Prevalence of Latent Autoimmune Diabetes in Adult Based on the Presence of GAD 65 Antibodies in North-Eastern Uttar Pradesh, India

Objective:The objective of this paper was (1) to study the prevalence of latent autoimmune diabetes in adult (LADA) in the region of north-eastern Uttar Pradesh, India, based on the positivity for glutamic acid decarboxylase 65 (GAD65) antibodies and (2) to compare the glycemic profile between GAD65-positive and GAD65-negative subjects. Materials and Methods?The subjects were of more than 30 years of age, with either recently diagnosed pre-diabetes/diabetes presenting with the hemoglobin A1c (HbA1c) level of ?5.7% or already diagnosed cases of type 2 diabetes mellitus (T2DM) who had no requirement of insulin therapy for at least 6 months from the time of their diagnosis. All the patients were natives of north-eastern Uttar Pradesh. The GAD65 test was done by the enzyme-linked immunosorbent assay. Further, the glycemic status of GAD-positive and GAD-negative subjects were compared on the basis of fasting blood sugar (FBS), fasting insulin (FI), and homeostatic model assessment for insulin resistance (HOMA-IR). The “unpaired t-test” was used to compare and assess the significance of differences between the glycemic profile of GAD65-positive and GAD65-negative subjects using the GraphPad Prism Scientific Software, San Diego, CA, United States. The p-value of <0.05 was considered to be significant. Results?A total of 77 patients were included in the study, with the age group ranging from 30 to 75 years (47.81?±?12.9 years) with the male–female ratio of 1:2.6. The prevalence of LADA was found to be 51.95%. On comparing GAD65-positive and GAD65-negative groups, a higher value of HbA1c levels and FBS were found in the former, whereas FI and HOMA-IR were found to be higher in the latter. On testing for significance of difference, only FI and HbA1c values were significant (p-value <0.0001). Conclusion?LADA can no longer be considered a rare type of diabetes mellitus, with the present study showing a high prevalence of LADA in this north eastern region of Uttar Pradesh. Identification of adult-onset diabetics accurately as LADA or true T2DM is very crucial for the appropriate treatment, as LADA patients require insulin inevitably and much earlier than true T2DM patients, who can be managed mostly on oral hypoglycemic agents with seldom requirement of insulin

Marcadores de inflamación y autoinmunidad en pacientes con diabetes tipo 1 / And inflammation markers in patients with diabetes autoimmunity type 1

To determine the serological levels of inflammatory markers and autoimmunity in patients with T1D compared with controls, and determined its relation to the duration of diabetes. Methods: We selected 139 patients with T1D without chronic complications of diabetes, and 110 control subjects without family history of diabetes. Serological ultrasensitive C-reactive protein levels (usCRP), interleukin- 6 and adhesion protein VCAM through ELISA assay were determined. Autoimmune profile was also analyzed through GAD65, IA-2 and ZnT8 autoantibodies. Results: Increased levels of usCRP 1.74 (0.10 to 13.6) vs 1.08 (0.40 to 3.70) ng/ml (p < 0.03), VCAM 236.0 (122.2 to 693.5) vs 185.4 (101.3 to 421.3) ng/ml, p < 0.02 and IL-6 1.73 (0.40 to 9.10) vs 1.28 (0.30 to 4.60) ng/ml, p < 0.05 was found in the group of T1D patients compared with the control group. When analyzing inflammatory markers according to age groups (0-10 years and > 10 years), the values of usCRP were higher in the second group. There was no significant association between patients with DM1 and autoimmune positive profile with a higher frequency of markers of inflammation. Conclusions: These results suggest the presence of pro-inflammatory state is considerably more frequent in patients with T1D. The increased level of usCRP and IL -6 and according to age of the patients could indicate a possible role of adiposity and weight gain during the adolescence in the higher frequency of inflammatory markers in T1D patients...

Are Spinal GABAergic Elements Related to the Manifestation of Neuropathic Pain in Rat?

Impairment in spinal inhibition caused by quantitative alteration of GABAergic elements following peripheral nerve injury has been postulated to mediate neuropathic pain. In the present study, we tested whether neuropathic pain could be induced or reversed by pharmacologically modulating spinal GABAergic activity, and whether quantitative alteration of spinal GABAergic elements after peripheral nerve injury was related to the impairment of GABAergic inhibition or neuropathic pain. To these aims, we first analyzed the pain behaviors following the spinal administration of GABA antagonists (1 microgram bicuculline/rat and 5 microgram phaclofen/rat), agonists (1 microgram muscimol/rat and 0.5 microgram baclofen/rat) or GABA transporter (GAT) inhibitors (20 microgram NNC-711/rat and 1 microgram SNAP-5114/rat) into naive or neuropathic animals. Then, using Western blotting, PCR or immunohistochemistry, we compared the quantities of spinal GABA, its synthesizing enzymes (GAD65, 67) and its receptors (GABAA and GABAB) and transporters (GAT-1, and -3) between two groups of rats with different severity of neuropathic pain following partial injury of tail-innervating nerves; the allodynic and non-allodynic groups. Intrathecal administration of GABA antagonists markedly lowered tail-withdrawal threshold in naive animals, and GABA agonists or GAT inhibitors significantly attenuated neuropathic pain in nerve-injured animals. However, any quantitative changes in spinal GABAergic elements were not observed in both the allodynic and non-allodynic groups. These results suggest that although the impairment in spinal GABAergic inhibition may play a role in mediation of neuropathic pain, it is not accomplished by the quantitative change in spinal elements for GABAergic inhibition and therefore these elements are not related to the generation of neuropathic pain following peripheral nerve injury.

