Metabolomic Profile of Insulin Resistance Women with Systemic Lupus Erythematosus

Abstract

The aims of this study were in systemic lupus erythematosus (SLE) patients: 1) to compare the metabolomic profile of insulin resistance (IR) with controls and 2) to correlate the metabolomic profile with other IR surrogates and SLE disease variables and vitamin levels. In this cross-sectional study, serum samples were collected from women with SLE (n=64) and gender- and age-matched controls (n=71), which were not diabetic. Serum metabolomic profiling was performed using UPLC-MS-MS (Quantse score). HOMA and QUICKI were carried out. Serum 25(OH)D concentrations were measured by chemiluminescent immunoassay. In women with SLE, the metabolomic Quantose score significantly correlated with HOMA-IR, HOMA2-IR, and QUICKI. Although concentrations of IR metabolites were not different between SLE patients and controls, fasting plasma insulin levels were higher and insulin sensitivity lower in SLE women. Interestingly, the Quantose IR score was significantly correlated with complement C3 levels (r=0.7; p=0.001). 25 (OH)D did not correlate with any metabolite or the Quantose IR index. Quantose IR may be a useful tool for IR assessment. There was a possible correlation between the metabolomic profile and complement C3 levels. The implementation of this metabolic strategy may help develop biochemical insight into metabolic disorders in SLE.

