Gestational Diabetes Tied to Youth-Onset Diabetes

Gestational diabetes was associated with higher risk among offspring for diabetes in childhood and adolescence, researchers in Canada reported.

In a retrospective cohort study, children born to mother's with gestation diabetes had nearly twice the incidence of youth-onset diabetes compared with mothers who didn't have gestational diabetes (4.52 per 10,000, 95% CI 4.47-4.57, vs 2.4 per 10,000, 95% CI 2.37-2.46), according to Andrea Blotsky, MD, of McGill University Health Centre in Montréal, and colleagues.

Children exposed to gestational diabetes in utero had a significantly higher risk for developing diabetes -- either type 1 or type 2 diabetes -- through the age of 22, they reported in CMAJ:

• Diagnosis from birth to age 22 years: adjusted hazard ratio 1.77 (95% CI 1.41-2.22)
• Birth to age 12 years: aHR 1.43 (95% CI 1.09-1.89)
• Age 12 to 22 years: aHR 2.53 (95% CI 1.67-3.85)

"Although type 1 and type 2 diabetes in parents are well-established risk factors for diabetes, we show that gestational diabetes mellitus may be a risk indicator for diabetes in the mother's children before age 22," said co-author Kaberi Dasgupta, MD, also of the McGill, in a statement.

She said the "link of diabetes in children and youth with gestational diabetes in the mother has the potential to stimulate clinicians, parents, and children and [the] youth themselves to consider the possibility of diabetes if offspring of a mother with gestational diabetes mellitus develop signs and symptoms such as frequent urination, abnormal thirst, weight loss or fatigue."

The analysis included 73,180 triads -- mothers, fathers, and offspring groups -- residing in Quebec. Triads were excluded if either of the parents had a history of diabetes prior to pregnancy. Triads were also excluded if either parent had a history of heart failure or cardiovascular disease prior to pregnancy, as the researchers said this could indicate "the possibility of underdiagnosed diabetes in these parents."

Gestational diabetes was noted according to ICD-10 codes recorded at outpatient visits ≤270 days before delivery. Diabetes in children was defined as one hospital or two outpatient diagnosis within a 2-year period.

Although the researchers weren't able to differentiate between type 1 or type 2 diabetes diagnoses in children, which was a study limitation, they noted that prior Canadian studies suggested that about 90%-95% of youth with diabetes have type 1 diabetes. Other study limitations included a lack of data on maternal BMI or weight gain throughout pregnancy.

The risk models were adjusted for potential confounders including mother's gestational age, macrosomia, offspring's sex, and other maternal demographics.

Other factors associated with offspring diabetes in the study included:

• Female sex: aHR 1.23 (95% CI 0.99-1.52)
• Birth weight <3,000 g (6.6 lbs): aHR 1.24 (95% CI 0.95-1.63)
• Birth weight ≥4,000 g (8.8 lbs): aHR 1.35 (95% CI 0.98-1.85)

Blotsky's group noted that a link with female sex was found previously, specifically for type 2 diabetes risk due to heightened insulin resistance in adolescence. While they acknowledged that insulin resistance does play a major role in development of type 2 diabetes, "the accelerator and overload hypotheses propose that insulin resistance increases destruction (apoptosis) of the insulin-producing β cells in the pancreas, heightening the autoimmune reaction to β cells in immunologically at-risk individuals and resulting in progression to type 1 diabetes."

The authors called for additional, longer-term research to look at outcomes of children with diabetes who were exposed to gestational diabetes, specifically to see if there's a difference in disease severity compared with other children with diabetes not tied to gestational diabetes.

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