DiabetesDBCANCT02072902
Diabetes, Glucose Control, Glucose Lowering Medications, and Cancer Risk: A 10-year Population-based Historical Cohort
An observational study of Diabetes and Cancer, run by Sheba Medical Center at 1 site in Israel.
Trial 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. Read more about this study
- Who is it for?
- Ages 21 to 90 years
- How many people
- 2,188,669 participants
- Where
- 1 siteIsrael
- Study dates
- Mar 2012to Dec 2016
- How long will I take part?
- 11 Years
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- Aged older than 21 and younger than 90 at study entry, January 1, 2002
- Insured by Clalit Health Services
Who cannot join
- Under age 21 at January 1, 2002
- Over age 90 at January 1, 2002
Trial locations and contacts
1 site in 1 country.
Israel1 site
The Gertner Institute for Epidemiology and Health Policy Research
Ramat Gan
About this study
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.
Read the detailed description
The study was based on electronic records from the largest health maintenance organization in Israel, Clalit Health Services, which insures and provides healthcare to 55% (3.9 million) of the nation's population. All persons between 21 and 90 years and registered with Clalit on January 1, 2002 (the date of study entry), without a previous history of cancer, were included in a closed cohort that was followed until December 31 2012.
All individuals were followed for cancer incidence, which was ascertained by record linkage to the Israel National Cancer Registry, established in 1960. The registry has benefited since 1982 from a national law mandating registration of cancer, and has greater than 95% coverage of solid tumors, and approximately 85% coverage of hematologic cancers [34].
Definitions of diabetes: Incident diabetes was defined as fulfillment of at least one of the following six criteria during 2002-12: (1) diabetes recorded in the Clalit Chronic Disease Registry; (2) a physician's diagnosis of diabetes, and one plasma glucose test > 125 mg/dL within 12 months; (3) one HbA1c measurement > 6.5%; (4) 2-hour plasma glucose level during an oral glucose tolerance test ≥ 200 mg/dL; (5) 3 or more purchases of glucose-lowering medication within 12 months; (6) 2 plasma glucose measurements > 125 mg/dL within 12 months. The date of the earliest defining criterion was considered the date of diagnosis.
Prevalent diabetes was defined as being recorded with diabetes in the Clalit Chronic Disease Registry on study entry, or fulfilling criterion #5 above (information on medication use was available from 1998) before study entry.
Types of cancer: The following cancers were investigated: liver (ICD-O-3 codes C22.0 and C22.1), pancreas (C25.0-C25.9), gallbladder (C23.9-C24.9), endometrium (C54.0-C54.9, C55.9), stomach (C16.0-C16.9), kidney (C64.9, C65.9, C66.9., C68.0-C68.9), benign brain and central nervous system (C70.0-C72.9 with behavior code 0), malignant brain (C70.0-C72.9 with behavior code 3), multiple myeloma (C42.1 with relevant morphology codes), colorectum (C18.0-C21.8), non-Hodgkin lymphoma (C02.4, C09.8. C09.9, C11.1, C14.2, C37.9, C42.2, C77 and all other sites for extra-nodal Non Hodgkin's lymphoma), lung (all: C34.0-C34.9), adenocarcinoma, squamous cell), leukemia (C42.0, C42.1, C42.2 with relevant morphology codes), ovary (C56.9), bladder (C67.0-C67.9), breast (C50.0-C50.9), thyroid (C73.9) and prostate (C61.9). Apart from benign brain tumors, all cancers included in the analysis were coded as invasive (behavior code = 3).
- Keywords
- Cohort, Historical, Prospective, Medications, Observational, Glucose, Control
- Medical subject headings
- Diabetes Mellitus, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: The population will be followed historically for incidence of cancer for a period of up to 11 years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Feb 2014 (estimated)
- Study startMar 2012
- Primary completionDec 2015
- Study completionDec 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for DiabetesStudies of the same condition, open and under way.
- More trials run by Sheba Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Other
- Enrolment
- 2,188,669 participants (actual)
- Target duration
- 11 Years
Sponsor and investigators
- Lead sponsor
- Sheba Medical Center
- Sponsor type
- Other government
- Collaborators
- European Foundation for the Study of Diabetes
- Responsible party
- Sponsor
- Investigators
- Rachel Dankner, MD MPH, Principal investigator, Gertner Institute, Sheba Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02072902
- Sponsor's protocol ID
- SHEBA-14-0050-RD-CTIL
- Acronym
- DBCA
- Status last verified
- Oct 2017
- First submitted
- 12 Feb 2014
- Last updated
- 18 Oct 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 22917080Dankner 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.
PubMed 27189066Dankner 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.
