Onset Of Type 1 Diabetes Mellitus Research Articles

Gamma-aminobutyric acid for delaying type 1 diabetes mellitus: an update.

The current gold-standard management of hyperglycemia in individuals with type 1 diabetes mellitus (T1DM) is insulin therapy. However, this therapy is associated with a high incidence of complications, and delaying the onset of this disease produces a substantially positive impact on quality of life for individuals with a predisposition to T1DM, especially children. This review aimed to assess the use of gamma-aminobutyric acid (GABA) to delay the onset of T1DM in children. GABA produces protective and proliferative effects in 2 ways, β cell and immune cell modulation. Various in vitro and in vivo studies have shown that GABA induces proliferation of β cells, increases insulin levels, inhibits β-cell apoptosis, and suppresses T helper 1 cell activity against islet antigens. Oral GABA is safe as no serious adverse effects were reported in any of the studies included in this review. These findings demonstrate promising results for the use of GABA treatment to delay T1DM, specifically in genetically predisposed children, through immunoregulatory effects and the ability to induce β-cell proliferation.

Systemic Inflammatory Response Index (SIRI) as a Predictive Marker for Adverse Outcomes in Children with New-Onset Type 1 Diabetes Mellitus.

(1) Background: Although most cases of new-onset type 1 diabetes mellitus (T1DM) are managed without serious events, life-threatening complications do arise in a subset of patients. Our objective was to assess the correlation between elevated SIRI values and adverse events related to the onset of T1DM. (2) Methods: This retrospective study, spanning ten years, included 187 patients with new-onset T1DM divided into three groups based on SIRI tertiles. The primary outcome was the occurrence of acute complications during hospital admission, while the secondary outcome was prolonged Intensive Care Unit (ICU) admission. (3) Results: Patients with high SIRI values were more likely to experience higher disease activity, leading to longer ICU admission times and more frequent complications. Multivariate logistic regression analysis revealed that the SIRI was independently associated with acute complications (p = 0.003) and prolonged ICU length of stay (p = 0.003). Furthermore, receiver operating characteristic analysis demonstrated the SIRI's superior predictive accuracy compared to venous pH (AUC = 0.837 and AUC = 0.811, respectively) and to the individual component cell lineages of the SIRI. (4) Conclusions: These findings emphasize the potential utility of the SIRI as a prognostic marker in identifying patients at increased risk during T1DM hospital admissions.

Prevalence of celiac disease in Moroccan children with type 1 diabetes mellitus: A 16-year cross-sectional study.

There is limited data available regarding the prevalence of celiac disease (CD) among children with type 1 diabetes mellitus (T1DM) in Arab countries and the Middle East. This cross-sectional study has been designed to explore the prevalence of CD specifically within the population of Moroccan children and adolescents diagnosed with type 1 diabetes mellitus (T1DM). This is a cross-sectional study of patients who underwent regular follow-up for T1DM at the Pediatric Endocrinology Unit, Abderrahim Harouchi Children's University Hospital in Casablanca, over a 16-year period from 2004 to 2020. Patients were screened for CD by measuring anti-tissue transglutaminase IgA, and those with positive antibodies underwent endoscopy assessment. All 550 patients regularly followed up with TIDM were screened for CD. Fifty-five (33 girls/22 boys) of the screened patients had histologically documented CD, yielding a prevalence of 10%. Nineteen (41.9%) patients had developed CD within the initial four years of diagnosis with T1DM. Therefore, among the six confirmed CD patients, the average age at the onset of T1DM was 3.7 years. For twenty-four (57.5%) of the patients, exhibited no apparent clinical indications of CD, and their condition was only identified through systematic screening. This study showed a high prevalence rate of CD associated with type 1 diabetes T1DM, particularly among young children. The results of this paper indicate one of the highest prevalence rates reported in the existing literature for the coexistence of CD and T1DM. These findings may suggest the necessity of a systematic screening of CD in T1DM patients.

