Electricity demand analysis and forecasting: The case of GADA special economic zone.

Ethiopia is a country in East Africa experiencing significant economic growth in recent years, with an increasing electricity demand. Ensuring sustainable and efficient energy for newly developed industries and economic zones is crucial. In this study, a 15-year electric power demand forecast for the new economic zone under construction is conducted. The electrical power demand forecast is done for the year 2025-2040 by using bottom-up forecasting approach for three different scenarios. Long-range Energy Alternatives Planning (LEAP) system software is used to analyze residential, industrial, and general business sector electric power demand. The analysis of the assessed scenario shows that the economic zone's electric power demand increases by 52.2 % from the base year 2025-2040 for the baseline scenario, due to anticipated rapid urbanization, growth in population, economic expansion, and anticipated political stability. Compared to the baseline scenario, the total power demand shows a growth of 68 % from the forecast year (2025) to 2040 for the aggressive scenario, which ensures sustainable and efficient energy options that can draw businesses from both domestic and international baselines. In contrast, the total power demand in the conservative scenario shows a growth of 30.3 % from the base year (2025) to 2040. This reduction in demand compared to the two scenarios indicates a reflection of how much electricity power demand could be if certain development conditions failed to be realized in the economy. In general, both results show a rapid increase in power demand compared to the base year. To address this increasing demand, a supply-side demand analysis can be done for reference and aggressive scenarios. The analysis result indicated that by 2040, supply-side demand from the national grid will increase by 93.5 % and 175.9 % for reference and aggressive scenarios, respectively, compared to the base year 2025 demand. Due to the huge gap between the supply and demand in the country, onsite off-grid generation can be considered to cover 25 % of the demand in the economic zone. Hence, with the support of off-grid generation, the demand from the national grid was reduced to 45 % and 107 % for reference and aggressive scenarios with the support of onsite generation. Hence, this research clearly shows that there is a serious need for large scale electricity generation and distribution planning and preparation to meet the continually increasing electric power demand in a sustainable manner to accommodate the growth and change required to develop the modern economic zones in the country.

Prevalence of Organ-Specific Autoimmunity in Patients With Type 1 Diabetes Mellitus.

INTRODUCTION: Type 1 diabetes mellitus (T1DM) is associated with other autoimmune disorders that are characterized by presence of organ-specific autoantibodies. The present study was undertaken to assess the prevalence of organ-specific autoantibodies among newly diagnosed T1DM subjects of India and to study its relationship with glutamic acid decarboxylase antibody (GADA). We also compared the clinical and biochemical parameters in GADA-positive and -negative T1DM subjects. METHODS: In a hospital-based cross-sectional study, we studied 61 patients with newly diagnosed T1DM ≤ 30 years of age. T1DM was diagnosed on the basis of acute onset of osmotic symptoms with or without ketoacidosis, severe hyperglycaemia [blood glucose > 13.9 mmol/l (>250 mg/dl)] and insulin requirement from the onset of diabetes. Subjects were screened for autoimmune thyroid disease (thyroid peroxidase antibody [TPOAb]), celiac disease (tissue transglutaminase antibody [tTGAb]), and gastric autoimmunity (parietal cell antibody [PCA]). RESULTS: Of the 61 subjects, more than one-third (38%) had at least one positive organ-specific autoantibody. In particular, 13 (21.3%) were found to be positive for TPOAb, nine (14.8%) were positive for tTGAb and 11 (18%) were positive for PCA. GADA was positive in 15 (25%) subjects. The frequency of TPOAb tended to be higher in patients who had GADA positivity compared with those with no circulating GADA (40% vs. 15.2%; p=0.07). Subjects positive for GADA were also more likely to be PCA positive compared with those who were GADA negative (40 vs.10.9%, p=0.02). There were no differences in frequency of diabetic ketoacidosis, body mass index, hemoglobin A1C (HbA1c), insulin requirement or fasting C-peptide in GADA-positive and -negative patients. CONCLUSION: We support the recommendation for regular screening of organ-specific autoantibodies, in particular TPOAb, tTGAb and PCA in all patients with T1DM. Detection of these autoantibodies at onset may prevent complications associated with delayed diagnosis of these disorders. We also conclude that there is higher frequency of TPOAb and PCA in GADA-positive T1DM patients as compared to negative ones. However, patients with positive GADA had similar clinical and biochemical parameters compared to GADA-negative subjects. Lastly, low GADA positivity in our study cohort as compared to Western populations suggests the heterogenous nature of T1DM in the Indian population.

