European Journal of Epidemiology

, Volume 22, Issue 10, pp 707–713 | Cite as

Metabolic risk factors associated with serum creatinine in a non-diabetic population

  • Jens Kronborg
  • Trond Jenssen
  • Inger Njølstad
  • Ingrid Toft
  • Bjørn O. Eriksen
Renal Disease


Insulin resistance, low HDL-cholesterol and microalbuminuria are important components of the metabolic syndrome as defined by WHO. Insulin resistance and low HDL-cholesterol are also common in chronic kidney disease (CKD), but it is not clear whether they are early or late phenomenons in the development of renal failure. This study examined whether low-grade albuminuria (microalbuminuria), lipoprotein fractions, and the insulin/glucose ratio (IGR)—a surrogate marker of insulin resistance—were related to renal function (expressed as serum creatinine) in persons without diabetes and with apparently normal renal function. The study included 4,131 men and women aged 55–75 years from the cross-sectional Tromsø IV survey (1994–1995). Lifestyle factors, waist circumference and blood pressure were included in the analyses. Gender stratified multivariate analysis was used to assess the relationship between serum creatinine and microalbuminuria, lipoprotein fractions and IGR. Serum creatinine was positively associated with microalbuminuria in men (β = 2.50, 95% confidence interval (CI) 0.66–4.34), but not in women. HDL-cholesterol and IGR were strongly associated with creatinine in both genders (HDL-cholesterol: Men: β = −4.82, 95% CI −6.27 to −3.37; women: β = −2.12, 95% CI −3.28 to −0.96. IGR: Second, third and fourth quartile compared with first quartile, men: β = 0.94, 95% CI −0.63 to 2.51; 2.10, 95% CI 0.52–3.69 and 2.40, 95% CI 0.75–4.04; women: β = 1.91, 95% CI 0.59–3.22; 2.61, 95% CI 1.28–3.95 and 3.20, 95% CI 1.80–4.60). These findings suggest that even early impairment of renal function may be associated with insulin resistance and dyslipidemia, regardless of renal albumin leakage.


Albuminuria Creatinine Cross-sectional studies HDL-cholesterol Insulin resistance Metabolic syndrome 



Albumin/creatinine ratio


Chronic kidney disease


Estimated glomerular filtration rate


End stage renal disease


Glomerular filtration rate


Homeostasis Model Assessment


Insulin/glucose ratio


Insulin resistance




Modification of Diet in Renal Disease



The present study was supported financially by The Norwegian Research Council, The Norwegian Foundation for Health and Rehabilitation, Innlandet Hospital Trust and University Hospital of North Norway Trust. We appreciate the superb technical assistance of Åse L. Bendikssen, Jorunn H. Eikrem and Hege Appelbom at the Laboratory of Metabolic Research, University of Tromsø.


