YKL-40, a Marker of Inflammation and Endothelial Dysfunction, Is Elevated in Patients With Type 1 Diabetes and Increases With Levels of Albuminuria

Abstract

OBJECTIVE -The inflammation marker YKL-40 is elevated in patients with type 2 diabetes and is associated with atherosclerosis and increased cardiovascular mortality. In the present study, YKL-40 levels were examined in patients with type 1 diabetes with increasing levels of albuminuria, known to be associated with an increased risk of cardiovascular disease.RESEARCH DESIGN AND METHODS -A total of 149 patients with type 1 diabetes attending Steno Diabetes Center were examined: 58 had normoalbuminuria (urinary albumin excretion rate Ͻ30 mg/24 h), 46 had persistent microalbuminuria (urinary albumin excretion rate 30 -300 mg/24 h), and 45 had persistent macroalbuminuria/diabetic nephropathy (urinary albumin excretion rate Ͼ300 mg/24 h). The control group consisted of 55 healthy individuals. Groups were matched according to sex and duration of diabetes (Ͼ30 years).RESULTS -Median levels [interquartile range] of serum YKL-40 were significantly higher in normoalbuminuria versus control (37 [29 -52] vs. 53 [32-105] ng/ml, P Ͻ 0.01) and were increasing with increasing levels of albuminuria (microalbuminuria 74 [45-160] ng/ml and diabetic nephropathy 117 [68 -215] ng/ml; P Ͻ 0.001 for all comparisons). YKL-40 levels correlated with the urinary albumin-to-creatinine ratio in the total group of participants (r 2 ϭ 0.25, P Ͻ 0.001). Significant but weak intercorrelations of YKL-40 were found with age, diastolic blood pressure, A1C, and serum creatinine. After adjustment for significant covariates, albuminuria was significantly associated with YKL-40 levels (P Ͻ 0.001).CONCLUSIONS -YKL-40 levels are elevated in patients with type 1 diabetes with an independent association between increasing YKL-40 levels and increasing levels of albuminuria. The present study is the first to suggest a role of YKL-40 in the gradually progressing vascular complications in patients with type 1 diabetes.

Evaluation of YKL-40 Serum Level in Patients with Type 1 Diabetes and Its Correlation with Their Metabolic and Renal Conditions

“…In line with some other studies (19,21), we found a higher YKL-40 serum level in the group of T1D patients. Such elevation has also been reported in pre-diabetic (13) as well as in type 2 diabetic patients (13,20).…”

“…A significant correlation between YKL-40 plasma levels and age has been a matter of agreement (19,20,22,23,25,26,(28)(29)(30) or disagreement (14, 31-34) (like ours) in different studies. Such pros (23,24,35) (like ours) and cons (13,14,19,27) issues are also true in the case of the significant correlation between YKL-40 plasma levels and BMI.…”

“…Such pros (23,24,35) (like ours) and cons (13,14,19,27) issues are also true in the case of the significant correlation between YKL-40 plasma levels and BMI.…”

“…YKL-40 is secreted by different human cells including inflammatory cells such as neutrophils (12) and macrophages (13). A substantial body of evidence indicates that YKL-40, as an inflammatory marker in different pathologies (14)(15)(16)(17), participates in diabetes as well as its complications including endothelial dysfunction (13), atherosclerosis (18), cardiovascular disease (19,20), and albuminuria (19).…”

“…Considering that there are little studies on the correlation of YKL-40 with HbA1C and diabetic nephropathy in T1D (19), we evaluated such correlation to suggest YKL-40 as both diagnostic and prognostic marker of T1D metabolic control as well as of diabetic nephropathy. …”