A comparison in women with newly diagnosed diabetes between those with and without a history of gestational diabetes: a new perspective.

AIMS: Previous gestational diabetes mellitus (GDM) entails increased risk of future diabetes. We describe the characteristics of women with previous GDM and compare with no previous GDM from the cohort Diabetes in Kalmar and Kronoberg (DKK) of 1248 adults, 40% women, with new diabetes, and factors affecting age and C-peptide levels at diagnosis of diabetes. METHODS: Age-at-diagnosis of diabetes, BMI, hypertension, hyperlipidemia, smoking, physical activity, and pre-existing myocardial infarction, stroke, or peripheral arterial insufficiency were registered at ordinary care visits close to diagnosis of diabetes, for the 43 women (9.4% of 456 from DKK with complete data for this analysis) with self-reported previous GDM (yes/no) and 86 controls without it, matched for date of diagnosis of diabetes. Blood samples were centrally analyzed for GADA and C-peptide for classification of diabetes. RESULTS: Women with previous GDM had lower mean age-at-diagnosis of diabetes, 53.4 vs 65.0 years, lower systolic blood pressure (SBP), 131.2 vs 137.5 mmHg, and fewer had pre-existing hypertension than without previous GDM (p < 0.001-0.05). Among antibody negative women with previous GDM, BMI (p = 0.024), hypertension (p = 0.023) and hyperlipidemia (p < 0.001) were associated with higher levels of C-peptide, while physical activity was inversely associated (p = 0.035), and SBP (p = 0.02) and hypertension (p = 0.016) were associated with age-at-diagnosis of diabetes. CONCLUSIONS: Women with previous GDM were a decade younger and had lower prevalence of hypertension at diagnosis of diabetes; C-peptide levels were associated with BMI, hypertension, and hyperlipidemia and showed a tendency to be lower, possibly indicating a phenotype with higher risk of overt cardiovascular disease later in life.

HLA-DQ-conferred risk for type 1 diabetes does not alter neutralizing antibody response to a widely used enterovirus vaccine, the poliovirus vaccine.

This study investigated whether children with HLA-DQ-conferred risk for type 1 diabetes (T1D) have an altered immune response to the widely-used enterovirus vaccine, namely poliovirus vaccine, and whether initiation of autoimmunity to pancreatic islets modulates this response. Neutralizing antibodies induced by the inactivated poliovirus vaccine against poliovirus type 1 (Salk) were analysed as a marker of protective immunity at the age of 18 months in a prospective birth cohort. No differences were observed in antibody titers between children with and without genetic risk for T1D (odds ratio [OR] = 0.90 [0.83, 1.06], p = 0.30). In the presence of the genetic risk, no difference was observed between children with and without islet autoimmunity (OR = 1.00 [0.78, 1.28], p = 1.00). This did not change when only children with the autoimmunity before 18 months of age were included in the analyses (OR = 1.00 [0.85, 1.18], p = 1.00). No effect was observed when groups were stratified based on autoantigen specificity of the first-appearing autoantibody (IAA or GADA). The children in each comparison group were matched for sex, calendar year and month of birth, and municipality. Accordingly, we found no indication that children who are at risk to develop islet autoimmunity would have a compromised humoral immune response which could have increased their susceptibility for enterovirus infections. In addition, the proper immune response supports the idea of testing novel enterovirus vaccines for the prevention of T1D among these individuals.

The prevalence of diabetes and thyroid related autoantibodies in Sri Lankan children with type 1 diabetes and their unaffected siblings - The utility of a new screening assay.

