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Introduction: The incidence of type-1 diabetes is on the rise, particularly in developed nations, and predominantly affects the youth. While genetic predisposition plays a substantial role, environmental factors, including alterations in the gut microbiota, are increasingly recognized as significant contributors to the disease. Methods: In this study, we utilized germ-free non-obese diabetic mice to explore the effects of microbiota colonization during early life on type-1 diabetes susceptibility. Results: Our findings reveal that microbiota introduction at birth, rather than at weaning, significantly reduces the risk of type-1 diabetes, indicating a crucial window for microbiota-mediated modulation of immune responses. This protective effect was independent of alterations in intestinal barrier function but correlated with testosterone levels in male mice. Additionally, early life colonization modulated T cell subset frequencies, particularly T helper cells and regulatory T cells, in the intestine, potentially shaping type-1 diabetes predisposition. Discussion: Our findings underscore the pivotal role of early-life microbial interactions in immune regulation and the development of autoimmune diseases. [ABSTRACT FROM AUTHOR]

Objective: There are very few reports on the prevalence of diabetic retinopathy (DR) in children and youth with type-1 diabetes (T1D). Studies have also found very low rates of referral for DR screening in children and youth with T1D. We conducted this study to determine the prevalence of DR, to study the reliability of ISPAD screening recommendations and to identify predictors of DR, its progression and regression in Indian children and youth with T1D. Methods: This study included 882 children and youth with T1D. Demographic data, anthropometry, blood pressure, sexual maturity rating, ophthalmological examination (slit lamp for cataract) and biochemical measurements were performed using standard protocols. Fundus images were captured using the Forus Health 3netra classic digital non-mydriatic fundus camera by the same experienced operator. De-identified images were assessed by a senior grader and ophthalmologist (Belfast Ophthalmic Reading Center). Severity of DR was graded as per the UK National Health Service (NHS) DR classification scale. Result: We report 6.4% and 0.2% prevalence of DR and cataract in Indian children and youth with T1D, respectively. All the subjects with DR had early non-proliferative DR. We report that amongst subjects with DR, only 2 subjects were aged less than 11 years and had duration of illness less than 2 years. Presence of hypertension and older age were significant predictors of DR (P <.05). Subjects with DR had significantly higher triglyceride concentrations (P <.05), of these, 6.9% had progression and 2.9% had regression at 1 year follow up; the change in glycaemic control was a significant positive predictor of progression of DR (P <.05). None of the participants included in the study progressed to develop sight-threatening DR. Conclusion: DR is not uncommon in Indian children and youth with T1D, thus screening for DR needs to be initiated early, particularly in older individuals with higher disease duration. Controlling blood pressure and triglyceride concentrations may prevent occurrence of DR. Improving glycaemic control may prevent progression of DR in Indian children and youth with T1D. Plain Language Summary: Diabetic retinopathy in Indian children with Type 1 Diabetes We found that 6.4% and 0.2% Indian children and youth with type-1 diabetes had diabetic retinopathy and cataract respectively. We report that amongst subjects with DR, only 2 subjects were aged less than 11 years and had duration of illness less than 2 years. Thus, International Society for Paediatric and Adolescent Diabetes (ISPAD) screening criteria must be implemented by all centres to avoid missing cases. Presence of high blood pressure, high triglyceride levels and older age were significant predictors of DR. Of the subjects with DR, 6.9% had progression and 2.9% had regression at 1 year follow up; the change in glycaemic control was a significant positive predictor of progression of DR. None of the participants included in the study progressed to develop sight-threatening DR. DR is not uncommon in Indian children and youth with T1D, hence, screening for DR needs to be initiated early, particularly in older individuals with higher disease duration. Controlling blood pressure and triglyceride concentrations may prevent occurrence of DR. Improving glycaemic control may prevent progression of DR in Indian children and youth with T1D. [ABSTRACT FROM AUTHOR]

This study aims to explore the relationship between self-efficacy, emotional autonomy, and diabetic control index in adolescents with type 1 diabetes. From January to September 2023, this cross-sectional study involved 112 adolescents aged 14–18 with type 1 diabetes who were seeking medical check-ups at the Medical Faculty Hospital in Konya, Turkey. Data collection included demographic information, the Diabetes Management Self-Efficacy Scale for Adolescents with Type 1 Diabetes, the Emotional Autonomy Scale, and diabetic control index values based on their most recent Hemoglobin A1c levels measurement. Data analysis was performed using SPSS statistical software, with statistical significance set at a p -value <0.05. The results showed a good overall self-efficacy score, indicating a balanced level of confidence in diabetes management. The emotional autonomy findings revealed a moderate level of independence, emphasizing a healthy process of differentiation from parents while acknowledging them as individuals. The ability of adolescents to openly discuss their diabetes may be associated with more favorable glycemic outcomes. However, high emotional autonomy was significantly associated with high Hemoglobin A1c levels. This study highlights positive outcomes in adolescent diabetes management, with strong self-efficacy and balanced emotional autonomy. Open communication about diabetes correlates with favorable glycemic outcomes, but caution is necessary as high emotional autonomy is linked to elevated Hemoglobin A1c levels. The importance of receiving parental support in managing diabetes, especially in adolescents with high emotional autonomy should be highlighted. • High emotional autonomy was associated with high Hemoglobin A1c levels. • The importance of receiving parental support, especially in adolescents with high emotional autonomy should be highlighted. • The findings underscore the crucial role of open communication, linking it to more favorable glycemic outcomes. [ABSTRACT FROM AUTHOR]

For individuals with Type-1 diabetes mellitus, accurate prediction of future blood glucose values is crucial to aid its regulation with insulin administration, tailored to the individual's specific needs. The authors propose a novel approach for the integration of a neural architecture search framework with deep reinforcement learning to autonomously generate and train architectures, optimized for each subject over model size and analytical prediction performance, for the blood glucose prediction task in individuals with Type-1 diabetes. The authors evaluate the proposed approach on the OhioT1DM dataset, which includes blood glucose monitoring records at 5-min intervals over 8 weeks for 12 patients with Type-1 diabetes mellitus. Prior work focused on predicting blood glucose levels in 30 and 45-min prediction horizons, equivalent to 6 and 9 data points, respectively. Compared to the previously achieved best error, the proposed method demonstrates improvements of 18.4 % and 22.5 % on average for mean absolute error in the 30-min and 45-min prediction horizons, respectively, through the proposed deep reinforcement learning framework. Using the deep reinforcement learning framework, the best-case and worst-case analytical performance measured over root mean square error and mean absolute error was obtained for subject ID 570 and subject ID 584, respectively. Models optimized for performance on the prediction task and model size were obtained after implementing neural architecture search in conjunction with deep reinforcement learning on these two extreme cases. The authors demonstrate improvements of 4.8 % using Long Short Term Memory-based architectures and 5.7 % with Gated Recurrent Units-based architectures for patient ID 570 on the analytical prediction performance by integrating neural architecture search with deep reinforcement learning framework. The patient with the lowest performance (ID 584) on the deep reinforcement learning method had an even greater performance boost, with improvements of 10.0 % and 12.6 % observed for the Long Short-Term Memory and Gated Recurrent Units, respectively. The subject-specific optimized models over performance and model size from the neural architecture search in conjunction with deep reinforcement learning had a reduction in model size which ranged from 20 to 150 times compared to the model obtained using only the deep reinforcement learning method. The smaller size, indicating a reduction in model complexity in terms of the number of trainable network parameters, was achieved without a loss in the prediction performance. [Display omitted] • Novel approach that combines NAS with DRL • Automatically generates architectures to predict future BG levels (Type-1 diabetes) • DRL method achieves significant improvement, surpassing state-of-the-art on OhioT1DM • 18.5 % improvement on MAE and 16.3 % on RMSE for a 30-min prediction horizon • 22.5 % improvement on MAE and 19.5 % on RMSE for a 45-min prediction horizon • Best- and worst-case performance for patient 570 and 584 (30-min prediction horizon) • Further improvements (up to 12.6%) by incorporating Bayesian optimization-based NAS [ABSTRACT FROM AUTHOR]

IntroductionThe incidence of type-1 diabetes is on the rise, particularly in developed nations, and predominantly affects the youth. While genetic predisposition plays a substantial role, environmental factors, including alterations in the gut microbiota, are increasingly recognized as significant contributors to the disease.MethodsIn this study, we utilized germ-free non-obese diabetic mice to explore the effects of microbiota colonization during early life on type-1 diabetes susceptibility.ResultsOur findings reveal that microbiota introduction at birth, rather than at weaning, significantly reduces the risk of type-1 diabetes, indicating a crucial window for microbiota-mediated modulation of immune responses. This protective effect was independent of alterations in intestinal barrier function but correlated with testosterone levels in male mice. Additionally, early life colonization modulated T cell subset frequencies, particularly T helper cells and regulatory T cells, in the intestine, potentially shaping type-1 diabetes predisposition.DiscussionOur findings underscore the pivotal role of early-life microbial interactions in immune regulation and the development of autoimmune diseases.

