Table 2.
Prospective associations between plasma vitamin C and carotenoids and incident type 2 diabetes in the EPIC-InterAct study*
| Hazard ratio (95% confidence interval)† | P value for trend | ||||||
|---|---|---|---|---|---|---|---|
| Group 1 | Group 2 | Group 3 | Group 4 | Group 5 | For each one standard deviation | ||
| Vitamin C, (median, µmol/L) | 17.0 | 32.8 | 42.3 | 51.2 | 64.9 | — | — |
| No of cases/person years | 2431/13 089 | 2042/13 166 | 1482/13 337 | 1256/14 898 | 949/17 420 | — | — |
| Model 1a | 1.0 (ref) | 0.84 (0.77 to 0.92) | 0.61 (0.53 to 0.71) | 0.53 (0.46 to 0.61) | 0.39 (0.31 to 0.50) | 0.71 (0.65 to 0.78) | <0.001 |
| Model 1b | 1.0 (ref) | 0.87 (0.80 to 0.96) | 0.65 (0.56 to 0.76) | 0.57 (0.50 to 0.66) | 0.43 (0.34 to 0.54) | 0.74 (0.68 to 0.80) | <0.001 |
| Model 2 | 1.0 (ref) | 0.94 (0.83 to 1.08) | 0.72 (0.60 to 0.87) | 0.68 (0.56 to 0.82) | 0.58 (0.47 to 0.72) | 0.82 (0.76 to 0.89) | <0.001 |
| Total carotenoids, (median, µmol/L) | 0.75 | 1.17 | 1.52 | 1.93 | 2.70 | — | — |
| No of cases/person years | 2952/10 116 | 1944/11 940 | 1316/14 155 | 1127/16 904 | 874/19 899 | — | — |
| Model 1a | 1.0 (ref) | 0.67 (0.61 to 0.74) | 0.43 (0.37 to 0.52) | 0.35 (0.28 to 0.42) | 0.24 (0.18 to 0.32) | 0.53 (0.47 to 0.61) | <0.001 |
| Model 1b | 1.0 (ref) | 0.72 (0.62 to 0.83) | 0.51 (0.44 to 0.60) | 0.43 (0.36 to 0.52) | 0.31 (0.24 to 0.40) | 0.60 (0.53 to 0.67) | <0.001 |
| Model 2 | 1.0 (ref) | 0.83 (0.74 to 0.92) | 0.64 (0.54 to 0.75) | 0.61 (0.53 to 0.70) | 0.51 (0.43 to 0.60) | 0.75 (0.68 to 0.82) | <0.001 |
| α carotene, (median, µmol/L) | 0.02 | 0.05 | 0.07 | 0.12 | 0.23 | — | — |
| No of cases/person years | 2629/10 061 | 1922/13 665 | 1571/15 458 | 1254/16 266 | 837/17 564 | — | — |
| Model 1a | 1.0 (ref) | 0.72 (0.65 to 0.80) | 0.54 (0.46 to 0.62) | 0.46 (0.41 to 0.52) | 0.29 (0.24 to 0.35) | 0.57 (0.48 to 0.68) | <0.001 |
| Model 1b | 1.0 (ref) | 0.75 (0.66 to 0.86) | 0.60 (0.52 to 0.69) | 0.53 (0.47 to 0.60) | 0.36 (0.30 to 0.43) | 0.65 (0.56 to 0.76) | <0.001 |
| Model 2 | 1.0 (ref) | 0.81 (0.70 to 0.94) | 0.72 (0.64 to 0.82) | 0.69 (0.59 to 0.79) | 0.53 (0.46 to 0.62) | 0.79 (0.72 to 0.88) | <0.001 |
| β carotene, (median, µmol/L) | 0.14 | 0.26 | 0.37 | 0.53 | 0.87 | — | — |
| No of cases/person years | 2911/8142 | 2064/11 861 | 1417/15 096 | 1035/17 520 | 786/20 395 | — | — |
| Model 1a | 1.0 (ref) | 0.68 (0.60 to 0.78) | 0.44 (0.40 to 0.49) | 0.33 (0.28 to 0.37) | 0.24 (0.20 to 0.28) | 0.48 (0.40 to 0.58) | <0.001 |
