Posterior reversible encephalopathy syndrome complicating hyperosmolar hyperglycemic syndrome.

Hyperosmolar hyperglycemic syndrome is a life-threatening diabetic emergency that manifests as altered mental status. An otherwise healthy 40-year-old man presented to our emergency department with headache and severe hypertension. Brain magnetic resonance imaging showed evidence of posterior reversible encephalopathy syndrome, a usually reversible neurological syndrome characterized by subcortical vasogenic oedema. This first reported case details posterior reversible encephalopathy syndrome concurrent with hyperosmolar hyperglycemic syndrome. Prompt diagnosis and management were essential to avoid non-reversible consequences.

Diazoxide-related Hyperglycemic Hyperosmolar State in a Child With Kabuki Syndrome.

Diazoxide is a commonly used first-line medication for the treatment of hyperinsulinism. Hyperglycemia may occur with diazoxide use. However, hyperglycemic hyperosmolar state (HHS) secondary to diazoxide is an exceedingly rare but potentially life-threatening adverse effect. We present a case of a 2-year-old with Kabuki syndrome and hyperinsulinism on diazoxide. She presented with 4 days of fever, respiratory symptoms, and lethargy. She was influenza B positive. Initial workup indicated HHS, with an elevated serum glucose (47.1 mmol/L [847.8 mg/dL]; reference range 3.9-6.0 mmol/L; 70-108 mg/dL), serum osmolality (357 mmol/kg H2O; reference 282-300 mmol/kg H2O) but absent urine ketones and no metabolic acidosis (venous pH 7.34). Her course was complicated by an acute kidney injury. Management in the hospital included discontinuation of diazoxide and intravenous fluid resuscitation, following which hyperglycemia and hyperosmolarity resolved. No insulin therapy was required. She remained normoglycemic without diazoxide for 2 weeks but subsequently required restarting of diazoxide for hypoglycemia. This case highlights the need for early recognition and prompt management of diazoxide-related HHS to reduce negative outcomes. We present the first case report of a child with Kabuki syndrome and hyperinsulinism with diazoxide-induced HHS.

Discovery of novel dihydro-pyrimidine hybrids: insight into the design, synthesis, biological evaluation and absorption, distribution, metabolism and excretion studies.

Aim: By keeping in aspects, the pharmacological potential of heterocyclic compounds, pyrimidine-based compounds were designed, synthesized and evaluated for α-amylase inhibitory potential.Materials & methods: Five new series 1a-l, 2a-d, 3a-d, 4a-d and 5a-d of 1,2,3,4-tetrahydroprimidine-5-carboxylate derivatives were designed by de novo method by taking Alogliptin as reference compound. Here in we describe synthesis and characterization of compounds as potential α-amylase inhibitor.Results: Structure activity relationship (SAR), in vitro analysis and molecular modelling approaches generate compounds 1 h, 1i, 1k and 4c as potential lead with good α-amylase inhibitory selection. However, compound 1k failed the criteria of optimization as drug lead by ADME studies while all other compounds showed optimum range for all in silico ADME parameters.Conclusion: Therefore, these compounds can serve as potential lead candidate in developing anti-diabetic therapy.

[Box: see text].

High versus low chloride load in adult hyperglycemic emergencies with acute kidney injury: a multicenter retrospective cohort study.

