Table 2.
Association between incident type 2 diabetes and cancer incidence (NHS: 1978-2014; HPFS: 1988-2014)
| Cancer outcomes | Women (NHS) |
Men (HPFS) |
Meta-analyzed HR (95% CI)a |
P heterogeneity | ||
|---|---|---|---|---|---|---|
| No diabetes | Diabetes | No diabetes | Diabetes | |||
| Composite cancer outcomes | ||||||
| Total cancer | ||||||
| Case/person-year | 32 147/3 156 447 | 3182/181 931 | 7755/896 795 | 765/58 905 | ||
| Age-adjusted model, HR (95% CI) | (Referent) | 1.24 (1.19 to 1.28) | (Referent) | 1.17 (1.09 to 1.26) | 1.22 (1.18 to 1.27) | .21 |
| Multivariable adjusted model, HR (95% CI)b | (Referent) | 1.29 (1.24 to 1.35) | (Referent) | 1.20 (1.11 to 1.29) | 1.27 (1.22 to 1.32) | .09 |
| Additionally adjusted for BMI, HR (95% CI)c | (Referent) | 1.22 (1.17 to 1.28) | (Referent) | 1.16 (1.07 to 1.25) | 1.21 (1.16 to 1.26) | .22 |
| Obesity-related cancerd | ||||||
| Case/person-year | 16 956/3 168 448 | 1820/182 934 | 2888/900 763 | 313/59 225 | ||
| Age-adjusted model, HR (95% CI) | (Referent) | 1.31 (1.25 to 1.37) | (Referent) | 1.42 (1.26 to 1.60) | 1.32 (1.27 to 1.39) | .22 |
| Multivariable adjusted model, HR (95% CI)b | (Referent) | 1.37 (1.29 to 1.46) | (Referent) | 1.46 (1.29 to 1.65) | 1.39 (1.32 to 1.47) | .39 |
| Additionally adjusted for BMI, HR (95% CI)c | (Referent) | 1.26 (1.18 to 1.34) | (Referent) | 1.37 (1.21 to 1.55) | 1.28 (1.21 to 1.35) | .23 |
| Diabetes-related cancere | ||||||
| Case/person-year | 20 807/3 165 042 | 2021/182 782 | 3677/900 047 | 399/59 163 | ||
| Age-adjusted model, HR (95% CI) | (Referent) | 1.28 (1.22 to 1.34) | (Referent) | 1.33 (1.20 to 1.47) | 1.28 (1.23 to 1.34) | .50 |
| Multivariable adjusted model, HR (95% CI)b | (Referent) | 1.34 (1.27 to 1.42) | (Referent) | 1.32 (1.19 to 1.47) | 1.34 (1.27 to 1.41) | .79 |
| Additionally adjusted for BMI, HR (95% CI)c | (Referent) | 1.25 (1.18 to 1.32) | (Referent) | 1.25 (1.13 to 1.40) | 1.25 (1.19 to 1.32) | .94 |
| Individual cancers | ||||||
| Colorectal cancer | ||||||
| Case/person-year | 2245/3 181 603 | 229/184 360 | 1030/902 189 | 109/59 345 | ||
| Age-adjusted model, HR (95% CI) | (Referent) | 1.24 (1.08 to 1.42) | (Referent) | 1.44 (1.17 to 1.76) | 1.30 (1.16 to 1.45) | .23 |
| Multivariable adjusted model, HR (95% CI)b | (Referent) | 1.20 (1.01 to 1.42) | (Referent) | 1.45 (1.19 to 1.78) | 1.30 (1.14 to 1.48) | .16 |
| Additionally adjusted for BMI, HR (95% CI)c | (Referent) | 1.13 (0.95 to 1.35) | (Referent) | 1.32 (1.08 to 1.63) | 1.21 (1.06 to 1.38) | .25 |
| Lung cancer | ||||||
| Case/person-year | 2679/3 181 921 | 261/184 406 | 776/902 687 | 98/59 386 | ||
| Age-adjusted model, HR (95% CI) | (Referent) | 1.03 (0.91 to 1.17) | (Referent) | 1.41 (1.14 to 1.75) | 1.12 (1.00 to 1.25) | .01 |
| Multivariable adjusted model, HR (95% CI)b | (Referent) | 1.12 (0.96 to 1.31) | (Referent) | 1.42 (1.14 to 1.76) | 1.21 (1.07 to 1.38) | .09 |
| Additionally adjusted for BMI, HR (95% CI)c | (Referent) | 1.20 (1.03 to 1.41) | (Referent) | 1.42 (1.14 to 1.77) | 1.27 (1.12 to 1.45) | .23 |
