Onset Of Diabetic Ketoacidosis Research Articles

Alpelisib-Induced Diabetic Ketoacidosis: A Pharmacovigilance Analysis of the FDA Adverse Event Reporting System and Review of the Literature

BackgroundAlpelisib is a PI3K inhibitor indicated with fulvestrant for treatment of advanced or metastatic hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, PIK3CA-mutated breast cancer. In the phase III SOLAR-1 trial, grade 3/4 hyperglycemic events were reported in 36.6% of patients receiving alpelisib-fulvestrant compared to 0.7% receiving placebo-fulvestrant. As case reports of diabetic ketoacidosis (DKA) have been associated with alpelisib use, the goal of this study was to characterize the FAERS reported cases of this severe adverse effect. MethodsA retrospective disproportionality analysis was performed using the FAERS database by calculating the reporting odds ratio (ROR) of DKA events with alpelisib from 2019 to 2022. A PubMed literature review of case reports characterizing alpelisib-induced DKA was performed. ResultsPharmacovigilance database analysis revealed significance in reporting among 87 DKA cases with alpelisib (ROR 9.84, 95% confidence interval 7.3-13.2), including hospitalization and death as reported outcomes. Review of 11 published case reports reveals median onset of DKA at 14 days with successful rechallenge possible. ConclusionSignificant association with reporting exists between DKA and alpelisib exposure. We observed similar median time to onset of hyperglycemia between our analysis compared to that reported in SOLAR-1. Considering early onset of this toxicity, it is imperative that patients be closely monitored when initiating alpelisib. Addition of a preemptive antihyperglycemic or escalation in those previously on antihyperglycemic medications is beneficial in decreasing the severity of hyperglycemia with alpelisib. Further study investigating risk factors is warranted to better elucidate which patients require preemptive therapy.

FRI629 A Mysterious Case Of Mother's Battle With Diabetic Ketoacidosis During Pregnancy

Abstract Disclosure: P.D. Sittirat: None. S.J. Choi: None. A. Gutierrez: None. M. Bashyam: None. Introduction: Changes in hormone regulatory mechanisms during pregnancy can increase the likelihood of diabetic ketoacidosis (DKA) in pregnant individuals. Despite the increased risk, the likelihood of DKA in pregnant individuals with diabetes mellitus is still low at around 0.5-3%. Management involves aggressive treatment following standard DKA protocols. We delve into a mysterious case of DKA in the second trimester of pregnancy. Case Presentation: A 31-year-old G1P0 woman at 24 weeks gestation with no past medical history presented with nausea, constipation associated with back and abdominal pain. Admission labs were significant for blood glucose 369 mg/dL, CO2 11 meq/L, anion gap 19 mEq/L, white blood cell 17.2 K/uL, HbA1c 9.5%, and serum ketones 3.9 mmol/L. Within 12 hours of admission into the intensive care unit for DKA, the patient was at 5-6 cm cervical dilation without signs of fetal distress. The newborn was delivered prematurely with complications of retinopathy and patent ductus arteriosus. Mother's lab studies showed negative for anti-GAD antibody, insulinoma associated 2 autoantibodies, islet cell antibody, and zinc transporter 8 antibody. C-peptide was low at 0.9 ng/mL (normal range 1.1 to 5.5 ng/mL). The patient was maintained on subcutaneous insulin which eventually tapered off at 2 months post-partum due to hypoglycemia. At 4 and 11-month follow-ups, her HbA1C was 5.8% and 5.5%, respectively. Her blood glucose was well controlled with a regular diet. She did get post-prandial spikes with a high carbohydrate diet. Discussion: Physiological changes in pregnancy make pregnant individuals more susceptible to DKA. Even so, the likelihood of DKA in pregnancy is rare. It is even rarer to have a new diagnosis of diabetes leading to DKA in pregnancy just before evaluation at the standard 28 weeks like the events precipitated in this case. DKA in pregnancy puts both the mother and fetus at risk for long-term complications. The maternal mortality rate in pregnancy with DKA is 5% to 15%, while the fetal mortality rate is 30% to 90%. The patient’s demographic background of being a young Caucasian, thin woman who presented with a new onset DKA and had a low C-peptide was more consistent with type 1 diabetes; however, all her antibodies were normal. It’s questionable if this patient has autoantibody negative new onset type 1 diabetes and is currently in remission. It's worth to mention that she had a history of mild Covid-19 infection at 8 weeks gestation but this new onset DKA developed at 24 weeks gestation. The chance of gestational diabetes was low due to low c-peptide on presentation. Annual follow-up of the patient is necessary to monitor her HbA1C while she is off diabetes medications. Presentation: Friday, June 16, 2023