Study of Profile of Young Diabetics with Special Reference to Type 2 Diabetes Mellitus

Abstract Background: Data about the frequency of type 2 diabetes mellitus (T2DM) among young subjects below 25 years of age are sparse in the Indian subcontinent. Aims and Objectives: The objective of this study was to study the frequency and clinical profile of T2DM among young diabetics. Materials and Methods: The study was a prospective observational study conducted in the Department of General Medicine and Pediatrics in JSS Hospital, Mysuru, Karnataka, India. The subjects with age of onset of diabetes mellitus below 25 years were included in the study. They were categorized according to the C-peptide values as type 1 diabetes mellitus (T1DM) and T2DM. The statistical analyses were performed using Statistical Package for the Social Sciences (SPSS version 25) computer program. Results: Of the 250 patients included in the study, 208 (83.2%) subjects had T1DM, 38 (15.2%) T2DM, and 4 (1.6%) maturity-onset diabetes of the young. The mean age of onset of T1DM was 13.7 ± 6.201 years and T2DM was 23.28 ± 3.68 years. Body mass index and waist circumference of young T2DM patients were more compared to T1DM, which were statistically significant (P < 0.0001), and family history showed strong positivity in patients with young T2DM compared to T1DM. Low-density lipoprotein-cholesterol, triglyceride, and total cholesterol were more in young T2DM patients compared to T1DM, which were statistically significant with P = 0.003, P = 0.0015, and P = 0.03, respectively. Conclusion: T2DM is now commonly occurring in young adults and children, probably due to a growing epidemic of childhood obesity and lifestyle. Obesity and dyslipidemia were more in T2DM compared to T1DM among young diabetics.

A Study of Diabetes in Young Individuals with Special Reference to Type 2 Diabetes Mellitus

Abstract Background: Type 2 diabetes mellitus (T2DM) in young individuals is a serious concern for the society. Literature suggests that the incidence of T2DM is not only increasing, but also there is a shift of age of onset of T2DM toward younger age groups in India and worldwide. However, data about the frequency of T2DM among young subjects below 25 years of age are sparse in the Indian subcontinent. Hence, the current study was undertaken to find out the frequency and clinical profile of young individuals with T2DM in the departments of internal medicine and pediatrics in a tertiary care hospital. Aims and Objectives: The aim of the study was to study the frequency and clinical profile of T2DM among young individuals with diabetes mellitus. Materials and Methods: The study was a cross-sectional observational study conducted in the Departments of General Medicine and Pediatrics at JSS Hospital, Mysuru, Karnataka, India, over a 2-year period. The subjects with age of onset of diabetes mellitus below 25 years were included in the study. They were categorized according to the C-peptide values as type 1 diabetes mellitus (T1DM) and T2DM. Maturity-onset diabetes of the young (MODY) was diagnosed with the age of onset of diabetes below 25 years with a strong family history of diabetes for three generations and no insulin requirement for metabolic control for 5 years after diagnosis. The statistical analyses were performed using the Statistical Package for the Social Sciences (SPSS version 25). Results: Of the 250 patients included in the study, 208 (83.2%) subjects were T1DM, 38 (15.2%) T2DM, and 4 (1.6%) with MODY. The mean age of onset of T1DM was 13.7 ± 6.201 years and T2DM was 23.28 ± 3.68 years. Body mass index (BMI) and waist circumference of young T2DM patients were more compared to T1DM, which were statistically significant P < 0.0001, and family history showed strong positivity in patients with young T2DM compared to T1DM. Low-density lipoprotein cholesterol (LDL-C), triglycerides (TGs), and total cholesterol (TC) were more in young T2DM patients compared to T1DM which were statistically significant with P = 0.003 (LDL), P = 0.0015 (TG), and P = 0.03 (TC), respectively. Conclusions: T2DM, previously considered a middle-aged or elderly condition, is now commonly occurring in young adults and children, probably due to a growing epidemic of childhood obesity and lifestyle. Obesity and dyslipidemia were more in T2DM compared to T1DM among young diabetics.

Adoptive transfer of immature dendritic cells with high HO-1 expression delays the onset of T1DM in NOD mice