Hyperglycemic emergencies frequently lead to acute kidney injury (AKI) and require treatment with large amount of intravenous fluids. However, the effects of chloride loading on this population have not yet been investigated. We conducted a multicenter, retrospective, cohort study in 21 acute-care hospitals in Japan. The study included hospitalized adult patients with diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic syndrome (HHS) who had AKI upon arrival. The patients were classified into high and low chloride groups based on the amount of chloride administered within the first 48 h of their arrival. The primary outcome was recovery from AKI; secondary outcome was major adverse kidney events within 30 days (MAKE30), including mortality and prolonged renal failure. A total of 390 patients with AKI, including 268 (69%) with DKA and 122 (31%) with HHS, were included in the study. Using the criteria of Kidney Disease Improving Global Outcomes, the severity of AKI in the patients was Stage 1 (n = 159, 41%), Stage 2 (n = 121, 31%), and Stage 3 (n = 110, 28%). The analysis showed no significant difference between the two groups in recovery from AKI (adjusted hazard ratio, 0.96; 95% CI 0.72-1.28; P = 0.78) and in MAKE30 (adjusted odds ratio, 0.91; 95% CI 0.45-1.76; P = 0.80). Chloride loading with fluid administration had no significant impact on recovery from AKI in patients with hyperglycemic emergencies.Trial Registration This study was registered in the UMIN clinical trial registration system (UMIN000025393, registered December 23, 2016).

COVID-19 Related Predisposition to Diabetic Ketoacidosis.

Background and aims Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can exacerbate hyperglycemia and can cause life-threatening diabetic ketoacidosis (DKA) in patients with diabetes mellitus (DM). The objective of this study is to compare the characteristics of diabetic COVID-19 patients with and without DKA and to determine the predictors of mortality in the setting of COVID-19 and DKA. Methods This is a retrospective single-center cohort study including patients admitted to our hospital with COVID-19 and DM from March 2020 to June 2020. Patients with DKA were filtered as per the diagnostic criteria set by the American Diabetes Association (ADA). Patients with hyperosmolar hyperglycemic state (HHS) were excluded. A retrospective analysis was performed, which included those who developed DKA and those with neither DKA nor HHS. The primary outcome measurement was mortality rate and predictors of mortality for DKA. Results Out of 301 patients with COVID-19 and DM, 30 (10%) had DKA and five (1.7%) had HHS. Mortality was significantly higher in the DKA group compared to the non-DKA/HHS group (36.6% vs 19.5%; OR: 2.38; p=0.03). After adjusting for parameters used for multivariate logistic model for mortality, DKA was no longer associated with mortality (OR: 2.08, p=0.35). The independent predictors for mortality were age, platelet count, serum creatinine, C-reactive protein, hypoxic respiratory failure, need for intubation, and need for vasopressors. Conclusion Our study demonstrates higher mortality rate in diabetic COVID-19 patients with DKA. Though direct and independent statistical association of mortality with DKA could not be proven in our multivariate logistic model, physicians must be vigilant in risk-stratifying and managing these patients in a timely manner.

Severe Hypokalemia Causing Ventricular Tachycardia: A Case Report.

Hypokalemia and hyperosmolar hyperglycemic syndrome (HHS) are two reversible but potentially fatal disorders that are important to identify and treat urgently. A 43-year-old patient presented to the ED with altered mental status and slurred speech, difficulty communicating, left-sided facial droop, and stool incontinence according to emergency medical services. This was preceded by 1.5 weeks of nausea, vomiting, polydipsia, and weight loss. On presentation, the patient was found tachycardic and tachypneic, with uncertain neurological deficits on physical exam, hyperglycemia, and electrocardiogram (EKG) abnormalities. Lab data were consistent with hyperosmolar hyperglycemic nonketotic coma. This case provides two important clinical scenarios in which cardiac EKG abnormalities and focal neurological deficits are the product of hyperosmolality and electrolyte abnormalities. Hypokalemia with EKG abnormalities consistent with a potential ischemic disease can progress into wide complex tachycardia and ventricular fibrillation. Hyperosmolar hyperglycemia may manifest with focal neurological deficits and without the classical presentation of a coma. Careful consideration of EKG and lab values in the context of clinical presentation may provide clues to resolvable etiologies. We report a case of a patient who presented to the ED with hypokalemia and HHS, both reversible but potentially fatal disorders that are important to identify and urgently treat.

COVID-19 Viral Infection Presenting With Diabetic Ketoacidosis, Hyperosmolar Hyperglycemic Syndrome, or Mixed Hyperglycemic Crisis: A Case Series.