Hyponatremia in new onset diabetic ketoacidosis: A comparative analysis before and during the COVID-19 pandemic

Hyponatremia in new onset diabetic ketoacidosis: A comparative analysis before and during the COVID-19 pandemic

Uncovering the alarming rise of diabetic ketoacidosis during COVID-19 pandemic: a pioneer African study and review of literature.

Reports around the world indicate that COVID-19 pandemic may be contributing to an increase in the incidence of new onset diabetic ketoacidosis (DKA). This has yet to be studied in Africa. We aimed to compare the incidence trend of new onset DKA before and during the COVID-19 pandemic, with a focus on the type of diabetes mellitus (DM).Materials and methodsThis was a cross sectional analytical study, over a 4-year period, between March 2018 until February 2022 conducted in the referral center: diabetology department of university hospital Farhat Hached Sousse, Tunisia. The study population included patients hospitalized for new onset DKA divided in two groups: G1: before COVID-19 pandemic and G2: during COVID-19 pandemic. Patients younger than 14, new onset DM not presenting with DKA, other types of diabetes (monogenic, secondary or pancreatic diabetes) were not included. A statistical analysis of the monthly incidence trend was conducted using the Jointpoint software providing the average monthly percentage of change (AMPC). a total of 340 patients were included:137 registered before the pandemic and 203 during the pandemic, representing a 48.17% increase. The mean monthly incidence of new onset DKA during COVID-19 pandemic was statistically higher than that before COVID-19 pandemic (8.42 ± 4.87 vs 5.75 ± 4.29 DKA per month) (p=0.049). The temporal trend of DKA during the 4-year study showed a significant upward trend with a change in AMPC of +0.2% (p=0.037). The incidence of type 1 diabetes (T1D) and type 2 diabetes (T2D) increased by 50% and 44% respectively during COVID-19 pandemic. Anti-glutamic acid decarboxylase (anti-GAD) antibodies' titers significantly increased in G2 compared with G1 (median of 330[Q1-Q3]=[58.5-1795]vs 92.5[Q1-Q3]=[22.5-1074] respectively)(p=0.021). The incidence trend of DKA showed an increase during the COVID-19 pandemic along with an increase of T1D and T2D implying that the pandemic may have been the underlying factor of this upward trend.

Utility of plasma beta-hydroxybutyrate to define resolution of diabetic ketoacidosis.

Diabetic ketoacidosis (DKA) is a common, life-threatening complication of type 1 diabetes (T1D) characterized by unregulated ketogenesis caused by relative or absolute insulin deficiency. DKA management requires frequent biochemical monitoring. Plasma ß-hydroxybutyrate (BOHB) has not been included in traditional definitions of DKA resolution. The aim of this study was to determine a cut-point level of BOHB to define DKA resolution in patients with T1D treated with intravenous (IV) insulin. We identified patients with T1D receiving IV insulin for DKA treatment at a quaternary children's hospital from January 1, 2017 through December 31, 2020 who had plasma measurements of BOHB after DKA onset and whose DKA resolved by traditional laboratory criteria (venous pH (vpH) ≥ 7.3, serum bicarbonate (HCO3 ) ≥ 15 mmol/L, and/or anion gap (AG) ≤ 14 mmol/L). Associations between plasma BOHB and vpH, HCO3 , and AG were evaluated via scatterplots. Receiver operating characteristic (ROC) curves and area under the curve (AUC) were used to evaluate BOHB cut-points to predict DKA resolution. We analyzed 403 patients with 471 unique encounters. Plasma BOHB showed the most robust relationship with AG. The ROC curve comparing plasma BOHB to the accepted definition of DKA resolution, AG ≤14 mmol/L, had an AUC of 0.92. A BOHB value of <1.5 mmol/L had a sensitivity of 83% and specificity of 87%; this cut-point correctly classified 86% of the observations. A plasma BOHB value of <1.5 mmol/L can be used to define resolution of DKA.

