Cemiplimab-Induced Hyperosmolar Hyperglycemic State With Concurrent Diabetic Ketoacidosis in a Patient Receiving Treatment for Cutaneous Squamous Cell Carcinoma.

The immune checkpoint inhibitor (ICI) cemiplimab is a human monoclonal antibody used in the treatment of locally advanced and metastatic cutaneous squamous cell carcinoma (CSCC) not amenable to surgery or radiation therapy. Although cemiplimab shows excellent efficacy with a good tolerability profile, it can cause side effects, including potentially life-threatening endocrinopathies. We discuss the case of a 77-year-old Caucasian female with CSCC treated with only three cycles of cemiplimab who presented with altered mental status and was found to have severe hyperglycemia, hyperosmolarity, ketonemia, glucosuria, and ketonuria concerning for hyperosmolar hyperglycemic syndrome (HHS) with concurrent diabetic ketoacidosis (DKA). The patient made a rapid recovery in the hospital while on standard therapies for HHS/DKA and cemiplimab was discontinued upon discharge. While there have been reports of cemiplimab-induced DKA, to our knowledge, this is the first reported case of cemiplimab-induced HHS-DKA. This report aims to shed light on cemiplimab-induced HHS-DKA and to underscore the need to elucidate the molecular mechanisms underlying ICI-induced diabetes mellitus (ICI-DM).

Comprehensive Review on the Virulence Factors and Therapeutic Strategies with the Aid of Artificial Intelligence against Mucormycosis.

Mucormycosis, a rare but deadly fungal infection, was an epidemic during the COVID-19 pandemic. The rise in cases (COVID-19-associated mucormycosis, CAM) is attributed to excessive steroid and antibiotic use, poor hospital hygiene, and crowded settings. Major contributing factors include diabetes and weakened immune systems. The main manifesting forms of CAM─cutaneous, pulmonary, and the deadliest, rhinocerebral─and disseminated infections elevated mortality rates to 85%. Recent focus lies on small-molecule inhibitors due to their advantages over standard treatments like surgery and liposomal amphotericin B (which carry several long-term adverse effects), offering potential central nervous system penetration, diverse targets, and simpler dosing owing to their small size, rendering the ability to traverse the blood-brain barrier via passive diffusion facilitated by the phospholipid membrane. Adaptation and versatility in mucormycosis are facilitated by a multitude of virulence factors, enabling the pathogen to dynamically respond to various environmental stressors. A comprehensive understanding of these virulence mechanisms is imperative for devising effective therapeutic interventions against this highly opportunistic pathogen that thrives in immunocompromised individuals through its angio-invasive nature. Hence, this Review delineates the principal virulence factors of mucormycosis, the mechanisms it employs to persist in challenging host environments, and the current progress in developing small-molecule inhibitors against them.

Atezolizumab-Induced Type 1 Diabetic Ketoacidosis in a Patient With Small Cell Lung Cancer and Pre-existing Type 2 Diabetes Mellitus.

In this report, we present a case of a 70-year-old male with small cell lung cancer (SCLC) and pre-existing type 2 diabetes mellitus (T2DM) who developed type 1 diabetic ketoacidosis (DKA) following treatment with atezolizumab plus chemotherapy. Despite well-controlled T2DM with oral hypoglycemic agents, the initiation of immune checkpoint inhibitors (ICIs) led to rapid deterioration into insulin-dependent status due to ICI-induced type 1 diabetes mellitus (T1DM). Vigilant monitoring for hyperglycemia and timely intervention is crucial during ICI therapy, considering the potentially life-threatening complications. Although the patient achieved extended progression-free survival (PFS) post-treatment, re-administration of atezolizumab resulted in a bullous pemphigoid-like rash, necessitating discontinuation of the drug and corticosteroid treatment. The impact of recurring immune-related adverse events (irAEs) on treatment efficacy warrants further investigation.

Pseudo-Hypobicarbonatemia in Patients With Hypertriglyceridemia.

Hypobicarbonatemia with an elevated anion gap on a metabolic panel is frequently the initial marker of a life-threatening condition such as diabetic ketoacidosis in a patient with epigastric pain. The two commonly used means of measuring bicarbonate levels are direct measurement from a metabolic panel and calculated measurement from arterial blood gas. In this case report, we would like to highlight a potentially serious deficiency in one of these two means and how it may lead to a dangerous misdiagnosis and subsequent mismanagement. We also shine a light on potential measures to counteract or prevent this undesirable outcome.

