The Role of Serum Methylglyoxal and Glyoxalase 1 on Diabetic Peripheral Neuropathy

Diabetic neuropathy (DN) is a characteristic microvascular complication linked to diabetes. It affects about 50% of those who have this ailment. It has been revealed that Advanced Glycation End Products (AGEs) play a role in the development of diabetic neuropathy. Patients diagnosed with type 2 diabetes (T2DM) have higher quantities of methylglyoxal (MG), particularly harmful precursor of AGEs. One of the numerous defensive mechanisms responsible for MG metabolism and prevention of the generation of AGEs is the glyoxalase system. The cytotoxic byproduct methylglyoxal (MG) is removed by the detoxifying enzyme glyoxalase 1 (GLO1) via converting it to D-lactate, which is not harmful to tissues. This study intends to unveil the role of serum methylglyoxal and glyoxalase 1 on the onset of diabetic peripheral neuropathy (DPN). The present research was designed as a case-control study; including 160 individuals (males and females) aged (30-60) years. The subjects were divided into three groups: group one includes 40 type 2 diabetic patients with peripheral neuropathy, group two includes 40 type 2 diabetic patients without peripheral neuropathy and group three includes 80 apparently healthy as the control. Blood specimens were collected from all patients conducted at the National Diabetes Center, Mustansiriyah University in Baghdad, Iraq. Serum was used to measure glyoxalase 1 and Methylglyoxal levels using Enzyme-Linked Immunosorbent Assay (ELISA) technique. Whole blood with ethylene diamine tetraacetic acid (EDTA) was employed to measure glycated hemoglobin (HbA1c) levels with standard biochemical technique (the CLOVER system).  Anthropometric measurements, such as height, weight, BMI and duration of diabetes were assessed. Individuals in control group showed higher serum level of glyoxalase 1 (26.4±4.06 ng/ml) than either patients with DPN (13.61±2.22 ng/ml) or patients with T2DM without peripheral neuropathy (15.25±1.68 ng/ml) with highly significant differences. In contrast, patients with DPN demonstrated higher level of methylglyoxal (29.45±6.06 ng/ ml) than either patients with T2DM without peripheral neuropathy (23.76±5.66 ng/ml) or controls (14.04±4.46 ng/ml) with highly significant differences.  In the context of Discrimination between Diabetic Peripheral Neuropathy and Diabetes Mellitus without Peripheral Neuropathy, glyoxalase 1 has an area under curve (AUC) of 0.776, 95% confidence interval [CI] been 0.671-0.882. The test's sensitivity and specificity were 73% and 72%, respectively, at the cut-off value of serum glyoxalase 1 = 13.94 ng/ml. The area under curve for methylglyoxal was 0.758, 95% confidence interval was 0.654-0.863, p < 0.001. The test's sensitivity and specificity were 63% and 70%, respectively; at a cut-off value of serum methylglyoxal = 27.57ng/ml. In the context of discrimination between DPN and controls, the area under curve for glyoxalase 1 was 0.997, 95% confidence interval was 0.992-1.0, p<0.001. Sensitivity and specificity were 99% and 97%, respectively, at a cut-off value of serum glyoxalase 1 = 19.45 ng/ml. The area under curve for methylglyoxal was 0.977, 95% confidence interval was 0.965-0.997, p<0.001. Sensitivity and specificity were 93% and 90%, respectively, at a cut-off value of serum methylglyoxal = 20.81 ng/ml. The findings demonstrated that decreased glyoxalase 1 levels and elevated serum methylglyoxal levels are contributing factors to the development of diabetic peripheral neuropathy in the group of patients under study.