Case Of Diabetic Ketoacidosis Research Articles

New onset diabetic ketoacidosis in a renal transplant recipient

Post-transplant diabetes mellitus (PTDM) is a well-known solid organ transplant complication, which can be related to immunosuppressants, particularly tacrolimus. We report an unusual presentation of PTDM with diabetic ketoacidosis (DKA). This is unique as PTDM typically resembles Type 2 DM, whereas DKA is associated with Type 1 DM and has rarely been reported as a complication of tacrolimus. A 38-year-old African American male on LCP-tacrolimus presented four months post kidney transplant with vomiting, weakness, poor appetite, and polyuria. Labs demonstrated hyperglycemia, ketonuria, and high anion gap metabolic acidosis. He was nonobese and had no personal or family history of Type 2 DM. DKA was suspected to be secondary to tacrolimus-induced pancreatic beta cell damage worsened by supratherapeutic tacrolimus levels. Latent autoimmune diabetes in adults (LADA) was diagnosed when further testing showed insulinopenia, low C-peptide, and anti-glutamic acid decarboxylase (GAD) autoantibodies. He required 120-units of subcutaneous insulin daily. Our literature review revealed only 16 other tacrolimus-induced DKA cases. No cases reported anti-GAD positivity and most showed beta cell toxicity reversibility with tacrolimus tapering or substitution. Our patient was early post-transplant with leukocytopenia, so tacrolimus was not exchanged. This unusual PTDM case may have resulted from both autoimmune and tacrolimus-induced beta cell destruction. Physicians should be aware of new onset LADA post-transplantation and tacrolimus toxicity leading to DKA, even in patients without traditional risk factors. Anti-GAD antibody screening in patients on tacrolimus who develop PTDM may identify patients less likely to recover beta cell function with immunosuppression augmentation which requires careful monitoring.

Diabetic Ketoacidosis and Adverse Outcomes Among Pregnant Individuals With Pregestational Diabetes in the United States, 2010-2020.

To assess the frequency of, risk factors for, and adverse outcomes associated with diabetic ketoacidosis (DKA) at delivery hospitalization among individuals with pregestational diabetes (type 1 and 2 diabetes mellitus) and secondarily to evaluate the frequency of and risk factors for antepartum and postpartum hospitalizations for DKA. We conducted a serial, cross-sectional study using the Agency for Healthcare Research and Quality's Healthcare Cost and Utilization Project Nationwide Readmissions Database from 2010 to 2020 of pregnant individuals with pregestational diabetes hospitalized for delivery. The exposures were 1) sociodemographic and clinical risk factors for DKA and 2) DKA. The outcomes were DKA at delivery hospitalization, maternal morbidity (nontransfusion severe maternal morbidity (SMM), critical care procedures, cardiac complications, acute renal failure, and transfusion), and adverse pregnancy outcomes (preterm birth, hypertensive disorders of pregnancy, and cesarean delivery) and secondarily DKA at antepartum and postpartum hospitalizations. Of 392,796 deliveries in individuals with pregestational diabetes (27.2% type 1 diabetes, 72.8% type 2 diabetes), there were 4,778 cases of DKA at delivery hospitalization (89.1% type 1 diabetes, 10.9% type 2 diabetes). The frequency of DKA at delivery hospitalization was 1.2% (4.0% with type 1 diabetes, 0.2% with type 2 diabetes), and the mean annual percentage change was 10.8% (95% CI, 8.2-13.2%). Diabetic ketoacidosis at delivery hospitalization was significantly more likely among those who had type 1 diabetes compared with those with type 2 diabetes, who were younger in age, who delivered at larger and metropolitan hospitals, and who had Medicaid insurance, lower income, multiple gestations, and prior psychiatric illness. Diabetic ketoacidosis during the delivery hospitalization was associated with an increased risk of nontransfusion SMM (20.8% vs 2.4%, adjusted odds ratio [aOR] 8.18, 95% CI, 7.20-9.29), critical care procedures (7.3% vs 0.4%, aOR 15.83, 95% CI, 12.59-19.90), cardiac complications (7.8% vs 0.8%, aOR 8.87, 95% CI, 7.32-10.76), acute renal failure (12.3% vs 0.7%, aOR 9.78, 95% CI, 8.16-11.72), and transfusion (6.2% vs 2.2%, aOR 2.27, 95% CI, 1.87-2.75), as well as preterm birth (31.9% vs 13.5%, aOR 2.41, 95% CI, 2.17-2.69) and hypertensive disorders of pregnancy (37.4% vs 28.1%, aOR 1.11, 95% CI, 1.00-1.23). In secondary analyses, the overall frequency of antepartum DKA was 3.1%, and the mean annual percentage change was 4.1% (95% CI, 0.3-8.6%); the overall frequency of postpartum DKA was 0.4%, and the mean annual percentage change was 3.5% (95% CI, -1.6% to 9.6%). Of 3,092 antepartum hospitalizations among individuals with DKA, 15.7% (n=485) had a recurrent case of DKA at delivery hospitalization. Of 1,419 postpartum hospitalizations among individuals with DKA, 20.0% (n=285) previously had DKA at delivery hospitalization. The above risk factors for DKA at delivery hospitalization were similar for DKA at antepartum and postpartum hospitalizations. The frequency of DKA at delivery hospitalization and antepartum hospitalizations for DKA increased between 2010 and 2020 among deliveries in individuals with pregestational diabetes in the United States. Diabetic ketoacidosis is associated with an increased risk of maternal morbidity and adverse pregnancy outcomes. Risk factors for DKA at delivery were similar to those for DKA during the antepartum and postpartum periods.

