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Later life diabetes risk was tied to a history of miscarriage, with what could be considered a dose response, according to a Danish study.

Women had a much higher chance of later developing type 2 diabetes if they had ever lost a pregnancy compared with women who had never experienced a pregnancy loss, reported Pia Egerup, MD, of Copenhagen University Hospital in Denmark, and colleagues.

As shown in their study online in , the chances of later developing diabetes increased if the woman lost more pregnancies compared with women who had been pregnant but never miscarried:

• One pregnancy loss: Odds ratio (OR) 1.18 (95% CI 1.13-1.23)

• Two pregnancy losses: OR 1.38 (95% CI 1.27-1.49)

• More than three pregnancy losses: OR 1.71 (95% CI 1.53-1.92)

For the analysis, the team compared data on nearly 25,000 Danish women with type 2 diabetes with about 250,000 controls free of diabetes; the women were matched based on age and education level.

Among women who later developed diabetes, about 19%, 4%, and 2% had one, two, or at least three pregnancy losses, respectively. But among women who never developed diabetes, only 17%, 3%, and 1% of them lost one, two, or three or more pregnancies, and the link remained statistically significant after the researchers adjusted for obesity status and history of gestational diabetes.

In a subgroup analysis, all women had an increased risk of developing type 2 diabetes later in life if they were expected to have a relatively low proportion of fetal aneuploidy or a high probability of an immunological background, the researchers noted.

"The association was strongest in women with a high likelihood of euploid pregnancy losses and a suspected immunological etiology behind their losses," the group explained, noting that possible causes of euploid losses included fetal chromosomal microdeletions, structural abnormalities, point mutations, and parental factors.

"Whether metabolic conditions at the time of pregnancy loss explain the association with type 2 diabetes or the association is caused by a shared etiology need to be explored in future studies," the investigators added.

Still, they said, it was not possible to rule out the possibility that the psychological distress of a pregnancy loss may be the catalyst for subsequent lifestyle changes that would be tied to diabetes risk, such as poor diet and lack of exercise.

Additionally, women who were never able to achieve a pregnancy had the highest risk of subsequently developing diabetes. Compared with women who experienced any number of pregnancy losses, women who never achieved a pregnancy had a more than 50% higher chance of developing diabetes (31.7% vs 25.1%; OR 1.56, 95% CI 1.51-1.61).

"These results should be interpreted with caution as the group encompasses women who have actively decided not to have children, women with chronic diseases making pregnancy impossible, and finally women with unexplained infertility," the researchers noted.

Egerup and co-authors suggested implementing regular HbA1c screening in clinical practice for higher-risk women, such as those who have lost three or more pregnancies.

Study limitations, the team said, included possible underestimation of miscarriages, since only pregnancy losses that were recorded in a hospital setting were included and those handled by a gynecologist or at home were not accounted for, and that pregnancy losses before 6-week gestation were often not recorded either.

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