Have interventions aimed at assisting general practitioners in facilitating earlier diagnosis of type 1 diabetes in children been successful in preventing acute complications? A systematic review.

BACKGROUND: Diabetic ketoacidosis (DKA) is a life-threatening emergency that can result from delayed diagnosis of type 1 diabetes mellitus (T1DM). Three-quarters of Australian children with a new diagnosis of T1DM visit their general practitioner (GP) the week prior to developing DKA, with similar trends observed internationally. OBJECTIVE: To summarise interventions in general practice to reduce diagnostic delay in paediatric T1DM and to evaluate their effectiveness. METHODS: Six databases (Ovid, Web of Science, CINAHL, Evidence-Based Medicine Reviews, Google Scholar and EMBASE) were searched. Any English language, less than 20 years study involving interventions targeting GPs specifically in the prevention of paediatric DKA, was included. Primary outcomes were (a) the number of children presenting to the hospital in DKA following diagnostic delay after a GP visit and (b) DKA rate. The secondary outcome was changes in GPs' behaviour regarding timeliness of referrals. Two reviewers completed title, abstract and full-text review, with conflicts resolved by a third reviewer. ROBINS-I risk of bias was used for appraisal. High heterogeneity among studies rendered meta-analysis unsuitable. Structured tabulation of results was completed for analysis. The date of last search was 2 July 2023. RESULTS: Eight studies were included (three conference abstracts and five peer-reviewed publications.) We identified six intervention types attempting to facilitate timely diagnosis of type 1 diabetes in the general practice setting: direct communication, indirect communication, education sessions, electronic clinical decision support tools, updated referral pathways and provision of glucose and/or ketone monitors. Due to the limited number of peer-reviewed studies identified by this review, we were not able to identify the extent to which these interventions were successful. CONCLUSION: Paucity of information regarding study methodology and high heterogeneity among study design and outcome measures limited our conclusions regarding acceptability, effectiveness and reach. Future studies should include GPs in their design and consider the sustainability of interventions in the long term. PROSPERO REGISTRATION NUMBER: CRD42023412504.

GLP-1 receptor agonist-induced diabetic ketoacidosis: A case report.

RATIONALE: Glucagon-like peptide-1 is an endogenous incretin that plays an active role in weight loss and hypoglycemia. Dulaglutide is a long-acting glucagon-like peptide-1 receptor agonist (GLP-1RA), which has been approved for the treatment of patients with type 2 diabetes (T2D). GLP-1RAs can increase insulin secretion and inhibit glucagon release, thereby leading to a decrease in blood glucose levels within the body. Specifically, GLP-1RAs control postprandial blood glucose levels by inhibiting hepatic glucose production and delaying gastric emptying. However, attention should be given to gastrointestinal adverse reactions. There are currently a few cases of GLP-1RA causing diabetic ketoacidosis (DKA). PATIENT CONCERNS: The following report details the case of a 50-year-old Chinese female who has been living with diabetes for 12 years. Initially diagnosed with T2D, she was subsequently identified as a patient with latent autoimmune diabetes in adults (LADA) following treatment. The patient presented severe nausea, vomiting, and fatigue 1 day after injecting dulaglutide 1 time and discontinuing insulin therapy. She was diagnosed with severe DKA in the emergency department. DIAGNOSES: LADA and DKA. INTERVENTIONS: Changed from dulaglutide to insulin therapy. OUTCOMES: After discontinuing dulaglutide and switching to insulin for blood glucose reduction, the patient's DKA was corrected, and blood glucose levels returned to normal. LESSONS: This case suggests that clinicians should be alert to patients with severe DKA in cases of severe gastrointestinal adverse reactions after the use of GLP-1RAs. In addition, in most countries, GLP-1RAs are administered to patients with T2D, but we should consider the use of GLP-1RAs in patients with type 1 diabetes and LADA.

Secondary diabetes mellitus in acromegaly: Case report and literature review.