AimsTo investigate the potential of imDCs with high expression of HO-1 in preventing or delaying the onset of Type 1 diabetes mellitus (T1DM) in non-obese diabetic (NOD) mice. Materials and methodsThe phenotypic features of DCs in each group were assessed using flow cytometry. Western blot analysis was used to confirm the high expression of HO-1 in imDCs induced with CoPP. Additionally, flow cytometry was used to evaluate the suppressive capacity of CoPP-induced imDCs on splenic lymphocyte proliferation. Finally, the preventive effect of CoPP-induced imDCs was tested in NOD mice. Key findingsCompared to imDCs, CoPP-induced imDCs exhibited a reduced mean fluorescence intensity (MFI) of the co-stimulatory molecule CD80 on their surface (P < 0.05) and significantly increased HO-1 protein expression (P < 0.05). Following LPS stimulation, the MFI of co-stimulatory molecules CD80 and CD86 on the surface of CoPP-induced imDCs remained at a lower level (P < 0.05). Furthermore, there was a reduced proliferation rate of lymphocytes stimulated with anti-CD3/28 antibodies. The adoptive transfer of CoPP-imDCs significantly reduced the incidence of T1DM (16.66 % vs. control group: 66.67 %, P = 0.004). Furthermore, at 15 weeks of age, the insulitis score was also decreased in the CoPP-induced imDC treatment group (P < 0.05). There were no significant differences in serum insulin levels among all groups. SignificanceImDCs induced with CoPP and exhibiting high expression of HO-1 demonstrate a robust ability to inhibit immune responses and effectively reduce the onset of diabetes in NOD mice. This finding suggests that CoPP-induced imDCs could potentially serve as a promising treatment strategy for T1DM.

SAT126 Relationship Between Type I Diabetes And Depression In The Pediatric Population

Abstract Disclosure: L.B. Greenblatt: None. M. Epelman: None. S. Demissie: None. Introduction: Type 1 diabetes mellitus (T1DM) is one of the most common chronic illnesses in children. Depression in children and adolescents with T1DM has been associated with negative diabetes related health outcomes, such as recurrent diabetes ketoacidosis. These associations can be bidirectional, where poor glycemic control can worsen symptoms of depression. Adolescents with T1DM and depression pose additional challenges to health care providers due to non-adherence to diabetes management. Objective: The aim of this study is to investigate the relationship between depression and age of onset, duration and T1DM control. We hypothesized that duration of diabetes mellitus positively correlates with depression symptoms. Patients diagnosed with T1DM in adolescence have higher depression scores compared to individuals diagnosed at a younger age. Methods: Individuals with T1DM 11 to 21 years old enrolled in the study. Patients with known psychiatric illnesses and intellectual disabilities were excluded. After obtaining informed consent and assent, participants were asked to complete age specific depression screening form PHQ-9. Forms were immediately scored by the investigator. Patients with moderate symptoms (score of 10 to 14) are provided a list of local mental health resources and individuals with severe depressive symptoms (score &amp;gt; 15) were referred to a pediatric psychiatrist for evaluation. Data on age, sex, ethnicity, age at diagnosis, diabetes duration, recent glycosylated hemoglobin (HbA1C), treatment methods (insulin pump vs injections) and continuous glucose monitor use were collected from patients’ electronic health records. Results: 34 patients, 61.7% female, were screened thus far. The mean age was 16 years and average age at diagnosis was 8 years. 22% of patients were on multiple daily injections and 78% on insulin pump therapy. Most patients (88%) were using continuous glucose monitors. Despite long term care, the average HbA1c was 8%. Girls had higher average PHQ-9 score (7.24) compared to boys (3.69). As expected, high PHQ-9 score was associated with poor diabetes control (r=0.35, p=0.044). There was a positive correlation between PHQ-9 score and duration of T1DM and negative correlation between PHQ-9 score and age at onset (p&amp;gt;0.05). Conclusion: Children and adolescents with T1DM are at risk of depression. Younger age of onset and longer duration of T1DM was associated with higher severity of depression symptoms as evident by PQH-9 score. Poor control, defined by high HbA1C, is positively correlated with depression score. Screening for depression and proper referral should be integrated into routine care for children and adolescents with T1DM. Presentation: Saturday, June 17, 2023

New-onset type 1 diabetes mellitus in the Paediatric Emergency Department: impact of the COVID-19 pandemic.

