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Microalbuminuria in Insulin Sensitivity in Patients with Growth Hormone-Secreting Pituitary Tumor

Endocrinology Unit (R.B., G. P., M. A.), Regina Elena Cancer Institute, 00128 Rome, Italy; Endocrinology (L.d.M., A.B., V.C., A.P.), Catholic University of Sacred Heart, 00168 Rome, Italy; Department of Molecular and Clinical Endocrinology and Oncology (R.P., R.A., G.L., A.C.), University "Federico II", 80125 Naples, Italy; and Department of Internal Medicine, Endocrinology, and Metabolic Diseases (V.G., M.M., S.G.), University of Turin, 10153 Turin, Italy

Address all correspondence and requests for reprints to: Roberto Baldelli, M.D., Ph.D., Endocrinology Unit, Regina Elena Cancer Institute-IRCCS, Via Elio Chianesi 53, 00128 Roma, Italy. E-mail: baldelli{at}ifo.it.

Context: Impaired glucose tolerance and diabetes mellitus are frequently present in acromegalic patients in whom the degree of impaired glucose metabolism seems directly correlated with GH levels. Microalbuminuria is reported to be directly correlated with insulin resistance, and both conditions predict cardiovascular disease mortality.

Objective: Our objective was to investigate the microalbuminuria levels as a marker of endothelial dysfunction in acromegalic patients.

Design: We conducted an observational, multicenter, open prospective study.

Subjects: Subjects included 74 patients with active acromegaly (52 with normal glucose tolerance, 16 with impaired glucose tolerance, and six with diabetes), and 50 healthy subjects matched for age, gender, and body mass index were studied as controls.

Results: In the whole group, mean GH and IGF-I levels were 24.2 ± 3.9 ng/ml and 700.1 ± 23.0 µg/liter, respectively. The insulin sensitivity index (ISI) in the patients was lower than in the controls (P < 0.0005). In impaired glucose tolerance and diabetic patients, microalbuminuria was higher than in normal glucose tolerance patients (P < 0.05 and P < 0.0005 respectively). Hypertensive patients had higher levels of microalbuminuria than normotensive ones (P < 0.005). The levels of microalbuminuria related to creatinine were directly correlated with fasting glucose levels (r = 0.27; P = 0.0019), fasting insulin levels (r = 0.28; P = 0.017), and insulin after 90 (r = 0.26; P = 0.027) and 120 min after glucose load (r = 0.26; P = 0.023) and indirectly correlated with ISI composite (P < 0.0001; r = –0.48). By a multivariate analysis, the log-ISI composite was the strongest predictor of microalbuminuria (t = –3.19; P = 0.0021).

Conclusions: Impairment of glucose tolerance in acromegaly is associated with high levels of microalbuminuria. For this reason, microalbuminuria should be part of cardiovascular risk assessment in these patients.