Biomarkers of renal dysfunction among Ghanaian patients with type 2 diabetes mellitus- a cross-sectional study

  • Brodrick Yeboah AmoahEmail author
  • George Awuku Asare
  • Francis Agyemang Yeboah
  • Christian Obirikorang
  • Bernice Asiedu
  • Arab Omaima Mohammed
Original Article


Type 2 diabetes mellitus (T2DM) is a heterogeneous collection of disorders characterized by reduced insulin sensitivity and increased glucose output. The abnormal vascular architecture observed within the first few years of diabetes onset suggests that complications such as nephropathy develop earlier in affected individuals than is generally known. Prompt determination of decline in renal function among diabetics is therefore very crucial. In the present study, we evaluated circulating levels of adiponectin, neutrophil gelatinase-associated lipocalin (NGAL), asymmetric dimethyl arginine (ADMA), and endothelial nitric oxide synthase traffic inducer (NOSTRIN) as novel biomarkers of renal dysfunction. One hundred and eight Ghanaian patients with T2DM were recruited for this study. Biochemical and immunoassays were employed in measuring the levels of the biomarkers for all participants. Metabolic syndrome indices including body mass index (BMI), serum glucose, and uric acid levels were not found to be associated with adiponectin concentrations. Fifteen participants had normal estimated glomerular filtration rate (eGFR), 79 had a mildly reduced eGFR, and 24 had moderately reduced eGFR representing 12.8, 66.9, and 20.3%, respectively. Proteinuria correlated significantly with decreasing eGFR. Serum levels of adiponectin, ADMA, and NOSTRIN (p = 0.002; p = 0.001; p = 0.012, respectively) were, however, found to be independently associated with estimated glomerular filtration rate (eGFR) among the type 2 diabetics. We observed that elevated circulating levels of adiponectin, ADMA, and NOSTRIN could be important in characterizing early CKD stages among type 2 diabetics.


Biomarkers Type 2 diabetes Complications Nephropathy 



Asymmetric dimethylarginine


Body mass index


Chronic kidney disease


Estimated glomerular filtration rate


Endothelial nitric oxide synthase


Enzyme-linked immunosorbent assay


Free fatty acid


Modification of diet in renal disease


Neutrophil gelatinase-associated lipocalin


Nitric oxide


Endothelial nitric oxide synthase traffic inducer


Type 2 diabetes mellitus



We wish to express our sincere appreciation to the entire staff of the National Diabetes Management and Research Centre, Ghana.

Authors’ contributions

ABY made extensive contributions to the concept and design of this study and also participated in the laboratory analyses of study samples as well as data interpretation.

AGA contributed to the design of the study and also provided considerable support for the laboratory analyses.

YFA assisted in designing this study and also provided logistical support for laboratory analyses.

OC was involved in in the analyses of data and drafting of the manuscript.

AB was involved in the laboratory analyses of the work and also processed, analyzed, and interpreted data.

AOM made substantial contributions to the sampling of participants, acquisition of data, and laboratory analyses.

AEA was involved in the recruitment of and blood sampling of study participants, acquisition of data, and laboratory analyses.


This project was carried out with the financial support of the office of research, innovation and development (ORID) of the University of Ghana. The funder, however, did not have any role in the design of the study, data collection, or in preparation of the manuscript.

Compliance with ethical standards

Ethics approval and consent to participate

Ethics clearance was obtained from NDMRC prior to the commencement of this study. Anthropometric measurements, blood samples, and records from hospital folders were collected after obtaining a written informed consent from subjects who volunteered to participate in the study. All data were kept confidential throughout the study.

Competing interests

The authors have declared that no competing interest exists.