RATIONALE: Acromegaly, predominantly resulting from a pituitary adenoma, is marked by excessive secretion of growth hormone (GH) and insulin-like growth factor-1 (IGF-1). However, normalization of blood glucose levels posttreatment is rarely achieved. This case study aims to highlight the diagnostic challenges posed by overlapping symptoms of acromegaly and diabetes, emphasizing the importance of precise diagnosis and effective treatment strategies for optimal patient outcomes. PATIENT CONCERNS: A 22-year-old male was hospitalized for diabetic ketoacidosis and exhibited classic signs of acromegaly, such as enlarged hands and feet, and distinct facial changes. DIAGNOSES: The patient's diagnosis of acromegaly, attributed to a pituitary adenoma, was confirmed through clinical observations, laboratory findings (notably raised serum GH and IGF-1 levels, and absence of GH suppression after glucose load during an OGTT), and pituitary MRI scans. INTERVENTIONS: The patient underwent 2 surgical tumor resections followed by gamma knife radiosurgery (GKRS). After treatment, GH, IGF-1, and blood glucose levels normalized without further need for hypoglycemic intervention. OUTCOMES: Posttreatment, the patient achieved stable GH, IGF-1, and blood glucose levels. The hyperglycemia was attributed to the GH-secreting tumor, and its resolution followed the tumor's removal. LESSONS: This case emphasizes the need for comprehensive assessment in patients with acromegaly to address coexisting diabetic complications. Surgical and radiotherapeutic management of acromegaly can lead to significant metabolic improvements, highlighting the importance of interdisciplinary care in managing these complex cases.

SGLT-2i associated diabetic ketoacidosis in the setting of cardiogenic shock.

Diabetic ketoacidosis (DKA) is a life-threatening complication of diabetes mellitus. Sodium-glucose co-transport inhibitors (SGLT-2i), a treatment for type 2 diabetes, have demonstrated a survival benefit in patients with heart failure with reduced ejection fraction (HFrEF). Many patients with HFrEF have been started on SGLT-2i and sometimes transitioned off insulin due to improved glycaemic control. SGLT-2i have demonstrated an association with DKA. Here, we present a case of simultaneous cardiogenic shock and DKA in the setting of recent transition from insulin to an SGLT-2i. DKA in conjunction with decompensated heart failure is a combination that will likely occur more frequently as SGLT-2i use becomes more widespread in patients with HFrEF, and its identification and management require special considerations. Volume status, potassium management and recognition of DKA in these patients must be approached differently than in other cases of DKA.

Integrating randomized controlled trials and non-randomized studies of interventions to assess the effect of rare events: a Bayesian re-analysis of two meta-analyses.

BACKGROUND: There is a growing trend to include non-randomised studies of interventions (NRSIs) in rare events meta-analyses of randomised controlled trials (RCTs) to complement the evidence from the latter. An important consideration when combining RCTs and NRSIs is how to address potential bias and down-weighting of NRSIs in the pooled estimates. The aim of this study is to explore the use of a power prior approach in a Bayesian framework for integrating RCTs and NRSIs to assess the effect of rare events. METHODS: We proposed a method of specifying the down-weighting factor based on judgments of the relative magnitude (no information, and low, moderate, serious and critical risk of bias) of the overall risk of bias for each NRSI using the ROBINS-I tool. The methods were illustrated using two meta-analyses, with particular interest in the risk of diabetic ketoacidosis (DKA) in patients using sodium/glucose cotransporter-2 (SGLT-2) inhibitors compared with active comparators, and the association between low-dose methotrexate exposure and melanoma. RESULTS: No significant results were observed for these two analyses when the data from RCTs only were pooled (risk of DKA: OR = 0.82, 95% confidence interval (CI): 0.25-2.69; risk of melanoma: OR = 1.94, 95%CI: 0.72-5.27). When RCTs and NRSIs were directly combined without distinction in the same meta-analysis, both meta-analyses showed significant results (risk of DKA: OR = 1.50, 95%CI: 1.11-2.03; risk of melanoma: OR = 1.16, 95%CI: 1.08-1.24). Using Bayesian analysis to account for NRSI bias, there was a 90% probability of an increased risk of DKA in users receiving SGLT-2 inhibitors and an 91% probability of an increased risk of melanoma in patients using low-dose methotrexate. CONCLUSIONS: Our study showed that including NRSIs in a meta-analysis of RCTs for rare events could increase the certainty and comprehensiveness of the evidence. The estimates obtained from NRSIs are generally considered to be biased, and the possible influence of NRSIs on the certainty of the combined evidence needs to be carefully investigated.

