Identification and validation of serum amino acids as diagnostic biomarkers for diabetic peripheral neuropathy

doi:10.4239/wjd.v16.i6.105592

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World Journal of Diabetes

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World J Diabetes. Jun 15, 2025; 16(6): 105592
Published online Jun 15, 2025. doi: 10.4239/wjd.v16.i6.105592

Table 1 Clinical characteristics of the participants in the two cohorts, n (%)

Variable	Training cohort			Validation cohort
Variable	DPN	T2DM	Normal	DPN	T2DM	Normal
n	84	82	50	112	93	58
Age (years)	63.74 ± 11.51	61.28 ± 14.68	61.96 ± 15.68	64.38 ± 11.34	62.98 ± 11.53	66.59 ± 15.82
Male	50 (59.52)	41 (50)	23 (46)	61 (54.46)	49 (52.69)	25 (43.10)
Diabetes duration (years)	11.87 ± 6.92^a	9.33 ± 6.86		12.35 ± 7.14^a	9.68 ± 6.78
BMI (kg/m²)	24.49 ± 4.16	24.72 ± 3.64	23.97 ± 3.78	24.83 ± 3.67	24.54 ± 3.29	24.02 ± 3.34
Hypertension	47 (55.95)	44 (53.66)	20 (40)	64 (57.14)	51 (54.84)	29 (50)
SBP (mmHg)	133.20 ± 12.61	133.46 ± 14.33	130.52 ± 10.80	133.31 ± 12.02	134.67 ± 12.40	131.22 ± 10.11
DBP (mmHg)	75.17 ± 9.92	75.38 ± 10.85	73.92 ± 10.07	75.08 ± 9.56	75.68 ± 8.99	75.84 ± 9.75
FT3 (pmol/L)	4.78 ± 0.65	4.80 ± 0.61	4.77 ± 0.91	4.68 ± 0.74	4.72 ± 0.73	4.60 ± 0.79
FT4 (pmol/L)	16.53 ± 2.18	16.48 ± 1.68	16.65 ± 2.52	16.49 ± 2.48	16.51 ± 2.46	16.70 ± 2.52
TSH (mIU/L)	1.94 ± 0.99	1.86 ± 0.92	2.08 ± 1.17	2.01 ± 1.04	2.10 ± 2.25	2.17 ± 1.00
ALB (g/L)	38.95 ± 3.41^b	39.54 ± 3.53^c	41.52 ± 4.17	38.74 ± 3.88^b	39.40 ± 3.53	41.04 ± 5.17
ALT (U/L)	20.63 ± 7.91	21.42 ± 8.52	20.89 ± 6.99	21.98 ± 9.33	21.06 ± 8.54	20.36 ± 8.05
AST (U/L)	20.79 ± 5.02	20.20 ± 5.15	21.26 ± 4.30	20.87 ± 5.43	20.65 ± 4.96	20.75 ± 4.81
Scr (μmol/L)	68.92 ± 14.28	66.17 ± 12.16	65.00 ± 12.99	67.46 ± 13.78	67.47 ± 12.05	64.90 ± 13.46
GFR (mL/minute/1.73 m²)	99.36 ± 9.20	101.17 ± 9.80	101.72 ± 10.83	99.06 ± 9.24	100.10 ± 9.40	100.82 ± 9.44
UA (mmol/L)	326.96 ± 92.50	322.86 ± 107.13	330.95 ± 94.19	332.44 ± 96.06	338.70 ± 98.43	329.08 ± 102.57
FBG (mmol/L)	8.24 ± 3.19^b	7.59 ± 2.77^c	6.08 ± 2.03	8.23 ± 3.93^b	7.67 ± 2.93^c	5.78 ± 1.69
TG (mmol/L)	1.65 ± 1.36	1.86 ± 1.25	1.62 ± 0.58	1.62 ± 1.32	1.58 ± 0.97	1.67 ± 0.47
HDL (mmol/L)	1.03 ± 0.22^b	1.01 ± 0.21^c	1.14 ± 0.20	1.07 ± 0.25	1.03 ± 0.26	1.11 ± 0.23
LDL (mmol/L)	2.75 ± 1.16	2.57 ± 0.87	2.45 ± 0.92	2.64 ± 1.01	2.77 ± 0.91	2.70 ± 0.94
HbA1c (%)	9.31 ± 2.43^b	8.68 ± 1.92^c	5.49 ± 0.46	9.23 ± 2.25^b	8.92 ± 2.42^c	5.37 ± 0.41
BNP (pg/mL)	34.55 ± 17.83	32.42 ± 14.29	35.72 ± 17.14	34.50 ± 20.54	35.09 ± 15.46	37.14 ± 21.84

