Adiposity, Dysmetabolic Traits, and Earlier Onset of Female Puberty in Adolescent Offspring of Women With Gestational Diabetes Mellitus: A Clinical Study Within the Danish National Birth Cohort

Abstract

OBJECTIVEOffspring of pregnancies affected by gestational diabetes mellitus (GDM) are at increased risk of the development of type 2 diabetes. However, the extent to which these dysmetabolic traits may be due to offspring and/or maternal adiposity is unknown. We examined body composition and associated cardiometabolic traits in 561 9- to 16-year-old offspring of mothers with GDM and 597 control offspring.RESEARCH DESIGN AND METHODSWe measured anthropometric characteristics; puberty status; blood pressure; and fasting glucose, insulin, C-peptide, and lipid levels; and conducted a DEXA scan in a subset of the cohort. Differences in the outcomes between offspring of mothers with GDM and control subjects were examined using linear and logistic regression models.RESULTSAfter adjustment for age and sex, offspring of mothers with GDM displayed higher weight, BMI, waist-to-hip ratio (WHR), systolic blood pressure, and resting heart rate and lower height. Offspring of mothers with GDM had higher total and abdominal fat percentages and lower muscle mass percentages, but these differences disappeared after correction for offspring BMI. The offspring of mothers with GDM displayed higher fasting plasma glucose, insulin, C-peptide, HOMA-insulin resistance (IR), and plasma triglyceride levels, whereas fasting plasma HDL cholesterol levels were decreased. Female offspring of mothers with GDM had an earlier onset of puberty than control offspring. Offspring of mothers with GDM had significantly higher BMI, WHR, fasting glucose, and HOMA-IR levels after adjustment for maternal prepregnancy BMI, and glucose and HOMA-IR remained elevated in the offspring of mothers with GDM after correction for both maternal and offspring BMIs.CONCLUSIONSIn summary, adolescent offspring of women with GDM show increased adiposity, an adverse cardiometabolic profile, and earlier onset of puberty among girls. Increased fasting glucose and HOMA-IR levels among the offspring of mothers with GDM may be explained by the programming effects of hyperglycemia in pregnancy.

Prevention of Type 2 diabetes after gestational diabetes directed at the family context: a narrative review from the Danish Diabetes Academy symposium

“…Today, several studies support the association between GDM and long-term health outcomes in the offspring. Moreover, a recent study by Grunnet and colleagues [21], including 600 offspring of mothers with GDM confirmed the evidence of insulin resistance and obesity, and further showed higher systolic blood pressure and an earlier onset of puberty among the GDM female offspring compared with control offspring. Longterm follow-up studies in groups of offspring of women with GDM indicate that the offspring are more likely to be overall and centrally obese, and to exhibit insulin resistance and glucose intolerance in early adulthood [18].…”

“…Specifically, Danish studies have shown that offspring (aged 18-27 years) of women with GDM have an eight-fold higher risk of Type 2 diabetes/prediabetes, a two-fold higher risk of overweight and a five-fold higher risk of metabolic syndrome than offspring from the background population [19,20]. Moreover, a recent study by Grunnet and colleagues [21], including 600 offspring of mothers with GDM confirmed the evidence of insulin resistance and obesity, and further showed higher systolic blood pressure and an earlier onset of puberty among the GDM female offspring compared with control offspring.…”

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

“…These findings are comparable with those of an analysis of 96 male and female Polish youth aged 7 to 16 years wherein Wilk et al detected unadjusted differences of 19.0 and 14.2 mg/dL higher total and LDL cholesterol, respectively, among GDM‐exposed (n = 50) vs unexposed participants (n = 46). In a recent study of greater than 1000 boys and girls in the Danish National Birth Cohort, Grunnet et al reported higher serum triglycerides (5% [95% CI, 1‐10%]) and lower HDL (−0.07 [95% CI, −0.11 to −0.02] mmol/L), as well as marginally higher LDL (0.06 [95% CI, −0.01 to 0.14] mmol/L) at 12 years of age among GDM‐exposed youth . However, these associations became null after adjusting for maternal and child BMI.…”

“…In utero exposure to GDM corresponded with an average of 0 to 0.14] mmol/L) at 12 years of age among GDM-exposed youth. 16 However, these associations became null after adjusting for maternal and child BMI.…”

Pubertal timing in boys and girls born to mothers with gestational diabetes mellitus: a systematic review

“…The populations studied were predominantly Caucasian. Four studies had comparable primary objectives to our review question, (26)(27)(28)(29) two studies looked at multiple predictors of pubertal timing (24,30), and one looked at multiple developmental outcomes in the offspring of mothers with GDM including pubertal timing (25).…”