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

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 <30 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 >300 mg/24 h). The control group consisted of 55 healthy individuals. Groups were matched according to sex and duration of diabetes (>30 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 < 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 < 0.001 for all comparisons). YKL-40 levels correlated with the urinary albumin-to-creatinine ratio in the total group of participants (r(2) = 0.25, P < 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 < 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.