Elevated Homocysteine as a Risk Factor for the Development of Diabetes in Women With a Previous History of Gestational Diabetes Mellitus: A 4-year Prospective Study

Abstract

Gestational diabetes mellitus (GDM) is a state of carbohydrate intolerance that first becomes apparent during pregnancy. An estimated 3% to 8% of all pregnancies in North America may be complicated by GDM. Affected women are at increased risk of later developing type 2 diabetes. Elevated blood levels of homocysteine have recently been recognized as a risk factor for cardiovascular disease. Both endothelial dysfunction and oxidative damage may be involved. The authors performed a prospective study designed to clarify the relationship between homocysteine and diabetes in 170 women with a history of GDM who had normal or impaired glucose tolerance, but not diabetes, at baseline (6 weeks postpartum). They were followed at annual intervals for up to 4 postpartum years by, among other measures, a 2-hour, 75-g oral glucose tolerance test. Diabetes developed in 18 women (10.6%) during a mean follow up of 2.94 years; 9 had normal glucose tolerance at baseline, and 9 had impaired glucose tolerance. At last follow up, another 43 (25.3%) had impaired glucose tolerance; 20 had normal glucose tolerance and 23 had impaired tolerance at baseline. The later development of diabetes was associated with prepregnancy obesity, early diagnosis of GDM, and high blood glucose. The women who developed diabetes also required insulin for GDM more often than others, but the difference did not meet statistical significance (P = 0.056). Fasting glucose and homocysteine levels were significantly higher in women who later developed diabetes than in those with impaired or normal glucose tolerance. The latest homocysteine level correlated positively with the fasting insulin level in women with diabetes or impaired glucose tolerance. The best predictor of future diabetes was the fasting blood glucose at the time GDM was diagnosed, but a homocysteine level above 6.4 mmol/L at baseline also was a relatively sensitive and specific predictive factor. Compared with women with relatively low homocysteine levels at baseline, those with higher levels had a greater than 3-fold increase in the risk of developing diabetes during follow up. In this prospective study, early postpartum elevation of the blood homocysteine level in a woman with a history of GDM was a risk factor for diabetes developing in the postpartum period. The authors suggest that measuring blood homocysteine 6 weeks postpartum will help to identify women with previous GDM who are at high risk of developing type 2 diabetes.