Phenotype and predictors of insulin independence in adults presenting with diabetic ketoacidosis: a prospective cohort study.

AIMS/HYPOTHESIS: The aim of this work was to describe the phenotype of adults presenting with a first episode of diabetic ketoacidosis (DKA) in Cape Town, South Africa, and identify predictors of insulin independence at 12 and 60 months after presentation. METHODS: A prospective, descriptive cohort study of all individuals, 18 years or older, presenting for the first time with DKA to four public-sector hospitals of the Groote Schuur Academic Health Complex was performed. Clinical, biochemical and laboratory data including GAD antibody and C-peptide status were collected at baseline. Insulin was systematically weaned and stopped in individuals who achieved normoglycaemia within the months after DKA. Individuals were followed for 12 months and then annually until 5 years after initial presentation with ketoacidosis. RESULTS: Eighty-eight individuals newly diagnosed with diabetes when presenting with DKA were included and followed for 5 years. The mean ± SD age was 35±10 years and the median (IQR) BMI at diagnosis was 28.5 (23.3-33.4) kg/m2. Overall, 46% were insulin independent 12 months after diagnosis and 26% remained insulin independent 5 years after presentation. Forty-one participants (47%) tested negative for anti-GAD and anti-IA-2 antibodies and had C-peptide levels >0.3 nmol/l; in this group, 68% were insulin independent at 12 months and 37% at 5 years after diagnosis. The presence of acanthosis nigricans was strongly associated with insulin independence (OR 27.1 [95% CI 7.2, 102.2]; p<0.001); a positive antibody status was associated with a lower likelihood of insulin independence at 12 months (OR 0.10 [95% CI 0.03, 0.36]; p<0.001). On multivariable analysis only acanthosis (OR 11.5 [95% CI 2.5, 53.2]; p=0.004) was predictive of insulin independence 5 years after diagnosis. CONCLUSIONS/INTERPRETATION: The predominant phenotype of adults presenting with a first episode of DKA in Cape Town, South Africa, was that of ketosis-prone type 2 diabetes. These individuals presented with obesity, acanthosis nigricans, negative antibodies and normal C-peptide and could potentially be weaned off insulin at follow-up. Classic type 1 diabetes (lower weight, antibody positivity, low or unrecordable C-peptide levels and long-term insulin dependence) was less common. The simple clinical sign of acanthosis nigricans is a strong predictor of insulin independence at 12 months and 5 years after initial presentation.

Factors influencing mortality in COVID-19-associated mucormycosis: The international ID-IRI study.

The emergence of COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), triggered a global pandemic. Concurrently, reports of mucormycosis cases surged, particularly during the second wave in India. This study aims to investigate mortality factors in COVID-19-associated mucormycosis (CAM) cases, exploring clinical, demographic, and therapeutic variables across mostly Asian and partly African countries. A retrospective, cross-sectional analysis of CAM patients from 22 medical centers across eight countries was conducted, focusing on the first 3 months post-COVID-19 diagnosis. Data collected through the ID-IRI included demographics, comorbidities, treatments, and outcomes. A total of 162 CAM patients were included. The mean age was 54.29 ± 13.04 years, with 54% male. Diabetes mellitus (85%) was prevalent, and 91% had rhino-orbital-cerebral mucormycosis. Surgical debridement was performed in 84% of the cases. Mortality was 39%, with advanced age (hazard ratio [HR] = 1.06, [P < .001]), rituximab use (HR = 21.2, P = .05), and diabetic ketoacidosis (HR = 3.58, P = .009) identified as risk factors. The mortality risk increases by approximately 5.6% for each additional year of age. Surgical debridement based on organ involvement correlated with higher survival (HR = 8.81, P < .001). The utilization of rituximab and diabetic ketoacidosis, along with advancing age, has been associated with an increased risk of mortality in CAM patients. A combination of antifungal treatment and surgical intervention has demonstrated a substantial improvement in survival outcomes.