| Melanoma | ||||||
| Case/person-year | 1019/3 182 641 | 66/184 515 | 1136/902 084 | 82/59 366 | ||
| Age-adjusted model, HR (95% CI) | (Referent) | 0.86 (0.67 to 1.11) | (Referent) | 0.83 (0.66 to 1.04) | 0.84 (0.71 to 1.00) | .82 |
| Multivariable adjusted model, HR (95% CI)b | (Referent) | 1.01 (0.74 to 1.39) | (Referent) | 0.89 (0.71 to 1.12) | 0.93 (0.77 to 1.12) | .52 |
| Additionally adjusted for BMI, HR (95% CI)c | (Referent) | 0.95 (0.69 to 1.30) | (Referent) | 0.89 (0.70 to 1.12) | 0.91 (0.75 to 1.10) | .75 |
| Non-Hodgkin lymphoma | ||||||
| Case/person-year | 1274/3 182 442 | 114/184 473 | 812/902 383 | 66/59 387 | ||
| Age-adjusted model, HR (95% CI) | (Referent) | 1.01 (0.83 to 1.22) | (Referent) | 1.02 (0.79 to 1.31) | 1.01 (0.87 to 1.18) | .95 |
| Multivariable adjusted model, HR (95% CI)b | (Referent) | 1.00 (0.78 to 1.28) | (Referent) | 1.02 (0.78 to 1.31) | 1.01 (0.84 to 1.20) | .93 |
| Additionally adjusted for BMI, HR (95% CI)c | (Referent) | 1.01 (0.79 to 1.30) | (Referent) | 0.99 (0.76 to 1.29) | 1.00 (0.84 to 1.20) | .91 |
| Pancreatic cancer | ||||||
| Case/person-year | 556/3 183 276 | 111/184 521 | 318/902 980 | 64/59 414 | ||
| Age-adjusted model, HR (95% CI) | (Referent) | 2.05 (1.66 to 2.52) | (Referent) | 2.16 (1.64 to 2.84) | 2.09 (1.77 to 2.46) | .76 |
| Multivariable adjusted model, HR (95% CI)b | (Referent) | 2.00 (1.54 to 2.60) | (Referent) | 2.29 (1.73 to 3.04) | 2.13 (1.76 to 2.58) | .49 |
| Additionally adjusted for BMI, HR (95% CI)c | (Referent) | 1.87 (1.43 to 2.44) | (Referent) | 2.34 (1.76 to 3.12) | 2.07 (1.70 to 2.52) | .26 |
| Bladder cancer | ||||||
| Case/person-year | 574/3 182 974 | 63/184 515 | 718/902 425 | 63/59 385 | ||
| Age-adjusted model, HR (95% CI) | (Referent) | 1.18 (0.91 to 1.54) | (Referent) | 0.98 (0.76 to 1.28) | 1.08 (0.89 to 1.30) | .34 |
| Multivariable adjusted model, HR (95% CI)b | (Referent) | 1.25 (0.90 to 1.73) | (Referent) | 0.92 (0.71 to 1.20) | 1.04 (0.85 to 1.28) | .16 |
| Additionally adjusted for BMI, HR (95% CI)c | (Referent) | 1.21 (0.87 to 1.68) | (Referent) | 0.91 (0.69 to 1.18) | 1.02 (0.82 to 1.25) | .19 |
| Kidney cancer | ||||||
| Case/person-year | 430/3 183 183 | 59/184 512 | 292/902 867 | 30/59 417 | ||
| Age-adjusted model, HR (95% CI) | (Referent) | 1.52 (1.15 to 2.00) | (Referent) | 1.28 (0.88 to 1.88) | 1.43 (1.14 to 1.79) | .49 |
| Multivariable adjusted model, HR (95% CI)b | (Referent) | 1.48 (1.05 to 2.07) | (Referent) | 1.22 (0.83 to 1.80) | 1.36 (1.05 to 1.76) | .48 |
| Additionally adjusted for BMI, HR (95% CI)c | (Referent) | 1.18 (0.83 to 1.66) | (Referent) | 1.18 (0.80 to 1.75) | 1.18 (0.91 to 1.53) | .99 |
| Esophagus cancer | ||||||
| Case/person-year | 114/3 183 447 | 14/184 561 | 138/903 025 | 25/59 422 | ||
| Age-adjusted model, HR (95% CI) | (Referent) | 1.21 (0.69 to 2.12) | (Referent) | 2.15 (1.39 to 3.33) | 1.73 (1.23 to 2.45) | .11 |
| Multivariable adjusted model, HR (95% CI)b | (Referent) | 1.66 (0.89 to 3.12) | (Referent) | 2.13 (1.36 to 3.33) | 1.96 (1.36 to 2.82) | .53 |
