Pyruvate Dehydrogenase Activity Is Decreased in Emergency Department Patients With Diabetic Ketoacidosis

Abstract

Objectives: The pyruvate dehydrogenase complex (PDH) is an essential enzyme in aerobic metabolism. Ketones are known to inhibit PDH activity, but the extent of this inhibition is unknown in patients with diabetic ketoacidosis (DKA). Methods:We enrolled adult patients presenting to the emergency department in hyperglycemic crisis. Patients were classified as DKA or hyperglycemia without ketoacidosis based on laboratory criteria. Healthy controls were also enrolled. PDH activity and quantity were measured in isolated peripheral blood mononuclear cells. We compared PDH values between groups and measured the relationship of PDH values to measures of acid-base status.Results: Twenty-seven patients (17 with DKA) and 31 controls were enrolled. Patients with DKA had lower PDH activity and quantity compared to the two other groups. PDH activity was significantly correlated with serum bicarbonate and pH and inversely correlated with the anion gap.Conclusions: DKA is associated with greater suppression of PDH activity than hyperglycemia without ketoacidosis, and this is correlated with measures of acid-base status. Future studies may determine whether PDH depression plays a role in the pathophysiology of DKA and whether modification of PDH could decrease time to DKA resolution.ACADEMIC EMERGENCY MEDICINE 2016;23:685-689

Pyruvate-Enriched Oral Rehydration Solution Improves Glucometabolic Disorders in the Kidneys of Diabetic db/db Mice

“…Various pathogenic insults, including critical injuries, such as bleeding, trauma and sepsis, diabetes, aging, and even cancer, may induce the PDH inhibition, leading to specifically distinct metabolic disturbances and acid-base imbalances in various respective insults. The PDH activity is decreased in diabetic animals and humans, and clinical diabetic ketoacidosis even appears more severe PDH inhibition [ 31 , 32 ]. Data here provided first evidence that oral pyruvate rejuvenated the HG-inhibited PDH activity in diabetes, as shown in Table 3 , where renal PDHa/t activities were comparably enhanced in two pyruvate groups.…”

Cuproptosis: potential new direction in diabetes research and treatment

“…In clinical studies, Lars W. Andersen et al. observed decreased PDC activity in DKA patients with diabetes ( 18 ). Indeed, PDC is not only associated with diabetes but also closely linked to its complications.…”