Inflammatory biomarkers predict higher risk of hyperglycemic crises but not outcomes in diabetic patients with COVID-19.

Background: Inflammation is a predictor of severe complications in patients with COVID-19 infection under a variety of clinical settings. A few studies suggested that COVID-19 infection was a trigger of hyperglycemic crises including diabetic ketoacidosis (DKA) and/or hyperglycemic hyperosmolar state (HHS). However, the association between inflammation and hyperglycemic crises in diabetic patients with COVID-19 infection is unclear. Methods: One hundred and twenty-four patients with type 2 diabetes mellitus (T2DM) and COVID-19 infection from January 2023 to March 2023 were retrospectively analyzed. Demographic, clinical, and laboratory data, especially inflammatory markers including white blood cell (WBC), neutrophils, neutrophil-to-lymphocyte ratio (NLR), c-reactive protein (CRP) and procalcitonin (PCT) were collected and compared between patients with or without DKA and/or HHS. Multivariable logistic regression analysis was conducted to explore the association between inflammatory biomarkers and the prevalence of hyperglycemic crises. Patients were followed up 6 months for outcomes. Results: Among 124 diabetic patients with COVID-19, 9 were diagnosed with DKA or HHS. Comparing COVID-19 without acute diabetic complications (ADC), patients with DKA or HHS showed elevated levels of c-reactive protein (CRP, P=0.0312) and procalcitonin (PCT, P=0.0270). The power of CRP and PCT to discriminate DKA or HHS with the area under the receiver operating characteristics curve (AUROC) were 0.723 and 0.794, respectively. Multivariate logistic regression indicated 1.95-fold and 1.97-fold increased risk of DKA or HHS with 1-unit increment of CRP and PCT, respectively. However, neither CRP nor PCT could predict poor outcomes in diabetic patients with COVID-19. Conclusion: In this small sample size study, we firstly found that elevated serum CRP and PCT levels increased the risk of hyperglycemic crises in T2DM patients with COVID-19 infection. More study is needed to confirm our findings.

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

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

The Possible Precipitating Role of SARS-CoV-2 in a Case of Late-Onset Hemichorea Due to a Hyperosmolar Hyperglycemic State: Case Report and Brief Literature Review.

Case report: An 83-year-old Italian female developed postural instability and gait disturbance associated with a concomitant hyperosmolar hyperglycemic state. Brain CT and MRI scans detected a lesion in the right putamen due to metabolic derangement. A month later, the patient started suffering from choreic movements along the left side of the body with brachio-crural distribution, approximately three weeks after SARS-CoV-2 infection. She was treated with tetrabenazine with complete resolution of the aberrant movements. Any attempt to reduce tetrabenazine caused a relapse of the symptoms. Discussion: In diabetic patients, choreic syndrome should be considered a rare event with a benign prognosis and favorable response to treatment. It is the result of a condition known as "diabetic striatopathy". The association of new-onset choreic movements, an episode of hyperglycemia, and a basal ganglia lesion is suggestive of this condition. Its pathophysiology remains unclear, and a lot of hypotheses are still debated. SARS-CoV-2 might have played a role in triggering the patient's motor symptoms. Conclusions: Our case report agrees with the general features of those reported in the literature about movement disorders in diabetic patients. The late onset of symptoms and the poor response to treatment seem to be atypical characteristics of the syndrome. Although speculative, we cannot exclude the role of SARS-CoV-2. This case can be added to the literature for further studies and reviews.

The silent diabetic decompensation epidemic during the SARS-CoV2 pandemic - The role of primary care in early diagnosis and prevention of severe diabetic decompensation.

