Methods
A retrospective cohort study aimed to evaluate the risk of T2DM according to FPG levels measured at 1st trimester in a large cohort of parturients with up to five years of follow-up postpartum. Women with missing FPG levels or with FPG levels equal to or over 126 mg/dl or if taken after 15+0 gestational weeks were excluded from the analysis. The study was approved by the local Institutional Review Board committee (10-18-08-21). Due to the retrospective nature of the study, informed consent was waived.
This study extracted data from a dataset encompassing more than five years of laboratory data cross-tabulated with a pregnancy registry and integrated with the Israeli national diabetes registry (INDR) collected by Mehuedet HMO (health maintenance organization). Mehuedet is one of four HMOs that Israeli residents must belong to under Israel’s universal healthcare framework. The dataset included all women with documented pregnancy (by pregnancy registry) with last menstrual period (LMP) between 1st January 2017 and 31st December 2020. LMP was determined by the primary physician at the first antenatal encounter and updated according to the 1st trimester crown-rump length measurement if the difference between them exceeded 7 days. Maternal data included maternal age, body mass index (BMI), and diagnosis of hypertension. Delivery data included gestational age at delivery and neonatal sex. All clinical data were retrieved from the parturient’s electronic medical records during pregnancy. Laboratory data included 1st trimester FPG level, the 50-gram glucose challenge test (GCT), and the 3-hour 100-gram oral glucose tolerance test (oGTT), if performed. T2DM diagnosis was retrieved from the INDR.
As per the 2001 guidelines set forth by the Israeli Ministry of Health, it is recommended that all parturients in Israel, regardless of their risk factors, undergo a FPG level test during their first trimester to rule out overt diabetes (>125 mg/dl). GDM is diagnosed using the two-step strategy: a 50-gram GCT followed by a 100-gram oGTT for screen-positive women (GCT≥140mg/dl). GDM is confirmed if the GCT result is above 200mg/dl or if there are two abnormal values on the oGTT, following the criteria established by Carpenter and Coustan8,9. For this analysis, we included all women without overt diabetes, according to FPG levels in 1sttrimester, and available FPG levels performed at less than 15+0 gestational weeks. For women with more than one pregnancy during the study period, only the first pregnancy was included to ensure the longest available follow-up time. Follow-up started at LMP and ended at the date of diabetes diagnosis, the date of data extraction (13 November 2022), or death—whichever occurred first.
T2DM was defined according to the INDR database. As previously described10, since 2012, all health medical organizations in Israel are requested by law to report cases of diabetes to the INDR. Diabetes diagnosis is updated daily to the registry and defined as meeting one or more of the following criteria: 1) HbA1C≥6.5% (47.5 mmol/ mol), 2) serum glucose concentrations ≥ 200 mg/dl (11.1 mmol/L) in two tests performed at an interval of at least one month, and 3) three or more purchases of glucose-lowering medications (determined as 3 to avoid misclassification of diabetes). The registry has a sensitivity of 95%, and the positive predictive value is 93% 10.