The classification of diabetes into type-1 (T1D) and type-2 (T2D) is a critical step in tailoring effective treatment strategies. This distinction relies on a nuanced evaluation of clinical and biochemical features. While age at diagnosis, autoimmune markers, and beta-cell function are among the crucial clinical parameters, biochemical indicators like C-peptide levels and antibody analyses play a pivotal role. This review comprehensively examines the utility of these features in accurately categorizing individuals into T1D and T2D subtypes, providing valuable insights for clinical practice. This scoping review systematically analyses 32 studies aimed at classifying T1D and T2D using various predictor variables. Clinical parameters including family history of diabetes, age at diagnosis, sex, history of insulin use, percent desirable weight or body mass index, waist, and blood pressure emerge as pivotal diagnostic tools. C-peptide measures, encompassing urinary C-peptide to creatinine ratio (UCPCR), and serum fasting and stimulated C-peptide levels further augment classification. Biochemical markers beyond C-peptide, such as serum level of adiponectin, triglycerides (TG), high-density lipoprotein–cholesterol (HDL-C), low-density lipoprotein (LDL-C), Total cholesterol, fasting and postprandial plasma glucose, and glycated hemoglobin (HbA1c), provide supplementary information for classification. Ketonuria and postglucagon or meal-stimulated C-peptide measurements contribute to nuanced classification, particularly in insulin-treated populations. Antibody analyses, particularly presence of GAD65, Zinc Transporter, and IA2 antibodies, highlight the autoimmune nature of T1D. In conclusion, this scoping review underscores the importance of a comprehensive approach that integrates clinical, biochemical, and immunological markers in accurately differentiating between T1D and T2D in clinical practice. [ABSTRACT FROM AUTHOR]

Layered nanocarriers are polymeric systems integrated with layers of glucose‐responsive polymers and polyethylene glycol monomethyl ether 2000 PEG2000 to enhance the targeting effect and release kinetics. The prime purpose of this research study is to demonstrate a controlled release of Quercetin from formulation of quercetin (Qu)‐based layered nanocarriers (LNCs) with higher stability and anti‐diabetic activity. The QuLNCs are synthesized using the nanoprecipitation method and optimized by Box‐Behnken design of the Design of Experiment (DoE) method. The Quercetin Nanoparticles (QuNPs) are prepared using Polyvinyl alcohol (PVA) and Poly (D,L‐ lactic‐co‐glycolic acid) (PLGA) polymers where the two layers of Phenylboronic acid (PBA) are conjugated using 3‐amino propyl‐triethoxysilane (APTES) as a functionalizing agent followed by PEGylation of the entire system using PEG2000. The optimized QuLNCs are characterized by various parameters like Particle size (PS), Zeta potential (ZP), % Entrapment efficiency (%EE), Attenuated total reflectance‐ Fourier Transform Infrared Spectroscopy (ATR‐FTIR), Differential scanning Calorimetry (DSC), Transmission electron microscopy (TEM), in vitro as well as in vivo studies. The QuLNCs showed a % entrapment efficiency of 82.846 ± 0.957% and release of 85.04 ± 3.21% of Qu for 24 h from the layered nanocarriers. The in vivo studies of QuLNCs exhibited a significant controlled release of quercetin for modulating blood glucose levels. Hence, these results proved QuLNCs system acts as a favorable approach for the treatment of type 1 diabetes to offer a longer duration of action. [ABSTRACT FROM AUTHOR]

Diabetes is a metabolic disorder due to insufficient insulin synthesis or inadequate insulin sensitivity. The Bergman’s minimal model describes the dynamics of blood glucose levels in type 1 diabetics. The model has control inputs in the form of insulin injections and covers external disturbance factors in the form of meal disturbances. This research developed a control design using an sliding mode adaptive control to reduce blood glucose levels in hyperglycemic patients and keep it within normal glucose levels. Sliding mode adaptive control is an adaptive controller updates the model based on measured performance while in operation. A numerical simulation of the proposed controller is carried out by giving eating disorders three times, namely at breakfast, lunch, and dinner. Based on the numerical simulation, to lower the high blood glucose in the hyperglicemic patient, the insulin injection should be given starting at 30 minutes before breakfast for the next four hour, with a maximal dose of injection is 13 mU/min. It can decrease the high blood pressure until 54.83%.

Background: Chronic uncontrolled hyperglycemia, a precursor to chronic low‐grade inflammation, is a leading cause of coronary artery disease (CAD) due to plaque buildup in type‐1 diabetes (T1D) patients. We evaluated levels of 22 inflammatory markers in cross‐sectional serum samples from 1222 subjects to evaluate their potential as risk factors for CAD in T1D patients. Hypothesis: Circulating levels of markers of inflammation may be the risk factors for incident CAD. Methods: The T1D subjects were divided into two groups: those without CAD (n = 1107) and with CAD (n = 115). Serum levels of proteins were assayed using multiplex immunoassays on a Luminex Platform. Differences between the two groups were made by univariate analysis. Multivariate logistic regression was used to ascertain the potential of proteins as risk factors for CAD. Influence of age, duration of diabetes, sex, hypertension, and dyslipidemia was determined in a stepwise manner. Serum levels of 22 proteins were combined into a composite score using Ridge regression for risk‐based stratification. Results: Mean levels of CRP, IGFBP1, IGFBP2, insulin‐like growth factors binding protein‐6 (IGFBP6), MMP1, SAA, sTNFRI, and sTNFRII were elevated in CAD patients (n = 115) compared to T1D patients without CAD (nCAD, n = 1107). After adjusting for age, duration of diabetes, sex, hypertension, and dyslipidemia, higher levels of sTNFRI (odds ratio [OR] = 2.18, 1.1 × 10−3), sTNFRII (OR = 1.52, 1 × 10−2), and IGFBP6 (OR = 3.62, 1.8 × 10−3) were significantly associated with CAD. The composite score based on Ridge regression, was able to stratify CAD patients into low, medium, and high‐risk groups. Conclusions: The results show activation of the TNF pathway in CAD patients. Evaluating these markers in serum can be a potential tool for identifying high‐risk T1D patients for intensive anti‐inflammatory therapeutic interventions. [ABSTRACT FROM AUTHOR]

T-cell-mediated autoimmune type 1 diabetes (T1D) is characterized by the immune-mediated destruction of pancreatic beta cells (b-cells). The increasing prevalence of T1D poses significant challenges to the healthcare system, particularly in countries with struggling economies. This review paper highlights the multifaceted roles of Peroxisome Proliferator-Activated Receptors (PPARs) in the context of T1D, shedding light on their potential as regulators of immune responses and b-cell biology. Recent research has elucidated the intricate interplay between CD4+ T cell subsets, such as Tregs and Th17, in developing autoimmune diseases like T1D. Th17 cells drive inflammation, while Tregs exert immunosuppressive functions, highlighting the delicate balance crucial for immune homeostasis. Immunotherapy has shown promise in reinstating self-tolerance and restricting the destruction of autoimmune responses, but further investigations are required to refine these therapeutic strategies. Intriguingly, PPARs, initially recognized for their role in lipid metabolism, have emerged as potent modulators of inflammation in autoimmune diseases, particularly in T1D. Although evidence suggests that PPARs affect the b-cell function, their influence on T-cell responses and their potential impact on T1D remains largely unexplored. It was noted that PPARa is involved in restricting the transcription of IL17A and enhancing the expression of Foxp3 by minimizing its proteasomal degradation. Thus, antagonizing PPARs may exert beneficial effects in regulating the differentiation of CD4+ T cells and preventing T1D. Therefore, this review advocates for comprehensive investigations to delineate the precise roles of PPARs in T1D pathogenesis, offering innovative therapeutic avenues that target both the immune system and pancreatic function. This review paper seeks to bridge the knowledge gap between PPARs, immune responses, and T1D, providing insights that may revolutionize the treatment landscape for this autoimmune disorder. Moreover, further studies involving PPAR agonists in non-obese diabetic (NOD) mice hold promise for developing novel T1D therapies. [ABSTRACT FROM AUTHOR]

