Alireza Esteghamati1, Mohsen Afarideh2, Sahar Feyzi3, Sina Noshad4, Manouchehr Nakhjavani5. 1. Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: esteghamati@tums.ac.ir. 2. Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: mhafarideh@gmail.com. 3. Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: sahar.feyzi@gmail.com. 4. Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: sina.noshad@gmail.com. 5. Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: nakhjavanim@tums.ac.ir.
Abstract
AIMS: Fetuin-A is a circulating glycoprotein capable of inhibiting insulin signaling both in vivo and in vitro and is positively associated with insulin resistance. Osteoprotegerin (OPG) acts as a regulatory molecule with increased levels in the early stages of diabetes and atherosclerosis, and is also associated with insulin resistance. We investigated the effects of pioglitazone and metformin as representative insulin-sensitizing therapies on fetuin-A and OPG levels. MATERIALS AND METHODS: In a randomized clinical trial setting (NCT02027103), 88 patients with newly diagnosed type 2 diabetes were randomly assigned to pioglitazone (30 mg/day, n=46) or metformin (1000 mg/day, n=42) for 12 weeks. Various anthropometric and metabolic parameters, fetuin-A, OPG, highly sensitive C-reactive protein (hsCRP), and homeostasis model assessment of insulin resistance (HOMA-IR) were measured at baseline and after three months. RESULTS: The reduction in fasting plasma glucose and haemoglobin A1c levels was comparable in the two arms. Pioglitazone resulted in a significant reduction in both fetuin-A and OPG in men, but only fetuin-A in women. Metformin was only effective in lowering OPG levels in women. When compared, both medications were equally effective with regard to fetuin-A and OPG reduction in women (p=0.413 and 0.359, respectively). In men, pioglitazone more effectively decreased fetuin-A levels in both uni- (p=0.011) and multivariate models (p=0.015) and OPG levels in only uni- (p=0.023) but not the multivariate model (p=0.547). CONCLUSIONS:Metformin and pioglitazone differentially affect fetuin-A and osteoprotegrin levels in diabetic women and men. The level of change may not necessarily be associated with the amelioration of insulin resistance.
RCT Entities:
AIMS: Fetuin-A is a circulating glycoprotein capable of inhibiting insulin signaling both in vivo and in vitro and is positively associated with insulin resistance. Osteoprotegerin (OPG) acts as a regulatory molecule with increased levels in the early stages of diabetes and atherosclerosis, and is also associated with insulin resistance. We investigated the effects of pioglitazone and metformin as representative insulin-sensitizing therapies on fetuin-A and OPG levels. MATERIALS AND METHODS: In a randomized clinical trial setting (NCT02027103), 88 patients with newly diagnosed type 2 diabetes were randomly assigned to pioglitazone (30 mg/day, n=46) or metformin (1000 mg/day, n=42) for 12 weeks. Various anthropometric and metabolic parameters, fetuin-A, OPG, highly sensitive C-reactive protein (hsCRP), and homeostasis model assessment of insulin resistance (HOMA-IR) were measured at baseline and after three months. RESULTS: The reduction in fasting plasma glucose and haemoglobin A1c levels was comparable in the two arms. Pioglitazone resulted in a significant reduction in both fetuin-A and OPG in men, but only fetuin-A in women. Metformin was only effective in lowering OPG levels in women. When compared, both medications were equally effective with regard to fetuin-A and OPG reduction in women (p=0.413 and 0.359, respectively). In men, pioglitazone more effectively decreased fetuin-A levels in both uni- (p=0.011) and multivariate models (p=0.015) and OPG levels in only uni- (p=0.023) but not the multivariate model (p=0.547). CONCLUSIONS:Metformin and pioglitazone differentially affect fetuin-A and osteoprotegrin levels in diabeticwomen and men. The level of change may not necessarily be associated with the amelioration of insulin resistance.
Authors: Marta Díaz; José Miguel Gallego-Escuredo; Abel López-Bermejo; Francis de Zegher; Francesc Villarroya; Lourdes Ibáñez Journal: Int J Endocrinol Date: 2018-07-19 Impact factor: 3.257