Association between mannose-binding lectin, high-sensitivity C-reactive protein and the progression of diabetic nephropathy in type 1 diabetes.
OBJECTIVE
Diabetic nephropathy has been associated with low-grade inflammation and activation of the complement system in cross-sectional studies. Data from prospective studies are sparse. We investigated the associations of the complement activator mannose-binding lectin (MBL) and the inflammatory marker high-sensitivity C-reactive protein (hsCRP) with the development of nephropathy in a large prospective study of patients with type 1 diabetes from the Finnish Diabetic Nephropathy (FinnDiane) Study.


METHODS
Baseline MBL and hsCRP were measured in 1,564 type 1 diabetes patients from the FinnDiane study, of whom 1,010 had a normal albumin excretion rate, 236 had microalbuminuria and 318 had macroalbuminuria. The main outcome was progression in renal disease during follow-up.


RESULTS
Both baseline MBL (p = 0.038) and hsCRP (p < 0.001) increased with increasing level of albuminuria. During 5.8 +/- 2.2 years of follow-up, progression to a higher albuminuria level or end-stage renal disease (ESRD) occurred in 201 patients. MBL levels were higher in progressors compared with non-progressors at all steps of progression, and in a covariate adjusted multivariate Cox-regression analysis MBL levels above the median were significantly associated with progression from macroalbuminuria to ESRD (hazard ratio 1.88, 95% CI 1.06-3.32, p = 0.030). In a univariate analysis, hsCRP levels above the median were significantly associated with progression from normal albumin excretion rate to microalbuminuria, but the association was only borderline significant after adjustment for covariates (hazard ratio 1.56, 95% CI 0.97-2.51, p = 0.068).


CONCLUSIONS
This study demonstrates that concentrations of both MBL and hsCRP are associated with the progression of renal disease in type 1 diabetes.
Hansen
T K
TK
Immunoendocrine Research Unit, Department of Endocrinology and Internal Medicine and Medical Research Laboratories, Clinical Institute, Aarhus University Hospital, Norrebrogade 42-44, DK-8000, Aarhus C, Denmark. tkh@dadlnet.dk
Forsblom
C
C
Saraheimo
M
M
Thorn
L
L
Wadén
J
J
Høyem
P
P
Østergaard
J
J
Flyvbjerg
A
A
Groop
P-H
PH
D000328:Adult; D002097:C-Reactive Protein / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000378:metabolism*; D003928:Diabetic Nephropathies / Q000209:etiology / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D037601:Mannose-Binding Lectin / Q000378:metabolism*; D008875:Middle Aged; D011446:Prospective Studies; D055815:Young Adult
D037601:Mannose-Binding Lectin; D002097:C-Reactive Protein
Diabetologia. 1999 Mar;42(3):351-7
10096789
N Engl J Med. 2008 Oct 30;359(18):1897-908
18971492
Diabetologia. 2007 Jul;50(7):1541-9
17473913
N Engl J Med. 2008 Nov 20;359(21):2195-207
18997196
J Clin Endocrinol Metab. 2003 Mar;88(3):1082-8
12629088
Diabetologia. 2003 Oct;46(10):1402-7
12928771
Diabetes. 2004 Jun;53(6):1570-6
15161763
Diabetes. 2004 Oct;53(10):2653-61
15448097
N Engl J Med. 2001 Apr 12;344(15):1140-4
11297706
Diabetologia. 2005 Jan;48(1):198-202
15616805
Am J Kidney Dis. 2004 Aug;44(2):224-38
15264180
Diabetes. 2009 Jul;58(7):1710-4
19366862
J Clin Endocrinol Metab. 2001 Nov;86(11):5383-8
11701711
J Clin Endocrinol Metab. 2003 Oct;88(10):4857-61
14557465
Diabetes. 2002 Apr;51(4):1157-65
11916939
Arch Intern Med. 2006 Oct 9;166(18):2007-13
17030835
Diabetes. 2005 May;54(5):1523-7
15855341
BMC Med Genet. 2009 Jan 22;10:5
19161617
J Diabetes Complications. 2008 May-Jun;22(3):153-63
18413218
BMJ. 2004 May 8;328(7448):1105
15096438
N Engl J Med. 2001 Apr 5;344(14):1058-66
11287977
Nat Clin Pract Cardiovasc Med. 2005 Jan;2(1):29-36; quiz 58
16265340
Hum Immunol. 2008 Feb;69(2):108-11
18361935
Diabetes Care. 2008 Dec;31(12):2338-43
18796620
Circulation. 2005 May 17;111(19):2446-53
15867184
J Am Coll Cardiol. 2007 Sep 18;50(12):1115-22
17868801
Diabetes. 2005 Oct;54(10):3002-6
16186405
Diabetes. 2006 Jun;55(6):1832-9
16731850