Exploring the Role of Metabolic Hormones in Amyotrophic Lateral Sclerosis
Abstract
:1. Introduction
2. Results
2.1. General Groups’ Characteristics
2.2. Metabolic Hormones: Control vs. ALS
2.3. Clinical, Paraclinical, and Metabolic Hormones’ Correlations
2.4. Subgroup Analysis: Based on Sex, ALS Subtype, Progression, and Evolution Patterns
3. Discussion
3.1. Role of Insulin and Glucose Metabolism in ALS
3.2. Role of Amylin in ALS
3.3. Role of GLP-1 in ALS
3.4. Role of Other Metabolic Hormones in ALS
3.5. Relationship among Metabolic Hormones, Genetic Mutations, and ALS
3.6. Limitations of the Study
- The study’s cross-sectional nature limits causal inference and precludes the establishment of temporal relationships between metabolic hormone levels and ALS progression. Longitudinal studies must elucidate the dynamic interplay between metabolic dysregulation and disease evolution over time.
- The study’s sample size, while sufficient for identifying correlations, may limit the extension of findings to broader ALS populations. Future studies with larger, more diverse cohorts must validate the observed associations across different demographic and clinical profiles.
- Despite efforts to control for confounding factors, the influence of unmeasured variables, such as dietary habits, physical activity, and medication use, must be considered. Future research incorporating comprehensive assessments of lifestyle factors and medication histories could better elucidate the independent effects of metabolic hormones on ALS progression.
- The clinical relevance of correlations requires further investigation.
4. Materials and Methods
4.1. Study Design and Study Population
4.2. Data Collection
4.3. Collection of Biological Samples
4.4. Measurements of Metabolic Hormones’ and Adipokines’ Multiplex Bead-Based Immunoassay
4.5. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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ALS | Control | |
---|---|---|
Number of patients | 44 | 40 |
Age (mean ± SD) (years) | 58.05 ± 12.14 | 56.97 ± 11.83 |
Sex ratio | 28:16 | 24:16 |
BMI | 25.07 ± 4.56 | NA |
FVC(%) | 75.73 ± 30.15 | NA |
ALSFRS-R | ||
Respiratory subscore | 10.95 ± 1.61 | NA |
Bulbar subscore | 9.64 ± 2.63 | NA |
Gross Motor subscore | 6.42 ± 3.23 | NA |
Fine Motor subscore | 7.24 ± 3.42 | NA |
Total score | 33.95 ± 7.92 | NA |
ALS SUBTYPE | ||
Bulbar | 9 (20.45%) | NA |
Spinal | 35 (79.55%) | NA |
PROGRESSION PATTERN | ||
Horizontal pattern | 21 (47.73%) | NA |
Vertical pattern | 23 (52.32%) | NA |
EVOLUTION FORM | ||
Slow evolution (DPR < 0.67) | 30 (68.18%) | NA |
Fast evolution (DPR ≥ 0.67) | 14 (31.82%) | NA |
KING’S COLLEGE ALS CLINICAL STAGING | ||
Stage 1 | 0 (0.00%) | NA |
Stage 2A | 4 (9.09%) | NA |
Stage 2B | 39 (68.18%) | NA |
Stage 3 | 10 (22.73%) | NA |
Stage 4 | 0 (0.00%) | NA |
Control | ALS | p-Value | |
---|---|---|---|
Amylin (pg/mL) | 156.78 ± 99.86 | 285.41 ± 359.87 | 0.028 |
C-peptide (pg/mL) | 6932.8 ± 2559.43 | 5162.95 ± 3792.84 | 0.007 |
Ghrelin (pg/mL) | 63.98 ± 60.78 | 42.4 ± 55.25 | 0.041 |