The heterogeneity between adult and adolescent type 1 diabetes / 中国实用内科杂志

25 year).The patients were analyzed for the clinical characteristics.Autoantibodies to glutamic acid decarboxylase 65(GAD65-Ab),insulin(I-Ab)and autoantobodies to protein tyrosine phosphatase-like proteins(IA2-Ab)were assayed.HLA-DRB1,DQA1,DQB1 alleles(HLA-DRB1*03,*04,*09,*15,DQB1*0201,*0302,*0601,DQA1*0301,*0501)were typing by PCR-sequence specific primer(PCR-SSP).Results A little higher proportion of males,a longer duration of disease; a higher BMI and WHR characterized the adult-onset patients.The adults have a higher level of triglycerides and 120 min C-peptides than adolescent.The frequency and level of IA2-Ab of the adolescents were higher than adults(47.1% vs 15.1% and 0.46 U?mL~ -1 vs 0.07 U?mL~ -1 ,respectively,P

Roles of Stem Cell Factor and c-kit Receptor in the Development of Cerebellar GABAergic Neurons / 대한해부학회지

Evidence that Stem cell factor (SCF) and c-Kit receptor tyrosine kinase are expressed in the cerebellum during postnatal development, suggests a possible contribution of the SCF/Kit signaling pathway in the cerebellar development. In the present study, we prepared cerebellar cultures from C57Bl/6J mouse at postnatal day 1and 7 to investigate the role of c-kit receptor and SCF in regulation of growth and differentiation in the postnatal cerebellar GABAergic cells. SCF increased the number of survival cerebellar cells and density of glutamic acid decarboxylase 65/67 (GAD65/67) and calbindin D-28K expression in the immunoblot analysis. SCF also improved the neurite extension of the interneuron neuritis and dendritogenesis of Purkinje cells. Treatment with c-Kit antibody accelerated cellular loss in serum-free media and decreased the growth ability and dendritogenesis of Purkinje cells and cerebellar inhibitory interneurons. Our data suggest that SCF and c-kit receptor are required for the normal growth of postnatal cerebellum and a possible involvement of functional regulation through the SCF/c-kit receptor pathways in the postnatal cerebellar development.

Immunocytochemical Localization of GABA Transporter-3 in the Guinea Pig Retina / 대한해부학회지

The cellular localization of the GABA transporter-3 (GAT-3) was examined in the guinea pig retina by immunocytochemistry, using antisera against GAT-3. GAT-3 immunoreactivity was localized to cell bodies in the inner nuclear layer, and labeled processes were densely distributed in the inner plexiform layer (IPL) close to the ganglion cell layer. All GAT-3 labeled cells exhibited GAD65 immunoreactivity. In addition, 67% of GAT-3 labeled amacrine cells showed carbohydrate epitope CD15 immunoreactivity. These results indicate that GAT-3 is involved in modulating the rod pathway in the IPL of the guinea pig retina via presumptive A17 amacrine cells.

Measurement of Anti-GAD65 Autoantibodies in Patients with Type 1 Diabetes Mellitus with / without Autoimmune Thyroid Diseases (Immunoblotting followed by Immunoprecipitation) / 대한내분비학회지

BACKGROUND: Type 1 diabetes mellitus is frequently associated with other autoimmune diseases. The broad concept of polyendocrinopathies takes into consideration that patients affected by at least one endocrine disease may have another autoimmune disorder or express specific autoantibodies. Anti-glutamic acid decarboxylase autoantibodies, now recognized as one of the major serological markers for type 1 diabetes has been reported to be higher in type 1 diabetes patients with autoimmune thyroid diseases (ATD) than in those without ATD. The objective of the present study was to evaluate the prevalences of GAD65 antibodies applying a newly developed assay(anti-GAD65) in type 1 diabetes patients with and without ATD. METHODS: We developed a new anti-GAD65 assay after mammalian expression of a recombinant GAD65 antigen. Since the detection of anti-GAD65 is rather complicated and insensitive due to inherent antigenic difference of antibody recognition in conventional assays, we applied this new approach in measuring anti-GAD autoantibodies and compared the result with ICA and anti-GAD measurement using the purified porcine GAD (anti-GAD) in 109 cases of type 1 diabetes, 29 of whom had concomitant ATD (mean age at diagnosis: 7.9 yr, mean duration of type 1 diabetes: 4.5 yrs). RESULTS: The overall prevalence of anti-GAD65 antibodies was 65% (71 of 109) in patients with Korean type 1 diabetes. Prevalences and titers of anti-GAD65 had not changed much after controlling for the duration and the status of concomitant ATD. In contrast, the prevalence of anti-GAD was 56%(61 of 109), while that of ICA(+) WAS 36% in type 1 diabetes patients. We found significant, but not strong association of anti-GAD65 either with anti-GAD(r=0.4, p<0.01) or with ICA(r=0.6, p< 0.001). CONCLUSION: From this, we could assess that autoantibodies are present at comparable sensitivity and specificity in Korean type 1 diabetes patients. This anti-GAD65 assay, another immunologic marker for type 1 diabetes might also confer disease susceptibility among Koreans, but no increase in the prevalence or in the titer in patients with ATD may suggest that this marker is unlikely to give much benefit, for the detection of the overlapping disease of type 1 diabetes and ATD.