Comparison over Time of Adverse Drug Reactions in Diabetes Patients Treated with Sodium-Glucose Cotransporter 2 Inhibitors.

BACKGROUNDS: The prescription of sodium-glucose cotransporter-2 (SGLT2) inhibitors have been increasing due to their additional benefits, including weight loss, cardioprotection and renoprotection. Accordingly, there are concerns about the potential rise in severe adverse drug reactions (ADRs), such as urinary tract infections, diabetic ketoacidosis, volume depletion, and hypoglycemia. The Society has announced recommendations on the proper use of SGLT2 inhibitors. We aimed to elucidate the recent occurrence of severe ADRs which need discontinuation of SGLT2 inhibitors or hospitalization. METHODS: In this retrospective cohort study, we identified 391 diabetic patients who were prescribed SGLT2 inhibitors upon admission to our hospital between April 2017 and March 2023. Of these, 68 patients who discontinued SGLT2 inhibitors for reasons other than ADRs were excluded. Patients were classified into the 2017 group and the 2020 group based on the treatment period of SGLT2 inhibitors, and the occurrence of ADRs and patient backgrounds were compared between the two groups. RESULTS: A total of 323 eligible patients were identified. Discontinuations of SGLT2 inhibitors decreased in the 2020 group (p < 0.05). However, discontinuations due to frailty increased (p < 0.05). Hospitalization due to ADRs, specifically those due to urinary tract infections, diabetic ketoacidosis, or volume depletion, did not specifically decrease (p = 0.273). CONCLUSIONS: This study indicated that there has been some improvement in the awareness of the proper use of SGLT2 inhibitors and there is still a need to continue enlightenment activities.

Factors contributing to diabetic ketoacidosis readmission in hospital settings in the United States: A scoping review.

BACKGROUND: Hospitalization of patients with DKA creates a significant burden on the US healthcare system. While previous studies have identified multiple potential contributors, a comprehensive review of the factors leading to DKA readmissions within the US healthcare system has not been done. This scoping review aims to identify how access to care, treatment adherence, socioeconomic status, race, and ethnicity impact DKA readmission-related patient morbidity and mortality and contribute to the socioeconomic burden on the US healthcare system. Additionally, this study aims to integrate current recommendations to address this multifactorial issue, ultimately reducing the burden at both individual and organizational levels. METHODS: The PRISMA-SCR (Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews) was used as a reference checklist throughout this study. The Arksey and O'Malley methodology was used as a framework to guide this review. The framework methodology consisted of five steps: (1) Identify research questions; (2) Search for relevant studies; (3) Selection of studies relevant to the research questions; (4) Chart the data; (5) Collate, summarize, and report the results. RESULTS: A total of 15 articles were retained for analysis. Among the various social factors identified, those related to sex/gender (n = 9) and age (n = 9) exhibited the highest frequency. Moreover, race and ethnicity (n = 8) was another recurrent factor that appeared in half of the studies. Economic factors were also identified in this study, with patient insurance type having the highest frequency (n = 11). Patient income had the second highest frequency (n = 6). Multiple studies identified a link between patients of a specific race/ethnicity and decreased access to treatment. Insufficient patient education around DKA treatment was noted to impact treatment accessibility. Certain recommendations for future directions were highlighted as recurrent themes across included studies and encompassed patient education, early identification of DKA risk factors, and the need for a multidisciplinary approach using community partners such as social workers and dieticians to decrease DKA readmission rates in diabetic patients. CONCLUSION: This study can inform future policy decisions to improve the accessibility, affordability, and quality of healthcare through evidence-based interventions for patients with DM following an episode of DKA.

Development and validation of a nomogram for screening patients with type 2 diabetic ketoacidosis.