Over a third of patients who developed mucormycosis after COVID-19 died. Older people, those on specific immunosuppressive treatments, and those with diabetic ketoacidosis had a higher risk of death. However, undergoing surgery as part of treatment significantly improved survival.

Comparison of clinical characteristics and treatment outcomes between initially diagnosed type 1 and type 2 diabetes mellitus patients presenting with diabetic ketoacidosis.

OBJECTIVE: Patients with type 1 diabetes (T1DM) and type 2 diabetes (T2DM) can present with diabetic ketoacidosis (DKA) as the first manifestation. Differentiating types of newly diagnosed diabetes could provide appropriate long-term management. Therefore, we conducted this study to compare clinical characteristics and outcomes between initially diagnosed type 1 and type 2 diabetes mellitus patients presenting with DKA. MATERIALS AND METHODS: A retrospective study was conducted on adult patients who presented with DKA as the first diagnosis of diabetes in our tertiary hospital between January 2005 and December 2019. Demographic data, precipitating causes, laboratory investigations, treatment, and outcomes were obtained by chart review. The primary outcome was to compare the clinical characteristics of initially diagnosed patients with T1DM and T2DM who presented with DKA. RESULTS: A total of 100 initially diagnosed diabetic patients who presented with DKA were analyzed (85 T2DM patients and 15 T1DM patients). Patients with T1DM were younger than patients with T2DM (mean age 33 ± 16.2 vs. 51 ± 14.5 years, p value < 0.001). Patients with T2DM had a higher body mass index, family history of diabetes, precipitating factors, plasma glucose, and lower renal function than those with T1DM. There was no difference in resolution time or DKA management between T1DM and T2DM patients. The overall mortality rate of DKA was 4%. CONCLUSION: In this population, most adult patients who presented with DKA had T2DM. Older age, obesity, a family history of diabetes, and the presence of precipitating factors were strong predictors of T2DM. We can implement the same clinical management for DKA in both T1DM and T2DM patients. However, T2DM patients had longer hospitalization than T1DM patients. After DKA resolution for 12 months, more than half of patients with T2DM could discontinue insulin. Therefore, the accurate classification of the type of diabetes leads to appropriate treatment.

Prevalence and prognosis of fulminant type 1 diabetes mellitus in The Middle East: a comparative analysis in a 5-year nationwide cohort.

PURPOSE: To analyze the prevalence and progression of fulminant type 1 diabetes (FT1D) in Qatar. METHODS: This retrospective study analyzed consecutive index- diabetic ketoacidosis (DKA) admissions (2015-2020) among patients with new-onset T1D (NT1D) in Qatar. RESULTS: Of the 242 patients, 2.5% fulfilled the FT1D diagnostic criteria. FT1D patients were younger (median-age 4-years vs.15-years in classic-T1D). Gender distribution in FT1D was equal, whereas the classic-T1D group showed a female predominance at 57.6% (n = 136). FT1D patients had a mean C-peptide of 0.11 ± 0.09 ng/ml, compared to 0.53 ± 0.45 ng/ml in classic-T1D. FT1D patients had a median length of stay (LOS) of 1 day (1-2.2) and a DKA duration of 11.25 h (11-15). The median (length of stay) LOS and DKA duration in classic-T1D patients were 2.5 days (1-3.9) and 15.4 h (11-23), respectively. The FT1D subset primarily consisted of moderate (83.3%) and severe 916.7%) DKA, whereas classic T1D had 25.4% mild, 60.6% moderate, and 14% severe DKA cases. FT1D was associated with a higher median white cell count (22.3 × 103/uL) at admission compared to classic T1D (10.6 × 103/uL). ICU admission was needed for 66.6% of FT1D patients, compared to 38.1% of classic-T1D patients. None of the patients in the FT1D group had mortality, while two died in the classic-T1D group. CONCLUSION: This is the first study establishing the existence of FT1D in ME, which presented distinctively from classic-T1D, exhibiting earlier age onset and higher critical care requirements. However, the clinical outcomes in patients with FT1D seem similar to classic T1D.

