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.