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.

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.

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.

Management of Hyperosmolar Hyperglycaemic State (HHS) in Adults: An updated guideline from the Joint British Diabetes Societies (JBDS) for Inpatient Care Group.

Hyperosmolar Hyperglycaemic State (HHS) is a medical emergency associated with high mortality. It occurs less frequently than diabetic ketoacidosis (DKA), affects those with pre-existing/new type 2 diabetes mellitus and increasingly affecting children/younger adults. Mixed DKA/HHS may occur. The JBDS HHS care pathway consists of 3 themes (clinical assessment and monitoring, interventions, assessments and prevention of harm) and 5 phases of therapy (0-60 min, 1-6, 6-12, 12-24 and 24-72 h). Clinical features of HHS include marked hypovolaemia, osmolality ≥320 mOsm/kg using [(2×Na+ ) + glucose+urea], marked hyperglycaemia ≥30 mmol/L, without significant ketonaemia (≤3.0 mmol/L), without significant acidosis (pH >7.3) and bicarbonate ≥15 mmol/L. Aims of the therapy are to improve clinical status/replace fluid losses by 24 h, gradual decline in osmolality (3.0-8.0 mOsm/kg/h to minimise the risk of neurological complications), blood glucose 10-15 mmol/L in the first 24 h, prevent hypoglycaemia/hypokalaemia and prevent harm (VTE, osmotic demyelination, fluid overload, foot ulceration). Underlying precipitants must be identified and treated. Interventions include: (1) intravenous (IV) 0.9% sodium chloride to restore circulating volume (fluid losses 100-220 ml/kg, caution in elderly), (2) fixed rate intravenous insulin infusion (FRIII) should be commenced once osmolality stops falling with fluid replacement unless there is ketonaemia (FRIII should be commenced at the same time as IV fluids). (3) glucose infusion (5% or 10%) should be started once glucose <14 mmol/L and (4) potassium replacement according to potassium levels. HHS resolution criteria are: osmolality <300 mOsm/kg, hypovolaemia corrected (urine output ≥0.5 ml/kg/h), cognitive status returned to pre-morbid state and blood glucose <15 mmol/L.

Safety and Effectiveness of the Use of an Electronic Glucose Monitoring System Versus Weight-Based Dosing Nomogram for Treatment of Diabetic Ketoacidosis and Hyperglycemic Hyperosmolar Syndrome in a VA Hospital.

OBJECTIVE: The objective of this study is to assess the safety and effectiveness of an electronic glucose monitoring system (eGMS) versus paper-based protocols (PBPs) to manage diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar syndrome (HHS) within the VA setting. METHODS: This study is a retrospective chart review of patients on an insulin drip, treated in the emergency department (ED) or intensive care unit (ICU) at Veteran Health Indiana for DKA or HHS. The primary outcome was evaluating the percentage of patients with hypoglycemia (blood glucose [BG] level <70 mg/dL) in patients admitted with DKA and HHS comparing an eGMS versus a PBP. A total of 168 patients were included in the analysis, with 84 patients in each group. RESULTS: The primary outcome comparing rates of hypoglycemia in the eGMS group versus the PBP group showed a lower rate of hypoglycemia in the eGMS group (0.024%) compared with the PBP group (0.060%); however, this difference was not found to be statistically significant (P = .90). Statistically significant secondary outcomes include the percentage of glucose checks drawn within the protocol recommendation (80.7% vs 52.6%, P = .02). CONCLUSIONS: While the primary endpoint of decreased hypoglycemia was not found to be statistically significant, it did reduce the overall number of hypoglycemia events in the eGMS group compared with the PBP group which may be clinically significant. This demonstrates that eGMS use has the potential to minimize hypoglycemia and glycemic variability in a critically-ill Veteran population by individualizing insulin drip titration based on a variety of patient-specific factors and providing reminders for staff to obtain BG checks in a timely manner.

A case of hyperglycemic hyperosmolar syndrome in a pug dog.

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

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

Association between heat exposure and hospitalization for diabetic ketoacidosis, hyperosmolar hyperglycemic state, and hypoglycemia in Japan.

