Effects of Obesity and Exercise on Hepatic and Pancreatic Lipid Content and Glucose Metabolism: PET Studies in Twins Discordant for BMI
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design
2.2. Participants
2.3. Training Intervention
2.4. Blood Tests
2.5. Euglycemic-Hyperinsulinemic Clamp and FDG-PET Study
2.6. Magnetic Resonance Imaging and Magnetic Resonance Spectroscopy
2.7. Oral Glucose Tolerance Test
2.8. Body Composition and Peak Aerobic Exercise Capacity Test
2.9. Statistical Analysis and Modeling
3. Results
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
ALP | alkaline phosphatase |
ALT | alanine aminotransferase |
[18F]FDG | 2-[18F]Fluoro-D-glucose |
GT | gamma-glutamyl transferase |
HIIT | high-intensity interval training |
IFG | impaired fasting glucose |
IGT | impaired glucose tolerance |
ISR | insulin secretion rate |
LFC | liver fat content |
MRI | magnetic resonance imaging |
MRS | magnetic resonance spectroscopy |
M-value | whole-body insulin-stimulated glucose uptake |
OGTT | oral glucose tolerance test |
PET | positron emission tomography |
PFC | pancreatic fat content |
PFR | potentiation factor ratio |
SD | standard deviation |
V̇O2peak | peak exercise capacity |
References
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Heavier | Leaner | |||
---|---|---|---|---|
Twin Pair ID | BMI (kg/m2) | Glycemic Status | BMI (kg/m2) | Glycemic Status |
1 | 42.6 | normal | 40.1 | IFG |
2 | 36.7 | IFG | 24.1 | normal |
3 | 30.8 | IFG, IGT | 25.4 | normal |
4 | 42.2 | IFG | 25.4 | normal |
5 | 33.8 | IFG | 27.8 | IFG, IGT |
6 | 30.1 | normal | 27.9 | normal |
7 | 47.0 | IFG | 42.7 | normal |
8 | 25.2 | IFG, IGT | 20.8 | IFG, IGT |
9 | 35.9 | normal | 27.4 | IFG |
10 | 47.7 | IFG | 29.3 | IFG |
11 | 31.1 | normal | 28.2 | normal |
12 | 37.2 | normal | 30.1 | normal |
Heavier | Leaner | p-Value | |||||
---|---|---|---|---|---|---|---|
Pre | Post | Pre | Post | Baseline | Time | Time*group | |
n | 12 | 11 | 12 | 10 | |||
Male/female | 4/8 | 4/7 | 4/8 | 4/6 | |||
Age, years | 40.4 (37.5;43.4) | 40.4 (37.5;43.4) | |||||
Weight, kg | 108.7 (91.8;125.7) | 108.0 (93.1;122.9) | 86.4 (72.4;100.3) | 86.9 (72.6;101.2) | 0.001 * | 0.95 | 0.37 |
BMI, kg/m2 | 36.7 (32.2;41.1) | 36.4 (32.4;40.4) | 29.1 (25.1;33.1) | 29.3 (25.3;33.2) | 0.001 * | 0.92 | 0.41 |
Waist circumference, cm | 117.7 (106.3;129.2) | 115.0 (106.8;123.1) | 96.5 (84.7;108.3) | 94.4 (82.3;106.6) | 0.001 * | 0.17 | 0.74 |
Fat-free mass, kg | 35.9 (31.0;40.7) | 36.2 (32.1;40.3) | 33.1 (29.0;37.2) | 33.9 (30.6;37.2) | 0.003 *† | 0.14 | 0.10 |
Fat mass, kg | 45.5 (33.8;57.3) | 44.5 (34.6;54.4) | 27.8 (17.9;37.7) | 26.9 (14.4;39.4) | 0.001 *† | 0.70 † | 0.97 † |
