Diabetes Mellitus, Type 2, Cancer
Conditions
Keywords
Drug Therapy
Brief summary
The purpose of this study was to evaluate whether treatment with pioglitazone is associated with risk of incident cancer at the 10 most common sites in a cohort of participants with recognized diabetes along with the assessment of association between diabetes severity and cancer risk.
Detailed description
The study enroll a large population of approximately 252467 participants. This epidemiology study of diabetes and cancer risk is an expansion study which would include estimation of cancer rate among KPNC members with or without diabetes and the relative risks of cancers associated with a diagnosis of diabetes. The study included diabetes participants who were KPNC members between 1997 and 2011. It also included a subset of participants who took the 1996/7 diabetes survey and Member Health Survey (MHS) in 1993, 1999, 2001 or 2003. This multi-center trial was conducted in the United States of America. The overall time to participate in this study was approximately 15.5 years. The participants were followed-up from January 1, 1997 up to December 31, 2011.
Interventions
OTHERNo Intervention
Sponsors
Takeda
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. has been in the KPNC diabetes registry Diabetes Mellitus (DM) registry, aged 40 years or older and are members of KPNC as of January 1, 1997 and had no prior diagnosis of the cancer of interest.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Age and Sex-Standardized Incidence Rates for the 10 Most Common Cancers Stratified by Diabetes Status | 15 years | Age and gender adjusted incidence rates, stratified by diabetes status, was calculated using the direct method (2000 US Census as standard), with further stratification on calendar year. Cancer incidence rates were calculated with attention to the proper allocation of at-risk person-time. The association between diabetes and risk of each of the 10 most common cancers was assessed using Cox proportional hazards regression models with control for available potential confounders: age, gender. Similarly, Cox regression technique was used to examine the association between diabetes status and cancer risk among survey responders with adjustment for additional potential confounding variable. |
| Hazard Ratio for Risk of 10 Common Cancers Associated With Diabetes | 15 years | The association between diabetes and risk of each of the 10 most common cancers was assessed by calculating hazard ratio using Cox proportional hazards regression models with control for available potential confounders: age, gender and calendar years. Cox regression techniques was used to examine the association between DM status and cancer risk with adjustment for potential confounding variables in the survey respondent cohort. |
Participant flow
Recruitment details
Participants took part in the study at 2 investigative sites in the United States from 01 July 1997 to 30 June 2011.
Pre-assignment details
Participants with a historical diagnosis of Type 2 diabetes mellitus (T2DM) with pioglitazone exposure identified from the Kaiser Permanente of Northern California(KPNC) Diabetes Registry (with or without diabetes) and had completed Member Health Survey (MHS) were enrolled in the epidemiology study.
Participants by arm
| Arm | Count |
|---|---|
| Full KPNC Cohort Participants who were members of the KPNC registry (with or without diabetes) were followed up to 15 years (1997-2011) in this epidemiological study. | 2,630,666 |
| Survey Responders Cohort A subset of KPNC members who completed the Kaiser Diabetes Registry Survey in 1994-1996 and among a random sample of KPNC members who completed the Member Health Survey (MHS), in 1996, 1999, 2002, or 2005 were followed up to 15 years (1997-2011) in this epidemiological study. | 107,495 |
| Total | 2,738,161 |
Baseline characteristics
| Characteristic | Full KPNC Cohort | Survey Responders Cohort | Total |
|---|---|---|---|