Cell-based therapy is an attractive approach, and encapsulation of therapeutic cells is a promising strategy because it prevents immune responses and allows transplanted cells to be retrieved in case of dysfunction. Bioartificial pancreas, in which insulin-secreting cells are encapsulated in a semipermeable membrane bag, is a new class of medical device for treating type-I diabetes. In this study, we developed a macroencapsulation device in which the pancreatic beta cell line MIN6 was encapsulated in a semipermeable bag made of an ethylene-vinyl alcohol copolymer membrane. In vitro evaluation of ATP and insulin levels revealed that MIN6 cells grown in Matrigel within the device secreted insulin in response to glucose levels. Transplantation of the device lowered blood glucose levels for 30 days in diabetic mice. Histological observation revealed that MIN6 cells formed spheroids in Matrigel, and no host cells were detected within the device. Blood levels of inflammatory cytokines in the transplanted mice were similar to those in non-transplanted mice, and antibody levels in the device were lower than those in the intraperitoneal fluid. These results suggest that the semipermeable ethylene-vinyl alcohol copolymer membrane developed in this study is useful for cell encapsulation in cell-based therapies, including beta-cell macroencapsulation for type-1 diabetes. [Display omitted] [ABSTRACT FROM AUTHOR]

Disorders of pubertal development are enlisted as associated conditions in children and adolescents with type-1 diabetes (T1D). We conducted this study with objective (1) To estimate the median age at onset of puberty and luteinizing hormone (LH) and sex-steroid concentrations in Indian adolescents with T1D and (2) To assess the impact of puberty on glycemic control and insulin resistance (IR). This cross-sectional study included 399 children and youth aged 6–23 years with T1D. Demographic, anthropometric, biochemical and pelvic ultrasound data were collected using standard protocols. IR was calculated using estimated glucose disposal rate and puberty was assessed using Tanner staging. Median age at onset of thelarche, pubarche and menarche were 11.3, 11.4 and 12.8 years in girls and that of gonadarche and pubarche were 10.6 and 12.7 years for boys. The mean LH and sex-steroid concentrations of subjects with T1D were similar to healthy subjects at each stage of puberty. The cut-offs of LH and sex-steroids derived from healthy Indian children yielded high sensitivity and specificity in determining pubertal onset. The prevalence of precocity, delayed puberty, ovarian cysts and polycystic ovaries was 0.9 , 5.1, 5.1 and 8.6 %, respectively. Glycaemic control and insulin sensitivity was poor in pubertal subjects. The age at onset of puberty, LH, and sex-steroid concentrations in subjects with T1D were like otherwise healthy Indian children with poor glycemic control and IR in pubertal subjects. Although most complications of T1D are associated with poor glycemic control, pubertal disorders were significantly low despite the less-than-optimal glycemic control. [ABSTRACT FROM AUTHOR]

Abstract Background Knowledge of the characteristics of first-ever cardiovascular events in type 1 diabetes may impact primary prevention strategies. This study describes the first-ever manifestation of cardiovascular disease (CVD) in patients with type 1 diabetes (T1D) in Catalonia (Spain) and evaluates differences according to age and sex. Methods Retrospective cohort study of patients with T1D > 30 years without CVD before 2010 registered in the SIDIAP database. The occurrence of a first cardiovascular event up to the end of 2016, the type of CV event and associations with baseline characteristics were analysed. Results Of 8412 patients, 884 suffered a first CV event (incidence rate 1.62 per 100 persons-years). Overall, peripheral vascular disease (39.5%) was the most frequent event. We observed a higher proportion of heart failure in women (21.7%) than in men (10.1%). In women, heart failure was the most frequent event in those > 65 years (40.5%). Decreased glomerular filtration rate (hazard ratio [HR] 5.42 [95% CI 4.32;6.80]), elevated albumin/creatinine ratio (HR 3.39 [95% CI [2.47;4.66], microvascular complications (HR 3.27 [95% CI 2.85;3.75]), and hypertension (HR 3.21 [95% CI [2.80;3.67]) were most strongly associated with a first CV event. HbA1c > 7.0% was associated with incident CVD only in patients aged

T-cell-mediated autoimmune type 1 diabetes (T1D) is characterized by the immune-mediated destruction of pancreatic beta cells (β-cells). The increasing prevalence of T1D poses significant challenges to the healthcare system, particularly in countries with struggling economies. This review paper highlights the multifaceted roles of Peroxisome Proliferator-Activated Receptors (PPARs) in the context of T1D, shedding light on their potential as regulators of immune responses and β-cell biology. Recent research has elucidated the intricate interplay between CD4+ T cell subsets, such as Tregs and Th17, in developing autoimmune diseases like T1D. Th17 cells drive inflammation, while Tregs exert immunosuppressive functions, highlighting the delicate balance crucial for immune homeostasis. Immunotherapy has shown promise in reinstating self-tolerance and restricting the destruction of autoimmune responses, but further investigations are required to refine these therapeutic strategies. Intriguingly, PPARs, initially recognized for their role in lipid metabolism, have emerged as potent modulators of inflammation in autoimmune diseases, particularly in T1D. Although evidence suggests that PPARs affect the β-cell function, their influence on T-cell responses and their potential impact on T1D remains largely unexplored. It was noted that PPARα is involved in restricting the transcription of IL17A and enhancing the expression of Foxp3 by minimizing its proteasomal degradation. Thus, antagonizing PPARs may exert beneficial effects in regulating the differentiation of CD4+ T cells and preventing T1D. Therefore, this review advocates for comprehensive investigations to delineate the precise roles of PPARs in T1D pathogenesis, offering innovative therapeutic avenues that target both the immune system and pancreatic function. This review paper seeks to bridge the knowledge gap between PPARs, immune responses, and T1D, providing insights that may revolutionize the treatment landscape for this autoimmune disorder. Moreover, further studies involving PPAR agonists in non-obese diabetic (NOD) mice hold promise for developing novel T1D therapies.

Background: A previous study compared insulin sensitivity indices for the detection of double diabetes (DD) in Indian adolescents with type-1 diabetes (T1D) and derived a cut-off to predict future risk for the development of metabolic syndrome (MS) in adolescents with T1D. We conducted the current study with the aim to validate these cut-offs for detecting DD among Indian subjects with T1D from various geographical locations. Methods: This multicentric cross-sectional study included 161 Indian adolescents with T1D. Demographic, anthropometric, clinical, and biochemical data were collected using standard protocols. Insulin sensitivity (IS) was calculated using various equations developed to determine insulin sensitivity in subjects with T1D. Metabolic syndrome was diagnosed using International Diabetes Federation (IDF) Consensus Definition 2017. Results: We report 4.3% prevalence of MS in Indian adolescents with T1D with an additional 29.8% of study participants at risk of development of MS. Low High density lipoprotein (HDL) (23.6%) was the commonest abnormal component of the MS definition. Insulin sensitivity calculated by an equation derived by the SEARCH group was the most appropriate index to identify MS and metabolic risk in Indian adolescents with T1D. The proposed cut-off of 5.48 had high specificity, positive predictive value, and negative predictive value in identifying the risk of the development of DD. Conclusions: Insulin sensitivity calculated by the equation proposed by the SEARCH group together with cut-offs derived in earlier study may be used effectively to identify risk of development of MS/DD in Indian adolescents with T1D from various geographical locations. [ABSTRACT FROM AUTHOR]

To assess the relationship of apolipoproteins with glycemic control and insulin resistance (IR) in Indian children and youth with type-1 diabetes (T1D) and to assess its utility in predicting metabolic risk (MR) and microvascular complications in these subjects. This cross-sectional study included 152 participants aged 6–23 years with T1D. Demographic, anthropometric, clinical, biochemical and body composition data were obtained using standard protocols. IR was calculated using estimated glucose disposal rate (eGDR) and metabolic syndrome (MS) was diagnosed using the international diabetes federation consensus definition 2017. Apolipoprotein ratio in subjects with T1D had negative and positive correlation with eGDR and HbA1c respectively. Positive correlation of Apolipoproten B and apolipoprotein ratio with urinary albumin creatinine ratio is noted. The ratio had area under curve of 0.766 and 0.737 to predict MR and microvascular complications respectively. The ratio cut-off of 0.536 yielded 77.1 % sensitivity and 61 % specificity to predict MR. On adding the apolipoprotein ratio as a predictor to the regression model developed to predict MR, the R2 and accuracy improved. The apolipoprotein ratio had significant correlation with IR, microalbuminuria and glycaemic control. The ratio also predicts risk of development of microvascular complications and maybe used to predict MR in subjects with T1D. [ABSTRACT FROM AUTHOR]

Background: India has the highest number of prevalent type-1 diabetes (T1D) cases in the under-20-year age population. Data on the anthropometry of underprivileged Indian children with T1D are scarce. In economically disadvantaged countries like India, poor growth in patients with T1D is a major concern due to limited accessibility and affordability. Besides, due to the double burden of malnutrition, the prevalence of obesity is increasing mirroring the global trends, which may lead to the development of insulin resistance. Objectives: This study aims to assess the prevalence of malnutrition in Indian children and youth with T1D and to identify the determinants of short stature. Methods: A registry-based cross-sectional analysis of data collected from various centres across India enrolled in the Changing Diabetes in Children (CDiC) programme. Results: We observed that 6.4% were undernourished (3.4% severe undernutrition) and 17.7% (overweight 13.2%) had combined overweight/obesity. 21.2% of participants had short stature (adjusted for mid-parental height) with 7.4% cases of familial short stature. Longer duration of illness and insulin requirement were significant positive predictors of short stature while glycaemic control, insulin regimen and mid-parental height did not have a significant relationship with short stature. Participants on basal-bolus regimen had significantly higher insulin requirements and better glycaemic control than the ones on mixed-split regimen. Conclusion: We report that around one-fifth of children and youth with T1D were overweight/obese and around a fourth were stunted, especially those with longer duration of diabetes and higher insulin requirements. Close monitoring of anthropometric parameters is necessary for all children with T1D to optimize growth and nutrition. [ABSTRACT FROM AUTHOR]

