Impact of Insulin Therapies on Cancer Incidence in Type 1 and Type 2 Diabetes: A Population-Based Cohort Study in Reggio Emilia, Italy
Abstract
:Simple Summary
Abstract
1. Introduction
1.1. Rationale
1.2. Aim
2. Research Design and Methods
2.1. Data Sources
2.2. Study Population
2.3. Patient Characteristics and Outcomes
2.4. Statistical Analyses
3. Results
3.1. Participants
3.2. Outcome—All Sites
3.2.1. Stomach
3.2.2. Colorectal Cancer
3.2.3. Liver
3.2.4. Pancreas
3.2.5. Bladder
3.2.6. Neuroendocrine Tumours (NETs)
3.2.7. Other Sites
4. Discussion
4.1. Key Results
4.2. Interpretation
4.3. Strengths and Limitations
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Characteristics | Population with DM1 (N = 758) | Population with DM2 (N = 21,190) | Population without DM (N = 379,103) | |||
---|---|---|---|---|---|---|
at Baseline | Mean | SD | Mean | SD | Mean | SD |
age | 46.1 | 14.6 | 65.8 | 11.4 | 47.6 | 16.4 |
age class | N | % | N | % | N | % |
<40 | 279 | 36.8 | 478 | 2.3 | 139,320 | 36.8 |
40–49 | 195 | 25.7 | 1535 | 7.2 | 82,802 | 21.8 |
50–59 | 139 | 18.3 | 3715 | 17.5 | 59,657 | 15.7 |
60–69 | 84 | 11.1 | 6391 | 30.2 | 48,133 | 12.7 |
70–79 | 55 | 7 | 6823 | 32.2 | 36,579 | 9.7 |
80+ | 8 | 1.1 | 2248 | 10.6 | 12,612 | 3.3 |
sex | ||||||
male | 410 | 52.9 | 11,823 | 55.8 | 185,144 | 48.8 |
female | 357 | 47.1 | 9367 | 44.2 | 193,959 | 51.2 |
citizenship | ||||||
Italian | 671 | 88.5 | 19,570 | 92.3 | 325,440 | 85.8 |
Foreign national | 87 | 11.4 | 1620 | 7.6 | 53,663 | 14.2 |
during follow up | N | % | N | % | N | % |
person-years | 3665 | 94,429 | 1,836,603 | |||
deaths 2012–2016 | 35 | 4.6 | 3599 | 17.0 | 14,630 | 3.9 |
relocations 2012–2016 | 0 | - | 14 | 0.1 | 714 | 0.2 |
cancers | 16 | 2.1 | 1689 | 8.0 | 12,882 | 3.4 |
Categories | All Sites | |||||||
---|---|---|---|---|---|---|---|---|
Patients with DM2 in Diet-Only as Reference | Population without DM as Reference | |||||||
N | IRR | 95% CI | N | IRR | 95% CI | |||
Population with no DM (N = 379,103) | - | - | - | - | 12,882 | 1.00 | - | - |
Population with DM (N = 21,948) | - | - | - | - | 1705 | 1.20 | 1.14 | 1.26 |
1. Type 1 diabetes (N = 758) | - | - | - | - | 16 | 0.73 | 0.45 | 1.19 |
2. Type 2 diabetes (N = 21,190) | - | - | - | - | 1689 | 1.21 | 1.14 | 1.27 |
2.1 Insulin alone or in any combination (N = 2282) | 180 | 1.19 | 0.94 | 1.51 | 180 | 1.21 | 1.04 | 1.40 |
2.2 Insulin alone (N = 1332) | 121 | 1.38 | 1.06 | 1.81 | 121 | 1.35 | 1.12 | 1.61 |
2.3 Untreated (diet only) (N = 4077) | 301 | 1.00 | - | - | 301 | 1.09 | 0.97 | 1.22 |
Colon-Rectum (C18–C20) | Pancreas (C25) | Liver (C22) | ||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Patients with DM2 in Diet-Only as Reference | Population without DM as Reference | Patients with DM2 in Diet-Only as Reference | Population without DM as Reference | Patients with DM2 in Diet-Only as Reference | Population without DM as Reference | |||||||||||||||||||
