Human splanchnic metabolism during diabetic ketoacidosis

Owen, Oliver E.; Block, Bradley; Patel, Mulchand S.; Boden, Guenther; McDonough, Michael T.; Kreulen, Thomas H.; Shuman, Charles R.; Reichard, George A.

doi:10.1016/0026-0495(77)90105-6

Cited by 46 publications

(31 citation statements)

References 36 publications

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“…However, in our patients in whom alcohol abstinence was observed for days to months during hospitalization, hepatic extraction of alanine and presumed gluconeogenesis from alanine was greater than previously reported after an overnight (5, 34) and 3-d (8) fasts or during moderate to severe diabetic ketoacidosis (11). This heightened gluconeogenesis from alanine and presumably from other amino acids derived primarily from accelerated protein degradation after an overnight fast may be partly responsible for the marked peripheral muscle wasting known in patients with alcoholic cirrhosis.…”

Section: Resultscontrasting

confidence: 70%

“…96±26 ,tmol of glutamine, and 74±32 umol of,-OHB/min per 1.73 m2, but there was no significant net exchange of alanine, glutamate, FFA, or AcAc. Renal extraction of glucose equivalents (lactate + pyruvate + glycerol + a-ketoglutarate equivalents/2 [11]) was 103±19…”

Section: Resultsmentioning

confidence: 99%

“…The analytical methods and the precision for the determination of blood glucose, lactate, pyruvate, glycerol, alanine, glutamine, glutamate, f-OHB, AcAc, plasma triglyceride and double-extracted plasma FFA, serum IRI, and plasma IRG have been published (8,11,12). Arterial and venous substrate and hormone concentrations were determined simultaneously in duplicate or triplicate.…”

Section: Substrate and Hormone Determinationsmentioning

confidence: 99%

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Hepatic, gut, and renal substrate flux rates in patients with hepatic cirrhosis.

Owen¹,

Reichle²,

Mozzoli³

et al. 1981

J. Clin. Invest.

284

141

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A B S T R A C T The roles of liver, kidney, and gut in maintaining fuel homeostasis were studied in 28 patients with severe hepatic cirrhosis, 25 of whom had alcohol-induced cirrhosis. Hepatic, portal, and renal blood flow rates were measured and combined with substrate concentration differences across liver, gut, and kidney to calculate the net flux of free fatty acids, ketone bodies, triglycerides, and glucose with selected glucose precursors, including glycerol, lactate, pyruvate, and amino acids. Data from the catheterization studies were related to hepatic histology, glycogen content, and activities of gluconeogenic enzymes and compared with data obtained from control patients. The effects of food deprivation on net flux of fuels across the liver, gut, and kidney were assessed after overnight and after 3 d of fasting.Activities of gluconeogenic enzymes were normal, but hepatic glycogen content was diminished in cirrhotic livers, probably as a consequence of extensive hepatic fibrosis. Extrahepatic splanchnic tissues (gut) had only a small influence on total splanchnic flux rates of carbohydrates, lipids and, amino acids. In cirrhotic patients, there was no mean renal glucose contribution to the bloodstream after an overnight or after a 3-d fast.After an overnight fast hepatic glucose production in patients with cirrhosis was diminished as a result of low-rate glycogenolysis. Hepatic gluconeogenesis and ketogenesis were increased. This pattern of hepatic metabolism mimics that seen in "normal" patients after more advanced stages of starvation. After 3 d of starvation, patients with hepatic cirrhosis have hepatic F. A. Reichle is presently chairman of surgery, Presbyterian-

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Section: Resultscontrasting

confidence: 70%

Section: Resultsmentioning

confidence: 99%

Section: Substrate and Hormone Determinationsmentioning

confidence: 99%

See 1 more Smart Citation

Hepatic, gut, and renal substrate flux rates in patients with hepatic cirrhosis.

Owen¹,

Reichle²,

Mozzoli³

et al. 1981

J. Clin. Invest.

284

141

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“…By combining measurements of arterial and hepatic venous ketone concentrations and estimation of splanchnic blood flow in patients with DKA, the liver was demonstrated to produce large amounts of ketones, and insulin treatment was demonstrated to reduce ketone production promptly. These findings were subsequently confirmed and extended with improved analytical techniques (73). To our knowledge, rates of ketogenesis have not been measured in hyperosmolar nonketotic patients using either organ balance or isotopic methods.…”

