Linking pre-diabetes with benign prostate hyperplasia. IGFBP-3: a conductor of benign prostate hyperplasia development orchestra?

• Published in: PloS one Vol. 8; no. 12; p. e81411
• Main Authors: Protopsaltis, Ioannis, Ploumidis, Achilles, Sergentanis, Theodoros N, Constantoulakis, Padelis, Tzirogiannis, Kostantinos, Kyprianidou, Chrysoula, Papazafiropoulou, Athanasia K, Melidonis, Andreas, Delakas, Dimitrios
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 19.12.2013; Public Library of Science (PLoS)
• Subjects: Aged; Aged, 80 and over; Analysis; Benign; Binding proteins; Blood pressure; Body mass index; Cancer surgery; Cholesterol; Conductors; Development and progression; Diabetes; Diabetes mellitus; Fasting; Gene expression; Glucose; Glucose tolerance; Homeostasis; Hospitals; Humans; Hyperplasia; Hypertension; Insulin; Insulin resistance; Insulin-Like Growth Factor Binding Protein 3 - metabolism; Insulin-like growth factor I; Insulin-like growth factor-binding protein 3; Insulin-like growth factors; Laboratories; Male; Mens health; Metabolic disorders; Metabolic syndrome; Middle Aged; Multivariate Analysis; Obesity; Pathogenesis; Prediabetic state; Prediabetic State - metabolism; Prostate; Prostate cancer; Prostatectomy; Prostatic Hyperplasia - metabolism; Prostatic Hyperplasia - physiopathology; Protein binding; Proteins; Real-Time Polymerase Chain Reaction; Researchers; Stroma; Studies; Type 2 diabetes; Ultrasound; Urogenital system; Urology; Waist Circumference - physiology; Greece
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0081411

Benign prostatic hyperplasia (BPH) represents a pattern of non-malignant growth of prostatic fibromuscular stroma. Metabolic disturbances such us pre-diabetes and metabolic syndrome may have a role in BPH pathophysiology. A potential explanation for the above relationship involves the insulin-like growth factor (IGF) axis as well as IGF binding proteins, (IGFBPs) of which the most abundant form is IGFBP-3. Therefore, the aim of the present study was to investigate the association between intra-prostatic levels of IGF-1, IGF-2 as well as to evaluate the role of locally expressed IGFBP-3 in BPH development in pre-diabetes. A total of 49 patients admitted to the Urology department of a tertiary urban Greek hospital, for transurethral prostate resection, or prostatectomy and with pre-diabetes [impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) or both] were finally included. The majority of the sample consisted of subjects with IGT (51.0%), followed by IFG and IGT (32.7%) and isolated IFG (16.3%). For all participants a clinical examination was performed and blood samples were collected. In addition, total prostate (TP) volume or transitional zone (TZ) volume were estimated by transrectal ultrasonography. The results of the multivariate analysis regarding TP volume showed that higher PSA (p<0.001), larger waist circumference (p=0.007) and higher IGFBP-3 expression levels (p<0.001) independently predicted higher TP volume. The results regarding the volume of the TZ showed that higher PSA (p<0.001), larger waist circumference (p<0.001) and higher IGFBP-3 expression levels (p=0.024) were independently associated with higher TZ volume. Our findings show that intra-prostatic levels of IGFBP-3, PSA and waist circumference, but not overall obesity, are positively associated with prostate volume. IGFBP-3 seems to be a multifunctional protein, which can potentiate or inhibit IGF activity.