Background
Methods
Subjects
Clinical examination
Biochemical measurements
Calculations, definitions and statistical analysis
Results
Men | Women |
P-value | |
---|---|---|---|
N = 11.819 |
N = 14.900 | ||
Age (years) | 46 ± 13 | 45 ± 13 | <0.001 |
BMI (kg/m2) | 26.5 ± 3.5 | 25.7 ± 4.4 | <0.001 |
Waist (cm) | 96 ± 10 | 87 ± 12 | <0.001 |
Waist-hip ratio | 0.97 ± 0.07 | 0.87 ± 0.07 | <0.001 |
FT3 | 5.46 ± 0.53 | 5.10 ± 0.52 | <0.001 |
FT4 | 16.1 ± 1.9 | 15.5 ± 1.8 | <0.001 |
TSH | 2.11 ± 0.85 | 2.20 ± 0.90 | <0.001 |
Normal weight/overweight | |||
/obesity (n,%) | 35.1/51.0/13.9 | 37.2/47.9/14.9 | NS |
Current/never smokers (%) | 17.5/42.3 | 33.1/43.4 | <0.001/NS |
Systolic BP (mmHg) | 131 ± 14 | 122 ± 15 | <0.001 |
Diastolic BP (mmHg) | 77 ± 9 | 72 ± 9 | <0.001 |
Heart rate (b/min) | 70 ± 11 | 72 ± 10 | <0.001 |
Creatinine (mcmol/l) | 83 ± 12 | 68 ± 9 | <0.001 |
Fasting glucose (mmol/l) | 5.2 ± 0.8 | 4.9 ± 0.7 | <0.001 |
HbA1c (%) | 5.6 ± 0.4 | 5.6 ± 0.4 | <0.001 |
Total cholesterol (mmol/l) | 5.16 ± 1.00 | 5.01 ± 0.98 | <0.001 |
HDL-cholesterol (mmol/l) | 1.29 ± 0.31 | 1.60 ± 0.39 | <0.001 |
LDL-cholesterol (mmol/l) | 3.38 ± 0.89 | 3.06 ± 0.88 | <0.001 |
Triglycerides (mmol/l) | 1.15 (0.84–1.66) | 0.86 (0.65–1.18) | <0.001 |
% with metabolic syndrome | 20.7 | 11.8 | <0.001 |
% with type 2 diabetes | 2.9 | 1.7 | <0.001 |
FT4 | FT3 | TSH | FT3FT4 | ||||||
---|---|---|---|---|---|---|---|---|---|
Model | β | P | β | P | β | P | β | P | |
SBP | 1 |
−0.048
|
<0.001
| 0.008 | 0.385 | 0.009 | 0.330 | 0.049 |
<0.001
|
2 | −0.013 | 0.147 |
0.096
|
<0.001
| 0.003 | 0.705 |
0.074
|
<0.001
| |
3 | −0.016 | 0.084 |
0.093
|
<0.001
| 0.003 | 0.741 |
0.075
|
<0.001
| |
4 | 0.015 | 0.098 |
0.081
|
<0.001
| 0.005 | 0.576 |
0.040
|
<0.001
| |
DBP | 1 |
−0.048
|
<0.001
|
−0.047
|
<0.001
| −0.017 | 0.066 | 0.009 | 0.304 |
2 | −0.005 | 0.584 |
0.054
|
<0.001
| −0.024 | 0.007 |
0.039
|
<0.001
| |
3 | −0.006 | 0.486 |
0.052
|
<0.001
| −0.027 | 0.002 |
0.039
|
<0.001
| |
4 | 0.020 | 0.023 |
0.041
|
<0.001
| −0.026 | 0.003 | 0.009 | 0.312 | |
HDL-C | 1 |
0.044
|
<0.001
|
−0.097
|
<0.001
| −0.016 | 0.086 |
−0.112
|
<0.001
|
2 |
0.060
|
<0.001
|
−0.072
|
<0.001
| −0.018 | 0.048 |
−0.103
|
<0.001
| |
3 |
0.065
|
<0.001
|
−0.063
|
<0.001
|
−0.032
|
<0.001
|
−0.100
|
<0.001
| |
4 | 0.023 | 0.008 |
−0.045
|
<0.001
|
−0.035
|
<0.001
|
−0.051
|
<0.001
| |
TG | 1 |