On the 14th of March 2020, the Spanish government decreed a state of alarm due to the coronavirus disease 2019 (COVID-19) pandemic, directly affecting healthcare. This situation led to delayed diagnosis of several serious diseases, and its impact on many diseases such as the onset of type 1 diabetes mellitus (T1DM) remains unknown. The aim of this study is to determine the impact of the COVID-19 pandemic on the onset of T1DM in children. A descriptive-observational study was performed using data from children younger than 18 years (n=115) admitted with diagnosis of T1DM. We compared the 8 months from May-December 2020 to the same timeframe in 2019. Our data show an increase of newly attended cases of T1DM in 2020, due to referral of Catalan children with onset of diabetes to our centre. Moreover, fewer patients presented with simple hyperglycaemia at the onset of the COVID-19 period. Delay in consulting the hospital, decreased access to the healthcare system, and avoidance of hospitals to minimize exposure to COVID-19 could have contributed to this finding. There were no differences in the number of days of hospitalization (including days in the paediatric intensive care uniy) between the years. The effects of the lockdown during the COVID-19 pandemic not only delayed the diagnosis of diabetes, but also its allowed time for its severity to increase. Future studies should focus on the influence of new variants of COVID-19 on the onset of T1DM during the postvaccination period.

A single center case series of immune checkpoint inhibitor-induced type 1 diabetes mellitus, patterns of disease onset and long-term clinical outcome.

Type 1 diabetes mellitus (T1DM) is a rare, but serious immune-related adverse event (irAE) of immune checkpoint inhibitors (ICIs). Our goal was to characterize treatment outcomes associated with ICI-induced T1DM through analysis of clinical, immunological and proteomic data. This was a single-center case series of patients with solid tumors who received ICIs and subsequently had a new diagnosis of T1DM. ICD codes and C-peptide levels were used to identify patients for chart review to confirm ICI-induced T1DM. Baseline blood specimens were studied for proteomic and immunophenotypic changes. Between 2011 and 2023, 18 of 3744 patients treated at Huntsman Cancer Institute with ICIs were confirmed to have ICI-induced T1DM (0.48%). Eleven of the 18 patients received anti-PD1 monotherapy, 4 received anti-PD1 plus chemotherapy or targeted therapy, and 3 received ipilimumab plus nivolumab. The mean time to onset was 218 days (range 22-418 days). Patients had sudden elevated serum glucose within 2-3 weeks prior to diagnosis. Sixteen (89%) presented with diabetic ketoacidosis. Three of 12 patients had positive T1DM-associated autoantibodies. All patients with T1DM became insulin-dependent through follow-up. At median follow-up of 21.9 months (range 8.4-82.4), no patients in the melanoma group had progressed or died from disease. In the melanoma group, best responses were 2 complete response and 2 partial response while on active treatment; none in the adjuvant group had disease recurrence. Proteomic analysis of baseline blood suggested low inflammatory (IL-6, OSMR) markers and high metabolic (GLO1, DXCR) markers in ICI-induced T1DM cohort. Our case series demonstrates rapid onset and irreversibility of ICI-induced T1DM. Melanoma patients with ICI-induced T1DM display excellent clinical response and survival. Limited proteomic data also suggested a unique proteomic profile. Our study helps clinicians to understand the unique clinical presentation and long-term outcomes of this rare irAE for best clinical management.

Sequential data mining of infection patterns as predictors for onset of type 1 diabetes in genetically at-risk individuals

Infections are implicated in the etiology of type 1 diabetes mellitus (T1DM); however, conflicting epidemiologic evidence makes designing effective strategies for presymptomatic screening and disease prevention difficult. Considering the temporality and combination in which infections occur may provide valuable insights into understanding T1DM etiology but is rarely studied due to limited longitudinal datasets and insufficient analytical techniques. The objective of this work was to demonstrate a computational approach to classify the temporality and combination of infections in presymptomatic T1DM. We present a sequential data mining pipeline that leverages routinely collected infectious disease data from a prospective cohort study, the Environmental Determinants of Diabetes in the Young (TEDDY) study, to extract, interpret, and compare infection sequences. We then utilize this pipeline to assess risk for developing presymptomatic biomarkers of islet autoimmunity and clinical onset of T1DM. Overall, we identified 229 significant sequential rules that increased the risk for developing presymptomatic biomarkers of islet autoimmunity or clinical onset of T1DM. Multiple significant sequential rules involving varicella increased the risk for all presymptomatic biomarker-specific outcomes, while a single significant sequential rule involving parasites significantly increased risk for T1DM. Significant sequential rules involving respiratory illnesses were differentially represented among the presymptomatic biomarkers of islet autoimmunity and clinical onset of T1DM. Risk for T1DM was significantly increased by a single episode of sixth disease at 12 months, representing the only single-event sequence that increased disease risk. Together, these findings provide the first insights into the timing and combination of infections in T1DM etiology, which may ultimately lead to personalized disease screening and prevention strategies. The sequential data mining pipeline developed in this work demonstrates how temporal data mining can be used to address clinically meaningful questions. This method can be adapted to other presymptomatic factors and clinical conditions.