Introduction: Increased prevalence of metabolic syndrome in Indian adolescents owing to the obesity epidemic leads to double diabetes (DD), which is associated with an increased risk of complications in type-1 diabetes (T1D). Metformin may be a useful intervention for the prevention and treatment of insulin resistance in T1D. We conducted this pilot randomized controlled trial with the objective of investigating the effect of metformin on insulin sensitivity in Indian adolescents with T1D. Method: This pilot randomized controlled trial was performed on 59 participants with T1D aged 10-19 years distributed uniformly by gender and puberty across two groups with a 3-month intervention period. The intervention group received metformin (weight less than 60 kg received 500 mg twice daily and more than 60 kg received 1 gm twice daily) and non-metformin group received standard of care for diabetes. Anthropometric, clinical details, biochemistry and insulin sensitivity indices (ISI) were evaluated using standard protocols at baseline and endline. Result: 22.2% of subjects from non-metformin group and 12.5% from metformin group were at the risk of the development of DD. The odds ratio and relative risk for the development of DD in non-metformin subjects were 2.0 and 1.4, respectively, as compared to participants in metformin group. The mean improvement in ISI ranged from 1.4% to 4.6% in participants on metformin as opposed to deterioration of -2% to -14.1% in non-metformin group. On performing the paired sample t-test, the reduction in ISI in non-metformin group was significant. Conclusion: Metformin may prevent deterioration in insulin sensitivity in Indian adolescents with T1D. [ABSTRACT FROM AUTHOR]

Meta-analysis studying the role of verapamil in improving C-peptide in people with recent-onset type-1 diabetes (T1DM) has not been conducted to date. We undertook this meta-analysis to address this knowledge gap. Electronic databases were systematically reviewed for RCTs having individuals with T1DM receiving verapamil in the treatment arm and placebo in the control arm over the standard of care. The primary outcome was to evaluate changes in the C-peptide area under the curve (AUC) at a one-year follow-up. Secondary outcomes were to assess alterations in C-peptide AUC, glycated hemoglobin (HbA1c), blood pressure, heart rate, and side effects at different time intervals over a one-year follow-up. From the initially screened 27 articles, data from two RCTs (112 patients) satisfied the inclusion criteria and were analyzed. Compared to placebo, C-peptide AUC in individuals receiving verapamil was not different at three months [MD 0.17 nmol/L (95%CI: -0.05-0.38); P = 0.13; I2 = 86%] but significantly higher at 1-year [MD 0.27 nmol/L (95%CI: 0.19-0.35); P < 0.01; I2 = 12%]. The verapamil arm showed similar changes in HbA1C at three months [MD 0.23% (95%CI: -0.43-0.90); P = 0.49; I2 = 88%] and 1-year [MD 0.18% (95% CI: -0.74 - 1.10); P = 0.70; I2 = 89%] compared to placebo. Occurrence of treatment-emergent adverse events [Risk ratio (RR) 1.90 (95%CI: 0.52-6.91); P = 0.33; I2 = 63%], serious adverse events [RR 1.40 (95%CI: 0.50-3.93); P = 0.53], constipation [RR4.11 (95%CI: 0.93-18.13); P = 0.06; I2 = 0%], headache [RR0.48 (95%CI: 0.16-1.43); P = 0.19; I2 = 0%], severe hypoglycemia [RR 0.87 (95%CI: 0.06 - 13.51); P = 0.92] were comparable across groups. Verapamil was well tolerated, and its use over one year was associated with significant improvements in C-peptide AUC though the HbA1c remained unchanged. [ABSTRACT FROM AUTHOR]

Introduction: The JAK/STAT signaling pathway is an important pathway used by cytokines and its excessive activation can lead to various diseases. This signaling pathway is essential for normal homeostasis. Dysregulation of this pathway contributes to the development of obesity and diabetes. This study aimed to investigate the effect of six weeks of endurance running exercises on the gene expression of the JAK1/STAT3 pathway in the basal ganglia of diabetic rats. Methods: In this experimental study, 40 male rats were randomly divided into four equal Healthy, Exercise, Diabetes, and Diabetes + Exercise groups. Diabetes was induced by a single intraperitoneal injection of streptozotocin (STZ, 50 mg/kg body weight). The incremental endurance exercise program was gradually implemented for six weeks, and five sessions per week. The first week started with a speed of 10 m/min for 10 minutes, and by the sixth week, it reached a speed of 18 m/min for 30 minutes. Forty-eight hours after the last exercise session, the rats were anesthetized and the brain tissue was removed from the skull to extract the basal ganglia. The extracted tissue was used to measure gene expression by the qPCR method. One-way ANOVA and LSD post hoc test were used to check the between-group differences. The significance level was considered smaller than 0.05. Results: Type-1 diabetes induction did not change JAK1/STAT3 gene expression in basal ganglia (P>0.05). The endurance exercise program decreased the gene expression values of JAK1 (P=0.009) and STAT3 (P=0.002) compared to the diabetes group. This decrease had a similar process for both genes. Conclusion: In the present study, six weeks of endurance running on the treadmill with moderate intensity decreased the gene expression of the JAK1/STAT3 pathway. Therefore, this exercise protocol can be suggested as a non-pharmacological tool without side effects to inhibit this pathway in diabetes to protect basal ganglia neurons. [ABSTRACT FROM AUTHOR]

Meta-analysis studying the role of verapamil in improving C-peptide in people with recent-onset type-1 diabetes (T1DM) has not been conducted to date. We undertook this meta-analysis to address this knowledge gap. Electronic databases were systematically reviewed for RCTs having individuals with T1DM receiving verapamil in the treatment arm and placebo in the control arm over the standard of care. The primary outcome was to evaluate changes in the C-peptide area under the curve (AUC) at a one-year follow-up. Secondary outcomes were to assess alterations in C-peptide AUC, glycated hemoglobin (HbA1c), blood pressure, heart rate, and side effects at different time intervals over a one-year follow-up. From the initially screened 27 articles, data from two RCTs (112 patients) satisfied the inclusion criteria and were analyzed. Compared to placebo, C-peptide AUC in individuals receiving verapamil was not different at three months [MD 0.17 nmol/L (95%CI: -0.05-0.38); P = 0.13; I2 = 86%] but significantly higher at 1-year [MD 0.27 nmol/L (95%CI: 0.19–0.35); P < 0.01; I2 = 12%]. The verapamil arm showed similar changes in HbA1C at three months [MD 0.23% (95%CI: -0.43–0.90); P = 0.49; I2 = 88%] and 1-year [MD 0.18% (95% CI: -0.74 – 1.10); P = 0.70; I2 = 89%] compared to placebo. Occurrence of treatment-emergent adverse events [Risk ratio (RR) 1.90 (95%CI: 0.52–6.91); P = 0.33; I2 = 63%], serious adverse events [RR 1.40 (95%CI: 0.50–3.93); P = 0.53], constipation [RR4.11 (95%CI: 0.93–18.13); P = 0.06; I2 = 0%], headache [RR0.48 (95%CI: 0.16–1.43); P = 0.19; I2 = 0%], severe hypoglycemia [RR 0.87 (95%CI: 0.06 – 13.51); P = 0.92] were comparable across groups. Verapamil was well tolerated, and its use over one year was associated with significant improvements in C-peptide AUC though the HbA1c remained unchanged.

Introduction: Increased prevalence of metabolic syndrome in Indian adolescents owing to the obesity epidemic leads to double diabetes (DD), which is associated with an increased risk of complications in type-1 diabetes (T1D). Metformin may be a useful intervention for the prevention and treatment of insulin resistance in T1D. We conducted this pilot randomized controlled trial with the objective of investigating the effect of metformin on insulin sensitivity in Indian adolescents with T1D. Method: This pilot randomized controlled trial was performed on 59 participants with T1D aged 10–19 years distributed uniformly by gender and puberty across two groups with a 3-month intervention period. The intervention group received metformin (weight less than 60 kg received 500 mg twice daily and more than 60 kg received 1 gm twice daily) and non-metformin group received standard of care for diabetes. Anthropometric, clinical details, biochemistry and insulin sensitivity indices (ISI) were evaluated using standard protocols at baseline and endline. Result: 22.2% of subjects from non-metformin group and 12.5% from metformin group were at the risk of the development of DD. The odds ratio and relative risk for the development of DD in non-metformin subjects were 2.0 and 1.4, respectively, as compared to participants in metformin group. The mean improvement in ISI ranged from 1.4% to 4.6% in participants on metformin as opposed to deterioration of -2% to -14.1% in non-metformin group. On performing the paired sample t-test, the reduction in ISI in non-metformin group was significant. Conclusion: Metformin may prevent deterioration in insulin sensitivity in Indian adolescents with T1D.