First onset of diabetic ketoacidosis in teenagers with COVID-19: a case report from a limited health care setting

Background: Diabetic ketoacidosis (DKA) has been well-known as the main complication that is a potentially fatal emergency in some teenagers with type 1 diabetes mellitus (DM). Although children with diabetes are not at high risk for severe COVID-19 infection, it can hypothetically lead to type 1 DM and severe DKA. The aim of this article is to briefly discuss a case of a teenager with DKA and COVID-19. Case: A 13 years old girl came in with abdominal pain, nausea, vomiting and dyspnea. She was alert but weak. Her blood pressure was 100/70 mmHg with 120 pulses and 35 breaths per minute. Oxygen saturation was at 99%. History of previous illness was denied. She was treated using a dyspepsia algorithm while waiting for the laboratory result. Later on, the test showed conditions of hyperglycemia, severe acidosis, ketonuria and a positive rapid COVID–19 antibody test. Hence, a diagnosis of DKA with probable COVID–19 was made and PCR for confirmation of COVID-19 diagnosis was scheduled. Oxygen support, rehydration, and insulin therapy were also given with a precautionary condition of possible COVID–19. In minutes, she developed respiratory distress that led her to be intubated and put on a ventilator. Due to a lack of facilities, a referral to a higher-level hospital was needed. However, since the referral process for probable COVID-19 patients required a long preparation, the patient died during the process. Conclusion: Besides early diagnosis and prompt treatment, a well-coordinated referral system is crucial in managing DKA patients with possible COVID–19.

A rare case of a mother with gestational diabetes complicated with fulminant type 1 diabetes mellitus post-delivery

Fulminant type 1 diabetes mellitus (FT1DM) is recognised as a novel subtype of type 1 diabetes mellitus characterised by the abrupt onset of insulin-deficient hyperglycaemia and ketoacidosis. Fulminant type 1 diabetes mellitus is known to be associated with pregnancy and had been associated with high fetal mortality. We report a case of a gestational diabetes mellitus (GDM) mother complicated with FT1DM immediately post-delivery. A 29-year-old Malay lady who was diagnosed with GDM at 19 weeks of pregnancy, underwent emergency lower segment caesarean section (EMLSCS) due to fetal distress at 36 weeks of gestation; 18 h post-EMLSCS, she developed abrupt onset Diabetic ketoacidosis (DKA) (blood glucose 33.5 mmol/L, pH 6.99, bicarbonate 3.6 mmol/L, ketone 4.4 mmol/L and HbA1c 6.1%). She received standard DKA treatment and discharged well. Her plasma C-peptide level 3 weeks later showed that she has no insulin reserve (C-peptide <33 pmol/L, fasting blood glucose (FBS) 28 mmol/L). Her pancreatic autoantibodies were negative. This case highlights that FT1DM not only can occur in pregnancy with normal glucose tolerance but can also complicate mother with GDM.

Diagnosis of a Rare Case of Acromegaly Secondary to Pituitary Macroadenoma Debuting as Sudden DKA

Acromegaly is an uncommon clinical syndrome that results from excessive secretion of growth hormone with an annual incidence of 6 to 8 cases per 1 million of individuals with a mean age of diagnosis between 40-45 years. Pituitary adenomas can be the principal reason for an overgrowth of the anterior pituitary somatotroph cells, and account for approximately one-third of all hormone-secreting pituitary adenomas with a prevalence of about 38-69 cases per 1 million and an incidence of 3-4 cases per 1 million individuals. The onset of acromegaly is insidious, and its progression is usually very slow. At the moment of diagnosis, approximately 75% of patients have presence of macro adenomas, but most cases are diagnosed after several laboratory workups and incidental brain imaging. A characteristic clinical presentation of pituitary adenomas could be secondary to mass effect. Metabolic presentation such as diabetes is one of the most common related conditions preceding the diagnosis of acromegaly. Clinical presentation with abrupt onset of DKA could be a determining factor on disease progression due to higher GH levels correlating with an increased prevalence of insulin resistance. We present a rare case of a 28y/o female G5P3A2 without previous PMHx who presented to ER with abdominal pain, general malaise, slurred speech, headache and gait difficulty of 3 days of evolution. Upon initial evaluation at ER patient was found with hyperglycemia of 317mg/dL, low central bicarbonate, high anion gap and positive serum ketones suggestive of DKA de novo. Based on neurological complaints, head CT performed showed an incidental parasellar/suprasellar/temporal hyperdense mass measuring 2.5cm x 2.6cm with optic chiasm compression features. Upon further specific questioning patient referred amenorrhea for the past 3 years, bitemporal hemianopsia, galactorrhea and marked facial feature changes, frontal bossing, weight gain, and acanthosis nigricans, for the past year. Pituitary adenoma workup revealed low prolactin levels (1.38), markedly increased growth hormone (501) and IGF-1 (893) suggesting diagnosis of acromegaly, most likely secondary to a functioning macroadenoma. Patient initially treated with Cabergoline, uncontrolled diabetes was managed and was referred to Neurosurgery service for further evaluation and tumor removal. Based on current literature, the incidence of acromegaly cases is low, more specifically when presenting with new onset diabetic ketoacidosis, insulin resistance and secondary to functioning macroadenomas. Medical awareness should be promoted to assess for careful consideration of signs and symptoms, workup, management and treatment to assess and minimize further health complications and physical burdens acromegaly and pituitary adenomas could pose for affected individuals.