AIM/HYPOTHESIS: Efficiency in controlling chronic diseases, especially in the primary care setting, is associated with reduced rates of hospitalizations. Poorly controlled diabetes is associated with severe diabetic decompensation, such as diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS). It is hypothesized that, in addition to the SARS-CoV2 pandemic, there was a parallel increase in decompensation of previously controlled chronic diseases, such as diabetes. In this work, the impact of the SARS-CoV2 pandemic on hospitalizations for severe diabetic decompensation in a Portuguese hospital was assessed. METHODS: A retrospective study by hospital clinical file consultation was performed and a cohort of 177 patients admitted to a Portuguese hospital with a diagnosis of DKA or hyperosmolar hyperglycemic state HHS, excluding SARS-CoV2 infected patients, between 2019 and 2020 was analysed. RESULTS: In the population not infected by SARS-CoV2, statistically significant differences were found in the relative number of hospitalizations (5.59 vs 3.79 hospitalizations for DKA/HHS per 1000 patients not infected with SARS-CoV2, p = 0.0093) and lethality due to DKA/HHS (0941 vs 0337 deaths from DKA/HHS per 1000 patients not infected with SARS-CoV2, p = 0.0251). This increase in hospitalizations and lethality was accompanied by a statistically significant increase in newly type 2 diabetes diagnosis in DKA/HHS hospital admissions (p = 0.0156) and by a statistically significant increase in average age of patients (56.3 ± 22.4 vs 69.1 ± 17.6, p < 0.001). DISCUSSION AND CONCLUSIONS: These results show the empirical perspective that the consequences of the pandemic also had a considerable impact on the control of chronic diseases such as diabetes, with a higher percentage of hospitalizations due to severe decompensation, especially in the elderly population.

[Treatment of acute diabetic metabolic crises in adults (Update 2023) : Hyperglycemic hyperosmolar state and ketoacidotic metabolic disorder]. / Therapie der akuten diabetischen Stoffwechselentgleisungen bei Erwachsenen (Update 2023) : Hyperglykämisch-hyperosmolare und ketoazidotische Stoffwechselentgleisung.

Diabetic ketoacidosis (DKA) and the hyperglycemic hyperosmolar state (HHS) represent potentially life-threatening situations in adults. Therefore, rapid comprehensive diagnostic and therapeutic measures with close monitoring of vital and laboratory parameters are required. The treatment of DKA and HHS is essentially the same and replacement of the mostly substantial fluid deficit with several liters of a physiological crystalloid solution is the first and most important step. Serum potassium concentrations need to be carefully monitored to guide its substitution. Regular insulin or rapid acting insulin analogues can be initially administered as an i.v. bolus followed by continuous infusion. Insulin should be switched to subcutaneous injections only after correction of the acidosis and stable glucose concentrations within an acceptable range.

Diabetes Ketoacidosis and Hyperosmolar Hyperglycemic Syndrome in Companion Animals.

Diabetes mellitus is a common endocrinopathy in dogs and cats. Diabetes ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) are life-threatening complications of diabetes resulting from an imbalance between insulin and the glucose counter-regulatory hormones. The first part of this review focuses on the pathophysiology of DKA and HHS, and rarer complications such as euglycemic DKA and hyperosmolar DKA. The second part of this review focuses on the diagnosis and treatment of these complications.

Bacteremia in patients with diabetic ketoacidosis: a cross-sectional study.

OBJECTIVES: To determine the incidence of bacteremia in patients with DKA. METHODS: We conducted a cross-sectional study of patients aged 18 years and older with a principal diagnosis of DKA or hyperglycemic hyperosmotic syndrome (HHS) who presented to our community hospital between 2008 and 2020. Using medical records from initial visits, we retrospectively calculated the incidence of bacteremia. This was defined as the percentage of subjects with positive blood cultures except for those with contamination. RESULTS: Among 114 patients with hyperglycemic emergency, two sets of blood cultures were collected in 45 of 83 patients with DKA (54%), and 22 of 31 patients with HHS (71%). The mean age of patients with DKA was 53.7 years (19.1) and 47% were male, while the mean age of patients with HHS was 71.9 years (14.9) and 65% were male. The incidences of bacteremia and blood culture positivity were not significantly different between patients with DKA and those with HHS (4.8% vs. 12.9%, P = 0.21 and 8.9% vs. 18.2%, P = 0.42, respectively). Urinary tract infection was the most common concomitant infection of bacteria, with E. coli as the main causative organism. CONCLUSION: Blood cultures were collected in approximately half of the patients with DKA, despite a nonnegligible number of them testing positive in blood culture. Promoting awareness of the need for taking blood culture is imperative for the early detection and management of bacteremia in patients with DKA. CLINICAL TRIAL REGISTRATION: UMIN trial ID - UMIN000044097; jRCT trial ID - jRCT1050220185.