−0.084
|
<0.001
| 0.011 | 0.246 |
0.057
|
<0.001
|
0.083
|
<0.001
|
2 |
−0.074
|
<0.001
| 0.040 |
<0.001
|
0.076
|
<0.001
|
0.092
|
<0.001
| |
3 |
−0.081
|
<0.001
| 0.027 | 0.005 |
0.068
|
<0.001
|
0.090
|
<0.001
| |
4 | −0.040
|
<0.001
| 0.010 | 0.286 |
0.070
|
<0.001
|
0.041
|
<0.001
| |
FBG | 1 |
−0.074
|
<0.001
|
−0.040
|
<0.001
| −0.003 | 0.710 |
0.038
|
<0.001
|
2 |
−0.042
|
<0.001
|
0.037
|
<0.001
| −0.009 | 0.333 |
0.062
|
<0.001
| |
3 |
−0.043
|
<0.001
|
0.036
|
<0.001
| −0.008 | 0.353 |
0.062
|
<0.001
| |
4 | −0.014 | 0.112 | 0.024 | 0.010 | −0.007 | 0.456 | 0.028 |
0.001
| |
Waist | 1 |
−0.143
|
<0.001
| −0.018 | 0.051 | −0.015 | 0.106 |
0.119
|
<0.001
|
2 |
−0.105
|
<0.001
|
0.079
|
<0.001
| −0.021 | 0.016 |
0.148
|
<0.001
| |
3 |
−0.106
|
<0.001
|
0.079
|
<0.001
| −0.021 | 0.017 |
0.148
|
<0.001
| |
4 | −0.002 | 0.657 |
0.036
|
<0.001
| −0.015 | 0.001 |
0.0125
|
<0.001
|
FT4 | FT3 | TSH | FT3FT4 | ||||||
---|---|---|---|---|---|---|---|---|---|
Model | β | P | β | P | β | P | β | P | |
SBP | 1 |
0.034
|
<0.001
|
0.040
|
<0.001
|
0.033
|
<0.001
| 0.006 | 0.455 |
2 |
0.027
|
<0.001
|
0.131
|
<0.001
| 0.025 | 0.001 |
0.081
|
<0.001
| |
3 |
0.028
|
<0.001
|
0.137
|
<0.001
| 0.023 | 0.002 |
0.083
|
<0.001
| |
4 |
0.054
|
<0.001
|
0.130
|
<0.001
| 0.018 | 0.015 |
0.054
|
<0.001
| |
DBP | 1 | −0.003 | 0.754 | 0.015 | 0.06 | 0.007 | 0.426 | 0.017 | 0.044 |
2 | −0.007 | 0.400 |
0.064
|
<0.001
| 0.002 | 0.823 |
0.058
|
<0.001
| |
3 | −0.006 | 0.461 |
0.068
|
<0.001
| 0.000 | 0.962 |
0.059
|
<0.001
| |
4 | 0.014 | 0.078 |
0.063
|
<0.001
| −0.004 | 0.658 |
0.037
|
<0.001
| |
HDL-C | 1 | 0.016 | 0.046 |
−0.112
|
<0.001
| 0.020 | 0.016 |
−0.106
|
<0.001
|
2 | 0.013 | 0.107 |
−0.079
|
<0.001
| 0.016 | 0.047 | −0.078 | <0.001 | |
3 | 0.023 | 0.005 |
−0.062
|
<0.001
| 0.001 | 0.877 |
−0.071
|
<0.001
| |
4 | −0.016 | 0.034 |
−0.052
|
<0.001
| 0.009 | 0.240 | −0.027 | <0.001 | |
TG | 1 |
−0.068
|
<0.001
|
0.046
|
<0.001
|
0.078
|
<0.001
|
0.105
|
<0.001
|
2
|
−0.073
|
<0.001
|
0.101
|
<0.001
|
0.073
|
<0.001
|
0.154
|
<0.001
| |
3
|
−0.083
|
<0.001
|
0.086
|
<0.001
|
0.087
|
<0.001
|
0.150
|
<0.001
| |
4 |
−0.051
|
<0.001
|
0.078
|
<0.001
|
0.080
|
<0.001
|
0.113
|
<0.001
| |
FBG | 1 | 0.000 | 0.964 | −0.011 | 0.161 |
0.036
|
<0.001
| −0.003 | 0.731 |
2 | −0.007 | 0.405 |
0.059
|
<0.001
|
0.029
|
<0.001
|
0.057
|
<0.001
| |
3
| −0.007 | 0.405 |