Key words

vitamin D - systemic lupus erythematosus - insulin resistance

Publikationsverlauf

Eingereicht: 24. August 2022

Angenommen nach Revision: 13. Mai 2023

Accepted Manuscript online:
13. Mai 2023

Artikel online veröffentlicht:
10. Juli 2023

• References

• 1 Fanouriakis A, Tziolos N, Bertsias G. et al. Update οn the diagnosis and management of systemic lupus erythematosus. Ann Rheum Dis 2021; 80: 14-25
• 2 Sanchez-Perez H, Tejera-Segura B, de Vera-Gonzalez A. et al. Insulin resistance in systemic lupus erythematosus patients: contributing factors and relationship with subclinical atherosclerosis. Clin Exp Rheumatol 2017; 35: 885-892
• 3 Yan B, Huang J, Zhang C. et al. Serum metabolomic profiling in patients with systemic lupus erythematosus by GC/MS. Mod Rheumatol 2016; 26: 914-922
• 4 Nicholson JK, Lindon JC.. Systems biology: Metabonomics. Nature 2008; 455: 1054-1056
• 5 Yan R, Jiang H, Gu S. et al. Fecal metabolites were altered, identified as biomarkers and correlated with disease activity in patients with systemic lupus erythematosus in a GC-MS-based metabolomics study. Front Immunol 2020; 11: 2138
• 6 Anderson JL, May HT, Horne BD. et al. Relation of vitamin D deficiency to cardiovascular risk factors, disease status, and incident events in a general healthcare population. Am J Cardiol 2010; 106: 963-968
• 7 Mok CC, Birmingham DJ, Leung HW. et al. Vitamin D levels in Chinese patients with systemic lupus erythematosus: relationship with disease activity, vascular risk factors and atherosclerosis. Rheumatology (Oxford) 2012; 51: 644-652
• 8 Yap KS, Northcott M, Hoi A. et al. Association of low vitamin D with high disease activity in an Australian systemic lupus erythematosus cohort. Lupus Sci Med 2015; 2: e000064
• 9 García-Carrasco M, Mendoza-Pinto C, Ayón-Aguilar J. et al. Serum levels of vitamin D in systemic lupus erythematosus patients (SLE) and their relationship with disease activity: longitudinal study. Gac Med Mex 2016; 152: 32-37
• 10 Reynolds JA, Haque S, Berry JL. et al. 25-Hydroxyvitamin D deficiency is associated with increased aortic stiffness in patients with systemic lupus erythematosus. Rheumatology (Oxford) 2012; 51: 544-551
• 11 Kamen DL, Oates JC.. A pilot study to determine if vitamin D repletion improves endothelial function in lupus patients. Am J Med Sci 2015; 350: 302-307
• 12 Chew C, Reynolds JA, Lertratanakul A. et al. Lower vitamin D is associated with metabolic syndrome and insulin resistance in systemic lupus: data from an international inception cohort. Rheumatology (Oxford) 2021; 60: 4737-4747
• 13 Vogt S, Wahl S, Kettunen J. et al. Characterization of the metabolic profile associated with serum 25-hydroxyvitamin D: a cross-sectional analysis in population-based data. Int J Epidemiol 2016; 45: 1469-1481
• 14 Hochberg MC.. Updating the American college of rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1997; 40: 1725
• 15 Petri M, Orbai A-M, Alarcón GS. et al. Derivationand validation of the systemic lupus international collaborating clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum 2012; 64: 2677-2686
• 16 Gladman DD, Ibanez D, Urowitz MB.. Systemic lupus erythematosus disease activity index 2000. J Rheumatol 2002; 29: 288-291
• 17 Gladman DD, Goldsmith CH, Urowitz MB. et al. The systemic lupus international collaborating clinics/American college of rheumatology (SLICC/ACR) damage index for systemic lupus erythematosus international comparison. J Rheumatol 2000; 27: 373-376
• 18 Wallace TM, Levy JC, Matthews DR.. Use and abuse of HOMA modeling. Diabetes Care 2004; 27: 1487-1495
• 19 Gordillo-Moscoso A, Valadéz-Castillo JF, Mandeville PB. et al. Comparison of equivalence and determination of diagnostic utility of min-mod and clamp methods for insulin resistance in diabetes free subjects: a meta-analysis. Endocrine 2004; 25: 259-263
• 20 Cobb J, Gall W, Adam K-P. et al. A novel fasting blood test for insulin resistance and prediabetes. J Diabetes Sci Technol 2013; 7: 100-110
• 21 Cobb J, Eckhart A, Motsinger-Reif A. et al. Hydroxybutyric acid is a selective metabolite biomarker of impaired glucose tolerance. Diabetes Care 2016; 39: 988-995
• 22 Tripathy D, Cobb JE, Gall W. et al. A novel insulin resistance index to monitor changes in insulin sensitivity and glucose tolerance: the ACT NOW study. J Clin Endocrinol Metab 2015; 100: 1855-1862
• 23 Holick MF.. Vitamin D deficiency. N Engl J Med 2007; 357: 266-281
• 24 Chung CP, Oeser A, Solus JF. et al. Inflammation-associated insulin resistance: differential effects in rheumatoid arthritis and systemic lupus erythematosus define potential mechanisms. Arthritis Rheum 2008; 58: 2105-2112
• 25 Sabio JM, Vargas-Hitos J, Zamora-Pasadas M. et al. Metabolic syndrome is associated with increased arterial stiffness and biomarkers of subclinical atherosclerosis in patients with systemic lupus erythematosus. J Rheumatol 2009; 36: 2204-2211
• 26 Contreras-Haro B, Hernandez-Gonzalez SO, Gonzalez-Lopez L. et al. Fasting triglycerides and glucose index: a useful screening test for assessing insulin resistance in patients diagnosed with rheumatoid arthritis and systemic lupus erythematosus. Diabetol Metab Syndr 2019; 11: 95
• 27 Quevedo-Abeledo JC, Sánchez-Pérez H, Tejera-Segura B. et al. Higher prevalence and degree of insulin resistance in patients with rheumatoid arthritis than in patients with systemic lupus erythematosus. J Rheumatol 2021; 48: 339-347
• 28 Gutiérrez-Solis AL, Datta Banik S, Méndez-González RM.. Prevalence of metabolic syndrome in Mexico: a systematic review and meta-analysis. Metab Syndr Relat Disord 2018; 16: 395-405
• 29 Hertle E, Stehouwer CDA, van Greevenbroek MMJ.. The complement system in human cardiometabolic disease. Mol Immunol 2014; 61: 135-148
• 30 Engström G, Hedblad B, Eriksson K-F. et al. Complement C3 is a risk factor for the development of diabetes: a population-based cohort study. Diabetes 2005; 54: 570-575
• 31 Onat A, Hergenç G, Can G. et al. Serum complement C3: a determinant of cardiometabolic risk, additive to the metabolic syndrome, in middle-aged population. Metabolism 2010; 59: 628-634
• 32 Wlazlo N, van Greevenbroek MMJ, Ferreira I. et al. Complement factor 3 is associated with insulin resistance and with incident type 2 diabetes over a 7-year follow-up period: the CODAM Study. Diabetes Care 2014; 37: 1900-1909
• 33 Bultink IEM, Turkstra F, Diamant M. et al. Prevalence of and risk factors for the metabolic syndrome in women with systemic lupus erythematosus. Clin Exp Rheumatol 2008; 26: 32-38
• 34 Manzi S, Ahearn JM, Salmon J.. New insights into complement: a mediator of injury and marker of disease activity in systemic lupus erythematosus. Lupus 2004; 13: 298-303
• 35 Gu X, Al Dubayee M, Alshahrani A. et al. Distinctive metabolomics patterns associated with insulin resistance and type 2 diabetes mellitus. Front Mol Biosci 2020; 7: 609806