Insulin resistance and inflammation may have an additional role in the link between cystatin C and cardiovascular disease in type 2 diabetes mellitus patients.
Recent studies suggest that serum cystatin C level is not only a sensitive marker for renal dysfunction but also a predictive marker for cardiovascular disease (CVD). However, the mechanism of this connection is not fully understood. We aimed to determine whether insulin resistance or various biomarkers of cardiovascular risk have a role in the link between cystatin C and CVD in type 2 diabetes mellitus patients. Anthropometric measurements and biochemical studies including inflammatory biomarkers were performed in 478 patients with type 2 diabetes mellitus. The degree of insulin resistance was assessed by homeostasis model assessment (HOMA-IR) and indicators of metabolic syndrome. Estimated glomerular filtration rate (eGFR) was derived from the Modification of Diet in Renal Disease study equation. After adjusting for age, sex, body mass index, and eGFR, the cystatin C level increased significantly in proportion to the number of metabolic syndrome components present (1.08 +/- 0.06, 1.19 +/- 0.04, 1.20 +/- 0.04, 1.23 +/- 0.04, and 1.37 +/- 0.06 mg/L; P < .0001); and HOMA-IR increased significantly in proportion to cystatin C quartiles (1.16 +/- 0.15, 1.40 +/- 0.13, 1.49 +/- 0.13, and 2.00 +/- 0.17; P < .0001) (means +/- SE). Albumin-creatinine ratio, fibrinogen, uric acid, homocysteine, high-sensitivity C-reactive protein, and lipoprotein(a) all showed significant correlations with cystatin C that were generally higher than those with eGFR. Cystatin C level was independently associated with HOMA-IR (beta = 0.0380, P = .0082), albumin-creatinine ratio (beta = 0.0004, P < .0001), uric acid (beta = 0.0666, P < .0001), and homocysteine (beta = 0.0087, P = .0004). In conclusion, cystatin C level was significantly associated with insulin resistance and biomarkers reflecting inflammation independent of renal function. These components may have a role in addition to that of eGFR in explaining the link between cystatin C and CVD in type 2 diabetes mellitus patients.
Lee
Seung-Hwan
SH
Division of Endocrinology and Metabolism, Department of Internal Medicine, The Catholic University of Korea, St Vincent's Hospital, Suwon 442-723, Korea.
Park
Shin-Ae
SA
Ko
Seung-Hyun
SH
Yim
Hyeon-Woo
HW
Ahn
Yu-Bae
YB
Yoon
Kun-Ho
KH
Cha
Bong-Yun
BY
Son
Ho-Young
HY
Kwon
Hyuk-Sang
HS
D000368:Aged; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D002318:Cardiovascular Diseases / Q000097:blood* / Q000150:complications; D055316:Cystatin C / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007249:Inflammation / Q000097:blood* / Q000150:complications; D007333:Insulin Resistance; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000150:complications; D008875:Middle Aged
D015415:Biomarkers; D055316:Cystatin C