Journal List > J Korean Diabetes Assoc > v.31(6) > 1062475

TOOLS
Yang, Kim, Lee, Kim, Nam, and Park: Inflammatory Markers are Associated with Microvascular Complications in Type 2 Diabetes
Original Articles
The Journal of Korean Diabetes Association

The Journal of Korean Diabetes Association 2007; 31(6): 472-479.

Published online: 30 November 2007

DOI: https://doi.org/10.4093/jkda.2007.31.6.472

Inflammatory Markers are Associated with Microvascular Complications in Type 2 Diabetes

Sun Mee Yang, Sung Yong Kim, Ki Young Lee, Yeun Sun Kim, Moon Suk Nam1, Ie Byung Park

Division of Endocrinology and Metabolism, Department of Internal Medicine, Gil Medical Center, Gachon University of Medicine and Science, Korea.

1Department of Internal Medicine, Inha University College of Medicine, Korea.

Received 30 July 2007       Accepted 11 October 2007

Copyright © 2007 Korean Diabetes Association

Abstract

Background

Inflammatory markers are known to be sensitive predictors of atherosclerotic disease such as coronary heart disease. Diabetic patients have higher level of inflammatory markers such as fibrinogen, high sensitivity C-reactive protein (hsCRP) or IL-6. We investigated the association of inflammatory markers with microvascular complications in type 2 diabetes.

Methods

We studied cross-sectionally 244 consecutive patients with type 2 diabetes without macrovascular disease such as cerebral infarct, coronary heart disease and peripheral arterial disease. The urinary albumin/creatinine ratio was determined in a morning, untimed, urine specimen. Ophthalmoscopic examinations were performed to evaluate diabetic retinopathy. Diabetic neuropathy was examined by 10-g monofilament, Neuropathic Disability Score and Michigan Neuropathy Screening Instrument.

Results

47 patients (23.5%) had diabetic retinopathy, 81 (34.6%) had nephropathy and 132 (54.2%) had neuropathy. Fibrinogen and erythrocyte sedimentation rate (ESR) were significantly higher in the patients with nephropathy, retinopathy and neuropathy than in those without (P = 0.009, 0.003 and 0.047; P = 0.011, 0.02 and 0.006 , respectively). There were no differences in the hsCRP and IL-6 level between in patients with microvascular complications and in those without. Inflammatory parameters were correlated with each other. The hsCRP was correlated with IL-6 (r = 0.40, P < 0.001) and fibrinogen (r = 0.45, P < 0.001), but fibrinogen was not significantly correlated with IL-6 (r = 0.13, P = 0.08).

Conclusion

Although IL-6, hsCRP and fibrinogen may be associated with microvascular complications in type 2 diabetes, we show that fibrinogen is a strong marker of microvascular complications.

Keywords: Fibrinogen, hsCRP, IL-6, Inflammatory makers, Microvascular complications, Type 2 diabetes

Figures and Tables

Table 1
Basal characteristics of type 2 diabetes
jkda-31-472-i001

BMI, body mass index; ACE inhibitors, angiotensin-converting enzyme inhibitors.

Table 2
Inflammatory markers and clinical data of type 2 diabetic patients with and without retinopathy
jkda-31-472-i002

Data are mean ± SD or %. BMI, body mass index; HDL, high density lipoprotein; LDL, low density lipoprotein; hsCRP, high sensitivity C-reactive protein.

Table 3
Inflammatory markers and clinical data of type 2 diabetic patients with and without nephropathy
jkda-31-472-i003

Data are mean ± SD or %. BMI, body mass index; HDL, high density lipoprotein; LDL, low density lipoprotein; hsCRP, high sensitivity C-reactive protein.

Table 4
Inflammatory markers and clinical data of type 2 diabetic patients with and without neuropathy
jkda-31-472-i004

Data are mean ± SD or %. BMI, body mass index; HDL, high density lipoprotein; LDL, low density lipoprotein; hsCRP, high sensitivity C-reactive protein.

Table 5
Logistic regression model with microvascular complications as dependent variables
jkda-31-472-i005

SBP, systolic blood pressure.

