Insulin-dependent Diabetes Research Articles

Mild Primary or Breakthrough SARS-CoV-2 Infection Promotes Autoantibody Production in Individuals with and without Neuro-PASC.

Patients with long COVID can develop humoral autoimmunity after severe acute SARS-CoV-2 infection. However, whether similar increases in autoantibody responses occur after mild infection and whether vaccination prior to SARS-CoV-2 breakthrough infection can limit autoantibody responses is unknown. In this study, we demonstrate that mild SARS-CoV-2 infection increases autoantibodies associated with rheumatic autoimmune diseases and diabetes in most individuals, regardless of vaccination status prior to infection. However, patients with long COVID and persistent neurologic and fatigue symptoms (neuro-PASC) have substantially higher autoantibody responses than convalescent control subjects at an average of 8 mo postinfection. Furthermore, high titers of systemic lupus erythematosus- and CNS-associated autoantibodies in patients with neuro-PASC are associated with impaired cognitive performance and greater symptom severity. In summary, we found that mild SARS-CoV-2 primary and breakthrough infections can induce persistent humoral autoimmunity in both patients with neuro-PASC and healthy COVID convalescents, suggesting that a reappraisal of mitigation strategies against SARS-CoV-2 is warranted to prevent transmission and potential development of autoimmunity.

Pro- and anti-inflammatory cytokines are the game-changers in childhood obesity-associated metabolic disorders (diabetes and non-alcoholic fatty liver diseases).

Childhood obesity is a chronic inflammatory epidemic that affects children worldwide. Obesity affects approximately 1 in 5 children worldwide. Obesity in children can worsen weight gain and raise the risk of obesity-related comorbidities like diabetes and non-alcoholic fatty liver disease (NAFLD). It can also negatively impact the quality of life for these children. Obesity disrupts immune system function, influencing cytokine (interleukins) balance and expression levels, adipokines, and innate and adaptive immune cells. The altered expression of immune system mediators, including interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-17 (IL-17), interleukin-18 (IL-18), transforming growth factor (TGF), tumor necrosis factor (TNF), and others, caused inflammation, progression, and the development of pediatric obesity and linked illnesses such as diabetes and NAFLD. Furthermore, anti-inflammatory cytokines, including interleukin-2 (IL-2), have been shown to have anti-diabetes and IL-1 receptor antagonist (IL-1Ra) anti-diabetic and pro-NAFLFD properties, and interleukin-10 (IL-10) has been shown to have a dual role in managing diabetes and anti-NAFLD. In light of the substantial increase in childhood obesity-associated disorders such as diabetes and NAFLD and the absence of an effective pharmaceutical intervention to inhibit immune modulation factors, it is critical to consider the alteration of immune system components as a preventive and therapeutic approach. Thus, the current review focuses on the most recent information regarding the influence of pro- and anti-inflammatory cytokines (interleukins) and their molecular mechanisms on pediatric obesity-associated disorders (diabetes and NAFLD). Furthermore, we discussed the current therapeutic clinical trials in childhood obesity-associated diseases, diabetes, and NAFLD.

Short-term outcomes after surgical aortic valve replacement in elderly patients - results of a comparative cohort study

BackgroundWith the introduction of transcatheter aortic valve implantation, the role of surgical aortic valve replacement (SAVR) in elderly patients has been called into question. We investigated the short-term outcomes of SAVR in the elderly population.MethodsAll patients aged ≥ 70 years who underwent isolated SAVR in our centre between 2008 and 2017 were included in the study. Survival at 30 days and 1 year were compared for patients aged 70–79 years (n = 809) versus patients aged ≥ 80 years (n = 322). Factors associated with poorer survival outcomes were identified using multivariable Cox regression analysis.ResultsPatients aged 70–79 years and patients aged ≥ 80 years had similar survival rates at 30 days (98.1% vs. 98.4%, p = 0.732) and 1 year (96.0% vs. 94.1%, p = 0.162) post-SAVR. This remained true after multivariable adjustment. Risk factors for 30 day all-cause mortality included insulin dependent diabetes (HR 6.17, 95% CI 1.32–28.92, p = 0.021) and increasing cardiopulmonary bypass time (HR 2.72, 95% CI 1.89–3.91, p < 0.0001). Significant risk factors for 1 year all-cause mortality were New York Heart Association (NYHA) class IV (HR 6.25, 95% CI 1.55–25.24, p = 0.010) and longer cardiopulmonary bypass time (HR 1.94, 95% CI 1.40–2.69, p < 0.0001). Similar results were obtained for cardiac-specific mortality.ConclusionsShort-term outcomes of SAVR are excellent in elderly patients and age alone is not a predictor of poorer outcomes. However, the increased risk of mortality in patients with insulin-dependent diabetes and those with severe functional impairment (NYHA class IV) should be carefully considered when selecting patients for SAVR in this elderly population.