OBJECTIVE AND BACKGROUND: The early detection of diabetic ketoacidosis (DKA) in patients with type 2 diabetes (T2D) plays a crucial role in enhancing outcomes. We developed a nomogram prediction model for screening DKA in T2D patients. At the same time, the input variables were adjusted to reduce misdiagnosis. METHODS: We obtained data on T2D patients from Mimic-IV V0.4 and Mimic-III V1.4 databases. A nomogram model was developed using the training data set, internally validated, subjected to sensitivity analysis, and further externally validated with data from T2D patients in Aviation General Hospital. RESULTS: Based on the established model, we analyzed 1885 type 2 diabetes patients, among whom 614 with DKA. We further additionally identified risk factors for DKA based on literature reports and multivariate analysis. We identified age, glucose, chloride, calcium, and urea nitrogen as predictors in our model. The logistic regression model demonstrated an area under the curve (AUC) of 0.86 (95%CI: 0.85-0.90]. To validate the model, we collected data from 91 T2D patients, including 15 with DKA, at our hospital. The external validation of the model yielded an AUC of 0.68 (95%CI: 0.67-0.70). The calibration plot confirmed that our model was adequate for predicting patients with DKA. The decision-curve analysis revealed that our model offered net benefits for clinical use. CONCLUSIONS: Our model offers a convenient and accurate tool for predicting whether DKA is present. Excluding input variables that may potentially hinder patient compliance increases the practical application significance of our model.

Trends in diabetic ketoacidosis- and hyperosmolar hyperglycemic state-related mortality during the COVID-19 pandemic in the United States: A population-based study.

BACKGROUND: During the pandemic, a notable increase in diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS), conditions that warrant emergent management, was reported. We aimed to investigate the trend of DKA- and HHS-related mortality and excess deaths during the pandemic. METHODS: Annual age-standardized mortality rates related to DKA and HHS between 2006 and 2021 were estimated using a nationwide database. Forecast analyses based on prepandemic data were conducted to predict the mortality rates during the pandemic. Excess mortality rates were calculated by comparing the observed versus predicted mortality rates. Subgroup analyses of demographic factors were performed. RESULTS: There were 71 575 DKA-related deaths and 8618 HHS-related deaths documented during 2006-2021. DKA, which showed a steady increase before the pandemic, demonstrated a pronounced excess mortality during the pandemic (36.91% in 2020 and 46.58% in 2021) with an annual percentage change (APC) of 29.4% (95% CI: 16.0%-44.0%). Although HHS incurred a downward trend during 2006-2019, the excess deaths in 2020 (40.60%) and 2021 (56.64%) were profound. Pediatric decedents exhibited the highest excess mortality. More than half of the excess deaths due to DKA were coronavirus disease 2019 (COVID-19) related (51.3% in 2020 and 63.4% in 2021), whereas only less than a quarter of excess deaths due to HHS were COVID-19 related. A widened racial/ethnic disparity was observed, and females exhibited higher excess mortality than males. CONCLUSIONS: The DKA- and HHS-related excess mortality during the pandemic and relevant disparities emphasize the urgent need for targeted strategies to mitigate the escalated risk in these populations during public health crises.

Management of diabetic ketoacidosis in children: Does early insulin glargine help improve outcomes?

BACKGROUND: Rebound hyperglycemia following the resolution of diabetic ketoacidosis (DKA) is common in pediatric patients with type 1 diabetes, increasing the risk of recurrent DKA and complicating the transition to subcutaneous insulin. Multiple studies suggest that early administration of long-acting insulin analogs during DKA management safely improves this transition. OBJECTIVE: This study aimed to determine whether early insulin glargine administration in children with DKA prevents rebound hyperglycemia and recurrent ketosis without increasing the rate of hypoglycemia or hypokalemia. METHODS: Patients aged <21 years presenting with DKA to Children's Mercy Kansas City between October 2012 and October 2016 were reviewed. They were categorized as Early (>4 h of overlap with intravenous [IV] insulin) and Late (<2 h of overlap) cohorts. RESULTS: We reviewed 546 DKA admissions (365 Early and 181 Late). Rebound hyperglycemia (>180 mg/dL) was lower in the Early group (66% vs. 85%, p ≤ 0.0001). Hypoglycemia (<70 mg/dL) during IV insulin administration was higher in the Early group than in the Late group (27% vs. 19%, p = 0.042). Hypoglycemia within 12 h of IV insulin discontinuation was lower in the Early group (16% vs. 26%, p = 0.012). Recurrent ketosis, hypokalemia, and cerebral edema were not different between the groups. CONCLUSIONS: Early glargine administration in pediatric DKA management is safe, decreases the rate of rebound hyperglycemia, and improves the transition to subcutaneous insulin. Hypoglycemia is less frequent following IV insulin discontinuation with early glargine, but the IV insulin rate may need to be reduced to minimize hypoglycemia during IV insulin infusion.