0.059
|
<0.001
|
0.029
|
<0.001
|
0.056
|
<0.001
| |
4 | 0.025 | 0.001 |
0.051
|
<0.001
| 0.023 | 0.002 | 0.020 | 0.011 | |
Waist | 1 |
−0.091
|
<0.001
| −0.011 | 0.175 | 0.018 | 0.032 |
0.081
|
<0.001
|
2 |
−0.096
|
<0.001
|
0.048
|
<0.001
| 0.012 | 0.137 |
0.134
|
<0.001
| |
3 |
−0.097
|
<0.001
|
0.047
|
<0.001
| 0.014 | 0.084 |
0.133
|
<0.001
| |
4 | −0.004 | 0.380 |
0.024
|
<0.001
| −0.005 | 0.284 |
0.024
|
<0.001
|
Quartile | MetS/Total, n (%) | model 1 | model 2 | model 3 | model 4 | |
---|---|---|---|---|---|---|
TSH | 1 | 578/2923 (19.8) | 1 | 1 | 1 | 1 |
2 | 595/2975 (20.0) | 1.014 (0.893–1.153) | 1.015 (0.892–1.155) | 1.030 (0.904–1.174) | 1.000 (0.861–1.161) | |
3 | 618 (2946 (21.0) | 1.077 (0.948–1.223) | 1.072 (0.943–1.219) | 1.116 (0.980–1.271) | 1.101 (0.949–1.276) | |
4 | 650/2975 (21.8) | 1.134 (1.000–1.286) | 1.110 (0.977–1.261) | 1.155 (1.015–1.314) | 1.214 (1.047–1.407) | |
FT4 | 1 | 796/2877 (27.7) | 1 | 1 | 1 | 1 |
2 | 635/3000 (21.2) |
0.702 (0.623–0.791) #
|
0.717 (0.635–0.809) #
|
0.704 (0.623–0.796) #
|
0.816 (0.709–0.939) #
| |
3 | 532/3014 (17.7) |
0.560 (0.495–0.635) #
|
0.596 (0.525–0.675) #
|
0.579 (0.509–0.657) #
|
0.733 (0.634–0.848) #
| |
4 | 478/2928 (16.3) |
0.510 (0.449–0.579) #
|
0.567 (0.498–0.646) #
|
0.545 (0.478–0.622) #
|
0.722 (0.621–0.839) #
| |
FT3 | 1 | 516/2655 (19.4) | 1 | 1 | 1 | 1 |
2 | 652/3300 (19.8) | 1.021 (0.897–1.161) | 1.192 (1.045–1.360) |
1.172 (1.026–1.339) #
| 1.174 (1.010–1.366) | |
3 | 695/3185 (21.8) | 1.157 (1.018–1.315) |
1.487 (1.302–1.699) #
|
1.458 (1.275–1.668) #
|
1.360 (1.167–1.586) #
| |
4 | 578/2679 (21.6) | 1.140 (0.998–1.303) |
1.652 (1.434–1.904) #
|
1.577 (1.366–1.821) #
|
1.491 (1.266–1.756) #
| |
FT3FT4 | 1 | 457/2945 (15.5) | 1 | 1 | 1 | 1 |
2 | 528/2958 (17.8) | 1.183 (1.031–1.357) | 1.241 (1.080–1.426) |
1.220 (1.060–1.405) #
| 1.234 (1.054–1.445) | |
3 | 667/2960 (22.5) |
1.584 (1.388–1.807) #
|
1.753 (1.533–2.005) #
|
1.731 (1.512–1.983) #
|
1.537 (1.318–1.791) #
| |
4 | 789/2956 (26.7) |
1.982 (1.743–2.255) #
|
2.263 (1.984–2.582) #
|
2.267 (1.984–2.590) #
|
1.674 (1.438–1.948) #
|
Quartile | MetS/Total, n (%) | model 1 | model 2 | model 3 | model 4 | |
---|---|---|---|---|---|---|
TSH | 1 | 388/3726 (10.4) | 1 | 1 | 1 | 1 |
2 | 428/3710 (11.5) | 1.122 (0.970–1.298) | 1.149 (0.989–1.334) | 1.192 (1.025–1.386) | 1.162 (0.984–1.372) | |