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

PurposeTo analyze the prevalence and progression of fulminant type 1 diabetes (FT1D) in Qatar.MethodsThis retrospective study analyzed consecutive index- diabetic ketoacidosis (DKA) admissions (2015–2020) among patients with new-onset T1D (NT1D) in Qatar.ResultsOf 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.ConclusionThis 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.

Re-emergence of a forgotten diabetes complication: Euglycemic diabetic ketoacidosis.

Diabetic ketoacidosis (DKA) is the most common emergency complication of diabetes. Euglycemic DKA (EDKA), on the other hand, has been known for many years but is a rare and under-recognized condition and constitutes a very small proportion of DKA cases. However, in recent years, an increase in the incidence of EDKA has been observed with the widespread use of sodium-glucose co-transporter 2 inhibitors, which have proven benefits in the treatment of diabetes mellitus and its cardiorenal complications, heart failure, and chronic kidney disease. Unlike classical DKA, these patients without significant hyperglycemia can easily be missed in emergency departments. EDKA should be kept in mind in patients with diabetes presenting with DKA but with a blood glucose level <250 mg/dL. The diagnostic and therapeutic approach after clinical suspicion in these patients is similar to classical DKA and is briefly summarized in this review. The most important point in treatment is that these patients are normoglycemic but have a significant insulin deficiency (relative or absolute). Therefore, insulin is the mainstay of the treatment and should be given together with dextrose solutions to avoid hypoglycemia.

Validation of the Diagnostic Accuracy Levels of International Classification of Diseases, 10th Revision Codes for Diabetic Ketoacidosis: A Multicentre, Cross-sectional Study of Adults

ObjectivesInternational Classification of Diseases (ICD) codes are commonly used to identify cases of diabetic ketoacidosis (DKA) in health services research, but they have not been validated. Our aim in this study was to assess the accuracy of ICD, 10th revision (ICD-10) diagnosis codes for DKA. MethodsWe conducted a multicentre, cross-sectional study using data from 5 hospitals in Ontario, Canada. Each hospitalization event has a single most responsible diagnosis code. We identified all hospitalizations assigned diagnosis codes for DKA. A true case of DKA was defined using laboratory values (serum bicarbonate ≤18 mmol/L, arterial pH ≤7.3, anion gap ≥14 mEq/L, and presence of ketones in urine or blood). Chart review was conducted to validate DKA if laboratory values were missing or the diagnosis of DKA was unclear. Outcome measures included positive predictive value (PPV), negative predictive value (NPV), sensitivity, and specificity of ICD-10 codes in patients with laboratory-defined DKA. ResultsWe identified 316,517 hospitalizations. Among these, 312,948 did not have an ICD-10 diagnosis code for DKA and 3,569 had an ICD-10 diagnosis code for DKA. Using a combination of laboratory and chart review, we identified that the overall PPV was 67.0%, the NPV was 99.7%, specificity was 99.6%, and sensitivity was 74.9%. When we restricted our analysis to hospitalizations in which DKA was the most responsible discharge diagnosis (n=3,374 [94.5%]), the test characteristics were PPV 69.8%, NPV 99.7%, specificity 99.7%, and sensitivity 71.9%. ConclusionICD-10 codes can identify patients with DKA among those admitted to general internal medicine.