On-label use of sodium-glucose cotransporter2 inhibitors might increase the risk of diabetic ketoacidosis in patients with type1 diabetes.

Aims/IntroductionThis study aimed to investigate the risk of diabetic ketoacidosis (DKA) in insulin‐treated type 1 diabetes patients administered sodium–glucose cotransporter 2 (SGLT2) inhibitors in real‐world clinical practice.Materials and MethodsWe carried out a real‐world, retrospective, observational cohort study using Japanese Medical Data Vision, a diagnosis procedure combination database. We identified insulin‐treated adult type 1 diabetes patients enrolled from December 2018 to October 2019. We assessed the incidence and risk of DKA in type 1 diabetes patients using SGLT2 inhibitors in an ‘on‐label’ manner. Cox multivariate regression analyses were carried out to determine clinical factors linked to SGLT2 inhibitor‐associated DKA.ResultsOf 11,475 type 1 diabetes patients, 1,898 (16.5%) were prescribed SGLT2 inhibitors. DKA occurred in 139 (7.3%) of these patients, with 20.2 incidences per 100 person‐years. These patients also showed significantly higher DKA rates than did those not receiving SGLT2 inhibitors (hazard ratio 1.66, 95% confidence interval 1.33–2.06; P < 0.001). The mean time until DKA onset in SGLT2 inhibitor‐treated type 1 diabetes patients was 30.6 ± 30.1 days. The risk of SGLT2 inhibitor‐associated DKA increased in type 1 diabetes patients irrespective of sex, age or body mass index. However, the risk did not increase in type 1 diabetes patients receiving continuous subcutaneous insulin infusion, which warrants further investigation because of the small number of type 1 diabetes patients receiving continuous subcutaneous insulin infusion.Conclusions‘On‐label’ SGLT2 inhibitor use might increase DKA risk among insulin‐treated type 1 diabetes patients irrespective of sex, age or body mass index. Both type 1 diabetes patients and healthcare providers should be wary of DKA, especially during the first month of initiating SGLT2 inhibitors.

Impact of Body Habitus on the Outcomes of Pediatric Patients With Diabetic Ketoacidosis.

To determine whether obese and overweight pediatric patients with new onset diabetic ketoacidosis (DKA) treated with continuous infusion insulin have increased time to subcutaneous insulin initiation or adverse events as compared with patients with normal body habitus. A retrospective, cohort study was designed that included patients 2 to 18 years of age admitted with new onset DKA who received continuous infusion insulin from January 1, 2011, to December 31, 2017. Patients were stratified according to BMI percentile with the primary outcome of time to initiation of subcutaneous insulin. Secondary endpoints included time to minimum beta-hydroxybutyrate, and incidence of hypoglycemia or other adverse events. A total of 337 patients (46.6% male, 9.6 ± 3.8 years of age) met study criteria. Patients were classified by body habitus as obese (7.7%, n = 26), overweight (7.1%, n = 24), normal body weight (58.8%, n = 198), or underweight (26.4%, n = 89), based on BMI percentile. Most patients were initiated on insulin at 0.1 unit/kg/hr (86.7%) for 16.7 ± 7.0 hours. Time from continuous infusion insulin initiation to subcutaneous insulin was not different between body habitus groups, nor was hypoglycemia or the use of mannitol (p > 0.05). Median time to lowest beta-hydroxybutyrate was greater for obese (26.4, IQR [13.9, 41.9]) and overweight (32.4, IQR [18.3, 47.0]) groups than for normal body habitus patients (16.5, IQR [12.3, 23.8]) (p < 0.05). Time to subcutaneous insulin and adverse events was not associated with body habitus, but obese and overweight patients may have delayed beta-hydroxybutyrate clearance.

