To investigate if oral glucose tolerance test (OGTT) associates with changes in maternal symptoms (ie, flushing, sweating), blood nonenzymatic advanced glycation end products (AGE), acute-phase reactive inflammatory markers, and oxidative stress.
Methods:
Prospective case–control study of patients screened for gestational diabetes mellitus (GDM). One hundred nonfasting, second-trimester consecutive pregnant women allocated to either 50 g OGTT or water. Five women who had a 3-hour fasting 100 g OGTT also enrolled. Maternal serum glucose, AGE, soluble receptor for AGE (sRAGE), interleukin (IL)-6, and C-reactive protein (CRP) were immunoassayed. Total radical-trapping antioxidant parameter (TRAP) estimated with antioxidant capacity-peroxyl assay. Data corrected for gestational age and maternal body mass index.
Results:
During 50 g OGTT there was a decrease in systolic blood pressure not accompanied by the onset of adverse clinical symptoms. There was a decrease in serum glucose levels 1 hour after water (P = .019) but not glucose ingestion. Serum CRP (P = .001) but not IL-6 was increased. The AGE, sRAGE, and TRAP levels remained unchanged. Similar results were seen during 100 g OGTT, except serum glucose was significantly elevated after 1 hour.
Conclusion:
Results suggest screening tools for gestational diabetes are safe and clinically well tolerated during pregnancy. Clinical Trial Registration: ClinicalTrials.gov NCT03029546.
WilkersonHLO’SullivanJB. A study of glucose tolerance and screening criteria in 752 unselected pregnancies. Diabetes. 1963;12:313–318.
2.
National Health and Nutrition Examination Survey (NHANES). Oral Glucose Tolerance Test (OGTT) Procedures Manual. Atlanta: Centers for Disease Control and Prevention, National Center for Health Statistics; 2007.
3.
AndradeHFPedrosaWDiniz MdeFPassosVM. Adverse effects during the oral glucose tolerance test in post-bariatric surgery patients. Arch Endocrinol Metab. 2016;60(4):307–313.
4.
BuhimschiIAZhaoGPettkerCM. The receptor for advanced glycation end products (RAGE) system in women with intraamniotic infection and inflammation. Am J Obstet Gynecol. 2007;196(2):181.e1–181.e13.
5.
ChavakisTBierhausANawrothPP. RAGE (receptor for advanced glycation end products): a central player in the inflammatory response. Microbes Infect. 2004;6(13):1219–1225.
6.
ForbesJMSourrisKCde CourtenMP. Advanced glycation end products (AGEs) are cross-sectionally associated with insulin secretion in healthy subjects. Amino Acids. 2014;46(2):321–326.
7.
TanKCShiuSWWongYTamX. Serum advanced glycation end products (AGEs) are associated with insulin resistance. Diabetes Metab Res Rev. 2011;27(5):488–492.
8.
ChoiKMYooHGKimHY. Association between endogenous secretory RAGE, inflammatory markers and arterial stiffness. Int J Cardiol. 2009;132(1):96–101.
9.
BaynesJWThorpeSR. Glycoxidation and lipoxidation in atherogenesis. Free Radic Biol Med. 2000;28(12):1708–1716.
10.
OttCJacobsKHauckeENavarrete SantosAGruneTSimmA. Role of advanced glycation end products in cellular signaling. Redox Biol. 2014;2:411–429.
11.
JensenLJFlyvbjergABjerreM. Soluble receptor for advanced glycation end product: a biomarker for acute coronary syndrome. Biomed Res Int. 2015. doi:10.1155/2015/815942.
12.
WillemsenSHartogJWvan VeldhuisenDJ. The role of advanced glycation end-products and their receptor on outcome in heart failure patients with preserved and reduced ejection fraction. Am Heart J. 2012;164(5):742–749.e3. doi:10.1016/j.ahj.2012.07.027.
13.
KierdorfKFritzG. RAGE regulation and signaling in inflammation and beyond. J Leukoc Biol. 2013;94(1):55–68.
14.
BartakovaVKollarovaRKuricovaKSebekovaKBelobradkovaJKankovaK. Serum carboxymethyl-lysine, a dominant advanced glycation end product, is increased in women with gestational diabetes mellitus. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2016;160(1):70–75.
15.
Committee on Practice Bulletins-Obstetrics. ACOG Practice Bulletin No. 190, February 2018: gestational diabetes mellitus. Obstet Gynecol. 2018;131(2):e49–e64. doi:10.1097/AOG.0000000000002501.
16.
VandorstenJPDodsonWCEspelandMA. NIH consensus development conference: diagnosing gestational diabetes mellitus. NIH Consens State Sci State. 2013;29(1):1–31.
17.
JabaudonMBlondonnetRRoszykL. Soluble forms and ligands of the receptor for advanced glycation end-products in patients with acute respiratory distress syndrome: an observational prospective study. PLoS One. 2015;10(8):e0135857.
18.