Section: Lipid and Ketone Metabolismmentioning

confidence: 63%

Management of Hyperglycemic Crises in Patients With Diabetes

et al. 2001

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Abbreviations: AaO 2 , alveolar-to-arteriolar oxygen; AKA, alcoholic ketoacidosis; ARDS, adult respiratory distress syndrome; BUN, blood urea nitrogen; CPT, carnitine palmitoyl-transferase; CSF, cerebrospinal fluid; DKA, diabetic ketoacidosis; FFA, free fatty acid; HHS, hyperosmolar hyperglycemic state; IRI, immunoreactive insulin; PaO 2 , arteriolar partial pressure of oxygen; RDKA, recurrent DKA.A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances. Management of Hyperglycemic Crises in Patients With Diabetes T E C H N I C A L R E V I E R e v i e w s / C o m m e n t a r i e s / P o s i t i o n S t a t e m e n t s 132DIABETES CARE, VOLUME 24, NUMBER 1, JANUARY 2001Technical Review noted in newly diagnosed obese type 2 diabetic patients (5,26,31). Therefore, the concept that the presence of DKA in type 2 diabetes is a rare occurrence is incorrect.The most common types of infections are pneumonia and urinary tract infection, accounting for 30-50% of cases (Table 4). Other acute medical illnesses as precipitating causes include alcohol abuse, trauma, pulmonary embolism, and myocardial infarction, which can occur both in type 1 and 2 diabetes (6). Various drugs that alter carbohydrate metabolism, such as corticosteroids, pentamidine, sympathomimetic agents, and ␣-and ␤-adrenergic blockers, and excessive use of diuretics in the elderly may also precipitate the development of DKA and HHS.The recent increased use of continuous subcutaneous insulin infusion pumps that use small amounts of short-acting insulin has been associated with an incidence of DKA that is significantly increased over the incidence seen with conventional methods of multiple daily insulin injections, in spite of the fact that most of the mechanical problems with insulin pumps have been resolved (6,(32)(33)(34). In the Diabetes Control and Complications Trial, the incidence of DKA in patients on insulin pumps was about twofold higher than that in the multipleinjection group over a comparable time period (35). This may be due to the exclusive use of short-acting insulin in the pump, which if interrupted leaves no reservoir of insulin for blood glucose control.Psychological factors and poor compliance, leading to omission of insulin therapy, are important precipitating factors for recurrent ketoacidosis. In young female patients with type 1 diabetes, psychological problems complicated by eating disorders may be contributing factors in up to 20% of cases of recurrent ketoacidosis (36,37). Factors that may lead to insulin omission in younger patients include fear of weight gain with good metabolic control, fear of hypoglycemia, rebellion against authority, and stress related to chronic disease (36). Noncompliance with insulin therapy has been found to be the leading precipitating cause for DKA in urban African-Americans and medically indigent patients (5,26). In addition, a recent study showed that diabetic patients without health insurance or with Medicaid alone had hospitali...

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“…Analytical methods and precision for determining blood glucose, lactate, pyruvate, glycerol, alanine, glutamine, glutamate, ,B-hydroxybutyrate (,3OHB),2 acetoacetate (AcAc), doubleextracted plasma free fatty acids (FFA), and triglycerides are published (14)(15)(16). Arterial and venous substrate concentrations were determined simultaneously in duplicate or triplicate.…”

Section: Methodsmentioning

confidence: 99%

Hepatic and renal metabolism before and after portasystemic shunts in patients with cirrhosis.

Owen¹,

Mozzoli²,

Reichle³

et al. 1985

J. Clin. Invest.

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Hepatic cirrhosis with portal hypertension and gastroesophageal hemorrhage is a disease complex that continues to be treated by surgical portasystemic shunts. Whether or not a reduction or diversion of portal blood flow to the liver adversely affects the ability of the liver to maintain fuel homeostasis via gluconeogenesis, glycogenolysis, and ketogenesis is unknown.11 patients with biopsy-proven severe hepatic cirrhosis were studied before and after distal splenorenal or mesocaval shunts. Hepatic, portal, and renal blood flow rates and glucose, lactate, pyruvate, glycerol, amino acids, ketone bodies, free fatty acids, and triglyceride arteriovenous concentration differences were determined to calculate net precursor-product exchange rates across the liver, gut, and kidney. The study showed that hepatic contribution of glucose and ketone bodies and the caloric equivalents of these fuels delivered to the blood was not adversely affected by either a distal splenorenal or mesocaval shunt. In addition to these general observations, isolated findings emerged. Mesocaval shunts reversed portal venous blood and functionally converted this venous avenue into hepatic venous blood. The ability of the kidney to make a substantial net contribution of ketone bodies to the blood was also observed.

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Human splanchnic metabolism during diabetic ketoacidosis

Cited by 46 publications

References 36 publications

Hepatic, gut, and renal substrate flux rates in patients with hepatic cirrhosis.

Hepatic, gut, and renal substrate flux rates in patients with hepatic cirrhosis.

Management of Hyperglycemic Crises in Patients With Diabetes

Hepatic and renal metabolism before and after portasystemic shunts in patients with cirrhosis.

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