Longitudinal association of inflammatory markers with markers of glycaemia and insulin resistance in European children

Abstract

Purpose Subclinical systemic inflammation may lead to development of type 2 diabetes, but there has been no investigation into its relationship with early progression of glycaemic deterioration and insulin resistance, especially in younger population. In this study we assessed longitudinal associations of pro‐ and anti‐inflammatory markers with markers that evaluate glycaemia and insulin resistance. Methods This study includes 6537 initially nondiabetic children (mean age at baseline = 6.2 years) with repeated measurements from the IDEFICS/I.Family cohort study (mean follow‐up = 5.3 years) from eight European countries. Markers of inflammation were used as independent variables and markers of glycaemia/insulin resistance as dependent variables. Associations were examined using two‐level growth model. Models were adjusted for sex, age, major lifestyle, metabolic risk factors, early life markers, and other inflammatory markers in final model. Results Children with 6 years of follow‐up showed that a one‐unit increase in z‐score of leptin level was associated with 0.38 (95% CI = 0.32 to 0.44) unit increase in HOMA‐IR z‐scores. Leptin continued to be associated with HOMA‐IR even when analysis was limited to children with no overall obesity, no abdominal obesity, and low to normal triglyceride levels. An inverse association was observed between IL‐15 and HOMA‐IR (β = −0.11, 95% CI = −0.15 to −0.07). Conclusions IL‐15 should be evaluated further in the prevention or treatment of prediabetes whereas leptin may prove to be useful in early detection of prediabetes via their association with markers of insulin resistance in European children.

Association between serum leptin concentrations and homeostasis model assessment-insulin resistance of 2.5 and higher in normal weight Japanese women

“…Studies on association between HOMA-IR and leptin in normal weight individuals were limited although significant association was reported in multiple studies in the general population and in diabetic patients 23 – 27 . We found two studies: one in European children 28 and the other in a general population in China 29 . Both studies found a significant and independent association between HOMA-IR and leptin in normal weight people.…”

The Level of Inflammatory Markers and Their Relationship with Fat Tissue Distribution in Children with Obesity and Type 2 Diabetes Mellitus

“…However, these associations must be confirmed for causality, as Mendelian randomization studies have yielded inconsistent results for some inflammatory markers. 28 Similar to adults, there are inconsistencies in the results of studies conducted on children.…”

Association between Urinary Advanced Glycation End Products and Subclinical Inflammation in Children and Adolescents: Results from the Italian I.Family Cohort

“…hs-CRP was measured with a single-plex assay, while Interferon gamma-induced protein 10 (IP-10), Interleukin 15 (IL-15), Interleukin 6 (IL-6), Interleukin 8 (IL-8), Tumor necrosis factor alpha (TNF-α), and interleukin-1 receptor antagonist (IL-1Ra) were run together on a 6-plex assay. The combination of biomarkers for the assays were decided based on the feasibility of combinations with the help of MSD customer support, as previously described [ 41 ].…”