| Additionally adjusted for BMI, HR (95% CI)c | (Referent) | 1.71 (0.90 to 3.26) | (Referent) | 1.93 (1.22 to 3.05) | 1.85 (1.28 to 2.69) | .76 |
| Leukemia | ||||||
| Case/person-year | 268/3 183 353 | 32/184 554 | 262/902 904 | 19/59 422 | ||
| Age-adjusted model, HR (95% CI) | (Referent) | 1.37 (0.95 to 1.99) | (Referent) | 0.83 (0.52 to 1.33) | 1.13 (0.84 to 1.51) | .10 |
| Multivariable adjusted model, HR (95% CI)b | (Referent) | 1.32 (0.83 to 2.08) | (Referent) | 0.86 (0.53 to 1.38) | 1.07 (0.77 to 1.49) | .20 |
| Additionally adjusted for BMI, HR (95% CI)c | (Referent) | 1.18 (0.74 to 1.88) | (Referent) | 0.79 (0.49 to 1.28) | 0.97 (0.69 to 1.36) | .25 |
| Liver cancer | ||||||
| Case/person-year | 82/3 183 470 | 32/184 552 | 43/903 100 | 12/59 433 | ||
| Age-adjusted model, HR (95% CI) | (Referent) | 3.94 (2.59 to 5.99) | (Referent) | 2.82 (1.47 to 5.41) | 3.57 (2.51 to 5.08) | .40 |
| Multivariable adjusted model, HR (95% CI)b | (Referent) | 4.12 (2.50 to 6.78) | (Referent) | 3.11 (1.59 to 6.10) | 3.73 (2.50 to 5.56) | .51 |
| Additionally adjusted for BMI, HR (95% CI)c | (Referent) | 3.80 (2.27 to 6.35) | (Referent) | 2.77 (1.39 to 5.51) | 3.39 (2.24 to 5.12) | .47 |
| Myeloma | ||||||
| Case/person-year | 281/3 183 299 | 30/184 540 | 183/902 968 | 10/59 429 | ||
| Age-adjusted model, HR (95% CI) | (Referent) | 1.25 (0.85 to 1.82) | (Referent) | 0.61 (0.32 to 1.16) | 1.03 (0.75 to 1.44) | .06 |
| Multivariable adjusted model, HR (95% CI)b | (Referent) | 1.51 (0.97 to 2.34) | (Referent) | 0.62 (0.33 to 1.19) | 1.14 (0.80 to 1.65) | .03 |
| Additionally adjusted for BMI, HR (95% CI)c | (Referent) | 1.44 (0.92 to 2.26) | (Referent) | 0.54 (0.28 to 1.04) | 1.06 (0.73 to 1.53) | .02 |
| Thyroid cancer | ||||||
| Case/person-year | 354/3 183 171 | 40/184 529 | 70/903 047 | 8/59 430 | ||
| Age-adjusted model, HR (95% CI) | (Referent) | 1.63 (1.16 to 2.27) | (Referent) | 1.74 (0.82 to 3.67) | 1.64 (1.21 to 2.23) | .88 |
| Multivariable adjusted model, HR (95% CI)b | (Referent) | 1.62 (1.08 to 2.44) | (Referent) | 1.65 (0.77 to 3.55) | 1.63 (1.14 to 2.34) | .97 |
| Additionally adjusted for BMI, HR (95% CI)c | (Referent) | 1.50 (0.99 to 2.27) | (Referent) | 1.45 (0.66 to 3.17) | 1.49 (1.03 to 2.15) | .94 |
| Gallbladder cancer | ||||||
| Case/person-year | 136/3 183 451 | 19/184 560 | 51/903 083 | 8/59 432 | ||
| Age-adjusted model, HR (95% CI) | (Referent) | 1.45 (0.89 to 2.36) | (Referent) | 1.79 (0.84 to 3.82) | 1.54 (1.02 to 2.32) | .65 |
| Multivariable adjusted model, HR (95% CI)b | (Referent) | 1.22 (0.66 to 2.24) | (Referent) | 2.01 (0.92 to 4.38) | 1.47 (0.91 to 2.39) | .32 |
| Additionally adjusted for BMI, HR (95% CI)c | (Referent) | 1.05 (0.56 to 1.96) | (Referent) | 1.94 (0.88 to 4.29) | 1.33 (0.81 to 2.17) | .23 |
| Sex-specific cancers | ||||||
| Breast cancer | ||||||
| Case/person-year | 12 064/3 172 217 | 1013/183 570 | — | — | — | — |
| Age-adjusted model, HR (95% CI) | (Referent) | 1.16 (1.09 to 1.24) | — | — | — | — |
