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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

¹ Unit of Endocrinology, Scientific Institute "Casa Sollievo della Sofferenza" San Giovanni Rotondo, Foggia, Italy
² Unit of Clinical Chemistry, Scientific Institute "Casa Sollievo della Sofferenza" San Giovanni Rotondo, Foggia, Italy
³ Department of Clinical Sciences, University "La Sapienza," Rome, Italy

Address correspondence and reprint requests to Salvatore De Cosmo, MD, Unit of Endocrinology Scientific Institute "Casa Sollievo della Sofferenza," 71013 San Giovanni Rotondo (FG), Italy. E-mail: sdecosm{at}tin.it

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_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 2.5 mg/mmol in men and 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.

Abbreviations: ACR, albumin-to-creatinine ratio • ARB, angiotensin II receptor 1 blocker • DBP, diastolic blood pressure • HOMA_IR, homeostasis model assessment of insulin resistance • SBP, systolic blood pressure • UAE, urinary albumin excretion

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