Background: There is limited information about diabetes and thyroid related autoantibodies in children with type 1 diabetes (T1D) or their siblings in Sri Lanka. Objectives: To assess in T1D children and their unaffected siblings the prevalence of autoantibodies to (1) glutamic acid decarboxylase (GADA), insulinoma associated antigen-2 (IA-2A) and zinc transporter 8 (ZnT8A) using 3 Screen ICA™ (3-Screen) and individual ELISA assays; (2) insulin (IAA); and (3) thyroid peroxidase (TPOA), thyroglobulin (TgA) and the TSH receptor (TSHRA). Methods: We selected - (a) consecutive T1D children, and (b) their unaffected siblings of both sexes, from the T1D Registry at Lady Ridgeway Hospital, Colombo. Results: The median age (IQR) of 235 T1D children and 252 unaffected siblings was 11 (8.4, 13.2) and 9 (5.4, 14.9) years respectively, and the duration of T1D was 23 (7, 54) months. (1) T1D children (a) 79.1% were 3-Screen positive; (b) all 3-Screen positives were individual antibody positive (GADA in 74%; IA-2A 31.1%; ZnT8A 38.7%); (c) and were younger (p=0.01 vs 3-Screen negatives); (d) multiple autoantibodies were present in 45.1%; (e) IA-2A (p=0.002) and ZnT8A (p=0.006) prevalence decreased with T1D duration. (f) TPOA and TgA prevalence was higher in T1D children compared to unaffected siblings (28%, p=0.001 and 31%, p=0.004, respectively). (2) Unaffected siblings (a) 6.3% were 3-Screen positive (p=0.001 vs T1D), and 2.4% were positive for IAA; (b) four subjects had two diabetes related autoantibodies, one of whom developed dysglycaemia during follow-up. Conclusions: The 3-Screen assay, used for the first time in Sri Lankan T1D children and their siblings as a screening tool, shows a high prevalence of T1D related Abs with a high correlation with individual assays, and is also a helpful tool in screening unaffected siblings for future T1D risk. The higher prevalence of thyroid autoantibodies in T1D children is consistent with polyglandular autoimmunity.

Associations between glutamic acid decarboxylase antibodies, oxidative stress markers, and cognitive capacity in adolescents who stutter.

In this study, we amid to evaluate the correlation between the change in the expressed levels of anti-GAD antibodies titers, oxidative stress markers, cytokines markers, and cognitive capacity in adolescents with mild stuttering. Eighty participants (60 male/20 female) with the age range of 10-18 years with moderate stutteringparticipated in this study. To assess the stuttering and cognitive function, stutteringseverity instrument (SSI-4; 4th edit.)and the LOTCA-7 scores assessment were applied respectively in all subjects. In addition, serum GAD antibodies, cytokines like TNF-α, CRP,and IL-6 withtotal antioxidant capacity and nitric oxide as oxidative stress markers were estimated using calorimetry and immunoassay techniques.The results showed that good cognitive capacity was reported in about 56.25 % of the study population (n = 45) with a 117.52 ± 6.3 mean LOTCA-7 score. However, abnormal cognitive function was identified in 43.75 % of the study population (n = 35); they were categorized into moderate (score 62-92, n = 35), and poor (score 31-62; n = 10). There were significant associations between cognitive capacity reported and all biomarkers. The expression of GAD antibodies is significantly associated with the degree of cognitive capacity among students with stuttering. Significant association with the reduction (P = 0.01) in LOTCA-7 score domains, particularly orientation, thinking operations, attention, and concentration among students with variable cognitive capacity compared to controls. In addition, the expressed higher GAD antibodies in students with moderate and poor cognitive capacity showed to be significantly correlated with both elevated concentrations of cytokines; TNF-α, CRP, and IL-6, and the reduction of TAC and nitric oxide (NO) respectively. This study concludes that abnormality of cognitive capacity showed to be associated with higher expression of GAD antibodies, cytokines, and oxidative stress in school students with moderate stuttering.

Anti-glutamic Acid Decarboxylase Antibody-Positive Gestational Diabetes Mellitus with Autoimmune Type 1 Diabetes Mellitus in the Early Postpartum Period: A Case Report and Literature Review.

