Diabetes Dateline
Spring/Summer 2009

Lifestyle Intervention and Metformin May Prevent Progression from Gestational Diabetes to Type 2 Diabetes

Among women with pre-diabetes, those who also have a history of diabetes during pregnancy, called gestational diabetes mellitus (GDM), have an even greater risk of developing type 2 diabetes than those with pre-diabetes alone. A new analysis from the Diabetes Prevention Program (DPP) shows that women with pre-diabetes and GDM were able to prevent or delay progression to type 2 diabetes with an intensive lifestyle intervention (ILS) or by taking the drug metformin.

“Both intensive lifestyle [intervention] and metformin are highly effective in delaying or preventing diabetes in women with pre-diabetes and a history of GDM,” according to Robert E. Ratner, M.D., DPP principal investigator, and co-authors, whose report was published in the December 2008 issue of The Journal of Clinical Endocrinology and Metabolism.

GDM is brought on by pregnancy and can lead to pregnancy-related complications, including high blood pressure and larger babies. Additionally, most women with GDM eventually develop type 2 diabetes. Pre-diabetes is defined as a blood glucose level higher than normal but not high enough to constitute diabetes.

Preventing Diabetes

Sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), the DPP, a multicenter clinical trial, enrolled 3,234 people with pre-diabetes, including 350 women with a history of GDM, and randomized them to one of three possible groups: an ILS group, which received diet modification and exercise counseling; a metformin group, which took 850 milligrams of the antidiabetic drug metformin twice daily; and a placebo control group, which took an inactive pill similar in appearance to metformin.

Over a 3-year period, the incidence of diabetes in the ILS and metformin groups was 58 and 31 percent lower, respectively, than the placebo group.

Diabetes is a condition in which the amount of blood glucose, also called blood sugar, is too high. Over time, elevated blood glucose damages blood vessels, leading to a variety of complications, including heart disease, stroke, blindness, and lower limb infections.

Type 2 diabetes, by far the most common kind of diabetes among adults, results from cells in the body failing to properly use insulin—a hormone used to transfer glucose from the bloodstream into cells. The body’s inability to properly use insulin is called insulin resistance. People with type 2 diabetes also make less insulin.

Progression to Diabetes

Because GDM was a known risk factor for the development of type 2 diabetes, DPP researchers compared outcomes of the 350 women in the study with a history of GDM with 1,416 women in the study with at least one live birth but no history of GDM.

After 3 years, among women randomized to the placebo group, those with a history of GDM had a 71 percent greater incidence of type 2 diabetes compared with women with no history of GDM.

“Those women randomized to placebo therapy represent uninterrupted progression of pre-diabetes within the DPP,” wrote Ratner and colleagues.

While taking metformin provided no statistically significant benefit to women without a history of GDM, it lowered incidence of diabetes 50 percent among women with a history of GDM. ILS, however, decreased diabetes incidence by about 50 percent, regardless of GDM history, when compared with respective placebo controls.

“GDM offers not just a warning for future DM but also an important opportunity to intervene and prevent incident cases,” wrote Jeffrey L. Ecker, M.D., associate professor of obstetrics, gynecology, and reproductive biology at Harvard Medical School, in a companion editorial. According to Ecker, the report by Ratner and colleagues emphasizes what previous DPP results argued: women with pre-diabetes after GDM should be encouraged to follow a plan of lifestyle modification or begin metformin treatment.

Ecker argued that DPP results should be a “call to action” for obstetricians, internists, and patients to follow up on GDM diagnoses after pregnancy to prevent progression to diabetes.

ILS clearly benefitted all groups in the study; however, women with a history of GDM had more difficulty maintaining target goals for physical activity, lost less weight in the first year of the intervention, and were quicker to regain weight over time. Metformin, one of the most widely prescribed medications for type 2 diabetes, is inexpensive and has relatively few side effects. In the DPP, metformin was particularly effective in younger and heavier participants.

The National Diabetes Information Clearinghouse, an information service of the NIDDK, offers free publications about gestational diabetes. For more information, go to www.diabetes.niddk.nih.gov.

NIH Publication No. 09–4562
August 2009

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