^aP < 0.05, comparison of diabetic peripheral neuropathy (DPN) patients with type 2 diabetes mellitus (T2DM) patients were significantly different.

^bP < 0.05, comparison of DPN patients with normal controls were significantly different.

^cP < 0.05, comparison of T2DM patients with normal controls were significantly different.

AUC: Area under the curve; T2DM: Type 2 diabetes mellitus; DPN: Diabetic peripheral neuropathy; TC: Training cohort; VC: Validation cohort; BMI: Body mass index; SBP: Systolic blood pressure; DBP: Diastolic blood pressure; FT3: Free triiodothyronine; FT4: Free thyroxine; TSH: Thyroid stimulating hormone; ALB: Albumin; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; Scr: Serum creatinine; GFR: Glomerular filtration rate; UA: Uric acid; FBG: Fasting blood glucose; TG: Triglyceride; HDL: High-density lipoprotein; LDL: Low-density lipoprotein; HbA1c: Glycated hemoglobin A1c; BNP: Brain natriuretic peptide.

Table 2 Serum levels of twenty amino acids among diabetic peripheral neuropathy patients, type 2 diabetes mellitus patients and normal individuals in the two cohorts

Variable	Training cohort			Validation cohort
Variable	DPN	T2DM	Normal	DPN	T2DM	Normal
Number	84	82	50	112	93	58
Glycine (μmol/L)	214.10 ± 50.54	216.41 ± 54.63	211.89 ± 58.25	221.68 ± 52.99	222.36 ± 54.04	219.34 ± 48.68
Serine (μmol/L)	121.10 ± 23.46	122.02 ± 24.47	121.12 ± 25.73	119.64 ± 25.01	120.37 ± 23.59	119.69 ± 28.05
Asparagine (μmol/L)	46.16 ± 12.30	47.80 ± 13.41	46.83 ± 10.54	45.61 ± 11.60	46.49 ± 14.25	44.85 ± 9.45
Arginine (μmol/L)	29.28 ± 12.61^a^,^b	40.87 ± 15.21^c	52.37 ± 11.73	27.44 ± 12.61^a^,^b	39.11 ± 12.64^c	55.55 ± 15.48
Alanine (μmol/L)	423.49 ± 121.55	429.40 ± 132.01	460.38 ± 137.59	442.13 ± 107.48	431.17 ± 137.76	451.38 ± 135.83
Homoproline (μmol/L)	28.37 ± 10.15^b	29.84 ± 12.01^c	21.73 ± 7.11	28.30 ± 10.28^b	29.14 ± 9.97^c	20.07 ± 6.90
Proline (μmol/L)	221.19 ± 79.16	223.31 ± 77.11	215.75 ± 82.67	235.44 ± 83.14	236.59 ± 96.97	238.85 ± 86.01
Valine (μmol/L)	276.17 ± 83.42^b	291.84 ± 89.69^c	239.45 ± 40.91	282.59 ± 88.93^b	280.52 ± 94.10^c	240.93 ± 60.67
Methionine (μmol/L)	25.91 ± 9.51	25.69 ± 8.81	25.32 ± 6.73	25.11 ± 8.83	27.13 ± 9.11	25.96 ± 7.74
Tyrosine (μmol/L)	65.77 ± 21.19^a^,^b	78.88 ± 20.77	77.39 ± 23.50	64.41 ± 20.13^a^,^b	74.66 ± 22.64	75.66 ± 16.40
Phenylalanine (μmol/L)	71.55 ± 16.70	72.38 ± 14.26	72.35 ± 15.88	71.81 ± 14.25	72.94 ± 16.05	70.58 ± 14.97