Background: India has the highest number of prevalent type-1 diabetes (T1D) cases in the under-20-year age population. Data on the anthropometry of underprivileged Indian children with T1D are scarce. In economically disadvantaged countries like India, poor growth in patients with T1D is a major concern due to limited accessibility and affordability. Besides, due to the double burden of malnutrition, the prevalence of obesity is increasing mirroring the global trends, which may lead to the development of insulin resistance. Objectives: This study aims to assess the prevalence of malnutrition in Indian children and youth with T1D and to identify the determinants of short stature. Methods: A registry-based cross-sectional analysis of data collected from various centres across India enrolled in the Changing Diabetes in Children (CDiC) programme. Results: We observed that 6.4% were undernourished (3.4% severe undernutrition) and 17.7% (overweight 13.2%) had combined overweight/obesity. 21.2% of participants had short stature (adjusted for mid-parental height) with 7.4% cases of familial short stature. Longer duration of illness and insulin requirement were significant positive predictors of short stature while glycaemic control, insulin regimen and mid-parental height did not have a significant relationship with short stature. Participants on basal-bolus regimen had significantly higher insulin requirements and better glycaemic control than the ones on mixed-split regimen. Conclusion: We report that around one-fifth of children and youth with T1D were overweight/obese and around a fourth were stunted, especially those with longer duration of diabetes and higher insulin requirements. Close monitoring of anthropometric parameters is necessary for all children with T1D to optimize growth and nutrition.

Interleukin-1 antagonism is a proposed biomarker and potential therapy for the delay and/or treatment of type 1 diabetes (T1D). We evaluated the role of circulating interleukin-1 receptor antagonist (IL-1ra) in a prospectively monitored cohort of T1D patients. In order to determine a mechanistic association between IL-1ra and T1D, we performed co-localization analyses between serum IL-1ra protein quantitative trait loci and T1D genome-wide analysis studies. Adjusting for human leukocyte antigen (HLA) genotypes, first degree relative status, gender, and age, serum levels of IL-1ra were lower in subjects who progressed to T1D compared to the controls (p = 0.023). Our results suggest that females have higher levels of IL-1ra compared to males (p = 0.005). The 2q14.1 region associated with serum IL-1ra levels is not associated with a risk of developing T1D. Our data suggest that IL-1 antagonism by IL-1ra is not an effective therapy in T1D, but IL-1ra may be a biomarker for progression to T1D.

Objective: Isolated pancreatic islets are valuable resources for a wide range of research, including cell replacementstudies and cell-based platforms for diabetes drug discovery and disease modeling. Islet isolation is a complex and stepwise procedure aiming to obtain pure, viable, and functional islets for in vitro and in vivo studies. It should be notedthat differences in rodent strains, gender, weight, and density gradients may affect the isolated islet’s properties. We evaluated the variables affecting the rat islet isolation procedure to reach the maximum islet yield and functionality, which would be critical for further studies on islet regenerative biology.Materials and Methods: The present experimental study compared the yield and purity of isolated islets from nondiabetic rats of two different strains. Next, islet particle number (IPN) and islet equivalent (IEQ) were compared between males and females, and the weight range that yields the highest number of islets was investigated. Moreover, the influence of three different density gradients, namely Histopaque, Pancoll, and Lymphodex, on final isolated islets purity and yield were assessed. Finally, the viability and functionality of isolated islets were measured.Results: The IEQ, IPN, and purity of isolated islets in 15 Lister hooded rats (LHRs) were significantly (P≤0.05) higher thanthose of the other strains. Male LHRs resulted in significantly higher IEQ compared to females (P≤0.05). Moreover, IPN and IEQ did not significantly vary among different weight groups. Also, the utilization of Histopaque and Pancoll leads to higher yield and purity. In vivo assessments of the isolated islets presented significantly reduced blood glucose percentage in the transplanted group on days 2-5 following transplantation.Conclusion: Based on these results, an optimal protocol for isolating high-quality rat islets with a constant yield, purity,and function has been established as an essential platform for developing diabetes research.

INTRODUCTION: Diabetic ketoacidosis (DKA) - a potentially preventable complication of type 1 diabetes mellitus (T1D) - is one of the most common chronic childhood diseases, and is associated with a significant risk of morbidity and mortality. The limited use of healthcare services due to fear of Coronavirus disease-2019 (COVID-19) transmission during the pandemic has raised concerns of delays in T1D diagnosis, among other diseases. This study investigated the presenting characteristics of newly diagnosed T1D patients assessed in a single clinic during the pandemic and compares them with the pre-pandemic period. METHODS: For the purpose of this study, the first year of the pandemic is referred to as the 'pandemic period', and the previous three years as the 'pre-pandemic period'. Patient files were reviewed retrospectively, the demographic and clinical characteristics and laboratory findings of the patients were recorded, and the findings from both periods were compared. RESULTS: The number of patients diagnosed with T1D in the pandemic period was 44, and in the pre-pandemic period 39 in 2017, 22 in 2018 and 18 in 2019. The two groups had similar age, sex, pubertal stage and anthropometric characteristics (p>0.05). Regarding the type of presentation, the frequency of DKA was significantly higher in the pandemic period (68.2%) than in the pre-pandemic period (40.5%) (p=0.006), and this difference was also observed in the comparison by years (p=0.016). The duration of symptoms (16.5+-10.7 vs. 23.5+-17.6 days) and the length of hospital stay (10+-3.9 vs. 15.2+-5.5 days) were significantly shorter in the pandemic period (p=0.032, and p0.05). However, pH (7.17+-0.16 vs. 7.26+-0.14) and bicarbonate (12.8+-6.3 vs. 16.6+-6.3) levels were significantly lower in the pandemic period (p0.05). The rate of anti-glutamic acid decarboxylase positivity was higher in the pandemic period (73.8% vs. 39.2%) (p=0.001) while the frequency of other diabetes-associated autoantibodies was similar between the groups (p>0.05). The polymerase chain reaction test for COVID-19 was negative in six patients with a history of contact. DISCUSSION AND CONCLUSION: There was an increased frequency and severity of DKA in children with newly diagnosed T1D in the pandemic period, and these findings justify concerns related to the diagnosis of other diseases during the pandemic. Studies to raise awareness of diabetes symptoms during the pandemic should be continued regularly to reach all segments of society. Our study provides an additional contribution to the literature in its coverage of the one-year period during the pandemic and its comparison with the previous three years.

Aim: This study aimed to establish the dose of streptozotocin required to induce Type -1 diabetes in Wistar rats. Background: Streptozotocin is currently employed worldwide to induce insulin-dependent diabetes mellitus also known as Type 1 diabetes mellitus in experimental animals. Though many reports on the use of streptozotocin induction of diabetes are reported in the literature, they were not reproducible. Moreover, there was no mention of the mortality associated with the same as well as the conditions followed during the study. Materials and Methods: In the present study, the dose, route, and solvent used for streptozotocin were investigated. Various doses of streptozotocin 55, 50, 40, and 35mg/kg dissolved in either freshly prepared cold 10mM sodium citrate buffer (pH 4.5) or normal saline solution was administered intraperitoneally as well as intravenously. For intraperitoneal administration, the dose-volume was 10mL/kg whereas for intravenous administration the dose-volume was 2mL/Kg. Different routes were employed to ascertain the cause of mortality for which an autopsy was performed. Besides mortality rate was also determined. Results and Discussion: The findings of the study revealed that a 35-40mg/kg dose of streptozotocin showed less percentage mortality and successful induction of diabetes. Conclusion: Mortality (10-20%) was observed at a dose of 35-40mg/kg streptozotocin. Therefore, streptozotocin (35-40mg/kg) was confirmed to be safe and effective for the induction of diabetes in Wistar rats. This paper highlights subtle intricacies observed during induction of diabetes in Wistar rats using streptozotocin. [ABSTRACT FROM AUTHOR]

