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Zonation of gluconeogenesis, ketogenesis and intracellular pH in livers from normal and diabetic ketoacidotic rats: evidence for intralobular redistribution of metabolic events in ketoacidosis.

ABSTRACT: The intralobular distribution of metabolism was examined in the livers from rats with severe diabetic ketoacidosis (DKA), perfused at pH 6.8, and compared with that in livers from normal starved animals perfused at either pH 7.4 or 6.8. With lactate and palmitate as substrates, the perivenous uptake of periportally synthesized glucose seen in normal livers at pH 7.4 was abolished during DKA; indeed, gluconeogenesis was most active in the perivenous region. Whereas in normal livers perfused at pH 7.4 the periportal region showed a markedly elevated intracellular pH (pH(i)) compared with the perivenous zone, this distribution of pH(i) was reversed in DKA, with an intermediate distribution in normal livers perfused at pH 6. 8. 3-Hydroxybutyrate was generated throughout the lobule. Some acetoacetate generated periportally was converted to 3-hydroxybutyrate more perivenously. A steep gradient of oxygen uptake along the radius of the lobule was apparent in all three groups; oxygen uptake was greatly decreased perivenously despite adequate oxygen supply. These findings are consistent with our previous observations of the lobular co-location of high pH(i) and gluconeogenesis, and might offer an explanation of how high gluconeogenic rates can continue in spite of severe systemic acidosis in DKA. The findings provide direct evidence for a marked redistribution of intralobular metabolism in DKA.

SUBMITTER: Burns SP

PROVIDER: S-EPMC1220551 | biostudies-other | 1999 Oct

REPOSITORIES: biostudies-other

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Project description:Background/objectiveThe prevalence of diabetic ketoacidosis (DKA) in gestational diabetes mellitus (GDM) is very low. We describe a patient with GDM in whom severe DKA with intrauterine fetal demise developed in the setting of nonadherence to therapy.Case reportA 33-year-old woman, G2P0010, with no preexisting diabetes mellitus (DM) presented at 30 weeks of gestation with acute-onset altered sensorium, nausea, and emesis. GDM was diagnosed at 15 weeks of gestation with a serum glucose level of 266 mg/dL (70-134 mg/dL) after 1-hour 50-gram glucose challenge test. Glycated hemoglobin (HbA1C) was 5.9% (41 mmol/mol) at the time of GMD diagnosis. Insulin was initiated at week 20 of gestation. On presentation, serum glucose level of 920 mg/dL (70-110 mg/dL), pH of 7.02 (7.32-7.43), anion gap level of 38 mmol (5-17 mmol), bicarbonate level of 5.0 mEq/L (22-29 mEq/L), and large serum ketones were found. Ultrasound showed intrauterine fetal demise. She received intravenous fluids and continuous insulin. Following the spontaneous delivery of a nonviable fetus, DKA was resolved. Negative antiglutamic acid decarboxylase, islet cell, and zinc transporter 8 antibodies, C-peptide level of 2.4 ng/dL (1.1-4.4 ng/dL), and HbA1C level of 9% (75 mmol/mol) were found. Inpatient management included basal-bolus and sliding scale insulin therapies. Metformin was added upon discharge 7 days after admission. The HbA1C levels were 5.3% (34 mmol/mol) and 5% (31 mmol/mol) at the 3- and 6-month follow-ups, respectively. Insulin was discontinued. Currently, the patient is on metformin and glucagon-like peptide 1 receptor agonist.DiscussionThe development of insulin resistance during pregnancy is driven by multiple factors. Approximately 1% to 2% of pregnant women with impaired glucose tolerance develop DKA; most cases occur in women with type 1 DM. The approximate incidence of DKA in GDM is 0.02%.ConclusionDKA complicating GDM is extremely infrequent, but it cannot be dismissed. Early recognition along with prompt and appropriate medical and obstetrical management is critical.

Project description:The target audience of this simulation is emergency medicine residents and medical students. The simulation is based on a real case of a 12-year-old male who presented obtunded with shortness of breath and hypothermia who was ultimately diagnosed with diabetic ketoacidosis (DKA) and pneumomediastinum. This case highlights the diagnosis and management of an adolescent with new onset diabetic ketoacidosis and pneumomediastinum with deterioration of status, as well as important ventilator settings if intubation is required in the setting of diabetic ketoacidosis. Type 1 diabetes is a common disease in the pediatric population with the prevalence being approximately 2.15 per 1000 youths and diabetic ketoacidosis being the presenting status in 30-40% of the patients.1 Physicians who evaluate a child with altered mental status must have diabetic ketoacidosis in their differential. In the setting of mechanical ventilation in patients with diabetic ketoacidosis (DKA), special care must be taken. Mechanical ventilation in these patients comes with increased risk, morbidity, and mortality. Risk factors for pneumomediastinum include lung disease such as asthma, chronic obstructive pulmonary disease (COPD), and malignancy, but also can occur in the acute setting of vomiting or trauma.2. By the end of the simulation, learners will be able to: 1) develop a differential diagnosis for an adolescent who presents obtunded with shortness of breath; 2) discuss the management of diabetic ketoacidosis; 3) discuss management of hypothermia in a pediatric patient; 4) discuss appropriate ventilator settings in a patient with diabetic ketoacidosis; and 5) demonstrate interpersonal communication with family, nursing, and consultants during high stress situations. This is a high-fidelity simulation that allows learners to manage the diagnosis and treatment of diabetic ketoacidosis and hypothermia in an adolescent patient. Participants participated in a debriefing after the simulation. There should be approximately 4-5 learners per case. This simulation was performed in 3 sessions. Each learner performed this simulation one time. The effectiveness of this case was evaluated by surveys given to learners after debriefing. Learners gave quantitative and qualitative results of their feedback using a 1-5 rating scale and open-ended written questions. This case was trialed with residents in their first through third years of training as well as fourth year medical students. Feedback was very positive, with 19 residents completing the post-simulation survey. They enjoyed the case and reported they would feel more comfortable in a comparable situation in the future. Four survey questions were asked of the participants. On average, learners stated they felt the simulation improved their ability to manage a pediatric DKA patient, and their knowledge of complications and appropriate ventilator settings improved (modes of 5, 4 and 5, respectively). Diabetic ketoacidosis is a common and critical diagnosis for emergency medicine physicians to consider in the setting of altered mental status in a pediatric patient. This simulation has multiple steps and is based on a real case of an obtunded and hypothermic pediatric patient who was ultimately diagnosed with diabetic ketoacidosis complicated by pneumomediastinum. Diabetic ketoacidosis, pneumomediastinum, hypothermia, altered mental status, pediatrics, adolescent, intubation, hypoxia, ventilator settings, cardiac arrest, emergency medicine, medical simulation.

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Zonation of gluconeogenesis, ketogenesis and intracellular pH in livers from normal and diabetic ketoacidotic rats: evidence for intralobular redistribution of metabolic events in ketoacidosis.

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