Altered thiol/disulfide homeostasis in patients with diabetes mellitus and its chronic complications

Aslanoğlu, Nuri; Keşkek, Şakir Özgür; Neşelioğlu, Salim; Eren, Funda

doi:10.20945/2359-4292-2025-0042

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Original • Arch. Endocrinol. Metab. 69 (5) • 2025 • https://doi.org/10.20945/2359-4292-2025-0042 linkcopy

Altered thiol/disulfide homeostasis in patients with diabetes mellitus and its chronic complications

Authorship SCIMAGO INSTITUTIONS RANKINGS

Objective: To evaluate the effect of diabetes mellitus and its chronic complications on thiol/disulfide homeostasis.

Methods: The study included 381 participants divided into six groups: healthy controls (Group 1; n = 91), patients with prediabetes (Group 2; n = 50), patients with diabetes mellitus without complications (Group 3; n = 70), patients with diabetic retinopathy (Group 4; n = 47), patients with diabetic nephropathy (Group 5; n = 70), and patients with diabetic foot (Group 6; n = 53). Thiol/disulfide homeostasis was determined by measuring the reduction reaction of oxidized thiols.

Results: Native thiol levels were low in patients with diabetes mellitus complications (Group 4, 264.7 ± 58.5 µmol/L; Group 5, 246.6 ± 67.5 µmol/L; Group 6, 174.3 ± 65.9 µmol/L), as were total thiol levels. The highest and lowest disulfide levels were observed in Group 1 (controls; 20.4 ± 5.2 µmol/L) and Group 6 (16.2 ± 5.7 µmol/L), respectively. The disulfide/native thiol ratio was increased in Groups 4, 5, and 6 compared with Groups 1, 2, and 3.

Conclusion: The presence of diabetes mellitus complications substantially decreased native thiol, total thiol, and disulfide levels.

Keywords:
Disulfides; Homeostasis; Diabetic angiopathies; Prediabetic state; Biomarkers

	Group 1 (n = 91)	Group 2 (n = 50)	Group 3 (n = 70)	Group 4 (n = 47)	Group 5 (n = 70)	Group 6 (n = 53)	p-values*
Sex, female	59 (64.8%)	24 (48%)	43 (61.4%)	32 (68.1%)	45 (64.3%)	32 (60.4%)	0.369
Age, years	49.4 ± 8.7	48.4 ± 10.4	50.0 ± 8.4	50.7 ± 5.6	51.8 ± 10.5	51.7 ± 6.4	0.250
BMI, kg/m²	26.7 ± 6.1	32.9 ± 7.6	32.2 ± 6.1	32.8 ± 6.0	32.0 ± 5.6	28.7 ± 5.9	0.914
HbA1c, %	5.3 ± 0.29	6.0 ± 0.3	8.9 ± 2.27	9.7 ± 2.49	9.8 ± 2.57	10.5 ± 2.33	0.001
HbA1c, mmol/mol	34.8 ± 4.8	42.2 ± 2.8	74.0 ± 25.1	82.7 ± 27.1	83.7 ± 28.0	92.3 ± 25.7	0.001
FPG, mg/dL	91.9 ± 8.6	105.9 ± 19.6	201.3 ± 93.2	235.5 ± 111.2	234.2 ± 110.7	301.0 ± 136.5	0.001
LDL cholesterol, mg/dL	116.6 ± 23.9	129.3 ± 51.9	125.9 ± 36.5	130.3 ± 44.5	136.6 ± 54.4	102.4 ± 36.3	0.001
Triglycerides, mg/dL	122.3 ± 60.7	173.4 ± 82.6	220.2 ± 197.6	223.5 ± 149.5	248.5 ± 188.2	196.0 ± 124.8	0.0001
HDL cholesterol, mg/dL	50.5 ± 11.7	46.3 ± 14.3	45.3 ± 8.4	39.4 ± 18.6	49.7 ± 16.4	34.9 ± 10.8	0.001
Creatinine, mg/dL	0.7 ± 0.1	0.7 ± 0.1	0.6 ± 0.2	0.7 ± 0.2	1.0 ± 0.8	1.3 ± 1.2	0.001
AST, U/L	19.6 ± 4.7	23.8 ± 5.8	23.3 ± 10.8	20.5 ± 8.9	20.9 ± 6.6	20.5 ± 29.7	< 0.0001
ALT, U/L	18.0 ± 8.7	24.9 ± 13.8	28.6 ± 18.0	21.7 ± 12.6	21.3 ± 10.3	16.9 ± 24.4	< 0.00001