Cardiovascular disease, COPD, and diabetes (DM) are associated with increased complications with COVID-19. A correlation between COVID-19 and diabetic ketoacidosis (DKA) or Hyperosmolar Hyperglycemic Syndrome (HHS) has been suggested; however, the precise mechanism remains unclear. We present a case series of six patients with COVID-19 infections who were found to have DKA, HHS, or mixed picture. Wedescribe an association between COVID-19 and hyperglycemic emergencies. Six patients (50% male, 50% female, mean age 47.667 ± 18.747) were identified from November 2021 to February 2022. Comorbidities included DM (83.3%), HTN (50%), as well as ESRD, A-Fib, ISLD, HIV, and dementia (each 16.7%). Common review of systems included nausea and vomiting (50%), abdominal pain (33.3%), dyspnea (33.3%), and decreased appetite (33.3%). Additional findings were dysarthria, facial droop, generalized weakness, productive cough, myalgias, and increased urinary frequency (16.7%). Patients were diagnosed with DKA (50%), mixed process (33.3%), andHHS(16.7%). In terms of COVID-19 symptoms, most patients were asymptomatic (83.3%), with one patient developing hypoxia. The survival rate was 100%. Infections can incite DKA/HHS; yet, COVID-19 may have factors that amplify this process, in the setting of pancreatic beta-cell dysfunction from the virus itself. This may contribute to why diabetic patients have a ten times higher risk of death if they develop COVID-19. This virus binds to ACE2 receptors in the pancreas and damages the islets, ultimately decreasing insulin release. Here, we introduce cases of DKA/HHS in the setting of COVID-19, to understand the relationship between how COVID-19 infections may exacerbate diabetic complications.

Case report: Hyperosmolar hyperglycemic syndrome secondary to PEG-asparaginase-induced hypertriglyceridemia and pancreatitis.

Pegylated (PEG)-asparaginase is an established treatment for acute lymphoblastic leukemias that exhibits an antitumor effect by depleting asparagine, an amino acid essential for leukemia cell protein synthesis. Pancreatitis with hypertriglyceridemia is a well-established toxidrome associated with PEG-asparaginase. However, impaired pancreatic synthetic function and hormone release have rarely been reported as a result of PEG-asparaginase pancreatitis. In this report, we present a 22-year-old woman recently diagnosed with T-acute lymphoblastic leukemia (T-ALL), who presented to the hospital with progressive weakness, confusion, blurry vision, hallucinations, and abdominal pain after induction treatment with daunorubicin, vincristine, PEG-asparaginase, and dexamethasone following the AYA protocol. She was found to have hypertriglyceridemia, acute pancreatitis, and hyperosmolar hyperglycemic syndrome. While pancreatitis and hypertriglyceridemia are commonly reported side effects of PEG-asparaginase, HHS related to these conditions has been sparsely reported. Providers should maintain awareness of this association and consider routine serial glucose monitoring of patients receiving PEG-asparaginase.

Fresh Cerebral Infarction-Like MRI Findings Mimicking Hyperosmolar Hyperglycemic Syndrome With Seizures.

Hyperosmolar hyperglycemic syndrome (HHS) is a severe diabetes-related condition. Patients with HHS can present with abnormal magnetic resonance imaging (MRI) findings similar to those of fresh cerebral infarction. Here, we present the case of a 95-year-old woman with HHS who was initially misdiagnosed with seizures due to fresh cerebral infarction of the pons. Her MRI revealed small abnormal lesions in bilateral pons which showed hyperintensity on T2-weighted imaging and diffusion-weighted imaging. Thus, the patient was initially diagnosed with seizures associated with fresh cerebral infarction of the pons. However, hyperglycemia and hyperosmolarity were later observed, and the patient was diagnosed with HHS. Intravenous insulin and saline infusions were administered, which led to improvements in laboratory findings and seizures. The MRI findings of the pons disappeared after the treatment of HHS. Cortical restricted diffusion is observed in about 60% of cases with HHS, even if no obstruction of the artery is detected. On the contrary, patients with HHS have an increased risk of stroke during the treatment of HHS. Therefore, it is crucial for clinicians to examine patients with neurological symptoms associated with HHS not only based on MRI findings but also on neurological examination over time. In conclusion, clinicians should be aware of fresh cerebral infarction-like MRI findings in patients with HHS.

