Department of Nutrition and Food Hygiene, Zhejiang University School of Public Health, and Center of Clinical Big Data and Analytics of The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
Copyright © 2022 Korean Diabetes Association
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
CONFLICTS OF INTEREST
No potential conflict of interest relevant to this article was reported.
AUTHOR CONTRIBUTIONS
Conception or design: M.Y., H.G.
Acquisition, analysis, or interpretation of data: H.G., J.Y., M.Y.
Drafting the work or revising: H.G., J.Y., W.P., M.Y.
Final approval of the manuscript: H.G., J.Y., W.P., M.Y.
FUNDING
This study was funded by Natural Science Foundation of Zhejiang Province (LGF18H260003) and Beijing Municipal Functional Peptide Engineering Research Center Foundation (2018).
Values are presented as mean±standard deviation, median (interquartile range), or number (%).
SMD, standard mean difference; HbA1c, glycosylated hemoglobin; INS, insulin; IR, insulin resistance; HS-CRP, high-sensitivity C-reactive protein; FET, ferritin; TRF, transferrin; Apo, apolipoprotein; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; LP-A, lipoprotein (a); TG, triglyceride; TC, total cholesterol; ALB, albumin; ALT, alanine aminotransferase; TP, total protein.
HRs by model |
Women |
Men |
|||||
---|---|---|---|---|---|---|---|
IO HR (95% CI) | Reduction in β, %b | P value | IO HR (95% CI) | Reduction in β, %b | P value | ||
Baseline risk factor adjustment (method 1) | |||||||
Model 1: age | 4.74 (2.29–9.79) | Reference | <0.001 | 3.28 (1.66–6.46) | Reference | 0.001 | |
Model 2: model 1+biologicalc | 3.18 (1.56–6.48) | 25.64 | 0.001 | 2.13 (0.99–4.57) | 36.48 | 0.053 | |
Model 3: model 2+dietd | 3.47 (1.69–7.14) | 20.05 | 0.001 | 2.11 (0.98–4.52) | 37.15 | 0.055 | |
Model 4: model 3+physical examinationse | 3.34 (1.55–7.2) | 22.56 | 0.002 | 1.85 (0.86–3.97) | 48.19 | 0.114 | |
Model 5: model 4+behavioralf | 3.35 (1.54–7.26) | 22.37 | 0.002 | 1.91 (0.88–4.13) | 45.49 | 0.100 | |
Baseline risk factor adjustment (method 2) | |||||||
Model 1+biologicalc | 3.18 (1.56–6.48) | 25.64 | 0.001 | 2.13 (0.99–4.57) | 36.48 | 0.053 | |
Model 1+dietd | 4.95 (2.36–10.36) | –2.76 | <0.001 | 3.16 (1.6–6.25) | 3.03 | 0.001 | |
Model 1+physical examinationse | 4.18 (1.97–8.88) | 8.03 | <0.001 | 2.31 (1.18–4.55) | 29.32 | 0.015 | |
Model 1+behavioralf | 4.72 (2.28–9.77) | 0.32 | <0.001 | 3.32 (1.69–6.54) | –1.18 | 0.001 |
HR, hazard ratio; IO, iron overload; CI, confidence interval.
a The model was adjusted for baseline risk factors,
b Percent reduction in β estimate ([β0–βn]/[β0]×100). β0 indicates an age adjusted reference model. βn indicates the remaining models, ln HR=β,
c Biological factors: high-sensitivity C-reactive protein, triglyceride, total cholesterol, apolipoprotein B, alanine aminotransferase, insulin resistance, low-density lipoprotein cholesterol,
d Diet factors: carbohydrate intake, fat intake, protein intake,
e Physical examinations factors: body mass index, systolic pressure,
f Behavioral factors: smoking status, alcohol status.