A case of newly diagnosed autoimmune diabetes in pregnancy presenting after acute onset of diabetic ketoacidosis

Abstract Objectives We present a case of immune-mediated diabetes mellitus, diagnosed in pregnancy upon presentation with diabetic ketoacidosis, found to have normal glucose control postpartum. Case presentation A 28-year-old medically uncomplicated G1P0 presented in diabetic ketoacidosis at 28.2 weeks gestation. Workup for pancreatic autoantibodies revealed indeterminate anti-islet cell antibodies and positive anti-glutamic acid antibodies. She was stabilized with intravenous fluids and insulin, and transitioned to long and short acting subcutaneous insulin. Her insulin requirements decreased over the course of her pregnancy. Spontaneous vaginal delivery occurred at 37 weeks. Her postpartum glucose control was normal without re-initiation of insulin. Conclusions The diagnosis of diabetic ketoacidosis during pregnancy should prompt further investigation into an underlying diagnosis of immune mediated diabetes. These patients should be followed closely in the postpartum period.

Chetoacidosi diabetica e urine scure: quale diagnosi?

During the onset of diabetic ketoacidosis (DKA), the appearance of hyperchromic urines is a rare occurrence even if already described in the literature. The patient with DKA presents an increased risk to suffer of macrohaematuria due to nephrolithiasis (associated or not with urinary tract infections) and renal vein thrombosis. False macrohaematuria in rhabdomyolysis with myoglobinuria can also occur. This paper describes a case of an 11-year-old boy with severe onset of DKA, with macrohaematuria from kidney stones. The causes of nephrolithiasis in children with DKA are also reported.

Prevalence of Diabetic Keto Acidosis and Associated Factors among Newly Diagnosed Patients with Type One Diabetic Mellitus at Dilla University Referral Hospital, September 9th/2017 – May 30th/2019: South Ethiopia; Crossectional Study

Abstract Background Diabetic Ketoacidosis (DKA) is one of the most serious acute complications of Diabetes Mellitus (DM) and the leading cause of morbidity and mortality in young adults with type 1 diabetes. The mortality rate for DKA ranges from 2 to 5% in developed countries and 6 to 24% in developing countries. Even though many DKA patients were seen in emergency unit of Ethiopian hospitals and health centers, little is known about precipitating factors and clinical-laboratory features of DKA among Ethiopian patients and information is scant to promote better health service to prevent mortality due to DKA. So the aim of this study is to assess the prevalence and associated risk factors of DKA in newly diagnosed Type 1 Diabetic patients in Dilla University Referral Hospital (DURH) from September 9th/2017-May 30th/2019. Methods Quantitative institutional based study was conducted among 421 newly diagnosed type one diabetic patients. Data was double entered from the paper-based abstraction sheet into Epi info version 7 and exported to SPSS version 20 for analysis. A descriptive analysis was performed. Bivariate and multivariate logistic analysis was done to identify factors associated with the magnitude of Keto acidosis. Variables with p-value less than 0.05 were declared as having significant association between factors and dependent variable. Result The magnitude of Diabetic Keto Acidosis (DKA) in newly diagnosed patients with type one diabetic Mellitus (T1DM) was found to be 38%. The significant predictors of Diabetic Keto Acidosis (DKA) among newly diagnosed patients with type one diabetic Mellitus (T1DM) were young age of the adult, family history of diabetes and infection prior to onset of Diabetic Keto Acidosis (DKA). Conclusion The overall magnitude of Diabetic Keto Acidosis (DKA) in adults with newly diagnosed type 1 diabetes is high. In particular, adults between 18-25 years of age have a high risk of Diabetic Keto Acidosis (DKA) at onset of diabetes mellitus. Young Age, first degree relatives with Diabetic Mellitus (DM) and infection prior to Diabetic Keto Acidosis (DKA) are found to be the significant explanatory variable of Diabetic Keto Acidosis (DKA) in primary onset of T1DM.