| Age, Customized 40 - 49 years | 1501084 participants 11.6 | 30256 participants 12.9 | 1531340 participants |
| Age, Customized 50 - 59 years | 570636 participants | 24585 participants | 595221 participants |
| Age, Customized 60 - 69 years | 322517 participants | 25582 participants | 348099 participants |
| Age, Customized 70 - 79 years | 170136 participants | 22028 participants | 192164 participants |
| Age, Customized greater than or equal to (>=) 80 years | 66293 participants | 5044 participants | 71337 participants |
| Race/Ethnicity, Customized Asian or Pacific Islander | 312730 Participants | 13508 Participants | 326238 Participants |
| Race/Ethnicity, Customized Black | 171604 Participants | 10167 Participants | 181771 Participants |
| Race/Ethnicity, Customized Hispanic | 322046 Participants | 11871 Participants | 333917 Participants |
| Race/Ethnicity, Customized Other | 87901 Participants | 2728 Participants | 90629 Participants |
| Race/Ethnicity, Customized Unknown | 396580 Participants | 1384 Participants | 397964 Participants |
| Race/Ethnicity, Customized White | 1339805 Participants | 67837 Participants | 1407642 Participants |
| Sex: Female, Male Female | 1353782 Participants | 54418 Participants | 1408200 Participants |
| Sex: Female, Male Male | 1276884 Participants | 53077 Participants | 1329961 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
Age and Sex-Standardized Incidence Rates for the 10 Most Common Cancers Stratified by Diabetes Status
Age and gender adjusted incidence rates, stratified by diabetes status, was calculated using the direct method (2000 US Census as standard), with further stratification on calendar year. Cancer incidence rates were calculated with attention to the proper allocation of at-risk person-time. The association between diabetes and risk of each of the 10 most common cancers was assessed using Cox proportional hazards regression models with control for available potential confounders: age, gender. Similarly, Cox regression technique was used to examine the association between diabetes status and cancer risk among survey responders with adjustment for additional potential confounding variable.
Time frame: 15 years
Population: Analysis population included participants from KPNC registry (with or without diabetes) and had completed the MHS in the epidemiology study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Full KPNC Cohort | Age and Sex-Standardized Incidence Rates for the 10 Most Common Cancers Stratified by Diabetes Status | Prostate, Diabetes Status: No | 380.2 Incidence per 100,000 person-years |
| Full KPNC Cohort | Age and Sex-Standardized Incidence Rates for the 10 Most Common Cancers Stratified by Diabetes Status | Prostate, Diabetes Status: Yes | 308.0 Incidence per 100,000 person-years |
| Full KPNC Cohort | Age and Sex-Standardized Incidence Rates for the 10 Most Common Cancers Stratified by Diabetes Status | Female Breast, Diabetes Status: No | 291.8 Incidence per 100,000 person-years |
| Full KPNC Cohort | Age and Sex-Standardized Incidence Rates for the 10 Most Common Cancers Stratified by Diabetes Status | Female Breast, Diabetes Status: Yes | 286.9 Incidence per 100,000 person-years |
| Full KPNC Cohort | Age and Sex-Standardized Incidence Rates for the 10 Most Common Cancers Stratified by Diabetes Status | Lung/Bronchus, Diabetes Status: No | 111.3 Incidence per 100,000 person-years |
| Full KPNC Cohort | Age and Sex-Standardized Incidence Rates for the 10 Most Common Cancers Stratified by Diabetes Status | Lung/Bronchus, Diabetes Status: Yes | 108.8 Incidence per 100,000 person-years |
| Full KPNC Cohort | Age and Sex-Standardized Incidence Rates for the 10 Most Common Cancers Stratified by Diabetes Status | Colon, Diabetes Status: No | 69.1 Incidence per 100,000 person-years |
| Full KPNC Cohort | Age and Sex-Standardized Incidence Rates for the 10 Most Common Cancers Stratified by Diabetes Status | Colon, Diabetes Status: Yes | 93.5 Incidence per 100,000 person-years |