Type 1 Diabetes Mellitus in the First Years of Life - Onset, Initial Treatment, and Early Disease Course.

OBJECTIVE: This study investigated the onset and the choice of treatment in children with very early onset of type 1 diabetes mellitus (T1D). METHODS: The study included 5,763 patients from the German Diabetes Patient Follow-up registry with onset of T1D in the first 4 years of life from January 2010 - June 2022. The analysis included diabetes-specific parameters, anthropometric data, and mode of treatment at onset, within the first and second year of T1D. Three groups were compared according to age at onset (G1: 223 patients 6-<12 months, G2: 1519 patients 12-<24 months, G3: 4001 patients 24-48 months). RESULTS: In 12.3% of all cases in childhood and adolescence, the incidence of diabetes in the first 4 years of life was rare. At the onset, clinical status was worse and diabetic ketoacidosis (DKA) rates were higher in G1 and G2 (52.3% and 46.5%, respectively) compared to G3 (27.3% (p<0.001)). G1 and G2 were significantly more likely to be treated with insulin pump therapy (CSII) 2 years after onset (98.1% and 94.1%, respectively)) compared to G3 (85.8%, p<0.001). Median HbA1c after 2 years did not differ between groups (G1: 7.27% (56.0 mmol/mol), G2: 7.34% (56.7 mmol/mol) and G3: 7.27% (56.0 mmol/mol)) or when comparing CSII vs MDI. The rate of severe hypoglycemia (SH) and DKA during the first 2 years of treatment did not differ among the three groups, ranging from 1.83-2.63/100 patient-years (PY) for DKA and 9.37-24.2/100 PY for SH. Children with T1D under 4 years of age are more likely to be diagnosed with celiac disease but less likely to have thyroiditis than older children with T1DM. CONCLUSIONS: Young children with T1D had high rates of DKA at onset and were predominantly treated with insulin pump therapy during the first 2 years. The median HbA1c for all three groups was<7.5% (58 mmol/mol) without increased risk of SH or DKA. The use of continuous glucose monitoring (CGM) was not associated with lower HbA1c in children under 48 months.

Feline acute patient physiologic and laboratory evaluation scores and other prognostic factors in cats with first-time diabetic ketoacidosis.

BACKGROUND: Acute Patient Physiologic and Laboratory Evaluation (APPLE) scores have not been reported in cats with diabetic ketoacidosis (DKA). HYPOTHESIS: In cats with DKA, APPLE scores will be significantly higher in non-survivors compared with survivors and these scores will predict mortality. ANIMALS: Sixty-eight cats with DKA. METHODS: Retrospective study. The APPLE scores, blood glucose concentration (BG), venous pH, and ketone concentrations were compared between survivors and non-survivors. Simple logistic regression was used to determine if these variables predict the binary variable of survival or non-survival, and if they did, an empirical optimal cut point for mortality prediction was calculated. RESULTS: The APPLEfast and APPLEfull scores were significantly higher in non-survivors (30 cats; 24.6 ± 7.4 and 45.2 ± 7.3 , respectively) compared with survivors (38 cats; 20.9 ± 6.2 and 41.7 ± 6.5 ; P = .01 and P = .02, respectively). The APPLEfast (P = .03) but not the APPLEfull scores (P = .06) predicted mortality. For every 1 unit increase in the APPLEfast score, the odds of death increased by 1.08 (95% confidence interval [CI], 1.006-1.17; P = .03). Median BG was significantly higher in non-survivors (431 mg/dL; range, 260-832 mg/dL) compared with survivors (343 mg/dL; range, 256-738 mg/dL; P = .01) and BG predicted mortality (P = .02). For every 1 mg/dL increase in BG, the odds of death increased by 1.004 (95% CI, 1.0006-1.008). Empirical optimal cut points for APPLEfast and BG mortality prediction were 24.5 and 358 mg/dL, respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: The APPLEfast score and BG predict mortality in cats with DKA and can be used to stratify populations by risk of mortality in clinical trials of DKA in cats.

