Novel glycoproteins identify preclinical atherosclerosis among women with previous preeclampsia regardless of type 1 diabetes status.

BACKGROUND AND AIMS: Information regarding inflammation and cardiovascular disease (CVD) risk in type 1 diabetes (T1D) or preeclampsia (PE) is scarce. We assessed differences in inflammation markers according to the presence of both conditions and their association with atherosclerosis. METHODS AND RESULTS: We recruited 112 women without CVD and last pregnancy ≥5 years previously (n = 28 per group): a)T1D and PE; b)T1D without PE; c)PE without T1D; and d)Controls (without T1D or PE). Groups were matched by several CVD risk factors, and diabetes duration and retinopathy in T1D. Carotid intima-media thickness (IMT) and plaque presence (IMT ≥1.5 mm) were assessed by ultrasonography. Inflammatory markers included classical variables (leucocytes and high-sensitivity C-reactive protein [hsCRP]) and glycoproteins by nuclear magnetic resonance (1H-NMR) spectroscopy (GlycA, GlycB, GlycF and the height/width [H/W] ratios of GlycA and GlycB). The age of the participants was 44.9 ± 7.8 years, and 20.5% harbored plaque. There were no differences in inflammatory markers among the four study groups. Overall, in multivariate-adjusted models, all 1H-NMR-glycoproteins (except GlycB) were positively associated with IMT measures (IMT of bulb and maximum-IMT of any carotid segment; p < 0.05). After dividing the sample according to PE status, previous findings remained largely unchanged. Furthermore, GlycF was independently associated with carotid plaque only in PE group (OR 5.08 [1.03-25.01] per 0.1 log-increments, p = 0.046). Neither leucocytes nor hsCRP were related to atherosclerosis. Regarding T1D status, non-uniform results were observed. CONCLUSIONS: High 1H-NMR-glycoprotein concentrations have a negative impact on carotid atherosclerosis among women with preeclampsia, regardless of T1D status.

Nuclear magnetic resonance lipoproteins are associated with carotid atherosclerosis in type 1 diabetes and pre-eclampsia.

AIMS: Persistence of lipoprotein abnormalities in type 1 diabetes (T1D) and/or pre-eclampsia could be associated with cardiovascular disease (CVD). We assessed differences in the advanced lipoprotein profiles according to the presence of both conditions and their differential association with atherosclerosis. MATERIAL AND METHODS: We recruited 112 women without CVD and last pregnancy ≥5 years previously, divided into four groups (n = 28 per group): (a) T1D and previous pre-eclampsia; (b) T1D without pre-eclampsia; (c) pre-eclampsia without T1D; and (d) controls (without T1D/pre-eclampsia). Groups were matched by several risk factors, and diabetes duration and retinopathy in T1D. Carotid intima-media thickness (IMT) and the presence of plaque (IMT ≥1.5 mm) were assessed by ultrasonography. The lipoprotein profile was evaluated by nuclear magnetic resonance (NMR) spectroscopy. RESULTS: The participants were 44.9 ± 7.8 years old. Carotid plaque presence was 20.5%, with a higher prevalence in T1D and/or pre-eclampsia vs controls (P < .05). High-density lipoprotein (HDL)-related variables differed among groups, mainly driven by an increase in T1D (P < .05), whereas triglyceride-related variables were increased in pre-eclampsia [medium very low-density lipoprotein (VLDL) particles and triglyceride enrichment in HDL and low-density lipoprotein (LDL)]. Overall, in multivariate-adjusted models, LDL-related variables were the most strongly associated with atherosclerosis (P < .05). In age- and statin-adjusted models, previous pre-eclampsia showed an independent association with triglyceride-related variables (plaque: medium-VLDL-particles, OR 1.550 [1.013-2.374]; HDL-cholesterol/HDL-triglycerides ratio, OR 0.411 [0.175-0.967]). Regarding T1D, HDL-parameters were also differentially associated (maximum-IMT: HDL-cholesterol/HDL-particles ratio, ß = -.258, P = .036). CONCLUSIONS: NMR lipoproteins were differentially and independently associated with atherosclerosis in T1D/pre-eclampsia. Further studies are needed to ascertain the role of NMR parameters as CVD biomarkers in this high-risk population.

