Abstract
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. This study includes 6537 initially nondiabetic children (mean age at baseline=6.2years) with repeated measurements from the IDEFICS/I.Family cohort study (mean follow-up=5.3years) 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. Children with 6years 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). 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.
Highlights
Inflammation plays a significant role in the pathogenesis of diabetes.[1]
An inverse association was observed between IL‐15 and HOMA‐IR (β = −0.11, 95% CI = −0.15 to −0.07)
As inflammatory markers may be used to refine diabetes risk prediction and better target individuals for lifestyle interventions, we aimed to investigate longitudinal associations between pro‐ and anti‐inflammatory markers and markers of glycaemia, and insulin resistance (HOMA‐IR) in European children
Summary
Inflammation plays a significant role in the pathogenesis of diabetes.[1] In the adult population, increased concentrations of proinflammatory and reduced anti‐inflammatory markers were significantly associated with the incidence of type 2 diabetes.[2,3,4] these associations need to be confirmed for causality, as Mendelian randomisation studies yielded inconsistent results for some inflammatory markers.[5,6,7,8] Previously, there have been prospective studies that have investigated associations between inflammatory markers and glycaemia or insulin resistance, measured at one‐time point.[9,10] few studies have addressed longitudinal associations between inflammatory markers and glycaemic traits[11,12,13] and even fewer studies have investigated on how inflammatory markers act in combination.[14] longitudinal studies investigating the association between low‐grade systemic inflammation and markers of glycaemic deterioration/insulin resistance in children are missing.[7,8]
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