Clinical Outcomes in Pediatric Patients With Type 1 Diabetes With Early Versus Late Diagnosis: Analysis From the DPV Registry.

OBJECTIVE: This study was conducted to evaluate the effects of early clinical diagnosis of type 1 diabetes by comparison of clinical parameters at diagnosis and during follow-up in patients with pediatric type 1 diabetes with early, intermediate, and late diagnosis. RESEARCH DESIGN AND METHODS: In a population-based analysis, data on 14,292 pediatric patients with type 1 diabetes diagnosed between 2015 and 2019 were retrieved from the Diabetes Prospective Documentation (DPV) registry in March 2023. Patients were divided into four groups: one with diabetic ketoacidosis (DKA) at diagnosis and three with early, intermediate, or late diagnosis based on age-dependent HbA1c terciles. Laboratory-measured HbA1c values and those estimated from continuous glucose monitoring were aggregated as a combined glucose indicator (CGI). Insulin dose-adjusted CGI values <9% were defined as partial remission. RESULTS: At diagnosis, patients had a median age of 9.8 years (IQR 6.8; 13.0). Three years later, patients with early diagnosis had lower CGI than patients with late diagnosis or DKA (mean [95% CI] 7.46% [7.40; 7.53] vs. 7.81% [7.75; 7.87] or 7.74% [7.68; 7.79], respectively; each P < 0.001). More patients experienced partial remission (12.6% [11.0; 14.4] vs. 9.1% [7.7; 10.7] or 8.6% [7.3; 10.0]; each P < 0.001), and 11.7% [10.2; 13.5] of patients with intermediate diagnosis were in partial remission. CONCLUSIONS: Early clinical diagnosis of type 1 diabetes may be beneficial for metabolic control and remission after 3 years of follow-up. Patients diagnosed early may represent a distinct group with better resources or with a different disease biology and slower ß-cell destruction, which needs further evaluation.

A View in the Dark: Two Cases of Acute Esophageal Necrosis in the Setting of Diabetic Ketoacidosis.

Acute esophageal necrosis (AEN), also known as Gurvits syndrome, is a rare and potentially life-threatening condition characterized by necrosis of the esophageal mucosa. Acute esophageal necrosis is often associated with critical conditions, such as myocardial infarction, diabetic ketoacidosis (DKA), coronavirus disease 2019 (COVID-19) infection, or post-surgical complications. Patients typically present with nausea, hematemesis, acute dysphagia, and melena. Given its high mortality rate, prompt detection with upper endoscopy and early initiation of treatment are crucial. Most cases of Gurvits syndrome are managed conservatively using intravenous fluids, proton pump inhibitors, and antibiotics. Herein, we present a case series of AEN in the setting of DKA. Both patients received supportive care and were discharged in a stable condition.

Diabetic ketoacidosis in youth with diabetes mellitus during the COVID-19 pandemic.