Visceral fat mass, kg | 5.9 (4.5;7.3) | 5.5 (4.4;6.5) | 3.1 (2.0;4.3) | 3.2 (2.0;4.4) | 0.002 *† | 0.07 | 0.29 |
Fat percentage, % | 40.6 (35.5;45.7) | 40.0 (35.9;44.1) | 30.4 (24.0;36.9) | 29.5 (20.3;38.7) | 0.001 * | 0.37 | 0.72 |
V̇O2peak, mL·kg−1·min−1 | 25.6 (22.7;28.5) | 28.3 (26.1;30.6) | 32.4 (27.3;37.4) | 35.1 (29.9;40.2) | 0.003 * | 0.001 * | 0.94 |
Triglycerides, mmol/L | 1.4 (0.9;1.9) | 1.2 (0.9;1.5) | 0.8 (0.6;1.0) | 0.8 (0.6;1.0) | 0.040 * | 0.54 † | 0.49 † |
FFA, mmol/L | 0.59 (0.51;0.67) | 0.68 (0.45; 0.91) | 0.52 (0.34;0.69) | 0.54 (0.14; 0.94) | 0.29 | 0.63 | 0.63 |
ALT, u/L | 33.8 (23.3;44.2) | 31.4 (22.3;40.6) | 31.6 (13.1;50.1) | 31.5 (17.7;45.3) | 0.30 † | 0.95 † | 0.42 † |
ALP, u/L | 59.4 (51.4;67.4) | 59.6 (51.5;67.8) | 51.8 (43.2;60.3) | 56.9 (47.2;66.7) | 0.08 † | 0.31 † | 0.11 † |
AST, u/L | 22.2 (18.7;25.6) | 22.6 (18.3;26.9) | 27.5 (15.8;39.2) | 25.8 (14.8;36.9) | 0.28 † | 0.86 † | 0.92 † |
CRP, mg/L | 2.8 (1.4;4.2) | 3.7 (1.3;6.2) | 2.1 (0.3;3.9) | 1.2 (−0.6;3.1) | 0.050 * | 0.69 † | 0.50 † |
M-value, μmol/kg*min | 23.1 (16.3;30.0) | 31.4 (20.4;42.3) | 37.6 (26.7;48.5) | 46.9 (31.7;62.1) | 0.007 * | 0.022 * | 0.82 |
Heavier | Leaner | p-Value | |||||
---|---|---|---|---|---|---|---|
Pre | Post | Pre | Post | Baseline | Time | Time*group | |
n | 12 | 11 | 12 | 10 | |||
Basal glucose, mmol/L | 5.7 (5.4;6.0) | 5.8 (5.6;6.1) | 5.5 (5.2;5.7) | 5.5 (5.2;5.7) | 0.39 | 0.37 | 0.42 |
Mean glucose, mmol/L | 7.5 (6.7;8.2) | 7.7 (7.0;8.3) | 6.9 (6.1;7.8) | 7.0 (6.1;7.9) | 0.17 | 0.68 | 0.78 |
2 h glucose, mmol/L | 6.5 (5.7;7.3) | 6.6 (5.7;7.4) | 6.1 (4.9;7.2) | 5.8 (4.3;7.4) | 0.32 | 0.84 | 0.52 |
Hba1c, mmol/mol | 36.5 (35.1;37.9) | 36.0 (34.2;37.7) | 34.9 (32.8;37.0) | 34.7 (32.2;37.1) | 0.047 *† | 0.58 | 0.68 |
Basal ins, pmol/L | 70.5 (54.4;86.6) | 63.5 (32.0;95.0) | 44.0 (28.5;59.5) | 49.0 (26.2;71.9) | 0.006 *† | 0.50 † | 0.71 † |
Mean insulin, pmol/L | 371.6 (229.9;513.3) | 339.4 (214.2;464.6) | 235.8 (163.3;308.4) | 258.2 (169.4;347.0) | 0.01 *† | 0.88 † | 0.66 † |
Basal insulin secretion rate, pmol∙min−1∙m−2 | 111.4 (97.5;125.2) | 111.0 (95.4;126.5) | 87.4 (69.4;105.4) | 86.2 (69.6;102.7) | 0.030 * | 0.80 | 0.88 |
Glucose sensitivity, pmol∙min−1∙m−2∙mM−1 | 92.5 (69.4;115.6) | 103.4 (75.3;131.5) | 98.5 (77.5;119.5) | 75.2 (48.6;101.9) | 0.66 | 0.44 | 0.049 * |
p = 0.36 | p = 0.049 * | ||||||
Rate sensitivity, pmol∙m−2 mM−1 | 1366.6 (906;1827) | 1169.9 (680;1660) | 1028.0 (668;1388) | 1107.5 (601;1614) | 0.049 * | 0.70 | 0.13 |
PFR, dimensionless | 1.4 (1.1;1.8) | 1.3 (0.9;1.6) | 1.7 (1.2;2.2) | 1.5 (0.9;2.1) | 0.48 † | 0.30 † | 0.52 † |
