Abstract
Objective and designYKL-40 is involved in inflammation and endothelial dysfunction, and is increased in patients with type 1 diabetes, with an independent association between increasing YKL-40 levels and increasing levels of albuminuria. YKL-40 is associated with atherosclerosis and an increased cardiovascular mortality in the general population. In the present study YKL-40 levels were examined in patients with type 2 diabetes (T2D) with increasing levels of albuminuria, known to be associated with an increased risk of cardiovascular disease.Materials and methodsOne-hundred-five patients with T2D were examined: 49 with normoalbuminuria (N, U-albumin/creatinine < 2.5 mg/mmol), 35 with persistent microalbuminuria (MA, 2.5-25 mg/mmol) and 21 with persistent macroalbuminuria/diabetic nephropathy (DN, > 25 mg/mmol). The control group consisted of 20 healthy individuals (C). Groups were matched according to age, gender and known duration of diabetes.ResultsMedian levels (interquartile range) of serum YKL-40 were significantly higher in N and MA vs. C (86 (55-137) ng/ml and 84 (71-147) ng/ml, respectively vs. 41 (33-55) ng/ml, p < 0.01) and even higher in patients with DN (120 (83-220) ng/ml, p < 0.001 for all comparisons). YKL-40 levels correlated with urinary albumin/creatinine-ratio in the total group of participants (r = 0.41, p < 0.001). Significant intercorrelations of YKL-40 were found with age, duration of diabetes, systolic blood pressure, lipid levels, HbA1c and HOMA-IR. After adjustment for significant covariates, albuminuria was significantly associated with YKL-40 levels (r = 0.32, p = 0.006).ConclusionsYKL-40 levels are elevated in patients with T2D with an independent association between increasing YKL-40 levels and increasing levels of albuminuria. The study suggests a role of YKL-40 in the progressing vascular complications in patients with T2D.
Highlights
Albuminuria is a well-established independent predictor for diabetic nephropathy and is a strong predictor for cardiovascular morbidity and mortality in both patients with type 1 (T1D) and type 2 diabetes (T2D) [1,2,3,4]
YKL-40 levels are elevated in patients with T2D with an independent association between increasing YKL-40 levels and increasing levels of albuminuria
The study suggests a role of YKL-40 in the progressing vascular complications in patients with T2D
Summary
Albuminuria is a well-established independent predictor for diabetic nephropathy and is a strong predictor for cardiovascular morbidity and mortality in both patients with type 1 (T1D) and type 2 diabetes (T2D) [1,2,3,4]. Individuals with diabetes have in YKL-40 is a glycoprotein involved in inflammation and endothelial dysfunction. It is a growth factor for various cell types and has an important role in extracellular matrix remodeling and angiogenesis [7,8]. In the last few years, several clinical studies have described elevated YKL-40 levels in several cardiovascular conditions, as well as described an association between YKL-40 and mortality. YKL-40 has been found to be associated with all-cause as well as cardiovascular mortality in both patients with stable ischemic heart disease (IHD) [9] and in the general population above 50 years of age without known diabetes or IHD [10]. YKL-40 levels are elevated both in patients with T1D and T2D known to be at high risk for the development of cardiovascular diseases [10,11,12], and in patients with T1D increasing levels of YKL-40 are seen with increasing levels of albuminuria, suggesting that YKL-40 might be able to be used as an early marker of CVD [11]
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