Oxidizing and reducing responses of granulocytes from type 2 diabetic patients Maria Regina Calsolari a , Leonardo Oliveira Medina a , Elaine Patrı ´cia Cunha a , Clara Arau ´jo Veloso a , Miriam Martins Chaves b , Adriana Bosco a , Jose ´ Augusto Nogueira-Machado a, 4 a Hospital Santa Casa de Miserico ´rdia de Belo Horizonte, MG, Brazil b Universidade Federal de Minas Gerais, MG, Brazil Received 19 October 2005; accepted 12 June 2006 Abstract Oxidizing/reducing response by granulocytes and a potential correlation between reactive oxygen species generation and triglyceride, total cholesterol, low-density lipoprotein, high-density lipoprotein, body mass index, fasting plasma glucose, glycemic control (hemoglobin A 1c ), or duration of diabetes were examined in type 2 diabetic patients and in healthy subjects. An increase in both oxidizing and reducing responses was observed in cells from diabetic patients relative to normoglycemic individuals. The increase in oxidizing response was nearly 2-fold higher, whereas the antioxidant response increased by 50%. Although reactive oxygen species generation from healthy subjects was correlated with levels of low-density lipoprotein (positive correlation), high-density lipoprotein (negative correlation), and body mass index (positive correlation), no such associations were observed in diabetic subjects, suggesting either an intrinsic perturbation in the oxidant/ antioxidant response or possibly due to the effect of the various medications being taken by these patients. These issues need further study. D 2006 Elsevier Inc. All rights reserved. 1. Introduction Diabetes mellitus is associated with increase in the generation of reactive oxygen species (ROS) [1,2]. The intake of glucose induces an increase in the generation of ROS and a decrease in the levels of antioxidant reserve [2,3]. Medications used in the treatment of diabetes, such as b-blockers and statins, decrease ROS generation by leukocytes [4,5], whereas fatty acids and triglycerides can stimulate their production [6]. It has been suggested that oxidized low-density lipoprotein (LDL) may produce a pro- inflammatory action, whereas high-density lipoprotein (HDL) possesses anti-inflammatory properties [7,8]. The aim of the present work was to study the balance between ROS generation and intracellular antioxidant defenses in resting human granulocytes derived from type 2 diabetic patients and from healthy subjects and to evaluate the potential correlation between the production of ROS and the levels of total cholesterol, LDL cholesterol and HDL cholesterol, triglycerides, body mass index (BMI), fasting plasma glucose, and glycemic control (hemoglobin A 1c [HbA 1c ]) in both groups. 2. Subjects and methods The ethical committee of the Hospital Santa Casa de Belo Horizonte approved this study. Appropriate informed consent was obtained from each participant. Healthy subjects (n = 16) and individuals with type 2 diabetes mellitus (n = 27) were selected based on (i) an age of between 30 and 75 years and (ii) a fasting glucose level of more than 140 mg/dL (determined on 2 separate occasions) for the diabetic group and less than 100 mg/dL for the control group. Smokers, pregnant women, those with alcohol abuse problem, dementia, inflammation, malignant disease, fasting glucose between 110 and 140 mg/dL, or infection were excluded from the study. The average ages were 56.0 F 13.0 and 59.6 F 11.0 for healthy individuals and diabetic patients, respectively. Diabetic patients were 0026-0495/$ – see front matter D 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.metabol.2006.06.015 4 Corresponding author. Nu ´cleo de Po ´s-Graduac ¸a ˜o e Pesquisa, Hospital Santa Casa de Miserico ´rdia de Belo Horizonte, Av. Francisco Sales, IIII, Santa Efige ˆnia-30150-221, Belo Horizonte, MG, Brazil. Tel.: +55 31 3238 88 38; fax: +55 31 3238 88 38. E-mail address: aunog.bh@terra.com.br (J.A. Nogueira-Machado). Metabolism Clinical and Experimental 55 (2006) 1426 – 1428 www.elsevier.com/locate/metabol