An extremely high blood glucose level in a child with hyperglycemic hyperosmolar state and type 1 diabetes.

OBJECTIVES: Hyperglycemic hyperosmolar state (HHS) is one of the most severe acute complications of diabetes mellitus (DM) characterized by severe hyperglycemia and hyperosmolality without significant ketosis and acidosis. What is new? Since HHS in the pediatric population is rare and potentially life-threatening, every reported case is very valuable for raising awareness among healthcare professionals. CASE PRESENTATION: A 7-year-old boy with previously diagnosed Joubert syndrome was admitted due to vomiting, polydipsia and polyuria started several days earlier. He was severely dehydrated, and the initial blood glucose level was 115 mmol/L. Based on clinical manifestations and laboratory results, he was diagnosed with T1DM and HHS. The treatment with intravenous fluid was started and insulin administration began later. He was discharged after 10 days without any complications related to HHS. CONCLUSIONS: Since HHS has a high mortality rate, early recognition, and proper management are necessary for a better outcome.

Managing People with Diabetes Fasting for Ramadan During the COVID-19 Pandemic: A South Asian Health Foundation Update.

The month of Ramadan forms one of the five pillars of the Muslim faith. Adult Muslims are obligated to keep daily fasts from dawn to sunset, with exceptions. This year Ramadan is due to begin on 23 April 2020 and the longest fast in the UK will be approximately 18 hours in length. In addition, due to the often high-calorie meals eaten to break the fast, Ramadan should be seen as a cycle of fasting and feasting. Ramadan fasting can impact those with diabetes, increasing the risk of hypoglycaemia, hyperglycaemia and dehydration. This year, Ramadan will occur during the global COVID-19 pandemic. Reports show that diabetes appears to be a risk factor for more severe disease with COVID-19. In addition, the UK experience has shown diabetes and COVID-19 is associated with dehydration, starvation ketosis, diabetic ketoacidosis and hyperosmolar hyperglycaemic state. This makes fasting in Ramadan particularly challenging for those Muslims with diabetes. Here, we discuss the implications of fasting in Ramadan during the COVID-19 pandemic and make recommendations for those with diabetes who wish to fast.

Diabetes at the front door. A guideline for dealing with glucose related emergencies at the time of acute hospital admission from the Joint British Diabetes Society (JBDS) for Inpatient Care Group.

People with diabetes account for nearly one-fifth of all inpatients in English and Welsh hospitals; of these, up to 90% are admitted as an emergency. Most are admitted for a reason other than diabetes with only 8% requiring admission for a diabetes-specific cause. Healthcare professionals working in emergency departments experience numerous clinical challenges, notwithstanding the need to know whether each individual with diabetes requires urgent admission. This document has been developed and written by experts in the field, and reviewed by the parent organizations of the Joint British Diabetes Societies for Inpatient Care-Diabetes UK, the Diabetes Inpatient Specialist Nurse Group and the Association of British Clinical Diabetologists. The document aims to support staff working in emergency departments and elsewhere by offering practical advice and tools for effective, appropriate and safe triage. Each section relates to the commonest diabetic specific emergencies and algorithms can be printed off to enable ease of access and use.

Hyperosmolar Hyperglycemic State.

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

Assessing water-electrolyte changes of hyperglycaemic hyperosmolar coma.

