In utero exposure to gestational diabetes mellitus and cardiovascular risk factors in youth: A longitudinal analysis in the EPOCH cohort

Abstract

Summary Objective To examine associations of maternal gestational diabetes mellitus (GDM) with offspring cardiovascular biomarkers from late childhood through adolescence. Methods We used mixed effects linear regression models to examine associations of maternal GDM (n = 92 cases of 597) with average offspring levels of serum lipids (total cholesterol, high‐density lipoprotein [HDL], low‐density lipoprotein [LDL], and triglycerides) and systolic blood pressure (SBP) across two research visits spanning approximately 10.6 and 16.9 years of age. In sex‐stratified analysis, we evaluated the impact of adjustment for sociodemographic characteristics, pubertal status, physical activity and total energy intake, maternal body mass index (BMI), GDM treatment, and child's BMI. Results After adjusting for child's age, pubertal status, race/ethnicity, and maternal education and smoking, GDM exposure was associated with higher total (0.38 [95% CI, 0.16‐0.61] mmol/L) and LDL cholesterol (0.34 [95% CI, 0.14‐0.53] mmol/L) in girls. These estimates were robust to adjustment for lifestyle characteristics and maternal BMI but were attenuated after accounting for GDM treatment with no appreciable change following further adjustment for current BMI. In boys, maternal GDM corresponded with 4.50 (1.90‐7.10) mmHg higher SBP. This association persisted after accounting for sociodemographic/lifestyle characteristics, maternal BMI, and GDM treatment but was attenuated after adjusting for current BMI. Conclusions Maternal GDM is related to offspring lipid profile and SBP in a sex‐specific manner.

Substantially Altered Expression Profile of Diabetes/Cardiovascular/Cerebrovascular Disease Associated microRNAs in Children Descending from Pregnancy Complicated by Gestational Diabetes Mellitus—One of Several Possible Reasons for an Increased Cardiovascular Risk

“…Only those predicted targets involved in ontologies of human diseases (obesity, hypertension, glucose intolerance, lipid metabolism disease, type 2 diabetes mellitus, heart septal defects and heart valve disease, heart disease, heart failure, venous insufficiency, and pulmonary embolism) reported by previous population-based cohort studies in children and young adults descending from GDM complicated pregnancies [ 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 ] are presented below.…”

“…Parallel, in 17-year-old offspring of mothers with GDM and higher mean BMI, systolic and diastolic BP values were observed when compared to no-recorded-GDM offspring [ 31 ]. Nevertheless, another recent study performed on youth (at the age of 10.6–16.9 years) demonstrated that maternal GDM was related to altered lipid profile and higher systolic blood pressure only in a sex-specific manner [ 32 ]. A higher total and LDL cholesterol were detected only in girls and a higher systolic blood pressure only in boys previously exposed in utero to GDM [ 32 ].…”

“…Nevertheless, another recent study performed on youth (at the age of 10.6–16.9 years) demonstrated that maternal GDM was related to altered lipid profile and higher systolic blood pressure only in a sex-specific manner [ 32 ]. A higher total and LDL cholesterol were detected only in girls and a higher systolic blood pressure only in boys previously exposed in utero to GDM [ 32 ]. Even a significant association between maternal GDM and the rate of hospitalization for subsequent cardiovascular related morbidities (pre-defined set of ICD-9 codes) was noted in an 18-year follow-up study [ 33 ].…”

Association Analysis in Children Born from Normal and Complicated Pregnancies—Cardiovascular Disease Associated microRNAs and the Incidence of Prehypertension/Hypertension, Overweight/Obesity, Valve Problems and Heart Defects

“…Lifelong cardiovascular risk of children descending from pregnancy-related complications is based on the presence of overweight/obesity (increased body mass index and/or wider waist circumference) [1][2][3][4][5][6][7][8][9][10][11], higher systolic and/or diastolic blood pressures [1,2,[6][7][8][12][13][14][15][16][17][18][19][20][21][22], higher nocturnal systolic and diastolic blood pressures [16], altered lipid profiles [6,21], altered metabolite pattern [23], impaired glucose tolerance [3,[5][6][7]24], alteration in the systemic and the pulmonary circulation [25], altered cardiac geometry and function [26][27][28][29] and the acceleration of pubertal timing [30].…”

Genetic Interactions with Intrauterine Diabetes Exposure in Relation to Obesity: The EPOCH and Project Viva Studies

“…The rapid increase in pediatric obesity in recent decades has created a looming public health crisis. Mounting evidence implicates early life contributions to adiposity and cardiometabolic profiles later in life [ 1 , 2 , 3 , 4 ], and childhood obesity in particular has been associated with adult obesity, as well as many related comorbidities and diseases [ 5 ]. Risk for obesity is multifactorial and begins even before birth, with influence from factors such as genetics and in utero exposures [ 6 , 7 , 8 ].…”