Gestational diabetes mellitus (GDM) is a state of pre-diabetic impaired glucose tolerance initially occurring during pregnancy. Although abnormalities in glucose metabolism normally resolve rapidly after delivery, women with GDM have a higher lifetime risk of developing diabetes mellitus than those without GDM; thus, postpartum healthcare is essential. Of all GDM patients, 5%-10% test positive for diabetes-related autoantibodies, which increase the risk of developing type 1 diabetes mellitus (T1DM). Autoantibody measurement in GDM screening remains debatable; however, it may be useful for the postnatal follow-up of GDM patients at high risk of developing T1DM. We treated a 29-year-old woman who was GDM positive for anti-glutamic acid decarboxylase antibody (GADA) requiring high-dose insulin therapy during pregnancy. As the patient tested positive for GADA, she received judicious postpartum management, allowing for early diagnosis of T1DM and resumption of treatment. Her insulin secretory capacity was preserved at 1 year after parturition, suggesting either slowly progressive insulin-dependent T1DM or latent autoimmune diabetes in adults. This was a rare case of slowly progressive insulin-dependent T1DM or latent autoimmune diabetes in adults in the early postpartum period, but the fact that GADA was positive during pregnancy enabled early treatment without overlooking it. Measuring diabetes-related autoantibodies in patients considered to be at a high risk for T1DM, such as those who are of slim build, young, or suffering from autoimmune thyroid disorders, may be important for appropriate individualized follow-up.

Gut microbiome and metabolic activity in type 1 diabetes: An analysis based on the presence of GADA.

Objective: Type 1 diabetes (T1D) progression is affected by circulating glutamic acid decarboxylase antibody (GADA) that persist for many years. This study aimed at investigating whether and how the gut microbiome and its correlated metabolites change in T1D with the presence of GADA. Methods: We used a radiobinding assay to measure GADA titers and identify the 49 T1D patients with GADA+ and 52 T1D patients with GADA-. The fresh feces and serum were analyzed using 16S rRNA gene sequencing and GC/MS. Then gut microbiome and serum metabolites were compared between the GADA+ patients and the GADA- patients. The association between gut microbial community and metabolites was assessed using the Spearman's rank correlation. Results: The gut microbiome in diversity, composition, and function differed between these two groups. The abundance of genus Alistipes, Ruminococcus significantly increased in patients with GADA+ compared to that observed in the samples of GADA-. There were 54 significantly altered serum metabolites associated with tryptophan metabolism, phenylalanine, and tyrosine biosynthesis in individuals with GADA+ compared with those of GADA-For the serum metabolites, compared with those of GADA-, there were 54 significantly different metabolites with tryptophan metabolism, phenylalanine, and tyrosine and tryptophan biosynthesis decreased in individuals with GADA+. The abundance of Alistipes was positively correlated with altered metabolites involved in tryptophan metabolism. Conclusion: We demonstrate that T1D patients with GADA+ are characterised by aberrant profiles of gut microbiota and serum metabolites. The abundance of Alistipes disturbances may participate in the development of T1D patients with GADA by modulating the host's tryptophan metabolism. These findings extend our insights into the association between the gut microbiota and tryptophan metabolism and GADA and might be targeted for preventing the development of T1D.

HbA1c as a time predictive biomarker for an additional islet autoantibody and type 1 diabetes in seroconverted TEDDY children.

OBJECTIVE: Increased level of glycated hemoglobin (HbA1c) is associated with type 1 diabetes onset that in turn is preceded by one to several autoantibodies against the pancreatic islet beta cell autoantigens; insulin (IA), glutamic acid decarboxylase (GAD), islet antigen-2 (IA-2) and zinc transporter 8 (ZnT8). The risk for type 1 diabetes diagnosis increases by autoantibody number. Biomarkers predicting the development of a second or a subsequent autoantibody and type 1 diabetes are needed to predict disease stages and improve secondary prevention trials. This study aimed to investigate whether HbA1c possibly predicts the progression from first to a subsequent autoantibody or type 1 diabetes in healthy children participating in the Environmental Determinants of Diabetes in the Young (TEDDY) study. RESEARCH DESIGN AND METHODS: A joint model was designed to assess the association of longitudinal HbA1c levels with the development of first (insulin or GAD autoantibodies) to a second, second to third, third to fourth autoantibody or type 1 diabetes in healthy children prospectively followed from birth until 15 years of age. RESULTS: It was found that increased levels of HbA1c were associated with a higher risk of type 1 diabetes (HR 1.82, 95% CI [1.57-2.10], p < 0.001) regardless of first appearing autoantibody, autoantibody number or type. A decrease in HbA1c levels was associated with the development of IA-2A as a second autoantibody following GADA (HR 0.85, 95% CI [0.75, 0.97], p = 0.017) and a fourth autoantibody following GADA, IAA and ZnT8A (HR 0.90, 95% CI [0.82, 0.99], p = 0.036). HbA1c trajectory analyses showed a significant increase of HbA1c over time (p < 0.001) and that the increase is more rapid as the number of autoantibodies increased from one to three (p < 0.001). CONCLUSION: In conclusion, increased HbA1c is a reliable time predictive marker for type 1 diabetes onset. The increased rate of increase of HbA1c from first to third autoantibody and the decrease in HbA1c predicting the development of IA-2A are novel findings proving the link between HbA1c and the appearance of autoantibodies.