| Model 1b | 1.0 (ref) | 0.70 (0.61 to 0.80) | 0.48 (0.43 to 0.54) | 0.38 (0.34 to 0.43) | 0.29 (0.26 to 0.34) | 0.55 (0.46 to 0.65) | <0.001 |
| Model 2 | 1.0 (ref) | 0.78 (0.69 to 0.88) | 0.60 (0.54 to 0.68) | 0.53 (0.47 to 0.60) | 0.45 (0.39 to 0.52) | 0.71 (0.62 to 0.82) | <0.001 |
| Lycopene, (median, µmol/L) | 0.15 | 0.28 | 0.41 | 0.56 | 0.82 | — | — |
| No of cases/person years | 2395/10 449 | 1879/12 779 | 1447/13 840 | 1299/16 393 | 1193/19 553 | — | — |
| Model 1a | 1.0 (ref) | 0.79 (0.69 to 0.90) | 0.66 (0.60 to 0.73) | 0.57 (0.48 to 0.69) | 0.50 (0.38 to 0.64) | 0.76 (0.68 to 0.85) | <0.001 |
| Model 1b | 1.0 (ref) | 0.89 (0.80 to 0.99) | 0.73 (0.65 to 0.82) | 0.68 (0.59 to 0.78) | 0.59 (0.47 to 0.75) | 0.81 (0.75 to 0.89) | <0.001 |
| Model 2 | 1.0 (ref) | 0.95 (0.86 to 1.06) | 0.84 (0.75 to 0.94) | 0.81 (0.71 to 0.92) | 0.79 (0.68 to 0.93) | 0.91 (0.85 to 0.98) | 0.01 |
| Lutein, (median, µmol/L) | 0.13 | 0.20 | 0.25 | 0.33 | 0.49 | — | — |
| No of cases/person years | 2508/11 727 | 1856/11 950 | 1464/13 668 | 1268/14 951 | 1117/2 0718 | — | — |
| Model 1a | 1.0 (ref) | 0.72 (0.66 to 0.79) | 0.52 (0.44 to 0.61) | 0.41 (0.32 to 0.51) | 0.30 (0.24 to 0.38) | 0.57 (0.48 to 0.68) | <0.001 |
| Model 1b | 1.0 (ref) | 0.79 (0.72 to 0.87) | 0.64 (0.57 to 0.71) | 0.56 (0.48 to 0.65) | 0.49 (0.42 to 0.56) | 0.70 (0.62 to 0.79) | <0.001 |
| Model 2 | 1.0 (ref) | 0.89 (0.78 to 1.01) | 0.75 (0.65 to 0.86) | 0.70 (0.59 to 0.82) | 0.65 (0.55 to 0.78) | 0.84 (0.77 to 0.91) | <0.001 |
| Zeaxanthin, (median, µmol/L) | 0.01 | 0.03 | 0.04 | 0.06 | 0.10 | — | — |
| No of cases/person years | 2159/13 624 | 1658/17 107 | 1510/18 591 | 1479/15 470 | 1407/8222 | — | — |
| Model 1a | 1.0 (ref) | 0.87 (0.74 to 1.01) | 0.77 (0.66 to 0.90) | 0.70 (0.58 to 0.85) | 0.55 (0.47 to 0.65) | 0.76 (0.68 to 0.85) | <0.001 |
| Model 1b | 1.0 (ref) | 0.92 (0.78 to 1.09) | 0.89 (0.78 to 1.01) | 0.84 (0.67 to 1.05) | 0.71 (0.59 to 0.86) | 0.87 (0.80 to 0.94) | <0.001 |
| Model 2 | 1.0 (ref) | 0.95 (0.84 to 1.07) | 0.98 (0.86 to 1.13) | 0.99 (0.78 to 1.27) | 0.86 (0.66 to 1.12) | 0.96 (0.88 to 1.05) | 0.34 |
| β cryptoxanthin, (median, µmol/L) | 0.05 | 0.12 | 0.20 | 0.32 | 0.61 | — | — |
| No of cases/person years | 2431/10 990 | 1712/15 889 | 1494/16 483 | 1379/15 438 | 1197/14 213 | — | — |
| Model 1a | 1.0 (ref) | 0.75 (0.63 to 0.89) | 0.63 (0.52 to 0.77) | 0.58 (0.49 to 0.69) | 0.42 (0.31 to 0.56) | 0.64 (0.55 to 0.75) | <0.001 |