The new face of diabetes mellitus — rhythm and conduction disorders

This review article is devoted to changes in heart rhythm against the background of type 2 diabetes mellitus, which is one of the most common endocrine diseases. In recent years, there has been an increasing association between type 2 diabetes mellitus and heart rhythm disorders. Arrhythmias such as tachycardia, bradycardia and atrial fibrillation are common in patients with type 2 diabetes and can have serious consequences on health and quality of life. Type 2 DM is increasingly common worldwide due to the rise in sedentary lifestyles, overweight, abdominal forms of obesity, and diets containing too much fat and carbohydrates. Insulin-independent diabetes is a metabolic disease responsible for autonomic neuropathy of the heart that affects both sympathetic and parasympathetic fibers, which can be explained by the adverse effect of blood glucose levels on heart rate variability (HRV). Although the gold standard is cardiovascular reflex tests to assess cardiovascular autonomic neuropathy, one of the most important is the measurement of heart rate variability (HRV). HRV is the variation between two consecutive contractions: the higher the variation, the higher the activity of the parasympathetic nervous system. A high HRV reflects the fact that a person can constantly adapt to changes in the microenvironment. Thus, low HRV is a marker of cardiovascular risk.

High glutamic acid decarboxylase antibody titers may be associated with a decline in β-cell function over time and future insulin deficiency in latent autoimmune diabetes in adults

AimsLatent autoimmune diabetes in adults (LADA) is characterized by positive islet-associated autoantibodies including glutamic acid decarboxylase antibody (GADA), and gradual decline in insulin secretion, progressing to insulin dependency. This cross-sectional study aimed to determine whether GADA by enzyme-linked immunosorbent assay (GADA-ELISA) titer of ≥180 U/mL could be associated with decline in β-cell function in participants with LADA. MethodsSixty-three participants with LADA were recruited and an association between insulin secretion capacity and disease duration was investigated. Insulin peptide-specific inflammatory immunoreactivity was investigated to determine the disease’s activity. ResultsThere was a significant inverse correlation between disease duration and C-peptide index in participants with GADA-ELISA titer of ≥180 U/mL (Spearman’s r (rs) = –0.516, p < 0.01). The positivity rate of insulin peptide-specific inflammatory immunoreactivity was significantly higher in those with ≥180 U/mL than in those with <180 U/mL (p < 0.05). In participants with human leukocyte antigen (HLA)-DRB1*04:05, a significant inverse correlation was observed between disease duration and C-peptide index in those with ≥180 U/mL (rs = −0.751, p < 0.01). ConclusionsGADA-ELISA titer of ≥180 U/mL, especially with HLA-DRB1*04:05, might reflect higher disease activity and may be associated with decline in β-cell function over time and future insulin dependency in LADA.

Advances in Islet Transplantation and the Future of Stem Cell-Derived Islets to Treat Diabetes.

β-Cell replacement for type 1 diabetes (T1D) can restore normal glucose homeostasis, thereby eliminating the need for exogenous insulin and halting the progression of diabetes complications. Success in achieving insulin independence following transplantation of cadaveric islets fueled academic and industry efforts to develop techniques to mass produce β cells from human pluripotent stem cells, and these have now been clinically validated as an alternative source of regulated insulin production. Various encapsulation strategies are being pursued to contain implanted cells in a retrievable format, and different implant sites are being explored with some strategies reaching clinical studies. Stem cell lines, whether derived from embryonic sources or reprogrammed somatic cells, are being genetically modified for designer features, including immune evasiveness to enable implant without the use of chronic immunosuppression. Although hurdles remain in optimizing large-scale manufacturing, demonstrating efficacy, durability, and safety, products containing stem cell-derived β cells promise to provide a potent treatment for insulin-dependent diabetes.

Ethical aspects in the prevention of insulin-dependent diabetes mellitus

Insulin-dependent diabetes mellitus (IDDM) seems to be on the rise today, especially in northern European populations. IDDM is a disease that leads to numerous complications (e.g., metabolic decompensation, macroangiopathy, microangiopathy, retinopathy, nephropathy etc.) and requires the individual to be on daily insulin administration, for life.