  1. 1.
    Sicree R, Shaw J, Zimmet P, Heart B. The global burden. Diabetes and impaired glucose tolerance Baker IDI Heart and Diabetes Institute. 2010.Google Scholar
  2. 2.
    González EM, Johansson S, Wallander M-A, Rodríguez LG. Trends in the prevalence and incidence of diabetes in the UK: 1996–2005. J Epidemiol Community Health. 2009;63(4):332–6. Scholar
  3. 3.
    Bruun JM, Lihn AS, Verdich C, Pedersen SB, Toubro S, Astrup A, et al. Regulation of adiponectin by adipose tissue-derived cytokines: in vivo and in vitro investigations in humans. Am J Physiol Endocrinol Metab. 2003;285(3):E527–E33. Scholar
  4. 4.
    Barazzoni R, Bernardi A, Biasia F, Semolic A, Bosutti A, Mucci M, et al. Low fat adiponectin expression is associated with oxidative stress in nondiabetic humans with chronic kidney disease—impact on plasma adiponectin concentration. Am J Phys Regul Integr Comp Phys. 2007;293(1):R47–54. Scholar
  5. 5.
    Zimmermann K, Opitz N, Dedio J, Renné C, Müller-Esterl W, Oess S. NOSTRIN: a protein modulating nitric oxide release and subcellular distribution of endothelial nitric oxide synthase. Proc Natl Acad Sci. 2002;99(26):17167–72. Scholar
  6. 6.
    Amoah AG, Owusu SK, Adjei S. Diabetes in Ghana: a community based prevalence study in Greater Accra. Diabetes Res Clin Pract. 2002;56(3):197–205. Scholar
  7. 7.
    Motala AA, Omar MA, Pirie FJ. Epidemiology of type 1 and type 2 diabetes in Africa. J Cardiovasc Risk. 2003;10(2):77–83. Scholar
  8. 8.
    Guo LL, Pan Y, Jin HM. Adiponectin is positively associated with insulin resistance in subjects with type 2 diabetic nephropathy and effects of angiotensin II type 1 receptor blocker losartan. Nephrol Dial Transplant. 2009;24(6):1876–83. Scholar
  9. 9.
    Kacso IM, Bondor CI, Kacso G. Plasma adiponectin is related to the progression of kidney disease in type 2 diabetes patients. Scand J Clin Lab Invest. 2012;72(4):333–9. Scholar
  10. 10.
    Njølstad PR, Sagen JV, Bjørkhaug L, Odili S, Shehadeh N, Bakry D, et al. Permanent neonatal diabetes caused by glucokinase deficiency. Diabetes. 2003;52(11):2854–60. Scholar
  11. 11.
    Kohei K. Pathophysiology of type 2 diabetes and its treatment policy. JMAJ. 2010;53(1):41–6.Google Scholar
  12. 12.
    DeFronzo RA. The triumvirate: β-cell, muscle, liver. A collusion responsible for NIDDM. Diabetes. 1988;37(6):667–87. Scholar
  13. 13.
    Duffaut C, Galitzky J, Lafontan M, Bouloumié A. Unexpected trafficking of immune cells within the adipose tissue during the onset of obesity. Biochem Biophys Res Commun. 2009;384(4):482–5. Scholar
  14. 14.
    Ma ZA, Zhao Z, Turk J. Mitochondrial dysfunction and β-cell failure in type 2 diabetes mellitus. Exp Diabetes Res 2011; 2012.Google Scholar
  15. 15.
    Allison SJ. Diabetes: Estimating GFR and GFR decline in patients with T2DM. Nat Rev Nephrol. 2013;9(5):246.CrossRefGoogle Scholar
  16. 16.
    Hojs R, Ekart R, Bevc S, Hojs N. Biomarkers of renal disease and progression in patients with diabetes. J Clin Med. 2015;4(5):1010–24. Scholar
  17. 17.
    Vallance P, Leone A, Calver A, Collier J, Moncada S. Endogenous dimethylarginine as an inhibitor of nitric oxide synthesis. J Cardiovasc Pharmacol. 1992;20:S60–S2.CrossRefGoogle Scholar
  18. 18.
    Böger RH, Bode-Böger SM, Szuba A, Tsao PS, Chan JR, Tangphao O, et al. Asymmetric dimethylarginine (ADMA): a novel risk factor for endothelial dysfunction. Circulation. 1998;98(18):1842–7. Scholar
