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. 2018 Jun 7;13(6):e0198626.
doi: 10.1371/journal.pone.0198626. eCollection 2018.

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

Fallon K Lutchmansingh  1 , Jean W Hsu  2 , Franklyn I Bennett  3 , Asha V Badaloo  4 , Norma McFarlane-Anderson  1 , Georgiana M Gordon-Strachan  5 , Rosemarie A Wright-Pascoe  6 , Farook Jahoor  2 , Michael S Boyne  4   6
Affiliations

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

Fallon K Lutchmansingh et al. PLoS One. .

Abstract

Aims/hypotheses: We 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.

Methods: In 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.

Results: Compared 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).

Conclusions: Compared 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.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1
(A-C). Glutathione metabolism in non-diabetic controls, diabetic patients without microvascular complications, and diabetic patients with complications. Notes: Data are means ± SD. * P < 0.01 compared to controls; ** P < 0.001 compared to controls.
Fig 2
Fig 2
Scatterplots of fasting blood glucose with glutathione concentration in erythrocytes (A) and absolute synthetic rate (B).
Fig 3
Fig 3
Scatterplots of HbA1c with glutathione concentration in erythrocytes (A) and absolute synthetic rate (B).
See this image and copyright information in PMC

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