Formation of large abscess tumor including gallstone in ileum during therapy for hyperosmolar hyperglycemic syndrome: a case report.

Hyperosmolar hyperglycemic status (HHS) is one of the most serious acute metabolic complications of diabetes mellitus (DM) and the patients with type 2 DM are immunocompromised host, especially when glycemic control is poor. Under hyperglycemic conditions, we have to pay much attention even for rare infection. Bouveret's syndrome is a rare type of gallstone ileus together with duodenal obstruction secondary to the passage of a stone through a cholecystoduodenal fistula. Herein, we reported a rare case with formation of large abscess tumor, including necrotic ileum and gallstone after taking therapy for HHS. She was under more rare conditions rather than Bouveret's syndrome, because large abscess tumor was formed not in the duodenal bulb but in the ileum together with necrotic ileitis and abdominal abscess with impacted gallstone. We should bear in mind that T2DM patients are immunocompromised host in particular under untreated or poorly controlled conditions and thereby they could have rare inflammatory diseases such as a large abscess tumor. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13340-021-00540-3.

COVID-19 Vaccines and Hyperglycemia-Is There a Need for Postvaccination Surveillance?

The COVID-19 vaccines currently in use have undoubtedly played the most significant role in combating the SARS-CoV-2 virus and reducing disease severity and the risk of death among those affected, especially among those with pre-existing conditions, such as diabetes. The management of blood glucose levels has become critical in the context of the COVID-19 pandemic, where data show two- to threefold higher intensive care hospital admissions and more than twice the mortality rate among diabetic COVID-19 patients when compared with their nondiabetic counterparts. Furthermore, new-onset diabetes and severe hyperglycemia-related complications, such as hyperosmolar hyperglycemic syndrome (HHS) and diabetic ketoacidosis (DKA), were reported in COVID-19 patients. However, irrespective of the kind of vaccine and dosage number, possible vaccination-induced hyperglycemia and associated complications were reported among vaccinated individuals. The current article summarizes the available case reports on COVID-19 vaccination-induced hyperglycemia, the possible molecular mechanism responsible for this phenomenon, and the outstanding questions that need to be addressed and discusses the need to identify at-risk individuals and promote postvaccination monitoring/surveillance among at-risk individuals.

Hyperosmolar hyperglycemic syndrome induced by diazoxide and furosemide in a 5-year-old girl.

Hyperglycemia and hyperosmolar hyperglycemic syndrome (HHS) are the rare adverse effects of diazoxide. Furosemide has been reported to worsen glucose tolerance and cause HHS. A 5-yr-old girl presented to the emergency department with complaints of tachycardia, polyuria, and lethargy for 1 wk prior to hospitalization. She was treated with two diuretics for aortic valve reflux disease and diazoxide for congenital hyperinsulinemia. She was diagnosed with HHS based on her serum glucose level of 529 mg/dL and serum osmotic pressure of 357 mOsm/kg. There were no findings suggestive of new-onset diabetes mellitus. She had fever on admission and, was diagnosed with a urinary tract infection. The blood diazoxide level at the time of hospitalization was 25 µg/dL. Diazoxide use, even in patients with low diazoxide levels, may cause hyperglycemia. Patients on diuretics and diazoxide must be carefully monitored, considering the risk of developing HHS.

Mesenteric venous thrombosis: A lethal complication of hyperglycemic crises.