The Knowledge, Attitudes, and Practices Regarding Diabetic Ketoacidosis Among Diabetic Patients in the Northern and Western Regions of Saudi Arabia.

Background and objective Diabetes mellitus (DM) is a chronic debilitating metabolic disease caused by insulin deficiency. Diabetic ketoacidosis (DKA) is a potentially fatal complication characterized by acute hyperglycemia and metabolic acidosis. In light of the high prevalence of DM in Saudi Arabia, we sought to investigate the knowledge, attitudes, and practices of the Saudi general population about DKA. Methods An online self-administered questionnaire was distributed through popular social media platforms among diabetics in the Saudi population. The survey questions involved demographic data; diabetes status including the time of diagnosis, current medications, and the latest HbA1c level; and an assessment of the knowledge about DKA through queries related to diagnostic criteria, definition, risk factors, symptoms, and preventive measures. Results Our study involved 400 participants, and 42.5% of them were able to correctly identify DKA as an emergency requiring immediate medical attention. Regarding the awareness of DKA's symptoms among the participants, 33.8% correctly identified excessive thirst as a key indicator, followed closely by frequent urination (31.8%), and the characteristic fruity breath odor (31.3%). As for the awareness of the participants of the causes of DKA, 33.8% correctly linked forgetting insulin injections to DKA development. Encouragingly, 39.8% of participants identified regular blood sugar monitoring as the most effective way to prevent DKA. Conclusions Most patients in our study demonstrated limited knowledge of DKA. However, a significant portion of them was able to identify it as an emergency. To prevent such events, raising awareness about DM and its complications may serve as the first step toward better outcomes in diabetic patients. We believe our findings can be used to devise quality-improving interventions in this field.

Post-burn Cervicofacial Necrotizing Fasciitis With Diabetic Ketoacidosis: A Report of a Case With a Favorable Outcome.

Post-burn necrotizing fasciitis (PBNF) is a serious and potentially life-threatening infection that occurs after a burn injury. It is characterized by rapid destruction of soft tissue and muscle and is usually caused by a bacterial infection. Diabetic ketoacidosis (DKA) is another serious complication of diabetes, which can occur when the body does not have enough insulin to break down glucose for energy. This causes the body to start breaking down fat for energy instead, leading to various complications. The present study discusses the association between PBNF and DKA in a patient with diabetes. Here is a case of a post-auricular abscess and a precipitated DKA. The abscess was located near the site of the previous burn injury that happened 20 years ago and was believed to have developed as a result of thick scar tissue. The patient was given adequate hydration, intravenous antibiotics, and insulin therapy. However, the abscess continued to grow with increasing insulin requirements and the patient underwent incision and drainage to remove the infected tissue, and an aggressive debridement was carried out. Thus, this case highlights the importance of closely monitoring blood sugar levels in patients with a history of burn injury and diabetes, as well as the potential for infections to precipitate DKA. Timely intervention, including incision and drainage, can lead to successful resolution of symptoms and improved outcomes.

Hashimoto Encephalopathy and Thyroid Storm by Diabetic Ketoacidosis and Acute Pancreatitis: A Case Report.

Hashimoto encephalopathy (HE) is a rare condition related to autoimmune origin characterized by high titers of antithyroid antibodies. Steroids are effective for treatment of HE, suggesting the autoimmunity as an underlying mechanism. In addition, anti-NH2-terminal of α-enolase antibodies (anti-NAE antibodies) is useful for diagnosis of HE. This report describes a 69-year-old woman developing both HE and thyroid storm (TS), following diabetic ketoacidosis (DKA) and acute pancreatitis. She had a history of Basedow's disease and uncontrolled type 2 diabetes mellitus, and her serum hemoglobin A1c was 10%. She complained of nausea and visited our hospital. She was diagnosed with DKA and acute pancreatitis. After admission, she went into cardiopulmonary arrest and she was diagnosed with TS after resuscitation. In addition, blood test collected during acute phase of TS revealed positive for not only anti-thyroid peroxidase (TPO) antibodies, thyroid stimulating hormone receptor antibodies and thyroid stimulating antibodies, but also anti-NAE antibodies. She was treated with intravenous steroids, potassium iodide and thiamazole under respirator and recovered sufficiently to do daily activities of life. We should keep in mind that there might be cases of HE in cases of TS presenting with central nervous system symptoms.