Islet Autoantibody Level Distribution in Type 1 Diabetes and Their Association With Genetic and Clinical Characteristics.

CONTEXT: The importance of the autoantibody level at diagnosis of type 1 diabetes (T1D) is not clear. OBJECTIVE: We aimed to assess the association of glutamate decarboxylase (GADA), islet antigen-2 (IA-2A), and zinc transporter 8 (ZnT8A) autoantibody levels with clinical and genetic characteristics at diagnosis of T1D. METHODS: We conducted a prospective, cross-sectional study. GADA, IA-2A, and ZnT8A were measured in 1644 individuals with T1D at diagnosis using radiobinding assays. Associations between autoantibody levels and the clinical and genetic characteristics for individuals were assessed in those positive for these autoantibodies. We performed replication in an independent cohort of 449 people with T1D. RESULTS: GADA and IA-2A levels exhibited a bimodal distribution at diagnosis. High GADA level was associated with older age at diagnosis (median 27 years vs 19 years, P = 9 × 10-17), female sex (52% vs 37%, P = 1 × 10-8), other autoimmune diseases (13% vs 6%, P = 3 × 10-6), and HLA-DR3-DQ2 (58% vs 51%, P = .006). High IA-2A level was associated with younger age of diagnosis (median 17 years vs 23 years, P = 3 × 10-7), HLA-DR4-DQ8 (66% vs 50%, P = 1 × 10-6), and ZnT8A positivity (77% vs 52%, P = 1 × 10-15). We replicated our findings in an independent cohort of 449 people with T1D where autoantibodies were measured using enzyme-linked immunosorbent assays. CONCLUSION: Islet autoantibody levels provide additional information over positivity in T1D at diagnosis. Bimodality of GADA and IA-2A autoantibody levels highlights the novel aspect of heterogeneity of T1D. This may have implications for T1D prediction, treatment, and pathogenesis.

Evaluation of the RSR 3 screen ICA™ and 2 screen ICA™ as screening assays for type 1 diabetes in Sweden.

AIM: The study aim was to evaluate the RSR 3 Screen ICA™ and 2 Screen ICA™ for detection of islet cell autoimmunity in healthy Swedish subjects and patients with newly diagnosed type 1 diabetes (T1D). METHODS: 3 Screen is designed for combined detection of autoantibodies to glutamic acid decarboxylase (GADA), to the islet antigen IA-2 (IA-2A) and to zinc transporter 8 (ZnT8A), while 2 Screen detects GADA and IA-2A. Serum samples from 100 T1D patients at onset and 200 healthy controls were studied. RESULTS: 3 Screen achieved 93% assay sensitivity and 97.5% specificity, while 2 Screen achieved 91% assay sensitivity and 98.5% specificity. Samples were also tested in assays for individual autoantibodies. There was only one 3 Screen positive healthy control sample (0.5%) that was positive for multiple autoantibodies (IA-2A and ZnT8A). In contrast, most of the 93 3 Screen positive patients were positive for multiple autoantibodies with 72% (67/93) positive for both GADA and IA-2A and 57% (53/93) positive for three autoantibodies (GADA, IA-2A and ZnT8A). Insulin autoantibodies (IAA, measured by radioimmunoassay) were positive in 13 patients and two healthy controls. CONCLUSION: 3 Screen achieved high sensitivity and specificity, suitable for islet cell autoimmunity screening in a healthy population. In the case of 3 Screen positivity, further assays for GADA, IA-2A and ZnT8A are required to check for multiple autoantibody positivity, a hallmark for progression to T1D. In addition, testing for IAA in children below two years of age is warranted.

Time-dependent effects on circulating cytokines in patients with LADA: A decrease in IL1-ra and IL-1 beta is associated with progressive disease.

