Altered maternal metabolism during mild gestational hyperglycemia as a predictor of adverse perinatal outcomes: A comprehensive analysis

Mild gestational hyperglycemia (MGH), as assessed using the normal oral glucose tolerance test (OGTT) and detection of an altered glycemic profile, is associated with adverse perinatal outcome. This study described the results of 40 years of research conducted at the Perinatal Diabetes Research Cent...

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Published in:	Biochimica et biophysica acta. Molecular basis of disease Vol. 1866; no. 2; p. 165478
Main Authors:	Rudge, Marilza Vieira Cunha, Barbosa, Angélica Mercia Pascon, Sobrevia, Luis, Gelaleti, Rafael Bottaro, Hallur, Raghavendra Lakshmana Shetty, Marcondes, João Paulo Castro, Salvadori, Daisy Maria Fávero, Prudêncio, Caroline Baldini, Magalhães, Claudia Garcia, Costa, Roberto, Abbade, Joelcio Francisco, Corrente, José Eduardo, Calderon, Iracema de Mattos Paranhos, Rudge, M.V., Calderon, I.M.P., Barbosa, A.P., Abbade, J., Costa, R.A.A., Magalhães, C.G., Salvadori, D.F., Gelaleti, R., Hallur, R.L.S., Marcondes, J.P., Floriano, J.F., Reyes, D.R.A., Sobrevia, L., Prudêncio, C.B., Pículo, F., Marini, G., Vesentini, G., Morceli, G., Negrato, C.A., Prazeres, H.D., Molina, S., Arantes, M., Cavassini, A.C., Kerche, L., De Luca, A.K.C., Corrêa-Silva, S., Bevilacqua, E., Moreli, J.B., Pietro, L., Daher, S., Fabio, S., Honorio-França, A.C., Queiroz, A.A., Hara, C.C.P., Boraschi, C.A.L., Pauletti, T.A.V.L., Jovanovic, L., Dias, A., Atallah, A.N., Ramos, M.D., Brasil, M.A.M., Rudge, C.V.C., Tristão, A., Del Nero, U., Mendonça, M., Witkin, S.S., Sartorão Filho, C.I., Nunes, S.K., Pinheiro, F.A., Quiroz, S.V., Pascon, T., Caldeirão, T.D., Oliveira, A.P., Nicolosi, B.F., Bolognani, C.V., Fagundes, D.L.G., Llanos, I.C.F., Vernini, J.M., Reis, L.B.S.M., Sirimarco, M.P., Basso, N.M., Maquesim, N.A.Q., Silva, S.A.L.C., Silva, S.C., Scudeller, T.T., Ayach, W., Almeida, A.P.M., Nicolosi, B.F.C.A., Lima, C.P., Luminoso, D., Vasconcellos, F.C., Ferraz, G.A.R., Migiolaro, H., Camargo, L.P., Macedo, M.L.S., Rodrigues, M.R.K., Anézio, P.H.O.
Format:	Journal Article
Language:	English
Published:	Netherlands Elsevier B.V 01-02-2020
Subjects:	Apoptosis Cytokines Gene expression Gestational diabetes mellitus Inflammatory mediators Insulin resistance IRS-1 gene Large for gestational age Mild gestational hyperglycemia Moderator analysis Natural killer cells Placenta IRS-1 gene Moderator analysis Large for gestational age Placenta Cytokines Gestational diabetes mellitus Mild gestational hyperglycemia Insulin resistance Natural killer cells Inflammatory mediators Gene expression Apoptosis
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Summary:	Mild gestational hyperglycemia (MGH), as assessed using the normal oral glucose tolerance test (OGTT) and detection of an altered glycemic profile, is associated with adverse perinatal outcome. This study described the results of 40 years of research conducted at the Perinatal Diabetes Research Centre at São Paulo State University (UNESP), Brazil, on the maternal MGH environment and placental markers. This study also described the unidirectional relationship between MGH and excessive fetal growth, also supplying moderator analysis. In addition to hyperglycemia, MGH is associated with an increased incidence of hypertension, metabolic syndrome, persistent insulin resistance after pregnancy, and high risk of developing type 2 diabetes mellitus (T2DM) after pregnancy. Structural changes and functional abnormalities resulting from MGH were observed in placenta. The fully adjusted model concluded that the predictor variable (MGH), which creates a complex environment for the fetus, has a direct effect on excessive birth weight and produces a z-score for ratios of birth weight to gestational age of ≥2. Maternal age, pre-pregnancy BMI, number of previous pregnancies, numbers of prenatal visits, and 1 h OGTT are moderator variables that impact MGH and excessive fetal growth. These results show that maternal MGH has some characteristics associated with similar long-term T2DM development and similar adverse perinatal results to those of gestational diabetes mellitus (GDM) mothers, making it an intermediate maternal and placental marker between normoglycemic and GDM mothers. •Moderator analysis indicates MGH as predictor variable of APO as LGA, PNM rate, ponderal index andexcessive fetal growth.•MGH increased maternal hypertension, MetS, persistent insulin resistance and T2DM development after pregnancy as GDM.•MGH placental markers are high weight, density, placental index, endarteritis, villi immaturityand villi vessels.•MGH fetal placental markers are ↑ apoptosis, ↓ BCL-2, ↑ VEGF +VEGFR-2, ↑ TNF-α /IL10, ↑ CD56+, ↑ IL-1β, ↑ TLR2/4 and NFkB.•The diabetic team approach may recognize MGH as an intermediate disease from normoglycemia to GDM.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-3 content type line 23 ObjectType-Review-1
ISSN:	0925-4439 1879-260X
DOI:	10.1016/j.bbadis.2019.05.014