Introduction Diabetes mellitus is still a raging disease not fully subdued globally, especially in Africa. Our study aims to evaluate the anti-diabetic potentials of Justicia carnea extracts [crude (JCC), free (JFP) and bound phenol (JBP) fractions], in streptozotocin (STZ)-induced type-1 diabetes in male albino rats. Materials and Methods About thirty (30) animals were induced for type 1 diabetes with STZ; thereafter, treatment began for 14 days, after which the animals were euthanized, blood/serum was collected, the liver was removed and divided into two portions, for biochemical and histopathological analyses. Standard procedures were used to evaluate the liver biomarkers, like alanine transaminase (ALT), fructose-1,6-bisphosphatase, glucose-6- phosphatase, hexokinase activities, albumin, bilirubin, hepatic glucose concentrations; antioxidant status and pro- and anti-inflammatory cytokines were similarly assessed. Results These results revealed that the extracts ameliorated the harmful effects of STZ-induced diabetes in the liver by enhancing the activities of liver-based biomarkers, reducing the concentrations of pro-inflammatory cytokines and increasing the anti-inflammatory cytokine. Discussion The results agreed with previous research, and the free phenol fraction showed excellent results compared to others Conclusion These suggested that J. carnea could serve as an alternative remedy in ameliorating liver complications linked to oxidative damage and inflammation in STZ-induced type-1 diabetes. [ABSTRACT FROM AUTHOR]

During the last decade, a rising interest in novel functional products containing probiotic microorganisms has been witnessed. As food processing and storage usually lead to a reduction of cell viability, freeze-dried cultures and immobilization are usually recommended in order to maintain adequate loads and deliver health benefits. In this study, freeze-dried (free and immobilized on apple pieces) Lacticaseibacillus rhamnosus OLXAL-1 cells were used to fortify grape juice. Juice storage at ambient temperature resulted in significantly higher (>7 log cfu/g) levels of immobilized L. rhamnosus cells compared to free cells after 4 days. On the other hand, refrigerated storage resulted in cell loads > 7 log cfu/g for both free and immobilized cells for up to 10 days, achieving populations > 109 cfu per share, with no spoilage noticed. The possible resistance of the novel fortified juice products to microbial spoilage (after deliberate spiking with Saccharomyces cerevisiae or Aspergillus niger) was also investigated. Significant growth limitation of both food-spoilage microorganisms was observed (both at 20 and 4 °C) when immobilized cells were contained compared to the unfortified juice. Keynote volatile compounds derived from the juice and the immobilization carrier were detected in all products by HS-SPME GC/MS analysis. PCA revealed that both the nature of the freeze-dried cells (free or immobilized), as well as storage temperature affected significantly the content of minor volatiles detected and resulted in significant differences in the total volatile concentration. Juices with freeze-dried immobilized cells were distinguished by the tasters and perceived as highly novel. Notably, all fortified juice products were accepted during the preliminary sensory evaluation. [ABSTRACT FROM AUTHOR]

The present study aimed at investigating the possible benefits of a dietary intervention with Corinthian currants, a rich source of phenolic compounds, on type 1 diabetes (T1D) using the animal model of the streptozotocin-(STZ)-induced diabetic rat. Male Wistar rats were randomly assigned into four groups: control animals, which received a control diet (CD) or a diet supplemented with 10% w/w Corinthian currants (CCD), and diabetic animals, which received a control diet (DCD) or a currant diet (DCCD) for 4 weeks. Plasma biochemical parameters, insulin, polar phenolic compounds, and inflammatory factors were determined. Microbiota populations in tissue and intestinal fluid of the caecum, as well as fecal microbiota populations and short-chain fatty acids (SCFAs), were measured. Fecal microbiota was further analyzed by 16S rRNA sequencing. The results of the study showed that a Corinthian currant-supplemented diet restored serum polar phenolic compounds and decreased interleukin-1b (IL-1b) (p < 0.05) both in control and diabetic animals. Increased caecal lactobacilli counts (p < 0.05) and maintenance of enterococci levels within normal range were observed in the intestinal fluid of the DCCD group (p < 0.05 compared to DCD). Higher acetic acid levels were detected in the feces of diabetic rats that received the currant diet compared to the animals that received the control diet (p < 0.05). Corinthian currant could serve as a beneficial dietary component in the condition of T1D based on the results coming from the animal model of the STZ-induced T1D rat. [ABSTRACT FROM AUTHOR]

Australia has a high prevalence of diabetes, with approximately 1.2 million Australians diagnosed with the disease. In 2012, the Australasian Diabetes Data Network (ADDN) was established with funding from the Juvenile Diabetes Research Foundation (JDRF). ADDN is a national diabetes registry which captures longitudinal information about patients with type-1 diabetes (T1D). Currently, the ADDN data are directly contributed from 42 paediatric and 17 adult diabetes centres across Australia and New Zealand, i.e., where the data are pre-existing in hospital systems and not manually entered into ADDN. The historical data in ADDN have been de-identified, and patients are initially afforded the opportunity to opt-out of being involved in the registry; however, moving forward, there is an increased demand from the clinical research community to utilise fully identifying data. This raises additional demands on the registry in terms of security, privacy, and the nature of patient consent. General Data Protection Regulation (GDPR) is an increasingly important mechanism allowing individuals to have the right to know about their health data and what those data are being used for. This paper presents a mobile application being designed to support the ADDN data collection and usage processes and aligning them with GDPR. The app utilises Dynamic Consent—an informed specific consent model, which allows participants to view and modify their research-driven consent decisions through an interactive interface. It focuses specifically on supporting dynamic opt-in consent to both the registry and to associated sub-projects requesting access to and use of the patient data for research purposes. [ABSTRACT FROM AUTHOR]

Background/Aim: Diabetes mellitus is a debilitating disease still prevailing in the developing world. This study aimed to examine the protective potentials of Cymbopogon citratus extracts (crude (CCC), free (CFP), and bound phenol (CBP) fractions), in streptozotocin (STZ)-induced type 1 diabetic male rats. Methods: Forty-five (45) animals of about 3–4 months were used for the study. About forty animals were induced with STZ. After induction and confirmation of diabetes, animals were grouped (five animals per group) into nine groups; group 1 (Control), group 2 received 50 mg/kg body weight (bw) (STZ). Groups 3, 4 and 5 were healthy animals and received C. citratus extracts (200 mg/kg bw CCC, 100 mg/kg bw CFP, and 100 mg/kg bw CBP) respectively; while groups 6 – 9 were diabetic group (induced with STZ) and later treated with C. citratus extracts (200 mg/kg bw CCC, 100 mg/kg bw CFP, 100 mg/kg bw CBP, and metformin (200 mg/kg bw) respectively for 14 days. Then, the animals were euthanized, blood/serum was collected, liver samples were collected and divided into two; for biochemical and histopathological studies. Liver biomarkers (ALT, AST, ALP, GGT), fructose-1,6-bisphosphatase, hexokinase, antioxidant enzymes (SOD, CAT, and GST) activities, albumin, bilirubin, hepatic glucose, GSH, MDA, pro-and anti-inflammatory cytokines concentrations, were estimated using standard protocols. Results: Our results revealed that C. citratus extracts counteracted the deleterious effects of type 1 diabetes induction with STZ by optimizing the liver biomarkers, antioxidants enzymes, MDA and GSH levels, reducing the levels of pro-inflammatory cytokines and increasing anti-inflammatory. Conclusion: Our results correlated with previous researches; the free phenols fraction revealed brilliant results above others. These suggested that C. citratus could serve as an alternative therapy in ameliorating liver complications linked to oxidative damage and inflammation in STZ-induced type-1 diabetes.

Exogenous insulin therapy is the mainstay treatment for Type-1 diabetes (T1D) caused by insulin deficiency. A fine-tuned insulin supply system is important to maintain the glucose homeostasis. In this study, we present a designed cell system that produces insulin under an AND gate control, which is triggered only in the presence of both high glucose and blue light illumination. The glucose-sensitive GIP promoter induces the expression of GI-Gal4 protein, which forms a complex with LOV-VP16 in the presence of blue light. The GI-Gal4:LOV-VP16 complex then promotes the expression of UAS-promoter-driven insulin. We transfected these components into HEK293T cells, and demonstrated the insulin was secreted under the AND gate control. Furthermore, we showed the capacity of the engineered cells to improve the blood glucose homeostasis through implantation subcutaneously into Type-1 diabetes mice.