Hypothermic Ventricular Fibrillation in Redo Minimally Invasive Mitral Valve Surgery: A Promising Solution for a Surgical Challenge.

Background: Minimally invasive mitral valve surgery (MIMVS) is a treatment for severe mitral valve pathologies. In redo cases, especially after coronary artery bypass grafting (CABG) surgery with patent mammary bypass grafts, establishing aortic clamping followed by antegrade cardioplegia application might be challenging. Here, we present the outcome of hypothermic ventricular fibrillation as an alternative to conventional cardioprotection. Methods: Patients who underwent MIMVS either received hypothermic ventricular fibrillation (study group, n = 48) or antegrade cardioprotection (control group, n = 840) and were observed for 30 postoperative days. Data were retrospectively analyzed and collected from January 2011 until December 2022. Results: Patients in the study group had a higher preoperative prevalence of renal insufficiency (p = 0.001), extracardiac arteriopathy (p = 0.001), insulin-dependent diabetes mellitus (p = 0.001) and chronic lung disease (p = 0.036). Furthermore, they had a longer surgery time and a lower repair rate (p < 0.001). No difference, however, was seen in postoperative incidences of stroke (p = 0.26), myocardial infarction (p = 1) and mitral valve re-operation (p = 1) as well as 30-day mortality (p = 0.1) and postoperative mitral valve insufficiency or stenosis. Conclusions: The patients who underwent redo MIMVS with hypothermic ventricular fibrillation did not have worse outcomes or more serious adverse events compared to the patients who received routine conventional cardioprotection. Therefore, the use of hypothermic ventricular fibrillation appears to be a promising cardioprotective technique in this challenging patient population requiring redo MIMVS.

Checkpoint Inhibitor-Induced Autoimmune Diabetes: An Autoinflammatory Disease.

Immunomodulatory agents targeting immune checkpoints are now the state-of-the-art for the treatment of many cancers, but at the same time have led to autoimmune side effects, including autoimmune diabetes: immune checkpoint inhibitor-induced diabetes (CPI-DM). Emerging research shows the importance of preexisting autoimmune disease risk that has been identified through genetics, and autoantibodies. Key associated clinical findings also include increased levels of lipase before diagnosis suggesting that the inflammatory process in the pancreas extends beyond the islets of Langerhans. There is selectivity for the blockade of programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) for this adverse event, consistent with the role of this checkpoint in maintaining tolerance to autoimmune diabetes.

Global research on type 1 diabetes: A bibliometric study during 2001-2022

Objective. Type 1 diabetes (T1D) publications have increased over the past three decades. However, there is no study to address and identify gaps in this area and to plan future research. This study aims to analyze the global scientific production of T1D in terms of overall structure and hotspots. Methodology. The research literature on T1D from 2001 to 2022 was obtained and examined from the Scopus database. We then performed bibliometric analysis and network visualization using MS Excel and VOSviewer software. Results and Discussion. The global T1D research comprised 20473 publications, which witnessed 6.19% and 58.91% annual average and 10-year cumulative growth during 2001-2022. These together received 596950 citations, with an average Citation Per Paper (CPP) of 29.16. Of the total global publications, 6030 (29.45%) received external funding support from international agencies and 19553 citations (with an average CPP of 32.43). The global publications were sourced from more than 150 countries and were published in 2665 journals by 63747 authors from 24899 organizations. There is an uneven distribution of countries, organizations, and authors in T1D research, wherein 88.37%, 45.15%, and 20.66% of the global literature was contributed by the top 12 countries and top 30 organizations and authors each. The most productive countries were the USA and UK, with a global share of 30% and 11.1% respectively. The most impactful countries were Finland and the UK regarding CPP &amp; Relative Citation Index (RCI). The Barbara Davis Center for Childhood Diabetes, USA, and the University of Colorado Anschutz Medical Campus, USA, were the most productive organizations, with 735 and 679 publications. Jaeb Center for Health Research, USA (77.03 and 2.64) and Harvard Medical School, USA (67.42 and 2.31) were the most impactful organizations regarding CPP &amp; RCI. Pediatric Diabetes (n=1447) and Diabetes Care (n=1191) were the most productive journals, with 1447 and 1191 papers. Diabetes and Diabetes Care registered the highest CPP (81.54 and 73.88 CPP). The most significant and frequently appearing keywords were “diabetes mellitus, type 1”) (92441), “insulin dependent diabetes mellitus” (95750), “metabolism” (24911), “genetics” (11229), “autoantibodies” (8942), “c peptide” (9931) and “pancreas islet beta cell” (7191). Only 5.54% (1134) of the global publications (considered highly-cited papers) received 100 to 4654 citations since their publications and registered a total of 220.28 CPP. Conclusion. This bibliometric study indicated that most of the contributions came from developed countries and only a meager contribution from developing countries, especially South Asia, despite a significant disease burden. This analysis provides a comprehensive overview of the present status of T1D research. It enables a better understanding of T1D research over the years. It should give the researchers structured information and a comprehensive analysis to help identify gaps in the research and the hot spots in this area of research.

