R Dankner1, L Keinan Boker2, P Boffetta3, R D Balicer4, H Murad5, A Berlin6, L Olmer5, N Agai7, L S Freedman8. 1. Unit for Cardiovascular Epidemiology, The Gertner Institute for Epidemiology and Health Policy Research, Sheba Medical Center, Tel Hashomer, Israel; Sackler Faculty of Medicine, Department of Epidemiology and Preventive Medicine, School of Public Health, Tel Aviv University, Ramat Aviv, Tel Aviv, Israel; Patient Oriented Research, The Feinstein Institute for Medical Research, Manhasset, North Shore, New York, United States. Electronic address: racheld@gertner.health.gov.il. 2. The Israel Center for Disease Control, Israel Ministry of Health, Israel; School of Public Health, Faculty of Social Welfare and Health Sciences, Haifa University, Haifa, Israel. 3. Tisch Cancer Institute and Institute for Translational Epidemiology, Icahn School of Medicine at Mount Sinai, New York NY, United States. 4. Clalit Health Services, Clalit Research Institute, Tel Aviv, Israel; Public Health Department, Ben-Gurion University of the Negev, Beer Sheva, Israel. 5. Unit for Biostatistics, The Gertner Institute for Epidemiology and Health Policy Research, Sheba Medical Center, Tel Hashomer, Israel. 6. Unit for Cardiovascular Epidemiology, The Gertner Institute for Epidemiology and Health Policy Research, Sheba Medical Center, Tel Hashomer, Israel; Clalit Health Services, Clalit Research Institute, Tel Aviv, Israel. 7. Unit for Cardiovascular Epidemiology, The Gertner Institute for Epidemiology and Health Policy Research, Sheba Medical Center, Tel Hashomer, Israel. 8. Sackler Faculty of Medicine, Department of Epidemiology and Preventive Medicine, School of Public Health, Tel Aviv University, Ramat Aviv, Tel Aviv, Israel; Unit for Biostatistics, The Gertner Institute for Epidemiology and Health Policy Research, Sheba Medical Center, Tel Hashomer, Israel.
Abstract
AIMS: This population-based historical cohort study examined whether poor glycemic-control (i.e., high glucose and HbA1c blood levels) in patients with diabetes is associated with cancer-risk. METHODS: From a large healthcare database, patients aged 21-89 years, diagnosed with diabetes before January 2002 (prevalent) or during 2002-2010 (incident), were followed for cancer during 2004-2012 (excluding cancers diagnosed within the first 2 years since diabetes diagnosis). Risks of selected cancers (all-sites, colon, breast, lung, prostate, pancreas and liver) were estimated according to glycemic-control in a Cox regression model with time-dependent covariates, adjusted for age, sex, ethnic origin, socioeconomic status, smoking and parity. Missing glucose or HbA1c values were imputed. RESULTS: Among 440,000 patients included in our analysis, cancer was detected more than 2 years after diabetes diagnosis in 26,887 patients (6%) during the follow-up period. Associations of poor glycemic-control with all-sites cancer and most specific cancers were either null or only weak (hazard ratios (HRs) for a 1% HbA1c or a 30 mg/dl glucose increase between 0.94 and 1.09). Exceptions were pancreatic cancer, for which there was a strong positive association (HRs: 1.26-1.51), and prostate cancer, for which there was a moderate negative association (HRs: 0.85-0.96). CONCLUSION: Overall, poor glycemic-control appears to be only weakly associated with cancer-risk, if at all. A substantial part of the positive association with pancreatic cancer is attributable to reverse causation, with the cancer causing poorer glycemic-control prior to its diagnosis. The negative association with prostate cancer may be related to lower PSA levels in those with poor control.
AIMS: This population-based historical cohort study examined whether poor glycemic-control (i.e., high glucose and HbA1c blood levels) in patients with diabetes is associated with cancer-risk. METHODS: From a large healthcare database, patients aged 21-89 years, diagnosed with diabetes before January 2002 (prevalent) or during 2002-2010 (incident), were followed for cancer during 2004-2012 (excluding cancers diagnosed within the first 2 years since diabetes diagnosis). Risks of selected cancers (all-sites, colon, breast, lung, prostate, pancreas and liver) were estimated according to glycemic-control in a Cox regression model with time-dependent covariates, adjusted for age, sex, ethnic origin, socioeconomic status, smoking and parity. Missing glucose or HbA1c values were imputed. RESULTS: Among 440,000 patients included in our analysis, cancer was detected more than 2 years after diabetes diagnosis in 26,887 patients (6%) during the follow-up period. Associations of poor glycemic-control with all-sites cancer and most specific cancers were either null or only weak (hazard ratios (HRs) for a 1% HbA1c or a 30 mg/dl glucose increase between 0.94 and 1.09). Exceptions were pancreatic cancer, for which there was a strong positive association (HRs: 1.26-1.51), and prostate cancer, for which there was a moderate negative association (HRs: 0.85-0.96). CONCLUSION: Overall, poor glycemic-control appears to be only weakly associated with cancer-risk, if at all. A substantial part of the positive association with pancreatic cancer is attributable to reverse causation, with the cancer causing poorer glycemic-control prior to its diagnosis. The negative association with prostate cancer may be related to lower PSA levels in those with poor control.
Authors: Christopher T Rentsch; Ruth E Farmer; Sophie V Eastwood; Rohini Mathur; Victoria Garfield; Aliki-Eleni Farmaki; Krishnan Bhaskaran; Nish Chaturvedi; Liam Smeeth Journal: BMJ Open Diabetes Res Care Date: 2020-08