PubMed 27257115Dankner 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.
PubMed 38175642Dankner 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.
PubMed 29673046
Study at a glance
From the registry record, last updated by the sponsor on 18 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Diabetes, Glucose Control, Glucose Lowering Medications, and Cancer Risk: A 10-year Population-based Historical Cohort
- ClinicalTrials.gov ID
- NCT02072902
- Acronym / sponsor ID
- DBCA / SHEBA-14-0050-RD-CTIL
- Keywords
- Cohort, Historical, Prospective, Medications, Observational, Glucose, Control
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 2,188,669 participants (actual)
- Lead sponsor
- Sheba Medical CenterOther government
- Collaborators
- European Foundation for the Study of Diabetes
- Study start
- Mar 2012 (actual)
- Primary completion
- Dec 2015 (actual)
- Study completion
- Dec 2016 (actual)
- First posted
- 27 Feb 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The study was based on electronic records from the largest health maintenance organization in Israel, Clalit Health Services, which insures and provides healthcare to 55% (3.9 million) of the nation's population. All persons between 21 and 90 years and registered with Clalit on January 1, 2002 (the date of study entry), without a previous history of cancer, were included in a closed cohort that was followed until December 31 2012.
All individuals were followed for cancer incidence, which was ascertained by record linkage to the Israel National Cancer Registry, established in 1960. The registry has benefited since 1982 from a national law mandating registration of cancer, and has greater than 95% coverage of solid tumors, and approximately 85% coverage of hematologic cancers [34].
Definitions of diabetes: Incident diabetes was defined as fulfillment of at least one of the following six criteria during 2002-12: (1) diabetes recorded in the Clalit Chronic Disease Registry; (2) a physician's diagnosis of diabetes, and one plasma glucose test > 125 mg/dL within 12 months; (3) one HbA1c measurement > 6.5%; (4) 2-hour plasma glucose level during an oral glucose tolerance test ≥ 200 mg/dL; (5) 3 or more purchases of glucose-lowering medication within 12 months; (6) 2 plasma glucose measurements > 125 mg/dL within 12 months. The date of the earliest defining criterion was considered the date of diagnosis.
Prevalent diabetes was defined as being recorded with diabetes in the Clalit Chronic Disease Registry on study entry, or fulfilling criterion #5 above (information on medication use was available from 1998) before study entry.
Types of cancer: The following cancers were investigated: liver (ICD-O-3 codes C22.0 and C22.1), pancreas (C25.0-C25.9), gallbladder (C23.9-C24.9), endometrium (C54.0-C54.9, C55.9), stomach (C16.0-C16.9), kidney (C64.9, C65.9, C66.9., C68.0-C68.9), benign brain and central nervous system (C70.0-C72.9 with behavior code 0), malignant brain (C70.0-C72.9 with behavior code 3), multiple myeloma (C42.1 with relevant morphology codes), colorectum (C18.0-C21.8), non-Hodgkin lymphoma (C02.4, C09.8. C09.9, C11.1, C14.2, C37.9, C42.2, C77 and all other sites for extra-nodal Non Hodgkin's lymphoma), lung (all: C34.0-C34.9), adenocarcinoma, squamous cell), leukemia (C42.0, C42.1, C42.2 with relevant morphology codes), ovary (C56.9), bladder (C67.0-C67.9), breast (C50.0-C50.9), thyroid (C73.9) and prostate (C61.9). Apart from benign brain tumors, all cancers included in the analysis were coded as invasive (behavior code = 3).
Study design
- Observational model
- Cohort
- Time perspective
- Other
- Target follow-up
- 11 Years
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 21 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (2 listed)
- Aged older than 21 and younger than 90 at study entry, January 1, 2002
- Insured by Clalit Health Services
Key exclusion criteria (2 listed)
- Under age 21 at January 1, 2002
- Over age 90 at January 1, 2002
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Hazard ratios for all-site and site specific cancer
Time frame: The population will be followed historically for incidence of cancer for a period of up to 11 years.
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Oct 2017.
- Background: PubMed 22917080Dankner 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.
- Results publication: PubMed 27189066Dankner 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.
- Results publication: PubMed 27257115Dankner 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.
- Derived from this study: PubMed 38175642Dankner 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.
- Derived from this study: PubMed 29673046Dankner 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rachel Dankner, MD MPH principal investigator
Gertner Institute, Sheba Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Diabetes and Cancer, run by Sheba Medical Center at 1 site in Israel.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Hazard ratios for all-site and site specific cancer (time frame: The population will be followed historically for incidence of cancer for a period of up to 11 years.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02072902, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Oct 2017.