Human splanchnic metabolism during diabetic ketoacidosis

Abstract

Splanchnic exchange rates of glucose, acetoacetate, β-hydroxybutyrate, lactate, pyruvate, glycerol, alanine, glutamine, glutamate, free fatty acids, and triglycerides were measured in eight patients during moderate to severe diabetic ketoacidosis. Their arterial glucose concentration was 20.68 (9.80–52.79) μmole/liter and total ketone-body concentration was 10.38 (6.04–15.81) mmole/liter. Net splanchnic glucose release was 0.77 (0.09–2.44) mmole/min. Gluconeogenesis accounted for about one-half of net splanchnic glucose release, assuming quantitative conversion of net splanchnic extracted lactate, pyruvate, glycerol, alanine, and α-ketoglutarate equivalents to glucose. Net splanchnic free fatty acid extraction was 0.24 (0.09–0.52) mmole/min. There was a positive correlation between free fatty acid uptake and ketone-body release. Net splanchnic acetoacetate release was 0.50 (0.05–0.92) mmole/min and β-hydroxybutyrate release was 0.35 (−0.16 to 0.84) mmole/min. Total ketone-body release was 0.85 (0.37–1.61) mmole/min. The wide ranges of net splanchnic glucose and ketone-body production rates show the heterogeneous characteristics of the diabetic patient in ketoacidosis. It is concluded that the hyperglycemia and hyperketonemia of diabetic ketoacidosis is due to the lack of reciprocity among rates of hepatic glycogenolysis, gluconeogenesis, and ketogenesis resulting in inappropriate net splanchnic release of glucose and ketone bodies.