GIP (pg/mL) | 4239.65 ± 5171.88 | 6218.95 ± 4669.2 | 0.027 |
GLP-1 (pg/mL) | 79.03 ± 128.5 | 132.86 ± 229.91 | 0.163 |
Glucagon (pg/mL) | 51.1 ± 16.69 | 72.8 ± 49.63 | 0.008 |
Insulin (pg/mL) | 476.43 ± 662.14 | 906.76 ± 1226.06 | 0.037 |
Leptin (pg/mL) | 7994.33 ± 4748.2 | 4662.66 ± 4238.2 | 0.000 |
MCP-1 (pg/mL) | 5524.93 ± 2275 | 6066.4 ± 4149.51 | 0.435 |
PP (pg/mL) | 2060.35 ± 2200.31 | 4992.27 ± 4890.14 | 0.000 |
PYY (pg/mL) | 116.55 ± 195.6 | 103.98 ± 84.48 | 0.583 |
BMI | Amylin | C-peptide | Ghrelin | GIP | GLP-1 | Glucagon | Insulin | Leptin | MCP-1 | PP | PYY | ||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
DPR | r | −0.223 | −0.230 | −0.255 | 0.074 | −0.046 | 0.131 | 0.142 | −0.303 | −0.217 | 0.153 | 0.018 | 0.103 |
p | 0.020 | 0.016 | 0.008 | 0.447 | 0.631 | 0.173 | 0.141 | 0.001 | 0.023 | 0.112 | 0.850 | 0.286 | |
ALSFRS-Respiratory | r | 0.320 | 0.260 | 0.075 | 0.001 | 0.165 | 0.151 | −0.069 | 0.411 | 0.162 | −0.224 | 0.053 | 0.044 |
p | 0.001 | 0.006 | 0.437 | 0.991 | 0.086 | 0.115 | 0.471 | 0.000 | 0.090 | 0.019 | 0.584 | 0.649 | |
ALSFRS-Bulbar | r | 0.288 | 0.237 | 0.083 | −0.122 | 0.039 | 0.033 | −0.085 | 0.307 | 0.105 | −0.274 | 0.116 | 0.124 |
p | 0.002 | 0.013 | 0.386 | 0.206 | 0.685 | 0.731 | 0.379 | 0.001 | 0.275 | 0.004 | 0.227 | 0.198 | |
ALSFRS-Gross Motor | r | −0.006 | −0.077 | −0.125 | 0.075 | 0.052 | 0.077 | 0.117 | −0.021 | 0.071 | −0.089 | −0.160 | 0.085 |
p | 0.951 | 0.427 | 0.192 | 0.435 | 0.588 | 0.425 | 0.222 | 0.825 | 0.460 | 0.356 | 0.094 | 0.379 | |
ALSFRS-Fine Motor | r | 0.396 | 0.288 | 0.093 | −0.107 | 0.124 | 0.169 | 0.092 | 0.341 | 0.210 | −0.148 | −0.062 | 0.079 |
p | 0.000 | 0.002 | 0.332 | 0.267 | 0.195 | 0.078 | 0.340 | 0.000 | 0.028 | 0.123 | 0.522 | 0.410 | |
ALSFRS-R Total score | r | 0.427 | 0.341 | 0.048 | 0.003 | 0.132 | 0.205 | 0.056 | 0.394 | 0.169 | −0.178 | 0.018 | 0.115 |
p | 0.000 | 0.000 | 0.617 | 0.977 | 0.170 | 0.032 | 0.562 | 0.000 | 0.077 | 0.063 | 0.852 | 0.233 | |
Time of diffusion | r | 0.124 | 0.113 | −0.155 | 0.117 | 0.006 | 0.268 | 0.226 | 0.137 | 0.152 | −0.298 | −0.082 | 0.112 |
p | 0.198 | 0.241 | 0.105 | 0.225 | 0.950 | 0.005 | 0.018 | 0.152 | 0.113 | 0.002 | 0.397 | 0.245 | |
Time of generalization | r | 0.115 | 0.117 | −0.163 | 0.128 | 0.002 | 0.263 | 0.221 | 0.138 | 0.130 | −0.297 | −0.076 | 0.110 |
p | 0.233 | 0.224 | 0.089 | 0.181 | 0.985 | 0.006 | 0.020 | 0.152 | 0.177 | 0.002 | 0.429 | 0.252 | |
BMI | r | 1.000 | 0.306 | 0.222 | −0.116 | −0.029 | 0.225 | −0.035 | 0.340 | 0.590 | −0.139 | −0.077 | −0.054 |
p | 0.001 | 0.020 | 0.229 | 0.761 | 0.018 | 0.715 | 0.000 | 0.000 | 0.148 | 0.424 | 0.578 | ||
FVC(%) | r | 0.281 | 0.245 | 0.134 | 0.145 | −0.015 | 0.051 | −0.083 | 0.340 | 0.182 | −0.245 | −0.003 | 0.151 |
p | 0.003 | 0.010 | 0.163 | 0.129 | 0.876 | 0.598 | 0.391 | 0.000 | 0.056 | 0.010 | 0.973 | 0.116 | |
Amylin | r | 0.306 | 1.000 | 0.529 | 0.146 | 0.493 | 0.104 | 0.146 | 0.748 | 0.237 | 0.020 | 0.300 | 0.091 |
p | 0.001 | 0.000 | 0.127 | 0.000 | 0.277 | 0.128 | 0.000 | 0.013 | 0.838 | 0.001 | 0.345 | ||
