Impaired fasting glucose is associated with lower glomerular filtration rate decline among men but not women –a large cohort study from Israel


      • The annual rate of GFR decline is lower among IFG patients in comparison to control
      • This effect was shown among men but not among women
      • A mechanism of glomerular hyperfiltration might explain our results



      Early stages of diabetes are associated with an increased glomerular filtration rate (GFR). Little is known, however, about the change in GFR among patients with impaired fasting glucose (IFG). We aimed to evaluate the yearly decline rate of GFR among IFG patients.


      A retrospective analysis of a large cohort of subjects attending a medical screening center in Israel. Patients with diabetes mellitus and patients with decreased estimated GFR (eGFR) were excluded. We divided the cohort into 2 subgroups; Healthy controls and impaired fasting control subjects. For each group, we calculated the average yearly estimated GFR decline (ΔeGFR). The results were adjusted for age, BMI, hypertension and smoking status.


      8176 subjects met the inclusion criteria. The median follow up time was 4.8 years (range 2.0 to 13.4). For the whole cohort (men and women), yearly ΔeGFR was −0.68 among healthy controls, and − 0.47 among IFG patients (p = .003). Among men, average yearly ΔeGFR in healthy controls and IFG patients was −0.7 and − 0.4, respectively (p = .0002). All results remained significant after adjusting for age, BMI, hypertension, smoking status and level of HDL and triglycerides. In contrast, among IFG women there was no significant difference in ΔeGFR in comparison with healthy women.


      Impaired fasting glucose is associated with a decreased rate of GFR reduction compared with healthy subjects. This effect is gender dependent - observed in men but not in women. A mechanism of glomerular hyperfiltration might be involved.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to European Journal of Internal Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Vora J.P.
        • Dolben J.
        • Dean J.D.
        • et al.
        Renal hemodynamics in newly presenting non-insulin dependent diabetes mellitus.
        Kidney Int. 1992; 41: 829-835
        • Nelson R.G.
        • Bennett P.H.
        • Beck G.J.
        • et al.
        Development and progression of renal disease in pima Indians with non-insulin-dependent diabetes mellitus. Diabetic renal disease study group.
        N Engl J Med. 1996; 335: 1636-1642
        • Rudberg S.
        • Persson B.
        • Dahlquist G.
        Increased glomerular filtration rate as a predictor of diabetic nephropathy--an 8-year prospective study.
        Kidney Int. 1992; 41: 822-828
        • Nathan D.M.
        • Davidson M.B.
        • Defronzo R.A.
        • et al.
        Impaired fasting glucose and impaired glucose tolerance: implications for care.
        Diabetes Care. 2007; 30: 753-759
        • Okada R.
        • Yasuda Y.
        • Tsushita K.
        • et al.
        Glomerular hyperfiltration in prediabetes and prehypertension.
        Nephrol Dial Transplant. 2012; 27: 1821-1825
        • Melsom T.
        • Mathisen U.D.
        • Ingebretsen O.C.
        • et al.
        Impaired fasting glucose is associated with renal hyperfiltration in the general population.
        Diabetes Care. 2011; 34: 1546-1551
        • Sun Z.-J.
        • Yang Y.-C.
        • Wu J.-S.
        • et al.
        Increased risk of glomerular hyperfiltration in subjects with impaired glucose tolerance and newly diagnosed diabetes.
        Nephrol Dial Transpl. 2015; : 1-7
        • Cachat F.
        • Combescure C.
        • Cauderay M.
        • et al.
        A systematic review of glomerular hyperfiltration assessment and definition in the medical literature.
        Clin J Am Soc Nephrol. 2015; 10: 382-389
        • Cohen E.
        • Nardi Y.
        • Krause I.
        • et al.
        A longitudinal assessment of the natural rate of decline in renal function with age.
        J Nephrol. 2014; 27: 635-641
        • Levey A.S.
        • Stevens L.A.
        • Schmid C.H.
        • et al.
        A new equation to estimate glomerular filtration rate.
        Ann Intern Med. 2009; 150: 604-612
        • Okada R.
        • Wakai K.
        • Naito M.
        • et al.
        Renal hyperfiltration in prediabetes confirmed by fasting plasma glucose and hemoglobin A1c.
        Ren Fail. 2012; 34: 1084-1090
        • Melsom T.
        • Schei J.
        • Stefansson V.T.N.
        • et al.
        Prediabetes and risk of glomerular hyperfiltration and albuminuria in the general nondiabetic population: a prospective cohort study.
        Am J Kidney Dis. 2016; 67: 841-850
        • Tomaszewski M.
        • Charchar F.J.
        • Maric C.
        • et al.
        Glomerular hyperfiltration : a new marker of metabolic risk.
        Kidney Int. 2007; 71: 816-821
        • Rakesh A.
        • Turner C.
        • Van Aken S.
        • et al.
        The relationship between microalbuminuria and glomerular filtration rate in young type 1 diabetic subjects: the Oxford regional prospective study.
        Kidney Int. 2005; 68: 1740-1749
        • Zerbini G.
        • Bonfanti R.
        • Meschi F.
        • et al.
        Persistent renal hypertrophy and faster decline of glomerular filtration rate precede the development of microalbuminuria in type 1 diabetes.
        55(9). 2006: 2620-2625
        • Dahlquist G.
        • Stattin E.
        • Rudberg S.
        Urinary albumin excretion rate and glomerular filtration rate in the prediction of diabetic nephropathy ; a long-term follow-up study of childhood onset type-1 diabetic patients.
        Nephrol Dial Transpl. 2001; 16: 1382-1386
        • Magee G.M.
        • Bilous R.W.
        • Cardwell C.R.
        • et al.
        Is hyperfiltration associated with the future risk of developing diabetic nephropathy?.
        A meta-analysis Diabetologia. 2009; 52: 691-697
        • Ruggenenti PiR
        • Porrinii E.
        • Gaspari F.
        • et al.
        Glomerular hyperfiltration and renal disease progression in type 2 diabetes.
        Diabetes Metab. 2012; 35: 2061-2068
        • Ficociello L.H.
        • Perkins B.A.
        • Roshan B.
        • et al.
        Renal hyperfiltration and the development of microalbuminuria in type 1 diabetes.
        Diabetes Care. 2009; 32: 8-12
      1. Chaiken R, Eckert-Norton M, Bard M, et al. Hyperfiltration in African-American patients with type 2 diabetes: Cross-sectional and longitudinal data Diabetes C. 1998;21(12):2129–2134.

