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Article

IGFBP1 as a metabolic‑neurodegenerative biomarker in spinocerebellar ataxia type 3

  • Authors:
    • Chungmin Chiu
    • Wenling Cheng
    • Tatsung Lin
    • Huiju Chang
    • Yujun Chang
    • Shihli Su
    • Chiaju Lee
    • Henhong Chang
    • Chinsan Liu
  • View Affiliations / Copyright

    Affiliations: Department of Chinese Medicine, Changhua Christian Hospital, Changhua 50006, Taiwan, R.O.C., Vascular and Genomic Center, Institute of ATP, Changhua Christian Hospital, Changhua 50006, Taiwan, R.O.C., Center of Regenerative Medicine and Tissue Repair, Institute of ATP, Changhua Christian Hospital, Changhua 50006, Taiwan, R.O.C., Big Data Center, Changhua Christian Hospital, Changhua 50006, Taiwan, R.O.C., Vascular Medicine and Diabetes Research Center, Institute of ATP, Changhua Christian Hospital, Changhua 50006, Taiwan, R.O.C., Department of Neurology, Changhua Christian Hospital, Changhua 50006, Taiwan, R.O.C., Graduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung 40447, Taiwan, R.O.C.
  • Article Number: 105
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    Published online on: February 10, 2026
       https://doi.org/10.3892/etm.2026.13100
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Abstract

Spinocerebellar ataxia type 3 (SCA3) is a progressive neurodegenerative disorder for which reliable metabolic biomarkers are lacking. Insulin‑like growth factor binding protein 1 (IGFBP1), a stress‑responsive protein regulated by insulin signaling, serves as an indicator of neurodegenerative burden. The present study aimed to measure the plasma levels of insulin, glucose, IGF1, IGF2, IGFBP1, IGFBP3 and neurofilament light chain (NfL) in patients with genetically confirmed SCA3 and age‑matched controls. In addition, the association between the above molecules and clinical severity were assessed using the scale for the Assessment and Rating of Ataxia score, body mass index (BMI) and NfL levels, whereas metabolic‑neurodegenerative interactions were assessed by stratifying patients by insulin tertiles. A total of 32 individuals with SCA3 and 36 age‑ and sex‑matched controls were enrolled in the current study. The results demonstrated that patients with SCA3 exhibited markedly elevated IGFBP1, IGF2 and free IGF1 levels, as well as reduced insulin and higher glucose‑to‑insulin ratios, thus indicating disrupted insulin signaling. IGFBP1 was positively associated with SARA score and NfL levels and negatively associated with BMI. Notably, patients in the lowest insulin tertile (<3.65 µIU/ml) showed significantly higher IGFBP1 and NfL levels compared with the remaining groups, thus suggesting that the insulin/IGFBP1/NfL axis was associated with ataxia severity. Collectively, IGFBP1 could be a promising peripheral biomarker reflecting both metabolic and neurodegenerative processes in SCA3 and could facilitate monitoring of disease stages.
View Figures

Figure 1

ROC curve analysis of IGFBP1 and
other insulin/IGF1 signaling-associated markers for distinguishing
early- and advanced-stage spinocerebellar ataxia type 3. ROC,
receiver operating characteristic; IGF, insulin-like growth factor;
IGFBP, IGF binding protein.

Figure 2

Correlation between plasma IGFBP1 and
clinical parameters. Spearman's correlation analyses between IGFBP1
and (A) scale for the assessment and rating of ataxia, (B)
neurofilament light chain, (C) body mass index and (D) CAG repeat
length in patients with spinocerebellar ataxia type 3. IGFBP1,
insulin-like growth factor binding protein 1; SARA, scale for the
assessment and rating of ataxia; NFL, neurofilament light chain;
BMI, body mass index.

Figure 3

Associations between insulin levels,
NfL and IGFBP1 in the spinocerebellar ataxia type 3 cohort.
Participants were stratified into tertiles based on plasma insulin
concentrations: First tertile (n=11; <3.65 µIU/ml), second
tertile (n=11; 3.65-9.35 µIU/ml) and third tertile (n=10; >9.35
µIU/ml). (A) Associations between insulin levels and
log-transformed IGFBP1 is shown. (B) Association between insulin
levels and plasma NfL are presented. Data are expressed as the
median ± interquartile range. Statistical significance was
determined by Kruskal-Wallis test followed by Dunn's post hoc test.
*P<0.05. NfL, neurofilament light chain; IGFBP1,
insulin-like growth factor binding protein 1.
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Copy and paste a formatted citation
Spandidos Publications style
Chiu C, Cheng W, Lin T, Chang H, Chang Y, Su S, Lee C, Chang H and Liu C: IGFBP1 as a metabolic‑neurodegenerative biomarker in spinocerebellar ataxia type 3. Exp Ther Med 31: 105, 2026.
APA
Chiu, C., Cheng, W., Lin, T., Chang, H., Chang, Y., Su, S. ... Liu, C. (2026). IGFBP1 as a metabolic‑neurodegenerative biomarker in spinocerebellar ataxia type 3. Experimental and Therapeutic Medicine, 31, 105. https://doi.org/10.3892/etm.2026.13100
MLA
Chiu, C., Cheng, W., Lin, T., Chang, H., Chang, Y., Su, S., Lee, C., Chang, H., Liu, C."IGFBP1 as a metabolic‑neurodegenerative biomarker in spinocerebellar ataxia type 3". Experimental and Therapeutic Medicine 31.4 (2026): 105.
Chicago
Chiu, C., Cheng, W., Lin, T., Chang, H., Chang, Y., Su, S., Lee, C., Chang, H., Liu, C."IGFBP1 as a metabolic‑neurodegenerative biomarker in spinocerebellar ataxia type 3". Experimental and Therapeutic Medicine 31, no. 4 (2026): 105. https://doi.org/10.3892/etm.2026.13100
Copy and paste a formatted citation
x
Spandidos Publications style
Chiu C, Cheng W, Lin T, Chang H, Chang Y, Su S, Lee C, Chang H and Liu C: IGFBP1 as a metabolic‑neurodegenerative biomarker in spinocerebellar ataxia type 3. Exp Ther Med 31: 105, 2026.
APA
Chiu, C., Cheng, W., Lin, T., Chang, H., Chang, Y., Su, S. ... Liu, C. (2026). IGFBP1 as a metabolic‑neurodegenerative biomarker in spinocerebellar ataxia type 3. Experimental and Therapeutic Medicine, 31, 105. https://doi.org/10.3892/etm.2026.13100
MLA
Chiu, C., Cheng, W., Lin, T., Chang, H., Chang, Y., Su, S., Lee, C., Chang, H., Liu, C."IGFBP1 as a metabolic‑neurodegenerative biomarker in spinocerebellar ataxia type 3". Experimental and Therapeutic Medicine 31.4 (2026): 105.
Chicago
Chiu, C., Cheng, W., Lin, T., Chang, H., Chang, Y., Su, S., Lee, C., Chang, H., Liu, C."IGFBP1 as a metabolic‑neurodegenerative biomarker in spinocerebellar ataxia type 3". Experimental and Therapeutic Medicine 31, no. 4 (2026): 105. https://doi.org/10.3892/etm.2026.13100
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