Treatment of septic shock in two pediatric patients with severe diabetic ketoacidosis using invasive hemodynamic monitoring: a case report.

BACKGROUND: Diabetic ketoacidosis (DKA) is a life-threatening complication of diabetes mellitus. DKA associated with shock is a rare condition that occurs due to the fluid deficit or septic shock. It is not easy to differentiate these two conditions by clinical judgment and laboratory findings. Although the fluid therapy is the mainstay in DKA treatment, it looks like a double-edged sword-underhydration may result in organ failure whereas overhydration may lead to pulmonary and cerebral edema (CE). CASE PRESENTATION: Herein, we report on two pediatric patients presenting with DKA and septic shock. The first patient was an 8-year-old boy newly diagnosed with type 1 diabetes mellitus (T1DM) who presented with DKA and septic shock. We used a device for continuous hemodynamic monitoring (proAQT) to estimate his volume status. The patient was extubated 48 hours of hospitalization; the DKA was resolved after 52 hours of admission. He was discharged home in good condition on the 5th day. The second patient was a 13-year-old girl, a known case of T1DM, who presented with mixed DKA- hyperosmolar-hyperglycemic state (HHS) and septic shock. She was intubated and treated according to the data derived from pulse Contour Cardiac Output (PiCCO). After 3 days, she was extubated and transferred to the ward in good condition. CONCLUSION: Using invasive hemodynamic monitoring in critically ill children with severe DKA and hypotension might guide the physicians for hydration and selecting the most appropriate inotrope.

Mind the gap: Measured and Calculated Osmolarity are Not Interchangeable in Diabetic Hyperglycemic Emergencies.

INTRODUCTION: Small case series have reported that diabetic ketoacidosis is associated with an elevated osmolar gap, while no previous studies have assessed the accuracy of calculated osmolarity in the hyperosmolar hyperglycemic state. The aim of this study was to characterize the magnitude of the osmolar gap in these conditions and assess whether this changes over time. METHODS: In this retrospective cohort study, two publicly available intensive care datasets were used: Medical Information Mart of Intensive Care IV and the eICU Collaborative Research Database. We identified adult admissions with diabetic ketoacidosis and the hyperosmolar hyperglycemic state who had measured osmolality results available contemporaneously with sodium, urea and glucose values. Calculated osmolarity was derived using the formula 2Na + glucose + urea (all values in mmol/L). RESULTS: We identified 995 paired values for measured and calculated osmolarity from 547 admissions (321 diabetic ketoacidosis, 103 hyperosmolar hyperglycemic states and 123 mixed presentations). A wide variation in the osmolar gap was seen, including substantial elevations and low and negative values. There was a greater frequency of raised osmolar gaps at the start of the admission, which tends to normalize by around 12-24 h. Similar results were seen regardless of the admission diagnosis. CONCLUSIONS: The osmolar gap varies widely in diabetic ketoacidosis and the hyperosmolar hyperglycemic state and may be highly elevated, especially at admission. Clinicians should be aware that measured and calculated osmolarity values are not interchangeable in this population. These findings should be confirmed in a prospective study.

A case of hyperglycemic hyperosmolar syndrome in a pug dog.

An 8-year-old spayed female pug dog that had recently been diagnosed with pancreatitis was brought to a veterinary clinic with polyuria, polydipsia, and seizures. The dog was diagnosed with hyperglycemic hyperosmolar syndrome, a rare complication of diabetes mellitus. The dog was hospitalized and was administered intravenous fluids and insulin therapy, and clinical signs improved.

