Nicotinamide Effects Oxidative Burst Activity of Neutrophils in Patients with Poorly Controlled Type 2 Diabetes Mellitus

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 A1c (HbA1c) 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 HbA1c 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), HbA1c, CRP, ESR, polymorphonuclear leukocyte (PNL) and neutrophil counts. Neutrophil functions were reassessed after the treatment period. Phagocytic activity represented as indexes were lower in diabetic patients when compared to healthy subjects, but the differences were not statistically significant (P > .05). Patients with diabetes mellitus had significantly lower oxidative burst indexes when compared to healthy controls (P values < .05). In diabetic patients, a negative correlation between neutrophil functions and HbA1c was found which was not statistically significant (P values > .05). Phagocytic indexes were similar in nicotinamide and placebo groups after treatment period (P > .05). But oxidative burst activity in patients receiving nicotinamide was greater when compared with placebo and the difference was statistically significant at 30 and 45 minutes (P values .04 and .03). This effect of nicotinamide may be due to increased NADH content and NADPH oxidase activity of the cell, which needs to be further studied. Impaired neutrophil functions may aggravate various infections in patients with diabetes mellitus and blood glucose regulation is an important target of treatment to improve neutrophil functions. But nicotinamide treatment may help to improve prognosis in diabetic patients with severe infections

Lower risk of hypoglycaemia and greater odds for weight loss with initiation of insulin detemir compared with insulin glargine in Turkish patients with type 2 diabetes mellitus: local results of a multinational observational study

BACKGROUND: The purpose of this analysis is to evaluate the safety and effectiveness of insulin initiation with once-daily insulin detemir (IDet) or insulin glargine (IGlar) in real-life clinical practice in Turkish patients with type 2 diabetes mellitus (T2DM). METHODS: This was a 24-week multinational observational study of insulin initiation in patients with T2DM. RESULTS: The Turkish cohort (n = 2886) included 2395 patients treated with IDet and 491 with IGlar. The change in glycosylated haemoglobin (HbA(1c)) from the pre-insulin levels was -2.21% [95% confidence interval (CI) -2.32, -2.09] in the IDet group and -1.88% [95% CI -2.17, -1.59] in the IGlar group at the final visit. The incidence rate of minor hypoglycaemia increased in both groups from the pre-insulin to the final visit (+0.66 and +2.23 events per patient year in the IDet and IGlar groups, respectively). Weight change in the IDet group was -0.23 kg [95% CI -0.49, 0.02 kg], and +1.55 kg [95% CI 1.11, 2.00 kg] in the IGlar group. Regression analysis with adjustment for previously identified confounders (age, gender, duration of diabetes, body mass index, previous history of hypoglycaemia, microvascular disease, number and change in oral anti-diabetic drug therapy, HbA(1c) at baseline and insulin dose) identified an independent effect of insulin type (IDet versus IGlar) with a risk of at least one episode of hypoglycaemia (odds ratio (OR): 0.33 [95% CI 0.21, 0.52], p <0.0001), and weight loss ≥1 kg (OR: 1.75 [95% CI 1.18, 2.59], p = 0.005), but not on HbA(1c) (+0.05% [95% CI -0.15, 0.25%], p = 0.6). CONCLUSIONS: Initiation of basal insulin analogues, IDet and IGlar, were associated with clinically significant glycaemic improvements. A lower risk of minor hypoglycaemia and greater odds of weight loss ≥1 kg was observed with IDet compared with IGlar. TRIAL REGISTRATION: NCT00825643 and NCT0074051

Glucose intolerance, insulin resistance, and C peptide levels in patients with spinal cord injury

Background: Diabetes mellitus, glucose intolerance, hyperinsulinemia, and insulin resistance are more common among spinal cord injury (SCI) survivors

Exploring the characteristics of suboptimally controlled patients after 24 weeks of basal insulin treatment: An individualized approach to intensification

Aim: To identify characteristics of suboptimally controlled patients with type 2 diabetes (T2DM) on basal insulin treatment who may benefit from intensive titration or further intensification of treatment

Lower risk of hypoglycaemia and greater odds for weight loss with initiation of insulin detemir compared with insulin glargine in Turkish patients with type 2 diabetes mellitus: local results of a multinational observational study

Background: The purpose of this analysis is to evaluate the safety and effectiveness of insulin initiation with once-daily insulin detemir (IDet) or insulin glargine (IGlar) in real-life clinical practice in Turkish patients with type 2 diabetes mellitus (T2DM)

Serum levels of p53 and cytochrome c in subjects with type 2 diabetes and impaired glucose tolerance

Purpose: To examine apoptotic markers in serum of subjects with diabetes and impaired glucose tolerance (IGT). Serum levels of p53 and cytochrome c, regulator molecules for apoptosis, were measured in subjects with type 2 diabetes, subjects with IGT and healthy controls. Methods: Forty one subjects with type 2 diabetes, 27 with IGT and 27 healthy volunteers were included in the study. Serum level of cytochrome c and p53 were measured with competitive ELISA. Results: Serum levels of p53 were lower in the group of subjects with type 2 diabetes (085±0.39 U/ml) than in controls (1.09±0.49 U/ml) (P < 0.05) and in the subjects with IGT (0.98±0.37 U/ml) (P < 0.05). There was no significant difference between the group with IGT and controls. Also, there was no difference for serum level of cytochrome c among the groups. In the group of subjects with type 2 diabetes, serum level of cytochrome c was mildly correlated with HbA1c (r:0.39, P < 0.05). Conclusion: The present study shows that the serum level of p53 is lower in the patients with type 2 diabetes than in controls or in subjects with IGT. No difference was seen among the the groups for the serum level of cytochrome c

Orlistat augments postprandial increases in glucagon-like peptide 1 in obese type 2 diabetic patients

OBJECTIVE - Orlistat leads to improved glycemic control in obese type 2 diabetic patients, which is attributed to decreased insulin resistance associated with weight loss. Glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) are gut hormones that are secreted in response to food intake, and they both stimulate insulin secretion. Orlistat decreases fat absorption and increases intestinal fat content, which may lead to increased secretion of these peptides. In this pilot study, we tested the hypothesis that increased levels of these intestinal hormones may be involved in the improvement of postprandial hyperglycemia observed previously with orlistat in type 2 diabetic patients

Celiac disease in an adult Turkish population with type 1 diabetes mellitus

Celiac disease is a frequent cause of morbidity among patients with type 1 diabetes mellitus. In this study our objective was to determine the prevalance of celiac diasease in a Turkish adult population with type 1 diabetes mellitus. Patients included 122 type 1 diabetes cases from adult diabetes clinic. Total IgA and IgA-antiendomysial antibody (AEA) assays were performed. Patients positive for IgA-AEA were asked to undergo small intestinal biopsy. Of the 122 patients, none was IgA deficient and 3 had positive IgA-AEA results (2.45%). All three of these patients had biopsies diagnostic of celiac disease. The body mass index (BMI) values of patients with positive AEA were significantly lower than normal (P = 0.024). Among the gastrointestinal complaints there was an association between early satiety and AEA positivity (P = 0.02). None of the other gastrointestinal complaints or age, duration of diabetes, glycosylated hemoglobin values, or insulin doses used were found to be related to AEA positivity. Celiac disease has a high prevalence among Turkish paients with type 1 diabetes mellitus. Screening for IgA-AEA during routine investigations of type 1 diabetic patients is important to prevent celiac-associated symptoms