Clinical Analysis of 17 Adult Patients With Fulminant Type 1 Diabetes Mellitus

To explore the clinical characteristics of adult patients with fulminant type 1 diabetes mellitus (FT1DM), a specific subtype of type 1 diabetes mellitus (T1DM). We collected the clinical data of patients who were admitted to West China Hospital, Sichuan University in 2010-2019 for FT1DM and type 1 diabetes mellitus (T1DM) presenting with diabetic ketoacidosis (DKA) at the onset. In addition, all the FT1DM patients were followed up. A total of 70 patients presenting with DKA at the onset of T1DM were admitted to and received treatment at West China Hospital in 2010-2019. Among them, 17 (24.3%) had FT1DM and 53 did not. The mean ages of the FT1DM patients and the non-FT1DM patients were (33.2±12.8) years and (27.5±11.2) years, and the mean body mass indices were (22.6±2.9) kg/m 2 and (19.2±2.9) kg/m 2, respectively. A total of 14 FT1DM cases had symptoms of upper respiratory tract infection or acute gastroenteritis before the onset of the disease and 4 cases were related to pregnancy. The median time from the onset of the disease to the first diagnosis of DKA of the FT1DM group (median [P 25-P 75]: 2 [1-4] days, P<0.001) was significantly shorter than that of the non-FT1DM group (median [P 25-P 75]: 30 [17-78] days). The mean maximum blood glucose levels at the time of the first visit to the doctor of the FT1DM patients ([39.9±11.4] mmol/L, P<0.001) were significantly higher than that of the non-FT1DM patients ([28.9±9.2] mmol/L), but the HbA1c (6.6%±0.6%, P<0.001) and glycosylated serum albumin (GA) (21.4%±3.0%, P=0.001) levels of the FT1DM patients were significantly lower than those of the non-FT1DM group (HbA1c: 12.8%±2.7%; GA: 44.8%±15.0%). The median serum amylase in the FT1DM group was significantly higher than that in the non-FT1DM group (101 [54-336] IU/L vs. 54 [42-166] IU/L, P=0.045) and the median serum lipase in the FT1DM group showed a trend of being higher than that in the T1DM group (81 [57-154] IU/L vs. 46 [28-195] IU/L, P=0.051). 8.7% of the non-FT1DM patients tested positive for anti-glutamic acid decarboxylase antibody (GAD-Ab), while the FT1DM patients all tested negative. At the time of discharge, the mean daily insulin dose of the FT1DM patients was (0.67±0.22) IU/kg, which was not significantly different from that of the non-FT1DM group ([0.74±0.29] IU/kg, P=0.349). After about 6.5 years of follow-up, the mean daily insulin dose of the FT1DM patients was (0.73±0.19) IU/kg, which was similar to the insulin dosage on discharge ( P=0.409). Compared with the non-FT1DM patients presenting with DKA at the onset, FT1DM patients have fewer typical diabetic symptoms, lower fasting C-peptide levels, higher serum amylase levels, and increased incidence of vomiting or other symptoms of gastrointestinal infections, and are more likely to be misdiagnosed. Therefore, it is very important for clinicians to correctly identify FT1DM as early as possible and administer early and long-term insulin replacement therapy.

Clinical profile and outcome of children presenting with diabetic ketoacidosis at a tertiary care hospital in Dakshina Kannada

Background: Diabetic ketoacidosis (DKA) is the most serious metabolic disturbance of type 1 diabetes mellitus (T1DM) and about 25 to 40% of the newly diagnosed T1DM children present with DKA. This research was conducted to study the clinical profile and identify the precipitating factors at time of presentation of DKA and to correlate the type onset of disease with the severity of DKA and the treatment outcome. Methods: Ambispective record based study of children admitted in in the paediatric ward of a tertiary care hospital with DKA between 01 July 2019 and 31 January 2022. Results: A total of 19 patients were enrolled and the mean age of presentation was 10.79±4.17 years with a female predominance. The family history of type 2 DM was noted in 73.7% and osmotic symptoms in 68.4% of the patients. 52.6% of the patients presented in severe DKA. Mean HbA1C noted was 15.14±2.74%. Acute Kidney Injury was present in 10.5% of the patients. Pneumonia was the major precipitating factor. The average length of hospital stay was 7.42±3.27 days. There was no significant correlation with the type of onset of T1DM and the treatment outcome. There was a significant reduction in HbA1c (p&lt;0.05) on follow-up. Conclusions: This study highlights the need for creating awareness, early referral and timely management of T1DM presenting not only in DKA but also during the ambulatory management.