Table 6
Correlation coefficients of fibrinogen, hsCRP and IL-6 with anthropometric, clinical and metabolic parameters
jkda-31-472-i006

ACR, urinary albumin to creatinine ratio; BMI, Body mass index; WBC, white blood cell.

References

1. Ross R. Atherosclerosis-an inflammatory disease. N Engl J Med. 1999. 340:115–126.
2. Ridker PM, Cushman M, Stampfer MJ, Tracy RP, Hennekens CH. Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med. 1997. 336:973–979.
3. Guha M, Bai W, Nadler JL, Natarajan R. Molecular mechanisms of tumor necrosis factor alpha gene expression in monocytic cells via hyperglycemia-induced oxidant stress dependent and independent pathways. J Biol Chem. 2000. 275:17728–17739.
4. Lin Y, Rajala MW, Berger JP, Moller DE, Barzilai N, Scherer PE. Hyperglycemia-induced production of acute phase reactants in adipose tissue. J Biol Chem. 2001. 276:42077–42083.
5. Aronson D, Bartha P, Zinder O, Kerner A, Markiewicz W, Avizohar O, Brook GJ, Levy Y. Obesity is the major determinant of elevated C-reactive protein in subjects with the metabolic syndrome. Int J Obes Relat Metab Disord. 2004. 28:674–679.
6. Calles-Escandon J, Cipolla M. Diabetes and endothelial dysfunction: a clinical perspective. Endocr Rev. 2001. 22:36–52.
7. Widlansky ME, Gokce N, Keaney JF, Vita JA. The clinical implications of endothelial dysfunction. J Am Coll Cardiol. 2003. 42:1149–1160.
8. Tracy RP. Inflammation, the metabolic syndrome and cardiovascular risk. Int J Clin Pract Suppl. 2003. 134:10–17.
9. Dandona P, Aljada A, Chaudhauri A, Bandyopadhyay A. The potential influence of inflammation and insulin resistance on the pathogenesis and treatment of atherosclerosis related complications in type 2 diabetes. J Clin Endocrinol Metab. 2003. 88:2422–2429.
10. Gomes MB, Nogueira VG. Acute-phase proteins and microalbuminuria among patients with type 2 diabetes. Diabetes Research and Clinical Practice. 2004. 66:31–39.
11. Izuora Kenneth E., Chase H. Peter, Jackson William E., Coll Joseph R., Osberg Iris M., Gottlieb Peter A., Rewers Marian J., Garg Satish K.. Inflammatory Markers and Diabetic Retinopathy in Type 1 Diabetes. Diabetes Care. 2005. 28:714–715.
12. Silkensen JR, Kasiske BL. Brenner & Rector's The Kidney: Laboratory Assessment of Kidney Disease. 2004. 7th ed. Philadelphia: W.B. Saunders;1125–1126.
13. McNeely MJ, Boyko EJ, Ahroni JH, Stensel VL, Reiber GE, Smith DG, Pecoraro RF. The independent contributions of diabetic neuropathy and vasculopathy in foot ulceration. How great are the risks? Diabetes Care. 1995. 18:216–219.
14. Feldman EL, Stevens MJ, Thomas PK, Brown MB, Canal N, Greene DA. A practical two-step quantitative clinical and electrophysiological assessment for the diagnosis and staging of diabetic neuropathy. Diabetes Care. 1994. 17:1281–1289.
16. Kang ES, Kim HJ, Ahn CW, Park CW, Cha BS, Lim KR, Lee HC. Relationship of serum high sensitivity C-reactive protein to metabolic syndrome and amicrovascular complications in type 2 diabetes. Diabetes Res Clin Pract. 2005. 69:151–159.
17. Pankewycz OG, Guan JX, Benedict JF. Cytokines as mediators of autoimmune diabetes and diabetic complications. Endocr Rev. 1995. 16:164–176.
18. Chakrabarti S, Cukiernik M, Hileeto D, Evans T, Chen S. Role of vasoactive factors in the pathogenesis of early changes of diabetic retinopathy. Diabetes Metab Res Rev. 2000. 16:393–407.