N | IRR | 95% CI | N | IRR | 95% CI | N | IRR | 95% CI | N | IRR | 95% CI | N | IRR | 95% CI | N | IRR | 95% CI | |||||||
Population with no DM (N = 379,103) | 1279 | 1.00 | - | - | 501 | 1.00 | - | - | 309 | 1.00 | - | - | ||||||||||||
Population with DM (N = 21,948) | 197 | 1.18 | 1.01 | 1.38 | 115 | 1.74 | 1.42 | 2.14 | 102 | 2.57 | 2.04 | 3.23 | ||||||||||||
1. Type 1 diabetes (N = 758) | 1 | 0.51 | 0.07 | 3.61 | 0 | - | - | - | 1 | 2.00 | 0.28 | 14.30 | ||||||||||||
2. Type 2 diabetes (N = 21,190) | 196 | 1.19 | 1.02 | 1.39 | 115 | 1.76 | 1.44 | 2.17 | 101 | 2.57 | 2.04 | 3.24 | ||||||||||||
2.1 Insulin alone or in any combination (N = 2282) | 20 | 1.32 | 0.64 | 2.74 | 20 | 1.13 | 0.72 | 1.76 | 17 | 1.72 | 0.70 | 4.21 | 17 | 2.39 | 1.47 | 3.88 | 21 | 3.28 | 1.46 | 7.37 | 21 | 5.06 | 3.24 | 7.90 |
2.2 Insulin alone (N = 1332) | 16 | 1.67 | 0.76 | 3.67 | 16 | 1.45 | 0.88 | 2.38 | 12 | 2.32 | 0.85 | 6.29 | 12 | 2.70 | 1.52 | 4.79 | 16 | 4.52 | 1.89 | 10.82 | 16 | 6.18 | 3.72 | 10.27 |
2.3 Untreated (diet only) (N = 4077) | 28 | 1.00 | - | - | 28 | 0.86 | 0.59 | 1.25 | 13 | 1.00 | - | - | 13 | 1.00 | 0.58 | 1.74 | 13 | 1.00 | - | - | 15 | 1.90 | 1.13 | 3.20 |
Trachea, Bronchus, and Lung Cancer (C33–C34) | Lymphoma (C81–C85, C96) | Stomach (C16) | ||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Patients with DM2 in Diet-Only as Reference | Population without DM as Reference | Patients with DM2 in Diet-Only as Reference | Population without DM as Reference | Patients with DM2 in Diet-Only as Reference | Population without DM as Reference | |||||||||||||||||||
N | IRR | 95% CI | N | IRR | 95% CI | N | IRR | 95% CI | N | IRR | 95% CI | N | IRR | 95% CI | N | IRR | 95% CI | |||||||
Population with no DM (N = 379,103) | 1414 | 1.00 | - | - | 582 | 1.00 | - | - | 503 | 1.00 | - | - | ||||||||||||
Population with DM (N = 21,948) | 247 | 1.24 | 1.08 | 1.42 | 68 | 1.14 | 0.86 | 1.43 | 91 | 1.29 | 1.02 | 1.61 | ||||||||||||
1. Type 1 diabetes (N = 758) | 0 | - | - | - | 2 | 1.94 | 0.48 | 7.80 | 0 | - | - | - | ||||||||||||
2. Type 2 diabetes (N = 21,190) | 247 | 1.25 | 1.09 | 1.44 | 66 | 1.09 | 0.84 | 1.41 | 91 | 1.30 | 1.04 | 1.63 | ||||||||||||
2.1 Insulin alone or in any combination (N = 2282) | 23 | 1.37 | 0.71 | 2.64 | 23 | 1.11 | 0.73 | 1.67 | 3 | 0.67 | 0.15 | 3.01 | 3 | 0.48 | 0.15 | 1.48 | 6 | 1.15 | 0.34 | 3.89 | 6 | 0.80 | 0.35 | 1.79 |
2.2 Insulin alone (N = 1332) | 11 | 0.78 | 0.40 | 1.84 | 11 | 0.83 | 0.46 | 1.51 | 3 | 1.13 | 0.25 | 5.10 | 3 | 0.79 | 0.25 | 2.46 | 4 | 1.20 | 0.29 | 4.90 | 4 | 0.84 | 0.31 | 2.26 |