ISR early, nmol/m2 | 13.1 (9.7;16.6) | 12.3 (8.8;15.8) | 10.0 (7.1;12.9) | 9.3 (6.3;12.3) | 0.004 * | 0.50 | 0.92 |
ISR late, nmol/m2 | 31.9 (28.5;35.4) | 29.1 (25.7;32.6) | 26.9 (20.9;32.9) | 25.7 (20.2;31.3) | 0.07 | 0.24 | 0.50 |
Total ISR, nmol/m2 | 45.1 (39.2;50.9) | 41.5 (35.8;47.2) | 36.9 (29.6;44.2) | 35.1 (27.9;42.2) | 0.021 * | 0.23 | 0.52 |
2 h OGIS, mL∙min−1∙m−2 | 375.0 (354.1;395.8) | 369.0 (349.8;388.2) | 414.7 (384.3;445.1) | 415.8 (389.9;441.6) | 0.037 * | 0.75 | 0.63 |
Baseline | Change | |||
---|---|---|---|---|
r | p | r | p | |
Liver fat percentage | ||||
ALT, U/L | 0.83 | <0.001 * | 0.49 | 0.05 *‡ |
AST, U/L | 0.64 | 0.005 * | 0.34 | |
ALP, U/L | 0.35 | 0.15 | 0.06 | 0.02 * |
Liver glucose uptake | ||||
ALT, U/L | −0.09 | 0.7 ‡ | 0.02 | 0.95 ‡ |
AST, U/L | −0.37 | 0.09 ‡ | −0.06 | 0.79 |
ALP, U/L | −0.04 | 0.85 | −0.18 | 0.45 |
GT, U/L | −0.40 | 0.06 † | −0.02 | 0.92 |
GT | ||||
Weight, kg | −0.09 | 0.68 | 0.46 | 0.04 *‡ |
BMI, kg/m2 | 0.03 | 0.90 | 0.47 | 0.03 *‡ |
Visceral fat, kg | 0.54 | 0.021 * | 0.12 | |
Triglycerides, mmol/L | 0.44 | 0.031 *‡ | 0.42 | 0.06 |
Glucose sensitivity | ||||
Pancreatic fat content, % | −0.26 | 0.29 | −0.08 | 0.77 |
M-value | ||||
Basal insulin, pmol/L | −0.70 | <0.001 * | −0.17 | 0.46 |
Mean insulin, pmol/L | −0.70 | <0.001 * | −0.24 | 0.31 |
Basal insulin secretion rate, pmol∙min−1∙m−2 | −0.70 | <0.001 * | 0.01 | 0.95 |
ISR early, nmol/m2 | −0.61 | 0.002 * | −0.27 | 0.23 |
ISR late, nmol/m2 | −0.76 | <0.001 * | −0.05 | 0.84 |
Total ISR, nmol/m2 | −0.83 | <0.001 * | −0.15 | 0.52 |
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Lietzén, M.S.; Mari, A.; Ojala, R.; Hentilä, J.; Koskensalo, K.; Lautamäki, R.; Löyttyniemi, E.; Parkkola, R.; Saunavaara, V.; Kirjavainen, A.K.; et al. Effects of Obesity and Exercise on Hepatic and Pancreatic Lipid Content and Glucose Metabolism: PET Studies in Twins Discordant for BMI. Biomolecules 2024, 14, 1070. https://doi.org/10.3390/biom14091070
Lietzén MS, Mari A, Ojala R, Hentilä J, Koskensalo K, Lautamäki R, Löyttyniemi E, Parkkola R, Saunavaara V, Kirjavainen AK, et al. Effects of Obesity and Exercise on Hepatic and Pancreatic Lipid Content and Glucose Metabolism: PET Studies in Twins Discordant for BMI. Biomolecules. 2024; 14(9):1070. https://doi.org/10.3390/biom14091070
Chicago/Turabian StyleLietzén, Martin S., Andrea Mari, Ronja Ojala, Jaakko Hentilä, Kalle Koskensalo, Riikka Lautamäki, Eliisa Löyttyniemi, Riitta Parkkola, Virva Saunavaara, Anna K. Kirjavainen, and et al. 2024. "Effects of Obesity and Exercise on Hepatic and Pancreatic Lipid Content and Glucose Metabolism: PET Studies in Twins Discordant for BMI" Biomolecules 14, no. 9: 1070. https://doi.org/10.3390/biom14091070