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

Rachel Dankner, Ran Balicer, Paolo Boffetta, Lital Keinan Boker, Sylvan Wallenstein, Laurence Freedman, Margalit Goldfracht, Jesse Roth, Ronald Tamler, Derek LeRoith, Rachel Dankner, Ran Balicer, Paolo Boffetta, Lital Keinan Boker, Sylvan Wallenstein, Laurence Freedman, Margalit Goldfracht, Jesse Roth, Ronald Tamler, Derek LeRoith

Abstract

Background: 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.

Methods/design: 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.

Discussion: 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.

Figures

Figure 1
Figure 1
The ten year follow-up of the four study groups, according to disease status at study entry: diabetes free (DF) or prevalent (DP), and cancer free (CF) or prevalent (CP). For the groups that are DF at study entry, diabetes incidence (DI) will be followed and associated with outcomes (green arrows pointing down). For the groups that are DP at study entry, glucose control and diabetes medications will be followed and associated with the outcomes (green arrows pointing to the right). All four groups will be followed for the study outcome: overall and specific cancers, including second primary neoplasms.
Figure 2
Figure 2
The study cohort according to diabetes and cancer status during the ten year follow-up period. DP - prevalent diabetes; DI - incident diabetes; DF - diabetes free; CP: prevalent cancer; CI - incident cancer; CF - cancer free.

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Source: PubMed

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