Women |
Men |
|||||||
---|---|---|---|---|---|---|---|---|
Case | Hazard ratio | 95% CI | P value | Case | Hazard ratio | 95% CI | P value | |
IO by age, yra | ||||||||
<52 | 1,593 | 5.23 | 0.43–62.95 | 0.093 | 1,326 | 7.13 | 2.35–21.63 | <0.001 |
≥52 | 1,538 | 4.47 | 2.13–9.36 | <0.001 | 1,322 | 1.28 | 0.36–4.49 | 0.705 |
IO by BMI, kg/m2b | ||||||||
<24 | 1,884 | 4.77 | 1.27–17.92 | 0.021 | 1,604 | 1.02 | 0.13–7.85 | 0.985 |
24≤ and <28 | 933 | 4.55 | 0.90–23.11 | 0.068 | 815 | 1.70 | 0.51–5.70 | 0.393 |
≥28 | 314 | 4.09 | 1.38–12.15 | 0.011 | 229 | 4.46 | 1.26–15.75 | 0.020 |
Characteristic | Women (n=3,131) |
Men (n=2,648) |
|||||||
---|---|---|---|---|---|---|---|---|---|
Non-iron overload (n=2,916) | Iron overload (n=215) | P value | SMD | Non-iron overload (n=2,196) | Iron overload (n=452) | P value | SMD | ||
Age, yr | 50.14±14.03 | 62.03±10.54 | <0.001 | 0.958 | 51.30±14.83 | 49.01±13.03 | 0.002 | 0.164 | |
Physical examinations | |||||||||
Height, cm | 155.52±6.37 | 153.73±6.40 | <0.001 | 0.280 | 166.38±6.68 | 166.78±6.65 | 0.241 | 0.061 | |
Weight, kg | 56.54±9.54 | 57.81±10.02 | 0.061 | 0.129 | 63.77±11.18 | 68.60±11.13 | <0.001 | 0.433 | |
BMI, kg/m2 | 23.34±3.46 | 24.37±3.46 | <0.001 | 0.299 | 22.96±3.32 | 24.60±3.31 | <0.001 | 0.493 | |
Systolic pressure, mm Hg | 122.82±19.51 | 131.97±21.12 | <0.001 | 0.450 | 125.74±17.65 | 125.91±15.86 | 0.850 | 0.010 | |
Diastolic pressure, mm Hg | 78.81±11.00 | 81.37±11.73 | 0.001 | 0.225 | 81.49±10.96 | 83.40±10.94 | 0.001 | 0.174 | |
Biological | |||||||||
Glucose, mmol/L | 5.08 (4.71–5.54) | 5.39 (5.01–6.17) | <0.001 | 0.457 | 5.09 (4.70–5.58) | 5.36 (4.89–5.89) | <0.001 | 0.307 | |
HbA1c, mmol/L | 5.50 (5.20–5.80) | 5.70 (5.40–6.10) | <0.001 | 0.345 | 5.50 (5.20–5.80) | 5.60 (5.20–6.00) | <0.001 | 0.225 | |
INS, μIU/mL | 10.45 (7.53–14.86) | 12.44 (8.49–18.73) | <0.001 | 0.102 | 10.05 (6.92–14.48) | 11.44 (7.75–16.65) | <0.001 | 0.056 | |
IR | |||||||||
No | 1,768 (60.6) | 106 (49.3) | 0.001 | 0.229 | 1,398 (63.7) | 242 (53.5) | <0.001 | 0.207 | |
Yes | 1,148 (39.4) | 109 (50.7) | 798 (36.3) | 210 (46.5) | |||||
Hemoglobin, g/L | 132.00 (122.00–140.00) | 133.00 (125.00–142.00) | 0.095 | 0.059 | 151.00 (141.00–162.00) | 155.00 (146.00–165.00) | <0.001 | 0.242 | |
HS-CRP, mg/L | 1.00 (0.00–2.00) | 2.00 (1.00–4.00) | <0.001 | 0.174 | 1.00 (1.00–2.00) | 1.00 (1.00–3.00) | <0.001 | 0.115 | |
FET, ng/mL | 46.38 (22.15–81.95) | 301.87 (235.48–499.30) | <0.001 | 2.217 | 105.24 (66.56–155.58) | 556.36 (416.61–787.13) | <0.001 | 2.628 | |
TRF, mg/gL | 291.00 (259.00–329.00) | 274.00 (246.00–308.00) | <0.001 | 0.380 | 277.00 (246.00–311.00) | 274.00 (245.00–311.25) | 0.588 | 0.001 | |
Apo-A, g/L | 1.12 (0.98–1.31) | 1.14 (0.96–1.36) | 0.549 | 0.048 | 1.09 (0.93–1.30) | 1.03 (0.88–1.23) | <0.001 | 0.181 | |
Apo-B, g/L | 0.88 (0.73–1.08) | 1.06 (0.85–1.25) | <0.001 | 0.564 | 0.88 (0.72–1.05) | 0.96 (0.81–1.15) | <0.001 | 0.334 | |
LDL-C, mmol/L | 2.94 (2.40–3.60) | 3.26 (2.60–4.14) | <0.001 | 0.302 | 2.88 (2.33–3.45) | 2.94 (2.26–3.65) | 0.300 | 0.053 | |
HDL-C, mmol/L | 1.45 (1.24–1.70) | 1.39 (1.15–1.61) | 0.004 | 0.178 | 1.36 (1.15–1.62) | 1.23 (1.02–1.50) | <0.001 | 0.288 | |