Un cas de syndrome hyperosmolaire hyperglycémique chez une chienne carlin. La chienne carlin femelle stérilisée âgée de 8 ans qui avait récemment reçu un diagnostic de pancréatite a été amenée dans une clinique vétérinaire avec une polyurie, une polydipsie et des convulsions. La chienne a été diagnostiquée avec le syndrome hyperosmolaire hyperglycémique, une complication rare du diabète sucré. La chienne a été hospitalisée et a reçu des fluides intraveineux et une insulinothérapie, et les signes cliniques se sont améliorés.(Traduit par Dr Serge Messier).

Hyperosmolar Hyperglycemic Crisis After Burn Injury in a Patient With Advanced Amyotrophic Lateral Sclerosis: A Case Report.

ABSTRACT: Metabolic disturbance in patients of amyotrophic lateral sclerosis is a rare presentation that might be related to disease progression and outcomes. Hypermetabolic status after major burn injury remains a critical issue in the modern medical care. Here, we present a rare case of a patient sporadic amyotrophic lateral sclerosis who suffered from minor burn injury (8% total body surface area), developing critical hyperosmolar hyperglycemic state during early hospitalization. Newly diagnosed diabetes is established and found related to the underlying disease of this patient. The accumulative metabolic alteration among vulnerable patients of amyotrophic lateral sclerosis and burn injury is noteworthy. Judicious monitoring of fluid and metabolic status helps to prevent the occurrence of acute hyperosmolar hyperglycemic state.

Lurasidone-induced hyperosmolar hyperglycemic syndrome: A case report.

INTRODUCTION: Lurasidone has few metabolic adverse effects and is recommended as an alternative when other antipsychotic drugs considerably increase body weight or blood sugar concentrations. CASE PRESENTATION: An 81-year-old man with bipolar disorder developed hyperosmolar hyperglycemic syndrome as a side effect of lurasidone. Routine monitoring of blood glucose concentrations led to the early detection and treatment of this disease, preventing life-threatening complications. DISCUSSION AND CONCLUSION: We describe a rare case of lurasidone-induced hyperosmolar hyperglycemic syndrome. The mortality rate of this syndrome is estimated to be up to 20%. This rate is significantly higher than that of diabetic ketoacidosis (currently <2%). Although lurasidone is considered to have a low risk of raising blood glucose concentrations, symptoms of hyperglycemia must be evaluated and blood glucose concentrations should be monitored regularly.

[Acquired Stomatocytosis in Hyperosmolar Hyperglycemic Derangement]. / Erworbene Stomatozytose beihyperosmolarer, hyperglykämer Entgleisung.

Acquired Stomatocytosis in Hyperosmolar Hyperglycemic Derangement Abstract. In the context of a suicidally motivated suspension of insulin therapy, a massive hyperosmolar hyperglycemic derailment occurred in pancreoprivic diabetes mellitus most likely due to aethyltoxicity. In the blood picture differentiation stomatocytes could be detected, the development of which will be discussed in more detail below.

Severe malnutrition as a cause of transient carbohydrate metabolism disorders which evolved into hyperosmolar hyperglycaemic state.

The hyperosmolar hyperglycaemic state (HHS) is a very severe condition characterised by hyperosmolality, hyperglycaemia and dehydration without significant ketosis. The article presents the case of a 14.5-year-old cachectic patient with diagnosed HHS. Appropriate treatment per the ISPAD Guidelines was implemented. After metabolic stabilisation was achieved, the patient was transferred for further treatment to the Pediatric Gastroenterology Department due to her life-threatening cachexia. Normal glucose levels were observed during hospitalisation and the patient required no further insulin supplementation. Unfortunately, two months after discharge from hospital, the patient suffered sudden death at home. The patient did not live until full diabetological diagnostics could be performed. The transient hyperglycaemia may have been caused by a very early stage of type 1 diabetes (pre-diabetes), malnutrition-related diabetes mellitus (MRDM) or stress-induced hyperglycaemia (SIH). The case demonstrates that HHS can develop not only secondary to diabetes, but also be a severe complication of transient carbohydrate metabolism disorders in the course of cachexia.

Acute stroke-like deficits associated with nonketotic hyperglycemic hyperosmolar state: an illustrative case and systematic review of literature.