Type 1 diabetes (T1D) outcome prediction plays a vital role in identifying novel risk factors, ensuring early patient care and designing cohort studies. TEDDY is a longitudinal cohort study that collects a vast amount of multi-omics and clinical data from its participants to explore the progression and markers of T1D. However, missing data in the omics profiles make the outcome prediction a difficult task. TEDDY collected time series gene expression for less than 6% of enrolled participants. Additionally, for the participants whose gene expressions are collected, 79% time steps are missing. This study introduces an advanced bioinformatics framework for gene expression imputation and islet autoimmunity (IA) prediction. The imputation model generates synthetic data for participants with partially or entirely missing gene expression. The prediction model integrates the synthetic gene expression with other risk factors to achieve better predictive performance. Comprehensive experiments on TEDDY datasets show that: (1) Our pipeline can effectively integrate synthetic gene expression with family history, HLA genotype and SNPs to better predict IA status at 2 years (sensitivity 0.622, AUC 0.715) compared with the individual datasets and state-of-the-art results in the literature (AUC 0.682). (2) The synthetic gene expression contains predictive signals as strong as the true gene expression, reducing reliance on expensive and long-term longitudinal data collection. (3) Time series gene expression is crucial to the proposed improvement and shows significantly better predictive ability than cross-sectional gene expression. (4) Our pipeline is robust to limited data availability. Availability : Code is available at https://github.com/compbiolabucf/TEDDY [ABSTRACT FROM AUTHOR]

The double burden of malnutrition accompanied by micronutrient deficiency is referred to as the triple burden of malnutrition (TBM). Very few studies have highlighted the TBM in children with type-1 diabetes. We conducted this study with the objective of estimating the TBM in Indian children and youth with type-1 diabetes (T1D) and to study role of anaemia in the development of complications associated with T1D. This cross-sectional observational study included 394 subjects with T1D. Demographic data, anthropometry, blood pressure, biochemical measurements, dual energy X-ray absorptiometry (DXA) and peripheral quantitative computed tomography were performed using standard protocols. Estimated glucose disposal rate (eGDR) and estimated glomerular filtration rate (eGFR) were calculated for all subjects. We report a 16, 5.8, and 16.2% prevalence of anaemia, underweight and overweight/obese suggesting TBM with microcytic hypochromic anaemia as the most common morphological form. Haemoglobin concentrations showed positive correlation with systolic and diastolic blood pressure. The presence of anaemia was a significant predictor of eGDR and macrovascular complications in T1D which could not be attributed to glycemic control. Bone health of anaemic T1D subjects was poor than subjects without anaemia on DXA scan after adjusting for confounders. No systematic pattern between Hb concentrations and eGFR or ACR was found. TBM in Indian children and youth with T1D is a significant health problem and anaemia is an important predictor in the development of macrovascular complications and poor bone health associated with T1D. However, its role in development of microvascular complications remains to be explored. [ABSTRACT FROM AUTHOR]

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The research study focused on the development and characterization of sustained release formulation of genistein (GEN)-loaded chitosan (CS) nanoparticles to deliver in the form of dry powder inhaler (DPI) via pulmonary route to offer higher stability and anti-diabetic activity. The GEN-loaded nanoparticles were prepared by cross-linking reaction of CS and sodium hexametaphosphate (SHMP). The optimized formulation displayed particle size (PS) of 684.2 ± 26.5 nm, zeta potential (ZP) of 19.6 ± 4.50 mV, % entrapment efficiency (% EE) of 87.33 ± 8.46 % and drug release profile of 85.48 ± 5.50 % for 48 h. The in-vivo studies exhibited a superior sustained release formulation of GEN in the regulation of blood glucose levels (BGLs). The powder showed the emitted fraction (EF) of 86.76 % and effective inhalation index (EI) of 85.41 %. The reduction of BGLs (85 %) was observed in the diabetic group. This might be due to the inhibition of proliferation of pancreatic β-cells (growth factor inhibition targeting cAMP and ERK1/2 pathway), antioxidative activity, reducing insulin resistance, and the adipose tissue mass and alteration of the hepatic glucose metabolism. Hence, these results proved the delivery of GEN in the form of DPI system as a favorable route for treating type-1 diabetes mellitus with a longer duration of action. [ABSTRACT FROM AUTHOR]

Diabetes mellitus, sometimes known as diabetes, is a widespread disease in the current technological period. Blood glucose levels in this condition are out of the normal range of 80 to 170 mg/dl, which puts the human body at risk for long-lasting illness. Diabetes raises a person's mortality risk. Many reviews have been written about mathematical modelling for diabetes. Various models have been presented in recent years for a number of diabetes-related topics, including glucose and insulin dynamics, management and the prevention of complications, and the epidemiology of diabetes in general. On a regular basis, reviews on mathematical models used for particular areas of diabetes are published. This study offers an overview of several mathematical models that deal with various elements of diabetes. [ABSTRACT FROM AUTHOR]

Objective: Isolated pancreatic islets are valuable resources for a wide range of research, including cell replacement studies and cell-based platforms for diabetes drug discovery and disease modeling. Islet isolation is a complex and stepwise procedure aiming to obtain pure, viable, and functional islets for in vitro and in vivo studies. It should be noted that differences in rodent strains, gender, weight, and density gradients may affect the isolated islet’s properties. We evaluated the variables affecting the rat islet isolation procedure to reach the maximum islet yield and functionality, which would be critical for further studies on islet regenerative biology. Materials and Methods: The present experimental study compared the yield and purity of isolated islets from nondiabetic rats of two different strains. Next, islet particle number (IPN) and islet equivalent (IEQ) were compared between males and females, and the weight range that yields the highest number of islets was investigated. Moreover, the influence of three different density gradients, namely Histopaque, Pancoll, and Lymphodex, on final isolated islets purity and yield were assessed. Finally, the viability and functionality of isolated islets were measured. Results: The IEQ, IPN, and purity of isolated islets in 15 Lister hooded rats (LHRs) were significantly (P≤0.05) higher than those of the other strains. Male LHRs resulted in significantly higher IEQ compared to females (P≤0.05). Moreover, IPN and IEQ did not significantly vary among different weight groups. Also, the utilization of Histopaque and Pancoll leads to higher yield and purity. In vivo assessments of the isolated islets presented significantly reduced blood glucose percentage in the transplanted group on days 2-5 following transplantation. Conclusion: Based on these results, an optimal protocol for isolating high-quality rat islets with a constant yield, purity, and function has been established as an essential platform for developing diabetes research. [ABSTRACT FROM AUTHOR]

Objective: Diabetic ketoacidosis (DKA) - a potentially preventable complication of type 1 diabetes mellitus (T1D) - is one of the most common chronic childhood diseases, and is associated with a significant risk of morbidity and mortality. The limited use of healthcare services due to fear of Coronavirus disease-2019 (COVID-19) transmission during the pandemic has raised concerns of delays in T1D diagnosis, among other diseases. This study investigated the presenting characteristics of newly diagnosed T1D patients assessed in a single clinic during the pandemic and compares them with the pre-pandemic period. Methods: For the purpose of this study, the first year of the pandemic is referred to as the "pandemic period", and the previous three years as the "pre-pandemic period". Patient files were reviewed retrospectively, the demographic and clinical characteristics and laboratory findings of the patients were recorded, and the findings from both periods were compared. Results: The number of patients diagnosed with T1D in the pandemic period was 44, and in the pre-pandemic period 39 in 2017, 22 in 2018 and 18 in 2019. The two groups had similar age, sex, pubertal stage and anthropometric characteristics (p>0.05). Regarding the type of presentation, the frequency of DKA was significantly higher in the pandemic period (68.2%) than in the pre-pandemic period (40.5%) (p=0.006), and this difference was also observed in the comparison by years (p=0.016). The duration of symptoms (16.5±10.7 vs. 23.5±17.6 days) and the length of hospital stay (10±3.9 vs. 15.2±5.5 days) were significantly shorter in the pandemic period (p=0.032, and p<0.001, respectively). There was no difference in the frequency of severe DKA between the pandemic (46.7%) and the pre-pandemic (37.5%) periods (p>0.05). However, pH (7.17±0.16 vs. 7.26±0.14) and bicarbonate (12.8±6.3 vs. 16.6±6.3) levels were significantly lower in the pandemic period (p<0.005). Additional signs of infection on admission were less frequent in the pandemic period (9.1%) than in the pre-pandemic period (27.8%) (p=0.027). The groups did not differ in terms of hemoglobin A1c, C-peptide, concurrent thyroid autoantibodies and tissue transglutaminase antibodies (p>0.05). The rate of anti-glutamic acid decarboxylase positivity was higher in the pandemic period (73.8% vs. 39.2%) (p=0.001) while the frequency of other diabetes associated autoantibodies was similar between the groups (p>0.05). The polymerase chain reaction test for COVID-19 was negative in six patients with a history of contact. Conclusion: There was an increased frequency and severity of DKA in children with newly diagnosed T1D in the pandemic period, and these findings justify concerns related to the diagnosis of other diseases during the pandemic. Studies to raise awareness of diabetes symptoms during the pandemic should be continued regularly to reach all segments of society. Our study provides an additional contribution to the literature in its coverage of the one-year period during the pandemic and its comparison with the previous three years. [ABSTRACT FROM AUTHOR]