RIPK1 is dispensable for cell death regulation in β-cells during hyperglycemia

ObjectiveReceptor-interacting protein kinase 1 (RIPK1) orchestrates the decision between cell survival and cell death in response to tumor necrosis factor (TNF) and other cytokines. Whereas the scaffolding function of RIPK1 is crucial to prevent TNF-induced apoptosis and necroptosis, its kinase activity is required for necroptosis and partially for apoptosis. Although TNF is a proinflammatory cytokine associated with β-cell loss in diabetes, the mechanism by which TNF induces β-cell demise remains unclear. MethodsHere, we dissected the contribution of RIPK1 scaffold versus kinase functions to β-cell death regulation using mice lacking RIPK1 specifically in β-cells (Ripk1β-KO mice) or expressing a kinase-dead version of RIPK1 (Ripk1D138N mice), respectively. These mice were challenged with streptozotocin, a model of autoimmune diabetes. Moreover, Ripk1β-KO mice were further challenged with a high-fat diet to induce hyperglycemia. For mechanistic studies, pancreatic islets were subjected to various killing and sensitising agents. ResultsInhibition of RIPK1 kinase activity (Ripk1D138N mice) did not affect the onset and progression of hyperglycemia in a type 1 diabetes model. Moreover, the absence of RIPK1 expression in β-cells did not affect normoglycemia under basal conditions or hyperglycemia under diabetic challenges. Ex vivo, primary pancreatic islets are not sensitised to TNF-induced apoptosis and necroptosis in the absence of RIPK1. Intriguingly, we found that pancreatic islets display high levels of the antiapoptotic cellular FLICE-inhibitory protein (cFLIP) and low levels of apoptosis (Caspase-8) and necroptosis (RIPK3) components. Cycloheximide treatment, which led to a reduction in cFLIP levels, rendered primary islets sensitive to TNF-induced cell death which was fully blocked by caspase inhibition. ConclusionsUnlike in many other cell types (e.g., epithelial, and immune), RIPK1 is not required for cell death regulation in β-cells under physiological conditions or diabetic challenges. Moreover, in vivo and in vitro evidence suggest that pancreatic β-cells do not undergo necroptosis but mainly caspase-dependent death in response to TNF. Last, our results show that β-cells have a distinct mode of regulation of TNF-cytotoxicity that is independent of RIPK1 and that may be highly dependent on cFLIP.

A novel start-loss mutation of the SLC29A3 gene in a consanguineous family with H syndrome: clinical characteristics, in silico analysis and literature review

BackgroundThe SLC29A3 gene, which encodes a nucleoside transporter protein, is primarily located in intracellular membranes. The mutations in this gene can give rise to various clinical manifestations, including H syndrome, dysosteosclerosis, Faisalabad histiocytosis, and pigmented hypertrichosis with insulin-dependent diabetes. The aim of this study is to present two Iranian patients with H syndrome and to describe a novel start-loss mutation in SLC29A3 gene.MethodsIn this study, we employed whole-exome sequencing (WES) as a method to identify genetic variations that contribute to the development of H syndrome in a 16-year-old girl and her 8-year-old brother. These siblings were part of an Iranian family with consanguineous parents. To confirmed the pathogenicity of the identified variant, we utilized in-silico tools and cross-referenced various databases to confirm its novelty. Additionally, we conducted a co-segregation study and verified the presence of the variant in the parents of the affected patients through Sanger sequencing.ResultsIn our study, we identified a novel start-loss mutation (c.2T > A, p.Met1Lys) in the SLC29A3 gene, which was found in both of two patients. Co-segregation analysis using Sanger sequencing confirmed that this variant was inherited from the parents. To evaluate the potential pathogenicity and novelty of this mutation, we consulted various databases. Additionally, we employed bioinformatics tools to predict the three-dimensional structure of the mutant SLC29A3 protein. These analyses were conducted with the aim of providing valuable insights into the functional implications of the identified mutation on the structure and function of the SLC29A3 protein.ConclusionOur study contributes to the expanding body of evidence supporting the association between mutations in the SLC29A3 gene and H syndrome. The molecular analysis of diseases related to SLC29A3 is crucial in understanding the range of variability and raising awareness of H syndrome, with the ultimate goal of facilitating early diagnosis and appropriate treatment. The discovery of this novel biallelic variant in the probands further underscores the significance of utilizing genetic testing approaches, such as WES, as dependable diagnostic tools for individuals with this particular condition.