141-LB: The Reality of Diabetic Ketoacidosis in Patients with Type 2 Diabetes Using SGLT2 Inhibitors Revealed by a Nationwide Claim-Based Database in Japan

Objective: Using a nationwide claim-based database in Japan, we investigated the reality of diabetic ketoacidosis (DKA) in patients with type 2 diabetes (T2D) treated with sodium-glucose cotransporter 2 (SGLT2) inhibitors. Research Design and Methods: We identified initiators of SGLT2 inhibitors in the claims data from April 2014 to June 2019, and investigated the incidence of DKA in patients with T2D. Moreover, in multivariable-adjusted Cox proportional hazard models, hazard ratio (HR) was calculated using age, sex, body mass index (BMI) and the use of continuous subcutaneous insulin infusion (herein referred to as insulin pumps). Furthermore, regarding DKA events as the objective variable, receiver operating characteristic (ROC) analysis was conducted to calculate a cut-off value for the periods from the initiation of the SGLT2 inhibitors. Results: During the observation period, among 173,025 initiators of SGLT2 inhibitors, patients with a diagnosis of DKA were 1,848 (1.1%), and those requiring inpatient treatment were 247 (0.14%). Factors associated with the diagnosis of DKA were 60- &amp;lt; 70years of age (HR, 1.59), BMI &amp;lt; 25kg/m2 (HR, 1.22) and the use of insulin pumps (HR, 4.61). Moreover, Factors associated with DKA requiring inpatient treatment were 60-70 years of age (HR, 2.64) and BMI &amp;lt; 25kg/m2 (HR, 1.31). As for the DKA events, ROC analysis revealed that the cut-off value was 60 days from the initiation of the SGLT2 inhibitors. Conclusions: This survey revealed that the risk of DKA calculated using real-world database was particularly pronounced among 60- &amp;lt; 70years of age and BMI &amp;lt; 25kg/m2 patients. Furthermore, it became clear that special attention should be paid to the onset of DKA for about 60 days from the initiation of the SGLT2 inhibitors. This information would provide guidance to avoid DKA with SGLT2 inhibitors and optimize the treatment of T2D, especially in Asian descent. Disclosure T. Horii: None. Y. Oikawa: None. T. Higashiyama: None. K. Atsuda: None. A. Shimada: Advisory Panel; Self; Astellas Pharma Inc. Speaker’s Bureau; Self; Eli Lilly Japan K.K., Novo Nordisk Inc., Sanofi-Aventis.

SAT-673 Acute Onset Type 1 Diabetes Mellitus Caused by the Checkpoint Inhibitor Nivolumab

Background. Checkpoint inhibitors are monoclonal antibodies that augment immune system antitumor activity. Nivolumab is a checkpoint inhibitor that targets the programmed cell death receptor 1 (PD-1). Approximately 15% of patients treated with checkpoint inhibitors experience endocrine immune-related adverse events (irAEs), with autoimmune thyroid disorders and hypophysitis the most common endocrine irAEs. We present a case of acute onset type 1 diabetes mellitus (T1D) complicating treatment with nivolumab. Case. An 84 year old female received nivolumab (Opdivo) for metastatic small cell lung cancer. She tolerated twelve cycles of treatment well, but after the thirteenth cycle, she developed polydipsia and polyuria that prompted her to seek medical attention. Laboratories in the emergency department were notable for plasma glucose 998 mg/dL, bicarbonate 13 mM, anion gap 24, and strongly positive serum and urine ketones. An insulin infusion and parenteral fluids promptly resolved diabetic ketoacidosis (DKA), and the patient was then managed with subcutaneous basal/bolus insulin. Antibody markers (e.g. anti-GAD65) for T1D were undetectable, and evaluation for other endocrine irAEs was unremarkable. Given the rapid onset of DKA and the patient’s advanced age, she was diagnosed with nivolumab-induced T1D and discharged home on exogenous insulin. Conclusions. In a recent meta-analysis of 38 immune checkpoint inhibitor trials and over 7,500 patients, T1D was the least common endocrine irAE. The incidence of T1D was 0.2% compared to 6.6% for hypothyroidism, 2.9% for hyperthyroidism, 1.3% for hypophysitis, and 0.7% for primary adrenal insufficiency. All but one case (12/13) of T1D occurred in patients treated with a PD-1 inhibitor. Markers of both cellular and humoral diabetes-associated autoimmunity have been demonstrated in patients with T1D during treatment with nivolumab, and autoimmune destruction of beta-cells is the presumed etiology of diabetes. However, diabetes autoantibodies are detected in only about 50% of cases, and the absence of humoral markers does not exclude the diagnosis of nivolumab-induced T1D. There is a slight male predominance among published cases of nivolumab-induced T1D, and though median onset of T1D1 is after 11 weeks of treatment, there is a wide range of recorded times to T1D onset. Approximately 70% of patients present in DKA, and the significant majority of patients have undetectable or low C-peptide levels. Unfortunately, loss of beta-cell function persists after stopping nivolumab, and lifelong exogenous insulin is required for diabetes management. Though nivolumab-induced T1D is rare, the high risk of DKA as in this patient’s case illustrates the importance of recognizing nivolumab as a potential cause of autoimmune diabetes in older patients receiving anti-PD-1 immunotherapy.

