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Diabetology & Metabolic Syndrome
Published in:

Open Access 01-12-2023 | Research

Evaluating glucose variability through OGTT in early pregnancy and its association with hypertensive disorders of pregnancy in non-diabetic pregnancies: a large-scale multi-center retrospective study

Authors: Sho Tano, Tomomi Kotani, Takafumi Ushida, Masato Yoshihara, Kenji Imai, Noriyuki Nakamura, Yukako Iitani, Yoshinori Moriyama, Ryo Emoto, Sawako Kato, Shigeru Yoshida, Mamoru Yamashita, Yasuyuki Kishigami, Hidenori Oguchi, Shigeyuki Matsui, Hiroaki Kajiyama

Published in: Diabetology & Metabolic Syndrome | Issue 1/2023

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Abstract

Background

Recent evidence suggests increased glucose variability (GV) causes endothelial dysfunction, a central pathology of hypertensive disorders of pregnancy (HDP). We aimed to investigate the association between GV in early pregnancy and subsequent HDP development among non-diabetes mellitus (DM) pregnancies.

Methods

This multicenter retrospective study used data from singleton pregnancies between 2009 and 2019. Among individuals who had 75 g-OGTT before 20 weeks of gestation, we evaluated GV by 75 g-OGTT parameters and examined its relationship with HDP development, defining an initial-increase from fasting-plasma glucose (PG) to 1-h-PG and subsequent-decrease from 1-h-PG to 2-h-PG.

Results

Approximately 3.0% pregnancies (802/26,995) had 75 g-OGTT before 20 weeks of gestation, and they had a higher prevalence of HDP (14.3% vs. 7.5%). The initial-increase was significantly associated with overall HDP (aOR 1.20, 95% CI 1.02–1.42), and the subsequent-decrease was associated with decreased and increased development of early-onset (EoHDP: aOR 0.56, 95% CI 0.38–0.82) and late-onset HDP (LoHDP: aOR 1.38, 95% CI 1.11–1.73), respectively.