BACKGROUND: Cytokines and chemokines participate in autoimmune processes at cellular targets which include insulin-producing beta cells. To which extent such participation is reflected in the circulation has not been conclusively resolved. AIM: We compared the time course of cytokines/chemokines in Latent Autoimmune Diabetes in Adults (LADA) patients heterogeneous for high or low autoimmune activity as determined by levels of antibodies against glutamic acid decarboxylase (GADA). METHODS: Serum samples to be measured were from a two-armed randomized controlled trial (RCT) in 68 LADA patients. The study encompassed 21 months with C-peptide as primary endpoint. We measured 27 immune mediators at baseline, at 9 and at 21 months (end of study). Results of measurements were analyzed by multiple linear regression. RESULTS: At baseline, a high body mass index (BMI) (>26 kg/m2) was associated with elevated levels of the interleukins (IL) IL-1 beta, IL-1ra, IL-2, IL-5, IL-6 and IL-13. Treatment during RCT (sitagliptin vs. insulin) did not affect the time course (21 months) of levels of cytokines/chemokines (by univariate analyses). However, levels of the cytokines IL-1ra and IL-1 beta decreased significantly (p < 0.04 or less) in patients with high vs. low GADA when adjusted for BMI, age, gender (male/female), treatment (insulin/sitagliptin) and study site (Norwegian/Swedish). CONCLUSIONS: In LADA, high levels of GADA, a proxy for high autoimmune activity and linked to a decline in C-peptide, was associated with a decrease of selected cytokines over time. This implies that the decline of IL-1ra and IL-1 beta in the circulation reflects autoimmune activity and beta cell demise in LADA.

Evaluating the Prognostic Value of Islet Autoantibody Monitoring in Islet Transplant Recipients with Long-Standing Type 1 Diabetes Mellitus.

(1) Background: The correlation between titers of islet autoantibodies (IAbs) and the loss of transplanted islets remains controversial. We sought to evaluate the prognostic utility of monitoring IAbs in diabetic patients after islet transplantation (ITx); (2) Methods: Twelve patients with Type 1 diabetes mellitus and severe hypoglycemia underwent ITx. Serum concentration of glutamic acid decarboxylase (GAD), insulinoma antigen 2 (IA-2), and zinc transport 8 (ZnT8) autoantibodies was assessed before ITx and 0, 7, and 75 days and every 3 months post-operatively; (3) Results: IA-2A (IA-2 antibody) and ZnT8A (ZnT8 antibody) levels were not detectable before or after ITx in all patients (median follow-up of 53 months (range 24-61)). Prior to ITx, GAD antibody (GADA) was undetectable in 67% (8/12) of patients. Of those, 75% (6/8) converted to GADA+ after ITx. In 67% (4/6) of patients with GADA+ seroconversion, GADA level peaked within 3 months after ITx and subsequently declined. All patients with GADA+ seroconversion maintained long-term partial or complete islet function (insulin independence) after 1 or 2 ITx. There was no correlation between the presence of IAb-associated HLA haplotypes and the presence of IAbs before or after ITx; (4) Conclusions: There is no association between serum GADA trends and ITx outcomes. IA-2A and ZnT8A were not detectable in any of our patients before or after ITx.

Current view of diagnosis and treatment of latent autoimmune diabetes in adults.

Latent Autoimmune Diabetes in Adults (LADA) is an autoimmune disease arising at adulthood. LADA is characterized by a less intensive autoimmune process, slower progression and a mild metabolic decompensation at onset compared with young-onset type 1 diabetes mellitus. The onset of LADA is usually in non-obese patients over 30, without prominent features of metabolic syndrome and insulin resistance. Nevertheless it may be falsely classified as type 2 diabetes, especially, when diagnosed in older age and for the possibility of non-insulin treatment for at least 6 months after diagnosis. LADA is treated early with insulin and combined with metformin in patients with a higher level of insulin resistance. Clinical studies suggested also effectivity of other oral antidiabetics enabling preservation of residual β-cell function, such as particularly incretines.

Associated autoimmunity in Type 1 Diabetes and latent autoimmune diabetes of adults: The role of glutamic-acid decarboxylase autoantibodies.