Rates of diabetic ketoacidosis with empagliflozin use during hospitalization for acute heart failure.

There is concern that sodium-glucose cotransporter-2 inhibitorsduring hospitalization for acute heart failure (aHF) may precipitate diabetic ketoacidosis (DKA). A retrospective study of all hospitalization encounters for aHF defined by a primary HF International Classification of Diseases (ICD)-10 code in 15 Kaiser Permanente Southern California medical centers hospitalized between January 1, 2021 and August 31, 2023 was performed to describe rates of DKA with empagliflozin use. DKA was defined by the presence of either a DKA ICD-10 code or ketoacidosis lab criteria (bicarbonate <18 mmol/L and urine ketone 1+ or more or elevated serum beta-hydroxybutyrate within 12 h) during hospitalization. Among 21,630 hospital encounters (15,518 patients) for aHF, 1678 (8%) had empagliflozin use. There were 2 (0.1%) probable DKA cases in empagliflozin encounters and 15 (0.1%) in nonexposed encounters. These rates were similar when stratified by diabetes status and ejection fraction. Empagliflozin may be safe during aHF hospitalization.

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.

THU382 It’s Not What It Seems - Metformin Induced Severe Lactic Acidosis Mimicking Euglycemic Diabetic Ketoacidosis

Abstract Disclosure: M. Shaukat: None. R. Memon: None. M. Mack: None. E. Galarza: None. R. Saeed: None. Diabetic Ketoacidosis (DKA) is a life-threatening complication and, occasionally, the initial presentation of Diabetes Mellitus (DM). DKA can rarely present without elevated blood glucose levels, known as Euglycemic DKA, now typically associated with SGLT-2 inhibitors. Metformin is known to cause lactic acidosis but has not been reliably associated with euglycemic DKA. We present a case of metformin-associated lactic acidosis with renal failure and ketosis mimicking euglycemic DKA. Case: 82-year-old female with a history of DM type 2 on metformin and hypertension presented to the Emergency Department (ED) with complaints of presyncope, vomiting and generalized weakness for two weeks. In the ED, her temp. was 90.3 F and BP was 66/28 mmHg. Her labs revealed a potassium of 5.4mmol/L, bicarbonate 5 mmol/L, Creatinine 3.68 mg/dL (baseline 0.7mg/dL), Anion gap (AG) 45mmol/L, Lactate 25.1 mmol/L and Beta-hydroxybutyrate of 21.4 mg/dL. CT Scan of the chest and abdomen showed a 2 cm liver mass and pancreatitis. She was taken to the ICU and started on antibiotics, IV fluids, and vasopressors. The following day, her lactate was 13.5mg/dL, AG was 37mmol/L and Beta-hydroxybutyrate increased to 53.5mg/dL. Her blood sugars remained between 140-180mg/dL and her hemoglobin A1c was in the prediabetic range at 6.1%. She was thought to be in metformin induced euglycemic diabetic ketoacidosis and was started on an insulin drip with 5% Dextrose and 0.45% Normal Saline. Nephrology was consulted and she underwent hemodialysis for metformin toxicity. She remained on the insulin drip for 48 hours after which she was successfully weaned off. She currently remains off on any antidiabetic medication and is doing well. Discussion: DKA is a life-threatening complication of DM that presents as hyperglycemia, ketonemia, and AGMA. Euglycemic DKA is distinguished by blood glucose levels less than 250mg/dL and is usually seen with pregnancy, fasting states and use of SGLT-2 inhibitors. Previous cases of metformin-associated lactic acidosis (MALA) and concurrent euglycemic DKA have been reported, out of which several patients were concurrently on SGLT-2 inhibitors. After a thorough literature review, we were unable to determine a causal mechanism linking metformin and euglycemic DKA. In the reported cases, we believe that renal failure from various causes precipitated MALA due to decrease metformin clearance, with ketosis caused by starvation and exacerbated by metformin-induced inhibition of hepatic gluconeogenesis, further aggravated by an increase in stress hormones resulting in increased insulin resistance and ultimately leading to the development of the severe ketoacidosis. Even though this phenomenon has previously been referred to as “Metformin-induced euglycemic DKA”, we believe that this is more akin to a mimic, rather than true DKA. Presentation: Thursday, June 15, 2023