LP-A, mg/dL | 83.00 (44.00–179.00) | 93.00 (52.50–200.00) | 0.151 | 0.108 | 75.00 (38.00–161.25) | 64.00 (30.75–134.75) | 0.001 | 0.083 | |
TG, mmol/L | 1.20 (0.83–1.76) | 1.70 (1.21–2.71) | <0.001 | 0.542 | 1.19 (0.81–1.86) | 1.84 (1.17–2.89) | <0.001 | 0.508 | |
TC, mmol/L | 4.80 (4.18–5.52) | 5.41 (4.65–6.17) | <0.001 | 0.501 | 4.72 (4.16–5.32) | 4.95 (4.38–5.81) | <0.001 | 0.337 | |
ALB, g/L | 46.90 (45.00–49.10) | 47.40 (45.55–49.75) | 0.011 | 0.183 | 47.40 (45.20–49.70) | 48.20 (46.00–50.40) | <0.001 | 0.197 | |
ALT, U/L | 16.00 (12.00–23.00) | 22.00 (15.00–34.50) | <0.001 | 0.460 | 20.00 (15.00–28.00) | 27.00 (18.00–42.00) | <0.001 | 0.448 | |
TP, g/L | 77.90 (74.70–81.30) | 77.80 (75.20–82.10) | 0.311 | 0.081 | 76.50 (73.10–79.80) | 76.30 (73.20–79.60) | 0.564 | 0.040 | |
Diet | |||||||||
Calorie, kcal | 1,994.50±605.06 | 1,935.67±586.26 | 0.168 | 0.099 | 2,366.86±691.93 | 2,357.75±678.95 | 0.798 | 0.013 | |
Carbohydrate, g | 278.29±94.09 | 267.27±90.88 | 0.097 | 0.119 | 327.23±107.88 | 318.21±107.60 | 0.106 | 0.084 | |
Fat, g | 70.05±38.54 | 68.72±35.48 | 0.626 | 0.036 | 80.58±39.30 | 81.97±42.67 | 0.500 | 0.034 | |
Protein, g | 61.77±21.00 | 61.56±21.58 | 0.884 | 0.010 | 72.57±24.80 | 74.10±23.97 | 0.230 | 0.063 | |
Behavioral | |||||||||
Smoke | |||||||||
No | 2,837 (97.3) | 204 (94.9) | 0.054 | 0.124 | 782 (35.6) | 175 (38.7) | 0.217 | 0.064 | |
Yes | 79 (2.7) | 11 (5.1) | 1,414 (64.4) | 277 (61.3) | |||||
Alcohol | |||||||||
No | 2,662 (91.3) | 198 (92.1) | 0.802 | 0.029 | 868 (39.5) | 140 (31.0) | 0.001 | 0.180 | |
Yes | 254 (8.7) | 17 (7.9) | 1,328 (60.5) | 312 (69.0) |
Characteristic | Women |
Men |
||||||
---|---|---|---|---|---|---|---|---|
Odds ratio | 95% CI | Z | P value | Odds ratio | 95% CI | Z | P value | |
Age | 1.07 | 1.06–1.09 | 10.12 | <0.001 | 1.00 | 0.99–1.01 | –0.66 | 0.507 |
HS-CRP | 1.00 | 0.99–1.01 | 1.24 | 0.214 | 1.02 | 1.00–1.03 | 2.50 | 0.013 |
TG | 1.26 | 1.15–1.38 | 5.06 | <0.001 | 1.23 | 1.15–1.31 | 6.45 | <0.001 |
Apo-B | 1.94 | 1.13–3.31 | 2.43 | 0.015 | 2.05 | 1.35–3.11 | 3.35 | 0.001 |
ALT | 1.02 | 1.01–1.03 | 5.87 | <0.001 | 1.01 | 1.01–1.02 | 4.84 | <0.001 |
IR | ||||||||
No | Reference | Reference | Reference | Reference | Reference | Reference | Reference | Reference |
Yes | 1.02 | 0.74–1.39 | 0.12 | 0.908 | 0.99 | 0.79–1.25 | –0.07 | 0.947 |
Carbohydrate | 1.00 | 1.00–1.00 | –0.73 | 0.468 | 1.00 | 1.00–1.00 | –1.30 | 0.194 |
Protein | 1.01 | 1.00–1.02 | 2.11 | 0.035 | 1.00 | 1.00–1.01 | 0.56 | 0.574 |
Fat | 1.00 | 0.99–1.00 | –0.65 | 0.514 | 1.00 | 1.00–1.00 | –0.22 | 0.823 |
BMI | 1.03 | 0.98–1.07 | 1.17 | 0.243 | 1.08 | 1.04–1.12 | 4.27 | <0.001 |
Systolic pressure | 1.00 | 0.99–1.01 | –0.64 | 0.520 | 1.00 | 0.99–1.00 | –1.38 | 0.167 |
Smoke | ||||||||
No | Reference | Reference | Reference | Reference | Reference | Reference | Reference | Reference |
Yes | 1.05 | 0.50–2.01 | 0.14 | 0.892 | 0.85 | 0.68–1.07 | –1.38 | 0.168 |
Alcohol | ||||||||
No | Reference | Reference | Reference | Reference | Reference | Reference | Reference | Reference |
Yes | 0.84 | 0.46–1.43 | –0.61 | 0.545 | 1.39 | 1.10–1.76 | 2.73 | 0.006 |
HRs by model | Women |
Men |
|||||
