Open Access Highly Accessed Study protocol

Diabetes, glucose control, glucose lowering medications, and cancer risk: A 10-year population-based historical cohort

Rachel Dankner123*, Ran Balicer45, Paolo Boffetta6, Lital Keinan Boker78, Sylvan Wallenstein9, Laurence Freedman10, Margalit Goldfracht4, Jesse Roth113, Ronald Tamler9 and Derek LeRoith9

Author Affiliations

1 Unit for Cardiovascular Epidemiology, The Gertner Institute for Epidemiology and Health Policy Research, Sheba Medical Center, Tel Hashomer, 52621, Israel

2 Sackler Faculty of Medicine, School of Public Health, Department of Epidemiology and Preventive Medicine, Tel Aviv University, Ramat Aviv, Tel Aviv, 69978, Israel

3 Patient Oriented Research, The Feinstein Institute for Medical Research Manhasset, North Shore, NY, 11030, USA

4 Clalit Health Services Research Institute, Arlozerov St. 105, Tel Aviv, 62908, Israel

5 School of Public Health, Ben-Gurion University of the Negev, Beer Sheba, Israel

6 Institute for Transitional Epidemiology, Mount Sinai School of Medicine, New York, NY, USA

7 Israel Center for Disease Control, Sheba Medical Center, Ramat Gan, Israel

8 School of Public Health, Haifa University, Haifa, Israel

9 Division of Endocrinology, Diabetes, and Bone Disease, Mount Sinai School of Medicine, New York, NY, USA

10 Biostatistics Unit, Gertner Institute for Epidemiology and Health Policy Research, Sheba Medical Center, Tel Hashomer, 52161, Israel

11 Albert Einstein College of Medicine, Yeshiva University, Bronx, NY, USA

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BMC Cancer 2012, 12:364  doi:10.1186/1471-2407-12-364

Published: 23 August 2012



Both diabetes and glucose-lowering medications have been associated with an increased risk of cancer incidence. This study will compare cancer incidence rates in individuals with and without diabetes; and will investigate, in individuals with diabetes, an association between glucose control and cancer incidence; and between the use of specific glucose-lowering medications, as well as no drug exposure, and cancer incidence.


This is a population based historical cohort study of all individuals aged 21 years or older (about 2,300,000) who were insured by Clalit Health Services, the largest health maintenance organization in Israel during a ten-year study period. Four study groups will be established according to the status of diabetes and cancer at study entry, Jan 1, 2002: cancer free, diabetes free; cancer free, diabetes prevalent; cancer prevalent, diabetes free; and cancer prevalent, diabetes prevalent. Individuals without diabetes at study entry will be followed for diabetes incidence, and all four groups will be followed for specific cancer incidence, including second primary neoplasms. Glucose control will be assessed by HbA1c and by fasting plasma glucose levels. Time dependent regression models for cancer incidence will account for glucose-lowering medications as they are added and changed over the follow-up period. A large number of demographic and clinical variables will be considered, including: age, gender, BMI, smoking status, concomitant medications, glucose control (assessed by HbA1c and by fasting plasma glucose) and cancer screening tests.


Strengths of this study include the large population; high quality comprehensive data; comparison to individuals without diabetes, and to those with diabetes but not treated with glucose-lowering medications; and the extensive range of variables available for analysis. The great increases in diabetes prevalence and in treatment options render this study particularly relevant and timely. The Israeli national healthcare system, characterized by high standard and uniform healthcare, offers an advantageous environment for its conduct.

Historical prospective; Incidence; Population based; Time dependent analysis