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.

Predicting readmission due to severe hyperglycemia after a hyperglycemic crisis episode.

AIM: This study aimed to investigate the readmission pattern and risk factors for patients who experienced a hyperglycemic crisis. METHODS: Patients admitted to MacKay Memorial Hospital for diabetic ketoacidosis (DKA) or hyperglycemic hyperosmolar state (HHS) between January 2016 and April 2019 were studied. The timing of the first readmission for hyperglycemia and other causes was recorded. Kaplan-Meier analysis was used to compare patients with hyperglycemia and all-cause readmissions. Cox regression was used to identify independent predictors for hyperglycemia and all-cause readmission post-discharge. RESULTS: The study cohort included 410 patients, and 15.3 % and 46.3 % of them had hyperglycemia and all-cause readmissions, respectively. The DKA and HHS group showed a similar incidence for hyperglycemia, with the latter group showing a higher incidence of all-cause readmissions. The significant predictors of hyperglycemia readmissions included young age, smoking, hypoglycemia, higher effective osmolality, and hyperthyroidism in the DKA group and higher glycated hemoglobin level in the HHS group. CONCLUSIONS: Patients who experienced DKA and HHS had similar hyperglycemia readmission rates; however, predictors in the DKA group were not applicable to the HHS group. Designing different strategies for different types of hyperglycemic crisis is necessary for preventing readmission.

Time trend in excess mortality in children with type 1 diabetes from 1987 to 2016 in mainland France.

BACKGROUND: Mortality risk for children with type 1 diabetes (T1D) is unknown in France and their causes of death are not well documented. AIM: To determine the standardized mortality ratios (SMRs) and causes of death in children aged 1-14 years with T1D from 1987 to 2016. METHODS: The French Center for Epidemiology on Medical Causes of Death collected all death certificates in mainland France. SMRs, corrected SMRs (accounting for missing cases of deaths unrelated to diabetes), and 95% confidence intervals were calculated. RESULTS: Of 146 deaths with the contribution of diabetes, 97 were due to T1D. Mean age at death of the subjects with T1D was 8.8 ± 4.1 years (54% males). The cause of death was diabetic ketoacidosis (DKA) in 58% of the cases (70% in subjects 1-4 years), hypoglycemia or dead-in-bed syndrome in 4%, related to diabetes but not described in 24%, and unrelated to diabetes in 14%. The SMRs showed a significant decrease across the years, except for the 1-4 age group. In the last decade (2007-2016), the crude and corrected SMRs were significantly different from 1 in the 1-4 age group (5.4 [2.3; 10.7] and 6.1 [2.8; 11.5]), no longer significant in the 5-9 age group (1.7 [0.6; 4.0] and 2.1 [0.8; 4.5]) and borderline significant in the 10-14 age group (1.7 [0.8; 3.2] and 2.3 [1.2; 4.0]). CONCLUSIONS: Children with T1D aged 1-4 years still had a high mortality rate. Their needs for early recognition and safe management of diabetes are not being met.

Hyperglycaemic hyperosmolar state in an obese prepubertal girl with type 2 diabetes: case report and critical approach to diagnosis and therapy.

INTRODUCTION: Isolated Hyperosmolar Hyperglycaemic Syndrome (HHS) is a life-threatening condition characterized by elevated serum glucose concentrations and hyperosmolality without significant ketosis. It is often described in obese adults with unknown Type 2 Diabetes (T2D), rarely in youth. In childhood the most common cause of metabolic glucose related derangement is Diabetic Ketoacidosis (DKA) in Type 1 Diabetes (T1D). Interestingly, both components can be combined with each other, thus the prevalent condition needs to be recognised implying a different therapeutic approach. CASE PRESENTATION: In this case, we report a prepubertal Caucasian obese girl admitted for two episodes of combined HHS/DKA in order to elucidate her clinical course taking into account the current pediatric recommendations based on adult guidelines for HHS. CONCLUSIONS: The treatment of HHS and even more of HHS/DKA in youth is still controversial as no specific guidelines for children are available especially during the prepubertal age. The description of our case might be helpful and offer relevant points for future consensus.

Clinical characteristics and outcome in patients with combined diabetic ketoacidosis and hyperosmolar hyperglycemic state associated with COVID-19: A retrospective, hospital-based observational case series.