Effectiveness of Insulin Pump Therapy Versus Multiple Daily Injections for Glycemic Control and Rate of Diabetic Ketoacidosis Among Children With Type 1 Diabetes Mellitus.

Background Advances in pump technology and the availability of insulin analogs, as well as the results of the Diabetes Control and Complications Trial (DCCT), which established the benefit of improved glycemic control, have all contributed to the increased use of insulin pump therapy in recent years, particularly in children. Purpose This research aims to compare the impact of insulin delivery method, i.e., continuous subcutaneous insulin infusion (CSII) or multiple daily injections (MDI) on glycemic control and the rate of diabetic ketoacidosis (DKA) among children with type 1 diabetes mellitus in Al Ahsa, Saudi Arabia. Methods  A retrospective cohort study was carried out in a diabetic center in Al Ahsa, Saudi Arabia, over 24 months (2020-2022) among children with type I diabetes mellitus (age group 1-14 years). Results  In total, 351 patients with diabetes were induced, with 316 (90%) on MDI and 35 (10%) on CSII. After six months of diagnosis, precisely 38 (12%) of patients with diabetes on the MDI regimen experienced DKA, compared to 4 (11.4%) of those on the CSII regimen, with no statistically significant difference (P=0.918). At six months and nine months of follow-up, the average hemoglobin A1c (HbA1c) was considerably higher in diabetic patients on MDI (8.9 ± 1.7% vs. 8.2 ± 1.5% and 9.1 ± 1.6% vs. 8.0 ± 1.3%, respectively, with a significant p-value ≤0.05). Conclusion In this study, we found that patients on the MDI regimen had considerably higher HbA1c levels than patients on the CSII regimen, but there was no statistically significant difference in DKA rates between them. This is a short-term follow-up study, and we recommend that patients be followed for a longer period of time for further accurate outcomes.

Extensive-Disease Small-Cell Lung Cancer With Severe Immune-Related Adverse Events Due to Atezolizumab Maintaining a Complete Response for Two Years: A Case Report.

A 75-year-old male with diabetes mellitus was referred to our hospital with an abnormal shadow on chest radiography, based on which he was diagnosed with extensive-disease small-cell lung cancer (ED-SCLC; cT2bN2M1a). The first-line therapy comprised atezolizumab, carboplatin, and etoposide. After four cycles, the patient achieved complete response (CR), and maintenance therapy was initiated with atezolizumab. However, even though CR was maintained, maintenance therapy was discontinued after 16 cycles due to persistent grade 2 anorexia and fatigue. Simultaneously, the HbA1c decreased to 5.5%, and antidiabetic therapy was discontinued. Six months after the last dose of atezolizumab, the patient visited the emergency room because of anorexia, dry mouth, and fatigue. Laboratory findings were as follows: blood glucose was 668 mg/dL, glycated hemoglobin (HbA1c) was 8.8%, urine ketone was 2+, sodium (Na) was 127 mmol/L, potassium (K) was 6.5 mmol/L, creatinine (Cre) was 1.43 mg/dL, and arterial pH was 7.29. Based on these findings, his presentation was consistent with fulminant type 1 diabetes mellitus (T1DM) complicated by diabetic ketoacidosis (DKA). Regular continuous insulin and saline administration was initiated in the intensive care unit, and acidosis and electrolyte abnormalities were corrected. His C-peptide was <0.03 ng/mL. His insulin secretory capacity was considered to be depleted, and he required continuous subcutaneous insulin injections. Glutamic acid decarboxylase and insulin autoantibodies were absent. The complete response persisted without further therapy until two years since the event.

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.