Sirolimus-induced Hypertriglyceridemia Leads to Acute Pancreatitis and Diabetic Ketoacidosis Post Stem Cell Transplant for Sickle Cell Disease.

Sirolimus (mammalian target of rapamycin inhibitor) is a potent immunosuppressive agent, used in patients receiving hematopoietic stem cell transplant (HSCT) for Graft vs Host disease prophylaxis. Compared to calcineurin inhibitors, sirolimus has no neurotoxicity or nephrotoxicity, but sirolimus causes dose-dependent thrombocytopenia, leukopenia, delayed wound healing, hyperlipidemia, and hypertriglyceridemia. Here we report a case of acute pancreatitis and diabetic ketoacidosis in a patient with sickle cell disease post haploidentical family donor HSCT which was managed conservatively without plasmapheresis. Based on our review of the literature, this is the first reported case of developing acute pancreatitis as an adverse effect of sirolimus-induced hypertriglyceridemia leading to diabetic ketoacidosis in a recipient of HSCT.

Sodium-glucose cotransporter-2 inhibitors (SGLT2) in frail or older people with type 2 diabetes and heart failure: a systematic review and meta-analysis.

OBJECTIVE: Sodium-glucose cotransporter-2 inhibitors (SGLT2Is) reduce cardio-metabolic and renal outcomes in patients with type 2 diabetes (T2D) but their efficacy and safety in older or frail individuals remains unclear. METHODS: We searched PubMed, Scopus, Web of Science, Cochrane CENTRA and Google Scholar and selected randomised controlled trials and observational studies comparing SGLT2Is versus placebo/other glucose-lowering agent for people with frailty or older individuals (>65 years) with T2D and heart failure (HF). Extracted data on the change in HbA1c % and safety outcomes were pooled in a random-effects meta-analysis model. RESULTS: We included data from 20 studies (22 reports; N = 77,083 patients). SGLT2Is did not significantly reduce HbA1c level (mean difference -0.13, 95%CI: -0.41 to 0.14). SGLT2Is were associated with a significant reduction in the risk of all-cause mortality (risk ratio (RR) 0.81, 95%CI: -0.69 to 0.95), cardiac death (RR 0.80, 95%CI: -0.94 to 0.69) and hospitalisation for heart failure (HHF) (RR 0.69, 95%CI: 0.59-0.81). However, SGLT2Is did not demonstrate significant effect in reducing in the risk of macrovascular events (acute coronary syndrome or cerebral vascular occlusion), renal progression/composite renal endpoint, acute kidney injury, worsening HF, atrial fibrillation or diabetic ketoacidosis. CONCLUSIONS: In older or frail patients with T2D and HF, SGLT2Is are consistently linked with a decrease in total mortality and the overall burden of cardiovascular (CV) events, including HHF events and cardiac death, but not protective for macrovascular death or renal events. Adverse events were more difficult to quantify but the risk of diabetic ketoacidosis or acute kidney injury was not significantly increase.

Persistent chronic calcific pancreatitis with intraductal calculi associated with secondary diabetes mellitus type 3 and diabetic ketoacidosis - A case report.

Diabetes mellitus type 3 refers to diabetes secondary to an existing disease or condition of the exocrine pancreas and is an uncommon cause of diabetes occurring due to pancreatogenic pathology. It accounts for 15-20% of diabetic patients in Indian and Southeast Asian continents. This is case report of a rare case of type 3 diabetes mellitus (T3DM) presenting with diabetic ketoacidosis (DKA). The patient was admitted for DKA along with complaint of hyperglycemia, blood glucose of 405 mg/dl with HbA1c level of 13.7%. Computed tomography evidence revealed chronic calcific pancreatitis with intraductal calculi and dilated pancreatic duct.

Clinical findings of acute necrotizing esophagitis complicated by diabetic ketoacidosis.