Conclusions

A pattern of marked initial-increase and minor subsequent-decrease (i.e., sustained hyperglycemia) was associated with EoHDP. Contrarily, the pattern of marked initial-increase and subsequent-decrease (i.e., increased GV) was associated with LoHDP. This provides a new perspective for future study strategies.
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Literature
1.
Garovic VD, Dechend R, Easterling T, Karumanchi SA, McMurtry Baird S, Magee LA, Rana S, Vermunt JV, August P, American Heart Association Council on H, et al. Hypertension in pregnancy: diagnosis, blood pressure goals, and pharmacotherapy: a scientific statement from the American Heart Association. Hypertension. 2022;79(2):e21–41.PubMedCrossRef
2.
Roberts JM, Hubel CA. The two stage model of preeclampsia: variations on the theme. Placenta. 2009;30:S32-37.PubMedCrossRef
3.
Vikse BE, Irgens LM, Leivestad T, Skjaerven R, Iversen BM. Preeclampsia and the risk of end-stage renal disease. N Engl J Med. 2008;359(8):800–9.PubMedCrossRef
4.
Tano S, Kotani T, Ushida T, Yoshihara M, Imai K, Nakano-Kobayashi T, Moriyama Y, Iitani Y, Kinoshita F, Yoshida S, et al. Annual body mass index gain and risk of hypertensive disorders of pregnancy in a subsequent pregnancy. Sci Rep. 2021;11(1):22519.PubMedPubMedCentralCrossRef
5.
Steegers EA, von Dadelszen P, Duvekot JJ, Pijnenborg R. Pre-eclampsia. Lancet. 2010;376(9741):631–44.PubMedCrossRef
6.
Tranquilli AL, Brown MA, Zeeman GG, Dekker G, Sibai BM. The definition of severe and early-onset preeclampsia. Statements from the International Society for the Study of Hypertension in Pregnancy (ISSHP). Pregnancy Hypertens. 2013;3(1):44–7.PubMedCrossRef
7.
Wikstrom AK, Larsson A, Akerud H, Olovsson M. Increased circulating levels of the antiangiogenic factor endostatin in early-onset but not late-onset preeclampsia. Reprod Sci. 2009;16(10):995–1000.PubMedCrossRef
8.
Esposito K, Nappo F, Marfella R, Giugliano G, Giugliano F, Ciotola M, Quagliaro L, Ceriello A, Giugliano D. Inflammatory cytokine concentrations are acutely increased by hyperglycemia in humans: role of oxidative stress. Circulation. 2002;106(16):2067–72.PubMedCrossRef
9.
Papachristoforou E, Lambadiari V, Maratou E, Makrilakis K. Association of glycemic indices (hyperglycemia, glucose variability, and hypoglycemia) with oxidative stress and diabetic complications. J Diabetes Res. 2020;2020:7489795.PubMedPubMedCentralCrossRef
10.
Ceriello A, Esposito K, Piconi L, Ihnat MA, Thorpe JE, Testa R, Boemi M, Giugliano D. Oscillating glucose is more deleterious to endothelial function and oxidative stress than mean glucose in normal and type 2 diabetic patients. Diabetes. 2008;57(5):1349–54.PubMedCrossRef
11.
Di Flaviani A, Picconi F, Di Stefano P, Giordani I, Malandrucco I, Maggio P, Palazzo P, Sgreccia F, Peraldo C, Farina F, et al. Impact of glycemic and blood pressure variability on surrogate measures of cardiovascular outcomes in type 2 diabetic patients. Diabetes Care. 2011;34(7):1605–9.PubMedPubMedCentralCrossRef
12.
Schisano B, Tripathi G, McGee K, McTernan PG, Ceriello A. Glucose oscillations, more than constant high glucose, induce p53 activation and a metabolic memory in human endothelial cells. Diabetologia. 2011;54(5):1219–26.PubMedCrossRef
13.
Habte-Asres HH, Murrells T, Nitsch D, Wheeler DC, Forbes A. Glycaemic variability and progression of chronic kidney disease in people with diabetes and comorbid kidney disease: retrospective cohort study. Diabetes Res Clin Pract. 2022;193:110117.PubMedCrossRef
14.
Quagliaro L, Piconi L, Assaloni R, Martinelli L, Motz E, Ceriello A. Intermittent high glucose enhances apoptosis related to oxidative stress in human umbilical vein endothelial cells: the role of protein kinase C and NAD(P)H-oxidase activation. Diabetes. 2003;52(11):2795–804.PubMedCrossRef
15.
Monnier L, Mas E, Ginet C, Michel F, Villon L, Cristol JP, Colette C. Activation of oxidative stress by acute glucose fluctuations compared with sustained chronic hyperglycemia in patients with type 2 diabetes. JAMA. 2006;295(14):1681–7.PubMedCrossRef
16.
Inaba Y, Tsutsumi C, Haseda F, Fujisawa R, Mitsui S, Sano H, Terasaki J, Hanafusa T, Imagawa A. Impact of glycemic variability on the levels of endothelial progenitor cells in patients with type 1 diabetes. Diabetol Int. 2018;9(2):113–20.PubMedCrossRef
17.
18.