3 | 451/3729 (12.1) | 1.184 (1.025–1.367) | 1.165 (1.005–1.351) | 1.219 (1.049–1.417) | 1.046 (0.885–1.236) | |
4 | 493/3735 (13.2) | 1.308 (1.136–1.507) # | 1.212 (1.053–1.061) | 1.288 (1.110–1.494) | 1.167 (0.990–1.375) | |
FT4 | 1 | 523/3784 (13.8) | 1 | 1 | 1 | 1 |
2 | 417/3707 (11.2) | 0.790 (0.689–0.907) |
0.761 (0.660–0.876) #
|
0.757 (0.656–0.874) #
| 0.854 (0.728–1.002) | |
3 | 423/3624 (11.7) | 0.824 (0.718–0.945) |
0.762 (0.661–0.877) #
|
0.758 (0.657–0.874) #
| 0.900 (0.767–1.057) | |
4 | 397/3785 (10.5) |
0.731 (0.636–0.840) #
|
0.651 (0.564–0.752) #
|
0.620 (0.535–0.717) #
| 0.819 (0.696–0.964) | |
FT3 | 1 | 317/3104 (10.2) | 1 | 1 | 1 | 1 |
2 | 482/4361 (11.1) | 1.095 (0.943–1.272) | 1.179 (1.011–1.375) | 1.154 (0.988–1.348) | 1.095 (0.923–1.299) | |
3 | 521/3897 (13.4) |
1.357 (1.170–1.574) #
|
1.644 (1.410–1.916) #
|
1.558 (1.334–1.819) #
|
1.515 (1.276–1.798) #
| |
4 | 439/3538 (12.4) | 1.245 (1.068–1.452) |
1.819 (1.550–2.134) #
|
1.707 (1.451–2.008) #
|
1.622 (1.354–1.942) #
| |
FT3FT4 | 1 | 374/3724 (10.0) | 1 | 1 | 1 | 1 |
2 | 392/3718 (10.5) | 1.056 (0.909–1.226) | 1.227 (1.051–1.432) | 1.217 (1.041–1.423) | 1.241 (1.045–1.473) | |
3 | 438/3726 (11.8) | 1.193 (1.031–1.381) |
1.557 (1.337–1.813) #
|
1.539 (1.319–1.795) #
|
1.423 (1.201–1.687) #
| |
4 | 556/3732 (14.9) |
1.568 (1.364–1.803) #
|
2.372 (2.045–2.751) #
|
2.329 (2.004–2.705) #
|
1.798 (1.522–2.125) #
|
Discussion
Author, year | N | Subjects’ age | Gender separation? | Corrections for confounders | Major findings | Ref |
---|---|---|---|---|---|---|
Roos, 2007 | 1581, 716 M | 28–75 yrs | No | Age, sex, HOMA-IR | FT4 negative association with TC, LDL-C, TG and waist, positive association with HDL-C, FT3 negative association with TC, LDL-C, TG | [3] |
Park, 2009 | 949 | Postmeno-pausal women | Women only | Age, BMI, HOMA-IR, FT4, exercise (3 levels), alcohol (3 levels) | TSH associated with TC, LDL-C, DBP and TG, MetS | [30] |
Kim, 2009 | 44,196, 25,147 M | 25–70 yrs | Yes | Age | Men: FT4 associated with BP, HDL-C, FBG, TG, and with WC in those over 50; Women: associated with BP, HDL-C, FBG, WC; no association with MetS, when adjusted for age | [4] |
Garduno-Garcia, 2010 | 3033 | 18–70 yrs | No | Age, sex | TSH associated with TC, TG, WC; FT4 associated with HDL-C, WC, HOMA-IR; 10% had SCH. | [31] |
