Differences in metabolic and hormonal milieu in diabetic- and alcohol-induced ketoacidosis

Umpiérrez, Guillermo E.; DiGirolamo, Mario; Tuvlin, Jeffrey A.; Isaacs, Scott; Bhoola, Snehal M.; Kokko, Juha P.

doi:10.1053/jcrc.2000.7900

Cited by 102 publications

(68 citation statements)

References 32 publications

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“…It is most frequent in patients who have long-term ethanol intake and liver disease and develop the syndrome after a period of binge drinking (39,112) and is associated with reduced food intake and episodes of vomiting; the latter might explain the concurrence of metabolic alkalosis noted in some patients (39,112,115,116).…”

Section: Epidemiologymentioning

confidence: 99%

“…Although oxidation of ethanol in the liver generates acetaldehyde, which is converted to acetate and acetyl CoA, a precursor of ketone bodies, the ketogenesis has been primarily attributed to stimulation of lipolysis and free fatty acids generation from the low insulin levels and development of increased levels of counterregulatory hormones such as epinephrine, cortisol, and glucagon in these patients (115). Excess production of acetoacetic acid and ␤-hydroxybutyric acid underlies the metabolic acidosis, with increased NADH favoring production of ␤-hydroxybutyrate compared with acetoacetate (115), the ratio of these ketones rising from the normal value of 3:1 to more than 9:1 (112)(113)(114)(115).…”

Section: Pathophysiologymentioning

confidence: 99%

“…Excess production of acetoacetic acid and ␤-hydroxybutyric acid underlies the metabolic acidosis, with increased NADH favoring production of ␤-hydroxybutyrate compared with acetoacetate (115), the ratio of these ketones rising from the normal value of 3:1 to more than 9:1 (112)(113)(114)(115). The increased NADH also favors increased lactic acid production; therefore, concomitant lactic acidosis even in the absence of impaired tissue perfusion is not uncommon (39,112,115). However, the increase in lactic acid production is small, and severe lactic acidosis in the absence of sepsis or hypotension is rare (39,112,114,115).…”

Section: Pathophysiologymentioning

confidence: 99%

“…The increased NADH also favors increased lactic acid production; therefore, concomitant lactic acidosis even in the absence of impaired tissue perfusion is not uncommon (39,112,115). However, the increase in lactic acid production is small, and severe lactic acidosis in the absence of sepsis or hypotension is rare (39,112,114,115).…”

Section: Pathophysiologymentioning

confidence: 99%

“…The metabolic acidosis is usually of the high anion gap variety. Hyperchloremic acidosis, described in patients with DKA is uncommon, even after treatment with saline (115). Hyponatremia, hypokalemia and/or hyperkalemia, and hypophosphatemia are also commonly found (39,112,117).…”

Section: Laboratory Findingsmentioning

confidence: 99%

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Toxic Alcohol Ingestions

Kraut¹,

Kurtz²

2008

Clinical Journal of the American Society of Nephrology

355

326

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Alcohol-related intoxications, including methanol, ethylene glycol, diethylene glycol, and propylene glycol, and alcoholic ketoacidosis can present with a high anion gap metabolic acidosis and increased serum osmolal gap, whereas isopropanol intoxication presents with hyperosmolality alone. The effects of these substances, except for isopropanol and possibly alcoholic ketoacidosis, are due to their metabolites, which can cause metabolic acidosis and cellular dysfunction. Accumulation of the alcohols in the blood can cause an increment in the osmolality, and accumulation of their metabolites can cause an increase in the anion gap and a decrease in serum bicarbonate concentration. The presence of both laboratory abnormalities concurrently is an important diagnostic clue, although either can be absent, depending on the time after exposure when blood is sampled. In addition to metabolic acidosis, acute renal failure and neurologic disease can occur in some of the intoxications. Dialysis to remove the unmetabolized alcohol and possibly the organic acid anion can be helpful in treatment of several of the alcohol-related intoxications. Administration of fomepizole or ethanol to inhibit alcohol dehydrogenase, a critical enzyme in metabolism of the alcohols, is beneficial in treatment of ethylene glycol and methanol intoxication and possibly diethylene glycol and propylene glycol intoxication. Given the potentially high morbidity and mortality of these intoxications, it is important for the clinician to have a high degree of suspicion for these disorders in cases of high anion gap metabolic acidosis, acute renal failure, or unexplained neurologic disease so that treatment can be initiated early. Table 1. Methanol, ethylene glycol, diethylene glycol, and propylene glycol intoxication and alcoholic ketoacidosis can produce hyperosmolality and metabolic acidosis (3-9). Isopropanol intoxication is usually associated with hyperosmolality alone (4,5). Importantly, several of these disorders can be fatal or produce irreversible tissue damage if they are not quickly recognized and treated appropriately (4 -15). Effect of Alcohols on Serum Osmolality and the Osmolal GapThe normal serum osmolality of 285 to 290 mOsm/L is due to sodium and its counterbalancing ions, bicarbonate and chloride, and glucose and urea. It can be calculated using the following equation:Serum osmolality (mOsm/L) ϭ 2 ϫ Na ϩ ϩ blood urea nitrogen (mg/dl)/2.8 ϩ glucose (mg/dl)/18. The serum osmolality measured by freezing point depression is usually within 10 mOsm/L of the calculated serum osmolality (16). Accumulation of low molecular weight substances in the serum (such as each of the alcohols) will raise the measured serum osmolality above that of the calculated serum osmolality, producing an osmolal gap (4,5,16 -18). The effect of each of the alcohols on serum osmolality is shown in Table 2. Methanol gives rise to the greatest increment in serum osmolality, followed by ethanol, isopropanol, ethylene glycol, propylene glycol, and diethylene glycol in that...