Acute necrotizing esophagitis (ANE) is a rare and potentially life-threatening complication of diabetic ketoacidosis (DKA). While its association with DKA is established, specific clinical characteristics that predict ANE in DKA patients remain less understood. This study aimed to identify these characteristics by analyzing data from 30 DKA patients admitted from January 2018 to September 2022. Seven patients in this study presented with ANE, forming the ANE group. The remaining 23 constituted the non-ANE group. We compared the clinical parameters and computed tomography (CT) between the groups. The mean age of participants was 57.7 ± 20.4 years, and their mean HbA1c was 11.1 ± 3.3%. Notably, ethanol intake was significantly higher in the ANE group (44.4 ± 25.4 g/day) compared to the non-ANE group (6.8 ± 14.0 g/day; p = 0.013). Additionally, sodium-glucose transport protein 2 inhibitor use was significantly more prevalent in the ANE group (p = 0.013). Gastrointestinal symptoms were also significantly more pronounced in the ANE group, with vomiting occurring in 85.7% of patients compared to only 13.0% in the non-ANE group. Admission CT scans revealed further distinguishing features, with the ANE group showing significantly higher rates of esophageal wall thickening, intra-esophageal effusion, and calcification of the celiac artery origin (p < 0.0001, 0.0038, 0.0038, respectively). In conclusion, our study suggests that heavy alcohol consumption and strong gastrointestinal symptoms in DKA patients warrant a heightened suspicion of ANE. Early consideration of CT or upper gastrointestinal endoscopy is recommended in such cases.

Effectiveness of a standardized scenario in teaching the management of pediatric diabetic ketoacidosis (DKA) to residents: a simulation cross-sectional study.

BACKGROUND: Diabetic ketoacidosis (DKA) is a frequent manifestation at the onset of type 1 diabetes mellitus in children, possibly associated with a wide range of complications, often as a consequence of wrong or delayed treatment. Due to its complex and risky management, direct exposure to real situations alone is not sufficient to achieve adequate skills in pediatric DKA for residents. Simulation could be a valuable aid, allowing to practice a standardized scenario of a complex real-world situation. We aimed to test the effectiveness of a standardized scenario of pediatric DKA in teaching its recognition and treatment. METHODS: We develop a standardized scenario able to guide step-by-step the learners through the flowchart of DKA management and considering alternative evolutions in the case of possible deviations from guidelines. It was a real-life simulation with the use of a high-fidelity pediatric simulator. It was played by 78 pediatrics 20 and emergency medicine residents. At the end of the simulation, a validated questionnaire was administered to collect feedback from participants regarding the impact of the simulation on learning. All materials to reproduce the DKA scenario are provided. RESULTS: Overall, the scenario was rated as realistic (mean score 4.37 ± 0.68, from 1 to 5) and relevant to professional training (4.72 ± 0.47), useful in increasing confidence in interpreting laboratory tests (3.97 ± 0.65), group organization and communication strategies (3.49 ± 0.94), and managing the treatment of DKA (3.46 ± 0.92). CONCLUSIONS: The use of a standardized scenario of pediatric DKA may be a valid tool to reinforce theoretical knowledge in residents, both in pediatrics and in emergency medicine, and to directly and safely practice pediatric DKA management.

Prevalence of sodium-glucose transporter 2 inhibitor-associated diabetic ketoacidosis in real-world data: A systematic review and meta-analysis.