Immune checkpoint inhibitors-induced diabetes mellitus (review).

Immune checkpoint inhibitors (ICIs) have become extensively utilized in the early-stage treatment of various cancers, offering additional therapeutic possibilities for patients with advanced cancer. However, certain patient populations are susceptible to experiencing toxic adverse effects from ICIs, such as thyrotoxicosis, rashes, among others. Specifically, ICIDM, induced by immune checkpoint inhibitors, exhibits characteristics similar to insulin-dependent diabetes mellitus (Type 1 Diabetes Mellitus, T1DM). ICIDM is characterized by a rapid onset and may coincide with severe ketoacidosis. Despite a favorable response to insulin therapy, patients typically require lifelong insulin dependence. After discussing the autoimmune adverse effects and the specifics of ICIs-induced diabetes mellitus (ICIDM), it is important to note that certain patient populations are particularly susceptible to experiencing toxic adverse effects from ICIs. Specifically, ICIDM, which is triggered by immune checkpoint inhibitors, mirrors the characteristics of insulin-dependent diabetes mellitus (Type 1 Diabetes Mellitus, T1DM). This article conducts an in-depth analysis of the literature to explore the pathogenesis, disease progression, and treatment strategies applicable to diabetes induced by immune checkpoint inhibitors (ICIDM).

Prediction of chromosomal abnormalities in the screening of the first trimester of pregnancy using machine learning methods: a study protocol

BackgroundFor women in the first trimester, amniocentesis or chorionic villus sampling is recommended for screening. Machine learning has shown increased accuracy over time and finds numerous applications in enhancing decision-making, patient care, and service quality in nursing and midwifery. This study aims to develop an optimal learning model utilizing machine learning techniques, particularly neural networks, to predict chromosomal abnormalities and evaluate their predictive efficacy.Methods/ designThis cross-sectional study will be conducted in midwifery clinics in Mashhad, Iran in 2024. The data will be collected from 350 pregnant women in the high-risk group who underwent screening tests in the first trimester (between 11-14 weeks) of pregnancy. Information collected includes maternal age, BMI, smoking habits, history of trisomy 21 and other chromosomal disorders, CRL and NT levels, PAPP-A and B-HCG levels, presence of insulin-dependent diabetes, and whether the pregnancy resulted from IVF. The study follows up with the women during their clinic visits and tracks the results of amniocentesis. Sampling is based on Convenience Sampling, and data is gathered using a checklist of characteristics and screening/amniocentesis results. After preprocessing, feature extraction is conducted to identify and predict relevant features. The model is trained and evaluated using K-fold cross-validation.DiscussionThere is a growing interest in utilizing artificial intelligence methods, like machine learning and deep learning, in nursing and midwifery. This underscores the critical necessity for nurses and midwives to be well-versed in artificial intelligence methods and their healthcare applications. It can be beneficial to develop a machine learning model, specifically focusing on neural networks, for predicting chromosomal abnormalities.Ethical codeIR.MUMS.NURSE.REC. 1402.134

Simultaneous Pancreas and Kidney Transplantation: An Initial Experience in Southern India