	Group 1	Group 2	Group 3	Group 4	Group 5	Group 6	p-values*
Native thiol, µmol/L	331.3 ± 48.2	295.9 ± 51.5	300.6 ± 52.2	264.7 ± 58.5	246.6 ± 67.5	174.3 ± 65.9	0.016
Total thiol, µmol/L	372.3 ± 49.0	334.1 ± 51.7	338.0 ± 50.2	303.9 ± 57.4	282.5 ± 71.0	201.8 ± 67.1	0.004
Disulfide, µmol/L	20.4 ± 5.2	19.0 ± 6.1	18.7 ± 5.3	18.7 ± 3.7	18.5 ± 6.5	16.2 ± 5.7	0.029
Disulfide/native thiol, %	6.35 ± 2.07	6.7 ± 2.9	6.6 ± 3.2	7.4 ± 2.2	8.2 ± 4.2	10.4 ± 4.3	<0.001
Disulfide/total thiol, %	5.6 ± 1.6	5.8 ± 2.1	5.7 ± 2.2	6.4 ± 1.6	6.9 ± 2.7	6.4 ± 2.7	0.001
Native thiol/total thiol, %	88.8 ± 3.1	88.3 ± 4.2	88.5 ± 4.3	87.2 ± 3.2	86.2 ± 5.5	83.1 ± 5.5	0.001

	Group 1 (n = 91)	Group 2+3 (n = 120)	Group 4+5+6 (n = 170)	p-value*
Sex, female	59 (64.8%)	67 (55.8%)	98 (57.6%)	0.387
Age, years	49.4 ± 8.7	49.3 ± 9.3	51.5 ± 8.1	0.181
BMI, kg/m²	26.7 ± 6.1	32.5 ± 6.7	31.2 ± 6.0	< 0.0001
HbA1c, %	5.3 ± 0.3	7.7 ± 2.2	10.0 ± 2.4	< 0.0001
HbA1c, mmol/mol	34.8 ± 4.7	60.7 ± 24.8	86.1 ± 27.2	< 0.0001
FPG, mg/dL	91.9 ± 8.6	162.9 ± 85.2	255.4 ± 122.7	< 0.001
LDL cholesterol, mg/dL	116.6 ± 23.9	131.7 ± 36.8	126.4 ± 46.2	0.003
Triglycerides, mg/dL	122.3 ± 60.7	201.9 ± 163.7	225.0 ± 160.1	< 0.0001
HDL cholesterol, mg/dL	50.5 ± 11.7	45.7 ± 11.0	42.1 ± 16.7	0.00003
Creatinine, mg/dL	0.7 ± 0.1	0.7 ± 0.1	1.2 ± 0.9	< 0.0001
AST, U/L	19.6 ± 4.7	23.5 ± 9.1	21.0 ± 17.7	< 0.0001
ALT, U/L	18.0 ± 8.7	27.1 ± 16.5	20.0 ± 16.5	< 0.0001

	Group 1 (n = 91)	Group 2+3 (n = 120)	Group 4+5+6 (n = 170)	p-value*
Native thiol, µmol/L	331.3 ± 48.2	298.6 ± 51.8	229.0 ± 74.5	0.001
Total thiol, µmol/L	372.3 ± 49.0	336.4 ± 50.6	263.2 ± 78.3	0.001
Disulfide, µmol/L	20.4 ± 5.2	18.8 ± 5.6	17.8 ± 5.7	0.0003
Disulfide/native thiol, %	6.4 ± 2.0	6.6 ± 3.0	8.6 ± 3.9	< 0.0001
Disulfide/total thiol, %	5.6 ± 1.6	5.7 ± 2.1	7.2 ± 2.6	< 0.00001
Native thiol/total thiol, %	88.8 ± 3.1	88.5 ± 4.2	85.5 ± 5.2	< 0.00001

	Native thiol	Total thiol	Disulfide
Age	r = -0.250 p < 0.0001	r = -0.262 p < 0.0001	r = -0.08 p = 0.116
BMI	r = -0.123 p = 0.016	r = -0.097 p = 0.05	r = 0.027 p = 0.591
Diabetes duration	r = -0.571 p < 0.0001	r = -0.607 p < 0.0001	r = -0.218 p < 0.0001
FPG	r = -0.429 p < 0.001	r = -0.438 p < 0.001	r = -0.211 p < 0.001
HbA1c	r = -0.479 p < 0.001	r = -0.463 p < 0.001	r = -0.169 p = 0.0009

Independent variables	Coefficient	Standard error	t	p-values
Constant	517.3170
BMI, kg/m²	-1.5832	0.4398	-3.600	0.0004
HbA1c, %	-4.2072	1.2604	-3.338	0.0009
Diabetes duration, years	-2.2989	0.5244	-4.384	< 0.0001
Age, years	-1.7561	0.3350	-5.241	< 0.0001
Diabetic foot	-80.9199	9.2986	-8.702	< 0.0001
Nephropathy	-29.5381	7.7047	-3.834	0.0002

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Comparison among all groups.

[2] Results expressed as n (%) or mean ± standard deviation.

[3] Group 1: healthy control subjects; Group 2: individuals with prediabetes; Group 3: patients with diabetes mellitus without complications; Group 4: patients with diabetic retinopathy; Group 5: patients with diabetic nephropathy; Group 6: patients with diabetic foot ulcers.

[4] BMI: body mass index; HbA1c: glycated hemoglobin; FPG: fasting plasma glucose; LDL: low-density lipoprotein; HDL: high-density lipoprotein; AST: aspartate aminotransferase; ALT: alanine transaminase.