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Gluconeogenesis and the protection of hepatic intracellular pH during diabetic ketoacidosis in rats.

ABSTRACT: Studies were made of the mechanism whereby hepatic gluconeogenesis is increased in diabetic ketoacidosis (DKA) despite evidence in vitro of inhibition of gluconeogenesis by systemic acidosis. In perfused livers taken from normal rats, marked inhibition of lactate uptake and glucose output was achieved by simulation of metabolic acidosis in the perfusate. In perfused livers obtained from animals with DKA, lactate uptake and glucose output were greater than in normal perfused liver at all values of perfusate pH, and it was not possible to demonstrate significant inhibition of gluconeogenesis from lactate by perfusate acidosis. Varying severity of acidosis was induced in rats by (a) HCl infusion, (b) NH4Cl ingestion or (c) experimental DKA. Hepatic intracellular pH (pHi) was measured in vivo by 31P-n.m.r. spectroscopy. Whereas at the severer degrees of systemic acidosis marked falls in hepatic pHi were seen in the HCl- and NH4Cl-treated animals, little fall was seen in rats with DKA. The protection of hepatic pHi in rats with DKA was not due to differences in respiratory compensation compared with the other groups. It is suggested that this protection of hepatic pHi in DKA may be responsible for the failure of acidotic inhibition of gluconeogenesis from lactate. Possible reasons for pHi protection in DKA are considered. There is no difference in hepatic energy status as assessed in vivo by ATP/Pi ratios between control, DKA and NH4Cl-treated rats. DKA rats show a striking decrease in hepatic glycerophosphoethanolamine content.

SUBMITTER: Beech JS

PROVIDER: S-EPMC1133494 | biostudies-other | 1989 Nov

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.

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Gluconeogenesis and the protection of hepatic intracellular pH during diabetic ketoacidosis in rats.

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