AIM: One of the risk factors for poor outcome with SARS-CoV-2 infection is diabetes mellitus; diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) are the most serious complications of diabetes mellitus. We aimed to explore the clinical characteristics and outcomes of COVID-19 patients presenting with combined DKA/HHS to our institution. METHODS: A retrospective, hospital based observation case series was performed on patients with SARS-CoV-2 admitted to Intensive Care Unit between 3/20/2020 and 4/20/2020. Inclusion criteria were: (1) Blood Glucose >250 mg/dL; (2) Serum bicarbonate <18 mmol/L; (3) Anion Gap >10; (4) serum pH <7.3; (5) ketonemia or ketonuria; (6) effective/calculated plasma osmolality >304 mOsm/kg and (7) positive SARS-CoV-2 RT-PCR. RESULTS: We reported 6 patients who presented during this period with combined DKA/HHS. Their median age was 50 years, all males, three Hispanic, and three African American. Hispanic patients, had more severe acidosis, and multiple comorbidities, with a higher mortality. The striking feature was that combined DKA/HHS was the initial presentation for COVID-19 for most of the cases. DISCUSSION: Our observational retrospective case series shows that diabetic patients are at risk of developing combined DKA/ HHS associated with COVID-19 and a substantial mortality. To our knowledge, we are first to report the clinical characteristics and outcome in this group of patients.

Acute Hyperglycemic Crises with Coronavirus Disease-19: Case Reports.

Since the first case was contracted by coronavirus disease-19 (COVID-19) in Daegu, Korea in February 2020, about 6,800 cases and 130 deaths have been reported on April 9, 2020. Recent studies have reported that patients with diabetes showed higher mortality and they had a worse prognosis than the group without diabetes. In poorly controlled patients with diabetes, acute hyperglycemic crises such as diabetic ketoacidosis (DKA) or hyperosmolar hyperglycemic state (HHS) also might be precipitated by COVID-19. Thus, intensive monitoring and aggressive supportive care should be needed to inadequately controlled patients with diabetes and COVID-19 infection. Here, we report two cases of severe COVID-19 patients with acute hyperglycemic crises in Korea.

[The Management of Blood Glucose Should be Emphasized in the Treatment of COVID-19].

Based on the higher mortality and the higher proportion of critically ill adults in coronavirus disease 2019 (COVID-19) patients with diabetes, good inpatient glycemic control is particularly important in the comprehensive treatment of COVID-19. Individualized blood glucose target goals and treatment strategies should be made according to specific circumstances of COVID-19 inpatients with diabetes. For mild patients, a strict glycemic control target (fasting plasma glucose (FPG) 4.4-6.1 mmol/L, 2-hour postprandial plasma glucose (2 h PG) 6.1-7.8 mmol/L) are recommended; a target for the glycemic control of common type patients (FPG 6.1-7.8 mmol/L, 2 h PG 7.8-10.0 mmol/L) and subcutaneous insulin deliver therapy are recommended; a target nonfasting blood glucose range of 10.0 mmol or less per liter for severe-type COVID-19 patients, a relatively Less stringent blood glucose control target (FPG 7.8-10.0 mmol/L, 2 h PG 7.8-13.9 mmol/L) for critically ill patients and intravenous insulin infusion therapy are recommended. Due to the rapid changes in the condition of some patients, the risk of diabetic ketoacidosis (DKA) or hyperglycemic hyperosmolar status (HHS) maybe occur during the treatment. Blood glucose monitoring, dynamic evaluation and timely adjustment of strategies should be strengthened to ensure patient safety and promote early recovery of patients.

Care of Children and Adolescents with Diabetes Mellitus and Hyperglycemia in the Inpatient Setting.

PURPOSE OF REVIEW: Children and adolescents with acute hyperglycemia and diabetes mellitus frequently have acute, potentially life-threatening presentations which require high-acuity care in an inpatient and often intensive care setting. This review discusses the evaluation and care of hyperglycemia and diabetes mellitus in hospitalized children in both critical and non-critical care settings, highlighting important differences in their care relative to adults. RECENT FINDINGS: Diabetic ketoacidosis remains highly prevalent at diagnosis among children with type 1 diabetes, and hyperglycemic hyperosmolar state is increasingly prevalent among children with type 2 diabetes. Recent clinical trials have investigated the potential benefits of various types of intravenous fluids and their rates of administration as well as the risks and benefits of intensive glucose control in critically ill children. The Endocrine Society has developed guidelines focused on managing hyperglycemic hyperosmolar state, outlining important aspects of care shown to decrease morbidity and mortality. In the non-critical illness setting, intensive therapy on newly diagnosed diabetes is increasingly recommended at the outset. With the increasing incidence of diabetes mellitus in children and adolescents, recent studies addressing acute diabetes emergencies help inform best practices for care of hospitalized children with hyperglycemia and diabetes.

