glycogen and Diabetic-Ketoacidosis

Exercise in diabetes patients has many benefits but also several risks, of which hypoglycemia is most often discussed. We present a case with recurrent keto-acidosis post-exercise, in which we hypothesize that glycogen replacement strategies were insufficient. Our experience in this case and review of the literature emphasize the importance of discussing glycogen replacement strategies with your diabetic athletes.

Topics: Adolescent; Athletes; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Exercise; Glycogen; Humans; Male; Physical Exertion; Recurrence

Topics: Blood Glucose; Diabetic Ketoacidosis; Fluid Therapy; Gluconeogenesis; Glycogen; Humans; Insulin

Glycogenic hepatopathy (GH) is an underdiagnosed complication of uncontrolled type 1 diabetes mellitus (T1DM). It appears as an acute relapsing hepatitis with reversible transaminase elevations secondary to excessive hepatic glycogen accumulation. Patients are often asymptomatic but can present with abdominal pain, nausea and vomiting. Physical examination shows hepatomegaly without splenomegaly. GH is diagnosed by biopsy as it is clinically indistinguishable from non-alcoholic fatty liver disease (NAFLD), a more common cause of hepatic dysfunction in diabetics. Here we describe a case of GH in a patient with uncontrolled type 1 diabetes whose clinical course was complicated by drug-induced liver injury. The patient initially presented with diabetic ketoacidosis and had a mild transaminitis, thought to be due to NAFLD. She developed profound transaminase elevations while receiving treatment with newer antipsychotic medications for her bipolar disorder. Liver biopsy showed evidence of resolving glycogenic hepatopathy with signs of drug-induced liver injury. This case report reviews the pathology and pathogenesis of GH and reminds the clinician to keep GH within the differential diagnosis for severe transaminitis in a patient with type 1 diabetes mellitus.

Topics: Abdominal Pain; Antipsychotic Agents; Biopsy; Bipolar Disorder; Chemical and Drug Induced Liver Injury; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Diagnosis, Differential; Dibenzocycloheptenes; Female; Glycogen; Hepatomegaly; Heterocyclic Compounds, 4 or More Rings; Humans; Liver; Magnetic Resonance Imaging; Young Adult

Topics: Adult; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Female; Glycogen; Hepatomegaly; Humans; Liver Diseases; Magnetic Resonance Imaging; Young Adult

Activities (mumol X min-1 X g liver) and zonal distributions of key enzymes of carbohydrate metabolism were studied in livers of streptozotocin-diabetic rats and compared to the values in alloxan-diabetes. Streptozotocin led to a non-ketotic diabetes with blood glucose being increased by more than fivefold but ketone bodies being in the normal range, while alloxan produced a ketotic diabetes with blood glucose, acetoacetate and beta-hydroxybutyrate being elevated by more than fivefold. Portal insulin was decreased to about 20% in streptozotocin- and more drastically to about 7% in alloxan-diabetes. Conversely, portal glucagon was increased in the two states to about 250% and 180%, respectively. The glucogenic key enzyme phosphoenolpyruvate carboxykinase (PEPCK) was enhanced in streptozotocin- and alloxan-diabetes to over 300%, while the glycolytic pyruvate kinase L (PKL) was lowered to 65% and 80%, respectively. The normal periportal to perivenous gradient of PEPCK of about 3:1, as measured in microdissected tissue samples, was maintained with elevated activities in the two zones. The normal periportal to perivenous gradient of PKL of 1:1.7 was diminished with lowered activities in the two zones. The glucogenic glucose-6-phosphatase (G6Pase) was increased in streptozotocin- and alloxan-diabetes to 130% and 140%, respectively, while the glucose utilizing glucokinase (GK) was decreased to 60% and 50%, respectively. The normal periportal to perivenous gradient of G6Pase, demonstrated histochemically, remained unaffected. Carnitine palmitoyltransferase (CPT) was increased to over 190% and acetyl-CoA carboxylase (ACC) was decreased to 60% in streptozotocin, non-ketotic diabetes, while the two enzymes were altered more drastically to 400% and 50%, respectively, in alloxan, ketotic diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Alloxan; Animals; Diabetes Mellitus, Experimental; Diabetic Ketoacidosis; Fatty Acids; Gluconeogenesis; Glucose-6-Phosphatase; Glycogen; Glycolysis; Liver; Male; Phosphoenolpyruvate Carboxykinase (GTP); Pyruvate Kinase; Rats; Rats, Inbred Strains; Streptozocin; Succinate Dehydrogenase

Significant alterations in heart carbohydrate and lipid metabolism are present 48 h after intravenous injection of alloxan (60 mg/kg) in rats. It has been suggested that uncoupling of oxidative phosphorylation occurs in the alloxanized rat heart in vivo, whereas normal oxidative metabolism has been demonstrated in alloxan-diabetic rat hearts perfused in vitro under conditions of adequate oxygen delivery. We examined the hypothesis that high-energy phosphate metabolism might be adversely affected in the alloxan-diabetic rat heart in vivo. Phosphocreatine and ATP were reduced by 58 and 45%, respectively (P is less than 0.001). Also, oxygen-dissociation curves were shifted to the left by 4 mmHg, and the rate of oxygen release from blood was reduced by 21% (P is less than 0.01). Insulin administration normalized heart high-energy phosphate compounds. ATP production was accelerated in diabetic hearts perfused in vitro with a well-oxygenated buffer. These studies support the hypothesis that oxidative ATP production in the alloxan-diabetic rat heart is reduced and suggest that decreased oxygen delivery may have a regulatory role in the oxidative metabolism of the diabetic rat heart.