AIMS: To determine the prevalence of Associated Autoimmune Diseases (AADs) in Latent Autoimmune Diabetes of Adults (LADA) versus autoimmune Type 1 Diabetes (T1D) and the role of glutamic-acid decarboxylase antibodies (GADA) and other factors. METHODS: Adults with autoimmune diabetes mellitus (DM) were recruited from the Diabetes Center of Nikaia-Piraeus Hospital. Demographic and clinical parameters were recorded and anti-pancreatic and organ-specific antibodies were measured. RESULTS: Of 160 patients, 33.75% had one AAD and 24.37% had two or more. Patients with LADA had higher overall prevalence of AADs, mainly autoimmune thyroiditis and gastritis. Celiac disease was present only in T1D. GADA positive patients had higher prevalence of AADs and multiple autoimmunity, especially thyroiditis and gastritis. Patients with LADA had higher rates of positive GADA or islet-cell antibodies (ICA). After controlling for LADA, GADA remained a significant predictor of AADs. Female gender and chronological age were also significant predictors of AADs. CONCLUSIONS: AADs were present in 58.13% of patients. Patients with LADA were more prone to a generalized autoimmune disorder than those with T1D. AADs development was significantly associated with female sex, older age and positive GADA, which proved an independent marker of associated autoimmunity.

Islet Autoimmunity in Adults With Impaired Glucose Tolerance and Recently Diagnosed, Treatment Naïve Type 2 Diabetes in the Restoring Insulin SEcretion (RISE) Study.

The presence of islet autoantibodies and islet reactive T cells (T+) in adults with established type 2 diabetes (T2D) have been shown to identify those patients with more severe ß-cell dysfunction. However, at what stage in the progression toward clinical T2D does islet autoimmunity emerge as an important component influencing ß-cell dysfunction? In this ancillary study to the Restoring Insulin SEcretion (RISE) Study, we investigated the prevalence of and association with ß-cell dysfunction of T+ and autoantibodies to the 65 kDa glutamic acid decarboxylase antigen (GADA) in obese pre-diabetes adults with impaired glucose tolerance (IGT) and recently diagnosed treatment naïve (Ndx) T2D. We further investigated the effect of 12 months of RISE interventions (metformin or liraglutide plus metformin, or with 3 months of insulin glargine followed by 9 months of metformin or placebo) on islet autoimmune reactivity. We observed GADA(+) in 1.6% of NdxT2D and 4.6% of IGT at baseline, and in 1.6% of NdxT2D and 5.3% of IGT at 12 months, but no significant associations between GADA(+) and ß-cell function. T(+) was observed in 50% of NdxT2D and 60.4% of IGT at baseline, and in 68.4% of NdxT2D and 83.9% of IGT at 12 months. T(+) NdxT2D were observed to have significantly higher fasting glucose (p = 0.004), and 2 h glucose (p = 0.0032), but significantly lower steady state C-peptide (sscpep, p = 0.007) compared to T(-) NdxT2D. T(+) IGT participants demonstrated lower but not significant (p = 0.025) acute (first phase) C-peptide response to glucose (ACPRg) compared to T(-) IGT. With metformin treatment, T(+) participants were observed to have a significantly lower Hemoglobin A1c (HbA1c, p = 0.002) and fasting C-peptide (p = 0.002) compared to T(-), whereas T(+) treated with liraglutide + metformin had significantly lower sscpep (p = 0.010) compared to T(-) participants. In the placebo group, T(+) participants demonstrated significantly lower ACPRg (p = 0.001) compared to T(-) participants. In summary, T(+) were found in a large percentage of obese pre-diabetes adults with IGT and in recently diagnosed T2D. Moreover, T(+) were significantly correlated with treatment effects and ß-cell dysfunction. Our results demonstrate that T(+) are an important component in T2D.

Genetic Background Behind the Amino Acid Profiles of Fermented Soybeans Produced by Four Bacillus spp.