Hyperglycaemic presentations in type 2 diabetes

BACKGROUND: Hyperosmolar hyperglycaemic state (HHS) is a syndrome that occurs in patients with type 2 diabetes mellitus (T2DM) and is comparable to diabetic ketoacidosis (DKA) seen in patients with type 1 diabetes. For a general practitioner working in a rural emergency department, recognition of HHS in a patient presenting with the triad of severe dehydration, hyperglycaemia and hyperosmolality is important to guide management and plan for disposition. OBJECTIVES: This article reviews the hyperglycaemic states that can occur in patients with T2DM. The reasons for the biochemical derangements in both HHS and DKA are outlined, with a focus on the recognition and management of HHS. DISCUSSION: Knowledge of the pathophysiology that influences HHS helps understand of its clinical presentation and treatment. HHS has a high mortality rate (5­20%), and having access to clinical guidelines from a referring hospital is useful to guide early management strategies.

Improvement in renal prognosis with prompt hemodialysis in hyperosmolar hyperglycemic state-related rhabdomyolysis: A case report.

RATIONALE: Acute kidney injury is common and correctable in patients with a hyperosmolar hyperglycemic state (HHS). Nevertheless, hyperglycemic crisis may also contribute to the development of rhabdomyolysis, which can worsen renal function and lead to high mortality in such patients. PATIENT CONCERNS: Herein, we report a case of hyperosmolar hyperglycemic state-related rhabdomyolysis and acute renal failure with an excellent outcome. DIAGNOSIS: A 26-year-old Asian female with underlying paranoid schizophrenia presented with newly diagnosed type 2 diabetes mellitus complicated with HHS. Her renal function deteriorated rapidly in spite of standard management for hyperglycemic crisis. Rhabdomyolysis was subsequently diagnosed according to the high levels of serum creatine kinase (CK) (37,710 U/L, normal range: 20-180 U/L) and myoglobin (5167.7 ng/mL, normal range: 14.3-65.8 ng/mL). INTERVENTIONS: After treatment failure of intravenous hydration plus loop diuretic agent for rhabdomyolysis related acute renal failure, temporary hemodialysis was performed 3 times to relieve oligouria and pulmonary edema. OUTCOMES: Her renal function recovered well after temporary renal replacement therapy. LESSONS: Rhabdomyolysis is a complication of HHS. Delayed detection can be fatal, and timely renal replacement therapy can result in an excellent prognosis. Therefore, it is crucial for clinicians to detect and treat such patients as early as possible to avoid impairing their renal function.

Pediatric Diabetic Ketoacidosis With Hyperosmolarity: Clinical Characteristics and Outcomes.

OBJECTIVE: Studies of hyperglycemic emergencies with hyperosmolality, including hyperglycemic hyperosmolar state (HHS) and "mixed presentation" with features of diabetic ketoacidosis (DKA) and HHS, are lacking in children. Objectives were to determine the incidence of DKA, HHS, and mixed presentation in a pediatric population, to characterize complications, and to assess accuracy of associated diagnosis codes. METHODS: Retrospective cohort study of 411 hyperglycemic emergencies in pediatric patients hospitalized between 2009 and 2014. Hyperglycemic emergency type was determined by biochemical criteria and compared to the associated diagnosis code. RESULTS: Hyperglycemic emergencies included: 333 DKA, 54 mixed presentation, and 3 HHS. Altered mental status occurred more frequently in hyperosmolar events ( P<.0001), and patients with hyperosmolarity had 3.7-fold greater odds of developing complications compared to those with DKA ( P = .0187). Of those with DKA, 98.5% were coded correctly. The majority (81.5%) of mixed DKA-HHS events were coded incorrectly. Events coded incorrectly had 3.1-fold greater odds of a complication ( P = .02). CONCLUSION: A mixed DKA-HHS presentation occurred in 13.8% of characterized hyperglycemic emergencies, whereas HHS remained a rare diagnosis (0.8%) in pediatrics. Hyperosmolar events had higher rates of complications. As treatment of hyperosmolarity differs from DKA, its recognition is essential for appropriate management. ABBREVIATIONS: AMS = altered mental status; DKA = diabetic ketoacidosis; EMR = electronic medical record; HHS = hyperglycemic hyperosmolar state; ICD-9 = International Classification of Diseases, Ninth Revision; ISPAD = International Society of Pediatric and Adolescent Diabetes; NODM = new-onset diabetes mellitus; T1DM = type 1 diabetes mellitus; T2DM = type 2 diabetes mellitus.

The Impact of Hyperosmolarity on Long-Term Outcome in Patients Presenting with Severe Hyperglycemic Crisis: A Population Based Study.

