Biochemical evidence of cell starvation in diabetic hemodialysis patients

Abstract

Recently, the ratio of patients with diabetes mellitus (DM) among hemodialysis (HD) patients has increased to become the largest sub-population. Their prognoses are significantly worse than those of patients without diabetes (non-DM). In the present study, 10 DM patients who did not take meals and 10 non-DM patients who took meals during HD sessions were investigated. The time courses of the change in plasma levels of metabolites during HD were determined. DM patients exhibited decreased plasma levels of lactate, pyruvate and alanine and dramatically increased levels of ketone bodies. At the end of HD, the plasma levels of lactate, pyruvate, alanine and ketone body were 0.46 ± 0.07, 0.026 ± 0.01, 0.12 ± 0.04 and 0.26 ± 0.04 mM (mean ± standard error), respectively. The profile was ‘hypolactatemia and hyperketonemia’, indicating non-homeostasis. Glycolysis and tricarboxylic acid cycle were suppressed, and the oxidation of fatty acid was accelerated, indicating starvation, even though high amounts of glucose (150 mg/dl) in dialysate were supplied continuously to the bloodstream. In contrast, the plasma levels of lactate, pyruvate, and alanine in the non-DM patients were increased, with the levels of ketone body remaining low during HD to maintain homeostasis, indicating accelerated glycolysis. Furthermore, their plasma levels of insulin increased from 8.1 ± 1.4 to 19.8 ± 3.4 μU/ml, which indicated endogenous secretion stimulated by glucose in dialysate and meal intake. In contrast, in the DM patients, the levels decreased from 19.2 ± 3.4 to 5.5 ± 1.1 μU/ml. This value was the lower limit of the normal range. The depletion of the insulin through extracorporeal circulation may inhibit the transportation of glucose from the blood into the muscles, with the consequence of cell starvation. Such cell starvation along with lipolysis every two days may accelerate proteolysis and affect the prognosis of DM patients.

1H Nuclear Magnetic Resonance (NMR)-Based Cerebrospinal Fluid and Plasma Metabolomic Analysis in Type 2 Diabetic Patients and Risk Prediction for Diabetic Microangiopathy

“…Alanine and histidine are glucogenic amino acids that participate in gluconeogenesis for energy generation, and their plasma levels are lower in T2DM patients during fasting status and cell starvation [38]. Histidine is a precursor of the free-radical scavenger carnosine, and it gained recognition as an anti-oxidant marker for anti-inflammatory and anti-oxidant properties [18,39].…”

“…Elevated α-hydroxybutyric acid (equal to 2-HB) level is a reliable indicator for impaired glucose tolerance and an early biomarker of diabetes in several cohorts [48]. The increase in plasma levels of PUFA and NAG in T2DM is associated with increased fatty acid oxidation during oxidative stress [38,49]. The plasma acetate level was significantly higher in diabetic patients in previous cohorts, and the production of acetate from pyruvate via acetyl-CoA is increased during fasting status [50].…”

An increase in circulating levels of branched-chain amino acids during hemodialysis with regard to protein breakdown: three case reports

“…In DM patients with various pathophysiological conditions, including insulin resistance, response to HD sessions regarding energy metabolism and AA behaviors differ from the response seen in non-DM patients [4][5][6].…”

Comparison of the Components of Three Types of Miso (Fermented Soybean Paste) by ¹H NMR Metabolomic Analysis

“…Comparison of the Components of Three Types of Miso (Fermented Soybean Paste) by 1 H NMR Metabolomic Analysis sis patients. [19][20][21] In this study, we compared the components of three types of miso by metabolomic analysis using 1 H NMR.…”