Abstract Introduction: Simultaneous pancreas-kidney transplantation (SPKT) is a well-documented therapy for insulin-dependent diabetes mellitus (IDDM) with end-stage renal disease (ESRD). Here, we share the initial reports of SPKT conducted at our institution. Patients and Methods: We performed five SPKT procedures in patients with IDDM and ESRD between April 2021 and April 2023. All grafts were procured from healthy, in-house, brain-dead donors. Results: The recipients included three males and two females, with a mean age of 35 ± 11.2 years. The mean duration of diabetes mellitus and time on dialysis were 17 ± 9.7 years and 21 ± 8.7 months, respectively. Donors had a mean age and body mass index of 27 ± 5.8 years and 23 ± 2.7 kg/m2. The mean glycated hemoglobin (HbA1c) and creatinine levels of donors at the time of donation were 5.6% ±0.27% and 0.98 ± 0.4 mg/dL. One recipient underwent pancreas removal due to a duodenal leak, and one developed kidney acute tubular necrosis. All recipients were on proper follow-up for a median period of 12 (4–18) months, with 100% patient survival, 80% pancreas, and 100% kidney survival. Average HbA1c, fasting blood sugar, and serum creatinine on follow-up were 5.5% ±0.7%, 84 ± 9.9 mg/dL, and 1 ± 0.16 mg/dL, respectively. Conclusion: In our initial experience with SPKT, recipient outcomes were comparable to results published in the literature. With proper graft selection, SPKT can be established in small-volume centers. Meticulous surgical technique and postoperative management remain key to the success of the transplant program.

The Impact of Kidney/Pancreas Transplantation on Peripheral Arterial Disease.

It is unclear whether kidney/pancreas (KP) transplantation will prevent the progression of peripheral arterial disease (PAD) in patients with insulin dependent diabetes (IDDM) and end-stage renal disease. We sought to determine the pre- and posttransplant prevalence of symptomatic PAD and changes in carotid artery intima-media thickness (IMT) in KP recipients. In this single center study, outcomes were compared between KP recipients with and without a history of PAD. A subset of recipients underwent pre- and posttransplant IMT measurements. Among the study group (N = 107), 18 (17%) recipients admitted to a pretransplant history of symptomatic PAD, comprised 11 foot infections and 7 amputations (5 minor and 2 major). Baseline characteristics of age, gender, race, years of diabetes, dialysis history, smoking history, years of hypertension, and history of coronary artery disease (CAD) were equivalent between PAD and non-PAD cohorts. At a median follow-up of 60 months (IQR: 28, 110), 16 (15%) KP recipients had suffered a PAD event. In multivariate analysis, a pretransplant history of PAD (hazard ratio [HR] 9.66, p < 0.001) and CAD (HR 3.33, p = 0.04) were independent predictors of posttransplant PAD events. Among a subset of 20 recipients (3 with PAD), mean IMT measurements pretransplant and at a median of 24 (range 18-24) months posttransplant, showed no evidence of disease progression. Based on IMT measurements and clinical results, KP transplantation stabilized PAD in most patients, but did not alter outcomes of symptomatic PAD recipients. A pretransplant history of PAD and CAD was an independent predictor of posttransplant PAD events.

Factors Affecting 30-Day Outcomes in Patients Undergoing Nontraumatic Upper Extremity Amputation: A Retrospective Descriptive Longitudinal Study.

Current literature concerning upper extremity amputations (UEAs) is very sparse. In this study, we conducted the first multicenter retrospective analysis aiming to identify risk factors associated with unfavorable outcomes in patients undergoing nontraumatic UEAs. A retrospective cohort study was conducted using the National Surgical Quality Improvement Program database. Adult patients who underwent nontraumatic UEAs between 2005 and 2021 were divided into two cohorts based on whether they experienced 30-day major morbidity (MM). Thereafter, multivariable binary logistic regression analysis was used to identify risk factors of MM. From a total of 2984 cases, MM was observed in 8.7% of patients. Factors associated with MM included American Society of Anesthesiologists classes 3 (odds ratio [OR], 2.974 [1.862 to 4.748]) and 4 (OR, 4.736 [2.857 to 7.848]), being underweight (OR, 2.370 [1.251 to 4.491]), and suffering from insulin-dependent diabetes (OR, 1.390 [1.018 to 1.898]). In addition, an infectious surgical indication was associated with an increased risk of MM compared with having a benign (OR, 0.648 [0.488 to 0.682]) or malignant (OR, 0.205 [0.091 to 0.462]) indication. Moreover, patients undergoing shoulder amputations were at an increased risk of MM compared with those undergoing amputations of the forearm/wrist (OR, 0.243 [0.072 to 0.819]) and hands/fingers (OR, 0.286 [0.095 to 0.861]). The risk factors identified for MM after nontraumatic UEAs should guide surgeons toward appropriately identifying high-risk patients and adequately counseling them preoperatively.