19. Hudson BI, Bucciarelli LG, Wendt T, Sakaguchi T, Lalla E, Qu W, Lu Y, Lee L, Stern DM, Naka Y, Ramasamy R, Yan SD, Yan SF, D'Agati V, Schmidt AM. Blockade of receptor for advanced glycation end-products:a new target for therapeutic intervention in diabetic complications and inflammatory disorders. Arch Biochem Biophys. 2003. 419:80–88.
20. Chaturvedi N, Sjoelie AK, Porta M, Aldington SJ, Fuller JH, Songini M, Kohner EM. EURODIAB Prospective Complications Study. Markers of insulin resistance are strong risk factors for retinopathy incidence in type 1 diabetes. Diabetes Care. 2001. 24:284–289.
21. Hayaishi-Okano R, Yamasaki Y, Katakami N, Ohtoshi K, Gorogawa S, Kuroda A, Matsuhisa M, Kosugi K, Nishikawa N, Kajimoto Y, Hori M. Elevated C-reactive protein associates with early-stage carotid atherosclerosis in young subjects with type 1 diabetes. Diabetes Care. 2002. 25:1432–1438.
22. Pickup JC, Mattock MB, Chusney GD, Burt D. NIDDM as a disease of the innate immune system: association of acute-phase reactants and interleukin-6 with metabolic syndrome X. Diabetologia. 1997. 40:1286–1292.
23. Pickup JC, Crook MA. Is type II diabetes mellitus a disease of the innate immune syste? Diabetologia. 1988. 41:1241–1248.
24. Young MJ, Bennett JL, Liderth SA, Veves A, Boulton AJ, Douglas JT. Rheological and microvasular parametes in diabetic peripheral neuropathy. Clin Sci(Colch). 1996. 90:183–187.
25. Bauduceau B, Renaudeau C, Mayaudon H, Helie C, Docorps M, Sonnet E, Yvert JP. Modification of hematological parameters in microvascular complications of diabetes. Diabetes Metab. 1995. 21:188–193.
26. Jones RL, Peterson CM. The fluid phase of coagulation and the accelerated atherosclerosis of diabetes mellitus. Diabetes. 1981. 30:Suppl 2. 33–38.
27. Coller BS, Frank RN, Milton RC, Gralmick HR. Plasma cofactors of platelet function: correlation with diabetic retinopathy and hemoglobin A1c: studies in diabetic patients and normal persons. Ann Intern Med. 1978. 88:311–316.
28. Jensen T, Stender S, Deckert T. Abnormalities in plasma concentrations of lipoproteins and fibrinogen in type 1 diabetic patients with increased urinary albumin. Diabetologia. 1988. 31:142–145.
29. Takebayashi K, Suetsugu M, Matsutomo R, Wakabayashi S, Aso Y, Inukai T. Correlation of High-sensitivity C-reactive Protein and Plasma Fibrinogen with Individual Complications in Patients with Type 2 Diabetes. Southern Medical Journal. 2006. 99:23–27.
30. Saraheimo M, Teppo AM, Forsblom C, Fagerudd J, Groop PH. Diabetic nephropathy is associated with low-grade inflammation in Type 1 diabetic patients. Diabetologia. 2003. 46:1402–1407.
31. Sesmilo G, Biller BMK, Llevadot J, Hayden D, Hanson G, Rifai N, Klibanski A. Effects of growth hormone administration on inflammatory and other cardiovascular risk markers in men with growth hormone deficiency. Ann Intern Med. 2000. 133:111–122.
32. Smith JF, Dykes R, Douglas JE, Krishnaswamy G, Berket S. Long-term exercise and atherogenic activity of blood mononuclear cells in persons at risk of developing ischemic heart disease. JAMA. 1999. 281:1722–1727.
33. Takeda T, Hoshida S, Nishino MJ, Tanouchi J, Otsu K, Hori M. Relationship between effects of statins, aspirin and angiotensin II modulators on high-sensitive C-reactive protein levels. Atherosclerosis. 2003. 169:155–158.
34. Henry JB. Clinical Diagnostics and Lab. Management by Laboratory Methods. 1996. 19th ed. Philadelphia: W.B. Saunders Company.
35. Simons A. Hematology, A Combined Theoretical and Technical Approach. 1997. 2nd ed. Boston, Oxford: Butterworth-Heineman;276–280.
TOOLS
Similar articles