PURPOSE: Although hyperglycemic crises can lead to a hypercoagulable state, few instances of associated mesenteric venous thrombosis (MVT) have been reported. Worsening abdominal pain in the context of shock requiring vasopressor support should prompt urgent further investigation. SUMMARY: A 44-year-old Hispanic male arrived at an emergency department with chief complaints of lethargy, polydipsia, and polyuria. His past medical history included type 2 diabetes, epilepsy, obesity, tobacco smoking, and noncompliance with his medications. On arrival the patient had a serum glucose concentration of >1,600 mg/dL, and hyperosmolar hyperglycemic syndrome (HHS) was diagnosed. The patient was admitted to the intensive care unit with respiratory failure and subsequently developed shock refractory to fluid resuscitation, necessitating vasopressor support. On hospital day 4, a computerized tomogram obtained for investigation of increasing abdominal tenderness revealed superior MVT and pneumatosis intestinalis. Despite an emergency laparotomy and enterectomy, the patient ultimately succumbed on hospital day 41 due to recurrent pneumonia complicated by acute respiratory distress syndrome and septic shock. CONCLUSION: Shock that is refractory to aggressive fluid resuscitation, necessitating pressor support, in the setting of HHS or diabetic ketoacidosis should prompt investigation for the underlying source of shock. Other etiologies, including hypovolemic, cardiogenic, and obstructive shock, should be considered; however, infection is the leading trigger of hyperglycemic crises. Although rarely reported, MVT should be considered in the diagnostic algorithm in the absence of an identified infectious source. Prompt investigation should include use of diagnostic modalities such as computed tomography to assess for MVT.

Updates in the Management of Hyperglycemic Crisis.

Diabetes mellitus (DM) affects the metabolism of primary macronutrients such as proteins, fats, and carbohydrates. Due to the high prevalence of DM, emergency admissions for hyperglycemic crisis, diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS) are fairly common and represent very challenging clinical management in practice. DKA and HHS are associated with high mortality rates if left not treated. The mortality rate for patients with DKA is < 1% and ~ 15% for HHS. DKA and HHS have similar pathophysiology with some few differences. HHS pathophysiology is not fully understood. However, an absolute or relative effective insulin concentration reduction and increased in catecholamines, cortisol, glucagon, and growth hormones represent the mainstay behind DKA pathophysiology. Reviewing the patient's history to identify and modify any modifiable precipitating factors is crucial to prevent future events. The aim of this review article is to provide a review of the DKA, and HHS management based on the most recently published evidence and to provide suggested management pathway of DKA of HHS management in practice.

A Case of Central Pontine Myelinolysis Occurred During Treatment of Hyperosmolar Hyperglycemic Syndrome.

Central pontine myelinolysis (CPM) is a rare demyelinating condition which has been reported to occur in a variety of clinical settings, but most commonly in association with a rapid rise in plasma osmolality during correction of chronic hyponatremia. The clinical consequences can vary from a mild motor weakness that resolves completely over time to the devastating locked-in syndrome. In this presentation, we report a case of hyperosmolar hyperglycemic syndrome (HHS) with ponto-occipital disintegration. A 71-year-old female was transferred to our ER by an ambulance due to consciousness disorder and continuous fever for 10 days. We diagnosed septic shock caused by urinary tract infection (UTI), cerebral multiple infarctions, acute kidney injury (AKI) and HHS without treatment for diabetes. Then, we started therapeutic interventions for them based on the guideline with severe control for blood sugar (BS; primary 1635 mg/dl) under insulin therapy and hypernatremia (primary 153 mEq/l) under crystal infusion control in advanced care unit, apparently on routine lab data. However, the initial serum sodium value of 153 mEq/l was slowly compensated to 148 mEq/l in 60 hours under guideline on routine lab data, the initial compensated sodium value with osmolality was changed from 178 mEq/l to 150 mEq/l in the period. She recovered from her primary diagnosis and unconsciousness. After stabilized sepsis and HHS, we detected CPM on brain MRI due to following up multiple cerebral infarctions with left leg paralysis and verbal disorder. She gradually recovered over several months with intensive rehabilitation and eventually regained near normal functional capacity with stabilized BS. When we consider HHS with hypernatremia, it may be necessary to pay attention to not only to BS control and sodium control according to the guideline but also to osmolality changes to prevent CPM.