Sodium-Glucose Cotransporter 2 Inhibitor (SGLT2i) Associated Diabetic Ketoacidosis in Oncology Patients: A Case Series and Literature Review.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) use is associated with an increased risk of diabetic ketoacidosis (DKA). The clinical data regarding the use of SGLT2i and its potential side effects in oncology patients is limited. We are retrospectively reporting four oncology patients with type 2 diabetes mellitus using SGLT2i who were admitted with DKA. The mean age of the patients was 61.25 years, and male to female ratio was 1:1. The duration of type 2 diabetes ranged from 10 to 20 years (mean 15.75 years) and the types of SGLT2i used were empagliflozin 25 mg and dapagliflozin 10 mg. The types of malignancy in our case series included squamous cell carcinoma of the cheek, ovarian cancer, and two patients had laryngeal carcinoma (squamous cell carcinoma). Diabetic ketoacidosis was diagnosed in three patients following chemotherapy or concurrent chemo-radiotherapy. Poor oral intake and infections were the main risk factors in our patients. Mean blood glucose level, anion gap, and bicarbonate level were 11.7 mmol/l, 32.25, and 5 mmol/l, respectively. The majority had moderate DKA based on pH (mean 7.13). The hospital course was complicated by acute kidney injury (n=4), infections (n=4) (urinary tract infections, and pneumonia), and three patients required critical care. The mean length of hospitalization was 19.2 days and no mortality was reported among our patients. SGLT2i-related DKA is an emerging complication recognized in oncology patients. Some of the risk factors for this complication are starvation, poor oral intake, and infection which are quite prevalent in oncology patients. Temporary holding of SGLT2i medication during this period might have a potential preventive role.

Risk of Diabetic Ketoacidosis Associated with Sodium Glucose Cotransporter-2 Inhibitors: A Network Meta-Analysis and Meta-Regression.

Background: Sodium glucose cotransporter-2 inhibitors (SGLT2is) represent an emerging class of drugs with diverse indications. Despite their therapeutic potential, concerns regarding safety, particularly diabetic ketoacidosis (DKA), remain contentious, with uncertainty regarding differences among various SGLT2is. This study aimed to conduct a network meta-analysis and meta-regression to evaluate the risk of SGLT2i-induced DKA and associated factors. Methods: We systematically searched electronic databases for randomized clinical trials assessing SGLT2is across indications, reporting incidences of DKA. Mixed treatment comparison pooled estimates (MTCPEs) were calculated, and odds ratios (OR) with 95% confidence intervals (95% CI) served as effect estimates. We analyzed differences across dose categories (low, medium, and high) and conducted a meta-regression analysis to identify risk factors. The strength of evidence for key comparisons was determined. Results: Our analysis included 73 articles encompassing 85,997 participants assessing the risk of DKA. SGLT2is were associated with a heightened risk of DKA compared to placebo/control interventions (OR: 1.83; 95% CI: 1.35, 2.46), a finding confirmed by bootstrap analysis. Among SGLT2is, dapagliflozin (OR: 1.9; 95% CI: 1.17, 3.08), sotagliflozin (OR: 1.93; 95% CI: 1.14, 3.25), canagliflozin (OR: 1.11; 95% CI: 1.11, 12.45), and ertugliflozin (OR: 3.92; 95% CI: 1.04, 14.77) exhibited increased DKA risk. No significant differences were observed among specific SGLT2is. Sub-group analyses revealed a high risk of DKA with low (OR: 1.98; 95% CI: 1.3, 2.95) and high doses (OR: 2.4; 95% CI: 1.7, 3.3), type 1 diabetes (OR: 3.6; 95% CI: 1.6, 8.1), type 2 diabetes (OR: 1.6; 95% CI: 1.3, 2.4), as well as a diabetes duration exceeding 10 years (OR: 3.4; 95% CI: 1.1, 10.8). The evidence of certainty for most comparisons was moderate. Conclusions: SGLT2 inhibitors (SGLT2is) have been found to elevate the risk of DKA. The key factors that significantly predict the likelihood of DKA include the presence of diabetes (whether T1D or T2D) and the duration of diabetes. Based on these findings, standard treatment guidelines should advise taking specific precautions against DKA in patients identified as high-risk.

Evaluation of a Protocol Change Promoting Lactated Ringers Over Normal Saline in the Treatment of Diabetic Ketoacidosis.

