Diabetes, Glucose Control, Glucose Lowering Medications, and Cancer Risk: A 10-year Population-based Historical Cohort

NCT02072902 | Completed

• 1 other identifier: SHEBA-14-0050-RD-CTIL
• Study Type: observational
• Target: 2,188,669
• Locations: 1 country
• Sites: 1

Brief Summary

This is a large nationwide population study, with 10 year follow-up, of the effect of diabetes, metabolic control and a large number of glucose-lowering medications, on total and site-specific cancer incidence and survival. The study is based on electronic medical records from the largest Israeli health maintenance organization in Israel, Clalit Health Services. 2,301,990 insurees age 21 years old or above at study entry, January 2002 will be included. Four study groups will be established according to the prevalence of diabetes and/or cancer on that date: neither diabetes nor cancer; prevalent diabetes but not cancer; prevalent cancer but not diabetes; both diabetes and cancer prevalence. Subjects free of diabetes at study entry will be followed for diabetes incidence, and all four groups will be followed until December 2012 for study outcomes. The cohort data file will be linked to the Israel National Cancer Registry for cancer morbidity. We will compare, after adjustment, all and site-specific cancer rates between individuals with and without diabetes; and investigate if metabolic control, as indicated by HbA1c and blood glucose levels, is related to cancer risk. Using time-dependent Cox proportionate hazard models, we will then evaluate differences in outcomes that associate with the use of one or a combination of glucose-lowering treatments, while stratifying by those who were already diagnosed with diabetes at study entry, and those diagnosed during follow-up. Data for a large number of potential confounding variables, including BMI, plasma glucose, HbA1c, hormone replacement therapy and comorbidities will help mitigate allocation bias. The accessibility and uniformity of the healthcare provided by Clalit Health Services, as well as data on cancer screening tests, will minimize the risk of surveillance bias.

Conditions

Diabetes; Cancer

Keywords

Cohort; Historical; Prospective; Medications; Observational; Glucose; Control

Outcome Measures

Primary Outcomes (1)

• Hazard ratios for all-site and site specific cancer

  The population will be followed historically for a period of up to 11 years whichever came first, cancer incidence, mortality, age 90, or end of follow-up.

  The population will be followed historically for incidence of cancer for a period of up to 11 years.

Study Arms (3)

diabetes free

No intervention

Diabetes prevalent

The exposure is diabetes morbidity present at study entery

Diabetes incidence

The exposure is diabetes incidence during study follow up

Eligibility Criteria

• Age: 21 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The cohort will include all individuals who were aged 21 years or older at study entry, January 1, 2002, and who were insured by Clalit Health Services, from one year prior to study entry, until the end of the study period, December 31, 2012, or until death, for those who did not survive until the end of follow-up.

You may qualify if:

• Aged older than 21 and younger than 90 at study entry, January 1, 2002
• Insured by Clalit Health Services

You may not qualify if:

• Under age 21 at January 1, 2002
• Over age 90 at January 1, 2002

Sponsors & Collaborators

• Sheba Medical Center: lead
• European Foundation for the Study of Diabetes: collaborator

Study Sites (1)

The Gertner Institute for Epidemiology and Health Policy Research

Ramat Gan, Israel

Location

Related Publications (5)

• Dankner R, Balicer R, Boffetta P, Boker LK, Wallenstein S, Freedman L, Goldfracht M, Roth J, Tamler R, LeRoith D. Diabetes, glucose control, glucose lowering medications, and cancer risk: a 10-year population-based historical cohort. BMC Cancer. 2012 Aug 23;12:364. doi: 10.1186/1471-2407-12-364.

  PMID: 22917080 BACKGROUND

• Dankner R, Boffetta P, Keinan-Boker L, Balicer RD, Berlin A, Olmer L, Murad H, Silverman B, Hoshen M, Freedman LS. Diabetes, prostate cancer screening and risk of low- and high-grade prostate cancer: an 11 year historical population follow-up study of more than 1 million men. Diabetologia. 2016 Aug;59(8):1683-91. doi: 10.1007/s00125-016-3972-x. Epub 2016 May 17.

  PMID: 27189066 RESULT

• Dankner R, Boffetta P, Balicer RD, Boker LK, Sadeh M, Berlin A, Olmer L, Goldfracht M, Freedman LS. Time-Dependent Risk of Cancer After a Diabetes Diagnosis in a Cohort of 2.3 Million Adults. Am J Epidemiol. 2016 Jun 15;183(12):1098-106. doi: 10.1093/aje/kwv290. Epub 2016 Jun 2.

  PMID: 27257115 RESULT

• Dankner R, Murad H, Agay N, Olmer L, Freedman LS. Glucagon-Like Peptide-1 Receptor Agonists and Pancreatic Cancer Risk in Patients With Type 2 Diabetes. JAMA Netw Open. 2024 Jan 2;7(1):e2350408. doi: 10.1001/jamanetworkopen.2023.50408.

  PMID: 38175642 DERIVED

• Dankner R, Freedman LS, Gerstein HC, Roth J, Keinan-Boker L. Newly diagnosed type 2 diabetes may serve as a potential marker for pancreatic cancer. Diabetes Metab Res Rev. 2018 Sep;34(6):e3018. doi: 10.1002/dmrr.3018. Epub 2018 Jun 17.

  PMID: 29673046 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus; Neoplasms

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Rachel Dankner, MD MPH

  Gertner Institute, Sheba Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Target Duration: 11 Years
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 12, 2014
• First Posted: February 27, 2014
• Study Start: March 1, 2012
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2016
• Last Updated: October 18, 2017

Record last verified: 2017-10

Locations

IL (1)