THU259 Alpelisib-induced Diabetic Ketoacidosis: Call For A Multidisciplinary Approach

Abstract Disclosure: N. Kalara: None. P. Rios: None. F. Vendrame: None. Introduction: Alpelisib is a p110a subunit phosphatidylinositol-3kinase inhibitor (PI3K) approved for treating hormone receptor-positive, human epidermal growth factor receptor 2-negative, PIK3CA mutated, advanced or metastatic breast cancer. PI3K signaling is essential for the metabolic action of insulin and the inhibition of p110a subunit is associated with hyperinsulinemia and hyperglycemia. In the combination (Alpelisib-Fulvestrant) arm of phase III SOLAR-1 study the all-grade incidence of hyperglycemia was 63%, but diabetic ketoacidosis (DKA) was also observed and reported in 0.7% of patients. To the best of our knowledge, less than 10 cases of Alpelisib-induced DKA have been reported in the literature. Here we describe an additional case. Case Description: A 62-year-old female with a history of metastatic breast cancer, hypertension, and prediabetes, presented with 3 days of nausea, vomiting, abdominal pain, weakness, polyuria, and polydipsia. Fifteen days prior to the presentation the HbA1c was 6.1% for which she was started on metformin 500 mg daily. Alpelisib 150 mg PO BID and Fluvestrant (Estrogen receptor antagonist) were also started the same day. The patient was told to stop the PIK3 inhibitor if the blood glucose increased above 200 mg/dL. The review of system was positive for fatigue, decreased appetite, malaise, 5 lbs weight loss during the previous week, and headache. She had no family history of any endocrinologic disease. The physical exam was unremarkable with no signs of insulin resistance. Laboratory tests revealed pH 7.31 (7.35-7.45), HCO3 10 mmol/L (22-26), PCO2 21 mmHg (35-45), glucose 884 mg/dL (74-106), sodium 120 mmol/L (136-145), K 5.2 mmol/L (3.5-5.1), Cl 93 mmol/L (98-107), CO2 7 mmol/L (21-32), anion gap 22 mmol/L (5-15), GFR 30 mL/min/1.73m2 (&amp;gt;60), Cr 1.80 mg/dL (0.5-1.02), BUN 43 mg/dL (7-18), beta-hydroxybutyrate 3 mmol/L (0.4-0.5), HbA1c 9.2% (4.2-5.6). Additional testing revealed C-peptide 2.3 ng/ml (1.1-4.4) with glucose 397 mg/dL. Results suggested a combined DKA and hyperosmolar hyperglycemic state (HHS). Alpelisib was discontinued and the patient was managed with insulin drip, fluids, electrolyte replacement, and eventually transitioned to a basal-bolus regimen (0.5U/kg). The patient was discharged on metformin and Insulin glargine with the recommendation to follow up with endocrinology and oncology. Conclusion: Our case highlights the importance of blood glucose and HbA1c screening before starting Alpelisib with emphasis on a multidisciplinary approach to monitor blood glucose levels to prevent DKA. Reference: 1. Farah SJ, Masri N, Ghanem H, Azar M. Diabetic ketoacidosis associated with alpelisib treatment of metastatic breast cancer. AACE Clin Case Rep. 2020;6(6):e349-e351. doi: 10.4158/ACCR-2020-0452 Presentation: Thursday, June 15, 2023

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

Euglycemic diabetic ketoacidosis development in a patient with type 2 diabetes receiving a sodium-glucose cotransporter-2 inhibitor and a carbohydrate-restricted diet

Sodium-glucose cotransporter-2 (SGLT2) inhibitors have become increasingly prescribed because of their proven protective effects on the heart and kidneys, and carbohydrate-restricted diets are popular therapeutic approaches for patients with obesity and diabetes. A 28-year-old obese woman with recently diagnosed diabetes developed euglycemic diabetic ketoacidosis (DKA) while on dapagliflozin, an SGLT2 inhibitor, and following a carbohydrate-restricted diet. She presented with nausea, vomiting, and epigastric pain. Hospital tests showed a blood glucose of 172 mg/dL, metabolic acidosis, and increased ketone levels, confirming euglycemic DKA. Treatment involved discontinuing dapagliflozin and administering fluids, glucose, and insulin. She recovered and was discharged on the fourth day. This is considered a case of euglycemic DKA induced by SGLT2 inhibitors and triggered by a carbohydrate-restricted diet. This case highlights the importance of physicians in confirming the symptoms and laboratory results of DKA, even in patients with normal blood glucose levels taking SGLT2 inhibitors and following carbohydrate-restricted diets. It is also crucial to advise patients to maintain an adequate carbohydrate intake.