Ricks J, Molnar MZ, Kovesdy CP, Shah A, Nissenson AR, Williams M, Kalantar-Zadeh K. Glycemic control and cardiovascular mortality in hemodialysis patients with diabetes: a 6-year cohort study. Diabetes. 2012;61(3):708–15.PubMedPubMedCentralCrossRef
19.
Jin YP, Su XF, Yin GP, Xu XH, Lou JZ, Chen JJ, Zhou Y, Lan J, Jiang B, Li Z, et al. Blood glucose fluctuations in hemodialysis patients with end stage diabetic nephropathy. J Diabetes Complications. 2015;29(3):395–9.PubMedCrossRef
20.
Danne T, Nimri R, Battelino T, Bergenstal RM, Close KL, DeVries JH, Garg S, Heinemann L, Hirsch I, Amiel SA, et al. International consensus on use of continuous glucose monitoring. Diabetes Care. 2017;40(12):1631–40.PubMedPubMedCentralCrossRef
21.
Buschur EO, Campbell K, Pyle L, Garcetti R, Joshee P, Demmitt JK, Snell-Bergeon JK, Polsky S. Exploratory analysis of glycemic control and variability over gestation among pregnant women with type 1 diabetes. Diabetes Technol Ther. 2021;23(11):768–72.PubMedPubMedCentral
22.
Perea V, Gimenez M, Amor AJ, Bellart J, Conget I, Vinagre I. Prepregnancy care in women with type 1 diabetes improves HbA1c and glucose variability without worsening hypoglycaemia time and awareness: glycaemic variability during prepregnancy care. Diabetes Res Clin Pract. 2019;154:75–81.PubMedCrossRef
23.
Foreman YD, Brouwers M, van der Kallen CJH, Pagen DME, van Greevenbroek MMJ, Henry RMA, Koster A, Wesselius A, Schaper NC, Stehouwer CDA. Glucose variability assessed with continuous glucose monitoring: reliability, reference values, and correlations with established glycemic indices-the maastricht study. Diabetes Technol Ther. 2020;22(5):395–403.PubMedCrossRef
24.
Meier JJ, Baller B, Menge BA, Gallwitz B, Schmidt WE, Nauck MA. Excess glycaemic excursions after an oral glucose tolerance test compared with a mixed meal challenge and self-measured home glucose profiles: is the OGTT a valid predictor of postprandial hyperglycaemia and vice versa? Diabetes Obes Metab. 2009;11(3):213–22.PubMedCrossRef
25.
Feig DS, Shah BR, Lipscombe LL, Wu CF, Ray JG, Lowe J, Hwee J, Booth GL. Preeclampsia as a risk factor for diabetes: a population-based cohort study. PLoS Med. 2013;10(4):e1001425.PubMedPubMedCentralCrossRef
26.
Li-Zhen L, Yun X, Xiao-Dong Z, Shu-Bin H, Zi-Lian W, Adrian Sandra D, Bin L. Evaluation of guidelines on the screening and diagnosis of gestational diabetes mellitus: systematic review. BMJ Open. 2019;9(5):e023014.PubMedPubMedCentralCrossRef
27.
Force USPST, Davidson KW, Barry MJ, Mangione CM, Cabana M, Caughey AB, Davis EM, Donahue KE, Doubeni CA, Kubik M, et al. Screening for gestational diabetes: US preventive services task force recommendation statement. JAMA. 2021;326(6):531–8.CrossRef
28.
Minschart C, Beunen K, Benhalima K. An update on screening strategies for gestational diabetes mellitus: a narrative review. Diabetes Metab Syndr Obes. 2021;14:3047–76.PubMedPubMedCentralCrossRef
29.
Sweeting AN, Ross GP, Hyett J, Molyneaux L, Constantino M, Harding AJ, Wong J. Gestational diabetes mellitus in early pregnancy: evidence for poor pregnancy outcomes despite treatment. Diabetes Care. 2016;39(1):75–81.PubMedCrossRef
30.
Wexler DJ, Powe CE, Barbour LA, Buchanan T, Coustan DR, Corcoy R, Damm P, Dunne F, Feig DS, Ferrara A, et al. Research gaps in gestational diabetes mellitus: executive summary of a national institute of diabetes and digestive and kidney diseases workshop. Obstet Gynecol. 2018;132(2):496–505.PubMedPubMedCentralCrossRef
31.
Itakura A, Shoji S, Shigeru A, Kotaro F, Junichi H, Hironobu H, Kamei Y, Eiji K, Shintaro M, Ryu M, et al. Guidelines for obstetrical practice in Japan: Japan Society of Obstetrics and Gynecology and Japan Association of Obstetricians and Gynecologists 2020 edition. J Obstet Gynaecol Res. 2023;49(1):5–53. https://​doi.​org/​10.​1111/​jog.​15438
32.
Kyozuka H, Yasuda S, Murata T, Fukuda T, Yamaguchi A, Kanno A, Sato A, Ogata Y, Hosoya M, Yasumura S, et al. Adverse obstetric outcomes in early-diagnosed gestational diabetes mellitus: The Japan Environment and Children’s study. J Diabetes Investig. 2021;12(11):2071–9.PubMedPubMedCentralCrossRef
33.
Brown MA, Magee LA, Kenny LC, Karumanchi SA, McCarthy FP, Saito S, Hall DR, Warren CE, Adoyi G, Ishaku S, et al. Hypertensive disorders of pregnancy: ISSHP classification, diagnosis, and management recommendations for international practice. Hypertension. 2018;72(1):24–43.PubMedCrossRef
34.
Itabashi K, Miura F, Uehara R, Nakamura Y. New Japanese neonatal anthropometric charts for gestational age at birth. Pediatr Int. 2014;56(5):702–8.PubMedCrossRef
