Plasma Branched-Chain Amino Acids and Risk of Incident Type 2 Diabetes: Results from the PREVEND Prospective Cohort Study
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Population
2.2. Baseline Assessment of BCAA
2.3. Clinical and Laboratory Measures
2.4. End Point of the Study
2.5. Statistical Analysis
3. Results
3.1. Baseline Characteristics
3.2. Associations at Baseline
3.3. Longitudinal Analysis
3.4. Effect of Inclusion of BCAA on Type 2 Diabetes Risk Prediction
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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All Participants | Quartiles of BCAA | p-Value * | ||||
---|---|---|---|---|---|---|
Q1 | Q2 | Q3 | Q4 | |||
♂ < 365.31 | ♂ 365.32–408.34 | ♂ 408.35–454.02 | ♂ > 454.023 | |||
♀ < 299.38 | ♀ 299.39–336.23 | ♀ 336.24–377.35 | ♀ > 377.36 | |||
Participants, n | 6244 | 1562 | 1560 | 1560 | 1562 | |
Sex, men, % | 49.4 | 49.4 | 49.4 | 49.3 | 49.4 | 0.99 |
Age, y | 53.1 ± 11.9 | 51.76 ± 13.25 | 52.77 ± 12.31 | 53.75 ± 12.37 | 54.34 ± 11.41 | <0.0001 |
Race, white, % | 95.4 | 96.3 | 96.2 | 95.8 | 93.2 | <0.0001 |
Education, high, % | 38.0 | 39.1 | 41.4 | 37.8 | 33.8 | <0.001 |
BMI, kg/m2 | 26.5 ± 4.2 | 24.7 ± 3.6 | 25.8 ± 3.7 | 26.7 ± 3.9 | 28.6 ± 4.4 | <0.0001 |
SBP, mm Hg | 125.6 ± 18.5 | 123.0 ± 18.6 | 123.6 ± 17.5 | 125.8 ± 18.5 | 130.3 ± 18.6 | <0.0001 |
DBP, mm Hg | 73.2 ± 9.0 | 71.9 ± 9.4 | 72.5 ± 8.8 | 73.4 ± 9.0 | 75.0 ± 8.7 | <0.0001 |
Parental history of CKD, % | 0.5 | 0.6 | 0.3 | 0.8 | 0.3 | 0.18 |
Parental history of T2D, % | 14.2 | 12.8 | 12.5 | 13.5 | 18.1 | <0.0001 |
Current smoking status, no % | 70.7 | 65.8 | 70.8 | 73.7 | 72.4 | <0.0001 |
Alcohol intake, never, % | 24.1 | 23.7 | 22.4 | 24.5 | 25.6 | 0.23 |
Antihypertensive drugs,% | 18.0 | 14.7 | 14.5 | 18.2 | 24.5 | <0.0001 |
Lipid-lowering drugs, % | 7.0 | 5.1 | 5.5 | 7.5 | 9.8 | <0.0001 |
Total BCAA, μM | 370.34 ± 88.63 | <365.31 | 365.32–408.34 | 408.35–454.02 | >454.023 | |
Valine, μM | 203.08 ± 46.58 | 156.32 ± 50.40 | 194.59 ± 20.71 | 215.14 ± 21.63 | 246.30 ± 31.10 | <0.0001 |
Leucine, μM | 124.68 ± 32.56 | 92.85 ± 31.17 | 118.95 ± 16.50 | 132.01 ± 18.48 | 154.90 ± 25.31 | <0.0001 |
Isoleucine, μM | 42.90 ± 16.13 | 30.01 ± 12.73 | 39.45 ± 10.35 | 45.02 ± 11.37 | 56.67 ± 16.43 | <0.0001 |
TC, mmol/L | 5.43 ± 1.03 | 5.22 ± 0.95 | 5.36 ± 1.02 | 5.51 ± 1.04 | 5.67 ± 1.06 | <0.0001 |
HDL-C, mmol/L | 1.25 ± 0.32 | 1.131 ± 0.37 | 1.129 ± 0.30 | 1.25 ± 0.29 | 1.17 ± 0.28 | <0.0001 |
TG, mmol/L | 1.09 (0.79–1.57) | 0.88 (0.65–1.20) | 1.01 (0.75–1.38) | 1.13 (0.84–1.61) | 1.47 (1.06–2.08) | <0.0001 |
Glucose, mmol/L | 4.84 ± 0.64 | 4.872 ± 0.60 | 4.75 ± 0.59 | 4.85 ± 0.60 | 5.03 ± 0.70 | <0.0001 |
Insulin, mU/L | 8.00 (5.70–11.80) | 6.50 (4.80–8.72) | 7.20 (5.20–10.25) | 8.30 (6.00–11.70) | 11.845 (7.70–16.62) | <0.0001 |
