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INTRODUCTION: Cardiovascular disease (CVD) is the leading cause of mortality in type 1 diabetes (T1D). However, there is a need for daily practice tools for identifying those more prone to suffer from these events. We aimed to assess the relationships between nuclear magnetic resonance (1H NMR)-based lipidomic analysis and several CVD risk variables (including preclinical carotid atherosclerosis) in individuals with T1D at high risk. METHODS: We included patients with T1D without CVD, with at least one of the following: age ≥ 40 years, diabetic kidney disease, or ≥ 10 years of evolution with another risk factor. The presence of plaque (intima-media thickness > 1.5 mm) was determined by standardized ultrasonography protocol. Lipidomic analysis was performed by 1H NMR. Bivariate and multivariate-adjusted differences in 1H NMR lipidomics were evaluated. RESULTS: We included n = 131 participants (49.6% female, age 46.4 ± 10.3 years, diabetes duration 27.0 ± 9.5 years, 47.3% on statins). Carotid plaques were present in 28.2% of the individuals (n = 12, with ≥ 3 plaques). Glucose (HbA1c), anthropometric (body mass index and waist circumference), and insulin resistance-related (fatty liver index and estimated glucose disposal rate) variables were those most associated with 1H NMR-derived lipidomic analysis (p < 0.01 for all). Regarding preclinical atherosclerosis, sphingomyelin was independently associated with carotid plaque presence (for 0.1 mmol/L increase, OR 0.50 [0.28-0.86]; p = 0.013), even after adjusting for age, sex, hypertension, statin use, mean 5-year HbA1c and diabetes duration. Furthermore, linoleic acid and ω-6 fatty acids remained independently associated with higher plaque burden (≥ 3 plaques) in multivariate models (0.17 [0.03-0.93] and 0.27 [0.07-0.97], respectively; p < 0.05 for both). CONCLUSION: In our preliminary study of individuals with T1D at high risk, several 1H NMR-derived lipidomic parameters were independently associated with preclinical atherosclerosis. Specifically, ω-6 fatty acids and linoleic acid seem promising for identifying those with higher plaque burden.
RESUMO
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.
