Inflammation and microalbuminuria in nondiabetic and type 2 diabetic subjects: The Insulin Resistance Atherosclerosis Study.
BACKGROUND
Microalbuminuria is a risk factor for cardiovascular disease, but the underlying pathomechanisms are still poorly understood. A relationship between C-reactive protein (CRP), a sensitive marker of inflammation, and atherosclerotic disease has been reported recently.


METHODS
We hypothesized that microalbuminuria might be associated with chronic inflammation and investigated the relationship of urinary albumin excretion, as assessed from the albumin-to-creatinine ratio (ACR), in an untimed morning urine specimen, and two inflammatory markers (CRP and fibrinogen) in the large, triethnic population of the Insulin Resistance Atherosclerosis Study (IRAS). After exclusion of subjects with macroalbuminuria, 1481 subjects were studied.


RESULTS
Both inflammatory markers were related to urinary ACR (r = 0.17 for CRP and r = 0.14 for fibrinogen, both P = 0.0001), an association that remained significant after adjustment for demographic variables, diabetic status, smoking, and use of angiotensin-converting enzyme inhibitors (P < 0.01). Mean levels of CRP and fibrinogen were elevated in microalbuminuric (N = 262) versus normoalbuminuric (N = 1219) subjects (5.37 +/- 0.47 vs. 3.80 +/- 0.15 mg/L and 295.7 +/- 4. 0 vs. 278.2 +/- 1.6 mg/dL, both P < 0.0001). The associations were consistent among nondiabetic and type 2 diabetic subjects and among the three ethnic groups of the IRAS (non-Hispanic whites, blacks, Hispanics). In a logistic regression model, fibrinogen was independently associated with microalbuminuria (P = 0.047), along with hypertension, female gender, waist circumference, and fasting blood glucose, while CRP was not independently related to microalbuminuria in this model (P = 0.26).


CONCLUSIONS
We have shown an association of CRP and fibrinogen with urinary albumin excretion in the microalbuminuric range in type 2 diabetic and nondiabetic individuals. Chronic inflammation therefore emerges as a potential mediator between microalbuminuria and macrovascular disease.
Festa
A
A
Department of Medicine, Division of Clinical Epidemiology, University of Texas Health Science Center at San Antonio, Texas 78228-3900, USA.
D'Agostino
R
R
Howard
G
G
Mykkänen
L
L
Tracy
R P
RP
Haffner
S M
SM
D000419:Albuminuria / Q000175:diagnosis* / Q000276:immunology; D001161:Arteriosclerosis / Q000175:diagnosis* / Q000276:immunology / Q000652:urine; D015415:Biomarkers; D001794:Blood Pressure; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000378:metabolism; D003404:Creatinine / Q000652:urine; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis* / Q000276:immunology / Q000652:urine; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D005951:Glucose Tolerance Test; D006801:Humans; D006977:Hypertension, Renal / Q000175:diagnosis / Q000276:immunology / Q000652:urine; D007333:Insulin Resistance / Q000276:immunology*; D007676:Kidney Failure, Chronic / Q000175:diagnosis* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009393:Nephritis / Q000175:diagnosis / Q000276:immunology / Q000652:urine
D015415:Biomarkers; D005340:Fibrinogen; D002097:C-Reactive Protein; D003404:Creatinine