Gestational diabetes may predict autoimmune diabetes risk
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Women diagnosed with gestational diabetes are more likely to be autoantibody positive and develop type 1 diabetes in the decade after delivery compared with pregnant women without gestational diabetes, data from a large Finnish cohort show.
Women with gestational diabetes are at high risk for developing type 2 diabetes later in life, but risk for type 1 diabetes is also increased, Kaisu Luiro-Helve, MD, PhD, consultant in obstetrics and gynecology and reproductive endocrinology at the University of Helsinki and Helsinki University Hospital, Finland, said during a virtual presentation at the European Congress of Endocrinology. Luiro-Helve and colleagues previously conducted a prospective, 6-year cohort study showing an association of islet cell autoantibodies (ICA) and glutamic acid decarboxylase autoantibodies (GADA), gestational diabetes diagnosis before age 30 years, and the need for insulin treatment during pregnancy as high-risk factors of progression to type 1 diabetes.
“We had this excellent cohort material, so it was natural for us to then define the controls from the same hospital, and follow both to better understand the risk,” Luiro-Helve told Healio. “To our knowledge it is the longest follow-up study to date.”
In a prospective cohort study, Luiro-Helve and colleagues analyzed data from 391 women with gestational diabetes and 391 age-, parity- and delivery date-matched controls who delivered from 1984 through 1994 and underwent autoantibody testing during the first trimester of pregnancy. Researchers assessed levels of four autoantibodies associated with type 1 diabetes: ICA, GADA, insulin autoantibodies (IAA) and insulinoma-associated antigen-2 autoantibodies (IA-2A). Women completed a follow-up questionnaire assessing later type 1 or type 2 diabetes diagnosis in 2012-2013. The mean follow-up time was 23 years.
Researchers observed single autoantibody positivity in 12% (n = 41) of the gestational diabetes cohort and in 2.3% (n = 8) of the control cohort.
In the gestational diabetes cohort, 2.6% (n = 9) tested positive for two autoantibodies and 2.3% (n = 8) tested positive for three autoantibodies, whereas only one woman in the control cohort had two autoantibodies detected.
ICA positivity was found in 12.5% of cases, followed by GADA (6%), IA-2A (4.9%) and IAA (1.2%). In the control cohort, GADA positivity was found in 1.4% of cases, followed by IA-2A (0.8%), IAA (0.6%) and ICA (0.3%).
All women with three positive autoantibodies developed type 1 diabetes within 7 years from pregnancy with gestational diabetes. Development of type 2 diabetes and gestational diabetes occurred independent of autoantibody positivity.
“We were expecting cases of type 2 diabetes, but we were surprised at how many women had the potential to develop type 1 diabetes,” Luiro-Helve told Healio. “Really, the fact that incidences were so high for both types of diabetes was surprising. Though, Finland does have the highest incidence of type 1 diabetes in the world, so we are not sure how reproduceable these findings are.”
Luiro-Helve said development of type 1 diabetes can be reliably predicted with GADA and ICA during early pregnancy; however, researchers still must determine how to best screen women and determine their risk.
“There are two questions: Who should be tested for gestational diabetes and who should be followed after,” Luiro-Helve said. “For this study, the women delivered from 1984 to 1994. Universal gestational diabetes screenings did not exist at that time; it was a risk-based screening. Today, universal screening for gestational diabetes is recommended. The tricky question is after that. The results of this study are not yet final, and that is the question we want to answer.”
Luiro-Helve said clinicians should look more closely at women with a gestational diabetes diagnosis who require insulin therapy, in which diet or metformin is not enough, or at women with a gestational diabetes diagnosis in the setting of normal BMI.
“If you are not the typical gestational diabetes candidate, but you have it, that may warrant more screening,” Luiro-Helve said. “Type 1 diabetes is not just a disease of the young. Type 1 usually occurs within 10 years of gestational diabetes, and that is the time when we need to stay alert and perhaps conduct another oral glucose tolerance test. Do not forget about these women after delivery.”
Perspective
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Luiro-Helve presented the findings of mean 23 years of follow-up of gestational diabetes to evaluate risk for developing type 1 diabetes in those women who had islet autoantibodies testing during the first trimester of pregnancy. The results show 4.9% of women with gestational diabetes had two or more antibodies. Those with three or more antibodies (2.3%) developed type 1 diabetes within 7 years.
Risk for type 2 diabetes after gestational diabetes is well known and therefore the American Diabetes Association recommends that women with a history of gestational diabetes mellitus should have lifelong screening for the development of diabetes or prediabetes at least every 3 years. However, this study highlighted an important point that those with multiple antibodies are at high risk for developing type 1 diabetes, like the nonpregnant population. Currently, there is no guidance on testing for antibodies in women with gestational diabetes due to limited data on benefits and risk of doing so. Therefore, type 1 diabetes is missed in women with gestational diabetes who develop diabetes in later life.
More studies are needed to understand benefits vs. risk for antibody screening in women with gestational diabetes before we can make some recommendation on antibody screening for type 1 diabetes prediction in this population.
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Luiro-Helve K, et al. Abstract #1479. Presented at: European Congress of Endocrinology; May 22-26, 2021 (virtual meeting).
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