AIM: We reported new methods to accurately estimate salt and water deficits during hyperglycaemic hyperosmolar coma (HC), valid under restricted boundary conditions. The accuracy of these estimates is herein verified over the unrestricted spectrum of abnormalities, to correctly evaluate any patient with just one algorithm that recognizes the boundary conditions pertaining to each abnormality, choosing the appropriate calculations. METHODS: A large number of cases of HC was simulated on computer by subtracting an exhaustive combination of water, sodium and chloride losses coupled to a large variety of gains in glucose. Altered solute concentrations were generated. From these true plasma concentrations generated by the computer, the losses of water and electrolytes were back-calculated with our new computational algorithm, by knowing in addition only the normal total body water and extra-cellular volume. The accuracy of the method was tested by comparing true to calculated values over the entire range of deranged values. In 100 patients admitted to hospital for HC these same computations were performed, where calculated data were validated by comparing them to true data obtained by balance studies performed during correction of the abnormality. RESULTS: Both in simulated and real cases of HC true and calculated data for the changes in Na and volume were significantly correlated (R (2)=0.76 and 0.50, respectively, P<0.01), while their mean values were not significantly different by paired "t" tests (P>0.05 for all). CONCLUSION: Our new computation algorithm, applicable to the bed-side, useful in accurately assessing the average water-electrolyte deficits of HC, can be used to guide correct re-infusion strategies.

Quantitative assessment of the abnormalities of hyperosmolar coma when glucose excess is larger than Na deficit.

Computing Na and water deficits of hyperosmolar coma (HC) is important in correcting the derangement, to avoid unwanted iatrogenic electrolyte derangements and brain oedema. This paper derives and applies formulas valid when GA (glucose accumulation) >2.DeltaNa (sodium loss), with or without DeltaV (water depletion). We built a model system and wrote the equations describing the relationships between volume and concentration of solutes within the body water compartments. HC was simulated on computer experiments by adding GA in different amounts combined with a large variety of DeltaNa and DeltaV. The ensuing concentrations in Na (PNaNone. (1)) and glucose (PG (1)) were used to identify the condition GA >2 . DeltaNa, DeltaV=0 or not equal 0, and then, with original formulas, to back calculate GA, DeltaNa and DeltaV. These same calculations were applied to 31 patients with HC. The procedure to recognize the conditions under investigation unerringly discarded all simulations except those characterized by GA >2 . DeltaNa, with or without DeltaV. When DeltaV=0, the computations yielded values identical to the true ones for GA and DeltaNa (R (2)=1.00, p<0.0001). When DeltaV was present, the correlation coefficients between calculated and true values were 0.92 (p<0.001) for GA, 0.73 (p<0.001) for DeltaNa, 0.74 (p<0.001) for DeltaV in computer experiments, while they were R (2)>0.47<0.95 (p<0.001) in patient studies. The accuracy in computing solute and water changes demonstrates the validity of our model system of HC, and of the calculation formulas, which can be used to quantitatively evaluate the deficits in Na and volume, as well as the addition of glucose, improving the effectiveness of treatment.

Hyperglycemic crises and their complications in children.

The object of this review is to provide the definitions and criteria for diabetic ketoacidosis (DKA) and the hyperglycemic hyperosmolar state (HHS), and convey current knowledge of the causes of permanent disability or mortality from complications of these conditions, of the risk factors for DKA and HHS, and of early indicators and contemporary treatment of suspected cerebral edema. The frequency of DKA at onset of type 1 diabetes mellitus (DM1) varies from 10-70%, depending on availability of health care and frequency of diabetes. At the onset of type 2 diabetes (DM2), DKA occurs in 5-52%. One study reported HHS in approximately 4% of new patients with DM2. Recurrent DKA rates are equally dependent on variability in medical services and socio-economic circumstances, and are estimated to be eight episodes per 100 patient years, with 20% of patients accounting for 80% of the episodes. Mortality for each episode of DKA internationally varies from 0.15-0.31%, with idiopathic cerebral edema accounting for two-thirds or more of this mortality. Other causes of death or disability include untreated DKA or HHS, hypokalemia, hypophosphatemia, hypoglycemia, other intracerebral complications, peripheral venous thrombosis, mucormycosis, rhabdomyolysis, acute pancreatitis, acute renal failure, sepsis, aspiration pneumonia, and other pulmonary complications. Population-based studies from the UK, Australia, the USA, and Canada report cerebral edema incidence in DKA of 0.5-2.0%. Published information does not support the notion that treatment factors are causal in cerebral edema. Younger age, greater severity of acidosis, degree of hypocapnia, and severity of dehydration have been suggested as risk factors in several studies. Bimodal distribution of the time of onset of cerebral edema and wide variation in brain imaging findings suggest the variability and likely multiple causation of the clinical picture. Functional brain scanning has indicated that DKA is accompanied by increased cerebral blood flow suggesting that the predominant mechanism of edema formation is a vasogenic process. A method of monitoring for diagnostic and major and minor signs of cerebral edema has been proposed and tested which indicates that intervention will be required in five individuals to provide early intervention for a single case of cerebral edema. The preferred intervention of mannitol infusion has typically been accompanied by intubation and hyperventilation, but recent evidence indicates outcome is adversely affected by aggressive hyperventilation. The prevention of DKA and HHS at the onset of diabetes mellitus requires a high degree of awareness and suspicion by primary care providers; prevention of recurrent DKA necessitates a diligent team effort.