35.
Kapur A, McIntyre HD, Hod M. Type 2 diabetes in pregnancy. Endocrinol Metab Clin. 2019;48(3):511–31.CrossRef
36.
Shou C, Wei Y-M, Wang C, Yang H-X. Updates in long-term maternal and fetal adverse effects of gestational diabetes mellitus. Maternal-Fetal Med. 2019;1(02):91–4.CrossRef
37.
Belkacemi L, Lash GE, Macdonald-Goodfellow SK, Caldwell JD, Graham CH. Inhibition of human trophoblast invasiveness by high glucose concentrations. J Clin Endocrinol Metab. 2005;90(8):4846–51.PubMedCrossRef
38.
Tao J, Xia LZ, Chen JJ, Zeng JF, Meng J, Wu S, Wang Z. High glucose condition inhibits trophoblast proliferation, migration and invasion by downregulating placental growth factor expression. J Obstet Gynaecol Res. 2020;46(9):1690–701.PubMedCrossRef
39.
Majali-Martinez A, Weiss-Fuchs U, Miedl H, Forstner D, Bandres-Meriz J, Hoch D, Djelmis J, Ivanisevic M, Hiden U, Gauster M, et al. Type 1 diabetes mellitus and the first trimester placenta: hyperglycemia-induced effects on trophoblast proliferation, cell cycle regulators, and invasion. Int J Mol Sci. 2021;22(20):10989.PubMedPubMedCentralCrossRef
40.
Vega M, Mauro M, Williams Z. Direct toxicity of insulin on the human placenta and protection by metformin. Fertil Steril. 2019;111(3):489–96.PubMedCrossRef
41.
Risso A, Mercuri F, Quagliaro L, Damante G, Ceriello A. Intermittent high glucose enhances apoptosis in human umbilical vein endothelial cells in culture. Am J Physiol Endocrinol Metab. 2001;281(5):E924-930.PubMedCrossRef
42.
Yogev, Chen, Hod, Coustan, Oats, McIntyre, Metzger, Lowe, Dyer, Dooley, et al. Hyperglycemia and adverse pregnancy outcome (HAPO) study: preeclampsia. Am J Obstet Gynecol. 2010;202(3):255.
43.
Zhou Z, Chen G, Fan D, Rao J, Li P, Wu S, Lin D, Ma H, Ye S, Zhang H, et al. Size and shape of associations of OGTT as well as mediating effects on adverse pregnancy outcomes among women with gestational diabetes mellitus: population-based study from Southern Han Chinese. Front Endocrinol (Lausanne). 2020;11:135.PubMedCrossRef
44.
Yogev Y, Xenakis EM, Langer O. The association between preeclampsia and the severity of gestational diabetes: the impact of glycemic control. Am J Obstet Gynecol. 2004;191(5):1655–60.PubMedCrossRef
45.
Sermer M, Naylor CD, Gare DJ, Kenshole AB, Ritchie JW, Farine D, Cohen HR, McArthur K, Holzapfel S, Biringer A, et al. Impact of increasing carbohydrate intolerance on maternal-fetal outcomes in 3637 women without gestational diabetes. The Toronto Tri-Hospital Gestational Diabetes Project. Am J Obstet Gynecol. 1995;173(1):146–56.PubMedCrossRef
46.
47.
Rolnik DL, Nicolaides KH, Poon LC. Prevention of preeclampsia with aspirin. Am J Obstet Gynecol. 2022;226(2s):S1108-s1119.PubMedCrossRef
48.
Chung ST, Ha J, Onuzuruike AU, Kasturi K, Galvan-De La Cruz M, Bingham BA, Baker RL, Utumatwishima JN, Mabundo LS, Ricks M, et al. Time to glucose peak during an oral glucose tolerance test identifies prediabetes risk. Clin Endocrinol (Oxf). 2017;87(5):484–91.PubMedCrossRef
49.
Cree-Green M, Xie D, Rahat H, Garcia-Reyes Y, Bergman BC, Scherzinger A, Diniz Behn C, Chan CL, Kelsey MM, Pyle L, et al. Oral glucose tolerance test glucose peak time is most predictive of prediabetes and hepatic steatosis in obese girls. J Endocr Soc. 2018;2(6):547–62.PubMedPubMedCentralCrossRef
50.
Wang C, Wei Y, Yang Y, Su R, Song G, Kong L, Yang H. Evaluation of the value of fasting plasma glucose in the first trimester for the prediction of adverse pregnancy outcomes. Diabetes Res Clin Pract. 2021;174:108736.PubMedCrossRef
51.
Stekkinger E, Zandstra M, Peeters LLH, Spaanderman MEA. Early-onset preeclampsia and the prevalence of postpartum metabolic syndrome. Obstet Gynecol. 2009;114(5):1076–84.PubMedCrossRef
Metadata
Title
Evaluating glucose variability through OGTT in early pregnancy and its association with hypertensive disorders of pregnancy in non-diabetic pregnancies: a large-scale multi-center retrospective study
Authors
Sho Tano
Tomomi Kotani
Takafumi Ushida
Masato Yoshihara
Kenji Imai
Noriyuki Nakamura
Yukako Iitani
Yoshinori Moriyama
Ryo Emoto
Sawako Kato
Shigeru Yoshida
Mamoru Yamashita
Yasuyuki Kishigami
Hidenori Oguchi
Shigeyuki Matsui
Hiroaki Kajiyama
Publication date
01-12-2023
Publisher
BioMed Central
Published in
Diabetology & Metabolic Syndrome / Issue 1/2023
Electronic ISSN: 1758-5996
DOI
https://doi.org/10.1186/s13098-023-01103-z

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