Nuclear Magnetic Resonance-Based Lipidomics in the Assessment of Cardiometabolic Risk in Type 1 Diabetes: An Exploratory Analysis

Abstract

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.

Keywords: Lipidomic analysis; Nuclear magnetic resonance; Preclinical atherosclerosis; Type 1 diabetes; Vascular ultrasonography.

Fig. 1

Associations between NMR lipidomics and clinical and laboratory parameters. Numbers in cells indicate Spearman’s R correlation index and the colour of each cell indicates the strength of association of that index according to the colour code shown in the right column. ACR albumin-to-creatinine ratio, ALAT alanine aminotransferase, BMI body mass index, eGDR estimated glucose disposal rate, eGFR estimated glomerular filtration rate, FLI fatty liver index, SBP systolic blood pressure, WBC white blood cells, WC waist circumference