Ruhla, 2010 | 1333, 481 M | >18 yrs | No | Age | TSH positively associated with BMI, TG, MetS; no data on FT4 or FT3 | [32] |
Park, 2011 | 5998, 3469 M | >18 yrs | No | Age, sex, BMI, smoking (y/n), alcohol (y/n), exercise (y/n) | TSH and FT4 associated with WC, FBG, HDL-C, FT4 also with DBP; higher TSH predicted MetS at follow-up | [5] |
Tarcin, 2012 | 211, 24 M | Obesity, 18–73 yrs | No | Age | FT3/FT4 negatively associated with FBG, TG, BP, TT3 positively with HOMA-IR, FBG, WC | [33] |
Waring, 2012 | 2119 | 70–79 yrs | No | Age, sex, race, BMI, smoking, HOMA-IR | TSH associated with MetS prevalence, in entire cohort with broad range of TSH levels, and in euthyroid range | [34] |
Oh, 2013 | 2760 | 18–39 | Women only | Age, BMI, HOMA-IR | TSH between 2.5 and 4.5 associated with BMI, WC, BP, TG | [35] |
Roef, 2014 | 2315, 1177 M | Middle-aged | No | Age, sex, height, current smoking | FT3 and FT3/FT4 ratio positively associated with BMI, WC, TG, BP, FBG, negatively with HDL-C; FT4 negatively associated with BMI, WC, TG | [36] |
Mehran, 2014 | 3755, 1709 M | ≥20 yrs | No | Age, sex, smoking, BMI, HOMA-IR | FT4 associated with HDL-C, LDL-C, TG, WC, BP, but not fasting glucose; no FT3 data | [37] |
Minami, 2015 | 283, 161 M | Children, 6–15 yrs | Yes | None | Higher FT3/FT4 ratio in boys with MetS; no difference thyroid function in girls with MetS | [38] |
Laclaustra, 2015 | 3533 M | 20–65 yrs | Men only | Age, alcohol consumption, smoking (never, former, current) | Higher TSH & lowest FT4 quintiles associated with higher MetS prevalence | [39] |
Kim, 2016 | 13,496, 8168 M | Middle-aged, 35–65 yrs | No | Age, sex, % body fat, smoking, HOMA-IR | Higher quartiles of T3 and T3/T4 ratio associated with MetS; only measured total T4 and T3 levels; modified MetS criteria | [6] |
Kim, 2017 | 12,037, 6950 M | Middle-aged, 35–65 yrs | No | Age, sex, smoking | Highest T3 quartile associated with highest 6-year MetS incidence; only measured total T4 and T3 levels; modified MetS criteria | [21] |
Ferrannini, 2017 | 940 | 30–60 yrs | No | Age, sex, BMI, WHR, family history of diabetes | Higher FT3 associated with decreased insulin sensitivity (insulin clamp), predicted follow-up increases in glycaemia | [22] |
Park, 2017 | 132,346, 66,991 M | >18 yrs | Yes | Age, BMI, smoking status, menopausal status (in women) | FT3FT4 ratio associated with increased risk of MetS parameters and insulin resistance | [7] |