New Players in Metabolic Syndrome
Abstract
1. Introduction
2. Materials and Methods
2.1. Study Design
2.2. Inclusion and Exclusion Criteria
2.2.1. Inclusion Criteria
- •
- Age (35–74);
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- BMI ≥ 30 kg/m2;
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- Prediabetes (fasting glucose between 6.1–6.9 mmol/L, values after a 120 min oral glucose tolerance test (OGTT) between 7.8–11.0 mmol/L, and/or an HbA1c between 5.7 and 6.4%);
- •
- Newly diagnosed diabetes (fasting glucose ≥7.0 mmol/L, values after a 120 min OGTT ≥11.1 mmol/L, and/or an HbA1c ≥6.5%), without therapy.
2.2.2. Exclusion Criteria
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- Liver dysfunction (liver enzymes ≥3 times above the reference range);
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- Chronic kidney disease (CKD) stages III–IV;
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- Heart failure (HF), classes III–IV NYHA;
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- Neoplastic disease.
2.3. Anthropometric Parameters
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- Weight, height, and waist and hip circumference;
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- Weight (kg) divided by height squared (m2) was used to compute BMI;
- •
- VAI = [WC/(36.68 + (1.88 × BMI)] × (TG/1.03) × (1.31/HDL) in males; VAI = [WC/(36.58 + (1.89 × BMI)] × (TG/0.81) × (1.52/HDL) for females.
2.4. Investigation of Glycemic Homeostasis
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- Using 75 g of glucose, the oral glucose tolerance test (OGTT) was conducted by measuring the glucose and immunoreactive insulin (IRI) at 0, 60, and 120 min.
- •
- If a patient’s HOMA index was greater than 2.5, they were deemed insulin resistant.
2.5. Metabolic Syndrome Was Defined by the Presence of Central Obesity (Defined as a Waist Circumference ≥80 cm for Women and ≥94 cm for Men) + Any Two of the Following Risk Factors (IDF Criteria)
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- Fasting glucose ≥ 5.6 mmol/L;
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- Blood pressure ≥ 130/≥ 85 mmHg;
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- Triglycerides ≥ 1.7 mmol/L;
- -
- HDL ≤ 1.03 mmol/L for men and ≤1.29 mmol/L for women.
2.6. Laboratory Investigation
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- Serum levels of FGF-21, sortilin, Metrnl, and nesfatin-1 were measured using standard ELISA techniques. Prior to the assay, the blood samples were centrifuged and kept at −80 °C.
2.7. Instrumental Investigation
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- Measurement of intima-media thickness (IMT) using a Panasonic Cardio Health station (Panasonic, Yogohoma, Japan);
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- Cardio-ankle vascular index (VaSera system, FUKUDA DENSHI CO., Tokyo, Japan);
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- Ankle-brachial index (ABI) (Elite Natus, Natus Medical Incorporated, Middleton, WI, USA);
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- Assessment of the autonomic nervous system through an evaluation of sudomotor function with FDA-approved Sudoscan (Itamar Medical Ltd., Caesarea, Israel);
- •
- Assessment of the peripheral nervous system through the neuropathy disability score.
2.8. Statistical Analysis
3. Results
4. Discussion
4.1. Clinical Significance
4.2. Limitations of This Study
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Obesity Group 1 | Prediabetes Group 2 | Diabetes Group 3 | 1/2 | 1/3 | 2/3 | |
---|---|---|---|---|---|---|
n | 80 | 60 | 60 | |||
Age years | 53.54 ± 9.09 | 53.74 ± 11.65 | 55.92 ± 11.02 | ns | ns | p < 0.05 |
BMI (kg/m2) | 34.65 ± 3.10 | 35.85 ± 4.97 | 34.69 ± 5.56 | ns | ns | ns |
WHR | 0.90 ± 0.09 | 0.91 ± 0.10 | 0.96 ± 0.16 | p < 0.05 | ns | p < 0.05 |