| Multivariable adjusted model, HR (95% CI)b | (Referent) | 1.30 (1.20 to 1.41) | — | — | — | — |
| Additionally adjusted for BMI, HR (95% CI)c | (Referent) | 1.26 (1.17 to 1.37) | — | — | — | — |
| Endometrial cancer | ||||||
| Case/person-year | 1799/3 181 864 | 241/184 344 | — | — | — | — |
| Age-adjusted model, HR (95% CI) | (Referent) | 1.88 (1.63 to 2.15) | — | — | — | — |
| Multivariable adjusted model, HR (95% CI)b | (Referent) | 1.79 (1.51 to 2.13) | — | — | — | — |
| Additionally adjusted for BMI, HR (95% CI)c | (Referent) | 1.26 (1.06 to 1.50) | — | — | — | — |
| Ovarian cancer | — | — | — | — | ||
| Case/person-year | 1090/3 182 610 | 70/184 504 | ||||
| Age-adjusted model, HR (95% CI) | (Referent) | 0.85 (0.67 to 1.09) | — | — | — | — |
| Multivariable adjusted model, HR (95% CI)b | (Referent) | 0.84 (0.61 to 1.15) | — | — | — | — |
| Additionally adjusted for BMI, HR (95% CI)c | (Referent) | 0.81 (0.59 to 1.11) | — | — | — | — |
| Fatal prostate cancer | ||||||
| Case/person-year | — | — | 721/902 446 | 45/59 397 | — | — |
| Age-adjusted model, HR (95% CI) | — | — | (Referent) | 0.94 (0.69 to 1.28) | — | — |
| Multivariable adjusted model, HR (95% CI)b | — | — | (Referent) | 1.02 (0.75 to 1.39) | — | — |
| Additionally adjusted for BMI, HR (95% CI)c | — | — | (Referent) | 0.98 (0.72 to 1.33) | — | — |
a
Estimates were meta-analyzed using random effect model. BMI = body mass index; CI = confidence interval; HPFS = Health Professionals Follow-up Study; HR = hazard ratio; NHS = Nurses’ Health Study.
b
Adjusting for age (month), ethnicity (White, African American, Asian, others), smoking status (never smoked, past smoker, currently smoke 1-14 cigarettes per day, 15-24 cigarettes per day, or ≥25 cigarettes per day), alcohol intake (0, 0.1-4.9, 5.0-9.9, 10.0-14.9, 15.0-29.9, and ≥30.0 g/d), multivitamin use (yes, no), physical activity (quintiles), total energy (quintiles), alternative healthy eating index (quintiles), family history of diabetes (yes, no), family history of cancer (yes, no), endoscopy screening (yes, no), and fasting glucose screening (yes, no). For women, insulin use (yes, no), oral hypoglycemic drug use (yes, no), mammography screening, postmenopausal hormone use (never, former, or current hormone use, or missing), and oral contraceptive use were further adjusted.
c
Cumulative-averaged BMI (calculated as weight in kilograms divided by height in meters squared) (<21.0, 21.0-22.9, 23.0-24.9, 25.0-26.9, 27.0-29.9, 30.0-32.9, 33.0-34.9, or ≥35.0 kg/m2) was additionally adjusted.
d
Including esophagus cancer, liver cancer, kidney cancer, myeloma, pancreatic cancer, colorectal cancer, gallbladder cancer, postmenopausal breast cancer, ovarian cancer, and thyroid cancer.
e
Including thyroid cancer, breast cancer, liver cancer, pancreatic cancer, endometrial cancer, esophagus cancer, colorectal cancer, kidney cancer, gallbladder cancer, ovarian cancer, non-Hodgkin lymphoma, leukemia, and bladder cancer.