Effects of Diabetic Ketoacidosis on Executive Function in Children With Type 1 Diabetes: Evidence From Wisconsin Card Sorting Test Performance

Diabetic ketoacidosis (DKA) in patients with type 1 diabetes mellitus (T1DM) is known to affect memory function, but little is known about its impact on executive function. This study aimed to determine whether a history of DKA was associated with changes in executive function in children with T1DM. The sample consisted of 99 patients with T1DM with histories of DKA, 82 patients with T1DM without DKA, and 100 healthy controls aged 7 to 18 years. Neuropsychological function and emotion assessments were performed in all participants. The Wisconsin Card Sorting Test (WCST) was used to assess executive function. Compared with healthy controls, the DKA group (but not the non-DKA group) had a significantly lower mean intelligence quotient (IQ; p = .006, Cohen d = 0.528) and a significantly higher rate of WCST perseverative errors (p = .006, Cohen d = 0.475). In the DKA group, the age at DKA onset was significantly associated with the IQ (p = .001) and the number of completed WCST categories (p = .046). Higher hemoglobin A1c levels were associated significantly with lower IQ (p < .001), increased rate of WCST perseverative errors (p = .015), and completion of fewer WCST categories (p = .027). DKA has implications for executive function in children with T1DM. These findings emphasize the importance of DKA prevention in patients with known T1DM, especially younger children with newly diagnosed T1DM.

Endocrinopatía múltiple autoinmune

Los autoanticuerpos son proteínas producidas en el organismo por la inducción de un antígeno propio del individuo el cual no reconocen y rechazan. Su aparición en sangre puede iniciarse tiempo antes de la presentación de síntomas o signos. El deterioro funcional de dos o más glándulas es una afectación endocrinológica múltiple que puede asociarse con otras patologías autoinmunes no endocrinas, tales como vitiligo, alopecia areata, gastritis autoinmune y anemia perniciosa. Se clasifica en tres síndromes poliendocrinos autoinmunes (SPA). En Europa la incidencia del tipo I es menor a 1:100000 por año y los 2 y 3 varían entre 1–2:100000 por año. Colombia no cuenta con registros que permitan calcularla. Se reporta el caso de un hombre de 18 años diagnosticado con hipotiroidismo autoinmune, a los 15 años de edad debutó con cetoacidosis diabética y a los 17 con posterior aparición de vitiligo. El manejo inicial se realizó con levotiroxina sódica y análogos de insulina. Este caso corresponde a un SPA tipo IIIA, ya que cursa con hipotiroidismo autoinmune, diabetes mellitus y como último hallazgo cronológico la asociación con vitiligo. La detección de una endocrinopatía autoinmune en pacientes jóvenes debe alertar sobre la posible existencia de un SPA.

345. Acute Onset Diabetic Ketoacidosis/Hyperosmolar Hyperglycemic State in Patients Taking Integrase Strand Transfer Inhibitors