BACKGROUND: The U.S. Food and Drug Administration (FDA) revised the labels of sodium-glucose transporter 2 (SGLT2) inhibitors in December 2015 to inform users regarding the risk of diabetic ketoacidosis (DKA). As more drugs of this class are approved and their indications are expanded, this serious adverse effect has been increasingly reported. OBJECTIVE: This review evaluated observational studies to inform the prevalence of SGLT2-inhibitor-associated DKA compared with other antihyperglycemic agents. METHODS: A systematic review was conducted in PubMed and EMBASE until 19 July 2022 (PROSPERO: CRD42022385425). We included published retrospective cohort active comparator/new user (ACNU) and prevalent new user studies assessing SGLT2-inhibitor-associated DKA prevalence in adult patients with type 2 diabetes mellitus (T2DM) against active comparators. We excluded studies which lacked 1:1 propensity score matching. The JBI Checklist for Cohort Studies guided the risk-of-bias assessments. Meta-analysis was conducted based on the inverse variance method in R software. RESULTS: Sixteen studies with a sample of 2,956,100 nonunique patients met the inclusion criteria. Most studies were conducted in North America (n = 9) and adopted the ACNU design (n = 15). Meta-analysis of 14 studies identified 33% higher DKA risk associated with SGLT2 inhibitors (HR = 1.33, 95% CI: 1.14-1.55, P < 0.01). Meta-regression analysis identified the study location (P = 0.02), analysis principle (P < 0.001), exclusion of chronic comorbidities (P = 0.007), and canagliflozin (P = 0.04) as significant moderator variables. CONCLUSIONS: Despite limitations related to heterogeneity, generalizability, and misclassification, the results of this study show that SGLT2 inhibitors increase the prevalence of DKA among adult T2DM patients in the real world. The findings supplement evidence from randomized controlled trials (RCTs) and call for continued vigilance.

Balanced crystalloids (RInger's lactate) versus normal Saline in adults with diabetic Ketoacidosis in the Emergency Department (BRISK-ED): a pilot randomised controlled trial.

BACKGROUND: Current diabetic ketoacidosis (DKA) treatment guidelines recommend using normal saline (NS); however, NS may delay DKA resolution by causing more hyperchloremic metabolic acidosis compared with balanced crystalloids. This study's objective was to determine the feasibility of a future multicentred randomised controlled trial (RCT) comparing intravenous Ringer's lactate (RL) with NS in managing ED patients with DKA. METHODS: We conducted a parallel-arm, triple-blind, pilot RCT of adults (≥18 years) with DKA at a Canadian academic tertiary care ED. The primary feasibility outcome was recruitment rate (target ≥41.3% of eligible participants over the 1-year study period); the primary efficacy outcome was time elapsed from ED presentation to DKA resolution. The superiority margin for a clinically significant difference was chosen to be a 40% time reduction to DKA resolution. We also assessed the need to break allocation concealment and loss to follow-up. Patients with clinical suspicion for DKA were screened for inclusion and enrolled patients were randomised 1:1 to receive RL or NS. Patients, clinicians and outcome assessors were blinded to allocation. RESULTS: We enrolled 52 (25 RL, 27 NS) of 60 eligible patients (86.7%), exceeding our target recruitment rate. There were more patients in the NS group with type 1 diabetes, and more patients in the RL group had an admission co-diagnosis in addition to DKA. For the 44 participants with confirmed laboratory evidence of resolution, median (IQR) time to DKA resolution for RL versus NS was 15.7 (10.4-18.8) and 12.7 (7.9-19.2) hours, respectively. There were no cases where blinding was broken, and there was no loss to follow-up. CONCLUSIONS: This pilot trial demonstrated our protocol's feasibility by exceeding our target recruitment rate. Our results may be used to inform future multicentre trials to compare the safety and efficacy of RL and NS in managing DKA in the ED. TRIAL REGISTRATION NUMBER: NCT04926740.

Clinical and Prognostic Features of Diabetic Ketoacidosis According to the Trigger of the Syndrome.

BACKGROUND: Diabetic ketoacidosis (DKA) is an acute metabolic, life-threatening complication of diabetes mellitus with a mortality rate that now stand at less than 1%. Although mortality is coupled with the etiology of DKA, literature on the influence of DKA etiology on patient outcome is scarce. OBJECTIVES: To study different triggers for DKA and their effect on outcomes. METHODS: We conducted a retrospective study that include 385 DKA patients from 2004 to 2017. The study compared demographics, clinical presentation, and mortality rates by different precipitating factors. RESULTS: Patients with DKA due to infections had a higher risk to develop in-hospital mortality after controlling for age and sex (odds ratio 4.40, 95% confidence interval 1.35-14.30), had a higher Charlson Comorbidity Index score, a higher risk of being mechanical ventilated (14% vs. 3%, P < 0.01), and a longer duration of hospitalization (5 days vs. 3 days, P < 0.001). CONCLUSIONS: It is crucial to find the triggers that precipitate DKA and start the treatment as early as possible in addition to the metabolic aspect of the treatment especially when the trigger is an infectious disease.

