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).

Hyperosmolar diabetic ketoacidosis-- review of literature and the shifting paradigm in evaluation and management.

BACKGROUND: Hyperosmolar diabetic ketoacidosis (H-DKA), a distinct clinical entity, is the overlap of diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS). AIM: We describe the clinical presentation, metabolic aberrations, and associated morbidity/mortality of these cases with H-DKA. We highlight the problem areas of medical care which require particular attention when caring for pediatric diabetes patients presenting with H-DKA. METHODS: In our study we reviewed the literature back to 1963 and retrieved twenty-four cases meeting the criteria of H-DKA: glucose >600 mg/dL, pH < 7.3, bicarbonate <15 mEq/L, and serum osmolality >320 mOsm/kg, while adding three cases from our institution. RESULTS: Average age of presentation of H-DKA was 10.2 years ± 4.5 years in females and 13.3 years ± 4 years in males, HbA1c was 13%. Biochemical parameters were consistent with severe dehydration: serum osmolality = 394.8±55 mOsm/kg, BUN = 48±22 mg/dL, creatinine = 2.81±1.03 mg/dL. Acute kidney injury, present in 12 cases, was the most frequent end-organ complication. CONCLUSION: Multi-organ involvement with AKI, rhabdomyolysis, pancreatitis, neurological and cardiac issues such as arrhythmias, are common in H-DKA. Aggressive fluid management, insulin therapy and supportive care can prevent acute and long term adverse outcomes in children and adolescents.

Some characteristics of hyperglycaemic crisis differ between patients with and without COVID-19 at a safety-net hospital in a cross-sectional study.

OBJECTIVE: To compare patients with DKA, hyperglycaemic hyperosmolar syndrome (HHS), or mixed DKA-HHS and COVID-19 [COVID (+)] to COVID-19-negative (-) [COVID (-)] patients with DKA/HHS from a low-income, racially/ethnically diverse catchment area. METHODS: A cross-sectional study was conducted with patients admitted to an urban academic medical center between 1 March and 30 July 2020. Eligible patients met lab criteria for either DKA or HHS. Mixed DKA-HHS was defined as meeting all criteria for either DKA or HHS with at least 1 criterion for the other diagnosis. RESULTS: A total of 82 participants were stratified by COVID-19 status and type of hyperglycaemic crisis [26 COVID (+) and 56 COVID (-)]. A majority were either Black or Hispanic. Compared with COVID (-) patients, COVID (+) patients were older, more Hispanic and more likely to have type 2 diabetes (T2D, 73% vs 48%, p < .01). COVID(+) patients had a higher mean pH (7.25 ± 0.10 vs 7.16 ± 0.16, p < .01) and lower anion gap (18.7 ± 5.7 vs 22.7 ± 6.9, p = .01) than COVID (-) patients. COVID (+) patients were given less intravenous fluids in the first 24 h (2.8 ± 1.9 vs 4.2 ± 2.4 L, p = .01) and were more likely to receive glucocorticoids (95% vs. 11%, p < .01). COVID (+) patients may have taken longer to resolve their hyperglycaemic crisis (53.3 ± 64.8 vs 28.8 ± 27.5 h, p = .09) and may have experienced more hypoglycaemia <3.9 mmol/L (35% vs 19%, p = .09). COVID (+) patients had a higher length of hospital stay (LOS, 14.8 ± 14.9 vs 6.5 ± 6.0 days, p = .01) and in-hospital mortality (27% vs 7%, p = .02). DISCUSSION: Compared with COVID (-) patients, COVID (+) patients with DKA/HHS are more likely to have T2D. Despite less severe metabolic acidosis, COVID (+) patients may require more time to resolve the hyperglycaemic crisis and experience more hypoglycaemia while suffering greater LOS and risk of mortality. Larger studies are needed to examine whether differences in management between COVID (+) and (-) patients affect outcomes with DKA/HHS.

Clinical profile and outcomes in COVID-19 patients with diabetic ketoacidosis: A systematic review of literature.