OBJECTIVES: We sought to determine if the early months of the coronavirus disease 2019 (COVID-19) pandemic influenced pediatric diabetic ketoacidosis (DKA) hospitalization characteristics. METHODS: This is a cross-sectional study of youth with laboratory-confirmed DKA admitted to a large tertiary children's hospital in the USA. Data were collected from admissions in March through July 2019 and March through July 2020, respectively. We evaluated the clinical characteristics of hospitalization, including demographic data and DKA severity. We used univariable ordinal logistic regression followed by multiple ordinal logistic regression to adjust for potential confounders. RESULTS: We included 137 children with diabetes admitted for DKA in the relevant period in 2019 and 173 patients admitted for DKA in the same period in 2020. Hemoglobin A1C (HbA1c) upon admission was higher in 2020 (median=12.2 %) than in 2019 (11.5 %, p=0.018). Children who were admitted with DKA in 2020 were less likely to be autoantibody positive than those in 2019 (83 vs. 91 %, p=0.028). In the univariable model, being admitted in 2020 was significantly associated with more severe DKA (p=0.038), as was HbA1c (p=0.001). After adjusting for HbA1c upon admission, admission year was no longer significantly associated with more severe DKA. CONCLUSIONS: In this study of pediatric diabetes of any type and duration of diabetes, youth admitted for DKA at the start of the COVID-19 pandemic, compared with those admitted during the year before, were more likely to have autoantibody-negative diabetes and had significantly higher HbA1c. Additionally, higher HbA1c seemed to mediate more severe DKA during the pandemic.

Association between COVID-19 and the incidence of type 1 diabetes in Portugal - a registry study.

BACKGROUND: Viral respiratory infections may precipitate type 1 diabetes (T1D). A possible association between the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, and the incidence of T1D is being determined. This study was carried out using Portuguese registries, aiming at examining temporal trends between COVID-19 and T1D. METHODS: Hospital data, comparing the incidence before and during the COVID-19 pandemic, from children and young adults diagnosed with new-onset T1D, was acquired beginning in 2017 and until the end of 2022. Data was obtained from nine different Portuguese hospital units. The impact of the COVID-19 pandemic, beginning in March 2020, was assessed comparing the annual numbers of new-onset T1D cases. The annual median levels of glucose, glycated hemoglobin (HbA1c) and fasting C-peptide at T1D diagnosis were compared. The annual number of diabetic ketoacidosis (DKA) episodes among new T1D cases was also assessed at two centers. RESULTS: In total, data from 574 newly diagnosed T1D patients was analyzed, including 530 (92.3%) children. The mean ages for child and adult patients were 9.1 (SD 4.4) and 32.8 (SD 13.6) years, respectively. 57.8% (331/573) were male, one patient had unknown sex. The overall median (25-75 percentiles) levels of glucose, HbA1c and fasting C-peptide at diagnosis were 454 mg/dL (356-568), 11.8% (10.1-13.4) and 0.50 µg/L (0.30-0.79), respectively. DKA at T1D diagnosis was present in 48.4% (76/157). For eight centers with complete 2018 to 2021 data (all calendar months), no overall significant increase in T1D cases was observed during the COVID-19 pandemic, i.e. 90 cases in 2018, 90 cases in 2019, 112 in 2020 and 100 in 2021 (P for trend = 0.36). Two of the centers, Faro (CHUA) and Dona Estefânia (CHULC) hospitals, did however see an increase in T1D from 2019 to 2020. No significant changes in glucose (P = 0.32), HbA1c (P = 0.68), fasting C-peptide (P = 0.20) or DKA frequency (P = 0.68) at the time of T1D diagnosis were observed over the entire study period. CONCLUSION: The T1D incidence did not increase significantly, when comparing the years before and during the COVID-19 pandemic, nor did key metabolic parameters or number of DKA episodes change.

A systematic review and meta-analysis comparing outcomes between using subcutaneous insulin and continuous insulin infusion in managing adult patients with diabetic ketoacidosis.