        • Premaratne E.
        • Verma S.
        • Ekinci E.I.
        • et al.
        The impact of hyperfiltration on the diabetic kidney.
        Diabetes Metab. 2017; 41: 5-17
        • Goldberg I.
        • Krause I.
        The role of gender in chronic kidney disease.
        EMJ. 2016; 1: 58-64
        • Yoo K.D.
        • Yoon H.
        • Hwang S.
        • et al.
        Different association between renal hyperfiltration and mortality by sex.
        Nephrology. 2017; 1;22: 804-810
        • Lee A.
        • Kercher L.J.
        • Kirk P.
        Impact of gender and endothelin on renal vasodilation and hyperfiltration induced by relaxin in conscious rats.
        Am J Physiol Regul Integr Comp Physiol. 2000 Oct. 1; 279: R1298-R1304
        • Alonso Y.
        • Jonatan L.
        • Mona D.
        • et al.
        Plasma levels of relaxin-2 are higher and correlated to C-peptide levels in early gestational diabetes mellitus.
        Endocrine. 2017; : 1-2
        • Szepietowska B.
        • Gorska M.
        • Szelachowska M.
        Plasma relaxin concentration is related to beta-cell function and insulin sensitivity in women with type 2 diabetes mellitus.
        Diabetes Res Clin Pract. 2017; 79: e1-e3
        • Michels W.M.
        • Grootendorst D.C.
        • Verduijn M.
        • et al.
        Performance of the Cockroft-Gault, MDRD and new CKD-EPI formulas in relation to GFR, age, and body size.
        Clin J Am Soc Nephrol. 2010; 5: 1003-1009
        • Zatz R.
        • Dunn B.R.
        • Meyer T.W.
        • et al.
        Prevention of diabetic glomerulopathy by pharmacological amelioration of glomerular capillary hypertension.
        J Clin Invest. 1986; 77: 1925-1930
        • Vallon V.
        • Gerasimova M.
        • Rose M.A.
        • et al.
        SGLT2 inhibitor empagliflozin reduces renal growth and albuminuria in proportion to hyperglycemia and prevents glomerular hyperfiltration in diabetic Akita mice.
        2014: 194-204
        • Wanner C.
        • Inzucchi S.
        • Lachin J.M.
        • et al.
        Empagliflozin and progression of kidney disease in type 2 diabetes.
        N Engl J Med. 2016; 375: 323-334