J Endocrinol Metab

Journal of Endocrinology and Metabolism, ISSN 1923-2861 print, 1923-287X online, Open Access

Article copyright, the authors; Journal compilation copyright, J Endocrinol Metab and Elmer Press Inc

Journal website https://jem.elmerpub.com

Original Article

Volume 16, Number 2, April 2026, pages 118-127

Neuroprotective and Neurodegenerative Markers in the Early Detection of Peripheral Neuropathy in Type 2 Diabetes Patients

↓ Figure 1. Box-whisker plots of serum (a) fibroblast growth factor 1 (FGF1), (b) heat shock protein 27 (HSP27), (c) semaphorin3A (Sema3A), and (d) nerve filament light chain (NFL) levels in diabetic neuropathy, diabetic patients, and control groups.

↓ Figure 2. Receiver operating characteristic (ROC) analyses for fibroblast growth factor 1 (FGF1), heat shock protein 27 (HSP27), semaphorin3A (Sema3A), and nerve filament light chain (NFL).

↓ **Table 1.** Clinical Characteristic Feature
Variable	Patients with DPN	Patients with DWN	Control
DPN: diabetic peripheral neuropathy; DWN: diabetic without neuropathy; SD: standard deviation.
Age, years (mean ± SD)	54.04 ± 8.345	47.44 ± 6.364	44.51 ± 6.291
Weight, kg (mean ± SD)	83.56 ± 14.995	85.31 ± 11.554	87.80 ± 13.069
Height, cm (mean ± SD)	168.33 ± 9.283	168.58 ± 7.911	175.87 ± 6.897
Duration of diabetes mellitus, years	5.32 ± 6.561	3.04 ± 2.518
HbA1c, % (mmol/mol) (mean ± SD)	9.3±1.9% (78 ± 21)	7.7±1.6% (60 ± 17)
Smoking
Yes	12 (26.7%)	10 (20.8%)	24 (53.3%)
No	33 (73.3%)	38 (79.2%)	21 (46.7%)
Pain sensation
Yes	7 (15.6%)
No	38 (84.8%)	48 (100%)	45 (100%)
Weakness
Yes	9 (20%)
No	36 (80%)	48 (100%)	45 (100%)
Numbness
Yes	40 (88.9%)
No	5 (11.1%)	48 (100%)	45 (100%)
Burning sensation
Yes	25 (55.6%)
No	20 (44.4%)	48 (100%)	45 (100%)
Family history
Yes	31 (68.9%)	23 (47.9%)
No	14 (31.1%)	25 (52.1%)	45 (100%)
Education
Primary	27 (60%)	18 (37.5%)	12 (26.7%)
Secondary	15 (33.1%)	22 (45.8%)	19 (42.3%)
Diploma	1 (2.3%)	3 (6.3%)	8 (17.8%)
Bachelor	2 (4.6%)	5 (10.4%)	6 (13.2%)
Severity of neuropathy
Mild	15 (37.7)
Moderate to severe	30 (62.3%)
Body mass index
Normal	11.1%	8.3%	17.8%
Overweight	40%	52.1%	48.9%
Obese class I	44.4%	25%	28.9%
Obese class II	4.5%	14.6%	4.4%

↓ Table 1. Clinical Characteristic Feature

Variable

Patients with DPN

Patients with DWN

Control

DPN: diabetic peripheral neuropathy; DWN: diabetic without neuropathy; SD: standard deviation.

Age, years (mean ± SD)

54.04 ± 8.345

47.44 ± 6.364

44.51 ± 6.291

Weight, kg (mean ± SD)

83.56 ± 14.995

85.31 ± 11.554

87.80 ± 13.069

Height, cm (mean ± SD)

168.33 ± 9.283

168.58 ± 7.911

175.87 ± 6.897

Duration of diabetes mellitus, years

5.32 ± 6.561

3.04 ± 2.518

HbA1c, % (mmol/mol) (mean ± SD)

9.3±1.9% (78 ± 21)

7.7±1.6% (60 ± 17)

Smoking

Yes

12 (26.7%)

10 (20.8%)

24 (53.3%)

33 (73.3%)

38 (79.2%)

21 (46.7%)

Pain sensation

Yes

7 (15.6%)

38 (84.8%)

48 (100%)

45 (100%)

Weakness

Yes

9 (20%)

36 (80%)

48 (100%)

45 (100%)

Numbness

Yes

40 (88.9%)

5 (11.1%)

48 (100%)

45 (100%)

Burning sensation

Yes

25 (55.6%)

20 (44.4%)

48 (100%)

45 (100%)

Family history

Yes

31 (68.9%)

23 (47.9%)

14 (31.1%)

25 (52.1%)

45 (100%)

Education

Primary

27 (60%)

18 (37.5%)

12 (26.7%)