WilliamsMAEnquobahrieDAZimmerJ. Maternal plasma advanced glycation end products concentrations in response to oral 50-gram glucose load in mid-pregnancy: a pilot study. Clin Lab. 2012;58(9-10):1045–1050.
19.
KobayashiRHashimotoYHatakeyamaHOkamotoT. Acute effects of repeated bouts of aerobic exercise on arterial stiffness after glucose ingestion. Clin Exp Hypertens. 2019;41(2):123–129. doi:10.1080/10641963.2018.1451535.
20.
MartineauMGRakerCDixonPH. The metabolic profile of intrahepatic cholestasis of pregnancy is associated with impaired glucose tolerance, dyslipidemia, and increased fetal growth. Diabetes Care. 2015;38(2):243–248.
21.
BankSJacksonWPKellerPMarksIN. Serum-insulin response to glucose in “pancreatic diabetes”. Postgrad Med J. 1968;44(509):214–217.
22.
SchwartzJGPhillipsWTBlumhardtMRLangerO. Use of a more physiologic oral glucose solution during screening for gestational diabetes mellitus. Am J Obstet Gynecol. 1994;171(3):685–691.
23.
BrownMARobinsonAJonesM. The white coat effect in hypertensive pregnancy: much ado about nothing?Br J Obstet Gynaecol. 1999;106(5):474–480.
24.
WalshLKRestainoRMNeuringerMManriqueCPadillaJ. Administration of tauroursodeoxycholic acid prevents endothelial dysfunction caused by an oral glucose load. Clin Sci (Lond). 2016;130(21):1881–1888.
25.
TackJArtsJCaenepeelPDe WulfDBisschopsR. Pathophysiology, diagnosis and management of postoperative dumping syndrome. Nat Rev Gastroenterol Hepatol. 2009;6(10):583–590.
26.
EmousMWolffenbuttelBHRTottéEvan BeekAP. The short- to mid-term symptom prevalence of dumping syndrome after primary gastric-bypass surgery and its impact on health-related quality of life. Surg Obes Relat Dis. 2017;13(9):1489–1500.
27.
MorrisCO’GradaCRyanM. Identification of differential responses to an oral glucose tolerance test in healthy adults. PLoS One. 2013;8(8):e72890.
28.
TakahashiKNakamuraHSatoHMatsudaHTakadaKTsujiT. Four plasma glucose and insulin responses to a 75 g OGTT in healthy young Japanese women. J Diabetes Res. 2018. doi:10.1155/2018/5742497.
29.
XuBChibberRRuggieroDKohnerERitterJFerroA. Impairment of vascular endothelial nitric oxide synthase activity by advanced glycation end products. FASEB J. 2003;17(10):1289–1291.
30.
McNultyMMahmudAFeelyJ. Advanced glycation end-products and arterial stiffness in hypertension. Am J Hypertens. 2007;20(3):242–247.
31.
ChenSJAikawaCMatsuiT. Quantitative analysis of methylglyoxal, glyoxal and free advanced glycation end-products in the plasma of Wistar rats during the oral glucose tolerance test. Biol Pharm Bull. 2015;38(2):336–369.
32.
PopovaEAMironovaRSOdjakovaMK. Non-enzymatic glycosylation and deglycating enzymes. Biotechnol Equip. 2010;24(3):1928–1935.
33.
ThorpeSRBaynesJW. Maillard reaction products in tissue proteins: new products and new perspectives. Amino Acids. 2003;25(3-4):275–281.
34.
FuMXRequenaJRJenkinsAJLyonsTJBaynesJWThorpeSR. The advanced glycation end product, Nepsilon-(carboxymethyl) lysine, is a product of both lipid peroxidation and glycoxidation reactions. J Biol Chem. 1996;271(17):9982–9986.
35.
GiardinoIEdelsteinDBrownleeM. Nonenzymatic glycosylation in vitro and in bovine endothelial cells alters basic fibroblast growth factor activity. A model for intracellular glycosylation in diabetes. J Clin Invest. 1994;94(1):110–117.
36.
SageATHoltby-OttenhofSShiYDamjanovicSSharmaAMWerstuckGH. Metabolic syndrome and acute hyperglycemia are associated with endoplasmic reticulum stress in human mononuclear cells. Obesity (Silver Spring). 2012;20(4):748–755.
37.
KarimaMKantarciAOhiraT. Enhanced superoxide release and elevated protein kinase C activity in neutrophils from diabetic patients: association with periodontitis. J Leukoc Biol. 2005;78(4):862–870.
38.
OmoriKOhiraTUchidaY. Priming of neutrophil oxidative burst in diabetes requires preassembly of the NADPH oxidase. J Leukoc Biol. 2008;84(1):292–301.
39.
MaSWTomlinsonBBenzieIF. A study of the effect of oral glucose loading on plasma oxidant: antioxidant balance in normal subjects. Eur J Nutr. 2005;44(4):250–254.