Isoleucine (μmol/L)	84.24 ± 27.50^b	86.90 ± 22.27^c	72.19 ± 24.26	83.39 ± 26.38^b	84.29 ± 24.99^c	70.21 ± 21.54
Leucine (μmol/L)	158.37 ± 31.22^b	164.74 ± 28.92^c	139.76 ± 26.81	153.83 ± 33.57^b	160.42 ± 30.52^c	132.30 ± 33.26
Hydroxyproline (μmol/L)	15.85 ± 5.75	15.39 ± 5.81	13.56 ± 5.57	15.35 ± 6.06	15.05 ± 6.48	16.74 ± 7.30
Threonine (μmol/L)	129.93 ± 30.88	129.25 ± 27.54	126.58 ± 31.02	122.08 ± 29.83	124.13 ± 28.55	126.92 ± 29.13
Tryptophane (μmol/L)	70.48 ± 29.87	66.63 ± 28.17	66.52 ± 25.53	67.34 ± 26.72	72.24 ± 26.78	67.85 ± 26.64
Glutamic acid (μmol/L)	186.17 ± 49.22^a^,^b	170.51 ± 37.05	156.29 ± 31.89	185.28 ± 48.05^a^,^b	169.88 ± 44.30	163.73 ± 35.35
Aspartic acid (μmol/L)	12.23 ± 4.53	11.82 ± 4.35	11.34 ± 3.35	11.45 ± 3.93	11.90 ± 4.36^c	10.11 ± 3.02
Histidine (μmol/L)	89.34 ± 14.46	92.49 ± 15.19^c	85.45 ± 12.98	89.37 ± 14.93	89.04 ± 17.64	85.43 ± 14.38
Lysine (μmol/L)	209.86 ± 54.74^b	203.83 ± 60.96	181.47 ± 39.72	191.68 ± 49.90	195.68 ± 55.03^c	174.38 ± 40.86

^aP < 0.05, comparison of diabetic peripheral neuropathy (DPN) patients with type 2 diabetes mellitus (T2DM) patients was significantly different.

^bP < 0.05, comparison of DPN patients with normal controls was significantly different.

^cP < 0.05, comparison of T2DM patients with normal controls was significantly different.

T2DM: Type 2 diabetes mellitus; DPN: Diabetic peripheral neuropathy.

Table 3 Backward stepwise logistic analysis of diabetic peripheral neuropathy and type 2 diabetes mellitus patients

Variables	Β	SE	Wald	P value
Arginine	-0.062	0.014	18.786	< 0.001
Tyrosine	-0.028	0.009	9.782	0.002
Glutamic acid	0.01	0.004	4.728	0.03
Duration	0.06	0.027	4.765	0.029
Constant	1.896	1.189	2.54	0.111

Table 4 Backward stepwise logistic analysis of type 2 diabetes mellitus patients and normal controls

Variables	β	SE	Wald	P value
Arginine	-0.072	0.019	14.218	< 0.001
Homoproline	0.06	0.027	4.808	0.028
Valine	0.01	0.004	6.879	0.009
Leucine	0.027	0.01	7.975	0.005
Glucose	0.246	0.109	5.047	0.025
Constant	-6.046	1.87	10.45	0.001

Citation: Xu WS, Xing H, Wang QQ, Qi H, He JT, Jin T, Kan YP, Sun SY, Wang JY, Lin FQ. Identification and validation of serum amino acids as diagnostic biomarkers for diabetic peripheral neuropathy. World J Diabetes 2025; 16(6): 105592
URL: https://www.wjgnet.com/1948-9358/full/v16/i6/105592.htm
DOI: https://dx.doi.org/10.4239/wjd.v16.i6.105592