Decompression sickness followed by diabetic ketoacidosis and sepsis shock: an unusual case report.

Decompression sickness (DCS) is caused by abrupt changes in extracorporeal pressure with varying severity. Symptoms range from mild musculoskeletal pain to severe organ dysfunction and death, especially among patients with chronic underlying disease. Here, we report an unusual case of a 49-year-old man who experienced DCS after a dive to a depth of 38 meters. The patient's symptoms progressed, starting with mild physical discomfort that progressed to disturbance of consciousness on the second morning. During hospitalization, we identified that in addition to DCS, he had also developed diabetic ketoacidosis, septic shock, and rhabdomyolysis. After carefully balancing the benefits and risks, we decided to provide supportive treatment to sustain vital signs, including ventilation support, sugar-reducing therapy, fluid replacement, and anti-infection medications. We then administered delayed hyperbaric oxygen (HBO2) when his condition was stable. Ultimately, the patient recovered without any sequelae. This is the first case report of a diver suffering from DCS followed by diabetic ketoacidosis and septic shock. We have learned that when DCS and other critical illnesses are highly suspected, it is essential to assess the condition comprehensively and focus on the principal contradiction.

[Normoglycaemic ketoacidosis induced by the use of sglt2 inhibitors : impact of intense physiological stress and fasting]. / Acidocétose normoglycémique induite par la prise de gliflozines en cas de stress physiologique intense et de jeûne.

Ketoacidosis is a serious complication of diabetes that only occurs in cases of absolute or severe relative insulin deficiency. This condition is rare in type 2 diabetes. The use of gliflozin during intense physiological stress associated with fasting can lead to the development of ketoacidosis without severe hyperglycaemia. The diagnosis of this normoglycaemic or euglycaemic diabetic ketoacidosis in the context of type 2 diabetes may be challenging. The treatment of metabolic acidosis cannot rely solely on symptomatic measures such as bicarbonate infusion. The demonstration of metabolic acidosis necessitates the search for an etiological diagnosis. The calculation of the anion gap is the cornerstone of the pathophysiological diagnosis of metabolic acidosis. In the context of diabetes, the occurrence of metabolic acidosis of unknown etiology requires its calculation and systematic measurement of ketones, even in the absence of severe hyperglycaemia. Only the etiological treatment of diabetic ketoacidosis, which is insulin therapy, allows for the lasting restoration of acid-base balance. Normoglycaemic ketoacidosis induced by the use of gliflozin during intense physiological stress associated with fasting should therefore be a recognized situation by healthcare providers.

L'acidocétose est une complication grave du diabète qui ne survient qu'en cas de déficit en insuline, absolu ou relatif sévère. Cette condition est rare dans le diabète de type 2. La prise de gliflozines en cas de stress physiologique intense, notamment associé à un jeûne, peut induire la survenue d'une acidocétose sans hyperglycémie sévère. Cette acidocétose diabétique dite normoglycémique ou euglycémique dans le cadre d'un diabète de type 2 est source d'errance diagnostique. Le traitement d'une acidose métabolique ne peut pas se satisfaire de l'instauration de mesures symptomatiques comme la perfusion de bicarbonates. La démonstration d'une acidose métabolique impose la recherche d'un diagnostic étiologique. Le calcul du trou anionique est la pierre angulaire du diagnostic physiopathologique d'une acidose métabolique. Dans le cadre du diabète, la survenue d'une acidose métabolique d'étiologie inconnue impose son calcul et le dosage systématique de la cétonémie, même en l'absence d'hyperglycémie sévère, a fortiori en cas de traitement par gliflozine. Seul le traitement étiologique d'une acidocétose diabétique, l'insulinothérapie, permet la restitution durable de l'équilibre acido-basique. L'acidocétose normoglycémique induite par la prise de gliflozines en cas de stress physiologique intense associé à un jeûne doit donc être une situation connue.

