Glutathione metabolism in type 2 diabetes and its relationship with microvascular complications and glycemia

Abstract

Aims/HypothesesWe hypothesized that there is decreased synthesis of glutathione (GSH) in type 2 diabetes (T2DM) especially in the presence of microvascular complications, and this is dependent on the degree of hyperglycemia.MethodsIn this case-control study, we recruited 16 patients with T2DM (7 without and 9 with microvascular complications), and 8 age- and sex-matched non-diabetic controls. We measured GSH synthesis rate using an infusion of [2H2]-glycine as isotopic tracer and collection of blood samples for liquid chromatography mass spectrometric analysis.ResultsCompared to the controls, T2DM patients had lower erythrocyte GSH concentrations (0.90 ± 0.42 vs. 0.35 ± 0.30 mmol/L; P = 0.001) and absolute synthesis rates (1.03 ± 0.55 vs. 0.50 ± 0.69 mmol/L/day; P = 0.01), but not fractional synthesis rates (114 ± 45 vs. 143 ± 82%/day; P = 0.07). The magnitudes of changes in patients with complications were greater for both GSH concentrations and absolute synthesis rates (P-values ≤ 0.01) compared to controls. There were no differences in GSH concentrations and synthesis rates between T2DM patients with and without complications (P-values > 0.1). Fasting glucose and HbA1c did not correlate with GSH concentration or synthesis rates (P-values > 0.17).ConclusionsCompared to non-diabetic controls, patients with T2DM have glutathione deficiency, especially if they have microvascular complications. This is probably due to reduced synthesis and increased irreversible utilization by non-glycemic mechanisms.

Identification of an oral microbiota signature associated with an impaired orosensory perception of lipids in insulin-resistant patients

“…Notably at the metabolic level, the diabetic status is characterized by a decrease of glutathione (GSH) biosynthesis. The fact that a GSH deficiency was recently reported in T2D patients [ 20 ] and the GSH synthesis was modulated by the gut microbiota through its action on the host amino acid metabolism [ 21 ] is in agreement with our observation. Although GSH is a major cellular antioxidant preventing tissues against the reactive oxygen species damages, the putative GSH deficit at the CVP level does not impact the fatty taste sensitivity of D patients.…”

Alterations in glutathione, nitric oxide and 3‑nitrotyrosine levels following exercise and/or hyperbaric oxygen treatment in mice with diet‑induced diabetes

“…GSH is irreversibly utilized when its product of oxidation (GSSG) is not recycled into GSH by glutathione reductase (15). The erythrocyte GSH levels are lower in patients with type 2 diabetes (16,17) and there are reports that have shown that GSH production gradually decreases in patients with diabetes with complications (18,19), and that this decrease is dependent on the degree of hyperglycemia (20). In a recent study it was shown that a high-fat diet resulted in GSH deficiency in the kidney of mice (21).…”

Glutathione Supplementation as an Adjunctive Therapy in COVID-19

“…Liposomal glutathione has been demonstrated to be able to augment Th1 cytokine response in patients suffering from HIV and M. tb infections [ 58 ]. Intracellular GSH concentration in erythrocytes is shown to be diminished in patients with type II diabetes [ 129 ]. Thus, we would expect these high-risk or immunocompromised populations to benefit in particular from liposomal GSH supplementation.…”