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Title: Evaluation of 1,5-anhydroglucitol as a marker of glycemic control In pregnancy complicated by type 1 diabetes mellitus

Abstract:

Pregnancy complicated by T1DM requires a very precise monitoring of glycemic control. This target is difficult to reach with the currently used methods of glycemic control. HbA1c, a long-term marker of glycemic control, does not reflect glycemic variability. Moreover, short-term hyperglycemic episodes are frequently missed by a routine daily 8-point glucose profile performed with glucose meters. Therefore, the currently used methods of glycemic assessment appear to be unreliable for the assessment of glycemic profiles in pregnancy complicated by T1DM and prevention of adverse outcomes. 1,5-AG is a novel marker of short-term glycemic control reflecting a period of the last 1-2 weeks. It is currently used as a marker of acute hyperglycemia, including PPHG. However, it has been previously shown, that 1,5-AG serum level depends on the renal glucose threshold which is decreased during pregnancy. Thus, 1,5-AG utility as a marker of glycemia in this particular group of patients warrants new studies.This dissertation concerns the evaluation of the applicability of 1,5-AG as a marker of glycemic control in pregnancy complicated by T1DM. The specific aims included: to assess 1,5-AG concentration in pregnant women with T1DM and physiological pregnancy, to analize the associations between 1,5-AG and other methods of metabolic control, to evaluate 1,5-AG discriminative accuracy in detecting ; PPHG, to search for the association between 1,5-AG and neonate birth weight, and to evaluate 1,5-AG as a biochemical predictor for LGA and macrosomia. ; There were 110 pregnant women with T1DM and 102 women in physiological pregnancy included into the study. Their serum 1,5-AG was measured with an ELISA assay. In most women with T1DM 1,5-AG level was measured in each trimester of pregnancy Subsequently, HbA1c level was assessed with HPLC. The data from SMBG and CGMS were analyzed for a 1 week period before blood collection for the laboratory measurements. In 85 women, birth weight data were collected. Characteristics involved clinical data concerning T1DM patients, pregnancy and newborns.Mean 1,5-AG serum concentration in T1DM group was 4,5 μg/ml which was threefold lower in comparison to physiological pregnancy. 1,5-AG was a better predictor of mean and mean maximal glycemias as measured by glucose meters than HbA1c. Glycemic profiles were recorded with CGMS in 58 pregnancies. 1.5-AG correlated significantly with the glycemic indices recorded by CGMS - area under the curve at 140 mg/dl, average maximal glucose and mean glucose while HbA1c correlated significantly only with mean glucose. Additionally, 1,5-AG concentration remained the strongest predictor of AUC-140 after adjusting in the multivariate model for HbA1c level, indices of SMBG and week of gestation. Birth weight wa ; s collected in 84 newborns. Of these neonates 27 were classified with LGA. In 92% of pregnancies, maternal HbA1C level was less than 6,1%. Mean 2nd and 3rd trimester 1,5-AG concentration was significantly lower in women with LGA in comparison with pregnancies with normal-weight newborns, and correlated significantly with birth weight. In a multivariate linear regression, 3rd trimester 1,5-AG was the strongest predictor independently associated with the newborn weight after adjusting for the possible confounders - week of birth, pre-pregnancy BMI and maternal age (p<1x10-6), and other glycemic control assessment methods: HbA1c and SMBG indices. The unadjusted risk of 1,5-AG for LGA was OR=0.34 [95%CI: 0.17-0.65; p<10-4], the risk of macrosomia was OR=0.17 [95%CI: 0.07-0.47; p=6x10-4]. When controlled for potential confounders, these findings persisted in the multivariate logistic regression as 3rd trimester 1,5-AG appeared as a strong predictor for neonate birth weight - its 1 µg/ml increase was associated with a threefold decrease in the risk of LGA and more than fivefold decrease of macrosomia. Additional ROC analysis revealed a sufficient AUC and high sensitivity of this marker as a clinical predictor of neonate LGA and macrosomia. This dissertation project is the first large scale, systematic analysis of 1,5-AG performance in monitoring metabolic control in pregnancy complic ; ated by T1DM. It was found that 1,5-AG level is an excellent biomarker of glycemic profiles in pregnancy complicated by T1DM. Additionally, its serum 3rd trimester level is a very good predictor of LGA and macrosomia. Thus, 1,5-AG clinical use should be considered in pregnancies complicated by T1DM for the assessment of glycemic control and the prediction of neonate birth weight.

Place of publishing:

Kraków

Level of degree:

2 - studia doktoranckie

Degree discipline:

endokrynologia ; położnictwo

Degree grantor:

Wydział Lekarski

Promoter:

Małecki, Maciej

Date issued:

2012

Identifier:

oai:dl.cm-uj.krakow.pl:3584

Call number:

ZB-118532

Language:

pol

Access rights:

nieograniczony

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Last modified:

Jun 26, 2023

In our library since:

Jul 18, 2013

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387

Number of object content views in PDF format

66

All available object's versions:

http://dl.cm-uj.krakow.pl:8080/publication/3584

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ZB-118532 Jun 26, 2023
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