Progression to overt nephropathy in type 2 diabetes: the Casale Monferrato Study.
OBJECTIVE
The first sign of diabetic nephropathy is microalbuminuria, but its predictive role of progression to overt nephropathy in type 2 diabetes has not yet been clarified. The aims of this study were to assess during 7 years of follow-up the incidence rate of overt nephropathy and the predictive role of microalbuminuria and other baseline variables (blood pressure, lipids, fibrinogen, uric acid, smoking, and HbA(1c) cumulative average during follow-up).


METHODS
A prospective population-based study was performed in Casale Monferrato, Italy, including 1,253 type 2 diabetic patients recruited at baseline (1991-1992), 765 with normoalbuminuria (albumin excretion rate [AER] <20 microg/min) and 488 with microalbuminuria (AER 20-200 microg/min). All measurements were centralized. A nested case-control study within the cohort was performed, selecting four control subjects, frequency matched for age and attained individual time of follow-up with each case. Conditional regression analysis was performed to assess variables independently associated with risk of progression to overt nephropathy.


RESULTS
Of 1,253 total patients, 1,103 (88.0%) were included in the follow-up examination (median 5.33 years); their age and duration of disease at baseline were 68.4 +/- 10.5 years and 10.4 +/- 6.6 years, respectively. Cases of overt nephropathy were 202, giving an incidence rate of 37.0/1,000 person-years (95% CI 32.3-42.6). In conditional logistic regression analyses, microalbuminuria provided a 42% increased risk with respect to normoalbuminuria (95% CI 0.98-2.06), independently of duration of diabetes, hypertension, and systolic blood pressure. Other variables independently associated with progression to overt nephropathy were HbA(1c) cumulative average (P = 0.002), apolipoprotein B (P = 0.013), fibrinogen (P = 0.02), and HDL cholesterol (P = 0.03).


CONCLUSIONS
Of type 2 diabetic patients, 3.7% progress every year to overt nephropathy. Microalbuminuria is associated with a 42% increased risk of progression to overt nephropathy. Other independent predictors are HbA(1c), HDL cholesterol, apolipoprotein B, and fibrinogen.
Bruno
Graziella
G
Department of Internal Medicine, Turin University, Turin, Italy. graziella.bruno@katamail.com
Merletti
Franco
F
Biggeri
Annibale
A
Bargero
Giuseppe
G
Ferrero
Stefania
S
Pagano
Gianfranco
G
Cavallo Perin
Paolo
P
D000368:Aged; D000419:Albuminuria / Q000175:diagnosis*; D001055:Apolipoproteins B / Q000097:blood; D015415:Biomarkers / Q000652:urine; D008076:Cholesterol, HDL / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000453:epidemiology*; D018450:Disease Progression; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D005500:Follow-Up Studies; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000453:epidemiology; D008297:Male; D018579:Patient Selection; D011446:Prospective Studies; D012044:Regression Analysis; D012307:Risk Factors; D012907:Smoking; D013997:Time Factors
D001055:Apolipoproteins B; D015415:Biomarkers; D008076:Cholesterol, HDL; D005340:Fibrinogen; D006442:Glycated Hemoglobin