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ARS Home » Plains Area » Houston, Texas » Children's Nutrition Research Center » Research » Publications at this Location » Publication #356083
Research Project: Pediatric Clinical Nutrition

Location: Children's Nutrition Research Center

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

Author
item LUTCHMANSINGH, FALLON - University Of The West Indies
item HSU, JEAN - Children'S Nutrition Research Center (CNRC)
item BENNETT, FRANKLYN - University Of The West Indies
item BADALOO, ASHA - University Of The West Indies
item MCFARLANE-ANDERSON, NORMA - University Of The West Indies
item GORDON-STRACHAN, GEORGIANA - University Of The West Indies
item WRIGHT-PASCOE, ROSEMARIE - University Of The West Indies
item JAHOOR, FAROOK - Children'S Nutrition Research Center (CNRC)
item BOYNE, MICHAEL - University Of The West Indies

Submitted to: PLOS ONE
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/22/2018
Publication Date: 6/7/2018
Citation: Lutchmansingh, F.K., Hsu, J.W., Bennett, F.I., Badaloo, A.V., McFarlane-Anderson, N., Gordon-Strachan, G.M., Wright-Pascoe, R.A., Jahoor, F., Boyne, M.S. 2018. Glutathione metabolism in type 2 diabetes and its relationship with microvascular complications and glycemia. PLoS One. 13(6):e0198626. https://doi.org/10.1371/journal.pone.0198626.
DOI: https://doi.org/10.1371/journal.pone.0198626

Interpretive Summary: When individuals with type 2 diabetes cannot control their sugar level and levels remain high for a long period, it may cause damage to small blood vessels in the body called microvascular complications, which includes damage to eyes, kidneys or nerves. In addition, it also increases the chances of damage to larger blood vessels, called macrovascular complications, which include heart attacks and strokes. individuals with type 2 diabetes also have a lower level of glutathione, which acts as an important antioxidant in our body. An antioxidant helps combat free radicals or oxidants or oxidative stress which are harmful chemicals produced in our bodies. High sugar levels in the bodies may increase oxidative stress. We wanted to find out how individuals with type 2 diabetes with and without microvascular complications produce glutathione in the bodies compared to healthy people. To solve this problem, we have developed methods called stable isotope tracer methods in which we can measure exactly how much glutathione is produced in the bodies. The results showed that the amount of glutathione produced in the bodies was lower in individuals with type 2 diabetes compared to healthy people and even lower in individuals with type 2 diabetes with microvascular complications. Thus, those with type 2 diabetes cannot make enough glutathione for body use, especially if they have microvascular complications.

Technical Abstract: 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. 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. 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). 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.