BACKGROUND: The purpose of this systematic review and meta-analysis was to synthesize the current literature to determine the safety and efficacy of using subcutaneous insulin compared to an intravenous (IV) insulin infusion in managing diabetic ketoacidosis (DKA). METHODS: We searched Ovid-Medline, EMBASE, SCOPUS, BIOSIS and CENTRAL from inception to April 26, 2024. Randomized controlled trials (RCTs) and observational studies that assessed the use of subcutaneous compared to intravenous insulin for the treatment of mild to moderate DKA were included. Data extraction and quality assessment were performed by two independent reviewers and disagreements were resolved through further discussion or by a third reviewer. The Cochrane Risk of Bias tool version 2.0 was used to evaluate the RCTs and the Risk of Bias in Non-randomized Studies of Interventions (ROBINS)-I tool was used to evaluate the observational studies. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria. Meta-analyses were conducted using random-effects models. We followed the PRISMA guidelines for reporting our findings. RESULTS: Six RCTs (245 participants) and four observational studies (8444 patients) met our inclusion criteria. Some studies showed a decreased length of stay (Mean Difference [MD] in days: -0.39; 95% CI: -2.83 to 2.08; I2: 0%) among individuals treated with subcutaneous insulin compared to intravenous insulin. There was no difference in the risk of all-cause mortality, time to resolution of DKA (MD in hours: 0.17; 95% confidence interval [CI]: -3.45 to 3.79; I2: 0%) and hypoglycemia (Risk Ratio [RR]: 1.02; 95% CI: 0.88 to 1.19; I2: 0%) between the two groups. CONCLUSION: Treatment of DKA with subcutaneous insulin may be a safe and effective alternative to IV insulin in selected patients. The limited available evidence underscores the need for further studies to explore optimal dosing, patient selection criteria and long-term outcomes.

Clinical features, biomarkers and diabetic ketoacidosis at diagnosis of type 1 diabetes among children and adolescents in Sana'a, Yemen.

INTRODUCTION: There is little published information on type 1 diabetes (T1D) in children in Yemen. We aimed to identify the clinical characteristics, biomarkers and diabetic ketoacidosis (DKA) at diagnosis of T1D among children and adolescents in a diabetes centre in Sana'a, Yemen. METHODS: A total of 485 children and adolescents aged ≤18 years diagnosed with T1D during the period 2010-2020 were included in the study. The variables investigated were demographic and clinical characteristics, biomarkers, subtypes of T1D, and the risk factors for severe DKA at diagnosis. RESULTS: At diagnosis, children aged <10 years compared with those aged ≥10 years had higher mean plasma glucose (p<0.001) and mean HbA1c (p=0.026), and lower mean C-peptide (pmol/L) (p=0.019), and a higher frequency of DKA at diagnosis than older children (p<0.001). A majority of the study population (383, 79%) presented in DKA . Children aged <10 years presenting with DKA had significantly longer median appraisal interval (p=0.009) and median total diagnosis interval (p=0.025), and significantly lower mean C-peptide (p=0.001) as compared with their peers without DKA. The prevalence of autoantibody-negative 'idiopathic' T1D was 36 (32%) of the total number tested for autoantibody and familial T1D 61 (12.6%) of all the study population. CONCLUSION: In Yemen children aged <10 years with new-onset T1D frequently faced the challenge of a delay in diagnosis and treatment initiation, with severe hyperglycaemia and a higher risk of DKA at diagnosis.

Association of sodium glucose co-transporter-2 inhibitors with risk of diabetic ketoacidosis among hospitalized patients: A multicentre cohort study.

INTRODUCTION: Sodium glucose co-transporter-2 inhibitors (SGLT-2i) are increasingly being used among hospitalized patients. Our objective was to assess the risk of diabetic ketoacidosis (DKA) among hospitalized patients receiving an SGLT-2i. RESEARCH DESIGN AND METHODS: We conducted a multicentre cohort study of patients hospitalized at 19 hospitals. We included patients over 18 years of age who received an SGLT-2i or a dipeptidyl peptidase-4 inhibitor (DPP-4i) in hospital. The primary outcome was the risk of DKA during their hospitalization. RESULTS: 61,517 patients received a DPP-4i and 11,061 received an SGLT-2i. The risk of inpatient DKA was 0.07 % (N = 41 events) among adults who received a DPP-4i and 0.18 % (N = 20 events) among adults who received an SGLT-2i; adjusted odds ratio of 3.30 (95 % CI: 1.85-5.72). CONCLUSIONS: In hospitalized patients, the absolute risk of DKA was 0.2 %, which corresponded to a three-fold higher relative risk.