C-peptide | r | 0.222 | 0.529 | 1.000 | 0.010 | 0.298 | −0.200 | −0.125 | 0.606 | 0.254 | −0.033 | 0.178 | 0.024 |
p | 0.020 | 0.000 | 0.920 | 0.002 | 0.036 | 0.193 | 0.000 | 0.008 | 0.734 | 0.063 | 0.806 | ||
Ghrelin | r | −0.116 | 0.146 | 0.010 | 1.000 | 0.205 | 0.148 | 0.317 | 0.098 | −0.095 | 0.026 | 0.321 | 0.259 |
p | 0.229 | 0.127 | 0.920 | 0.032 | 0.122 | 0.001 | 0.307 | 0.324 | 0.784 | 0.001 | 0.006 | ||
GIP | r | −0.029 | 0.493 | 0.298 | 0.205 | 1.000 | 0.212 | 0.316 | 0.482 | −0.048 | 0.054 | 0.569 | 0.234 |
p | 0.761 | 0.000 | 0.002 | 0.032 | 0.026 | 0.001 | 0.000 | 0.617 | 0.576 | 0.000 | 0.014 | ||
GLP-1 | r | 0.225 | 0.104 | −0.200 | 0.148 | 0.212 | 1.000 | 0.581 | 0.160 | 0.068 | −0.280 | 0.358 | 0.483 |
p | 0.018 | 0.277 | 0.036 | 0.122 | 0.026 | 0.000 | 0.094 | 0.479 | 0.003 | 0.000 | 0.000 | ||
Glucagon | r | −0.035 | 0.146 | −0.125 | 0.317 | 0.316 | 0.581 | 1.000 | 0.074 | −0.129 | 0.043 | 0.484 | 0.567 |
p | 0.715 | 0.128 | 0.193 | 0.001 | 0.001 | 0.000 | 0.445 | 0.181 | 0.654 | 0.000 | 0.000 | ||
Insulin | r | 0.340 | 0.748 | 0.606 | 0.098 | 0.482 | 0.160 | 0.074 | 1.000 | 0.299 | −0.028 | 0.305 | 0.179 |
p | 0.000 | 0.000 | 0.000 | 0.307 | 0.000 | 0.094 | 0.445 | 0.002 | 0.772 | 0.001 | 0.062 | ||
Leptin | r | 0.590 | 0.237 | 0.254 | −0.095 | −0.048 | 0.068 | −0.129 | 0.299 | 1.000 | −0.132 | −0.112 | −0.026 |
p | 0.000 | 0.013 | 0.008 | 0.324 | 0.617 | 0.479 | 0.181 | 0.002 | 0.168 | 0.242 | 0.786 | ||
MCP-1 | r | −0.139 | 0.020 | −0.033 | 0.026 | 0.054 | −0.280 | 0.043 | −0.028 | −0.132 | 1.000 | −0.001 | −0.143 |
p | 0.148 | 0.838 | 0.734 | 0.784 | 0.576 | 0.003 | 0.654 | 0.772 | 0.168 | 0.995 | 0.137 | ||
PP | r | −0.077 | 0.300 | 0.178 | 0.321 | 0.569 | 0.358 | 0.484 | 0.305 | −0.112 | −0.001 | 1.000 | 0.421 |
p | 0.424 | 0.001 | 0.063 | 0.001 | 0.000 | 0.000 | 0.000 | 0.001 | 0.242 | 0.995 | 0.000 | ||
PYY | r | −0.054 | 0.091 | 0.024 | 0.259 | 0.234 | 0.483 | 0.567 | 0.179 | −0.026 | −0.143 | 0.421 | 1.000 |
p | 0.578 | 0.345 | 0.806 | 0.006 | 0.014 | 0.000 | 0.000 | 0.062 | 0.786 | 0.137 | 0.000 |
Slow Evolution | Fast Evolution | p | |
---|---|---|---|
Amylin (pg/mL) | 343.86 ± 409.63 | 162.96 ± 178.86 | 0.014 |
Insulin (pg/mL) | 1116.35 ± 1365.25 | 437.51 ± 685.87 | 0.007 |
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Moțățăianu, A.; Mănescu, I.B.; Șerban, G.; Bărcuțean, L.; Ion, V.; Bălașa, R.; Andone, S. Exploring the Role of Metabolic Hormones in Amyotrophic Lateral Sclerosis. Int. J. Mol. Sci. 2024, 25, 5059. https://doi.org/10.3390/ijms25105059
Moțățăianu A, Mănescu IB, Șerban G, Bărcuțean L, Ion V, Bălașa R, Andone S. Exploring the Role of Metabolic Hormones in Amyotrophic Lateral Sclerosis. International Journal of Molecular Sciences. 2024; 25(10):5059. https://doi.org/10.3390/ijms25105059
Chicago/Turabian StyleMoțățăianu, Anca, Ion Bogdan Mănescu, Georgiana Șerban, Laura Bărcuțean, Valentin Ion, Rodica Bălașa, and Sebastian Andone. 2024. "Exploring the Role of Metabolic Hormones in Amyotrophic Lateral Sclerosis" International Journal of Molecular Sciences 25, no. 10: 5059. https://doi.org/10.3390/ijms25105059