OBJECTIVETo assess whether gestational diabetes mellitus (GDM) can be prevented by a moderate lifestyle intervention in pregnant women who are at high risk for the disease. RESEARCH DESIGN AND METHODSTwo hundred ninety-three women with a history of GDM and/or a prepregnancy BMI of ‡30 kg/m 2 were enrolled in the study at <20 weeks of gestation and were randomly allocated to the intervention group (n = 155) or the control group (n = 138). Each subject in the intervention group received individualized counseling on diet, physical activity, and weight control from trained study nurses, and had one group meeting with a dietitian. The control group received standard antenatal care. The diagnosis of GDM was based on a 75-g, 2-h oral glucose tolerance test at 24-28 weeks of gestation. RESULTSA total of 269 women were included in the analyses. The incidence of GDM was 13.9% in the intervention group and 21.6% in the control group ([95% CI 0.40-0.98%]; P = 0.044, after adjustment for age, prepregnancy BMI, previous GDM status, and the number of weeks of gestation). Gestational weight gain was lower in the intervention group (20.58 kg [95% CI 21.12 to 20.04 kg]; adjusted P = 0.037). Women in the intervention group increased their leisure time physical activity more and improved their dietary quality compared with women in the control group. CONCLUSIONSA moderate individualized lifestyle intervention reduced the incidence of GDM by 39% in high-risk pregnant women. These findings may have major health consequences for both the mother and the child. A slide set summarizing this article is available online.Clinical trial reg. no. NCT01698385, clinicaltrials.gov.

Insulin sensitivity decreases for the first time in females at the time of menarche. A much more profound decrease in insulin sensitivity is observed at the end of pregnancy. This physiological insulin resistance is not accompanied by a rise in overall sympathetic activity as reflected in plasma noradrenaline levels, but there is evidence of moderate sympathetic overactivity in muscle and the heart. Pre-eclampsia is characterized by increased insulin resistance, sympathetic overactivity and a particular lipid profile. Thus it is the first manifestation of metabolic syndrome. Women with a history of pre-eclampsia have persistent insulin resistance after pregnancy associated with increased sympathetic activity of the cardiovascular system, and coronary artery disease later in life. Aging is accompanied by a greater increase in sympathetic traffic in women than in men, and inflammation (measured via C-reactive protein) seems to be more strongly related to metabolic syndrome in women than in men. The clinical relevance of these observations remains to be shown. As the key factors of metabolic syndrome, such as insulin resistance and sympathetic overactivity, are closely inter-related, treatment should be aimed at cutting the vicious circle at many points: lifestyle modification (diet, increasing exercise) as a basis of therapy, use of insulin sensitizers (e.g. metformin) to decrease insulin resistance, central sympatholytics (e.g. moxonidine), and AT-receptor blockers or angiotensin-converting enzyme (ACE) inhibitors to overcome sympathetic overactivity, hypertension and inflammation.