Skip to main content
SpringerLink
Log in

Serum cystatin C and prediabetes in non-obese US adults

  • DIABETES MELLITUS
  • Published:
European Journal of Epidemiology Aims and scope Submit manuscript

Abstract

Diabetes mellitus is the leading cause of end stage renal disease. Cystatin C, a marker of early renal impairment has been shown to be associated with diabetes. However, it is not clear if cystatin C is associated with prediabetes, an early stage in the hyperglycemic continuum where prevention efforts have been shown to be effective in delaying or preventing the onset of diabetes. We examined 2,033 participants from the National Health and Nutrition Examination Survey 1999–2002, aged ≥20 years (female 47.2 %) who were free of diabetes mellitus, chronic kidney disease and with body mass index <30 kg/m2. Prediabetes (n = 541) was defined as a 2-h glucose concentration of 140–199 mg/dL, or a fasting glucose concentration of 110–125 mg/dL, or an A1C value of 5.7–6.4 %. Cystatin C levels were categorized into gender-specific quartiles for analysis. Elevated levels of serum cystatin C were associated with prediabetes after adjusting for potential confounders including serum total cholesterol, systolic blood pressure, body mass index and C-reactive protein. Compared to those with cystatin C in the lowest quartile, the multivariable odds ratio (95 % confidence interval) of prediabetes among those in the highest quartile was 2.08 (1.09–3.97), p for trend = 0.02. Although, this association was stronger among women and non-Hispanic whites, there was no significant interaction by sex (p = 0.1) or by race-ethnicity (p = 0.6). Our findings suggest that elevated levels of serum cystatin C are associated with prediabetes in a nationally representative sample of non-obese US adults.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis. 2002;39:S1–266.

    Google Scholar 

  2. Fox CS, Larson MG, Leip EP, Meigs JB, Wilson PW, Levy D. Glycemic status and development of kidney disease: the Framingham Heart Study. Diabetes Care. 2005;28:2436–40.

    Article  PubMed  Google Scholar 

  3. Mussap M, Dalla VM, Fioretto P, et al. Cystatin C is a more sensitive marker than creatinine for the estimation of GFR in type 2 diabetic patients. Kidney Int. 2002;61:1453–61.

    Article  PubMed  CAS  Google Scholar 

  4. Coll E, Botey A, Alvarez L, et al. Serum cystatin C as a new marker for noninvasive estimation of glomerular filtration rate and as a marker for early renal impairment. Am J Kidney Dis. 2000;36:29–34.

    Article  PubMed  CAS  Google Scholar 

  5. Jeon YK, Kim MR, Huh JE, et al. Cystatin C as an early biomarker of nephropathy in patients with type 2 diabetes. J Korean Med Sci. 2011;26:258–63.

    Article  PubMed  CAS  Google Scholar 

  6. Willems D, Wolff F, Mekahli F, Gillet C. Cystatin C for early detection of renal impairment in diabetes. Clin Biochem. 2009;42:108–10.

    Article  PubMed  CAS  Google Scholar 

  7. Sahakyan K, Lee KE, Shankar A, Klein R. Serum cystatin C and the incidence of type 2 diabetes mellitus. Diabetologia. 2011;54:1335–40.

    Article  PubMed  CAS  Google Scholar 

  8. American Diabetes Association. Standards of medical care in diabetes–2010. Diabetes Care. 2010;33 Suppl 1:S11–61.

  9. Cowie CC, Rust KF, Ford ES, et al. Full accounting of diabetes and pre-diabetes in the U.S. population in 1988–1994 and 2005–2006. Diabetes Care. 2009;32:287–94.

    Article  PubMed  Google Scholar 

  10. Donahue RP, Stranges S, Rejman K, Rafalson LB, Dmochowski J, Trevisan M. Elevated cystatin C concentration and progression to pre-diabetes: the Western New York study. Diabetes Care. 2007;30:1724–9.

    Article  PubMed  CAS  Google Scholar 

  11. Lafarge JC, Naour N, Clement K, Guerre-Millo M. Cathepsins and cystatin C in atherosclerosis and obesity. Biochimie. 2010;92:1580–6.

    Article  PubMed  CAS  Google Scholar 

  12. Young JA, Hwang SJ, Sarnak MJ, et al. Association of visceral and subcutaneous adiposity with kidney function. Clin J Am Soc Nephrol. 2008;3:1786–91.

    Article  PubMed  Google Scholar 

  13. Shankar A, Teppala S. Relationship between body mass index and high cystatin levels among US adults. J Clin Hypertens (Greenwich). 2011;13:925–30.

    Article  CAS  Google Scholar 

  14. National Center for Health Statistics. The National Health and Nutrition Examination Survey 1999–2000: Survey Operations Manuals, Brochures, Consent Documents. Available at: http://www.cdc.gov/nchs/nhanes/nhanes1999-2000/current_nhanes99_00.htm

  15. National Center for Health Statistics. The National Health and Nutrition Examination Survey 2001–2002: Survey Operations Manuals, Brochures, Consent Documents. Available at: http://www.cdc.gov/nchs/nhanes/nhanes2001-2002/current_nhanes_01_02.htm

  16. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2011;34 Suppl 1:S62–9.

    Google Scholar 

  17. Finney H, Newman DJ, Gruber W, Merle P, Price CP. Initial evaluation of cystatin C measurement by particle-enhanced immunonephelometry on the Behring nephelometer systems (BNA, BN II). Clin Chem. 1997;43:1016–22.

