Diabetic nephropathy is associated with low-grade inflammation in Type 1 diabetic patients.
OBJECTIVE
Increased concentrations of C-reactive protein and interleukin-6, a finding suggestive of the presence of inflammation, have been observed in Type 2 diabetes. In such patients, C-reactive protein was predictive of diabetic nephropathy. Studies on low-grade inflammatory markers and nephropathy in Type 1 diabetic patients have shown conflicting results. Therefore we studied whether low-grade inflammation is associated with diabetic nephropathy in Type 1 diabetic patients.


METHODS
We divided 194 Type 1 diabetic patients into three groups from the Finnish Diabetic Nephropathy Study based upon their albumin excretion rate. Patients with normoalbuminuria (n=67) had no antihypertensive medication or signs of cardiovascular disease, while patients with microalbuminuria (n=64) or macroalbuminuria (n=63) were all treated with an angiotensin-converting enzyme inhibitor, a drug that could attenuate low-grade inflammation. As a measure of insulin sensitivity we used estimated glucose disposal rate. C-reactive protein was measured by radioimmunoassay and interleukin-6 by high sensitivity enzyme immunoassay.


RESULTS
C-reactive protein was higher in micro- and macroalbuminuric patients compared to normoalbuminuric patients (normoalbuminuria 2.0+/-1.7, microalbuminuria 2.6+/-1.7, macroalbuminuria 2.9+/-2.5 mg/l; p=0.016), while interleukin-6 increased in parallel with the severity of the renal disease (1.9+/-1.5, 2.9+/-3.3, 3.6+/-3.1 ng/l; p<0.0001). In multiple regression analysis albumin excretion rate was the only variable independently associated with C-reactive protein (p=0.03), whereas albumin excretion rate (p=0.0003), HDL-cholesterol (p=0.0135) and duration of diabetes (p=0.0176) were independently associated with interleukin-6.


CONCLUSIONS
Low-grade inflammatory markers are associated with diabetic nephropathy in Type 1 diabetic patients. The predictive value needs to be assessed.
Saraheimo
M
M
Division of Nephrology, Department of Medicine, Helsinki University Central Hospital, and Folkhälsan Research Centre, Bimedicum Helsinki, University of Helsinki, Finland.
Teppo
A-M
AM
Forsblom
C
C
Fagerudd
J
J
Groop
P-H
PH
D000328:Adult; D000419:Albuminuria / Q000209:etiology / Q000378:metabolism; D015415:Biomarkers / Q000032:analysis; D002097:C-Reactive Protein / Q000378:metabolism; D008076:Cholesterol, HDL / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000150:complications*; D003928:Diabetic Nephropathies / Q000150:complications* / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D006801:Humans; D007249:Inflammation / Q000209:etiology* / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D012720:Severity of Illness Index; D013997:Time Factors
D015415:Biomarkers; D008076:Cholesterol, HDL; D015850:Interleukin-6; D002097:C-Reactive Protein