., Irwin, J.-A., Langan, A., McCance, D. R., Mousavi, M., Young, I., Gutierrez, J., Jimenez, J., Lawrence, J. M., Sacks, D. A., Takhar, H. S., Tanton, E., Brickman, W. J., Howard, J., Josefson, J. L., Miller, L., Bjaloncik, J., Catalano, P. M., Davis, A., Koontz, M., Presley, L., Smith, S., Tyhulski, A., Li, A. M., Ma, R. C., Ozaki, R., Tam, W. H., Wong, M., Yuen, C. S. M., Clayton, P. E., Khan, A., Vyas, A., Maresh, M., Benzaquen, H., Glickman, N., Hamou, A., Hermon, O., Horesh, O., Keren, Y., Lebenthal, Y., Shalitin, S., Cordeiro, K., Hamilton, J., Nguyen, H. Y., Steele, S., Chen, F., Dyer, A. R., Huang, W., Kuang, A., Jimenez, M., Lowe, L. P., Lowe, W. L., Metzger, B. E., Nodzenski, M., Reisetter, A., Scholtens, D., Talbot, O., Yim, P., Dunger, D., Thomas, A., Horlick, M., Linder, B., Unalp-Arida, A., & Grave, G.
Affiliations
  • Northwestern University Feinberg School of Medicine, Chicago, IL
  • Royal Victoria Hospital, Belfast, U.K.
  • Royal Manchester Children’s Hospital, Manchester University Hospitals NHS Foundation Trust, Manchester Academic Healthy Sciences Centre, School of Medical Sciences, Faculty of Biology, Medicine, and Health, University of Manchester, Manchester, U.K.
Venue
Diabetes Care
Published
2019-01-17
Volume
42
Issue
3
Pages
372-380
ISSN
  • 0149-5992 (ISSN-L)
  • 1935-5548
OpenAlex
W2910413249
Cited by
574
References
47
Citations by year
2026: 51 · 2025: 81 · 2024: 88 · 2023: 86 · 2022: 95 · 2021: 86 · 2020: 65 · 2019: 22
FWCI
72.84
Type
journal article
Language
en
Open access
Locations
  • Diabetes Care (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Research Explorer (The University of Manchester) (publishedVersion, other-oa)
Funders
National Institute of Diabetes and Digestive and Kidney Diseases and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (1U01-DK-094830)
Topics
  • Health Sciences › Medicine › Obstetrics and Gynecology › Gestational Diabetes Research and Management
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
Keywords
gestational diabetes mellitus, impaired glucose tolerance, impaired fasting glucose, type 2 diabetes, insulin resistance, beta-cell compensation, oral disposition index, insulin sensitivity, insulinogenic index, maternal hyperglycemia, offspring of diabetic mothers
MeSH terms
Adolescent, Adult, Blood Glucose, Child, Diabetes Mellitus, Type 2, Female, Follow-Up Studies, Glucose, Glucose Tolerance Test, Humans, Hyperglycemia, Insulin Resistance, Male, Prediabetic State, Pregnancy, Pregnancy Outcome, Prenatal Exposure Delayed Effects, Risk Factors, Diabetes, Gestational, Glucose Intolerance

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