Strains of four Bacillus spp. were respectively inoculated into sterilized soybeans and the free amino acid profiles of the resulting cultures were analyzed to discern their metabolic traits. After 30 days of culture, B. licheniformis showed the highest production of serine, threonine, and glutamic acid; B. subtilis exhibited the highest production of alanine, asparagine, glycine, leucine, proline, tryptophan, and lysine. B. velezensis increased the γ-aminobutyric acid (GABA) concentration to >200% of that in the control samples. B. sonorensis produced a somewhat similar amino acid profile with B. licheniformis. Comparative genomic analysis of the four Bacillus strains and the genetic profiles of the produced free amino acids revealed that genes involved in glutamate and arginine metabolism were not common to the four strains. The genes gadA/B (encoding a glutamate decarboxylase), rocE (amino acid permease), and puuD (γ-glutamyl-γ-aminobutyrate hydrolase) determined GABA production, and their presence was species-specific. Taken together, B. licheniformis and B. velezensis were respectively shown to have high potential to increase concentrations of glutamic acid and GABA, while B. subtilis has the ability to increase essential amino acid concentrations in fermented soybean foods.

Latent Autoimmune Diabetes in Adults: A Review of Clinically Relevant Issues.

Latent autoimmune diabetes in adults (LADA) is still a poorly characterized entity. However, its prevalence may be higher than that of classical type 1 diabetes. Patients with LADA are often misclassified as type 2 diabetes. The underlying autoimmune process against ß-cell has important consequences for the prognosis, comorbidities, treatment choices and even patient-reported outcomes with this diabetes subtype. However, there is still an important gap of knowledge in many areas of clinical relevance. We are herein focusing on the state of knowledge of relevant clinical issues than may help in the diagnosis and management of subjects with LADA.

Saudi children with celiac disease: are they at risk of developing type-1 diabetes mellitus?

Objectives Patients with type-1 diabetes mellitus (T1DM) and celiac disease (CeD) share the same genetic susceptibility alleles. The diabetes-associated autoantibodies (DAA) may be detected in CeD patients. The aim of this study is to describe the prevalence of DAA in children with CeD. Methods This is a cross-sectional study of children with CeD. The CeD patients were divided into two groups; group 1 (n=23) included patients with isolated CeD and group 2 included patients with combined T1DM and CeD. The study was conducted at King Abdulaziz University Hospital (KAUH) in 2012-2014. DAA, including glutamic acid decarboxylase antibodies (GADA) and protein tyrosine phosphatase-2 antibodies (IA-2), were measured by enzyme-linked immunosorbent assay (ELISA) in both groups. Clinical, demographic, and laboratory data were collected from the patients' medical charts. Results DAA were determined in 23 patients in group-1 and 18 patients in group-2. Group-1 comprised 43.5% males and 56.5% females; the mean age was 15 ± 3.7 years (with a range of 5-18 years). The prevalence of GADA and IA-2 was 69.6 and 4%, respectively. Group-2 comprised 55.6% males and 44.4% females; the mean age was 15.1 ± 2.8 years (with a range of 7-18 years). The prevalence of GADA and IA-2 was 66.7 and 22.2%, respectively. No significant differences were found between both groups in the prevalence of GADA (p=1.0) or IA-2 (p=0.15). Conclusions Saudi children with CeD have higher prevalence of GADA than reported in a number of other Western studies. Long-term follow-up data is required before recommending routine screening for DAA.

Influence of Age on Partial Clinical Remission among Children with Newly Diagnosed Type 1 Diabetes.

Partial clinical remission (PCR) is a transitory period characterized by the residual endogenous insulin secretion following type 1 diabetes (T1D) diagnosis and introducing the insulin therapy. Scientific interest in PCR has been recently increasing, as this phase could be crucial to preserve functional beta cells after T1D onset, also taking advantage of new therapeutic opportunities. The aim of this study was to assess the frequency, duration and associated factors of PCR in children newly diagnosed with T1D. Our cohort study included 167 pediatric patients aged 13.8 ± 4.1 years. The association of clinical and laboratory factors with the occurrence and duration of PCR was evaluated via logistic regression and multivariable generalized linear model, respectively. PCR occurred in 63.5% of the examined patients. Patients who achieved the remission phase were significantly older, and they had lower daily insulin requirement compared with non-remitters. PCR was positively associated to body mass index (OR = 1.11; p = 0.032), pH value (OR 49.02; p = 0.003) and c-peptide levels (OR 12.8; p = 0.002). The average duration of PCR was 13.4 months, and older age at diagnosis was the only predictor factor. Two years after diagnosis remitter patients had lower HbA1c and daily insulin requirement.