WSR | 0.64 ± 0.06 | 0.65 ± 0.07 | 0.65 ± 0.07 | ns | ns | ns |
Waist cm | 104.58 ± 10.38 | 106.17 ± 11.68 | 108.36 ± 13.96 | ns | ns | ns |
Obesity Group 1 | Prediabetes Group 2 | Diabetes Group 3 | 1/2 | 1/3 | 2/3 | |
---|---|---|---|---|---|---|
N | 80 | 60 | 60 | |||
SBP (mmHg) | 130 [120–139.5] | 120 [112.5–130] | 130 [120–140] | ns | ns | ns |
DBP (mmHg) | 80 [70–90] | 80 [72.3–80] | 80 [72.3–87.5] | ns | ns | ns |
Tchol (mmol/L) | 5.33 (1.21) | 5.29 (1.08) | 5.55 (1.26) | ns | ns | ns |
LDL (mmol/L) | 3.33 (1.05) | 3.20 (0.99) | 3.23 (1.10) | ns | ns | ns |
HDL (mmol/L) | 1.35 (0.30) | 1.24(0.31) | 1.08 (0.30) | p < 0.05 | p < 0.05 | p < 0.05 |
TG (mmol/L) | 1.29 [0.87–1.67] | 1.55 [1.28–2.07] | 1.94 [1.38–1.94] | p < 0.05 | p < 0.001 | p < 0.05 |
Hypertesion | 76.3% | 85.5% | 84.7% | ns | ns | ns |
Smoking % | 26.6% | 18.0% | 33.9% | ns | ns | ns |
Dyslipidemia % | 46.3% | 62.9% | 79.3% | ns | p < 0.05 | ns |
Variable | FGF21 | NEFA | METRNL | SORT |
---|---|---|---|---|
Age | 0.112 | −0.010 | −0.014 | −0.039 |
BMI | 0.068 | 0.088 | 0.101 | 0.041 |
WC (cm) | 0.176 | 0.175 | 0.288 * | 0.158 |
HC (cm) | 0.029 | −0.112 | 0.010 | 0.091 |
WHR | 0.093 | 0.297 * | 0.353 ** | 0.189 |
WSR | 0.099 | 0.208 | 0.176 | 0.078 |
VAI | 0.330 ** | 0.022 | 0.355 ** | 0.117 |
FAT (%) | 0.064 | 0.048 | 0.145 | 0.031 |
SBP (mmHg) | 0.003 | 0.011 | 0.068 | 0.047 |
DBP (mmHg) | −0.007 | 0.075 | 0.125 | 0.013 |
Tchol (mmol/L) | 0.042 | 0.048 | 0.021 | 0.063 |
VLDL(mmol/L) | 0.296 ** | 0.021 | 0.127 | 0.189 |
HDL (mmol/L) | −0.289 * | −0.002 | −0.032 | −0.157 |
LDL (mmol/L) | 0.044 | 0.060 | 0.014 | 0.071 |
TG (mmol/L) | 0.296 ** | 0.015 | 0.128 | 0.187 |
Gluc 0 min (mmol/L) | 0.119 | 0.282 * | 0.190 | 0.393 ** |
Gluc 60 min (mmol/L) | 0.047 | 0.227 | 0.081 | 0.126 |
Gluc 120 min (mmol/L) | 0.072 | 0.391 ** | 0.082 | 0.351 ** |
IRI 0 min (mU/L) | 0.295 * | 0.238 * | 0.272 * | 0.142 |
IRI 60 min (mU/L) | 0.318 ** | 0.138 | 0.285 * | 0.134 |
IRI 120 min (mU/L) | 0.276 * | 0.242 | 0.122 | 0.186 |
ASAT (U/L) | 0.098 | −0.113 | 0.099 | 0.174 |
ALAT (U/L) | 0.235 * | −0.110 | 0.119 | 0.189 |
GGT (U/L) | 0.418 *** | −0.009 | 0.074 | 0.239 * |
Creat (mkmol/L) | 0.124 | −0.142 | −0.156 | 0.048 |
Uric acid (mkmol/L) | 0.411 *** | −0.004 | 0.088 | 0.028 |
HOMA-IR | 0.270 * | 0.256 * | 0.268 * | 0.100 |
CPK (U/L) | 0.049 | −0.110 | 0.272 * | −0.030 |
HbA1c% | 0.166 | 0.136 | 0.181 | 0.497 ** |
ACR (mg/mmol) | 0.155 | −0.024 | 0.389 * | 0.082 |
eGFR | −0.098 | 0.175 | 0.024 | 0.018 |
95% CI | ||||||
---|---|---|---|---|---|---|
Pathology State | Biomarker | Value | ORs | Upper limit | Lower limit | p |
Metabolic syndrome | FGF-21 | ≥285.6/<285.6 | 11.400 | 3.001 | 43.307 | <0.001 |
Insulin resistance | FGF-21 | ≥269/<269 | 8.000 | 2.272 | 28.170 | 0.001 |
Insulin resistance | METRNL | ≥0.285/<0.285 | 6.400 | 1.859 | 22.036 | 0.003 |
Dyslipidemia | FGF-21 | ≥275.7/<275.7 | 4.024 | 1.566 | 10.336 | 0.004 |
Carbohydrate disorders | Sortilin | ≥0.59/<0.59 | 5.784 | 1.515 | 10.182 | 0.028 |
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Nedeva, I.; Assyov, Y.; Karamfilova, V.; Kamenov, Z.; Dobrev, P.; Velikova, T.; Vodenicharov, V. New Players in Metabolic Syndrome. Metabolites 2025, 15, 380. https://doi.org/10.3390/metabo15060380
Nedeva I, Assyov Y, Karamfilova V, Kamenov Z, Dobrev P, Velikova T, Vodenicharov V. New Players in Metabolic Syndrome. Metabolites. 2025; 15(6):380. https://doi.org/10.3390/metabo15060380
Chicago/Turabian StyleNedeva, Iveta, Yavor Assyov, Vera Karamfilova, Zdravko Kamenov, Pavel Dobrev, Tsvetelina Velikova, and Vlayko Vodenicharov. 2025. "New Players in Metabolic Syndrome" Metabolites 15, no. 6: 380. https://doi.org/10.3390/metabo15060380
APA StyleNedeva, I., Assyov, Y., Karamfilova, V., Kamenov, Z., Dobrev, P., Velikova, T., & Vodenicharov, V. (2025). New Players in Metabolic Syndrome. Metabolites, 15(6), 380. https://doi.org/10.3390/metabo15060380