Serum creatinine, µmol/L | 84.55 ± 20.64 | 83.43 ± 30.66 | 83.97 ± 16.32 | 85.14 ± 15.35 | 85.64 ± 16.16 | 0.132 |
eGFR, mL/min/1.73m2 | 92.80 ± 17.00 | 95.45 ± 17.64 | 93.57 ± 16.51 | 91.79 ± 16.33 | 90.38 ± 17.05 | <0.0001 |
UAE, mg/24h | 8.53 (6.02–15.08) | 8.15 (5.94–13.82) | 8.23 (5.88–13.62) | 8.41 (5.98–14.85) | 9.65 (6.50–18.20) | 0.101 |
HOMA-IR, (mU mmol/L2)/22.5 | 1.70 (1.17–2.61) | 1.40 (1.02–1.93) | 1.54 (1.10–2.24) | 1.78 (1.25–2.60) | 2.53 (1.66–3.85) | <0.0001 |
HOMA-β, % | 132.5 (90.6–200.0) | 116.9 (82.5–178.6) | 128.5 (90.0–190.0) | 133.3 (96.0–193.5) | 160.0 (110.5–237.1) | <0.0001 |
HOMA-β/HOMA-IR | 79.78 (50.90–113.63) | 79.79 (55.1–113.6) | 79.79 (55.1–113.6) | 79.79 (50.9–113.6) | 60.0 (40.9–88.9) | <0.0001 |
HOMA-IR, (mU mmol/L2)/22.5 | HOMA-β, % | |||
---|---|---|---|---|
β (95% CI) | p-Value | β (95% CI) | p-Value | |
Crude Model | 28.92 (27.16, 30.67) | <0.0001 | 20.46 (18.67, 22.25) | <0.0001 |
Model 1 | 26.80 (25.18, 28.43) | <0.0001 | 21.01 (19.38, 22.64) | <0.0001 |
Model 2 | 30.95 (27.83, 34.07) | <0.0001 | −4.73 (−7.77, −1.70) | 0.002 |
Variables | Univariable | Multivariable | ||
---|---|---|---|---|
β (95% CI) | p-Value | β (95% CI) | p-Value | |
Sex, female vs. male | 69.29 (65.24, 73.33) | <0.0001 | 55.31 (48.32, 62.30) | <0.0001 |
Age, years/10 | 0.58 (0.39, 0.76) | <0.0001 | −0.04 (−0.38, 0.31) | 0.828 |
Caucasian, yes vs. no | 7.61 (2.36, 12.86) | 0.0004 | 5.73 (0.01, 11.44) | 0.049 |
BMI, kg/m2 | 5.17 (4.67, 5.68) | <0.0001 | 2.44 (1.76, 3.13) | <0.0001 |
High education, yes vs. no | 0.20 (−0.87, 1.28) | 0.7107 | 0.40 (−0.67, 1.48) | 0.463 |
SBP, mm Hg | 0.81 (0.70, 0.93) | <0.0001 | −0.09 (−0.31, 0.12) | 0.893 |
DBP, mm Hg | 1.92 (1.69, 2.16) | <0.0001 | 0.15 (−0.27, 0.57) | 0.392 |
Parental history of CKD, yes vs. no | 9.50 (−20.38, 39.38) | 0.533 | 8.44 (−24.63, 41.52) | 0.616 |
Parental history of T2D, yes vs. no | 10.22 (3.94, 16.51) | 0.0001 | 7.91 (1.03, 14.80) | 0.024 |
Current smoking, yes vs. no | −7.94 (−12.85, −3.03) | 0.0001 | −4.76 (−10.52, 1.01) | 0.105 |
Alcohol consumption, yes vs. no | 11.51 (6.36, 16.66) | <0.0001 | 9.01 (3.06, 14.96) | 0.003 |
Antihypertensive drugs, yes vs. no | 24.35 (18.55, 30.14) | <0.0001 | 3.78 (−3.19, 10.75) | 0.287 |
Lipid-lowering drugs, yes vs. no | 24.87 (16.22, 33.52) | <0.0001 | 8.16 (−1.48, 17.80) | 0.097 |
TC, mmol/L | 7.04 (4.92, 9.15) | <0.0001 | 4.38 (1.58, 7.19) | 0.002 |
HDL-C, mmol/L | −60.34(−67.05, −53.63) | <0.0001 | −20.54 (−30.64,−10.44) | <0.0001 |
TG, mmol/L | 25.51 (23.23, 27.78) | <0.0001 | 3.61 (0.61, 6.62) | 0.018 |
Serum creatinine, µmol/L | 71.16 (61.64, 80.68) | <0.0001 | 12.23 (−6.78, 31.24) | 0.207 |
eGFR, mL/min/1.73m2 | −0.44 (−0.57, −0.31) | <0.0001 | −0.01 (−0.29, 0.27) | 0.956 |