BackgroundA few case reports have noted uncontrolled hyperglycemia in patients switched to dolutegravir. Several cohort studies have found increased weight gain among patients treated with integrase inhibitors (INSTI). We present clinical observations among 3 patients admitted to hospital for diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) while receiving INSTIs for the management of HIV.MethodsCase 1: A 44-year-old man with HIV and dyslipidemia presented with altered mental status and lethargy. A fingerstick glucose was >600 mg/dL. Chemistries revealed glucose of 1,600 mg/dL and an elevated β-hydroxybutyrate. HbA1c was 12.4%. His antiretroviral regimen consisted of cEVG/TAF/FTC for the last 3 years. Previous HbA1c levels were 5.7% and 6.2% (Figure 1). Case 2: A 55-year-old woman with HIV, hypertension, dyslipidemia, and obesity presented with polyuria and polydipsia. The blood glucose level was >1,200 mg/dL with an anion gap >30 and HbA1c of 15%. Previous HbA1c levels ranged between 5.6 and 5.8% (Figure 2). She had been taking ABC/FTC/DTG for 2 years.Case 3: A 64 yo man with a history of HIV, hypertension, and obesity presented with polyuria and polydipsia. The blood glucose level was 1,152 mg/dL with no anion gap and HbA1c of 13.4%. Six months before, he had been switched from a c/DRV- based ART regimen to ABC/FTC/DTG. Previous HbA1c levels ranged between 5.8% and 6.2% (Figure 3).ResultsDiscussion: In the first 2 patients, the presentation with acute onset DKA occurred more than a year after being on an INSTI-based regimen; however, the latter patient presented with HHS within 6 months of being switched to an INSTI-containing regimen. The mechanism of action of INSTIs causing weight gain or an association with hyperglycemia is still under investigation.ConclusionAlthough the temporal onset of DKA and HHS while receiving INSTIs was not precise, the possible association of INSTIs and their direct effects on insulin resistance and diabetes warrant additional attention from post-market data. Meanwhile, providers should monitor INSTI-treated patients closely, especially those with features of metabolic syndrome. Disclosures All authors: No reported disclosures.

Recurrent diabetic ketoacidosis.

The purpose of this study is to examine risk factors for recurrence of diabetic ketoacidosis and determine interventions to prevent future admissions. Review article. Recurrent diabetic ketoacidosis is a serious and not uncommon health problem. Diabetic ketoacidosis is associated with severe morbidity and mortality and hospital admissions due to this problem constitute a serious economic burden on the healthcare system. Younger age at diabetic ketoacidosis onset, poor baseline glycemic control and elevated HbA1C, patient comorbidities, depression, alcohol or substance abuse, particularly active cocaine use, have been associated with recurrent diabetic ketoacidosis. In addition, socioeconomic factors (such as ethnic minority status, use of public health insurance and underinsurance), psychosocial, economic, and behavioral factors (including financial constraint, stretching a limited insulin supply, and homelessness) have been all reported to be associated with readmission among diabetic ketoacidosis patients. Identifying high-risk patients during the first diabetic ketoacidosis admission and performing relevant interventions (repeated instructions of insulin use, social help and involvement of family members in medical treatment, collaboration with the patient's primary care physician in order to establish a close and frequent follow up program) may help prevent future admissions. Further studies need to take place to determine whether early interventions with those factors prevent future admissions.

Diabetic ketoacidosis in children newly diagnosed with type 1 diabetes mellitus: Role of demographic, clinical, and biochemical features along with genetic and immunological markers as risk factors. A 20-year experience in a tertiary Belgian center.

Diabetic ketoacidosis (DKA) is the leading cause of morbidity and mortality in children with type 1 diabetes (T1D). Little is known about the association between genetic and immunological markers and the risk for DKA at onset of T1D. The aim of this study was to create a model foreseeing the onset of DKA in newly diagnosed patients. This retrospective study included 532 T1D children (aged <18 years at diagnosis) recruited in our hospital, from 1995 to 2014. DKA and its severity were defined according to the criteria of ISPAD. Genetic risk categories for developing T1D were defined according to the Belgian Diabetes Registry. Multivariate statistical analyses were applied to investigate risk factors related to DKA at diagnosis. Overall 42% of patients presented DKA at diagnosis. This study outlined the major risk of DKA at diagnosis for younger children (<3 years) and for those belonging to ethnic minorities. Children carrying neutral genotypes had a 1.5-fold increased risk of DKA at diagnosis than those with susceptible or protective genotypes, a paradoxical observation not previously reported. Only solitary positive IA-2A increased the risk of DKA at diagnosis. The proposed model could help to predict the probability of DKA in 70% of newly diagnosed cases. This was the first reported implication of IA-2A positivity and neutral genotypes predisposing to DKA at diagnosis regardless of its severity. Earlier diagnosis through genetic and immunological screening of high-risk children could decrease DKA incidence at diabetes onset.