Insulin resistance in children with juvenile systemic lupus erythematosus and ınvestigation of the possibly responsible factors

Abstract

Objective Insulin resistance (IR) has been described in adults with systemic lupus erythematosus (SLE), though its mechanism has not been fully clarified. In this study, it was aimed to investigate insulin sensitivity for the first time in children with juvenile SLE (jSLE) by considering the effect of the already known contributing factors of IR. Method This is a cross-sectional study including 43 patients with jSLE and the same number of healthy controls matched for age, gender, pubertal stage, body mass index, and physical activity level. IR, as calculated by both homeostatic model assessment for insulin resistance (HOMA-IR) and a relatively new method, triglyceride glucose (TyG) index, was compared between the patients and their matched controls, also among the patients stratified by disease duration, corticosteroid use, and disease activity. Results Insulin resistance in the patient group was higher than the controls according to both HOMA-IR and TyG index (p < 0.001 for both). In the patient group, no significant effect of disease duration, corticosteroid use, disease activity, and levels of anti-dsDNA, anti-cardiolipin IgM, anti-cardiolipin IgG, C3, and C4 on IR was demonstrated. Conclusion Children with jSLE were found to have higher IR even after neutralizing the effects of the contributing factors which are expected to aggravate IR. This elevation in IR in jSLE seems not to be associated with corticosteroid use, disease duration, disease activity, or autoantibody levels. Thus, the presence of IR in jSLE cannot be explained solely with neither the already known contributing factors nor the increased inflammation of the disease.

Lupus pathogenesis and autoimmunity are exacerbated by high fat diet-induced obesity in MRL/lpr mice

“…Our results may only reflect partial aspects of the HFD response in lupus. Lupus and obesity might be interconnected through other pathways to induce these immunological dysfunctions in HFD-associated lupus, such as proinflammatory soluble mediators generated by white adipose tissue,27 gut microbiota,28 29 oxidative stress,30 insulin resistance,31 increased body fat percentage and decreased muscle mass,32 oestrogen metabolism33 and vitamin D deficiency 34. Indeed, we found that serum MCP-1 level was significantly higher in the HFD group than the RD group, suggesting MCP-1 may play a role in HFD-associated lupus pathogenesis as observed in human patients with lupus by accelerating atherosclerosis and leading vascular damage (online supplemental figure S6).…”

The metabolic effects of APOL1 in humans

“…Similarly to infections, SLE is associated with enhanced interferon secretion and insulin resistance. Compared to healthy controls, insulin resistance and the prevalence of metabolic syndrome, diabetes, and hypertension are higher in patients with SLE (adults and children) compared to healthy subjects [ 39 , 77 , 78 , 92 , 101 ]. Furthermore, the fasting plasma level of glucagon and the glucagon response to a meal tolerance test are increased in SLE patients compared to healthy subjects [ 77 ].…”