Pyuria in Children with Diabetic Ketoacidosis.

Acute kidney injury occurs frequently during pediatric diabetic ketoacidosis (DKA). We reviewed urinalyses from 561 children with DKA; pyuria was detected in 19% overall and in 40% of children with more comprehensive urine testing (≥3 urinalyses) during DKA.

Euglycemic Diabetic Ketoacidosis Caused by Alcoholic Pancreatitis and Starvation Ketosis.

Starvation ketosis and pancreatitis are uncommon and underrecognized etiologies of euglycemic diabetic ketoacidosis (DKA). Euglycemic DKA is associated commonly with pregnancy, use of insulin en route to the hospital, and use of sodium-glucose cotransporter-2 (SGLT-2) inhibitors. A 58-year-old male with past medical history of type II diabetes mellitus and alcoholism presented with chief complaint of nausea, vomiting, and poor oral intake for several weeks. Despite extensive history of diabetes and no recent SGLT-2 inhibitor use, his labs were consistent with euglycemic DKA. His imaging and clinical history also confirmed alcoholic pancreatitis. The patient was admitted for euglycemic DKA secondary to starvation ketosis and alcoholic pancreatitis. His anion gap and beta-hydroxybutyrate rapidly cleared with initiation of the DKA protocol. This case teaches us that clinicians should consider early initiation of the DKA protocol even in the setting of euglycemia, when a patient presents with high-anion-gap metabolic acidosis, a high beta-hydroxybutyrate level, and a clinical picture of pancreatitis and starvation.

Euthyroid sick syndrome and its association with complications of type 1 diabetes mellitus onset.

OBJECTIVE: To evaluate (i) the prevalence and association of euthyroid sick syndrome (ESS) [decreased FT3 and/or FT4 and normal/decreased TSH] with severity indexes of type 1 diabetes mellitus (T1DM) onset such as diabetic ketoacidosis (DKA) and kidney damage [acute kidney injury (AKI) based on KDIGO criteria, acute tubular necrosis (ATN), renal tubular damage (RTD)], (ii) relationship between clinical/metabolic parameters at T1DM onset and thyroid hormones, and (iii) ESS as a prognostic indicator of delayed recovery from kidney damage. METHODS: A total of 161 children with T1DM onset were included. RTD was defined by abnormal urinary beta-2-microglobulin and/or neutrophil gelatinase-associated lipocalin (NGAL) and/or tubular reabsorption of phosphate <85% and/or fractional excretion of Na>2%. ATN was defined by RTD+AKI. RESULTS: Of 161 participants, 60 (37.3%) presented ESS. It was more prevalent in case of more severe T1DM presentation both in terms of metabolic derangement (DKA) and kidney function impairment (AKI, RTD and ATN). Only ATN, however, was associated with ESS at adjusted analysis. FT3 inversely correlated with serum triglycerides and creatinine, and urinary calcium/creatinine ratio and NGAL. Participants with euthyroidism showed earlier recovery from AKI than those with ESS. ESS spontaneously disappeared. CONCLUSIONS: ESS is associated with T1DM onset severity and spontaneously disappears. ESS delayed the recovery from AKI. IMPACT: This is the first longitudinal study describing in detail the relationship between clinical/metabolic factors at type 1 diabetes mellitus (T1DM) onset and thyroid hormones, with particular attention to the relationship between diabetic ketoacidosis (DKA)-related kidney function impairment and euthyroid sick syndrome (ESS). Participants with more severe T1DM onset presentation both in terms of metabolic derangement and kidney function impairment had an increased prevalence of ESS. Children with ESS had a slower recovery from acute kidney injury compared with those without ESS. ESS spontaneously disappeared in all participants.

Identification of predictive factors of diabetic ketoacidosis in type 1 diabetes using a subgroup discovery algorithm.