BACKGROUND AND AIM: To conduct a systematic literature review and analyze the demographic/biochemical parameters and clinical outcomes of COVID-19 patients with diabetic ketoacidosis (DKA) and combined DKA/HHS (hyperglycemic hyperosmolar syndrome). METHODS: PubMed, Scopus, Embase, and Google Scholar databases were systematically searched till August 3, 2020 to identify studies reporting COVID-19 patients with DKA and combined DKA/HHS. A total of 19 articles reporting 110 patients met the eligibility criteria. RESULTS: Of the 110 patients, 91 (83%) patients had isolated DKA while 19 (17%) had DKA/HHS. The majority of the patients were male (63%) and belonged to black ethnicity (36%). The median age at presentation ranged from 45.5 to 59.0 years. Most of the patients (77%) had pre-existing type 2 diabetes mellitus. Only 10% of the patients had newly diagnosed diabetes mellitus. The median blood glucose at presentation ranged from 486.0 to 568.5 mg/dl, being higher in patients with DKA/HHS compared to isolated DKA. The volume of fluid replaced in the first 24 h was higher in patients with DKA/HHS in contrast to patients with DKA alone. The in-hospital mortality rate was 45%, with higher mortality in the DKA/HHS group than in the isolated DKA group (67% vs. 29%). pH was lower in patients who had died compared to those who were discharged. CONCLUSION: DKA in COVID-19 patients portends a poor prognosis with a mortality rate approaching 50%. Differentiating isolated DKA from combined DKA/HHS is essential as the latter represents nearly one-fifth of the DKA cases and tends to have higher mortality than DKA alone.

Multicentre analysis of hyperglycaemic hyperosmolar state and diabetic ketoacidosis in type 1 and type 2 diabetes.

AIMS: To compare diabetes patients with hyperglycaemic hyperosmolar state (HHS), diabetic ketoacidosis (DKA), and patients without decompensation (ND). METHODS: In total, 500,973 patients with type 1 or type 2 diabetes of all ages registered in the diabetes patient follow-up (DPV) were included. Analysis was stratified by age (≤ / > 20 years) and by manifestation/follow-up. Patients were categorized into three groups: HHS or DKA-during follow-up according to the most recent episode-or ND. RESULTS: At onset of diabetes, HHS criteria were met by 345 (68.4% T1D) and DKA by 9824 (97.6% T1D) patients. DKA patients had a lower BMI(-SDS) in both diabetes types compared to ND. HbA1c was higher in HHS/DKA. During follow-up, HHS occurred in 1451 (42.2% T1D) and DKA in 8389 patients (76.7% T1D). In paediatric T1D, HHS/DKA was associated with younger age, depression, and dyslipidemia. Pump usage was less frequent in DKA patients. In adult T1D/T2D subjects, metabolic control was worse in patients with HHS/DKA. HHS and DKA were also associated with excessive alcohol intake, dementia, stroke, chronic kidney disease, and depression. CONCLUSIONS: HHS/DKA occurred mostly in T1D and younger patients. However, both also occurred in T2D, which is of great importance in the treatment of diabetes. Better education programmes are necessary to prevent decompensation and comorbidities.

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.

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.

[Diabetic emergencies : Hypoglycemia, ketoacidotic and hyperglycemic hyperosmolar nonketotic coma]. / Diabetologische Notfälle : Hypoglykämie, ketoazidotisches und hyperglykämisches Koma.

The diabetic emergencies diabetic ketoacidosis (DKA), hyperglycemic hyperosmolar state (HHS) and hypoglycemia represent severe and potentially life-threatening complications of diabetes mellitus that require prompt diagnostics and treatment. Absolute or relative insulin insufficiency is characteristic of DKA und HHS along with severe dehydration. They differ by the prevalence of ketone bodies and the severity of acidosis; however, the treatment regimens are similar. In contrast, hypoglycemia is the limiting factor for achieving ambitious glucose targets. This article decribes the clinical presentation, diagnostics and emergency management of these metabolic derangements.

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.

Expedited diagnosis and management of inpatient hyperosmolar hyperglycemic nonketotic syndrome.