BACKGROUND: Current guidelines recommend normal saline (NS) for fluid resuscitation in the management of patients presenting with diabetic ketoacidosis (DKA). However, previous prospective studies have demonstrated improvement in patient-specific outcomes, including time to DKA resolution, when balanced crystalloid fluids are used. METHODS: We conducted a single institution, retrospective cohort study of adult patients admitted with DKA before and after a protocol change within our institution, which shifted the default resuscitative and maintenance fluid in our DKA management protocol from NS to lactated Ringer's solution (LR). The primary outcome was time from DKA clinical presentation until DKA resolution. The secondary outcome was time to discontinuation of DKA protocol insulin drip. RESULTS: Of 246 patients meeting inclusion criteria, 119 were in the NS group (preprotocol change, where NS was the default resuscitative fluid) and 127 to the LR group (postprotocol change, where LR was the default resuscitative fluid). Time to DKA resolution was significantly decreased in the LR group (mean = 17.1 hours; standard deviation [SD] = 11.0) relative to the NS group (mean = 20.6 hours; SD = 12.2; P = .02). Duration of DKA protocol insulin drip was shorter in the LR group (mean = 16.0 hours; SD = 8.7) compared with the NS group (mean = 21.4 hours; SD = 12.5; P < .001). CONCLUSIONS: In this retrospective cohort study, protocolized DKA intravenous fluid management with LR resulted in shorter time to resolution of DKA and reduced duration of DKA protocol insulin drip.

Psychiatric and Substance Use Disorders and Their Association With Clinical Outcomes in Diabetic Ketoacidosis and Hyperosmolar Hyperglycemic Syndrome.

BACKGROUND AND OBJECTIVE: Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) are life-threatening conditions that send nearly 180,000 patients to the intensive care unit each year, with mortality rates up to 5-10%. Little is known about the impact of concurrent psychiatric disorders on specific DKA/HHS outcomes. Identifying these relationships offers opportunities to improve clinical management, treatment planning, and mitigate associated morbidity and mortality. METHODS: We conducted a retrospective review including adult DKA/HHS admissions within a large Massachusetts hospital system from 2010 to 2019. We identified patients admitted inpatient for DKA or HHS, then filtered by International Classification of Disease-9-CM and International Classification of Disease-10-CM codes for psychiatric diagnoses that were present in patients electronic medical record at any point in this observational period. Outcomes included the number of inpatient admissions for DKA/HHS, age of death, rates of discharging against medical advice (AMA) from any inpatient admission, and end-stage renal disease/dialysis status. Multivariate regression was conducted using R software to control for variables across patients and evaluate relationships between outcomes and concurrent psychiatric disorders. Significance was set at P < 0.05. RESULTS: Seven thousand seven hundred fifty-six patients were admitted for DKA or HHS, 66.9% of whom had a concurrent psychiatric disorder. Of these patients, 54.5% were male, 70.4% were White, and they had an average age of 61.6 years. This compares with 26.1% with concurrent psychiatric condition within the general diabetes population, 52.1% of whom were male, 72.1% were White, and an average age of 68.2 years. A concurrent psychiatric disorder was associated with increased odds of rehospitalization (adjusted odds ratio [aOR] = 1.62 95% confidence interval [CI] 1.35-1.95, P < 0.001), of being diagnosed with end-stage renal disease and on dialysis (aOR = 1.02 95% CI 1.002-1.035, P = 0.02), and of leaving AMA (aOR = 6.44 95% CI 4.46-9.63, P < 0.001). The average age of death for those with a concurrent psychiatric disorder had an adjusted mean difference in years of -7.5 years (95% CI -9.3 to 5.8) compared to those without a psychiatric disorder. CONCLUSIONS: Of patients with DKA/HHS, 66.9% have a concurrent psychiatric disorder. Patients with a concurrent psychiatric disorder admitted for DKA/HHS were more likely to have multiple admissions, to leave AMA, to be on renal dialysis, and to have a lower age of mortality.

A Re-audit of the Management of Diabetic Ketoacidosis (DKA): The Importance of the Seven-Day Working Inpatient Diabetes Specialist Nurse Service.