  19. 19.
    Ravani P, Tripepi G, Malberti F, Testa S, Mallamaci F, Zoccali C. Asymmetrical dimethylarginine predicts progression to dialysis and death in patients with chronic kidney disease: a competing risks modeling approach. J Am Soc Nephrol. 2005;16(8):2449–55. Scholar
  20. 20.
    Baylis C. Arginine, arginine analogs and nitric oxide production in chronic kidney disease. Nat Clin Pract Nephrol. 2006;2(4):209–20. Scholar
  21. 21.
    Yilmaz MI, Sonmez A, Saglam M, Yaman H, Cayci T, Kilic S, et al. Reduced proteinuria using ramipril in diabetic CKD stage 1 decreases circulating cell death receptor activators concurrently with ADMA. A novel pathophysiological pathway? Nephrol Dial Transplant. 2010;25(10):3250–6. Scholar
  22. 22.
    Jorsal A, Tarnow L, Frystyk J, Lajer M, Flyvbjerg A, Parving H-H, et al. Serum adiponectin predicts all-cause mortality and end stage renal disease in patients with type I diabetes and diabetic nephropathy. Kidney Int. 2008;74(5):649–54. Scholar
  23. 23.
    Paragas N, Nickolas TL, Wyatt C, Forster CS, Sise M, Morgello S, et al. Urinary NGAL marks cystic disease in HIV-associated nephropathy. J Am Soc Nephrol. 2009;20(8):1687–92. Scholar
  24. 24.
    Yang Y-H, He X-J, Chen S-R, Wang L, Li E-M, Xu L-Y. Changes of serum and urine neutrophil gelatinase-associated lipocalin in type-2 diabetic patients with nephropathy: one year observational follow-up study. Endocrine. 2009;36(1):45–51. Scholar
  25. 25.
    Mitsnefes MM, Kathman TS, Mishra J, Kartal J, Khoury PR, Nickolas TL, et al. Serum neutrophil gelatinase-associated lipocalin as a marker of renal function in children with chronic kidney disease. Pediatr Nephrol. 2007;22(1):101–8. Scholar
  26. 26.
    Kovacevic I, Hu J, Siehoff-Icking A, Opitz N, Griffin A, Perkins AC, et al. The F-BAR protein NOSTRIN participates in FGF signal transduction and vascular development. EMBO J. 2012;31(15):3309–22. Scholar
  27. 27.
    Kirsch T, Kaufeld J, Korstanje R, Hentschel DM, Staggs L, Bollig F, et al. Knockdown of the hypertension-associated gene NOSTRIN alters glomerular barrier function in zebrafish (Danio Rerio) novelty and significance. Hypertension. 2013;62(4):726–30. Scholar
  28. 28.
    Afrifa J, Essien-Baidoo S, Ephraim RK, Nkrumah D, Dankyira DO. Reduced eGFR, elevated urine protein and low level of personal protective equipment compliance among artisanal small scale gold miners at Bibiani-Ghana: a cross-sectional study. BMC Public Health. 2017;17(1):601.CrossRefGoogle Scholar
  29. 29.
    Ekawanti A, Krisnayanti BD. Effect of mercury exposure on renal function and hematological parameters among artisanal and small-scale gold miners at Sekotong, West Lombok, Indonesia. J Health Pollut. 2015;5(9):25–32. Scholar
  30. 30.
    Morisky DE, Green LW, Levine DM. Concurrent and predictive validity of a self-reported measure of medication adherence. Med Care. 1986;24(1):67–74. Scholar
  31. 31.
    MacIsaac RJ, Ekinci EI, Jerums G. Markers of and risk factors for the development and progression of diabetic kidney disease. Am J Kidney Dis. 2014;63(2):S39–62. Scholar
  32. 32.
    Rodriguez-Poncelas A, Garre-Olmo J, Franch-Nadal J, Diez-Espino J, Mundet-Tuduri X, Barrot-De la Puente J, et al. Prevalence of chronic kidney disease in patients with type 2 diabetes in Spain: PERCEDIME2 study. BMC Nephrol. 2013;14(1):46.CrossRefGoogle Scholar
  33. 33.