Incidence of new-onset type 1 diabetes during Covid-19 pandemic: A French nationwide population-based study

AimThe association between infection with SARS-CoV-2 and the development of new-onset type 1 diabetes mellitus (T1DM) is unclear. The aim of this study was to examine the impact of the Covid-19 pandemic on the hospitalization rates for new-onset T1DM and diabetic ketoacidosis at diagnosis, in metropolitan France. MethodsThis nationwide retrospective cohort study included hospital data on all patients aged 1 to 35 years old, hospitalized in France due to onset of T1DM, in 2020 and 2021 compared to 2019. ResultsApart from a decrease during the lockdown in 2020, the number of hospitalizations due to new-onset T1DM was not significantly different in 2020 and 2021 than it was in 2019. In the regions most affected by Covid-19 and covering 7,995,449 inhabitants aged from 1 to 35 years old, standardized hospitalization rates were not significantly different in 2020 and in 2021 compared with 2019. The number of hospitalizations for diabetic ketoacidosis at diagnosis was not significantly different after week 14 in 2020 and in 2021 compared with 2019. ConclusionIn this nationwide study, the incidence of hospitalizations for new-onset T1DM and the incidence of diabetic ketoacidosis at diagnosis was not increased during the Covid-19 pandemic in 2020 and 2021. Our results support the fact that infection with SARS-CoV-2 does not promote the development of T1DM.

Teplizumab in Type 1 Diabetes Mellitus: An Updated Review.

Type 1 diabetes mellitus (T1DM) is a chronic autoimmune condition characterized by the irreversible destruction of the β cells of the pancreas, which leads to a lifelong dependency on exogenous insulin. Despite the advancements in insulin delivery methods, the suboptimal outcomes of these methods have triggered the search for therapies that may prevent or reverse the disease. Given the autoimmune aetiology of T1DM, therapies counteracting the immune-mediated destruction of the β-cells are the obvious target. Although several treatment strategies have been attempted to target cellular, humoral and innate immunity, very few have had a clinically meaningful impact. Of all the available immunomodulatory agents, cluster of differentiation (CD) 3 antibodies have exhibited the most promising preclinical and clinical results. Muromonab-CD3, which also happened to be a murine CD3 antibody, was the first monoclonal antibody approved for clinical use and was primarily indicated for graft rejection. The adverse effects associated with muromonab-CD3 led to its withdrawal. Teplizumab, a newer CD3 antibody, has a better side-effect profile because of its humanized nature and non-Fc-receptor-binding domain. In November 2022, teplizumab became the first immunomodulatory agent to be licensed by the US Food and Drug Administration for delaying the onset of T1DM in high-risk adults and children over 8 years old. The mechanism seems to be enhancing regulatory T-cell activity and promoting immune tolerance. This article reviews the mechanism of action and the clinical trials of teplizumab in individuals with T1DM or at risk of developing the disease.

The relationship between GAD65 autoantibody and the risk of T1DM onset.

Type 1 diabetes mellitus (T1DM) is a well-known autoimmune disease, characterized by β-cell destruction in pancreas islet cells, which results insulin deficiency and subsequent hyperglycemic sequelae. While there is screening for type 2 DM that leads to better glycemic control and outcome, the majority of T1DM patients are diagnosed when much of the pancreatic cells and their function are disturbed. The aim of this article is to present an overview of the effective factors in the positivity of Glutamic acid decarboxylase antibody )GADA( and identifying the high-risk individuals for T1DM. We searched English literature available at National Library of Medicine via PubMed, and Google Scholar through December 2020. Finally, 79 papers have been included in the study. Studies were summarized based on the number of positive autoantibodies and onset of T1DM over time and GADA correlation with different variables. GADA is an easy marker to measure that can be detected many months prior to the clinical presentation and remains positive even after early childhood.