PURPOSE: This practice improvement project was formulated to determine accuracy rate in differentiating between two hyperglycemic crises (diabetes ketoacidosis [DKA] and hyperosmolar hyperglycemic nonketotic syndrome [HHNKS]) in a clinical population of individuals who manifested hyperglycemia and diabetes mellitus (DM). We hypothesized that HHNKS was commonly misdiagnosed as DKA. Our primary aim was to determine frequency of correct HHNKS diagnoses. A second aim was to review the literature and present an evidence-based protocol to assist providers with the differential diagnosis of HHNKS from DKA. DATA SOURCES: Electronic health records (N = 911) were selected by ICD-9 codes for hyperglycemia, DKA, and HHNKS. A retrospective record review indicated n = 436 met the blood glucose level depicting HHNKS. Additional laboratory findings were compared with diagnostic criteria from the literature. CONCLUSIONS: HHNKS was commonly misdiagnosed and mismanaged as DKA. Only n = 9 (5%) patients with type 2 DM were correctly diagnosed and managed as having HHNKS. Of the records misdiagnosed with DKA, 74 (39%) actually manifested HHNKS clinical features. Of these, n = 24 (36%) were readmitted within 2 weeks. IMPLICATIONS FOR PRACTICE: Early recognition of HHNKS is essential for appropriate condition management. HHNKS-specific algorithms are essential for expediting accurate diagnosis, managing appropriately, minimizing mortality, reducing stay length, and avoiding readmissions.

Evaluation of point-of-care blood glucose measurements in patients with diabetic ketoacidosis or hyperglycemic hyperosmolar syndrome admitted to a critical care unit.

BACKGROUND: Point-of-care (POC) blood glucose (BG) measurement is currently not recommended in the treatment of patients presenting with diabetic ketoacidosis (DKA) or hyperglycemic hyperosmolar syndrome (HHS). METHODS: We prospectively evaluated and compared capillary and venous POC BG values with laboratory venous glucose in patients with DKA or HHS admitted to one critical care unit over 8 months. RESULTS: Venous laboratory glucose was strongly correlated with venous (r = 0.98) and capillary (r = 0.96) POC glucose values, though POC glucose values were higher than venous laboratory values (venous POC 21 ± 3 mg/dl, capillary POC 30 ± 4 mg/dl; both p < .001). Increased plasma osmolality had no effect on glucose meter error, while acidemia (pH < 7.3) was associated with greater glucose meter error (p = .04) independent of glucose levels. Comparing hypothetical insulin infusion rates based on laboratory venous glucose to actual infusion rates based on POC glucose values showed that 33/61 insulin infusion rates would have been unchanged, while 28 out of 61 rates were on average 7% ± 2% higher. There were no instances of hypoglycemia in any of the patients. CONCLUSIONS: Overall, both venous and capillary POC BG values were safe for the purpose of titrating insulin infusions in patients with severe hyperglycemia. Acidemia, but not hyperosmolality, increased POC BG value errors.

Hyperglycemic crisis.

BACKGROUND: Hyperglycemic crisis is a metabolic emergency associated with uncontrolled diabetes mellitus that may result in significant morbidity or death. Acute interventions are required to manage hypovolemia, acidemia, hyperglycemia, electrolyte abnormalities, and precipitating causes. Despite advances in the prevention and management of diabetes, its prevalence and associated health care costs continue to increase worldwide. Hyperglycemic crisis typically requires critical care management and hospitalization and contributes to global health expenditures. OBJECTIVE: Diagnostic and resolution criteria and management strategies for diabetic ketoacidosis and hyperosmolar hyperglycemic crisis are provided. A discussion of prevalence, mortality, pathophysiology, risk factors, clinical presentation, differential diagnosis, evaluation, and management considerations for hyperglycemic crisis are included. DISCUSSION: Emergency physicians confront the most severe sequelae of uncontrolled diabetes and provide crucial, life-saving management. With ongoing efforts from diabetes societies to incorporate the latest clinical research to refine treatment guidelines, management and outcomes of hyperglycemic crisis in the emergency department continue to improve. CONCLUSION: We provide an overview of the evaluation and treatment of hyperglycemic crisis and offer a concise, targeted management algorithm to aid the practicing emergency physician.