Anti-GAD-65 antibody positivity in an 11-year-old boy with diabetes and pancreatic calcification: Exploring the role of autoimmunity in type 3c diabetes

ABSTRACT Chronic calcific pancreatitis in children is rare, and type 3c diabetes (T3cD) with extensive pancreatic calcification in the first decade of life is even rarer. We describe a case of T3cD in an 11-year-old boy who presented with hyperglycemic osmotic symptoms. Initial pancreatic autoantibody testing was positive for high titer, creating a diagnostic dilemma. This article examines the role of autoimmunity in the pathogenesis of post-pancreatitis diabetes and emphasizes the importance of performing pancreatic imaging before, or in addition to, carrying out pancreatic autoantibody tests, even in pediatric diabetes cases. This unique case also highlights the shortcomings in the current diagnostic criteria for T3cD.

Simple meal announcements and pramlintide delivery versus carbohydrate counting in type 1 diabetes with automated fast-acting insulin aspart delivery: a randomised crossover trial in Montreal, Canada

In type 1 diabetes, carbohydrate counting is the standard of care to determine prandial insulin needs, but it can negatively affect quality of life. We developed a novel insulin-and-pramlintide closed-loop system that replaces carbohydrate counting with simple meal announcements. We performed a randomised crossover trial assessing 14 days of (1) insulin-and-pramlintide closed-loop system with simple meal announcements, (2) insulin-and-placebo closed-loop system with carbohydrate counting, and (3) insulin-and-placebo closed-loop system with simple meal announcements. Participants were recruited at McGill University Health Centre (Montreal, QC, Canada). Eligible participants were adults (aged ≥18 years) and adolescents (aged 12-17 years) with type 1 diabetes for at least 1 year. Participants were randomly assigned in a 1:1:1:1:1:1 ratio to a sequence of the three interventions, with faster insulin aspart used in all interventions. Each intervention was separated by a 14-45-day wash-out period, during which participants reverted to their usual insulin. During simple meal announcement interventions, participants triggered a prandial bolus at mealtimes based on a programmed fixed meal size, whereas during carbohydrate counting interventions, participants manually entered the carbohydrate content of the meal and an algorithm calculated the prandial bolus based on insulin-to-carbohydrate ratio. Two primary comparisons were predefined: the percentage of time in range (glucose 3·9-10·0 mmol/L) with a non-inferiority margin of 6·25% (non-inferiority comparison); and the mean Emotional Burden subscale score of the Diabetes Distress Scale (superiority comparison), comparing the insulin-and-placebo system with carbohydrate counting minus the insulin-and-pramlintide system with simple meal announcements. Analyses were performed on a modified intention-to-treat basis, excluding participants who did not complete all interventions. Serious adverse events were assessed in all participants. This trial is registered on ClinicalTrials.gov, NCT04163874. 32 participants were enrolled between Feb 14, 2020, and Oct 5, 2021; two participants withdrew before study completion. 30 participants were analysed, including 15 adults (nine female, mean age 39·4 years [SD 13·8]) and 15 adolescents (eight female, mean age 15·7 years [1·3]). Non-inferiority of the insulin-and-pramlintide system with simple meal announcements relative to the insulin-and-placebo system with carbohydrate counting was reached (difference -5% [95% CI -9·0 to -0·7], non-inferiority p<0·0001). No statistically significant difference was found in the mean Emotional Burden score between the insulin-and-pramlintide system with simple meal announcements and the insulin-and-placebo system with carbohydrate counting (difference 0·01 [SD 0·82], p=0·93). With the insulin-and-pramlintide system with simple meal announcements, 14 (47%) participants reported mild gastrointestinal symptoms and two (7%) reported moderate symptoms, compared with two (7%) participants reporting mild gastrointestinal symptoms on the insulin-and-placebo system with carbohydrate counting. No serious adverse events occurred. The insulin-and-pramlintide system with simple meal announcements alleviated carbohydrate counting without degrading glucose control, although quality of life as measured by the Emotional Burden score was not improved. Longer and larger studies with this novel approach are warranted. Juvenile Diabetes Research Foundation.

Access to Diabetes Care Should Be a Universal Right for People With Type 1 Diabetes: Lessons Learned From the Norwegian Childhood Diabetes Registry.

Access to Diabetes Care Should Be a Universal Right for People With Type 1 Diabetes: Lessons Learned From the Norwegian Childhood Diabetes Registry.