Diabetic Ketoacidosis at the Onset of Type 1 Diabetes Mellitus Among Children and Adolescents in Jeddah, Saudi Arabia: A Study From the Emergency Department

Background: Diabetic ketoacidosis (DKA) is a life-threatening complication of type 1 diabetes mellitus (T1DM) and a leading cause of morbidity and mortality in children. We aim to assess the frequency, clinical characteristics, biochemical findings, and outcomes of DKA at the onset of T1DM in young children and adolescents.Design and methods: This retrospective cohort study analyzed the medical records of patients ≤ 16 years old seen in the emergency department at King Abdulaziz University Hospital, Jeddah, Saudi Arabia, between April 2015 and June 2019. The severity of DKA was classified according to the International Society for Pediatric and Adolescent Diabetes (ISPAD) criteria.Results: Out of 207 patients with T1DM, 53 presented with DKA as a new onset. The mean age was 8.51 ± 3.81 years, with the majority being 5-10 years old (52.8%). Polyuria (98.1%), polydipsia (86.8%), weight loss (62.3%), and abdominal pain and vomiting (45.3%) were the most frequent symptoms. Mean random blood glucose was 424.09 ± 108.67 mg/dL and mean venous pH was 7.15 ± 0.36 mmol/L. Of patients, 66% had no associated complications, 24.4% had hypokalemia, 20.8% developed hypoglycemia, and 18.9% developed hyperchloremic metabolic acidosis. One patient had cerebral edema and coma. Based on metabolic acidosis, 24.5% had mild DKA, an equal percentage had severe DKA, and 9.4% had moderate DKA. Of patients, 88.7% were admitted to the pediatric ward and 15.1% to the intensive care unit.Conclusion: A total of 25% of patients diagnosed with T1DM below the age of 17 years presented with DKA. No permanent disabilities or deaths were reported. Forming a registry dedicated to T1DM is needed to follow up on these patients, especially among school-age children, as well as aid in the development of future research locally.

Urinary Albumin Creatinine Ratio has no Significant Association with Retinopathy in Individuals with Type 1 Diabetes Mellitus

Background The relationship between diabetic retinopathy (DR) and nephropathy in type 1 diabetes mellitus (T1DM) is controversial. This study assessed the utility of the spot urinary albumin creatinine ratio (UACR) as a parameter for correlating diabetic nephropathy with DR in individuals with T1DM in Basrah. Methods The study was a cross-sectional observational study of 216 patients with T1DM (16–49 years old) with different DR types. We used demographic variables, different T1DM-related variables (onset and duration of T1DM, glycemic control, latency between T1DM and DR onset, age of onset of DR), and biochemical investigations, such as spot UACR, renal function tests, glycated hemoglobin (HbA1c), anti-glutamic acid decarboxylase-65 (anti-GAD-65) antibody, lipid profile, and thyrotropin. We used ordinal regression analysis to test for the possible primary covariates and adjusted the findings with an analysis of covariates (ANCOVA). Results The patient population showed a slight male preponderance, and uncontrolled T1DM with high HbA1c was found in 93% of the cohort. The mean UACR was 64.37 ± 8.99 mg/g. Normal UACR levels were seen in approximately 60% of the cohort (n=129). Sixty-five individuals were reported to have DR, with a median age of onset of 34 ± 8 years and a median latency period of 13 ± 7 years. UACR had no significant relationship with DR development at any association level, with or without adjustment for the composite regression factors. Conclusion There was no significant association between UACR at any level and DR development before and after adjustment for all of the possible covariates in this study.

Oral Health Assessment in Children and Adolescents with Type 1 Diabetes

Abstract: Objective: To assess oral health status in relation to diabetes-related variables in a cohort of children and adolescents with type 1 diabetes mellitus (T1DM). Study design: Eighty-eight children and adolescents with T1DM (median age: 12 years; range: 6-17 years) had received a comprehensive oral health examination performed by a single dentist and included, simplified oral hygiene index (OHI-S), gingival-index (GI), dental caries indices (DMFT and dft) and stimulated salivary flow rate (SSFR; ml/min). Results: Significantly higher frequency of patients had fair oral hygiene and moderate gingivitis (P<0.001). Significantly lower stimulated salivary flow rate was detected in patients within late childhood group (P=0.038). Increased prevalence of permanent dental caries was observed in late adolescent period (P=0.001). There was significant increase in primary dental caries in children diagnosed with diabetes before six years (P=0.004). Patient´s age was positively correlated with SSFR, gingival-index and DMFT-index. DMFT-index was positively correlated with T1DM duration and HbA1c level. There was significant positive correlation between OHI-S and GI. Conclusion: Children and adolescents with T1DM displayed unfavorable oral health profiles that have been strongly linked to patient´s age, age at onset and duration of T1DM and level of metabolic control. Regular recall dental visits must be considered.