Sodium-glucose cotransporter-2 inhibitors for hypergycemia in phosphoinositide 3-kinase pathway inhibition.

Phosphoinositide 3-kinase (PI3K) inhibition is used for the treatment of certain cancers, but can cause profound hyperglycemia and insulin resistance, for which sodium-glucose cotransporter-2 (SGLT2) inhibitors have been proposed as a preferred therapy. The objective of this research is to assess the effectiveness and safety of SGLT2 inhibitors for hyperglycemia in PI3K inhibition. We conducted a single-center retrospective review of adults initiating the PI3K inhibitor alpelisib. Exposure to different antidiabetic drugs and adverse events including diabetic ketoacidosis (DKA) were assessed through chart review. Plasma and point-of-care blood glucoses were extracted from the electronic medical record. Change in serum glucose and the rate of DKA on SGLT2 inhibitor versus other antidiabetic drugs were examined as co-primary outcomes. We identified 103 patients meeting eligibility criteria with median follow-up of 92days after starting alpelisib. When SGLT2 inhibitors were used to treat hyperglycemia, they were associated with a decrease in mean random glucose by -46mg/dL (95% CI -77 to -15) in adjusted linear modeling. Five cases of DKA were identified, two occurring in patients on alpelisib plus SGLT2 inhibitor. Estimated incidence of DKA was: alpelisib plus SGLT2 inhibitor, 48 DKA cases per 100 patient-years (95% CI 6, 171); alpelisib with non-SGLT2 inhibitor antidiabetic drugs, 15 (95% CI 2, 53); alpelisib only, 4 (95% CI 0.1, 22). SGLT2 inhibitors are effective treatments for hyperglycemia in the setting of PI3K inhibition.

The Case Files

The Case Files

Deaths From Alcoholic and Diabetic Ketoacidosis at Autopsy-A Comparison Study.

Diabetes mellitus and alcoholism are common disorders that may result in sudden death. Ketoacidosis may occur in both conditions. Diagnosis is based on history, and post-mortem findings including biochemistry and toxicology. This study compares deaths from alcoholic and diabetic ketoacidosis from two centres with large autopsy workloads. In the study period 9332 deaths were autopsies with 151 deaths diagnosed as ketoacidosis (1.6%) with 82 (0.9 %) being diabetic ketoacidosis (DKA) and 48 (0.5%) alcoholic ketoacidosis (AKA) deaths. There were more male deaths in each group. The median age for DKA deaths was 51 years (range 19-79). The median age for AKA deaths was 55 years (range was 34-78). The BMI range in DKA deaths was 12.5 to 40.4 kg/m2, with a median of 21.9. The comparative figures for AKA deaths was a range of 11.3 - 38.3 with a median of 20.2. Acetone concentrations were statistically higher in diabetic compared with alcoholic deaths, mean of 33.7 mg/100 mL in DKA cases versus mean of 16.9 mg/100 mL in AKA cases. Both DKA and AKA deaths are seen more commonly in males than female and are typically people with low BMIs in their 50s.

Abstract #1394296: The First Reported Case of Lorlatinib-Associated Diabetic Ketoacidosis

