Quantification of lipoproteins by proton nuclear magnetic resonance spectroscopy (1H-NMRS) improves the prediction of cardiac autonomic dysfunction in patients with type 1 diabetes.

AIMS: To assess if advanced characterization of serum glycoprotein and lipoprotein profile, measured by proton nuclear magnetic resonance spectroscopy (1H-NMRS) improves a predictive clinical model of cardioautonomic neuropathy (CAN) in subjects with type 1 diabetes (T1D). METHODS: Cross-sectional study (ClinicalTrials.gov Identifier: NCT04950634). CAN was diagnosed using Ewing's score. Advanced characterization of macromolecular complexes including glycoprotein and lipoprotein profiles in serum samples were measured by 1H-NMRS. We addressed the relationships between these biomarkers and CAN using correlation and regression analyses. Diagnostic performance was assessed by analyzing their areas under the receiver operating characteristic curves (AUCROC). RESULTS: Three hundred and twenty-three patients were included (46% female, mean age and duration of diabetes of 41 ± 13 years and 19 ± 11 years, respectively). The overall prevalence of CAN was 28% [95% confidence interval (95%CI): 23; 33]. Glycoproteins such as N-acetylglucosamine/galactosamine and sialic acid showed strong correlations with inflammatory markers such as high-sensitive C-reactive protein, fibrinogen, IL-10, IL-6, and TNF-α. On the contrary, we did not find any association between the former and CAN. A stepwise binary logistic regression model (R2 = 0.078; P = 0.003) retained intermediate-density lipoprotein-triglycerides (IDL-TG) [ß:0.082 (95%CI: 0.005; 0.160); P = 0.039], high-density lipoprotein-triglycerides (HDL-TGL)/HDL-Cholesterol [ß:3.633 (95%CI: 0.873; 6.394); P = 0.010], and large-HDL particle number [ß: 3.710 (95%CI: 0.677; 6.744); P = 0.001] as statistically significant determinants of CAN. Adding these lipoprotein particles to a clinical prediction model of CAN that included age, duration of diabetes, and A1c enhanced its diagnostic performance, improving AUCROC from 0.546 (95%CI: 0.404; 0.688) to 0.728 (95%CI: 0.616; 0.840). CONCLUSIONS: When added to clinical variables, 1H-NMRS-lipoprotein particle profiles may be helpful to identify those patients with T1D at risk of CAN.

Untargeted metabolomics identifies a plasma sphingolipid-related signature associated with lifestyle intervention in prepubertal children with obesity.

OBJECTIVE: Childhood obesity is a strong risk factor for adult obesity and metabolic diseases, including type 2 diabetes and cardiovascular disease. Early lifestyle intervention in children with obesity reduces future disease risk. The objective of this study is to identify metabolic signatures associated with lifestyle intervention in prepubertal children with obesity. METHODS: Thirty-five prepubertal children (7-10 years) with obesity (body mass index (BMI)>2 standard deviations) were enrolled in the study and participated in a 6-month-long lifestyle intervention program. Physiological and biochemical data and blood samples were collected both at baseline and after the intervention. A liquid chromatography-mass spectrometry (LC-MS)-based metabolomics approach was applied to obtain a comprehensive profiling of plasma samples, identifying 2581 distinct metabolite. Principal component analysis (PCA) was performed to consolidate all features into 8 principal components. Associations between metabolites and physiological and biochemical variables were investigated. RESULTS: The intervention program significantly decreased mean (95% CI) BMI standard deviation score from 3.56 (3.29-3.84) to 3.11 (2.88-3.34) (P<0.001). PCA identified one component (PC1) significantly altered by the intervention (Bonferroni adjusted P=0.008). A sphingolipid metabolism-related signature was identified as the major contributor to PC1. Sphingolipid metabolites were decreased by the intervention, and included multiple sphingomyelin, ceramide, glycosylsphingosine and sulfatide species. Changes in several sphingolipid metabolites were associated with intervention-induced improvements in HbA1c levels. CONCLUSIONS: Decreased circulating sphingolipid-related metabolites were associated with lifestyle intervention in prepubertal children with obesity, and correlated to improvements in HbA1c.

Obesity rather than regional fat depots marks the metabolomic pattern of adipose tissue: an untargeted metabolomic approach.

OBJECTIVE: This study compares the patterns of visceral (VIS) and subcutaneous (SC) adipose tissue (AT)-derived metabolites from non-obese (BMI 24-26 kg/m2) and obese subjects (BMI > 40 kg/m2) with no major metabolic risk factors other than BMI. METHODS: SC- and VIS- AT obtained from obese (Ob) and non-obese (NOb) subjects during surgery were incubated to obtain their metabolites. Differences related to obesity or anatomical provenances of AT were assessed using an untargeted metabolomics approach based on gas chromatography-mass spectrometry. RESULTS: The overall effect of obesity on the metabolite profile resulted more remarkable than the effect of regional AT. Only the depletion of 2-ketoisocaproic (2-KIC) acid reached statistical significance for the SC-AT alone, although it was observed in both depots. Obesity induced more significant changes in several amino acids levels of the VIS-AT metabolites. On the one hand, higher released levels of glutamine and alanine were detected in the VIS- obese AT, whereas on the other, the VIS- obese AT presented a diminished uptake of essential amino acids (methionine, threonine, lysine), BCAAs, leucine, and serine. CONCLUSION: This study shows that obesity markedly affects the amino acid metabolic signature of the AT before the clinical onset of other significant metabolic alterations aside from BMI.