The Impact of SARS-CoV-2 Pandemic on the New Cases of T1DM in Children. A Single-Centre Cohort Study.

Type 1 diabetes mellitus (T1DM) represents one of the most frequent chronic illnesses affecting children. The early diagnosis of this disease is crucial, as it plays a key role in preventing the development of a life-threatening acute complication: diabetic ketoacidosis. The etiopathogenetic role of viral infections has long been suggested and emerging data are pointing towards a complex bidirectional relationship between diabetes and COVID-19. The aim of this study is to assess the impact of the COVID-19 pandemic on the incidence and severity of new T1DM cases in children in Romania. We analyzed the differences between a group of 312 patients diagnosed with T1DM in the period 2003–2019 and a group of 147 children diagnosed during the pandemic. The data were investigated using statistical analysis of a series of relevant variables. The total number of newly diagnosed T1DM increased by 30.08% in the period March 2020–February 2021 compared to the previous years. The patients in the pandemic group had a higher mean age at the onset of T1DM, were less frequently living in an urban area, and presented a higher mean value of HbA1c. Diabetic ketoacidosis at the onset of T1DM was 67.40% more frequent, and a higher percentage of these patients presented with a severe form. The duration of T1DM symptoms did not differ significantly between the two groups. A number of 8 patients associated SARS-CoV-2 infection at the time of T1DM diagnosis.

Effects of the Rate of Impaired Insulin Secretion on Bone Mineral Density in Type 1 Diabetes

Background: Type 1 Diabetes mellitus (T1DM) is a well-known condition associated with low bone mineral density (BMD) and bone fracture, in which one of the risk factor is impaired endogenous insulin secretion. However, the association between the rate of impaired insulin secretory capacity in T1DM and BMD remains to be elucidated. Objective: To clarify the effect of the rate of impaired insulin secretion on BMD in T1DM. Patients and Methods: This a retrospective single-center cross-sectional study, in which consecutive one-hundred seventy Japanese patients with T1DM at Kobe University Hospital were registered. According to the diagnostic criteria of The Japan Diabetes Society, patients were stratified into three subtypes; acute-onset (AO) (n =51, male 25%, 39 ± 15 years), slowly-progressive (SP) (n =37, male 37%, 57 ± 14 years), and fulminant (F) (n =12, male 33%, 51 ± 15 years) mainly by insulin secretory capacity at onset of T1DM. Lumbar spine (LS) and femoral neck (FN) BMD Z-score between three groups were evaluated. Results: The LS BMD is lower in AO than SP (p =0.03), while no differences were observed compared to F (SP/AO/F; 0.38 ± 1.08/-0.25 ± 0.96/-0.35 ± 1.01). The FN BMD also tended to be lower in AO than in SP (p =0.08) and in F (p =1.00) (SP/AO/F;0.03 ± 1.01/-0.44 ± 0.96/-0.35 ± 0.70). To identify the factors associated with decreased BMD, the multivariate regression analysis was performed using AO and SP. The LS BMD was associated with the pathogenic group (p =0.01). Since a negative correlation was seen between durations and CPR both in AO and SP group (p <0.01, p <0.01), we divided these subjects into following 5 groups; 1 to 4, 5 to 9, 10 to 14, 15 to 19, and more than 20 years. In these groups, the CPR was lower in AO than in SP in 1 to 4 years (p <0.01). Intriguingly, LS BMD was started to decline in 5 to 9 years (p =0.03) and was still continued in 10 to 14 years (p =0.01). In FN, BMD was started to decline in 10 to 14 years (p =0.01), suggesting the BMD decline followed by impaired insulin secretion. However, the difference of both BMD and CPR between AO and SP groups were not seen in more than 15 years group, indicating this tangent BMD difference is link to the difference of insulin secretion. Conclusions: This study firstly showed that pathogenic subtypes of T1DM differently affected on BMD. A detailed examination of each disease period showed that BMD continued to decrease as impaired insulin secretion.