2.3 Untreated (diet only) (N = 4077) | 39 | 1.00 | - | - | 39 | 0.99 | 0.72 | 1.37 | 16 | 1.00 | - | - | 16 | 1.34 | 0.81 | 2.21 | 14 | 1.00 | - | - | 14 | 1.00 | 0.59 | 1.71 |
Corpus Uteri (C54) | Breast (C50) | Ovary (C56) | ||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Patients with DM2 in Diet-Only as Reference | Population without DM as Reference | Patients with DM2 in Diet-Only as Reference | Population without DM as Reference | Patients with DM2 in Diet-Only as Reference | Population without DM as Reference | |||||||||||||||||||
N | IRR | 95% CI | N | IRR | 95%CI | N | IRR | 95% CI | N | IRR | 95% CI | N | IRR | 95% CI | N | IRR | 95% CI | |||||||
Population with no DM (N = 379,103) | 333 | 1.00 | - | - | 2056 | 1.00 | - | - | 200 | 1.00 | - | - | ||||||||||||
Population with DM (N = 21,948) | 41 | 1.49 | 1.06 | 2.08 | 145 | 0.97 | 0.81 | 1.15 | 25 | 1.56 | 1.02 | 2.39 | ||||||||||||
1. Type 1 diabetes (N = 758) | 0 | - | - | - | 4 | 1.13 | 0.42 | 3.01 | 0 | - | - | - | ||||||||||||
2. Type 2 diabetes (N = 21,190) | 41 | 1.52 | 1.09 | 2.13 | 141 | 0.96 | 0.81 | 1.15 | 25 | 1.60 | 1.04 | 2.46 | ||||||||||||
2.1 Insulin alone or in any combination (N = 2282) | 5 | 2.64 | 0.57 | 12.35 | 5 | 1.60 | 0.66 | 3.88 | 14 | 0.85 | 0.38 | 1.90 | 14 | 0.84 | 0.50 | 1.43 | 3 | 0.97 | 0.16 | 5.72 | 3 | 1.69 | 0.54 | 5.33 |
2.2 Insulin alone (N = 1332) | 3 | 3.29 | 0.55 | 19.80 | 3 | 1.68 | 0.58 | 5.27 | 8 | 0.83 | 0.31 | 2.36 | 8 | 0.86 | 0.43 | 1.73 | 2 | 1.42 | 0.18 | 11.16 | 2 | 2.00 | 0.50 | 8.12 |
2.3 Untreated (diet only) (N = 4077) | 5 | 1.00 | - | - | 5 | 0.94 | 0.39 | 2.28 | 30 | 1.00 | - | - | 30 | 1.05 | 0.73 | 1.50 | 6 | 1.00 | - | - | 6 | 1.97 | 0.86 | 4.46 |
Kidney (C64) | Bladder (C67, D09, D41.4) | Prostate (C61) | ||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Patients with DM2 in Diet-Only as Reference | Population without DM as Reference | Patients with DM2 in Diet-Only as Reference | Population without DM as Reference | Patients with DM2 in Diet-Only as Reference | Population without DM as Reference | |||||||||||||||||||
N | IRR | 95% CI | N | IRR | 95% CI | N | IRR | 95% CI | N | IRR | 95% CI | N | IRR | 95% CI | N | IRR | 95% CI | |||||||
Population with no DM (N = 379,103) | 434 | 1.00 | - | - | 894 | 1.00 | - | - | 1172 | 1.00 | - | - | ||||||||||||
Population with DM (N = 21,948) | 57 | 1.10 | 0.83 | 1.46 | 168 | 1.28 | 1.09 | 1.52 | 160 | 0.91 | 0.77 | 1.08 | ||||||||||||
1. Type 1 diabetes (N = 758) | 0 | - | - | - | 4 | 3.00 | 1.12 | 8.02 | 3 | 1.59 | 0.51 | 4.95 | ||||||||||||
2. Type 2 diabetes (N = 21,190) | 57 | 1.11 | 0.84 | 1.48 | 164 | 1.27 | 1.07 | 1.50 | 157 | 0.91 | 0.78 | 1.08 | ||||||||||||