  1. 1.
    Muntner P, Coresh J, Smith JC, Eckfeldt J, Klag MJ. Plasma lipids and risk of developing renal dysfunction: the atherosclerosis risk in communities study. Kidney Int 2000;58(1):293–301.PubMedCrossRefGoogle Scholar
  2. 2.
    Mänttäri M, Tiula E, Alikoski T, Manninen V. Effects of hypertension and dyslipidemia on the decline in renal function. Hypertension 1995;26(4):670–5.PubMedGoogle Scholar
  3. 3.
    The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993;329(14):977–86.Google Scholar
  4. 4.
    Mogensen CE. Microalbuminuria predicts clinical proteinuria and early mortality in maturity-onset diabetes. N Engl J Med 1984;310(6):356–60.PubMedCrossRefGoogle Scholar
  5. 5.
    Borch-Johnsen K, Feldt-Rasmussen B, Strandgaard S, Schroll M, Jensen JS. Urinary albumin excretion. An independent predictor of ischemic heart disease. Arterioscler Thromb Vasc Biol 1999;19(8):1992–7.PubMedGoogle Scholar
  6. 6.
    Alberti KG, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med 1998;15(7):539–53.PubMedCrossRefGoogle Scholar
  7. 7.
    Boden G. Pathogenesis of type 2 diabetes. Insulin resistance. Endocrinol Metab Clin North Am 2001;30(4):801–15.PubMedCrossRefGoogle Scholar
  8. 8.
    Ginsberg HN. Insulin resistance and cardiovascular disease. J Clin Invest 2000;106(4):453–8.PubMedCrossRefGoogle Scholar
  9. 9.
    Chen J, Muntner P, Hamm LL, Fonseca V, Batuman V, Whelton PK, et al. Insulin resistance and risk of chronic kidney disease in nondiabetic US adults. J Am Soc Nephrol 2003;14(2):469–77.PubMedCrossRefGoogle Scholar
  10. 10.
    Kurella M, Lo JC, Chertow GM. Metabolic syndrome and the risk for chronic kidney disease among nondiabetic adults. J Am Soc Nephrol 2005;16(7):2134–40.PubMedCrossRefGoogle Scholar
  11. 11.
    Van Biesen W, Vanholder R, Veys N, Verbeke F, Delanghe J, De Bacquer D, et al. The importance of standardization of creatinine in the implementation of guidelines and recommendations for CKD: implications for CKD management programmes. Nephrol Dial Transplant 2006;21(1):77–83.PubMedCrossRefGoogle Scholar
  12. 12.
    Jorde R, Burhol PG, Schulz TB, Waldum HL, Lygren I, Jenssen T, et al. The effect of a 34-h fast on the meal-induced rises in plasma GIP, serum insulin, and blood glucose in man. Scand J Gastroenterol 1981;16(1):109–12.PubMedGoogle Scholar
  13. 13.
    He J, Klag MJ, Caballero B, Appel LJ, Charleston J, Whelton PK. Plasma insulin levels and incidence of hypertension in African Americans and whites. Arch Intern Med 1999;159(5):498–503.PubMedCrossRefGoogle Scholar
  14. 14.
    Sullivan CS, Beste J, Cummings DM, Hester VH, Holbrook T, Kolasa KM, et al. Prevalence of hyperinsulinemia and clinical correlates in overweight children referred for lifestyle intervention. J Am Diet Assoc 2004;104(3):433–6.PubMedCrossRefGoogle Scholar
  15. 15.
    Verhave JC, Hillege HL, Burgerhof JG, Gansevoort RT, de Zeeuw D, de Jong PE. The association between atherosclerotic risk factors and renal function in the general population. Kidney Int 2005;67(5):1967–73.PubMedCrossRefGoogle Scholar
  16. 16.
    Schaeffner ES, Kurth T, Curhan GC, Glynn RJ, Rexrode KM, Baigent C, et al. Cholesterol and the risk of renal dysfunction in apparently healthy men. J Am Soc Nephrol 2003;14(8):2084–91.PubMedGoogle Scholar
  17. 17.
    Rubins HB, Robins SJ, Collins D, Fye CL, Anderson JW, Elam MB, et al. Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group. N Engl J Med 1999;341(6):410–8.PubMedCrossRefGoogle Scholar
  18. 18.
    Shai I, Rimm EB, Hankinson SE, Curhan G, Manson JE, Rifai N, et al. Multivariate assessment of lipid parameters as predictors of coronary heart disease among postmenopausal women: potential implications for clinical guidelines. Circulation 2004;110(18):2824–30.PubMedCrossRefGoogle Scholar
  19. 19.
    Fliser D, Pacini G, Engelleiter R, Kautzky-Willer A, Prager R, Franek E, et al. Insulin resistance and hyperinsulinemia are already present in patients with incipient renal disease. Kidney Int 1998;53(5):1343–7.PubMedCrossRefGoogle Scholar
  20. 20.
    Sechi LA, Catena C, Zingaro L, Melis A, De Marchi S. Abnormalities of glucose metabolism in patients with early renal failure. Diabetes 2002;51(4):1226–32.PubMedCrossRefGoogle Scholar
  21. 21.
    Wannamethee SG, Shaper AG, Durrington PN, Perry IJ. Hypertension, serum insulin, obesity and the metabolic syndrome. J Hum Hypertens 1998;12(11):735–41.PubMedCrossRefGoogle Scholar
  22. 22.
    Perry IJ, Wannamethee SG, Shaper AG, Alberti KG. Serum true insulin concentration and the risk of clinical non-insulin dependent diabetes during long-term follow-up. Int J Epidemiol 1999;28(4):735–41.PubMedCrossRefGoogle Scholar
  23. 23.
    Regalado M, Yang S, Wesson DE. Cigarette smoking is associated with augmented progression of renal insufficiency in severe essential hypertension. Am J Kidney Dis 2000;35(4):687–94.PubMedGoogle Scholar
  24. 24.
    Halimi JM, Giraudeau B, Vol S, Cacès E, Nivet H, Lebranchu Y, et al. Effects of current smoking and smoking discontinuation on renal function and proteinuria in the general population. Kidney Int 2000;58(3):1285–92.PubMedCrossRefGoogle Scholar
  25. 25.
    Vikse BE, Vollset SE, Tell GS, Refsum H, Iversen BM. Distribution and determinants of serum creatinine in the general population: the Hordaland Health Study. Scand J Clin Lab Invest 2004;64(8):709–22.PubMedCrossRefGoogle Scholar
  26. 26.
    Pinto-Sietsma SJ, Mulder J, Janssen WM, Hillege HL, de Zeeuw D, de Jong PE. Smoking is related to albuminuria and abnormal renal function in nondiabetic persons. Ann Intern Med 2000;133(8):585–91.PubMedGoogle Scholar
  27. 27.
    Briganti EM, Branley P, Chadban SJ, Shaw JE, McNeil JJ, Welborn TA, et al. Smoking is associated with renal impairment and proteinuria in the normal population: the AusDiab kidney study. Australian Diabetes, Obesity and Lifestyle Study. Am J Kidney Dis 2002;40(4):704–12.PubMedCrossRefGoogle Scholar
  28. 28.
    Vervoort G, Willems HL, Wetzels JF. Assessment of glomerular filtration rate in healthy subjects and normoalbuminuric diabetic patients: validity of a new (MDRD) prediction equation. Nephrol Dial Transplant 2002;17(11):1909–13.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2007

Authors and Affiliations

  • Jens Kronborg
    • 1
    • 2
    • 3
  • Trond Jenssen
    • 1
    • 4
  • Inger Njølstad
    • 5
  • Ingrid Toft
    • 1
    • 6
  • Bjørn O. Eriksen
    • 1
    • 6
    • 7
  1. 1.Institute of Clinical MedicineUniversity of Tromsø TromsøNorway
  2. 2.Department of Internal MedicineInnlandet Hospital Trust, LillehammerLillehammerNorway
  3. 3.LillehammerNorway
  4. 4.Department of NephrologyRikshospitalet University HospitalOsloNorway
  5. 5.Institute of Community MedicineUniversity of Tromsø TromsøNorway
  6. 6.Department of NephrologyUniversity Hospital of North Norway TromsøNorway
  7. 7.Clinical Research CenterUniversity Hospital of North Norway TromsøNorway

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