Nicotinamide effects oxidative burst activity of neutrophils in patients with poorly controlled type 2 diabetes mellitus

• Published in: Experimental diabesity research 2004-04, Vol.5 (2), p.155-162
• Main Authors: Osar, Zeynep, Samanci, Tülay, Demirel, Gülderen Yanikkaya, Damci, Taner, Ilkova, Hasan
• Format: Article
• Language: English
• Subjects: Blood Glucose - drug effects; Blood Glucose - metabolism; Body Mass Index; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - drug therapy; Female; Humans; Hypoglycemic Agents - therapeutic use; Male; Middle Aged; Neutrophils - drug effects; Neutrophils - physiology; Niacinamide - pharmacology; Phagocytosis - drug effects; Reference Values; Respiratory Burst - drug effects; Respiratory Burst - physiology
• ISSN: 1543-8600; 2314-6745; 2314-6753; 1543-8619
• DOI: 10.1080/15438600490424244

Neutrophil functions are impaired in patients with diabetes mellitus. Bacterial phagocytosis and oxidative burst activity are reduced at high glucose concentrations in diabetic patients. Defects in neutrophil oxidative burst capacity are of multifactorial origin in diabetes mellitus and correlate with glucose levels. It has been reported that neutrophil NADPH oxidase activity is impaired and superoxide production is reduced in diabetic patients with or without any infections. Nicotinamide is a vitamin B3 derivative and a NAD precursor with immunomodulatory effects. In vitro studies demonstrated that nicotinamide increases NAD and NADH content of beta cells. The authors hypothesized that nicotinamide may restore the impaired oxidative burst capacity of neutrophils in diabetic patients by increasing the NADH content as an electron donor and possibly through NADPH oxidase activity of the cell. In order to test the hypothesis, this placebo-controlled and open study was designed to evaluate neutrophil functions in infection-free poorly controlled type 2 diabetic patients as compared to healthy subjects and assess the effects of nicotinamide on neutrophil phagocytosis as well as oxidative burst activity. Thirty patients with type 2 diabetes mellitus were enrolled in the study. Sixteen were females and 14 were males, with a mean age 58 +/- 10. All patients were on sulphonylurea treatment and their hemoglobin A(1c) (HbA(1c)) levels were above 7.5%. The control group consisted of 10 voluntary healthy subjects. Diabetic and control subjects were not significantly different in terms of age, body mass index (BMI), leucocyte and neutrophil counts, C-reactive protein (CRP) level, and erythrocyte sedimentation rate (ESR), but HbA(1c) and fasting glucose levels were significantly higher in patients with diabetes mellitus. Phagocytic activity and respiratory burst indexes were measured by flow cytometric analyses as previously described by Rothe and Valet (Methods Enzyml., 233, 539-548, 1994) and compared in diabetic subjects and healthy controls. Diabetic patients were grouped to receive either 50 mg/kg oral nicotinamide (n = 15) or placebo (n = 15) for a period of 1 month. The 2 groups did not differ in terms of treatment, frequency of hypertension, BMI, diabetes duration, age, fasting plasma glucose (FPG), HbA(1c), CRP, ESR, polymorphonuclear leukocyte (PNL) and neutrophil counts. Neutrophil functions were reassessed after the treatment period. Phagocytic activity repre