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Section: Epidemiologymentioning

confidence: 99%

Section: Pathophysiologymentioning

confidence: 99%

Section: Pathophysiologymentioning

confidence: 99%

Section: Pathophysiologymentioning

confidence: 99%

Section: Laboratory Findingsmentioning

confidence: 99%

See 3 more Smart Citations

Toxic Alcohol Ingestions

Kraut¹,

Kurtz²

2008

Clinical Journal of the American Society of Nephrology

355

326

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Diabetic Ketoacidosis and Hyperglycemic Hyperosmolar State

Kitabchi

Umpiérrez

Murphy

2003

International Textbook of Diabetes Mellitus

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The two most serious acute metabolic emergencies seen in diabetes are diabetic ketoacidosis (DKA), which is responsible for more than 100 000 hospital admissions per year in the United States, and hyperosmolar hyperglycemic state (HHS), which is seen in approximately 10 cases per 100 000 people in the general population. Mortality rates in DKA range from 2 to 5% and from 5 to 35% in HHS. The most common precipitating factors in DKA and HHS include infections and omission or inadequate diabetes therapy. Absolute or ineffective insulin levels lead to a series of biochemical events culminating in hyperglycemia, ketosis, and acidosis in DKA and severe hyperglycemia and dehydration without ketosis in HHS. Major therapeutic goals of both emergencies include improvement of organ perfusion by increasing circulatory volume, gradual reduction of osmolality, gradual correction of serum glucose, clearance of both serum and urine of ketones (in DKA), and normalization of electrolyte levels. Careful and frequent monitoring is the most important aspect of management in both conditions. An algorithm for treatment of both DKA and HHS is discussed. Improved education and access to health care, early treatment of hyperglycemia, and monitoring hospitalized patients for elevations in blood glucose continue to be areas that could impact the incidence of these potentially fatal disease states.

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Diabetic Ketoacidosis ¹

2016

Obstetric Clinical Algorithms

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Diabetic ketoacidosis (DKA) is the most common acute hyperglycaemic emergency in people with diabetes mellitus. A diagnosis of DKA is confirmed when all of the three criteria are present -'D', either elevated blood glucose levels or a family history of diabetes mellitus; 'K', the presence of high urinary or blood ketoacids; and 'A', a high anion gap metabolic acidosis. Early diagnosis and management is paramount to improve patient outcome. The mainstays of treatment include restoration of circulating volume, insulin therapy, electrolyte replacement and treatment of any underlying precipitating event. Without optimal treatment, DKA remains a condition with an appreciable, although largely preventable morbidity and mortality. In this Primer, we discuss the epidemiology, pathogenesis, risk factors and diagnosis of DKA, as well as we provide practical recommendations for management of DKA in adults and children. [H1] IntroductionDiabetic ketoacidosis (DKA) is the most common acute hyperglycaemic emergency in people with diabetes mellitus. DKA is the consequence of an absolute (that is, total absence of) or relative (that is, levels insufficient to supress ketone production) lack of insulin and concomitant elevation of counter-regulatory hormones, usually resulting in the triad of hyperglycaemia, metabolic acidosis and ketosis (elevated levels of ketones in the blood or urine; serum ketone concentration of >3.0mmol/l), often accompanied by varying degrees of circulatory volume depletion [G]. DKA occurs mostly in people with uncontrolled type 1 diabetes mellitus (T1DM, which results from the autoimmune destruction of the β-cells of the islets of Langerhans), but can also occur in adults with poorly controlled type 2 diabetes mellitus (T2DM, a result of impaired insulin secretion or action) under stressful conditions such as acute medical or surgical illnesses and, in adolescents, new onset T2DM (also known as ketosis-prone T2DM) (Figure 1). Although any illness or physiological stress can precipitate DKA, the most frequent causes are infections, particularly urinary tract infections and gastroenteritis 1,2 . DKA was previously considered to be a key clinical feature of T1DM, but has been documented in children and adults with newly diagnosed T2DM 2,3 . Although ketosis-prone T2DM can occur in all populations, epidemiological data suggest that people of African or Hispanic origin seem to be at greater risk 2 . This predisposition likely has a genetic component, but this has yet to be elucidated. Most often individuals with ketosis-prone T2DM have obesity and a strong family history of T2DM and evidence of insulin resistance. Despite presenting with DKA and decreased insulin concentrations, on immunological testing these individuals have the same frequency of the typical autoimmune markers of T1DM such as islet cell, insulin, glutamic acid decarboxylase, and protein tyrosine phosphatase autoantibodies as those who present with HHS and their β-cell function recovers with restoration of insulin secretion quickly after trea...

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Differences in metabolic and hormonal milieu in diabetic- and alcohol-induced ketoacidosis

Cited by 102 publications

References 32 publications

Toxic Alcohol Ingestions

Toxic Alcohol Ingestions

Diabetic Ketoacidosis and Hyperglycemic Hyperosmolar State

Diabetic Ketoacidosis ¹

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Differences in metabolic and hormonal milieu in diabetic- and alcohol-induced ketoacidosis

Cited by 102 publications

References 32 publications

Toxic Alcohol Ingestions

Toxic Alcohol Ingestions

Diabetic Ketoacidosis and Hyperglycemic Hyperosmolar State

Diabetic Ketoacidosis 1

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Product

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Diabetic Ketoacidosis ¹