Autoantibodies predicting diabetes mellitus type I in celiac disease

Celiac disease (CD) and diabetes mellitus type I (DM-I) are both autoimmune diseases. Abnormal first-phase insulin response (FPIR) is associated with the prediabetic phase. Glutamic acid decarboxylase (GAD) and islet cell antibodies (ICAs) - especially the tyrosine phosphatase-like protein IA-2 antibodies - are considered to be serological markers of DM-I future development. The aim of this study is to investigate the presence of autoantibodies (GAD, IA-2) in individuals with CD, on a gluten-free diet, who have normal intestinal morphology. Thirty patients with CD (4-22, mean 15 years), 30 newly diagnosed diabetic children (2.5-16, mean 10 years) and 30 healthy subjects (7-35, mean 18 years) were investigated. Serum GAD and IA-2 autoantibodies were assessed by a quantitative enzyme-linked immunosorbent assay (ELISA) method in all patients and controls. Seven CD patients (23%), 28 diabetic children (93%) and none in the control group had positive GAD and IA-2 antibodies. The FPIR was normal in CD patients (>/=46 mU/l). Conclusions: GAD and IA-2 antibodies are detected in 23% of patients with CD. These patients may be at risk to develop DM-I. Regular follow-up and determination of FPIR for the early diagnosis of the prediabetic phase in patients with CD having circulating autoantibodies is recommended.     

Changes in the erythrocyte glutathione concentration in the course of diabetes mellitus

This study aims to evaluate the significance of the changes of erythrocyte reduced glutathione (GSH) in the course of diabetes mellitus including the pre-diabetes stage and cardiovascular disease co-morbidity. A total of 222 participants (female:male, 107:115) were selected and their erythrocyte GSH levels were measured. The participants were divided into four groups: (i) control; (ii) those with blood glucose level > or =5.6 mmol/l but < 6.9 mmol/l as pre-diabetes mellitus with no other pathology; (iii) diabetes without co-morbidity; and (iv) those with diabetes mellitus and cardiovascular disease. Statistical analysis was by ANOVA followed by a Fisher's LSD post hoc test. We observed that GSH concentration was significantly different between groups (P < 0.04). The Fisher's post hoc test indicated significant differences in erythrocyte GSH levels between the pre-diabetes mellitus and diabetes mellitus groups compared to control (P < 0.005 and P < 0.05, respectively). A statistically significant change (P < 0.001) involving an initial fall followed by a rise in erythrocyte GSH levels was observed when diabetes mellitus and diabetes mellitus+cardiovascular disease groups were combined and assessed with respect to period of diabetes. We conclude that oxidative stress is already present in the pre-diabetes stage as determined by the fall in GSH, representing the initial phase of oxidative stress in diabetes mellitus progression. This finding provides evidence that antioxidant markers such as GSH could be a useful tool for pre-diabetes mellitus screening.     

Changes in the erythrocyte glutathione concentration in the course of diabetes mellitus

Abstract

This study aims to evaluate the significance of the changes of erythrocyte reduced glutathione (GSH) in the course of diabetes mellitus including the pre-diabetes stage and cardiovascular disease co-morbidity. A total of 222 participants (female:male, 107:115) were selected and their erythrocyte GSH levels were measured. The participants were divided into four groups: (i) control; (ii) those with blood glucose level ≥5.6 mmol/l but < 6.9 mmol/l as pre-diabetes mellitus with no other pathology; (iii) diabetes without co-morbidity; and (iv) those with diabetes mellitus and cardiovascular disease. Statistical analysis was by ANOVA followed by a Fisher's LSD post hoc test. We observed that GSH concentration was significantly different between groups (P < 0.04). The Fisher's post hoc test indicated significant differences in erythrocyte GSH levels between the pre-diabetes mellitus and diabetes mellitus groups compared to control (P < 0.005 and P < 0.05, respectively). A statistically significant change (P < 0.001) involving an initial fall followed by a rise in erythrocyte GSH levels was observed when diabetes mellitus and diabetes mellitus+cardiovascular disease groups were combined and assessed with respect to period of diabetes. We conclude that oxidative stress is already present in the pre-diabetes stage as determined by the fall in GSH, representing the initial phase of oxidative stress in diabetes mellitus progression. This finding provides evidence that antioxidant markers such as GSH could be a useful tool for pre-diabetes mellitus screening.     