    Ephraim RK, Arthur E, Owiredu W, Adoba P, Agbodzakey H, Eghan BA. Chronic kidney disease stages among diabetes patients in the Cape Coast Metropolis. Saudi J Kidney Dis Transplant. 2016;27(6):1231–8. Scholar
  34. 34.
    Haase-Fielitz A, Bellomo R, Devarajan P, Story D, Matalanis G, Dragun D, et al. Novel and conventional serum biomarkers predicting acute kidney injury in adult cardiac surgery—a prospective cohort study. Crit Care Med. 2009;37(2):553–60. Scholar
  35. 35.
    Constantin J-M, Futier E, Perbet S, Roszyk L, Lautrette A, Gillart T, et al. Plasma neutrophil gelatinase-associated lipocalin is an early marker of acute kidney injury in adult critically ill patients: a prospective study. J Crit Care. 2010;25(1):176. e1–6.CrossRefGoogle Scholar
  36. 36.
    Komura N, Kihara S, Sonoda M, Maeda N, Tochino Y, Funahashi T, et al. Increment and impairment of adiponectin in renal failure. Cardiovascular Research. 2009;86(3):471-7Google Scholar
  37. 37.
    Devarajan P. The use of targeted biomarkers for chronic kidney disease. Advances in chronic kidney disease. 2010;17(6):469-79Google Scholar
  38. 38.
    Bolignano D, Lacquaniti A, Coppolino G, Donato V, Campo S, Fazio MR, et al. Neutrophil gelatinase-associated lipocalin (NGAL) and progression of chronic kidney disease. Clin J Am Soc Nephrol. 2009;4(2):337–44. Scholar
  39. 39.
    Yang Z, Laubach VE, French BA, Kron IL. Acute hyperglycemia enhances oxidative stress and exacerbates myocardial infarction by activating nicotinamide adenine dinucleotide phosphate oxidase during reperfusion. J Thorac Cardiovasc Surg. 2009;137(3):723–9. Scholar
  40. 40.
    Isobe T, Saitoh S, Takagi S, Takeuchi H, Chiba Y, Katoh N, et al. Influence of gender, age and renal function on plasma adiponectin level: the Tanno and Sobetsu study. Eur J Endocrinol. 2005;153(1):91–8. Scholar
  41. 41.
    Kadowaki T, Yamauchi T. Adiponectin and adiponectin receptors. Endocr Rev. 2005;26(3):439–51. Scholar
  42. 42.
    Doumatey A, Zhou J, Huang H, Adeleye J, Balogun W, Fasanmade O, et al. Circulating adiponectin is associated with renal function independent of age and serum lipids in west africans. International journal of nephrology. 2012;2012Google Scholar
  43. 43.
    Cardounel AJ, Cui H, Samouilov A, Johnson W, Kearns P, Tsai A-L, et al. Evidence for the pathophysiological role of endogenous methylarginines in regulation of endothelial NO production and vascular function. J Biol Chem. 2007;282(2):879–87. Scholar
  44. 44.
    Sydow K, Münzel T. ADMA and oxidative stress. Atheroscler Suppl. 2003;4(4):41–51. Scholar
  45. 45.
    Kielstein JT, Böger RH, Bode-Böger SM, Frölich JC, Haller H, Ritz E, et al. Marked increase of asymmetric dimethylarginine in patients with incipient primary chronic renal disease. J Am Soc Nephrol. 2002;13(1):170–6.PubMedGoogle Scholar

Copyright information

© Research Society for Study of Diabetes in India 2018

Authors and Affiliations

  • Brodrick Yeboah Amoah
    • 1
    Email author
  • George Awuku Asare
    • 1
  • Francis Agyemang Yeboah
    • 2
  • Christian Obirikorang
    • 2
  • Bernice Asiedu
    • 1
  • Arab Omaima Mohammed
    • 1
  1. 1.Chemical Pathology Unit, Medical Laboratory Sciences Department, SBAHS, CHSUniversity of GhanaAccraGhana
  2. 2.Department of Molecular Medicine, School of Medical SciencesKNUSTKumasiGhana

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