WASHINGTON – Women with a history of gestational diabetes have a sustained long-term risk of developing type 2 diabetes, and this risk continues to be modifiable with either metformin or lifestyle intervention, according to a 10-year follow-up of women who participated in the National Institutes of Health–funded Diabetes Prevention Program trial.
"Even years out from their index pregnancy, women with a history of gestational diabetes are at a significantly increased and sustained risk [compared with women without a GDM history] of developing type 2 [diabetes] ... despite similar baseline metabolic status and despite similar clinical evidence of risk," said Dr. Vanita R. Aroda, who has served as a subinvestigator in the Diabetes Prevention Program (DPP).
Post-hoc analyses of follow-up data from the Diabetes Prevention Program Outcomes Study (DPPOS) show that while lifestyle intervention was similarly effective in reducing risk for all parous women (regardless of whether they had GDM), metformin was effective only in women with a history of GDM, Dr. Aroda reported at the annual meeting of the Diabetes in Pregnancy Study Group of North America.
The original DPP enrolled more than 3,000 individuals at high risk of developing diabetes. Participants were at least 25 years old, were overweight or obese, and had impaired glucose tolerance with fasting plasma glucose levels of 92-125 mg/dL and glucose levels of 140-199 mg/dL 2 hours after a 75-g oral glucose tolerance test.
Approximately 2,100 of the participants were women, 350 of whom had GDM "about 12 years prior," explained Dr. Aroda of Georgetown University, Washington.
Participants were randomized in the main study to placebo, lifestyle intervention, or metformin for approximately 3 years. In women with a history of GDM, lifestyle intervention and metformin reduced the progression to diabetes over this time by 53% and 50%, compared with placebo.
The effects of metformin were greater in these women than in the population as a whole, for which the risk reduction from metformin was 31%. For women without a history of GDM, the risk reduction from metformin was insignificant. Lifestyle intervention – which involved at least 7% weight loss, 150 minutes of activity per week, and a low-fat diet – was similarly effective for all groups.
The long-term DPPOS began after the DPP concluded, with the majority of the original cohort continuing in the follow-up. All participants in the DPPOS received basic lifestyle education at this point, because of its proven benefits. Those originally randomized to the lifestyle group received additional education/support, while those originally assigned to receive metformin or placebo continued in these study groups.
At a mean of 10 years’ follow-up, women with a history of GDM in the placebo group had a 65% higher risk of developing type 2 diabetes compared with women without a history of GDM – despite the fact these women were approximately 9 years younger than those without the GDM history, and an average of 20 years past their index pregnancy, Dr. Aroda said.
Metformin and lifestyle reduced progression to diabetes similarly among those with a GDM history (41% and 35%), compared with placebo. These intervention effects were greater than in those without a GDM history, who saw a 28% risk reduction from lifestyle and an insignificant reduction with metformin.
"For women with a history of GDM, the effectiveness of the initial interventions – lifestyle and metformin – was sustained. There were very nice risk reductions with both," Dr. Aroda said.
The GDM and non-GDM cohorts of women had a similar baseline body mass index and similar fasting and post–oral glucose tolerance test glucose levels. It is not clear why women without prior GDM had a lesser response to metformin, but "it could be that these women had healthier beta-cell function," she said.
Dr. Aroda reported that she receives consulting fees and grant support from Novo Nordisk and Sanofi-Aventis, as well as grant support from Bristol-Myers Squibb, GlaxoSmithKline, Integrium, Takeda Pharmaceuticals, and Boehringer Ingelheim Vetmedica GmbH.