Factors affecting plasma beta-thromboglobulin in diabetes mellitus

Plasma beta-thromboglobulin, hemoglobin A1c and serum creatinine were measured in 56 diabetic patients. Patients with diabetic complications had a significantly higher beta-thromboglobulin level than the controls, but patients without complications did not differ from the controls. beta-Thromboglobulin correlated positively with serum creatinine and the highest values were encountered in patients with abnormal creatinine concentration. There were, however, patients with normal creatinine but high plasma beta-thromboglobulin levels. In these patients the abnormal beta-thromboglobulin level most probably indicates undue stimulation of platelets. There was no correlation between beta-thromboglobulin and hemoglobin A1c.     

Zinc kinetics in insulin-dependent diabetes mellitus patients

Zinc has an important role in the control of carbohydrate metabolism, and diabetic patients are at risk for zinc deficiency. However, there are conflicting data concerning nutritional zinc status. In order to investigate this topic, 10 normal and 10 insulin-dependent diabetic patients were studied following venous zinc tolerance test. Our results found no evidence of zinc deficiency or of changes on the kinetic parameters of zinc in patients with insulin-dependent diabetes mellitus following a venous zinc tolerance test.     

N-acetyl-beta-D-glucosaminidase in lymphocytes of patients with diabetes mellitus

In 55 patients with diabetes mellitus the significant quantitative increase in numbers of N-acetyl-beta-D-glucosaminidase-positive lymphocytes in the peripheral blood has been examined by cytochemical methods. The enzyme-positive lymphocytes of these patients were characterized by prevalence of extralysosomal localization of the enzyme and a decrease in the numbers of those cells having intact enzyme-positive lysosomes. No association between these alterations and therapy with insulin or oral hypoglycemic drug and overweight could be stated.     

Serum thyroglobulin concentration in patients with diabetes mellitus

The serum thyroglobulin (Tg) concentration was measured in 97 patients with diabetes mellitus (39 males, 58 females). Hyper Tg-nemia which exceeds the normal range (1.0-26.6 ng/ml) was observed in 10 patients (3 out of 21 cases treated with diet alone, 3 out of 50 cases treated with oral hypoglycemic agents, 4 out of 26 cases treated with insulin). There was no significant correlation between concentrations of serum Tg and triiodothyronine (T3), thyroxine (T4), fasting plasma glucose (FPG), and hemoglobin A1c (HbA1c). However, a positive correlation was observed between serum concentrations of Tg and thyroid stimulating hormone (TSH). Patients with diabetes were divided into three groups according to the mode of treatment (Group I; diet alone, n = 21, Group II; oral hypoglycemic agents, n = 50, Group III; insulin, n = 26). No significant difference in the serum Tg concentration was observed among the three groups. They were also divided into two groups; normal Tg-nemia (Group A, n = 87) and hyper Tg-nemia (Group B, n = 10). There was no difference between levels of T3, T4, FPG, and HbA1c in the two groups. The serum TSH concentration measured by double antibody RIA and two site immunoradiometric assay in Group B was significantly higher than that in Group A. These results suggest that hyper Tg-nemia in patients with diabetes could be due to the increased TSH concentration which reflects latent subclinical primary hypothyroidism in them.     

N-acetyltransferase 2 polymorphism in patients with diabetes mellitus

The arylamine N-acetyltransferases (NATs) are a unique family of enzymes that catalyse the transfer of an acetyl group from acetyl-CoA to the terminal nitrogen of hydrazine and arylamine drugs and carcinogens. Human arylamine NATs are known to exist as two isoenzymes, NAT1 and NAT2. The objective of this study was to identify whether the genetic polymorphism of NAT2 plays a role in susceptibility to Diabetes Mellitus (DM). Ninety-seven patients with DM and 104 healthy controls were enrolled in the study. NAT2*5A, NAT2*6A, NAT2*7A/B and NAT2*14A polymorphisms were detected by using real time PCR with LightCycler (Roche Diagnostics GmbH, Mannheim, Germany). According to our data, the NAT2*5A and NAT2*6A mutant genotypes and NAT2*14A heterozygous genotype were associated with an increased risk of development of DM (OR = 47.06; 95%CI: 10.55-209.77 for NAT 2*5A, OR = 18.48; 95%CI: 3.83-89.11 for NAT2*6A and OR = 18.22; 95%CI: 6.29-52.76 for NAT2*14A). However, the NAT2*7A/B gene polymorphism carried no increased risk for developing DM disease. After grouping according to phenotypes as either slow or fast acetylators, NAT2*6A slow acetylator was found to be a significant risk factor for DM (OR = 6.09; 95%CI: 1.99-18.6, p = 0.02). The results indicate that NAT2 slow acetylator genotypes may be an important genetic determinant for DM in the Turkish population.     