Lorlatinib is a third-generation tyrosine kinase inhibitor that inhibits anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 (ROS1). Although 2-10% of patients with non-small cell lung cancer developed hyperglycemia in phase 2 and 3 studies of lorlatinib, only one case has subsequently reported hyperglycemia >500 mg/dL, and no cases of diabetic ketoacidosis (DKA) have been previously reported. Phase 1 trials in neuroblastoma are ongoing. A 34-year-old woman with ALK-mutated paraspinal neuroblastoma presented with DKA 14 months after initiation of lorlatinib. Prior to starting lorlatinib, her hemoglobin A1c had been 5.0% (n: < 5.7%). After 12 months of therapy, her A1c increased to 7.8%, prompting the initiation of metformin 500 mg daily. However, two months later she was admitted for DKA with a blood glucose of 591 mg/dL (n: 65-99 mg/dL), CO2 17 mmol/L (n: 20-30 mmol/L), anion gap 18 (n: 8-12), moderate serum ketones, and 3+ ketonuria. Her A1c was 14.8%, C-peptide was 1.2 ng/mL (n: 1.1-4.3 ng/mL), and her glutamic acid decarboxylase-65 and islet antigen-2 autoantibodies were negative. She was also found to be incidentally positive for COVID-19 but was asymptomatic without any oxygen requirement. The patient’s DKA was successfully treated with IV insulin infusion, and she was discharged after 3 days with insulin glargine 27 units twice daily and insulin aspart 16 units with meals. One month later, her hemoglobin A1c had improved to 9.4%, and the patient’s oncologist discontinued lorlatinib due to sustained remission of her neuroblastoma and her complication of DKA. After stopping lorlatinib, her blood glucose rapidly improved, and she self-discontinued all her insulin in the following 3 weeks. One month later, she was seen in endocrine clinic only taking metformin 500 mg twice daily with fasting and post-prandial blood glucose ranging 86-107 mg/dL. This is the first reported case of DKA associated with lorlatinib. This case highlights the importance of close glucose monitoring and the risk of severe hyperglycemia and DKA while on lorlatinib therapy. Discontinuation of lorlatinib results in rapid improvement of glycemic control, and glucose-lowering treatments should be promptly deescalated to avoid hypoglycemia.

A UK nationwide study of adults admitted to hospital with diabetic ketoacidosis or hyperosmolar hyperglycaemic state and COVID-19.

To investigate characteristics of people hospitalized with coronavirus-disease-2019 (COVID-19) and diabetic ketoacidosis (DKA) or hyperosmolar hyperglycaemic state (HHS), and to identify risk factors for mortality and intensive care admission. Retrospective cohort study with anonymized data from the Association of British Clinical Diabetologists nationwide audit of hospital admissions with COVID-19 and diabetes, from start of pandemic to November 2021. The primary outcome was inpatient mortality. DKA and HHS were adjudicated against national criteria. Age-adjusted odds ratios were calculated using logistic regression. In total, 85 confirmed DKA cases, and 20 HHS, occurred among 4073 people (211 type 1 diabetes, 3748 type 2 diabetes, 114 unknown type) hospitalized with COVID-19. Mean (SD) age was 60 (18.2) years in DKA and 74 (11.8) years in HHS (p < .001). A higher proportion of patients with HHS than with DKA were of non-White ethnicity (71.4% vs 39.0% p = .038). Mortality in DKA was 36.8% (n = 57) and 3.8% (n = 26) in type 2 and type 1 diabetes respectively. Among people with type 2 diabetes and DKA, mortality was lower in insulin users compared with non-users [21.4% vs. 52.2%; age-adjusted odds ratio 0.13 (95% CI 0.03-0.60)]. Crude mortality was lower in DKA than HHS (25.9% vs. 65.0%, p = .001) and in statin users versus non-users (36.4% vs. 100%; p = .035) but these were not statistically significant after age adjustment. Hospitalization with COVID-19 and adjudicated DKA is four times more common than HHS but both associate with substantial mortality. There is a strong association of previous insulin therapy with survival in type 2 diabetes-associated DKA.

Pancreatic adverse events in patients treated with immune checkpoint inhibitors.

The inhibition of cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) and programmed cell death-1 (PD-1) has been a target for multiple drugs to enhance the T-cell antitumor activity. However, these immune checkpoint inhibitors (ICIs) come with a panel of immune-related adverse events (irAEs) that include mainly endocrine, skin, and gastrointestinal effects. We report seven cases of pancreatic irAEs in patients treated with ICIs at our institute. This is a case series; data was collected through chart review by 3 different data collectors and was analyzed separately by 2 physicians. Of these seven cases, two had diabetic ketoacidosis (DKA), while five had pancreatitis diagnosed by a substantial rise in serum lipase. Pancreatitis was asymptomatic in two cases. A pancreatic biopsy in one case revealed type 2 autoimmune pancreatitis. The ICIs used included pembrolizumab, nivolumab, durvalumab, and avelumab. Treatment included steroids and holding the ICI therapy: three cases had complete resolution of pancreatitis while two cases required either a prolonged taper or a second course of prednisone for recurrence of pancreatitis. On the other hand, the DKA cases were treated with withdrawal of the ICI and starting insulin with no steroid therapy. Pancreatitis and DKA are rare adverse events of ICIs that can be controlled by holding the ICI with or without starting steroids. Rechallenging the patient with the same ICI is possible in selected cases.