Background Diabetic ketoacidosis (DKA) is a life-threatening metabolic emergency due to insulin deficiency in patients with diabetes mellitus. The United Kingdom national survey and local audits of the management of DKA have revealed several areas of suboptimal care, and room for improvement, necessitating the need for intensified education, updating local guidelines, and increased recruitment of seven-day working inpatient diabetes specialist nurses. Therefore, this project aimed to re-audit our adherence to the DKA treatment guidelines. Methodology A retrospective re-audit examining patient admissions with DKA between October 2022 and September 2023. A list of 18 standards/criteria, adopted from the Joint British Diabetes Society (JBDS) DKA treatment guidelines was used for this re-audit. Results were compared with that of the previous audit. Results We had 126 patients admitted with DKA between October 2022 and September 2023. There were 62 males and 64 females with an average (range) age of 46.5 (19-92) years. Eighty percent had type 1 diabetes, and common precipitating factors for admission included infection and poor adherence to insulin treatment. The median (IQR) length of hospital stay was 2.1 (1.0-5.1) days. Compared to the previous audit, improvements occurred in 11 of 18 standards/criteria. This included timely commencement of intravenous fluids and fixed-rate insulin, commencing glucose infusion to prevent hypoglycemia, potassium replacement, continuation of long-acting insulin during treatment, timely conversion to variable-rate insulin infusion, and conversion to the usual subcutaneous insulin regimen. Additionally, 124 patients (98.4%) were reviewed at least once by the inpatient diabetes specialist nurses (DSN) during their admission. Complications of treatment, namely, iatrogenic hypoglycemia and transient hypokalemia occurred in 13 (10.3%) and 40 (31.7%) patient admissions, respectively. Conclusions This re-audit demonstrated improved adherence to the guidelines during several steps in the management of DKA. It also demonstrated room for improvement regarding other aspects of care. The importance of continued education, accurate documentation, and the presence of seven-day working inpatient DSN cover cannot be overemphasized.

Euglycemic Diabetic Ketoacidosis Presenting as Hypoglycemia in a Patient With Type 2 Diabetes and Von Gierke's Disease.

Von Gierke's disease (VGD) is rarely associated with type 2 diabetes mellitus (DM2). We present a case of VGD with DM2 that presented with hypoglycemia in the setting of diabetic ketoacidosis (DKA) in a young male with VGD using the sodium-glucose co-transporter 2 (SGLT2) inhibitor empagliflozin. The patient required resuscitation with fluids containing glucose prior to the administration of insulin for DKA protocol with significant clinical improvement. This case demonstrates a rare presentation of DKA with hypoglycemia.

Diabetic Ketoacidosis and Hypertriglyceridemia-Induced Acute Pancreatitis Requiring Plasmapheresis: A Case Report of a Rare Presentation of Type 2 Diabetes Mellitus in Adults.

The triad of diabetic ketoacidosis, hypertriglyceridemia, and acute pancreatitis is a rare presentation of diabetes mellitus type 2 in adults. We report a case of a 41-year-old male who presented at the emergency department with a sudden onset of severe abdominal pain. Diagnosis of diabetic ketoacidosis, hypertriglyceridemia, and acute pancreatitis was made. Triglyceride level was 6056 mg/dL and glycated hemoglobin was 12.6%. Vigorous fluid therapy and continuous infusion of insulin were started, but due to maintained symptoms, a single plasmapheresis session was performed, with significant clinical improvement. This case emphasizes the diagnostic challenges of the triad and highlights the potential role of plasmapheresis in rapidly reducing triglyceride levels.

Association of COVID with Mycosis in General.

BACKGROUND: The COVID-19 pandemic caused by SARS-CoV-2 is a respiratory disease which created havoc worldwide, was accompanied by another peculiar, otherwise rare, secondary fungal infection Mucormycosis which was observed at exceptionally high incidence in India during the second wave of COVID-19. The article explores possible links between the two infectious diseases to understand a higher-than-normal occurrence of Mucormycosis in COVID-19 patients. Coronavirus enters the patients through ACE-2 and many other receptors like- NRP-1, TfR, CD-126, and CD-26. Virus bind to cells possessing these receptors and affect their proper functioning, disturbing homeostatic metabolism and resulting in conditions like hyperglycemia, Diabetic Ketoacidosis (DKA), low serum pH, iron overload, anemia, hypoxia, and immunosuppression as explained in the article. All these outcomes provide a very supportive environment for the attack and spread of Mucormycosis fungi. The major receptor for Mucormycosis in humans is the GRP-78. Its expression is upregulated by coronavirus entry and by hyperferritinemia, hyperglycemia, and acidic conditions prevalent in COVID patients, thus providing an easy entry for the fungal species. Upregulation of GRP-78 furthermore damages pancreatic ß-cells and intensifies hyperglycemia, showing quite a synergic relationship. Inordinate rise of Mucormycosis cases in India might be explained by facts like- India possessing a large proportion of diabetic patients, emergence of a very deadly strain of coronavirus- Delta strain, higher doses of steroids and antibodies used to treat patients against this strain, overburdened health care services, sudden much higher need of oxygen supply and use of industrial oxygen could explain the Mucormycosis outbreak observed in India during the second wave of COVID-19. OBJECTIVE: The present review discusses the functional interdependence between COVID-19 and Mucormycosis and summarizes the possible synergic links between COVID and Mucormycosis. CONCLUSION: The receptors and metabolic pathways affected by COVID-19 result in severe physiological conditions- hyperglycemia, DKA, anemia, iron overload, immunosuppression, and hypoxia. All these conditions not only increase the expression of GRP-78, the major receptor for entry of fungi but also play a crucial role in providing quality media for Mucormycosis fungus to establish and grow. Hence explains the fungal epidemic observed in India during the second wave of COVID-19 in India.

