Epidemiology, microbiology, and diagnosis of infection in diabetic ketoacidosis and hyperosmolar hyperglycemic syndrome: A multicenter retrospective observational study.

AIMS: We investigated the characteristics of infection and the utility of inflammatory markers in diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic syndrome (HHS). METHODS: A multicenter, retrospective observational study in 21 acute-care hospitals was conducted in Japan. This study included adult hospitalized patients with DKA and HHS. We analyzed the diagnostic accuracy of markers including C-reactive protein (CRP) and procalcitonin (PCT) for bacteremia. Multiple regression models were created for estimating bacteremia risk factors. RESULTS: A total of 771 patients, including 545 patients with DKA and 226 patients with HHS, were analyzed. The mean age was 58.2 (SD, 19.3) years. Of these, 70 tested positive for blood culture. The mortality rates of those with and without bacteremia were 14 % and 3.3 % (P-value < 0.001). The area under the curve (AUC) of CRP and PCT for diagnosis of bacteremia was 0.85 (95 %CI, 0.81-0.89) and 0.76 (95 %CI, 0.60-0.92), respectively. Logistic regression models identified older age, altered level of consciousness, hypotension, and higher CRP as risk factors for bacteremia. CONCLUSIONS: The mortality rate was higher in patients with bacteremia than patients without it. CRP, rather than PCT, may be valid for diagnosing bacteremia in hyperglycemic emergencies. TRIAL REGISTRATION: This study is registered in the UMIN clinical trial registration system (UMIN000025393, Registered December 23, 2016).

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).

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.

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).

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.

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.

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.

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.

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.

[A geriatric case of hyperosmolar hyperglycemic state with osmotic demyelination syndrome that manifested with dysphagia].

The patient was an 84-year-old man who had been on insulin therapy for type 2 diabetes mellitus for 55 years. He had undergone bile duct stenting to avoid obstruction due to adenocarcinoma of the bile duct. The patient had suffered from fever and anorexia for two weeks, and had subsequently stopped insulin therapy. Since he showed signs of impaired consciousness, he was taken to the emergency room, and was diagnosed with a hyperosmotic hyperglycemic state (HHS) based on the following laboratory findings: blood glucose, 632 mg/dL; plasma osmolality, 391 mOsm/kg·H2O; and serum Na, 163 mEq/L, with urine ketone bodies±and sepsis (Klebsiella pneumoniae). He was therefore admitted to the hospital. His blood glucose and serum Na levels slowly improved following the administration of fluids, insulin, and antibiotics. The patient's consciousness disturbance also improved. However, on the third day after admission, dysphagia was newly observed when the patient resumed eating, and swallowing endoscopy revealed a delayed gag reflex and pharyngeal retention of saliva. Cranial magnetic resonance imaging showed a high-intensity area in the central pontine, which was considered to be caused by osmotic demyelination syndrome (ODS). The patient's oral intake ability recovered with swallowing rehabilitation. ODS is a rare complication of HHS. We report a case of HHS with ODS, in which the patient's chief complaint was dysphagia, which should be distinguished from other diseases.

Hyperosmolar Hyperglycaemic State (HHS) complicated by life-threatening large vessel occlusive arterial thrombosis - A mini case series and important reminder for clinicians.

Hyperosmolar Hyperglycaemic State (HHS) is a known life-threatening complication of Type 2 Diabetes Mellitus (T2DM). As the incidence of T2DM continues to grow, it is important to remember some of its lesser-known complications. HHS has been described in the literature to result in small vessel thrombosis, leading to coronary or cerebral arterial thrombosis, resulting in acute myocardial infarction or cerebrovascular accidents. The underlying pathology of this relates to the prothrombotic and hyperviscous state caused by HHS. On our review of the literature, however, we are unable to find a consistent description or HHS complicated by large vessel thrombotic occlusion. The authors of this paper present a mini case series describing two cases of HHS which were complicated by life or limb-threatening large vessel occlusive arterial thrombosis. This is particularly unique as we have otherwise only been able to identify single case reports in the existing literature from other authors. The purpose of this case discussion is to highlight this rare complication of HHS and to encourage clinicians to remember that HHS is not just a physiological or biochemical derangement, can also lead to true surgical emergencies requiring immediate treatment.

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.

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.

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.

Hyperosmolar hyperglycemic coma in an infant with neonatal diabetes mellitus.

Neonatal diabetes mellitus (NDM) is a rare disease distinct from type 1 diabetes mellitus (T1DM). While T1DM results from autoimmune destruction of pancreatic beta cells, NDM arises from genetic mutations to insulin production and secretion pathways. We present a case of an infant presenting to the emergency department with shock and poor responsiveness, found to have neonatal DM with hyperosmotic hyperglycemic syndrome (HHS). This report distinguishes NDM from T1DM, illustrating the subtle but clinically significant differences in pathophysiology and implications for initial management of NDM in the emergency department setting.

Hyperosmolar hyperglycaemic state causing atypical status epilepticus with hippocampal involvement.

Diabetes mellitus may arise abruptly and decompensate suddenly, leading to a hyperglycaemic hyperosmolar state. Coma often ensues, although this usually reverses after the metabolic abnormalities have resolved. Acute symptomatic seizures can also occur in patients who are conscious, although these usually resolve after osmolarity and glycaemia have normalised. We describe an elderly woman who failed to regain vigilance despite prompt treatment; the cause was an unusual non-convulsive status epilepticus arising from the mesial temporal lobe and promoting a progressive and selective hippocampal involvement. During follow-up, her seizures recurred after stopping antiseizure medication and she developed hippocampal sclerosis, although she subsequently became seizure-free with antiseizure medications. Patients who are unresponsive in a hyperglycaemic hyperosmolar state may be having subclinical epileptiform discharges and risk developing permanent brain damage and long-term epilepsy.