Type 2 diabetes mellitus: phylogenetic motifs for predicting protein functional sites

Diabetes mellitus, commonly referred to as diabetes, is a medical condition associated with abnormally high levels of glucose (or sugar) in the blood. Keeping this view, we demonstrate the phylogenetic motifs (PMs) identification in type 2 diabetes mellitus very likely corresponding to protein functional sites. In this article, we have identified PMs for all the candidate genes for type 2 diabetes mellitus. Glycine 310 remains conserved for glucokinase and potassium channel KCNJ11. Isoleucine 137 was conserved for insulin receptor and regulatory subunit of a phosphorylating enzyme. Whereas residues valine, leucine, methionine were highly conserved for insulin receptor.Occurrence of proline was very high for calpain 10 gene and glucose transporter.     

Type 2 diabetes mellitus: phylogenetic motifs for predicting protein functional sites

Diabetes mellitus, commonly referred to as diabetes, is a medical condition associated with abnormally high levels of glucose (or sugar) in the blood. Keeping this view, we demonstrate the phylogenetic motifs (PMs) identification in type 2 diabetes mellitus very likely corresponding to protein functional sites. In this article, we have identified PMs for all the candidate genes for type 2 diabetes mellitus. Glycine 310 remains conserved for glucokinase and potassium channel KCNJ11. Isoleucine 137 was conserved for insulin receptor and regulatory subunit of a phosphorylating enzyme. Whereas residues valine, leucine, methionine were highly conserved for insulin receptor. Occurrence of proline was very high for calpain 10 gene and glucose transporter.     

Probability based approach for predicting the course of disease in diabetic retinopathy patients

The number of Diabetes patients has risen in both the developing and the developed nations. It is associated with lot complications retinopathy, nephropathy, neuropathy etc. Diabetic retinopathy is one of the leading causes of preventable blindness. Diabetic patients have to be monitored at regular intervals to detect any signs of retinopathy and deterioration of vision and timely intervention. This requires lot of time and cost both on the part of the patient and the specialist. Therefore there is a need to differentiate the ' high risk ' patients from the ' low risk ' patients, so that the high risk ones can be managed more rigorously while the low risk patients can be referred for less frequent screenings and checkups. Data of around 100 patients with Grade 1 retinopathy was collected. Their physiological parameters with their DR grading after 3 years was recorded. Physiological parameters which were having a higher impact on the course of Retinopathy were taken (e.g. Mild blood urea, Hypertension and Smoking in this case). Transition probabilities of going from one stage to other were calculated. Probability of having a single physiological parameter in a given stage of DR at a given point of time was calculated. Probability of various combinations of these physiological parameters in a given stage of disease was calculated. Then by knowing the present stage of that disease future stage (3 years later in this case) of the disease can be predicted. Based on these predictions, the ' high risk ' patients are differentiated from the ' low risk ' patients and are accordingly referred for screenings and interventions.     

Cytochemical indices of leukocytes in patients with diabetes mellitus

Cytochemical indices of leukocytes were determined in 16 patients with diabetes mellitus in the period of unbalancing and balancing. The following tests were made: content of glycogen and lipids, acid phosphatase (AP), alkaline phosphatase (AIP), myeloperoxidase (MPO) and nonspecific alpha-naphtol acetate esterase (NANAE) activity. In unbalanced diabetics an evident decrease in the activity of AP and MPO could be noted as well as a decrease of glycogen content and an increase of lipid content. An insignificant decrease could be observed in the activity of ALP and NANAE in granulocytes. A slight increase in the activity of NANAE in monocytes would be found. Balancing this disease induced the increase of all parameters in granulocytes except MPO activity. It is interesting to note that balancing diabetes mellitus deepened the observed changes in the decrease or increase of tested parameters. The presented findings clearly indicate the role of metabolic disorders in diabetes mellitus on the activity of some neutrophilic enzymes and the glycogen and the content of lipids in neutrophils.     

Disorders of colonic motility in patients with diabetes mellitus

Motility disturbances of the colon can give significant symptoms in patients with diabetes mellitus. Constipation is a common complaint in these patients. Diarrhea associated with a generalized autonomic neuropathy can be very troublesome. There is a disturbance in the gastrocolonic response to eating in patients with diabetes mellitus who have constipation. These patients have no postprandial increase in colonic motility. However, their colonic smooth muscle contracts normally to the exogenous administration of neostigmine or metoclopramide. Stool softeners used in combination with the smooth muscle stimulants (neostigmine or metoclopramide) are helpful in treating constipation in patients with diabetes mellitus. Diarrhea can be treated with loperamide or diphenoxylate. Biofeedback may be useful in treating incontinence associated with diarrhea in these patients.