BACKGROUND: An increase in extreme heat events has been reported along with global warming. Heat exposure in ambient temperature is associated with all-cause diabetes mortality and all-cause hospitalization in diabetic patients. However, the association between heat exposure and hospitalization for hyperglycemic emergencies, such as diabetic ketoacidosis (DKA), hyperosmolar hyperglycemic state (HHS), and hypoglycemia is unclear. The objective of our study is to clarify the impact of heat exposure on the hospitalization for DKA, HHS, and hypoglycemia. METHODS: Data of daily hospitalizations for hyperglycemic emergencies (i.e., DKA or HHS) and hypoglycemia was extracted from a nationwide administrative database in Japan and linked with temperature in each prefecture in Japan during 2012-2019. We applied distributed lag non-linear model to evaluate the non-linear and lagged effects of heat exposure on hospitalization for hyperglycemic emergencies. RESULTS: The pooled relative risk for hyperglycemic emergencies of heat effect (the 90th percentile of temperature with reference to the 75th percentile of temperature) and extreme heat effect (the 99th percentile of temperature with reference to the 75th percentile of temperature) over 0-3 lag days was 1.27 (95 %CI: 1.16-1.39) and 1.64 (95 %CI: 1.38-1.93), respectively. The pooled relative risk for heat effect on hospitalization for hypoglycemia and extreme heat effect over 0-3 lag days was 1.33 (95 %CI: 1.17-1.52) and 1.65 (95 %CI: 1.29-2.10), respectively. These associations were consistent by type of hyperglycemic emergencies and type of diabetes and were generally consistent by regions. DISCUSSION: Heat exposure was associated with hospitalizations for DKA, HHS and hypoglycemia. These results may be useful to guide preventive actions for the risk of fatal hyperglycemic emergencies and hypoglycemia.

What Is the Optimal Speed of correction of the Hyperosmolar Hyperglycemic State in Diabetic Ketoacidosis? An Observational Cohort Study of U.S. Intensive Care Patients.

OBJECTIVE: The international guidelines for the treatment of diabetic ketoacidosis (DKA) advise against rapid changes in osmolarity and glucose; however, the optimal rates of correction are unknown. We aimed to evaluate the rates of change in tonicity and glucose level in intensive care patients with DKA and their relationship with mortality and altered mental status. METHODS: This is an observational cohort study using 2 publicly available databases of U.S. intensive care patients (Medical Information Mart for Intensive Care-IV and Electronic Intensive Care Unit), evaluating adults with DKA and associated hyperosmolarity (baseline Osm ≥300 mOsm/L). The primary outcome was hospital mortality. The secondary neurologic outcome used a composite of diagnosed cerebral edema or Glasgow Coma Scale score of ≤12. Multivariable regression models were used to control for confounding factors. RESULTS: On adjusted analysis, patients who underwent the most rapid correction of up to approximately 3 mmol/L/hour in tonicity had reduced mortality (n = 2307; odds ratio [OR], 0.21; overall P < .001) and adverse neurologic outcomes (OR, 0.44; P < .001). Faster correction of glucose levels up to 5 mmol/L/hour (90 mg/dL/hour) was associated with improvements in mortality (n = 2361; OR, 0.24; P = .020) and adverse neurologic events (OR, 0.52; P = .046). The number of patients corrected significantly faster than these rates was low. A maximal hourly rate of correction between 2 and 5 mmol/L for tonicity was associated with the lowest mortality rate on adjusted analysis. CONCLUSION: Based on large-volume observational data, relatively rapid correction of tonicity and glucose level was associated with lower mortality and more favorable neurologic outcomes. Avoiding a maximum hourly rate of correction of tonicity >5 mmol/L may be advisable.

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.

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

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

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.

Profile and outcomes of patients admitted with hyperglycemic emergencies in the Buea Regional Hospital in Cameroon.

INTRODUCTION: hyperglycemic emergencies (diabetic ketoacidosis and hyperglycemic hyperosmolar state) are the most common serious acute metabolic complications of diabetes which result in significant morbidity and mortality. There is paucity of data on hyperglycemic emergencies in Cameroon. The objective of this study was to investigate the precipitants and outcomes of patients admitted for hyperglycemic emergencies in the Buea Regional Hospital in the South West Region of Cameroon. METHODS: in this retrospective study the medical records of patients admitted for hyperglycemic emergencies between 2013 and 2016 in the medical unit of the Buea Regional Hospital were reviewed. We extracted data on demographic characteristics, admission clinical characteristics, precipitants, and treatment outcomes. Logistic regression was used to determine predictors of mortality. RESULTS: data were available for 60 patients (51.7% females) admitted for hyperglycemic emergencies. The mean age was 55.2±16.3 (range 18-86). Overall there were 51 (85%) cases of hyperosmolar hyperglycemic state. Twenty six (43.3%) of the patients had hypertension. The most common precipitants of hyperglycemic emergencies were infections (41.7%), newly diagnosed diabetes (33.3%) and non-adherence to medications (33.3%). Mean admission blood glucose was 574mg/dl±70.0mg/dl. The median length of hospital stay was 6 days. Overall case fatality rate was 21.7%. Six (46.2%) deaths were related to infections. Predictors of mortality were a Glasgow coma score <13(p<0.001), a diastolic blood pressure <60 mmHg (p=0.034) and a heart rate >90(0.057) on admission. CONCLUSION: admission for hyperglycemic emergencies in this semi-urban hospital is associated with abnormally high case fatality. Infections, newly diagnosed diabetes and non-adherence to medications are the commonest precipitants of hyperglycemic emergencies. Public health measures to reduce morbidity and mortality from hyperglycemic crisis are urgently needed.

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.