Secondary

15 (33.1%)

22 (45.8%)

19 (42.3%)

Diploma

1 (2.3%)

3 (6.3%)

8 (17.8%)

Bachelor

2 (4.6%)

5 (10.4%)

6 (13.2%)

Severity of neuropathy

Mild

15 (37.7)

Moderate to severe

30 (62.3%)

Body mass index

Normal

11.1%

8.3%

17.8%

Overweight

40%

52.1%

48.9%

Obese class I

44.4%

25%

28.9%

Obese class II

4.5%

14.6%

4.4%

↓ **Table 2.** Concentration of FGF1, HSP27, Sema3, and NFL in DPN and Control Groups
Parameters	Patients with DPN, median (range)	Control, median (range)	P value	OR	95% CI
CI: confidence interval; DPN: diabetic peripheral neuropathy; FGF1: fibroblast growth factor 1; HSP27: heat shock protein 27; NFL: nerve filament light chain; OR: odd ratio; Sema3A: semaphorin3A.
FGF1, ng/mL	505 (582)	434 (797)	0.370	0.998	0.994	1.002
HSP27, ng/mL	45 (64.77)	37.42 (47.12)	0.003	1.112	1.036	1.194
Sema3A, ng/mL	2.47 (3.64)	1.43 (3.18)	0.034	3.207	1.094	9.395
NFL, ng/mL	5.64 (9.04)	4.79 (5.53)	0.029	1.590	1.048	2.41

↓ Table 2. Concentration of FGF1, HSP27, Sema3, and NFL in DPN and Control Groups

Parameters

Patients with DPN, median (range)

Control, median (range)

P value

95% CI

Lower bound

Upper bound

CI: confidence interval; DPN: diabetic peripheral neuropathy; FGF1: fibroblast growth factor 1; HSP27: heat shock protein 27; NFL: nerve filament light chain; OR: odd ratio; Sema3A: semaphorin3A.

FGF1, ng/mL

505 (582)

434 (797)

0.370

0.998

0.994

1.002

HSP27, ng/mL

45 (64.77)

37.42 (47.12)

0.003

1.112

1.036

1.194

Sema3A, ng/mL

2.47 (3.64)

1.43 (3.18)

0.034

3.207

1.094

9.395

NFL, ng/mL

5.64 (9.04)

4.79 (5.53)

0.029

1.590

1.048

2.41

↓ **Table 3.** Concentration of FGF1, HSP27, Sema3A, NFL in the DPN and DWN Groups
Parameters	Patients with DPN, median (range)	Patients with DWN, median (range)	P value	OR	95% CI
CI: confidence interval; DPN: diabetic peripheral neuropathy; DWN: diabetic without neuropathy; FGF1: fibroblast growth factor 1; HSP27: heat shock protein 27; NFL: nerve filament light chain; OR: odd ratio; Sema3A: semaphorin3A.
FGF1, ng/mL	505 (582)	481.5 (1,025)	0.609	0.990	0.984	0.996
HSP27, ng/mL	45 (64.77)	40.45 (59.70)	0.016	1.064	0.982	1.152
Sema3A, ng/mL	2.47 (3.64)	1.66 (2.89)	0.027	1.996	1.517	2.074
NFL, ng/mL	5.64 (9.04)	5.37 (24.95)	0.360	0.864	0.625	1.195

↓ Table 3. Concentration of FGF1, HSP27, Sema3A, NFL in the DPN and DWN Groups

Parameters

Patients with DPN, median (range)

Patients with DWN, median (range)

P value

95% CI

Lower bound

Upper bound

CI: confidence interval; DPN: diabetic peripheral neuropathy; DWN: diabetic without neuropathy; FGF1: fibroblast growth factor 1; HSP27: heat shock protein 27; NFL: nerve filament light chain; OR: odd ratio; Sema3A: semaphorin3A.

FGF1, ng/mL

505 (582)

481.5 (1,025)

0.609

0.990

0.984

0.996

HSP27, ng/mL

45 (64.77)

40.45 (59.70)

0.016

1.064

0.982

1.152

Sema3A, ng/mL

2.47 (3.64)

1.66 (2.89)

0.027

1.996

1.517

2.074

NFL, ng/mL

5.64 (9.04)

5.37 (24.95)

0.360

0.864

0.625

1.195

↓ **Table 4.** Concentration of Parameters Under Study With Respect to Severity in Patients With DPN
Parameters	DPN patients	P-value
DPN: diabetic peripheral neuropathy; FGF1: fibroblast growth factor 1; HSP27: heat shock protein 27; N: number of samples; NFL: nerve filament light chain; Sema3A: semaphorin3A.
FGF1, ng/mL	771 (544)	475.5 (582)	0.008
HSP27, ng/mL	40.9 (25.61)	47.12 (57.95)	0.029
Sema3A, ng/mL	2.62 (2.15)	1.86 (3.64)	0.198
NFL, ng/mL	5.63 (4.7)	5.79 (8.03)	0.152

↓ Table 4. Concentration of Parameters Under Study With Respect to Severity in Patients With DPN

Parameters

DPN patients

P-value

Mild (N = 15), median (range)

Moderate to severe (N = 30), median (range)

DPN: diabetic peripheral neuropathy; FGF1: fibroblast growth factor 1; HSP27: heat shock protein 27; N: number of samples; NFL: nerve filament light chain; Sema3A: semaphorin3A.

