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.

Mortality Due to Hyperglycemic Crises in the US, 1999-2022.

This study analyzes trends in US mortality attributed to both diabetic ketoacidosis and hyperosmolar hyperglycemic state from 1999-2022.

Clinical profile of patients with diabetic ketoacidosis and hyperglycemic hyperosmolar syndrome in Japan: a multicenter retrospective cohort study.

INTRODUCTION: Diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar syndrome (HHS) are life-threatening complications of diabetes mellitus. Their clinical profiles have not been fully investigated. METHODS: A multicenter retrospective cohort study was conducted in 21 acute care hospitals in Japan. Patients included were adults aged 18 or older who had been hospitalized from January 1, 2012, to December 31, 2016 due to DKA or HHS. The data were extracted from patient medical records. A four-group comparison (mild DKA, moderate DKA, severe DKA, and HHS) was performed to evaluate outcomes. RESULTS: A total of 771 patients including 545 patients with DKA and 226 patients with HHS were identified during the study period. The major precipitating factors of disease episodes were poor medication compliance, infectious diseases, and excessive drinking of sugar-sweetened beverages. The median hospital stay was 16 days [IQR 10-26 days]. The intensive care unit (ICU) admission rate was 44.4% (mean) and the rate at each hospital ranged from 0 to 100%. The in-hospital mortality rate was 2.8% in patients with DKA and 7.1% in the HHS group. No significant difference in mortality was seen among the three DKA groups. CONCLUSIONS: The mortality rate of patients with DKA in Japan is similar to other studies, while that of HHS was lower. The ICU admission rate varied among institutions. There was no significant association between the severity of DKA and mortality in the study population. TRIAL REGISTRATION: This study is registered in the UMIN clinical Trial Registration System (UMIN000025393, Registered 23th December 2016).

Incidence and Characteristics of the Hyperosmolar Hyperglycemic State: A Danish Cohort Study.

OBJECTIVE: The hyperosmolar hyperglycemic state (HHS) is a rare and life-threatening complication of diabetes. We aimed to estimate the incidence of HHS and describe the clinical and biomarker profiles of patients with HHS, including subgroups with acidosis and acute kidney injury. RESEARCH DESIGN AND METHODS: This nationwide, descriptive cohort study used Danish registry data during years 2016-2018 to identify acutely admitted patients fulfilling the hyperglycemia and hyperosmolarity criteria of HHS (glucose ≥33 mmol/L and osmolarity [2 × sodium + glucose] ≥320 mmol/L). RESULTS: We identified 634 patients (median age, 69 years (first quartile; third quartile: 58; 79) who met the criteria of HHS among 4.80 million inhabitants aged ≥18 years. The incidence rates were 16.5 and 3.9 per 10,000 person-years among people with known type 1 (n = 24,196) and type 2 (n = 251,357) diabetes, respectively. Thirty-two percent of patients with HHS were not previously diagnosed with diabetes. Patients were categorized as pure HHS (n = 394) and combined HHS and diabetic ketoacidosis (HHS-DKA; n = 240). The in-hospital mortality rate for pure HHS was 17% and 9% for HHS-DKA. CONCLUSIONS: The incidence of HHS was higher among patients with type 1 diabetes compared with type 2 diabetes. HHS is a spectrum of hyperglycemic crises and can be divided in pure HHS and HHS-DKA. In one-third of patients, HHS was the debut of their diabetes diagnosis.

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.

Risk Factors for Hyperosmolar Hyperglycemic State in Pediatric Type 2 Diabetes.