Nuclear magnetic resonance-based metabolomic analysis in the assessment of preclinical atherosclerosis in type 1 diabetes and preeclampsia.

AIMS: Evaluate the role of plasma metabolomics in atherosclerosis according to the presence of type 1 diabetes (T1D) or previous preeclampsia. METHODS: We recruited 105 women without cardiovascular disease and last pregnancy ≥5 years previously, divided according to the presence of T1D or previous preeclampsia. Preclinical atherosclerosis was defined as the presence of carotid plaque (intima-media thickness ≥1.5 mm) assessed by ultrasonography. Metabolomics were evaluated by nuclear magnetic resonance (NMR). Bivariate and multivariate-adjusted differences in NMR-metabolomics were evaluated. RESULTS: The participants were 44.9 ± 8.1 years-old; 20% harbored plaques. There were significant differences in lipidic-, energetic- and nitrogen-related metabolites according to the presence of T1D/preeclampsia (p < 0.05). In multivariate-adjusted models (by age, statins, blood pressure and T1D/preeclampsia), only lipidomic-related metabolites were associated with atherosclerosis in the whole sample. However, stronger associations were observed in women with previous preeclampsia (vs. without; per 0.5 mmol/L increments); phosphatidylcholine, OR 4.08 (1.32-27.22); free cholesterol, 5.18 (1.22-21.97); saturated fatty acids, OR 2.99 (1.37-6.48); w-7, OR 2.29 (1.15-4.56); and w-9 fatty acids, OR 1.49 (1.00-2.23). CONCLUSIONS: NMR-metabolomics showed a differential pattern according to the presence of T1D/preeclampsia in relation to preclinical atherosclerosis. Since most of these metabolites mirror lifestyle factors, they could help tailor dietetic advice in high-risk women.

Preeclampsia Is Associated With Increased Preclinical Carotid Atherosclerosis in Women With Type 1 Diabetes.

PURPOSE: Although preeclampsia (PE) is a well-established cardiovascular risk factor (CVRF) in the general population, its role in type 1 diabetes (T1D) has been scarcely studied. We assessed the association between PE and preclinical atherosclerosis in T1D. METHODS: We recruited 112 women without cardiovascular disease and last pregnancy ≥5 years before: (1) T1D and previous PE (T1D+/PE+; n = 28); (2) T1D without preeclampsia (T1D+/PE-; n = 28); (3) previous PE without T1D (T1D-/PE+; n = 28); and (4) controls (without T1D or PE; T1D-/PE-; n = 28). Groups were matched by age, several CVRFs, and diabetes duration and retinopathy (in T1D participants). Carotid intima-media thickness (IMT) and the presence of plaque (IMT ≥ 1.5 mm) were assessed by standardized ultrasonography protocol. RESULTS: Mean age of the participants was 44.9 ± 7.8 years (14.3% hypertension and 21.4% active smokers). Groups including T1D (T1D+/PE+ and T1D+/PE-) more frequently presented hypertension and statin treatment (23.2% vs 5.4% and 37.5% vs 8.9%; respectively; P < 0.01), without differences in other CVRFs. Carotid plaques were observed in 20.5%. In multivariate models adjusted for age, CVRF, and statins, both T1D and PE showed a similar impact on the presence of plaque, with odds ratios (95% confidence interval), 5.45 (1.36-21.9) and 4.24 (1.04-17.3), respectively. Both entities showed an additive effect when combined, both in common carotid-IMT (T1D+/PE- or T1D-/PE+, ß = 0.198; T1D+/PE+, ß = 0.297) and in the presence of plaque (8.53 [1.07-68.2] and 28.1 [2.67-296.4], respectively). CONCLUSIONS: Previous PE was independently associated with preclinical atherosclerosis in T1D. Further studies are needed to ascertain its usefulness for stratifying risk in T1D women.