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Increased Urinary Albumin Excretion, Insulin Resistance, and Related Cardiovascular Risk Factors in Patients With Type 2 Diabetes: Evidence of a sex-specific association

De Cosmo, Salvatore, Minenna, Antonio, Ludovico, Oznelle, Mastroianno, Sandra, Di Giorgio, Anna, Pirro, Leonardo, Trischitta, Vincenzo
Diabetes care 2005 v.28 no.4 pp. 910-915
albumins, blood pressure, excretion, homeostasis, hyperlipidemia, hypertension, insulin, insulin resistance, insulin-dependent diabetes mellitus, men, noninsulin-dependent diabetes mellitus, obesity, odds ratio, pathogenesis, patients, risk, risk factors, triacylglycerols, waist circumference, women
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. RESEARCH DESIGN AND METHODS-- A total of 363 men and 349 women, aged 61 ± 9 years, with a disease duration of 11 ± 9 years and HbA[subscript 1c] levels of 8.6 ± 2.0% were included. Insulin resistance was derived from the homeostasis model assessment of insulin resistance (HOMA[subscript IR]), and UAE was derived from the albumin-to-creatinine ratio (ACR) defined as increased if the value was [>/=]2.5 mg/mmol in men and [>/=]3.5 mg/mmol in women. ACR was correlated with HOMA[subscript IR] (r = 0.15, P = 0.0001), independently of age, disease duration, blood pressure, HbA[subscript 1c], triglycerides, waist circumference, and smoking. RESULTS:--When the two sexes were investigated separately, a significant correlation between ACR and HOMA[subscript 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[subscript 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.