Diabetes Metab J > Volume 40(2); 2016 > Article
Kang: Response: The Association of Serum Cystatin C with Glycosylated Hemoglobin in Korean Adults (Diabetes Metab J 2016;40:62-9)
We sincerely appreciate the interests and comments on our study, "The association of serum cystatin C with glycosylated hemoglobin in Korean adults," which was published in Diabetes & Metabolism Journal [1].
Cystatin C is an endogenous protein that is known to be affected little by age, race, and muscle mass [2]. It is not only used as a biomarker of renal function but also has positive associations with obesity, insulin resistance, hypertension [3,4], and cardiovascular mortality [5]. In this study with Korean adults, we demonstrated that serum cystatin C levels were significantly increased in subjects with diabetic conditions (prediabetes plus diabetes) compared with those who have normal glucose levels as defined by glycosylated hemoglobin (HbA1c) levels. Furthermore, our findings showed that higher levels of serum cystatin C were associated with increased prevalence of diabetic conditions, and we extended the positive association between cystatin C and the incidence of diabetes further to Asian as well as Western populations.
First, Dr. Kim pointed out the significant inverse associations, observed between cystatin C and prediabetes in quartile 2 (0.72 to 0.82 mg/L) compared with the lowest quartile (quartile 1, <0.72 mg/L) in men and other race-ethnicities in the study of Sabanayagam et al. [6], and between cystatin C and diabetic conditions in the group with the fourth serum cystatin C levels (1.0 mg/L) compared with the lowest group (first <0.8 mg/L) in the multivariable model of total subjects and men in our study [1]. These results would mainly be due to the lowest incidence of prediabetes in subjects in quartile 2 (quartile 1, 13.1%; quartile 2, 9.6%; quartile 3, 17.6%; quartile 4, 33.2%) in a previous study [6] and the lowest prevalence of diabetic conditions in the group with the fourth, especially in men (first, 35.7%; second, 29.5%; third, 29.6%; fourth, 26.0%; fifth, 39.5%) in our study [1]. Unfortunately, we also could not suggest a clear-cut reason for these variability in the incidence of diabetes among subjects outside the highest and the lowest cystatin C level groups, particularly in men or non-Western populations, indicating the need for further large-scaled studies.
Second, we agree with Dr. Kim's opinion that HbA1c can be affected by variable conditions including anemia, liver cirrhosis, and chronic kidney disease [7] as well as age and race. Considering this point, we excluded those aged >70 years and those with liver disease or abnormal serum creatinine as described [1]. Moreover, the hemoglobin levels of total subjects were more than 10 g/dL in our data, and the effect of anemia may be negligible. It may be useful to use other markers, such as glycated albumin [8], that are known to be better diagnostic indices of glycemic control in future studies.
We would like to thank Dr. Kim for the interest in our study and thoughtful comments.


CONFLICTS OF INTEREST: No potential conflict of interest relevant to this article was reported.


1. Sim EH, Lee HW, Choi HJ, Jeong DW, Son SM, Kang YH. The association of serum cystatin C with glycosylated hemoglobin in Korean adults. Diabetes Metab J 2016;40:62-69.
2. Ferguson MA, Waikar SS. Established and emerging markers of kidney function. Clin Chem 2012;58:680-689.
PubMed  PMC 
3. Servais A, Giral P, Bernard M, Bruckert E, Deray G, Isnard Bagnis C. Is serum cystatin-C a reliable marker for metabolic syndrome? Am J Med 2008;121:426-432.
4. Shankar A, Teppala S. Relationship between body mass index and high cystatin levels among US adults. J Clin Hypertens (Greenwich) 2011;13:925-930.
PubMed  PMC 
5. Shlipak MG, Sarnak MJ, Katz R, Fried LF, Seliger SL, Newman AB, Siscovick DS, Stehman-Breen C. Cystatin C and the risk of death and cardiovascular events among elderly persons. N Engl J Med 2005;352:2049-2060.
6. Sabanayagam C, Wong TY, Xiao J, Shankar A. Serum cystatin C and prediabetes in non-obese US adults. Eur J Epidemiol 2013;28:311-316.
7. Hare MJ, Shaw JE, Zimmet PZ. Current controversies in the use of haemoglobin A1c. J Intern Med 2012;271:227-236.
8. Raghav A, Ahmad J. Glycated serum albumin: a potential disease marker and an intermediate index of diabetes control. Diabetes Metab Syndr 2014;8:245-251.

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