Predictors of the early impairment of renal disease in human obesity.

Abstract

The mechanisms underlying the association of the increased albumin excretion rate (AER) with adiposity have yet to be clarified. We therefore investigated (1) the predictors of AER after 3 months of lifestyle intervention in a large cohort of nondiabetic obese women and (2) the relationships between AER and the adipose tissue gene expression of adipokines linked to inflammation and insulin resistance. A total of 269 obese nondiabetic women (age 49.9+/-13.1 years, body mass index (BMI) 36.8+/-4.6 kg m(-2)) participated in this program. Measurements used were anthropometrics parameters, blood pressure, oral glucose tolerance test, lipids, creatinine, AER, homeostasis model assessment of insulin resistance (HOMA-IR) and glomerular filtration rate at baseline and after 3 months of lifestyle intervention. At baseline, in a subgroup of 34 women, subcutaneous adipose tissue biopsy was carried out for the analysis of mRNA expression levels of adiponectin, suppressor of cytokine signaling 3 (SOCS-3), tumor necrosis factor alpha (TNF-alpha), pentraxine 3 (PTX-3), angiotensinogen and angiotensin-converting enzyme, and a blood sample was also taken from this group for the measurement of circulating adiponectin, interleukin-6, TNF-alpha and PTX-3. Microalbuminuria was defined as albumin/creatinine ratio >or=3.5 mg mmol(-1). Real-time PCR was used to quantify mRNA. Six percent of obese women had microalbuminuria. When dividing the whole cohort into three groups according to AER changes (decrease, stability and increase), we noted that 2 h glucose, insulin and HOMA-IR significantly decreased (P<0.05 for all) only in women who had a decrease in AER, whereas BMI and waist circumference significantly decreased in all the three groups (P<0.05). At baseline, higher AER was associated to significantly higher adipose tissue mRNA expression levels of SOCS-3 and PTX-3 (P<0.05) and to higher TNF-alpha and angiotensinogen expression. In obese women, weight loss alone is not sufficient to induce the AER decrease that occurs only with a concomitant improvement in glucose homeostasis. The adipose tissue gene expression profile seems to favor the early renal impairment often seen in obese subjects.