    PubMed  CAS  Google Scholar 

  18. Newman DJ. Cystatin C. Ann Clin Biochem. 2002;39:89–104.

    Article  PubMed  CAS  Google Scholar 

  19. National Center for Health Statistics. Laboratory procedures used for NHANES 1999–2000. Available at: http://www.cdc.gov/nchs/nhanes/nhanes1999-2000/lab99_00.htm (2008). Accessed 25 Feb 2011.

  20. National Center for Health Statistics. Laboratory procedures used for NHANES 2001–2002. Available at: http://www.cdc.gov/nchs/nhanes/nhanes2001-2002/lab01_02.htm (2008). Accessed 25 Feb 2011.

  21. Selvin E, Manzi J, Stevens LA, et al. Calibration of serum creatinine in the National Health and Nutrition Examination Surveys (NHANES) 1988–1994, 1999–2004. Am J Kidney Dis. 2007;50:918–26.

    Article  PubMed  CAS  Google Scholar 

  22. Randers E, Erlandsen EJ. Serum cystatin C as an endogenous marker of the renal function—a review. Clin Chem Lab Med. 1999;37:389–95.

    Article  PubMed  CAS  Google Scholar 

  23. Shlipak MG, Praught ML, Sarnak MJ. Update on cystatin C: new insights into the importance of mild kidney dysfunction. Curr Opin Nephrol Hypertens. 2006;15:270–5.

    Article  PubMed  CAS  Google Scholar 

  24. Alehagen U, Dahlstrom U, Lindahl TL. Cystatin C and NT-proBNP, a powerful combination of biomarkers for predicting cardiovascular mortality in elderly patients with heart failure: results from a 10-year study in primary care. Eur J Heart Fail. 2009;11:354–60.

    Article  PubMed  CAS  Google Scholar 

  25. Ristiniemi N, Lund J, Tertti R, et al. Cystatin C as a predictor of all-cause mortality and myocardial infarction in patients with non-ST-elevation acute coronary syndrome. Clin Biochem. 2012;45:535–40.

    Article  PubMed  CAS  Google Scholar 

  26. Harmoinen AP, Kouri TT, Wirta OR, et al. Evaluation of plasma cystatin C as a marker for glomerular filtration rate in patients with type 2 diabetes. Clin Nephrol. 1999;52:363–70.

    PubMed  CAS  Google Scholar 

  27. Servais A, Giral P, Bernard M, Bruckert E, Deray G, Isnard BC. Is serum cystatin-C a reliable marker for metabolic syndrome? Am J Med. 2008;121:426–32.

    Article  PubMed  CAS  Google Scholar 

  28. Lee SH, Park SA, Ko SH, et al. Insulin resistance and inflammation may have an additional role in the link between cystatin C and cardiovascular disease in type 2 diabetes mellitus patients. Metabolism. 2010;59:241–6.

    Article  PubMed  CAS  Google Scholar 

  29. Shlipak MG, Katz R, Cushman M, et al. Cystatin-C and inflammatory markers in the ambulatory elderly. Am J Med. 2005;118:1416.

    Article  PubMed  Google Scholar 

  30. Leung-Tack J, Tavera C, Martinez J, Colle A. Neutrophil chemotactic activity is modulated by human cystatin C, an inhibitor of cysteine proteases. Inflammation. 1990;14:247–58.

    Article  PubMed  CAS  Google Scholar 

  31. Reffelmann T, Krebs A, Ittermann T, et al. Mild renal dysfunction as a non-traditional cardiovascular risk factor?-Association of cystatin C-based glomerular filtration rate with flow-mediated vasodilation. Atherosclerosis. 2010;211:660–6.

    Article  PubMed  CAS  Google Scholar 

  32. Donahue RP, Rejman K, Rafalson LB, Dmochowski J, Stranges S, Trevisan M. Sex differences in endothelial function markers before conversion to pre-diabetes: does the clock start ticking earlier among women? The Western New York Study. Diabetes Care. 2007;30:354–9.

    Article  PubMed  Google Scholar 

  33. Thorand B, Baumert J, Kolb H, et al. Sex differences in the prediction of type 2 diabetes by inflammatory markers: results from the MONICA/KORA Augsburg case-cohort study, 1984–2002. Diabetes Care. 2007;30:854–60.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

NIH/NIEHS grants 1 R01 ES021825-01 and 5 R03ES018888-02 (AS) and Singapore Ministry of Health’s National Medical Research Council under its Talent Development Scheme R927/36/2012 (CS).

Author information

Authors and Affiliations

  1. Office of Clinical Sciences, Duke-NUS Graduate Medical School, Singapore, Singapore

    Charumathi Sabanayagam

  2. Singapore Eye Research Institute, 11 Third Hospital Avenue, #06–13, SNEC Bldg, Singapore, 168751, Singapore

    Charumathi Sabanayagam & Tien Yin Wong

  3. Department of Ophthalmology, National University of Singapore, Singapore, Singapore

    Charumathi Sabanayagam & Tien Yin Wong

  4. Department of Community Medicine, West Virginia University School of Medicine, Morgantown, WV, USA

    Jie Xiao & Anoop Shankar

Authors
  1. Charumathi Sabanayagam
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tien Yin Wong
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jie Xiao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Anoop Shankar
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Charumathi Sabanayagam.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sabanayagam, C., Wong, T.Y., Xiao, J. et al. Serum cystatin C and prediabetes in non-obese US adults. Eur J Epidemiol 28, 311–316 (2013). https://doi.org/10.1007/s10654-013-9781-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10654-013-9781-3

Keywords

Search

Navigation