Early Subclinical Atherosclerosis in Gestational Diabetes: The Predictive Role of Routine Biomarkers and Nutrigenetic Variants

Abstract

Gestational diabetes mellitus (GDM) can be considered a silent risk for out-of-pregnancy diabetes mellitus (DM) and cardiovascular disease (CVD) later in life. We aimed to assess the predictive role of 3^rd trimester lipid profile during pregnancy for the susceptibility to markers of subclinical atherosclerosis (CVD susceptibility) at 3 years in a cohort of women with history of GDM. A secondary aim is to evaluate the usefulness of novel nutrigenetic markers, in addition to traditional parameters, for predicting early subclinical atherosclerosis in such women in order to plan adequate early prevention interventions. We assessed 28 consecutive GDM women in whom we collected socio-demographic characteristics and clinical and anthropometric parameters at the 3^rd trimester of pregnancy. In a single blood sample, from each patient, we assessed 9 single nucleotide polymorphisms (SNPs) from 9 genes related to nutrients and metabolism, which were genotyped by High Resolution Melting analysis. All women then attended a 3-year-postpartum follow-up and on that occasion performed an oral glucose tolerance test (OGTT, with 75 g oral glucose), the measurement of carotid artery intima-media thickness (cIMT), and analyses of metabolic parameters. In addition, we evaluated the physical activity level and the adherence to Mediterranean diet (MedDiet) using the International Physical Activity Questionnaire (IPAQ-short version) and PREDIMED questionnaires. We found an association between 3^rd trimester triglycerides and cIMT (p = 0.014). We also found significant associations between the APOA5 CC genotype and cIMT after adjustments for age and body mass index (p = 0.045) and between the interaction CC APOA5/CC LDLR and cIMT (p = 0.010). At the follow-up, the cohort also featured a mean BMI in the overweight range and a high mean waist circumference. We found no difference in the MedDiet adherence, physical activity, and smoking but an inverse correlation between the PREDIMED and the IPAQ scores with the IMT. In conclusion, this preliminary study provides insight into the predictive role of lipid profile during pregnancy and of some genetic variants on cIMT taken as a parameter of subclinical CVD susceptibility in GDM.

Figure 1

Nonparametric correlation analysis between cIMT and lipid profile during 3^rd trimester of pregnancy.

Figure 2

Box-whisker graphs of cIMT values with respect to APOA5 genotypes. Box-whisker plots show the 25^th and 75^th percentile range (box) with Tukey 95% confidence intervals (whiskers) and median values (transverse lines in the box). p value in figure is relative to Kruskal-Wallis test.