| Model 1b | 1.0 (ref) | 0.77 (0.65 to 0.91) | 0.74 (0.64 to 0.87) | 0.66 (0.56 to 0.78) | 0.51 (0.38 to 0.69) | 0.75 (0.67 to 0.84) | <0.001 |
| Model 2 | 1.0 (ref) | 0.81 (0.68 to 0.97) | 0.81 (0.69 to 0.95) | 0.83 (0.72 to 0.96) | 0.72 (0.56 to 0.93) | 0.88 (0.81 to 0.96) | 0.001 |
| Composite biomarker score (median) | −0.66 | −0.31 | −0.05 | 0.23 | 0.74 | — | — |
| Fruit and vegetable intake (median, g/day) | 274 | 357 | 396 | 452 | 508 | — | — |
| No of cases/person years | 2752/10 909 | 1719/13 249 | 1249/14 624 | 1047/15 582 | 770/17 471 | — | — |
| Model 1a | 1.0 (ref) | 0.61 (0.53 to 0.70) | 0.43 (0.35 to 0.53) | 0.32 (0.24 to 0.43) | 0.22 (0.17 to 0.30) | 0.55 (0.48 to 0.63) | <0.001 |
| Model 1b | 1.0 (ref) | 0.67 (0.59 to 0.77) | 0.52 (0.44 to 0.62) | 0.42 (0.33 to 0.52) | 0.31 (0.25 to 0.39) | 0.61 (0.55 to 0.69) | <0.001 |
| Model 2 | 1.0 (ref) | 0.77 (0.68 to 0.87) | 0.66 (0.54 to 0.80) | 0.59 (0.48 to 0.72) | 0.50 (0.40 to 0.62) | 0.75 (0.67 to 0.83) | <0.001 |
Sample size is 19 255 for vitamin C, 19 907 for carotenoids, and 18 276 for the composite biomarker score. Numbers (N) of cases and person years (subcohort) by the biomarker split into five equal groups (group 1, the lowest; group 5, the highest) are presented. Model 1a: adjusted for age (as underlying timescale), sex and centre; model 1b: model 1a+physical activity, smoking status, employment, marital status, education, alcohol intake, total energy intake, high density lipoprotein cholesterol, and low density lipoprotein cholesterol; model 2: model 1b+adiposity (body mass index and waist circumference). Model 1b and model 2 of plasma vitamin C were not adjusted for high and low density lipoprotein cholesterol.
Hazard ratios for groups 1-4 (compared with group 1) and for each one standard deviation (SD) of each biomarker, were estimated from country-specific, Prentice weighted Cox regression models; estimates were then combined across countries by random effects meta-analysis. P value for trend was calculated as the trend per group for each biomarker. The plasma composite biomarker score was generated by calculating the average of the z scores of vitamin C and six individual carotenoids. Standard deviation was 19.2 µmol/L for vitamin C, 0.83 µmol/L for total carotenoids, 0.12 µmol/L for α carotene, 0.41 µmol/L for β carotene, 0.27 µmol/L for lycopene, 0.15 µmol/L for lutein, 0.04 µmol/L for zeaxanthin, 0.29 µmol/L for β cryptoxanthin, and 0.57 for the composite biomarker score.