The role of insulin sensitivity (IS) in the development and progression of metabolic syndrome (MS) in subjects with type-1 diabetes (T1D) is being increasingly recognized. As patients with T1D lack endogenous insulin secretion, measurement of insulin concentration by immunoassay or by indices such as homeostasis model of assessment for insulin resistance (HOMA-IR) is not helpful in assessing IS. Hence, some equations have been developed and validated against data from euglycemic-hyper-insulinemic clamp tests (the gold standard) to estimate IS. 1) To assess IS using available equations (EDC, SEARCH and CACTI) and relationship of IS with MS and microalbuminuria in adolescents with T1D, (2) To compare the predictive value of these equations for detection of MS and derive a cut-off to predict the future risk of development of MS and microalbuminuria and (3) To identify the most accurate non-invasive and easy-to-use equation for detecting patients with double diabetes (DD) in a clinical setting. This cross-sectional study included 181 adolescents aged 12–18 years with T1D. Demographic data and laboratory measurements were performed using standard protocols. IS was calculated using following equations:(1) EDC=24.31−12.22×(WHR)−3.29×(hypertension)−0.57×(HbA1c), (2) SEARCH=exp(4.64725−0.02032(waist)−0.09779(HbA1c)−0.00235(Triglycerides), (3)CACTI-exA=exp(4.1075–0.01299×(waist)−1.05819×(insulin dose)−0.00354×(Triglycerides)−0.00802×(DBP)). IS determined by all three methods had significant negative correlation (p<0.05) with MS as well as with microalbuminuria. The cut-off value of 5.485 mg/kg/min by SEARCH method for determining IS had the highest sensitivity and specificity in identifying MS. IS by SEARCH equation may be used in routine clinical practice to detect DD in Indian adolescents with T1D at risk of developing metabolic as well as microvascular complications. [ABSTRACT FROM AUTHOR]

Introduction: The incidence of type-1 diabetes is on the rise, particularly in developed nations, and predominantly affects the youth. While genetic predisposition plays a substantial role, environmental factors, including alterations in the gut microbiota, are increasingly recognized as significant contributors to the disease., Methods: In this study, we utilized germ-free non-obese diabetic mice to explore the effects of microbiota colonization during early life on type-1 diabetes susceptibility., Results: Our findings reveal that microbiota introduction at birth, rather than at weaning, significantly reduces the risk of type-1 diabetes, indicating a crucial window for microbiota-mediated modulation of immune responses. This protective effect was independent of alterations in intestinal barrier function but correlated with testosterone levels in male mice. Additionally, early life colonization modulated T cell subset frequencies, particularly T helper cells and regulatory T cells, in the intestine, potentially shaping type-1 diabetes predisposition., Discussion: Our findings underscore the pivotal role of early-life microbial interactions in immune regulation and the development of autoimmune diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Fernandez Trigo, Kalbermatter, Yilmaz and Ganal-Vonarburg.)

It is oftentimes the case in studies of disease progression that subjects can move into one of several disease states of interest. Multistate models are an indispensable tool to analyze data from such studies. The Environmental Determinants of Diabetes in the Young (TEDDY) is an observational study of at-risk children from birth to onset of type-1 diabetes (T1D) up through the age of 15. A joint model for simultaneous inference of multistate and multivariate nonparametric longitudinal data is proposed to analyze data and answer the research questions brought up in the study. The proposed method allows us to make statistical inferences, test hypotheses, and make predictions about future state occupation in the TEDDY study. The performance of the proposed method is evaluated by simulation studies. The proposed method is applied to the motivating example to demonstrate the capabilities of the method.

Closed-loop control systems for precise control of therapeutic gene expression are promising candidates for personalized treatment of chronic ailments such as diabetes. Pancreatic iβ-cells are engineered with blue-light-inducible melanopsin to drive rapid insulin release by vesicular secretion from intracellular stores. In this work, a glucose-operated widget (GLOW) is designed as a component of a closed-loop control system for diabetes treatment by employing a probe that emits blue fluorescence in a glucose-concentration-dependent manner as a real-time glucose sensor to precisely control insulin release from these iβ-cells. As proof-of-concept of the complete control system, the probe is encapsulated together with iβ-cells in alginate-poly-(L-lysine) hydrogel-microbeads(400 µm in diameter and containing about 500 cells) called GLOW iβ (GLOW with iβ-cells), are subcutaneously implanted into type-1-diabetic (T1D) mice. Illumination by UV-A light at 390 nm results in glucose-concentration-dependent blue-light emission from the probe at 445 nm that in turn induces glucose-concentration-dependent insulin release from the iβ-cells in a fully reversible manner. Activation of the injected GLOW iβ at 390 nm for 15 min effectively restores normoglycemia within 60-120 min in a closed-loop manner in these diabetic mice. The system is robust, as normoglycemia is well maintained by daily activation for at least 7 days., (© 2024 The Author(s). Advanced Materials published by Wiley‐VCH GmbH.)

Due to prolonged hyperglycemia many of the diabetic patients suffer from complications such as liver damage. Diabetic patients are known to have the need for liver surgeries more than non-diabetic do. The ischemia reperfusion injuries (IRI) are one of the main complications of these surgeries and the IRI-related increase in oxidative stress has been known to be higher in diabetic patients. Metformin and aerobic exercise are important tools being used especially in type-2 diabetes. However, their effects and roles in liver IRI in type-1 diabetic patients are not known. This study aimed to investigate the effects of metformin and exercise on hepatic IRI in diabetes in streptozotocin induced type-1 diabetic mice. Diabetes was induced by streptozotocin and two weeks after the disease developed, mice were started to treat with metformin and/or aerobic exercise during four-weeks. Blood glucose levels of the mice were measured again and the glucose tolerance test (OGTT) was performed for each mouse. The day after OGTT, ischemia was performed for 45 minutes in the liver and then reperfusion was provided for 5 hours. The liver of the mice was isolated at the end of the experiments. The malondialdehyde, superoxide dismutase and nitrite levels were measured with colorimetric analysis. Metformin reduced the insulin resistance alone and together with aerobic exercise. Oxidative stress in the liver after IRI was diminished both with metformin and/or aerobic exercise in diabetic mice. Our study indicated that metformin accompanied with aerobic exercise might be an important treatment strategy for preventing the IRI in the liver of type-1 diabetic patients. [ABSTRACT FROM AUTHOR]

The present study aimed at investigating the possible benefits of a dietary intervention with Corinthian currants, a rich source of phenolic compounds, on type 1 diabetes (T1D) using the animal model of the streptozotocin-(STZ)-induced diabetic rat. Male Wistar rats were randomly assigned into four groups: control animals, which received a control diet (CD) or a diet supplemented with 10% w/w Corinthian currants (CCD), and diabetic animals, which received a control diet (DCD) or a currant diet (DCCD) for 4 weeks. Plasma biochemical parameters, insulin, polar phenolic compounds, and inflammatory factors were determined. Microbiota populations in tissue and intestinal fluid of the caecum, as well as fecal microbiota populations and short-chain fatty acids (SCFAs), were measured. Fecal microbiota was further analyzed by 16S rRNA sequencing. The results of the study showed that a Corinthian currant-supplemented diet restored serum polar phenolic compounds and decreased interleukin-1b (IL-1b) (p < 0.05) both in control and diabetic animals. Increased caecal lactobacilli counts (p < 0.05) and maintenance of enterococci levels within normal range were observed in the intestinal fluid of the DCCD group (p < 0.05 compared to DCD). Higher acetic acid levels were detected in the feces of diabetic rats that received the currant diet compared to the animals that received the control diet (p < 0.05). Corinthian currant could serve as a beneficial dietary component in the condition of T1D based on the results coming from the animal model of the STZ-induced T1D rat.

During the last decade, a rising interest in novel functional products containing probiotic microorganisms has been witnessed. As food processing and storage usually lead to a reduction of cell viability, freeze-dried cultures and immobilization are usually recommended in order to maintain adequate loads and deliver health benefits. In this study, freeze-dried (free and immobilized on apple pieces) Lacticaseibacillus rhamnosus OLXAL-1 cells were used to fortify grape juice. Juice storage at ambient temperature resulted in significantly higher (>7 log cfu/g) levels of immobilized L. rhamnosus cells compared to free cells after 4 days. On the other hand, refrigerated storage resulted in cell loads > 7 log cfu/g for both free and immobilized cells for up to 10 days, achieving populations > 109 cfu per share, with no spoilage noticed. The possible resistance of the novel fortified juice products to microbial spoilage (after deliberate spiking with Saccharomyces cerevisiae or Aspergillus niger) was also investigated. Significant growth limitation of both food-spoilage microorganisms was observed (both at 20 and 4 °C) when immobilized cells were contained compared to the unfortified juice. Keynote volatile compounds derived from the juice and the immobilization carrier were detected in all products by HS-SPME GC/MS analysis. PCA revealed that both the nature of the freeze-dried cells (free or immobilized), as well as storage temperature affected significantly the content of minor volatiles detected and resulted in significant differences in the total volatile concentration. Juices with freeze-dried immobilized cells were distinguished by the tasters and perceived as highly novel. Notably, all fortified juice products were accepted during the preliminary sensory evaluation.