Management of hyperglycemic emergencies.

The prevalence of diabetes mellitus makes the occurrence of hyperglycemic emergencies a key component in clinical practice. The expert nurse is well positioned to manage both diabetic ketoacidosis and hyperosmolar hyperglycemic states. Patient care management includes a high index of suspicion for awareness for the possibility of diabetic ketoacidosis or hyperosmolar hyperglycemic states in patients based on a multifactorial etiology, evidence-based treatment of the emergent episode, and tertiary prevention to prevent recurrent episodes.

[Diabetic metabolic emergencies]. / Akut anyagcserekrízisek diabetes mellitusban.

Diabetic ketoacidosis and hyperglycaemic hyperosmolar syndrome are two acute complications of diabetes that may result in high mortality. Effective standardized treatment protocols, as well as prompt identification and treatment of the precipitating cause, are important factors affecting outcome. The authors review the pathomechanism, clinical features, complications and current recommendations for management of ketoacidosis and hyperglycaemic hyperosmolar syndrome. In patients with type 2 diabetes may develop anaerobic (type A) lactic acidosis from tissue hypoxia, while aerobic (type B) lactic acidosis is a rare complication of biguanide therapy if contraindications to metformin are observed. Mortality remains very high, especially when serious comorbidities are present. Hypoglycaemia is a major factor preventing patients with both type 1 and type 2 diabetes from achieving near-normal plasma glucose targets. The authors summarize clinical presentation and therapeutic possibilities of hypoglycaemia on the basis of the literature.

Diagnosis and treatment of diabetic ketoacidosis and the hyperglycemic hyperosmolar state.

Diabetic ketoacidosis and the hyperglycemic hyperosmolar state are the most serious complications of diabetic decompensation and remain associated with excess mortality. Insulin deficiency is the main underlying abnormality. Associated with elevated levels of counterregulatory hormones, insulin deficiency can trigger hepatic glucose production and reduced glucose uptake, resulting in hyperglycemia, and can also stimulate lipolysis and ketogenesis, resulting in ketoacidosis. Both hyperglycemia and hyperketonemia will induce osmotic diuresis, which leads to dehydration. Clinical diagnosis is based on the finding of dehydration along with high capillary glucose levels with or without ketones in the urine or plasma. The diagnosis is confirmed by the blood pH, serum bicarbonate level and serum osmolality. Treatment consists of adequate correction of the dehydration, hyperglycemia, ketoacidosis and electrolyte deficits.

Prognostic factors of hyperglycemic hyperosmolar nonketotic state.