Hyperglycemic Crisis in Patients With Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like Episodes (MELAS).

BACKGROUND: Diabetes mellitus is the most commonly encountered endocrinopathy in patients with mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), which manifests as multisystemic organ failure. Whether the management of diabetes mellitus in MELAS requires special consideration is not fully clarified. METHODS: In this single-center study, we retrospectively reviewed the medical records of patients with MELAS to elucidate the clinical characteristics of MELAS-associated diabetes mellitus. RESULTS: Four patients among a total of 25 individuals with MELAS who were treated in the study institution developed diabetes mellitus. One patient had well-controlled diabetes mellitus, whereas the remaining three patients experienced hyperglycemic crisis as the first manifestation of diabetes mellitus. Two of the three patients were children aged four and six years. The hyperglycemic events occurred after surgery, infection, and status epilepticus, respectively. None of the three patients had diabetes mellitus previously based on randomly measured serum glucose levels that were within the normal range before the hyperglycemic crisis. Glycated hemoglobin levels measured during the hyperglycemic crisis indicated prediabetes in two patients and diabetes mellitus in one patient. Two patients recovered, whereas one patient died after developing multiorgan failure. CONCLUSIONS: Fulminant-onset diabetes mellitus occurring in patients with MELAS underscore the importance of routine measurement for glycated hemoglobin and more intense evaluation of glucose intolerance regardless of the patient age and lack of symptoms. Clinicians should be aware of the potential acute onset of hyperglycemic crisis in patients with MELAS, especially in individuals with aggravating factors.

Prediabetes Directly Deteriorates into Diabetic Ketoacidosis and Hyperosmolar Hyperglycemic Syndrome Triggered by Acute Pancreatitis: A Case Report Illustrating a "Chicken and Egg" Paradigm in Ketosis-Prone Diabetes.

INTRODUCTION: Diabetic crises occur most often in patients with type 1 diabetes and occasionally in type 2 diabetes, especially under stressful conditions. However, a diabetic crisis occurring directly from prediabetes is an unusual phenomenon. CASE REPORT: A 45-year-old woman presented with postprandial left upper quadrant abdominal pain, nausea, and vomiting. She had a past medical history of prediabetes with impaired fasting glucose and HbA1c 6.4%. On admission, routine laboratory tests showed high anion gap metabolic acidosis (pH 6.92), anion gap 41 mmol/L, blood glucose 931 mg/dL, beta-hydroxybutyrate 28 mmol/L, and calculated effective osmolarity 322 mOsm/kg; she was diagnosed with diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic syndrome (HHS), and DKA-related abdominal pain. Later, the patient was found to have elevated lipase and amylase, and diagnosed with acute pancreatitis. Since DKA can induce abdominal pain and nonspecific lipase elevation, both of which are characteristics of acute pancreatitis, while acute pancreatitis can conversely trigger DKA, there exists a "chicken and egg" paradigm. Therefore, the differential diagnosis is discussed. CONCLUSION: It is important to differentiate DKA from concomitant causes of abdominal pain to avoid missing the underlying etiology, which can be the trigger for DKA. During diabetic crises, treating the underlying trigger is just as important as managing metabolic derangements in order to achieve favorable outcomes; meanwhile, managing acute pancreatitis-associated hyperglycemia can promote recovery. Additionally, diabetic crisis that directly evolves from prediabetes illustrates an atypical form of diabetes called ketosis-prone diabetes; we briefly discuss its clinical characteristics, classification, and follow-up.