UAE, mg/24h | 0.01 (−0.00, 0.03) | 0.095 | −0.02 (−0.04, −0.01) | 0.005 |
HOMA-IR, (mU mmol/L2)/22.5 | 28.92 (27.16, 30.67) | <0.0001 | 22.21 (17.82, 26.59) | <0.0001 |
HOMA-β, % | 20.46 (18.67, 22.25) | <0.0001 | −0.89 (−5.01, 3.24) | 0.673 |
Q1 | Q2 | p-Value | Q3 | p-Value | Q4 | p-Value | BCAA Per 1 SD Increment | p-Value | |
---|---|---|---|---|---|---|---|---|---|
Participants, n | 1561 | 1561 | 1561 | 1561 | 6244 | ||||
Events, n | 27 | 44 | 72 | 158 | 301 | ||||
HR (95% CI) | HR (95% CI) | HR (95% CI) | HR (95% CI) | ||||||
Crude Model | (ref) | 1.65 (1.01, 2.66) | 0.042 | 2.67 (1.71, 4.14) | <0.0001 | 6.15 (4.08, 9.24) | <0.0001 | 1.80 (1.64, 1.98) | <0.0001 |
Model 1 | (ref) | 1.58 (0.97, 2.56) | 0.064 | 2.56 (1.62, 4.05) | <0.0001 | 6.12 (3.92, 9.55) | <0.0001 | 1.76 (1.59, 1.96) | <0.0001 |
Model 2 | (ref) | 1.41 (0.85, 2.32) | 0.178 | 1.87 (1.17, 3.00) | 0.009 | 3.49 (2.19, 5.55) | <0.0001 | 1.46 (1.29, 1.65) | <0.0001 |
Model 3 | (ref) | 1.41 (0.85, 2.33) | 0.175 | 1.87 (1.17, 3.01) | 0.008 | 3.56 (2.24, 5.65) | <0.0001 | 1.48 (1.31, 1.68) | <0.0001 |
Model 4 | (ref) | 1.45 (0.88, 2.41) | 0.142 | 1.84 (1.15, 2.94) | 0.010 | 3.14 (1.99, 4.97) | <0.0001 | 1.39 (1.23, 1.57) | <0.0001 |
Model 5a | (ref) | 1.50 (0.89, 2.53) | 0.124 | 1.91 (1.17, 3.10) | 0.009 | 2.80 (1.72, 4.53) | <0.0001 | 1.28 (1.13, 1.46) | 0.0001 |
Model 5b | (ref) | 1.59 (0.94, 2.68) | 0.079 | 2.12 (1.30, 3.44) | 0.002 | 3.64 (2.26, 5.87) | <0.0001 | 1.41 (1.25, 1.60) | <0.0001 |
Model 5c | (ref) | 1.46 (0.87, 2.46) | 0.149 | 1.70 (1.04, 2.77) | 0.033 | 2.32 (1.42, 3.78) | 0.0007 | 1.19 (1.04, 1.35) | 0.008 |
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Flores-Guerrero, J.L.; Osté, M.C.J.; Kieneker, L.M.; Gruppen, E.G.; Wolak-Dinsmore, J.; Otvos, J.D.; Connelly, M.A.; Bakker, S.J.L.; Dullaart, R.P.F. Plasma Branched-Chain Amino Acids and Risk of Incident Type 2 Diabetes: Results from the PREVEND Prospective Cohort Study. J. Clin. Med. 2018, 7, 513. https://doi.org/10.3390/jcm7120513
Flores-Guerrero JL, Osté MCJ, Kieneker LM, Gruppen EG, Wolak-Dinsmore J, Otvos JD, Connelly MA, Bakker SJL, Dullaart RPF. Plasma Branched-Chain Amino Acids and Risk of Incident Type 2 Diabetes: Results from the PREVEND Prospective Cohort Study. Journal of Clinical Medicine. 2018; 7(12):513. https://doi.org/10.3390/jcm7120513
Chicago/Turabian StyleFlores-Guerrero, Jose L., Maryse C. J. Osté, Lyanne M. Kieneker, Eke G. Gruppen, Justyna Wolak-Dinsmore, James D. Otvos, Margery A. Connelly, Stephan J. L. Bakker, and Robin P. F. Dullaart. 2018. "Plasma Branched-Chain Amino Acids and Risk of Incident Type 2 Diabetes: Results from the PREVEND Prospective Cohort Study" Journal of Clinical Medicine 7, no. 12: 513. https://doi.org/10.3390/jcm7120513