INTRODUCTION: Nonketotic hyperglycemic hyperosmolar state (NKHHS) is associated with a wide spectrum of neurological syndromes including acute stroke-like deficits. Clinical features and etiology have not been established yet. METHODS: Here we provide a case illustration and systematic review on non-epileptic acute neurological deficits in NKHSS. The systematic literature search followed PRISMA guidelines and a predefined protocol, including cases of NKHSS with acute stroke-like presentation. RESULTS: The database search yielded 18 cases. Hemianopia was the most common clinical presentation (73%), followed by partial or total anterior circulation syndrome (26%). Patients with symptoms of acute anterior circulation infarct were significantly older (69.5 ± 5.1 vs. 52.2 ± 13.9 years; p = 0.03) and showed higher mean glucose levels at the admission vs. those with hemianopia (674.8 ± 197.2 vs. 529.4 ± 190.8 mg/dL; p = 0.16). Brain MRI was performed in 89% of patients, resulting abnormal in 71% of them, especially hemianopic (91%). Subcortical hypointensities in T2-FLAIR MR sequences were present in all the analyzed cases. Cortical DWI hyperintensities were also common (64%). EEG showed diffuse or focal slow wave activity in 68% of patients, especially with visual hallucinations (85%). Neurological symptoms completely resolved in 78% of patients within 6 (IQR 3-10) days, following aggressive treatment and glucose normalization. CONCLUSIONS: Our results suggest neuronal dysfunction on a metabolic basis as the leading cause of acute neurological deficits in NKHHS. Despite the generally favorable prognosis, prompt identification and aggressive treatment are crucial to avoid irreversible damage. Larger cohort studies are needed to confirm our findings.

Hyperosmolar hyperglycaemic state as a stroke cause or stroke mimic: an illustrative case and review of literature.

Hyperosmolar hyperglycaemic state (HHS) is a life-threatening metabolic complication of type 2 diabetes (T2DM) that often presents with neurological symptoms. A 74-year-old man with known T2DM presented to the emergency department with collapse, left-sided weakness and slurred speech (National Institutes of Health Stroke Scale (NIHSS) 3) and a biochemical profile consistent with HHS. When he further deteriorated (NIHSS 20), he was managed for concurrent ischaemic stroke. All his symptoms fully resolved after 24 hours, which coincided with establishment of normoglycaemia. Subsequent magnetic resonance imaging (MRI) of the head revealed a tiny parietal lobe infarct. Two further cases of HHS mimicking ischaemic stroke have been reported with symptoms and imaging findings resolving with treatment of HHS. Our case demonstrates how HHS can also accentuate symptoms of a minor stroke, highlighting the importance of excluding ischaemic stroke in HHS patients with neurological dysfunction. We recommend consideration of early MRI and/or computed tomography angiography in this cohort, especially in those appropriate for intervention.

Dramatic recovery without steroid therapy and withdrawal from insulin therapy in a subject with hyperglycemic and hyperosmolar syndrome and depletion of insulin secretory capacity induced by type 2 autoimmune pancreatitis: A case report.

INTRODUCTION: Autoimmune pancreatitis (AIP) is characterized by the involvement of autoimmune mechanisms and is classified as type 1, together with infiltration of IgG4-positive cells, and type 2 with poor serological abnormal findings. In clinical practice, AIP is often treated with steroid therapy. PATIENT CONCERNS: An 81-year-old Japanese woman had thirst and appetite loss in the previous 5 days; thus, she visited a local doctor. The patient had no abdominal or back pain. She had no history of diabetes mellitus, but at that time blood glucose level and HbA1c were as high as 633 mg/dL and 9.7%, respectively, and she was referred to our institution. DIAGNOSIS: Based on various clinical findings in this patient, we diagnosed her with hyperglycemic and hyperosmolar syndrome and depletion of insulin secretory capacity induced by type 2 AIP. INTERVENTIONS AND OUTCOMES: The patient completely recovered without steroid therapy and was withdrawn from insulin therapy. CONCLUSIONS: We should bear in mind the possibility of AIP when the sudden onset of hyperglycemia together with enlargement of the pancreas are observed in subjects without a history of diabetes mellitus.