FGF1, ng/mL

771 (544)

475.5 (582)

0.008

HSP27, ng/mL

40.9 (25.61)

47.12 (57.95)

0.029

Sema3A, ng/mL

2.62 (2.15)

1.86 (3.64)

0.198

NFL, ng/mL

5.63 (4.7)

5.79 (8.03)

0.152

↓ **Table 5.** Associations Between the Parameters Under Study and Diabetic Neuropathy
Parameters	β	P-value	OR	95% CI
β coefficient (per unit increase in serum biomarker level; ng/mL). CI: confidence interval; FGF1: fibroblast growth factor 1; HSP27: heat shock protein 27; NFL: nerve filament light chain; OR: odd ratio; Sema3A: semaphorin3A.
FGF1, ng/mL	−0.010	< 0.001	0.990	0.985	0.995
HSP27, ng/mL	1.052	0.112	1.053	0.988	1.123
Sema3A, ng/mL	3.007	< 0.001	6.223	4.327	9.512
NFL, ng/mL	−0.087	0.530	0.917	0.699	1.203

↓ Table 5. Associations Between the Parameters Under Study and Diabetic Neuropathy

Parameters

P-value

95% CI

Lower bound

Upper bound

β coefficient (per unit increase in serum biomarker level; ng/mL). CI: confidence interval; FGF1: fibroblast growth factor 1; HSP27: heat shock protein 27; NFL: nerve filament light chain; OR: odd ratio; Sema3A: semaphorin3A.

FGF1, ng/mL

−0.010

< 0.001

0.990

0.985

0.995

HSP27, ng/mL

1.052

0.112

1.053

0.988

1.123

Sema3A, ng/mL

3.007

< 0.001

6.223

4.327

9.512

NFL, ng/mL

−0.087

0.530

0.917

0.699

1.203

↓ **Table 6.** Association Between Variables (Age, Duration, BMI) and Diabetic Neuropathy
Variables	β	P-value	OR	95% CI
BMI: body mass index; CI: confidence interval; OR: odds ratio.
Age	0.129	< 0.001	1.137	1.061	1.219
Duration	0.589	< 0.001	1.802	1.430	2.270
BMI	−0.041	0.432	0.960	0.867	1.063

↓ Table 6. Association Between Variables (Age, Duration, BMI) and Diabetic Neuropathy

Variables

P-value

95% CI

Lower

Upper

BMI: body mass index; CI: confidence interval; OR: odds ratio.

Age

0.129

< 0.001

1.137

1.061

1.219

Duration

0.589

< 0.001

1.802

1.430

2.270

BMI

−0.041

0.432

0.960

0.867

1.063

↓ **Table 7.** Coordinates of ROC Curve for Serum FGF1, HSP27, Sema3A, and NFL
Parameters	FGF1	HSP27	Sema3A	NFL
AUC: area under the curve; CI: confidence interval; FGF1: fibroblast growth factor 1; HSP27: heat shock protein 27; NFL: nerve filament light chain; ROC: receiver operating characteristic; Sema3A: semaphorin3A.
AUC	0.469	0.746	0.783	0.625
Cutoff value	476.5	40.113	1.493	4.919
Sensitivity	60%	75.6%	80%	73.3%
Specificity	56.3%	54.4%	60%	68.8%
95% CI	0.350–0.588	0.534–0.758	0.521–746	0.437–674
Accuracy	57.5%	61.3%	66.5%	70.3%

↓ Table 7. Coordinates of ROC Curve for Serum FGF1, HSP27, Sema3A, and NFL

Parameters

FGF1

HSP27

Sema3A

NFL

AUC: area under the curve; CI: confidence interval; FGF1: fibroblast growth factor 1; HSP27: heat shock protein 27; NFL: nerve filament light chain; ROC: receiver operating characteristic; Sema3A: semaphorin3A.

AUC

0.469

0.746

0.783

0.625

Cutoff value

476.5

40.113

1.493

4.919

Sensitivity

60%

75.6%

80%

73.3%

Specificity

56.3%

54.4%

60%

68.8%

95% CI

0.350–0.588

0.534–0.758

0.521–746

0.437–674

Accuracy

57.5%

61.3%

66.5%

70.3%