AIMS: We compared characteristics of patients with hyperglycemic hyperosmolar state (HHS) and patients with severe hyperglycemia without the signs of hyperosmolarity and ketoacidosis; analyzed long-term all-cause mortality and potential prognostic factors. METHODS: The studied population included 261 749 adults. HHS was diagnosed in patients with plasma glucose >33.0 mmol/L, ketonuria <1+, and serum osmolarity >320 mmol/L. Patients with plasma glucose >33.0 mmol/L, ketonuria <1+ and serum osmolarity <320 mmol/L were considered as controls (nHHS). RESULTS: During the 5-year period, we observed 68 episodes of HHS in 66 patients and 51 patients with nHHS. Patients with HHS were significantly older, had lower BMI, higher serum C-reactive protein and used diuretics and benzodiazepines more frequently. Mortality rates one, three and 12 months after admission were 19.0, 32.1 and 35.7% in the HHS group, and 4.8, 6.3 and 9.4% in the nHHS group (P<0.001). However, after adjustment for patient age, these differences were not statistically significant. In multivariate Cox regression in HHS group, mortality was positively associated with age, male gender, leukocyte count, amylase, presence of dyspnea and altered mental status, and the use of benzodiazepines, ACE inhibitors and sulphonylureas, while it was inversely associated with plasma glucose, bicarbonate, and the use of thiazides and statins. A nomogram derived from these variables had an accuracy of 89% in predicting lethal outcome. CONCLUSIONS: Infection, use of furosemide and benzodiazepines may be important precipitating factors of HHS. Prospective clinical trials are mandatory to analyze the safety of ACE-inhibitors and benzodiazepines in elderly patients with diabetes.

A case report of hyperosmolar hyperglycemic state in a 7-year-old child: An unusual presentation of first appearance of type 1 diabetes mellitus.

RATIONALE: A hyperosmolar hyperglycemic state (HHS) is a rare presentation of a hyperglycemic crisis in children with diabetes mellitus. As this condition can be fatal and has high morbidity, early recognition and proper management are necessary for a better outcome. Here, we report a rare case of HHS as the first presentation of type 1 diabetes mellitus (T1DM) in a 7-year-old girl. PATIENT CONCERNS: The patient was admitted due to polyuria and weight loss in the past few days. The initial blood glucose level was 1167mg/dL. DIAGNOSES: On the basis of clinical manifestations and laboratory results, she was diagnosed with T1DM and HHS. INTERVENTIONS: Treatment was started with intravenous fluid and regular insulin. OUTCOMES: She was discharged without any complications related to HHS and is being followed up in the outpatient clinic with split insulin therapy. LESSONS: As the incidence of T1DM is increasing, emergency physicians and pediatricians should be aware of HHS to make an early diagnosis for appropriate management, as it can be complicated in young children with T1DM.

Treatment of Diabetic Ketoacidosis (DKA)/Hyperglycemic Hyperosmolar State (HHS): Novel Advances in the Management of Hyperglycemic Crises (UK Versus USA).

PURPOSE OF REVIEW: Diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS) are diabetic emergencies that cause high morbidity and mortality. Their treatment differs in the UK and USA. This review delineates the differences in diagnosis and treatment between the two countries. RECENT FINDINGS: Large-scale studies to determine optimal management of DKA and HHS are lacking. The diagnosis of DKA is based on disease severity in the USA, which differs from the UK. The diagnosis of HHS in the USA is based on total rather than effective osmolality. Unlike the USA, the UK has separate guidelines for DKA and HHS. Treatment of DKA and HHS also differs with respect to timing of fluid and insulin initiation. There is considerable overlap but important differences between the UK and USA guidelines for the management of DKA and HHS. Further research needs to be done to delineate a unifying diagnostic and treatment protocol.

Hyperosmolar Hyperglycemic State.

Hyperosmolar hyperglycemic state is a life-threatening emergency manifested by marked elevation of blood glucose and hyperosmolarity with little or no ketosis. Although there are multiple precipitating causes, underlying infections are the most common. Other causes include certain medications, nonadherence to therapy, undiagnosed diabetes mellitus, substance abuse, and coexisting disease. In children and adolescents, hyperosmolar hyperglycemic state is often present when type 2 diabetes is diagnosed. Physical findings include profound dehydration and neurologic symptoms ranging from lethargy to coma. Treatment begins with intensive monitoring of the patient and laboratory values, especially glucose, sodium, and potassium levels. Vigorous correction of dehydration is critical, requiring an average of 9 L of 0.9% saline over 48 hours in adults. After urine output is established, potassium replacement should begin. Once dehydration is partially corrected, adults should receive an initial bolus of 0.1 units of intravenous insulin per kg of body weight, followed by a continuous infusion of 0.1 units per kg per hour (or a continuous infusion of 0.14 units per kg per hour without an initial bolus) until the blood glucose level decreases below 300 mg per dL. In children and adolescents, dehydration should be corrected at a rate of no more than 3 mOsm per hour to avoid cerebral edema. Identification and treatment of underlying and precipitating causes are necessary.