---|---|---|---|---|---|---|---|
IO HR (95% CI) | Reduction in β, % |
P value | IO HR (95% CI) | Reduction in β, % |
P value | ||
Baseline risk factor adjustment (method 1) | |||||||
Model 1: age | 4.74 (2.29–9.79) | Reference | <0.001 | 3.28 (1.66–6.46) | Reference | 0.001 | |
Model 2: model 1+biological |
3.18 (1.56–6.48) | 25.64 | 0.001 | 2.13 (0.99–4.57) | 36.48 | 0.053 | |
Model 3: model 2+diet |
3.47 (1.69–7.14) | 20.05 | 0.001 | 2.11 (0.98–4.52) | 37.15 | 0.055 | |
Model 4: model 3+physical examinations |
3.34 (1.55–7.2) | 22.56 | 0.002 | 1.85 (0.86–3.97) | 48.19 | 0.114 | |
Model 5: model 4+behavioral |
3.35 (1.54–7.26) | 22.37 | 0.002 | 1.91 (0.88–4.13) | 45.49 | 0.100 | |
Baseline risk factor adjustment (method 2) | |||||||
Model 1+biological |
3.18 (1.56–6.48) | 25.64 | 0.001 | 2.13 (0.99–4.57) | 36.48 | 0.053 | |
Model 1+diet |
4.95 (2.36–10.36) | –2.76 | <0.001 | 3.16 (1.6–6.25) | 3.03 | 0.001 | |
Model 1+physical examinations |
4.18 (1.97–8.88) | 8.03 | <0.001 | 2.31 (1.18–4.55) | 29.32 | 0.015 | |
Model 1+behavioral |
4.72 (2.28–9.77) | 0.32 | <0.001 | 3.32 (1.69–6.54) | –1.18 | 0.001 |
Women |
Men |
|||||||
---|---|---|---|---|---|---|---|---|
Case | Hazard ratio | 95% CI | P value | Case | Hazard ratio | 95% CI | P value | |
IO by age, yr |
||||||||
<52 | 1,593 | 5.23 | 0.43–62.95 | 0.093 | 1,326 | 7.13 | 2.35–21.63 | <0.001 |
≥52 | 1,538 | 4.47 | 2.13–9.36 | <0.001 | 1,322 | 1.28 | 0.36–4.49 | 0.705 |
IO by BMI, kg/m2 |
||||||||
<24 | 1,884 | 4.77 | 1.27–17.92 | 0.021 | 1,604 | 1.02 | 0.13–7.85 | 0.985 |
24≤ and <28 | 933 | 4.55 | 0.90–23.11 | 0.068 | 815 | 1.70 | 0.51–5.70 | 0.393 |
≥28 | 314 | 4.09 | 1.38–12.15 | 0.011 | 229 | 4.46 | 1.26–15.75 | 0.020 |
Values are presented as mean±standard deviation, median (interquartile range), or number (%). SMD, standard mean difference; HbA1c, glycosylated hemoglobin; INS, insulin; IR, insulin resistance; HS-CRP, high-sensitivity C-reactive protein; FET, ferritin; TRF, transferrin; Apo, apolipoprotein; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; LP-A, lipoprotein (a); TG, triglyceride; TC, total cholesterol; ALB, albumin; ALT, alanine aminotransferase; TP, total protein.
CI, confidence interval; HS-CRP, high-sensitivity C-reactive protein; TG, triglyceride; Apo, apolipoprotein; ALT, alanine aminotransferase; IR, insulin resistance; BMI, body mass index.
HR, hazard ratio; IO, iron overload; CI, confidence interval. The model was adjusted for baseline risk factors, Percent reduction in β estimate ([β0–βn]/[β0]×100). β0 indicates an age adjusted reference model. βn indicates the remaining models, ln HR=β, Biological factors: high-sensitivity C-reactive protein, triglyceride, total cholesterol, apolipoprotein B, alanine aminotransferase, insulin resistance, low-density lipoprotein cholesterol, Diet factors: carbohydrate intake, fat intake, protein intake, Physical examinations factors: body mass index, systolic pressure, Behavioral factors: smoking status, alcohol status.
BMI, body mass index; CI, confidence interval; IO, iron overload. The model was adjusted for high-sensitivity C-reactive protein (HS-CRP), The model was adjusted for age and HS-CRP.