BACKGROUND: To delineate the prognostic factors of patients suffering from hyperglycemic hyperosmolar nonketotic state (HHNK) in Taiwan. METHODS: We reviewed the charts of patients who had been admitted to the Division of Endocrinology and Metabolism of Kaohsiung Veterans General Hospital from 1992 to 1998 due to HHNK. General and clinical data were collected. The influential factors for prognosis were determined. RESULTS: One hundred and nineteen patients fulfilling the criteria of HHNK were included in our study. The mean age was 67.8 +/- 11.7 years with male predominance. Twenty-nine patients died which produced a fatality rate of 24.4%. Eighty-six (72.3%) cases occurred in patients with known diabetic history, while another thirty-three (27.7%) occurred in patients with no diabetic history. Most patients received oral antidiabetic drugs before HHNK episodes. The patients who died had shorter length of inpatient stay than did survivors. The leading precipitating factor was infection (57.1%), followed by poor compliance of medication (21.0%) and undiagnosed diabetes (10.9%). Fifty patients (42%) had a history of stroke. The risk factors for death included precipitation of HHNK by infection and low Glasgow coma scale (GCS) on admission. Old age itself did not contribute to death. Severity of hyperglycemia or hyperosmolarity was also not an important prognostic factor. Multiple logistic regression revealed that low GCS on admission was the most influential factor of leading to death. Most of the patients who died did so due to underlying precipitating factors. CONCLUSIONS: Neither age nor osmolarity, but underlying precipitating factors and state of consciousness were the most influential factors affecting the prognosis of HHNK.

Diabetes emergencies in the patient with type 2 diabetes.

Type 2 diabetes has traditionally been associated with the development of hyperglycemic hyperosmolar nonketotic syndrome (HHNKS), yet evidence suggests that diabetic ketoacidosis (DKA) is increasing among this population. Patients with type 2 diabetes may develop DKA or HHNKS and require hospitalization. In addition, patients with type 2 diabetes, hospitalized for other medical or surgical conditions, are clearly at risk for the development of metabolic decompensation during hospitalization. This article explores the acute complications of type 2 diabetes and some of the issues associated with managing these patients in the hospital setting.

Glycemic crises in patients with hematologic malignancies.

Persons with hematologic malignancies such as leukemia, lymphoma, or myeloma often have coexisting medical conditions. Among these may be diabetes mellitus. The physiologic and psychologic stress of diagnosis and treatment may precipitate the life-threatening complications of DKA or HHNS in this group of patients. People with personal risk factors may develop diabetes mellitus secondary to diagnosis and treatment and present with either DKA or HHNS. It is essential that the health care team have a heightened awareness of potential complications. These are complex syndromes involving severe hyperglycemia, metabolic acidosis, fluid and electrolyte imbalances, and neurologic and cardiovascular collapse. Working collaboratively with the critical care team to provide optimal care, nurses play an essential role in the management of these challenging complications of diabetes mellitus.

Dextromethorphan in nonketotic hyperglycinaemia: metabolic variation confounds the dose-response relationship.

Nonketotic hyperglycinaemia (NKH) is an inborn error of the glycine cleavage system resulting in seizures and mental retardation. Two prior reports noted an anticonvulsant effect from high-dose dextromethorphan (DM) in this disorder, although the two reported patients demonstrated widely disparate DM requirements and drug levels. We report two children with NKH who also demonstrated disparate and variable DM metabolism which markedly influenced the dose-concentration-response relationship. Levels of DM and its primary metabolite dextrorphan (DX) were utilized to guide DM therapy and exhibited patterns reflective of the extensive and poor metabolizer phenotypes for CYP2D6, the cytochrome P450 isoform responsible for DM metabolism. In the patient who appeared to represent the extensive metabolizer (EM) phenotype, treatment with the non-specific cytochrome P450 inhibitor cimetidine was required to reduce biotransformation of DM to DX and, thus, to increase DM plasma concentrations. In the patient with the apparent poor metabolizer (PM) phenotype, a change in the DM preparation to a sustained-release form and increase in the dosing interval was required to lower DM plasma concentrations. These cases demonstrate the importance of CYP2D6 phenotype in providing safe and effective DM therapy to patients with NKH.