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.