Impact of COVID-19 Lockdown on Occurrence of Acute Complications of Type 1 and Type 2 Diabetes and Overall Glycemic Management.

OBJECTIVES: The association of diabetes, and COVID-19 infection has been studied extensively; however, the occurrence of diabetic ketoacidosis (DKA) or hyperglycemic/hyperosmolar states (HHS) in adults during the lockdown has not been well characterized. In this study, we aimed to identify the impact of the lockdown on occurrence and severity of DKA/HHS admissions and glycemic management. METHODS: A retrospective chart review was conducted of patients admitted to Hamilton Health Sciences with a diagnosis of DKA or HHS from April to September 2019 (pre-lockdown) and from April to September 2020 (lockdown). Adult (≥18 years old) nonpregnant patients with a single admission in the study period were included for study. RESULTS: There were 229 admissions related to diabetes, with 171 admissions meeting the inclusion criteria (n=92 pre-lockdown, n=79 lockdown). In the lockdown group, 51.8% of the patients had type 2 diabetes mellitus, with 96.2% of admissions secondary to DKA. When comparing the 2 periods, the lockdown group trended toward higher rates of death (5.4% vs 10.1%, p=0.247) and euglycemic DKA (17.6% vs 24.4%, p=0.403). There were more new diagnoses of type 1 diabetes mellitus in the lockdown group compared with the pre-lockdown group (7.3% vs 16.7%, p=0.230). The average glycated hemoglobin was lower in the lockdown group compared with the pre-lockdown group (11.8% vs 10.4%, p=0.032). CONCLUSIONS: Overall, this study is among the first in Canada to assess the impact of the COVID-19 lockdown on admissions due to DKA and HHS. Although no significant differences were noted in severity of admissions, there was a trend toward more new diagnoses of type 1 diabetes mellitus presenting in DKA during the lockdown period.

Sodium-Glucose Cotransporter 2 Inhibitors Should Be Avoided for the Inpatient Management of Hyperglycemia.

OBJECTIVE: Hyperglycemia in patients with type 2 diabetes mellitus is frequently encountered in the hospital setting. The recent guidelines for the management of inpatient hyperglycemia have included the use of dipeptidyl peptidase 4 inhibitors as an alternative to standard insulin therapy in select patients. This raises the question of the inpatient use of sodium-glucose cotransporter 2 inhibitors (SGLT2i), which have gained increasing popularity in the outpatient setting because of beneficial cardiovascular and renal outcomes. This article describes the risks associated with the use of SGLT2i for the management of inpatient hyperglycemia. METHODS: A literature review was performed using PubMed and Google Scholar for studies assessing the inpatient use of SGLT2i. Search terms included "SGLT2 inhibitors," "euglycemic DKA," "inpatient hyperglycemia," "DPP4 inhibitors," "hypovolemia," and "urinary tract infections." Studies not written in English were excluded. Forty-eight articles were included. RESULTS: Review of the literature showed significant safety concerns with the use of SGLT2i for the inpatient management of hyperglycemia. Hospitalized patients treated with SGLT2i were at increased risk of diabetic ketoacidosis, euglycemic diabetic ketoacidosis, hypovolemia, and urinary tract infections. When compared head-to-head, SGLT2i were not more effective for inpatient glycemic control than dipeptidyl peptidase 4 inhibitors and did not reduce insulin requirements when used in combination with insulin. Although SGLT2i can be considered for the treatment of congestive heart failure, they should be started close to or at the time of discharge. CONCLUSION: Although SGLT2i are a preferred pharmacotherapy class for the outpatient management of type 2 diabetes mellitus, there are considerable safety concerns when using them in a hospital setting, and avoidance is recommended.