Background: There is a paucity of data on the risk factors for the hyperosmolar hyperglycemic state (HHS) compared with diabetic ketoacidosis (DKA) in pediatric type 2 diabetes (T2D). Methods: We used the national Kids' Inpatient Database to identify pediatric admissions for DKA and HHS among those with T2D in the years 2006, 2009, 2012, and 2019. Admissions were identified using ICD codes. Those aged <9yo were excluded. We used descriptive statistics to summarize baseline characteristics and Chi-squared test and logistic regression to evaluate factors associated with admission for HHS compared with DKA in unadjusted and adjusted models. Results: We found 8,961 admissions for hyperglycemic emergencies in youth with T2D, of which 6% were due to HHS and 94% were for DKA. These admissions occurred mostly in youth 17-20 years old (64%) who were non-White (Black 31%, Hispanic 20%), with public insurance (49%) and from the lowest income quartile (42%). In adjusted models, there were increased odds for HHS compared to DKA in males (OR 1.77, 95% CI 1.42-2.21) and those of Black race compared to those of White race (OR 1.81, 95% CI 1.34-2.44). Admissions for HHS had 11.3-fold higher odds for major or extreme severity of illness and 5.0-fold higher odds for mortality. Conclusion: While DKA represents the most admissions for hyperglycemic emergencies among pediatric T2D, those admitted for HHS had higher severity of illness and mortality. Male gender and Black race were associated with HHS admission compared to DKA. Additional studies are needed to understand the drivers of these risk factors.

DKA/HHS insulin infusion protocol adherence and patient outcomes in Shellharbour Hospital.

BACKGROUND: Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycaemic state (HHS) are medical emergencies requiring prompt assessment and management to avoid complications. AIMS: To examine adherence to the hospital DKA/HHS insulin infusion protocol, assess outcomes in patients admitted with DKA or HHS, and determine if improvements have been observed from a similar audit in 2016. METHODS: An audit was conducted on 40 patients admitted to Shellharbour Hospital with DKA or HHS. Protocol adherence was assessed in the domains of fluid replacement, potassium replacement, use of the correct insulin infusion schedule, timing of commencement of dextrose infusion and appropriate transition to subcutaneous insulin. The outcomes assessed included length of hospital stay, duration of insulin infusion, time to euglycaemia, intensive care unit (ICU) transfer, overlap between insulin infusion and subcutaneous insulin, diabetes team review and incidence and management of hypoglycaemia. RESULTS: The proportion of cases that adhered to the components of the insulin infusion protocol is as follows: fluid replacement (40%), potassium replacement (72.5%), correct insulin schedule (82.5%), appropriate commencement of intravenous dextrose (80%) and appropriate transition to subcutaneous insulin (87.5%). Appropriate overlap between insulin infusion and subcutaneous insulin occurred in 62.5% of patients. Eighty-five per cent of patients were reviewed by the diabetes team. Three per 40 patients experienced hypoglycaemia, and none of the three patients was treated as per protocol. Compared to the 2016 audit, there was a significant improvement in potassium replacement but a decrease in appropriate fluid replacement. CONCLUSION: This audit highlights areas in DKA/HHS management requiring improvement. These include fluid and potassium replacement and appropriate overlap between subcutaneous insulin and insulin infusion.

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.

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

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

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.

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.

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.

Hyperglycaemic hyperosmolar state and cerebral thrombophlebitis in paediatrics: A case report.

INTRODUCTION: Hyperglycaemic hyperosmolar state (HHS) is a known complication of type 2 diabetes mellitus; however, carbonated carbohydrate fluid intake may precipitate a more severe presentation of type 1 diabetes mellitus with hyperosmolar state. The management of these patients is not easy and can lead to severe complications such as cerebral venous thrombosis. METHODS: We present the case of a 21-month-old boy admitted for consciousness disorders revealing a hyperglycaemic hyperosmolar state on a new-onset type 1 diabetes and who developed cerebral venous thrombosis. RESULTS AND CONCLUSION: Emergency physicians should be aware of HHS in order to start the appropriate treatment as early as possible and to monitor the potential associated acute complications. This case highlights the importance of decreasing very gradually the osmolarity in order to avoid cerebral complications. Cerebral venous thrombosis in HHS paediatric patients is rarely described, and it is important to recognize that not all episodes of acute neurological deterioration in HHS or diabetic ketoacidosis are caused by cerebral oedema.