September 11, 2018
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Untreated gestational diabetes may increase risk for future maternal diabetes, obesity in children

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Women with mild gestational diabetes identified after pregnancy were more likely to go on to develop prediabetes or type 2 diabetes during the next decade, whereas children born to mothers with the condition were more likely to have overweight or obesity at follow-up, according to findings published in JAMA.

Boyd E. Metzger

“The risks associated with gestational diabetes are not limited to pregnancy outcome, but extend through the lifetime,” Boyd E. Metzger, MD, professor emeritus of endocrinology at Northwestern University Feinberg School of Medicine, told Endocrine Today. “Studies are needed to see if treating a mother’s gestational diabetes can also reduce the long-term risks of obesity in children.”

In the United States, women with gestational diabetes are typically diagnosed using the Carpenter-Coustan criteria, which requires two abnormal glucose values over 3 hours vs. one abnormal value during a 2-hour 75-g oral glucose tolerance test required by the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria.

“Approximately twice as many women are diagnosed with gestational diabetes using the IADPSG criteria compared with the Carpenter-Coustan criteria,” Metzger and colleagues wrote. “Whether women meeting the IADPSG criteria for gestational diabetes and their offspring are at risk for long-term adverse outcomes is unclear.”

Metzger and colleagues analyzed data from 4,697 mothers (mean age, 42 years) and 4,832 children (mean age, 11 years; 51% boys) who participated in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study, a population-based study of women who underwent a 75-g OGTT at approximately 28 weeks’ gestation. Researchers used post-hoc criteria from the IADPSG to define gestational diabetes, which included a fasting plasma glucose of at least 92 mg/dL, a 1-hour plasma glucose level of at least 180 mg/dL or a 2-hour plasma glucose of at least 153 mg/dL. Within the cohort, 427 women (1.8%) were informed of OGTT results based on FPG, 2-hour plasma glucose level or both; remaining participants were not treated.

During follow-up study visits occurring between February 2013 and December 2016, women underwent a 2-hour, 75-g OGTT after an 8-hour overnight fast. Nonfasting samples were obtained from women who reported having diabetes treated with oral medication or insulin at follow-up.

Primary maternal outcome was a composite of prediabetes or type 2 diabetes. Primary outcome for children was overweight or obesity (defined by age- and sex-specific BMI); secondary outcomes included greater than 85th percentile for body fat percentage, waist circumference and the sum of skinfolds (triceps, subscapular and suprailiac).

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Maternal diabetes outcomes

During a median follow-up of 11.4 years, 10.7% of women with gestational diabetes developed type 2 diabetes and 41.5% developed prediabetes. Among women without gestational diabetes, 1.6% developed type 2 diabetes and 18.4% developed prediabetes. After multiple variable adjustment, women with gestational diabetes were nearly 3.5 times more likely to develop the composite endpoint of prediabetes or type 2 diabetes vs. women without gestational diabetes (OR = 3.44; 95% CI, 2.85-4.14), with a risk difference of 25.7% (95% CI, 21.7-29.7).

When stratified by diabetes type, women with gestational diabetes were nearly 5.5 times more likely to develop type 2 diabetes vs. women without gestational diabetes (adjusted OR = 5.44; 95% CI, 3.68-8.08) and three times more likely to develop prediabetes (aOR = 3.07; 95% CI, 2.53-3.73).

Future overweight, obesity risk in offspring

Among children of mothers with gestational diabetes, 39.5% had overweight vs. 28.6% of children born to mothers without gestational diabetes. In early models, gestational diabetes was positively associated with childhood overweight or obesity, but the association did not persist after adjustment for maternal BMI during pregnancy (OR = 1.21; 95% CI, 1-1.46).

Children born to mothers with gestational diabetes were twice as likely to have obesity during follow-up vs. children born to mothers without gestational diabetes (19.1% vs. 9.9%), according to researchers. In a fully adjusted model, children born to mothers with gestational diabetes were more likely to be obese (OR = 1.58; 95% CI, 1.24-2.01), have a high body fat percentage (OR = 1.35; 95% CI, 1.08-1.68), high waist circumference (OR = 1.34; 95% CI, 1.08-1.67) and high sum of skinfold measurements (OR = 1.57; 95% CI, 1.27-1.95). In a model adjusted for maternal BMI, mean differences among offspring of mothers with gestational diabetes vs. offspring of mothers without gestational diabetes were attenuated, persisting only for high body fat percentage, high waist circumference and high sum of skinfolds, but not BMI.

Comparing criteria

The researchers noted that the study was not designed to compare women with vs. without gestational diabetes defined by the Carpenter-Coustan criteria; however, exploratory analyses showed that outcome frequencies for mothers and children were progressively higher across mothers without gestational diabetes, those with IADPSG-defined gestational diabetes and those with Carpenter-Coustan-defined gestational diabetes (P < .001 for all). – by Regina Schaffer

For more information:

Boyd E. Metzger, MD, can be reached at Northwestern University Feinberg School of Medicine, Endocrinology, 300 E. Superior, Suite 12-703, Chicago, IL 60611; email: bem@northwestern.edu.

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Disclosures: Metzger reports no relevant financial disclosures. One study author reports he has received grant support from AstraZeneca, Bayer and Pfizer and speakers’ fees from Boehringer Ingelheim and Takeda.