Serum Amylase as a Prognostic Factor in Diabetic Ketoacidosis

Abstract Objective: The study’s objectives were to learn about the impact of serum amylase levels on morbidity and mortality of diabetic ketoacidosis (DKA) patients. Methodology: This is a single-center cross-sectional study of 100 patients admitted to the Medicine Intensive Care Unit at Shyam Shah Medical College and SGM Hospital Rewa between January 2021 and June 2022. Results: Mean duration of hospital stay in DKA patients with serum amylase level &lt;140 U/L was 10.56± 5.04 days while DKA patients with serum amylase level ≥140 U/L was 23.75 + 1.66 Days. The mean amylase level in death cases of DKA was 198.32 IU/L and in recovered cases of DKA was 87.22 IU/L. Conclusion: In our study, we discovered that as serum amylase levels rise so does the length of hospital stay. Amylase levels were extremely high in death cases.

Factors associated with prolonged intensive care unit treatment and organ failure in pediatric patients with diabetic ketoacidosis

Context: Patients with diabetic ketoacidosis (DKA) have potential complications, such as respiratory failure, cerebral edema, or acute renal injury, all of which can lead to a prolonged hospital course. Aims: This study identified risk factors for prolonged intensive care unit (ICU) stay and organ failure in pediatric patients with DKA. Materials and Methods: Patients with DKA aged <19 years admitted to the pediatric ICU of our hospital between June 2011 and May 2021 were enrolled. Demographic characteristics, initial Glasgow Coma Scale score, source of admission, biochemical values, ICU length of stay (LOS), and hospital LOS were collected. The primary outcome was to identify factors associated with prolonged (≥48 h) ICU treatment. The secondary outcomes were to identify factors associated with respiratory failure, cerebral injury, or acute renal failure. Results: This study enrolled 137 patients. Nonemergency room admission was associated with longer ICU LOS [adjusted odds ratio (aOR), 3.14; 95% confidence interval (CI) 1.01–9.82] compared with admission from the emergency room. Older age (aOR, 0.89; 95% CI, 0.80–0.99) and underweight (aOR, 0.33; 95% CI, 0.12–0.95) were associated with shorter ICU LOS. Conclusions: Recognizing the risk factors associated with prolonged ICU LOS in pediatric patients with DKA may help clinicians with the early identification of critical DKA cases.

SGLT-2 inhibitors and euglycemic diabetic ketoacidosis/diabetic ketoacidosis in FAERS: a pharmacovigilance assessment.

To investigate the main feature and the association between euglycemic diabetic ketoacidosis (euDKA) /diabetic ketoacidosis (DKA) and sodium-dependent glucose transporters 2 inhibitors (SGLT-2i) from the FDA adverse event reporting system (FAERS). Cases of SGLT-2i-associated with euDKA/DKA were extracted from the FAERS database and compared with the reports for other hypoglycemia agents (ATC10 class). Disproportionality analyses used the reporting odds ratio (ROR) and information components (IC). The lower limit of the IC 95% credibility interval for IC > 0 is considered a reported signal, with at least 3 cases. A total of 10,195 cases of euDKA (n = 1680) and DKA (n = 8515) associated with SGLT-2i were identified from the FAERS. The SGLT-2i was associated with higher reporting of euDKA and DKA compared to other hypoglycemia agents (ROR = 16.69 [95% CI 14.89-18.70], IC = 3.27 [95% CI 2.91-3.66] for euDKA; ROR = 16.44 [95% CI 15.72-17.20], IC = 3.19 [95% CI 3.05-3.34] for DKA). In available data, the median onset time of euDKA/DKA was 31days, and canagliflozin had the longest onset time (96.5days for euDKA and 75days for DKA) compared with dapagliflozin and empagliflozin (p < 0.05). Male patients predominate in euDKA (51.9%), and female patients predominate in DKA (53.7%). Most patients discontinue the treatment (95.5% for euDKA, 93.9% for DKA), and approximately 49.0% (n = 3658) of patients had symptomatic remission after discontinuation of SGLT-2i, and 2.3% (n = 173) of patients had no remission. About 75.6% (n = 6126) of patients need hospitalization after euDKA/DKA. Post-marketing data showed that SGLT-2i was significantly associated with higher reporting of euDKA/DKA. Although euDKA/DKA is rare, clinicians should be aware of SGLT-2i-associated euDKA/DKA events.