Topics: Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Animals; Blood Glucose; Blood Pressure; Diabetes Mellitus, Experimental; Diabetic Ketoacidosis; Diphosphoglyceric Acids; Erythrocytes; Ether; Fatty Acids, Nonesterified; Glucosephosphates; Glycogen; Heart Rate; Hydrogen-Ion Concentration; Insulin; Male; Myocardium; Oxygen; Pentobarbital; Phosphocreatine; Rats

Topics: Animals; Cricetinae; Diabetes Mellitus; Diabetic Ketoacidosis; Diabetic Nephropathies; Diabetic Retinopathy; Disease Models, Animal; Female; Glucose; Glycogen; Glycosuria; Histocytochemistry; Islets of Langerhans; Kidney; Male; Retina

Male rats rendered diabetic by the intravenous injection of streptozotocin (150mg/kg) were treated with a long-acting insulin for 1 week, then allowed to develop ketoacidosis. By using sampling techniques designed to avoid the use of anaesthesia and extended anoxic periods, sequential measurements of metabolic intermediates were made in blood, liver, cerebrospinal fluid and brain at 24h intervals after the last insulin injection. Measurements in blood and liver suggested a rapid increase in hepatic glycogenolysis and gluconeogenesis and peripheral-depot lipolysis between 24 and 48h after the last insulin injection, whereas blood and liver ketone-body and triglyceride concentrations rose more slowly. The changing metabolic patterns occurring with increasing time of insulin deprivation stress the importance of sequential compared with static measurements in experimental diabetes. Data are presented for brain metabolic intermediates in diabetic ketoacidosis, and support recent evidence that glucose plays a less important role in brain oxidative metabolism in ketotic states.

Topics: Animals; Antibodies; Blood Glucose; Body Weight; Brain; Diabetes Mellitus; Diabetic Ketoacidosis; Gluconeogenesis; Glycogen; Insulin; Ketone Bodies; Lipid Mobilization; Liver; Male; Organ Size; Radioimmunoassay; Rats; Streptozocin; Time Factors; Triglycerides

Topics: Animals; Blood Glucose; Diabetes Mellitus; Diabetic Ketoacidosis; Fatty Acids, Nonesterified; Glucose; Glycerol; Glycogen; Insulin; Ketone Bodies; Lactates; Liver; Male; Physical Exertion; Rats; Streptozocin

Topics: Animals; Antigens; Blood Glucose; Carbon Dioxide; Chlorides; Diabetes Mellitus, Experimental; Diabetic Coma; Diabetic Ketoacidosis; Disease Models, Animal; Fatty Acids, Nonesterified; Glycogen; Hydrocortisone; Insulin; Ketone Bodies; Liver; Male; Osmolar Concentration; Potassium; Rats; Sodium; Urea

Topics: Adipose Tissue; Age Factors; Animals; Biological Assay; Carbon Isotopes; Diabetes Mellitus; Diabetic Ketoacidosis; Diaphragm; Epididymis; Glycogen; Humans; Insulin; Male; Methods; Rats

Topics: Amino Acids; Diabetes Mellitus; Diabetic Ketoacidosis; Gluconeogenesis; Glucose; Glycogen; Glycolysis; Humans; Insulin

Topics: Dehydration; Diabetic Coma; Diabetic Ketoacidosis; Fructose; Glucagon; Glucose; Glycogen; Humans; Hypoglycemia; Hypotonic Solutions; Injections, Intravenous; Insulin; Insulin Secretion; Ketone Bodies; Lipid Metabolism; Male; Oxygen Consumption; Potassium; Water; Water-Electrolyte Balance

Topics: Adolescent; Body Weight; Child; Dehydration; Diabetic Coma; Diabetic Ketoacidosis; Drug Therapy; Fluid Therapy; Glycogen; Glycosuria; Humans; Hyperglycemia; Infant; Infant, Newborn; Insulin; Metabolism; Parenteral Nutrition; Water-Electrolyte Balance

Topics: Diabetes Mellitus; Diabetic Ketoacidosis; Glycogen; Glycogenolysis; Liver; Liver Glycogen

Topics: Diabetes Mellitus; Diabetic Ketoacidosis; Glycogen; Humans; Liver; Liver Glycogen; Muscles; Needles

Topics: Acidosis; Biopsy; Diabetes Mellitus; Diabetic Ketoacidosis; Glycogen; Humans; Liver; Liver Glycogen