Metabolic Problems in the Offspring of Women with Gestational Diabetes and Obesity: An Opportunity for Prevention

diabetes, gestational, type 2 diabetes, prediabetic state, obesity, adolescence, puberty, risk factors

Puberty is a critical period of life when body composition is defined and abnormalities associated with insulin resistance may become clinically apparent (1). Weight problems and increased adiposity during puberty are associated with obesity and metabolic problems later in life (2, 3). In recent decades, increasing incidence rates of gestational diabetes mellitus (GDM) and youth-onset type 2 diabetes (Y2DM) have been observed. Whether GDM and concurrent obesity in the pregnant mother indicate a worse metabolic prognosis in peripubertal children than when either is observed alone is unknown.

In a new report of the Hyperglycemia and Adverse Pregnancy Outcome Follow-up Study (HAPO FUS), Josefson et al described the association of increasing maternal glucose levels and weight during midpregnancy with adiposity in peripubertal offspring (4). Furthermore, the risk of adverse outcomes in those children was reported based on an analysis of the different combinations of maternal overweight/obesity and GDM.

The HAPO FUS is an epidemiological study that evaluated the maternal body mass index (BMI) and glucose levels at 28 weeks of pregnancy and determined the perinatal outcomes of the newborns. The follow-up study determined the metabolic outcome in the offspring during childhood. In this new study, 4832 mothers and their 10- to 14-year-old children were evaluated. Maternal BMI was assessed as a continuous variable or classified as underweight, normal, overweight, and obese. Maternal glycemia was determined as the sum of basal glucose level and the levels at 60 and 120 minutes of the oral glucose tolerance test. Gestational diabetes mellitus was diagnosed based on the International Association of Diabetes and Pregnancy Study Groups (IADPSG)/WHO criteria. The BMI and body composition in the offspring were also evaluated as continuous or categorical variables.

Josefson et al showed that increasing maternal glycemia, even after having been adjusted by maternal BMI, was positively and significantly associated with different measures of fat mass in their children but not with the children’s BMI (4). This positive association of maternal glycemia with the children’s adiposity was observed when assessed by both plethysmography and the sum of skinfold thickness and waist circumference.

Maternal BMI was associated with the children´s BMI. An additive effect of maternal BMI and glucose levels on the risk of obesity in the offspring was shown. The highest risk of obesity was observed in those children whose mothers had been obese and had had GDM during pregnancy, with an odds ratio (OR) of 6.1 for obesity in the child. The OR was only 3.54 in children whose mothers had been obese but had not had GDM and 1.73 in those whose mothers had not been obese but had had GDM.

Recently, a new publication from the HAPO FUS showed a high-risk of glucose intolerance in the peripubertal offspring of women with GDM (5). The proportion of children who had impaired glucose tolerance was 2 times higher in the group whose mothers had had GDM (10.6%) than in the group of children whose mothers had not had GDM (5%). Maternal fasting glucose during pregnancy was associated with childhood fasting glucose levels (6); moreover, the offspring of women with GMD were more insulin resistant and had decreased compensatory β-cell function. These data indicate that these children exhibit several elements of adverse metabolic profile, suggesting a high risk of progressing to type 2 diabetes as adults or developing GDM when they become pregnant.

Whether the data observed in the HAPO FUS are still valid with the current management of GDM is unknown. The pregnant women in the HAPO cohort were recruited during the 2000–2006 period. A recent publication showed that the offspring of mothers with GDM born between 2011 and 2013 had significantly less macrosomia and lower adiposity than the children born to women with GDM between 2001 and 2009 (7). Differences in growth curves during infancy were observed in the 2 groups of children. These data suggest that the actual management of GDM could alter the data that are reported in the HAPO FUS cohort.

However, the most critical question that arises from these data is this: What preventive measures should pediatricians recommend to their patients to stop this vicious cycle? Women with a history of GDM are at high risk for developing type 2 diabetes, and they benefit the most from diabetes prevention programs, as shown in the Diabetes Prevention Program (8). Advice regarding preventive measures should be provided not only to these high-risk women but also to their children.

In conclusion, the HAPO FUS study has shown that concurrent elevated maternal weight and glycemia during midpregnancy are associated with a long-term increased metabolic risk in the peripubertal offspring. Increasing glycemia during midpregnancy is associated with adiposity in 10- to 14-year-old children. Peripubertal children whose pregnant mothers were obese and had GDM have a high risk of developing obesity and glucose intolerance at a young age. Therefore, the combination of elevated maternal BMI and glycemia presents an opportunity to begin early metabolic prevention not only in mothers but also in their children. Pediatricians should be aware of the risk of obesity and type 2 diabetes in these children and should make a special effort to promote a healthy lifestyle in this high-risk group.

Acknowledgments

Financial Support: E.C. is partly funded by Fondo Nacional de Ciencia y Tecnología (FONDECYT) grant #1170895 from the Government of Chile.

Additional Information

Disclosure Summary: The author has nothing to disclose.

Data Availability: Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.