Women who develop gestational diabetes mellitus (GDM) during their first pregnancy have a 30-50% chance of a recurrence of GDM in a subsequent pregnancy (1), and the rate of recurrence is higher in ethnic groups(2,3). The progression of GDM to type 2 diabetes later in life occurs at a rate of 26-47%(4,5),and it occurs more rapidly in ethnic groups that have a high prevalence of type 2 diabetes(4,5). We previously reported that patients with type 2 diabetes have an atherogenic lipoprotein profile that includes an abundance of small and dense LDL and HDL particles (6). To our knowledge, there are no reports on the lipoprotein profile of patients with GDM. Therefore, we initiated this study 1) to examine whether there are changes in the lipoproteins of GDM patients that are similar to those seen in type 2 patients and 2) to determine whether the lipoprotein profile is affected differently in African-American women with GDM versus Caucasian women with GDM.
We recruited 18 Caucasian women (12 nondiabetic and 6 GDM women) and 17 African-American women (7 nondiabetic and 10 GDM women). The participants were classified as having GDM according to the criteria of the National Diabetes Advisory Board. The Institutional Review Board for human subject research at East Carolina University approved all protocols. Fasting plasma glucose and insulin concentrations were determined as previously described(7). Lipid concentrations and lipoprotein subpopulation distributions were determined by a nuclear magnetic resonance (NMR) spectroscopy(7).
Consistent with the results of others(8,8,9,10,11),we found that VLDL triglyceride levels were higher in the GDM patients than in the control subjects (1.17 vs. 0.94 mmol/l), but the HDL (1.85 vs. 1.73 mmol/l) and LDL cholesterol (3.82 vs. 4.12 mmol/l) levels were similar in the two groups. The analysis of the lipoproteins by NMR showed that, when compared with control subjects, GDM patients had higher concentrations of large VLDL(0.439 vs. 0.251 mmol/l), small LDL (1.052 vs. 0.731 mmol/l), and HDL3 (0.763 vs. 0.692 mmol/l), but lower concentrations of large LDL (2.54 vs. 3.20 mmol/l). A comparison of the GDM patients with their respective control subjects showed that large VLDL was more abundant in the Caucasian patients than in the control subjects (0.650 vs. 0.270 mmol/l),whereas small LDL was elevated in African-American patients compared with their control subjects (0.813 vs. 0.190 mmol/l). These changes in the subpopulation distribution of the three major classes of lipoproteins are similar to those found in the patients with type 2 diabetes.
There was a more pronounced ethnic influence on the lipid concentration and the lipoprotein subpopulation distribution. The Caucasian women, as a group,had significantly higher plasma and VLDL triglyceride levels (1.26 vs. 0.825 mmol/l) and lower HDL cholesterol (1.66 vs. 1.93 mmol/l) levels than the African-American women. Koukkou et al.(11) reported that African-American women had significantly lower plasma triglyceride, total cholesterol, LDL cholesterol, and higher HDL cholesterol levels. We found similar trends for total cholesterol (5.93 vs. 6.57 mmol/l) and LDL cholesterol (3.62 vs. 4.32 mmol/l) levels that did not reach statistical significance because of the small sample size in our study. In addition, the Caucasian women had significantly smaller HDL (9.36 vs. 9.86 nm) and LDL (20.7 vs. 21.0 nm) particle diameters than the African-American women. In both cases, these elevations were seen in Caucasian control subjects compared with African-American control subjects (HDL 9.43 vs. 10.03 nm; LDL 20.73 vs. 21.20 nm), whereas differences between Caucasian GDM patients and African-American GDM patients were only seen in HDL size (9.22 vs. 9.74 nm). Thus, it appears that pregnancy with and without the complication of GDM does not affect the plasma lipid concentrations of African-American women as drastically as it effects their Caucasian counterparts.
The subpopulation distribution of the three major classes of lipoproteins also showed an ethnic influence. In comparison with the African-American women, we found that the Caucasian women, with or without GDM, had higher concentrations of large VLDL (0.397 vs. 0.273 mmol/l), small LDL (1.18 vs. 0.56 mmol/l) and HDL3 (0.776 vs. 0.670 mmol/l), but significantly lower concentrations of HDL2 (0.921 vs. 1.21 mmol/l). Furthermore,when compared with African-American women with GDM, Caucasian women with GDM had higher concentrations of large VLDL (0.650 vs. 0.312 mmol/l) and small LDL(1.45 vs. 0.813 mmol/l), but lower concentrations of HDL2 (0.815 vs. 1.21). In the control group, on the other hand, Caucasian women had higher concentrations of small LDL (1.05 vs. 0.190 mmol/l) and HDL3 (0.747 vs. 0.599 mmol/l) than the African-American women.
The results from this study show that the lipoprotein subpopulation distribution of patients with GDM was similar to that of women with type 2 diabetes. In addition, it appears that pregnancy with and without the complication of GDM has a milder effect on the plasma lipid and lipoprotein subpopulation distribution of African-American women, as a group, than that of Caucasian women, as a group. Therefore, further studies are needed to determine if these differences are maintained postpartum, and whether they affect the risk for early cardiovascular disease differently in Caucasian versus African-American women.