AIM: To identify predictive factors for diabetic ketoacidosis (DKA) by retrospective analysis of registry data and the use of a subgroup discovery algorithm. MATERIALS AND METHODS: Data from adults and children with type 1 diabetes and more than two diabetes-related visits were analysed from the Diabetes Prospective Follow-up Registry. Q-Finder, a supervised non-parametric proprietary subgroup discovery algorithm, was used to identify subgroups with clinical characteristics associated with increased DKA risk. DKA was defined as pH less than 7.3 during a hospitalization event. RESULTS: Data for 108 223 adults and children, of whom 5609 (5.2%) had DKA, were studied. Q-Finder analysis identified 11 profiles associated with an increased risk of DKA: low body mass index standard deviation score; DKA at diagnosis; age 6-10 years; age 11-15 years; an HbA1c of 8.87% or higher (≥ 73 mmol/mol); no fast-acting insulin intake; age younger than 15 years and not using a continuous glucose monitoring system; physician diagnosis of nephrotic kidney disease; severe hypoglycaemia; hypoglycaemic coma; and autoimmune thyroiditis. Risk of DKA increased with the number of risk profiles matching patients' characteristics. CONCLUSIONS: Q-Finder confirmed common risk profiles identified by conventional statistical methods and allowed the generation of new profiles that may help predict patients with type 1 diabetes who are at a greater risk of experiencing DKA.

COVID-19 associated ketosis and diabetic ketoacidosis: A rapid review.

SARS-CoV-2 infection could disrupt the endocrine system directly or indirectly, which could result in endocrine dysfunction and glycaemic dysregulation, triggering transient or persistent diabetes mellitus. The literature on the complex relationship between COVID-19 and endocrine dysfunctions is still evolving and remains incompletely understood. Thus, we conducted a review on all literature to date involving COVID-19 associated ketosis or diabetic ketoacidosis (DKA). In total, 27 publications were included and analysed quantitatively and qualitatively. Studies included patients with DKA with existing or new onset diabetes. While the number of case and cohort studies was limited, DKA in the setting of COVID-19 seemed to increase risk of death, particularly in patients with new onset diabetes. Future studies with more specific variables and larger sample sizes are needed to draw better conclusions.

Increased Use of Hyperosmolar Therapy for Suspected Clinically Apparent Brain Injury in Pediatric Patients with Diabetic Ketoacidosis during the Peak of the COVID-19 Pandemic.

The incidence of pediatric diabetic ketoacidosis (DKA) increased during the peak of the COVID-19 pandemic. The objective of this study was to investigate whether rates of hyperosmolar therapy administration for suspected clinically apparent brain injury (CABI) complicating DKA also increased during this period as compared to the three years immediately preceding the pandemic and to compare the characteristics of patients with suspected CABI before the pandemic, patients with suspected CABI during the peak of the pandemic, and those with DKA but without suspected CABI during the pandemic. Patients aged ≤18 years presenting with DKA before (March 11, 2017-March 10, 2020) and during the peak of the pandemic (March 11, 2020-March 10, 2021) were identified through a rigorous search of two databases. Predefined criteria were used to diagnose suspected CABI. Biochemical, clinical, and sociodemographic data were collected from a comprehensive review of the electronic medical record. The proportion of patients with DKA who received hyperosmolar therapy was significantly higher (P = 0.014) during the pandemic compared to the prepandemic period; however, this was only significant among patients with newly diagnosed diabetes. Both groups with suspected CABI had more severe acidosis, lower Glasgow Coma Scale scores, and longer hospital admissions (P< 0.001 for all) than cases without suspected CABI. During the pandemic, the blood urea nitrogen concentration was significantly higher in patients with suspected CABI than those without suspected CABI, suggesting they were more severely dehydrated. The clinical, biochemical, and sociodemographic characteristics of patients with suspected CABI were indistinguishable before and during the pandemic. In conclusion, administration of hyperosmolar therapy for suspected CABI was more common during the peak of the COVID-19 pandemic, possibly a result of delayed presentation, highlighting the need for increased awareness and early recognition of the signs and symptoms of diabetes and DKA, especially during future surges of highly transmissible infections.