Lang, Florian, Gillian L. Busch, Markus Ritter, Harald Volkl, Siegfried Waldegger, Erich Gulbins, and Dieter Haussinger. Functional Significance of Cell Volume Regulatory Mechanisms. Physiol. Rev. ...

Functional Significance of Cell Volume Regulatory Mechanisms

Diabetic ketoacidosis (DKA) and the hyperosmolar hyperglycemic state (HHS) are the two most serious acute metabolic complications of diabetes. DKA is responsible for more than 500,000 hospital days per year (1,2) at an estimated annual direct medical expense and indirect cost of 2.4 billion USD (2,3). Table 1 outlines the diagnostic criteria for DKA and HHS. The triad of uncontrolled hyperglycemia, metabolic acidosis, and increased total body ketone concentration characterizes DKA. HHS is characterized by severe hyperglycemia, hyperosmolality, and dehydration in the absence of significant ketoacidosis. These metabolic derangements result from the combination of absolute or relative insulin deficiency and an increase in counterregulatory hormones (glucagon, catecholamines, cortisol, and growth hormone). Most patients with DKA have autoimmune type 1 diabetes; however, patients with type 2 diabetes are also at risk during the catabolic stress of acute illness such as trauma, surgery, or infections. This consensus statement will outline precipitating factors and recommendations for the diagnosis, treatment, and prevention of DKA and HHS in adult subjects. It is based on a previous technical review (4) and more recently published peer-reviewed articles since 2001, which should be consulted for further information.

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Table 1 
Diagnostic criteria for DKA and HHS



Recent epidemiological studies indicate that hospitalizations for DKA in the U.S. are increasing. In the decade from 1996 to 2006, there was a 35% increase in the number of cases, with a total of 136,510 cases with a primary diagnosis of DKA in 2006—a rate of increase perhaps more rapid than the overall increase in the diagnosis of diabetes (1). Most patients with DKA were between the ages of 18 and 44 years (56%) and 45 and 65 years (24%), with only 18% of patients <20 years of age. Two-thirds of DKA patients were considered to have type 1 diabetes and …

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Hyperglycemic Crises in Adult Patients With Diabetes

Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) are two of the most serious acute complications of diabetes. These hyperglycemic emergencies continue to be important causes of morbidity and mortality among patients with diabetes in spite of major advances in the understanding of their pathogenesis and more uniform agreement about their diagnosis and treatment. The annual incidence rate for DKA estimated from population-based studies ranges from 4.6 to 8 episodes per 1,000 patients with diabetes (1,2), and in more recent epidemiological studies in the U.S., it was estimated that hospitalizations for DKA during the past two decades are increasing (3). Currently, DKA appears in 4-9% of all hospital discharge summaries among patients with diabetes (4,5). The incidence of HHS is difficult to determine because of the lack of population-based studies and the multiple combined illnesses often found in these patients. In general, it is estimated that the rate of hospital admissions due to HHS is lower than the rate due to DKA and accounts for <1% of all primary diabetic admissions (4,5,6).

Treatment of patients with DKA and HHS uses significant health care resources, which increases health care costs. In 1983, the cost of hospitalization for DKA in Rhode Island for 1 year was estimated to be $225 million (2). It was recently reported that treatment of DKA episodes represents more than one of every four health care dollars spent on direct medical care for adult patients with type 1 diabetes and for one of every two dollars in those patients experiencing multiple episodes of ketoacidosis (7). Based on an annual average of ∼100,000 hospitalizations for DKA in the U.S. (4) and estimated annual mean medical care charges of ∼$13,000 per patient experiencing a DKA episode (7), the annual hospital cost for patients …

https://care.diabetesjournals.org/content/diacare/24/1/131.full.pdf

Management of Hyperglycemic Crises in Patients With Diabetes

Recommendations concerning fluid management have been modified to reflect recent findings from a randomized controlled clinical trial showing no difference in cerebral injury in patients rehydrated at different rates with either 0.45% or 0.9% saline. This article is protected by copyright. All rights reserved.

ISPAD Clinical Practice Consensus Guidelines 2018: Diabetic ketoacidosis and the hyperglycemic hyperosmolar state.

Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) are the two most serious acute metabolic complications of diabetes. Most patients with DKA have autoimmune type 1 diabetes; however, patients with type 2 diabetes are also at risk during the catabolic stress of acute illness such as trauma, surgery, or infection. Table 1 outlines the diagnostic criteria and electrolyte and fluid deficits for both disorders. The mortality rate in patients with DKA is <5% in experienced centers, whereas the mortality rate of patients with HHS still remains high at ∼11% (1–8). Death in these conditions is rarely due to the metabolic complications of hyperglycemia or ketoacidosis but rather relates to the underlying precipitating illness. The prognosis of both conditions is substantially worsened at the extremes of age and in the presence of coma and hypotension (7,9–11)

This consensus statement will outline precipitating factors and recommendations for the diagnosis, treatment, and prevention of DKA and HHS in adult subjects. It is based on a previous technical review and more recently published peer-reviewed articles since 2001, which should be consulted for further information.

Although the pathogenesis of DKA is better understood than that of HHS, the basic underlying mechanism for both disorders is a reduction in the net effective action of circulating insulin coupled with a concomitant elevation of counterregulatory hormones, such as glucagon, catecholamines, cortisol, and growth hormone (1,3,4,8–13). DKA and HHS can fall anywhere along the disease continuum of diabetic metabolic derangements. At one extreme, pure DKA without significant hyperosmolarity typically indicates the total or relative absence of insulin (seen in type 1 diabetes). At the other extreme, HHS without ketoacidosis typically occurs with lesser degrees of insulin deficiency, as seen in type 2 diabetes. However, …

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Hyperglycemic Crises in Adult Patients With Diabetes: A consensus statement from the American Diabetes Association

ObjectiveDiscussion of abnormal plasma sodium concentrations with an emphasis on the pathogenesis, diagnosis, and treatment.Data SourcesRelevant literature in the English language and the authors' clinical experience.Study SelectionNo special study has been carried out for the present discussion.Dat

Disorders of sodium metabolism: hypernatremia and hyponatremia.

It is widely believed that the cerebral salt-wasting syndrome (CSWS) exists as an entity distinct from the syndrome of inappropriate ADH secretion, and that it is characterized by evidence of severe renal salt wasting that results in volume depletion and hyponatremia. Proof of the existence of CSWS as an entity requires documentation of renal salt wasting and volume depletion. The present review has been undertaken to examine the evidence that the CSWS is a separate entity. In this effort, we have discussed various methods of documentation of volume depletion, and then reviewed reported cases of CSWS to determine whether volume depletion and renal salt wasting have been clearly demonstrated. Our review has led us to conclude that not one case of purported CSWS has demonstrated clear evidence of volume depletion and renal salt wasting. If renal salt wasting had been proven in these cases, we would conclude that the likely site of renal salt transport was the proximal tubule. The proximal site of salt transport defect has been suggested by the absence of hyperreninemia and hypokalemia, which would be a distinguishing feature of Bartter's syndrome and Gitelman's syndrome.

Cerebral salt-wasting syndrome. We need better proof of its existence.

The present communication seeks to resolve the mechanism of metabolic acidosis that persists after ketonemia has cleared; the reason for the approximate equality of excess anion gap and reduction in serum bicarbonate at the time of admission despite substantial prior urinary loss of ketone anions; the mechanism of transformation of normochloremic acidosis to hyperchloremic acidosis during the recovery phase of DKA

Mechanism of Normochloremic and Hyperchloremic Acidosis in Diabetic Ketoacidosis

Bartter’s syndrome is generally attributed to a primary defect in salt reabsorption either in the ascending limb of Henle’s loop or in the proximal tubule. 2 siblings presented here have all the clini

Man S. Oh

Papers

Disorders of sodium metabolism: hypernatremia and hyponatremia.

Cerebral salt-wasting syndrome. We need better proof of its existence.

Mechanism of Normochloremic and Hyperchloremic Acidosis in Diabetic Ketoacidosis

Bartter's syndrome due to a defect in salt reabsorption in the distal convoluted tubule.

Consumpton of CO2 in metabolism of acetate as an explanation for hypoventilation and hypoxemia during hemodialysis.