Increased urinary albumin excretion, insulin resistance, and related cardiovascular risk factors in patients with type 2 diabetes: evidence of a sex-specific association.
OBJECTIVE
While the relevant role of insulin resistance in the pathogenesis of increased urinary albumin excretion (UAE) is well established in type 1 diabetes, its contribution in type 2 diabetes is controversial. Our aim was to investigate whether insulin resistance was associated with increased UAE in a large cohort of patients with type 2 diabetes.


METHODS
A total of 363 men and 349 women, aged 61 +/- 9 years, with a disease duration of 11 +/- 9 years and HbA(1c) levels of 8.6 +/- 2.0% were included. Insulin resistance was derived from the homeostasis model assessment of insulin resistance (HOMA(IR)), and UAE was derived from the albumin-to-creatinine ratio (ACR) defined as increased if the value was > or =2.5 mg/mmol in men and > or =3.5 mg/mmol in women. ACR was correlated with HOMA(IR) (r = 0.15, P = 0.0001), independently of age, disease duration, blood pressure, HbA(1c), triglycerides, waist circumference, and smoking.


RESULTS
When the two sexes were investigated separately, a significant correlation between ACR and HOMA(IR) was reached in men (n = 363; r = 0.21, P = 0.0001) but not women (n = 349; r = 0.08, P = 0.14), suggesting that insulin resistance and sex may interact (P for interaction = 0.04) in determining UAE. When men were subgrouped into quartiles of HOMA(IR), those of the third and fourth quartile (i.e., the most insulin resistant) were at higher risk to have increased ACR than patients of the first quartile (third quartile: odds ratio 2.2 [95% CI 1.2-4.2], P = 0.01) (fourth quartile: 4.1 [2.2-7.9], P = 0.00002). Finally, ACR was significantly higher in men with two or more insulin resistance-related cardiovascular risk factors (i.e., abdominal obesity, dyslipidemia, and arterial hypertension) than in men with fewer than two insulin resistance-related cardiovascular risk factors (0.90 [0.2-115.1] vs. 1.56 [0.1-1367.6], respectively, P = 0.005).


CONCLUSIONS
In type 2 diabetic patients, increased UAE is strongly associated with insulin resistance and related cardiovascular risk factors. This association seems to be stronger in men than in women.
De Cosmo
Salvatore
S
Unit of Endocrinology Scientific Institute Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Foggia, Italy. sdecosm@tin.it
Minenna
Antonio
A
Ludovico
Oznelle
O
Mastroianno
Sandra
S
Di Giorgio
Anna
A
Pirro
Leonardo
L
Trischitta
Vincenzo
V
D000368:Aged; D000419:Albuminuria / Q000453:epidemiology*; D001794:Blood Pressure; D015992:Body Mass Index; D002318:Cardiovascular Diseases / Q000453:epidemiology*; D015331:Cohort Studies; D003404:Creatinine / Q000652:urine; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000503:physiopathology* / Q000652:urine; D003925:Diabetic Angiopathies / Q000453:epidemiology*; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007333:Insulin Resistance; D007558:Italy; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D044465:White People
D003404:Creatinine; D006442:Glycated Hemoglobin