DNA damage in leukocytes and serum nitrite concentration are negatively associated in type 1 diabetes.

Chronic hyperglycaemia leads to DNA damage in diabetes and might be associated with nitrosative stress. In this study, we aimed at assessing the level of DNA strand breaks in leukocytes, serum nitrite and nitrate in patients with type 1 diabetes and healthy controls and associations of these parameters with diabetes-related outcomes in a prospective study. The level of DNA damage was determined in 71 patients with type 1 diabetes and 57 healthy controls by comet assay and scored with arbitrary units (AU). The chemiluminescence method was used to measure nitrite and nitrate. Clinical information and data on consumption of alcohol, physical activity and smoking were collected. Progression of complications in patients with diabetes was assessed after a follow-up time of 4-5 years. We observed a higher level of DNA damage in leukocytes of patients with type 1 diabetes compared with healthy subjects [type 1 diabetes AU 50 (36-74.5); control AU 30 (24.1-43), P < 0.001]. According to regression, type 1 diabetes leads to a 2-fold increase in DNA damage. In the group of type 1 diabetes, DNA damage correlated positively with total cholesterol (R = 0.262, P = 0.028) and negatively with serum glucose level (R = -0.284; P = 0.018) and serum nitrite (R = -0.335; P = 0.008). DNA damage was not significantly associated with HbA1c, diabetes duration, complications and lifestyle factors. However, DNA damage > 57 AU was associated with statistically significantly lower serum nitrite and 1.52 higher risk of progression of complications of diabetes over the follow-up period. The latter result was not statistically significant due to insufficient study power [relative risk 1.52 (95% confidence interval = 0.68, 3.42, P = 0.31)]. Our results confirm that type 1 diabetes is associated with a higher level of DNA strand breaks in leukocytes when compared with the reference group and demonstrate the negative association between DNA damage and serum nitrite concentration.

Nitric oxide metabolism is impaired by type 1 diabetes and diabetic nephropathy.

Diabetes leads to reduced nitric oxide bioavailability, resulting in endothelial dysfunction. However, overproduction of nitric oxide due to hyperglycaemia is associated with oxidative stress and tissue damage. The objective of this study was to characterise nitric oxide production (NO) and added nitrite and nitrate (NO2 -+NO3 -) concentration in the blood and urine of patients with and without diabetic nephropathy. A total of 268 patients with type 1 diabetes and 69 healthy subjects were included. Diabetic nephropathy was defined as macroalbuminuria and/or estimated glomerular filtration rate below 60 ml/min/1.73 cm2. NO2 -+NO3 - concentration was measured by Griess reaction. Production of NO was detected by electron paramagnetic resonance spectroscopy. Blood NO was demonstrated to be higher (P<0.001) and serum NO2 -+NO3 - was lower (P=0.003) in patients with type 1 diabetes and no nephropathy vs. healthy subjects. However, serum NO2 -+NO3 - concentration in patients with diabetes and nephropathy did not differ from the levels observed in healthy controls. Urine excretion of NO2 -+NO3 - was significantly decreased in patients with nephropathy, compared with patients without diabetic kidney disease (P=0.006) and healthy subjects (P=0.010). A significant positive correlation was observed between urine NO2 -+NO3 - and estimated glomerular filtration rate in patients with type 1 diabetes (P=0.002) and healthy subjects (P=0.008). Estimated glomerular filtration rate, albuminuria and diabetic nephropathy status were significant predictors of the whole blood NO and NO2 -+NO3 - in serum and urine in patients with type 1 diabetes, as identified by linear regression models. The present study concludes that NO metabolism is impaired by type 1 diabetes and diabetic nephropathy.

Low Prevalence of Celiac Disease among Patients with Functional Gastrointestinal Disorders in Latvia.

BACKGROUND AND AIMS: Studies suggest that the prevalence of celiac disease (CD) is increased in individuals with functional gastrointestinal disorders (FGIDs), in particular, irritable bowel syndrome (IBS); however, the evidence is conflicting. We aimed to analyze the prevalence of CD in patients with FGIDs in Latvia. METHODS: This retrospective study included patients with FGIDs, referred for a gastroenterologist consultation in a secondary gastroenterology practice unit. Patients were divided into three groups - patients only with IBS (IBS group), patients only with functional dyspepsia (FD) (FD group), patients with mixed symptoms IBS and FD (Mixed group). Patient levels of tissue transglutaminase IgA (tTG-IgA) and/or antiendomysial IgA group antibodies (EMA-IgA) were evaluated. Four duodenal biopsies were obtained and reported according to Marsh classification. Patients diagnosed or being referred for confirmation of CD were excluded from the study. RESULTS: Overall, 1,833 FGIDs patients were enrolled. Celiac serology was available for 1,570 patients, duodenal histology for 582 patients, both histology and serology for 319 patients. In total, celiac seropositivity was present in 1.78% (28/1570) (3.18% in IBS group, 0.90% in FD group and 1.11% of cases in the mixed group). Fifteen patients had histopathological changes (2.58%; 15/582). Three IBS patients (2.36%) were both serology and biopsy positive. None of the FD patients had CD. CONCLUSION: Prevalence of biopsy-proven CD in patients from Latvia with FGIDs was low. Routine screening for CD could be considered only among patients with IBS.