Associations of the Inflammatory Marker YKL-40 with Measures of Obesity and Dyslipidaemia in Individuals at High Risk of Type 2 Diabetes.

INTRODUCTION: Circulating levels of the inflammatory marker YKL-40 are elevated in cardiovascular disease and obesity-related type 2 diabetes (T2D), and serum YKL-40 levels are related to elements of dyslipidaemia. OBJECTIVE: We aimed to investigate the associations between serum YKL-40 and obesity-related traits in a Danish sample of non-diabetic relatives to T2D patients and, furthermore, to estimate the heritability of YKL-40. RESEARCH DESIGN AND METHODS: 324 non-diabetic individuals with family relation to a T2D patient were included in the study. The participants underwent oral- and intravenous glucose tolerance tests for estimation of glucose tolerance and surrogate measures of insulin sensitivity. Anthropometric measures were retrieved and biochemical measures of the plasma lipid profile and serum YKL-40 levels were obtained. Association-analyses between serum YKL-40 and obesity-related traits and estimates of the narrow sense heritability of YKL-40 were based on a polygenic variance component model. RESULTS: Fasting serum levels of YKL-40 were positively associated with waist-hip-ratio (p<0.001) and fasting plasma triglyceride levels (p<0.001). None of the insulin sensitivity indexes were significantly associated with YKL-40. According to the AE model, the familiality-estimate h2 of YKL-40 was 0.45 (SE 0.13). When the ACE-model was applied, the heritability-estimate h2 of YKL-40 did not reach statistical significance. CONCLUSIONS: Our results suggest a role of serum YKL-40 in obesity-related low grade inflammation, but do not indicate that YKL-40 is directly involved in the development of T2D.

Increased levels of the calcification marker matrix Gla Protein and the inflammatory markers YKL-40 and CRP in patients with type 2 diabetes and ischemic heart disease.

OBJECTIVE AND DESIGN: Low grade inflammation is of pathogenic importance in atherosclerosis and in the development of cardiovascular disease (CVD) and type 2 diabetes (T2D). Matrix GLA protein (MGP), an inhibitor of medial calcification of arteries, is increased in patients with atherosclerosis. In the present study levels of markers of calcification (MGP) and inflammation (YKL-40, hsCRP) were evaluated in patients with T2 D and/or ischemic heart disease (IHD). MATERIALS AND METHODS: The study population consisted of 1) patients with T2D (n = 45); 2) patients with IHD (n = 37); patients with both T2D and IHD (n = 20) and 4) healthy controls (n = 20). Biochemical parameters were measured in venous blood samples. RESULTS: Levels of MGP, YKL-40 and hsCRP were increased in patients with IHD and/or T2D (p < 0.0001) and patients with T2D and IHD had higher MGP levels (p < 0.001). In multiple linear regression analyses MGP was associated with patient category (r = 0.36, p < 0.001), and HDL-cholesterol levels (r = 0.29, p < 0.001) adjusting for the significant covariates. CONCLUSIONS: In patients with T2D and/or IHD we found increased levels of plasma MGP indicative of a progressing calcification process. This process is paralleled by increased levels of YKL-40 and hsCRP, which most likely reflect the concomitant low grade inflammatory state in these patients.