2.1 Insulin alone or in any combination (N = 2282) | 5 | 0.92 | 0.22 | 3.75 | 5 | 0.94 | 0.39 | 2.27 | 20 | 1.13 | 0.56 | 2.29 | 20 | 1.50 | 0.96 | 2.33 | 16 | 0.89 | 0.42 | 1.89 | 16 | 0.92 | 0.57 | 1.52 |
2.2 Insulin alone (N = 1332) | 1 | 0.42 | 0.04 | 4.73 | 1 | 0.30 | 0.04 | 2.16 | 14 | 1.58 | 0.72 | 3.48 | 14 | 1.64 | 0.97 | 2.78 | 13 | 1.20 | 0.53 | 2.70 | 13 | 1.17 | 0.68 | 2.02 |
2.3 Untreated (diet only) (N = 4077) | 8 | 1.00 | - | - | 8 | 0.79 | 0.39 | 1.59 | 35 | 1.00 | - | - | 35 | 1.35 | 0.97 | 1.90 | 35 | 1.00 | - | - | 35 | 1.02 | 0.73 | 1.43 |
Neuroendocrine Carcinoma (all) | Neuroendocrine Carcinoma (only Pancreas and Digestive Tract) | |||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Patients with DM2 in Diet-Only as Reference | Population without DM as Reference | Patients with DM2 in Diet-Only as Reference | Population without DM as Reference | |||||||||||||
N | IRR | 95% CI | N | IRR | 95% CI | N | IRR | 95% CI | N | IRR | 95% CI | |||||
Population with no DM (N = 379,103) | 381 | 1.00 | - | - | 113 | 1.00 | - | - | ||||||||
Population with DM (N = 21,948) | 59 | 1.29 | 0.97 | 1.70 | 11 | 0.95 | 0.31 | 1.79 | ||||||||
1. Type 1 diabetes (N = 758) | 0 | - | - | - | 0 | - | - | - | ||||||||
2. Type 2 diabetes (N = 21,190) | 59 | 1.37 | 0.99 | 1.73 | 11 | 0.97 | 0.51 | 1.82 | ||||||||
2.1 Insulin alone or in any combination (N = 2282) | 7 | 3.44 | 1.04 | 11.38 | 7 | 1.44 | 0.68 | 3.05 | 0 | - | - | - | 0 | - | - | - |
2.2 Insulin alone (N = 1332) | 0 | - | - | - | 0 | - | - | - | 0 | - | - | - | 0 | - | - | - |
2.3 Untreated (diet only) (N = 4077) | 9 | 1.00 | - | - | 9 | 0.99 | 0.51 | 1.93 | 0 | 1.00 | - | - | 0 | - | - | - |
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Vicentini, M.; Ballotari, P.; Venturelli, F.; Ottone, M.; Manicardi, V.; Gallo, M.; Greci, M.; Pinotti, M.; Pezzarossi, A.; Giorgi Rossi, P. Impact of Insulin Therapies on Cancer Incidence in Type 1 and Type 2 Diabetes: A Population-Based Cohort Study in Reggio Emilia, Italy. Cancers 2022, 14, 2719. https://doi.org/10.3390/cancers14112719
Vicentini M, Ballotari P, Venturelli F, Ottone M, Manicardi V, Gallo M, Greci M, Pinotti M, Pezzarossi A, Giorgi Rossi P. Impact of Insulin Therapies on Cancer Incidence in Type 1 and Type 2 Diabetes: A Population-Based Cohort Study in Reggio Emilia, Italy. Cancers. 2022; 14(11):2719. https://doi.org/10.3390/cancers14112719
Chicago/Turabian StyleVicentini, Massimo, Paola Ballotari, Francesco Venturelli, Marta Ottone, Valeria Manicardi, Marco Gallo, Marina Greci, Mirco Pinotti, Annamaria Pezzarossi, and Paolo Giorgi Rossi. 2022. "Impact of Insulin Therapies on Cancer Incidence in Type 1 and Type 2 Diabetes: A Population-Based Cohort Study in Reggio Emilia, Italy" Cancers 14, no. 11: 2719. https://doi.org/10.3390/cancers14112719