Complications in type 2 diabetes (T2D) arise from hyperglycemia-induced oxidative stress. Here, we examined the effectiveness of supplementation with the endogenous antioxidant glutathione (GSH) during anti-diabetic treatment. A total of 104 non-diabetic and 250 diabetic individuals on anti-diabetic therapy, of either sex and aged between 30 and 78 years, were recruited. A total of 125 diabetic patients were additionally given 500 mg oral GSH supplementation daily for a period of six months. Fasting and PP glucose, insulin, HbA1c, GSH, oxidized glutathione (GSSG), and 8-hydroxy-2-deoxy guanosine (8-OHdG) were measured upon recruitment and after three and six months of supplementation. Statistical significance and effect size were assessed longitudinally across all arms. Blood GSH increased (Cohen’s d = 1.01) and 8-OHdG decreased (Cohen’s d = −1.07) significantly within three months (p < 0.001) in diabetic individuals. A post hoc sub-group analysis showed that HbA1c (Cohen’s d = −0.41; p < 0.05) and fasting insulin levels (Cohen’s d = 0.56; p < 0.05) changed significantly in diabetic individuals above 55 years. GSH supplementation caused a significant increase in blood GSH and helped maintain the baseline HbA1c overall. These results suggest GSH supplementation is of considerable benefit to patients above 55 years, not only supporting decreased glycated hemoglobin (HbA1c) and 8-OHdG but also increasing fasting insulin. The clinical implication of our study is that the oral administration of GSH potentially complements anti-diabetic therapy in achieving better glycemic targets, especially in the elderly population.
Sustained hyperglycemia in type 2 diabetes is associated with low levels of the endogenous antioxidant glutathione (GSH), which leads to oxidative stress and tissue damage. It is therefore important to investigate whether oral GSH supplementation would restore GSH levels, and also help improve redox state and glycaemia in diabetic individuals. We conducted a pragmatic clinical trial to assess effectiveness of oral GSH supplementation along with anti-diabetic treatment. 104 non-diabetic and 250 diabetic individuals were recruited. All the 250 diabetic individuals were on anti-diabetic therapy; of these 125 were given oral GSH supplementation additionally for a period of six months. Fasting and PP glucose and insulin, HbA1c, GSH and the oxidative DNA damage marker 8-OHdG were measured at the recruitment time and after three and six months of supplementation. GSH supplementation increased blood GSH and decreased 8-OHdG significantly within three months in diabetic individuals. It also reduced HbA1c within three months and stabilized it thereafter in diabetic population overall. Patients above 55 years benefited more as evidenced by a significant decrease in HbA1c and 8-OHdG and an increase in fasting insulin. Data suggest that GSH supplementation can be used as an adjunct therapy to anti-diabetic treatment to achieve better glycemic targets, especially in elderly population.
Oral GSH supplementation along with antidiabetic treatment was shown to restore the body stores of GSH significantly and reduce oxidative DNA damage (8-OHdG) in Indian Type 2 diabetic (T2D) patients over 6 months in our recent clinical study. Post hoc analysis of the data also suggested that elder patients benefit from improved HbA1c and fasting insulin. We modeled longitudinal changes in diabetic individuals using a linear mixed-effects (LME) framework and obtained i) the distribution of individual trajectories with and without GSH supplementation and ii) the overall rates of changes in the different study arms. Serial changes in elder and younger diabetic individuals were also modeled independently to examine differences in their progression. The average linear trajectories obtained from the model explain how biochemical parameters in T2D patients progress over 6 months on GSH supplementation. Model estimates show improvements in erythrocytic GSH of 108 µM per month and a reduction in 8-OHdG at a rate of 18.5 ng/μg DNA per month in T2D patients. GSH replenishes faster in younger people than in the elder. 8-OHdG reduced more rapidly in the elder (24 ng/μg DNA per month) than in younger (12 ng/μg DNA per month) individuals. Interestingly, elder individuals show a substantial reduction in HbA1c (0.1% per month) and increased fasting insulin (0.6 µU/mL per month). Changes in GSH correlate strongly with changes in HbA1c, 8-OHdG, and fasting insulin in the elder cohort. The model estimates strongly suggest it improves the rate of replenishment in erythrocytic GSH stores and reduces oxidative DNA damage. Elder and younger T2D patients respond differently to GSH supplementation: It improves the rate of reduction in HbA1c and increases fasting insulin in elder patients. These model forecasts have clinical implications that aid in personalizing treatment targets for using oral GSH as adjuvant therapy in diabetes.
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