| Full KPNC Cohort | Age and Sex-Standardized Incidence Rates for the 10 Most Common Cancers Stratified by Diabetes Status | Non-Hodgkin lymphoma, Diabetes: No | 39.5 Incidence per 100,000 person-years |
| Full KPNC Cohort | Age and Sex-Standardized Incidence Rates for the 10 Most Common Cancers Stratified by Diabetes Status | Non-Hodgkin lymphoma, Diabetes: Yes | 45.6 Incidence per 100,000 person-years |
| Full KPNC Cohort | Age and Sex-Standardized Incidence Rates for the 10 Most Common Cancers Stratified by Diabetes Status | Corpus uteri, Diabetes Status: No | 55.9 Incidence per 100,000 person-years |
| Full KPNC Cohort | Age and Sex-Standardized Incidence Rates for the 10 Most Common Cancers Stratified by Diabetes Status | Corpus uteri, Diabetes Status: Yes | 112.1 Incidence per 100,000 person-years |
| Full KPNC Cohort | Age and Sex-Standardized Incidence Rates for the 10 Most Common Cancers Stratified by Diabetes Status | Pancreas, Diabetes Status: No | 18.8 Incidence per 100,000 person-years |
| Full KPNC Cohort | Age and Sex-Standardized Incidence Rates for the 10 Most Common Cancers Stratified by Diabetes Status | Pancreas, Diabetes Status: Yes | 47.3 Incidence per 100,000 person-years |
| Full KPNC Cohort | Age and Sex-Standardized Incidence Rates for the 10 Most Common Cancers Stratified by Diabetes Status | Kidney/Renal Pelvis, Diabetes Status: No | 23.5 Incidence per 100,000 person-years |
| Full KPNC Cohort | Age and Sex-Standardized Incidence Rates for the 10 Most Common Cancers Stratified by Diabetes Status | Kidney/Renal Pelvis, Diabetes Status: Yes | 39.5 Incidence per 100,000 person-years |
| Full KPNC Cohort | Age and Sex-Standardized Incidence Rates for the 10 Most Common Cancers Stratified by Diabetes Status | Rectal, Diabetes Status: No | 24.6 Incidence per 100,000 person-years |
| Full KPNC Cohort | Age and Sex-Standardized Incidence Rates for the 10 Most Common Cancers Stratified by Diabetes Status | Rectal, Diabetes Status: Yes | 31.1 Incidence per 100,000 person-years |
| Full KPNC Cohort | Age and Sex-Standardized Incidence Rates for the 10 Most Common Cancers Stratified by Diabetes Status | Melanoma, Diabetes Status: No | 42.5 Incidence per 100,000 person-years |
| Full KPNC Cohort | Age and Sex-Standardized Incidence Rates for the 10 Most Common Cancers Stratified by Diabetes Status | Melanoma, Diabetes Status: Yes | 30.6 Incidence per 100,000 person-years |
| Survey Responders Cohort | Age and Sex-Standardized Incidence Rates for the 10 Most Common Cancers Stratified by Diabetes Status | Rectal, Diabetes Status: Yes | 31.9 Incidence per 100,000 person-years |
| Survey Responders Cohort | Age and Sex-Standardized Incidence Rates for the 10 Most Common Cancers Stratified by Diabetes Status | Prostate, Diabetes Status: No | 421.9 Incidence per 100,000 person-years |
| Survey Responders Cohort | Age and Sex-Standardized Incidence Rates for the 10 Most Common Cancers Stratified by Diabetes Status | Corpus uteri, Diabetes Status: No | 59.7 Incidence per 100,000 person-years |
| Survey Responders Cohort | Age and Sex-Standardized Incidence Rates for the 10 Most Common Cancers Stratified by Diabetes Status | Prostate, Diabetes Status: Yes | 281.9 Incidence per 100,000 person-years |
| Survey Responders Cohort | Age and Sex-Standardized Incidence Rates for the 10 Most Common Cancers Stratified by Diabetes Status | Kidney/Renal Pelvis, Diabetes Status: Yes | 34.5 Incidence per 100,000 person-years |
| Survey Responders Cohort | Age and Sex-Standardized Incidence Rates for the 10 Most Common Cancers Stratified by Diabetes Status | Female Breast, Diabetes Status: No | 310.7 Incidence per 100,000 person-years |
| Survey Responders Cohort | Age and Sex-Standardized Incidence Rates for the 10 Most Common Cancers Stratified by Diabetes Status | Corpus uteri, Diabetes Status: Yes | 106.2 Incidence per 100,000 person-years |
| Survey Responders Cohort | Age and Sex-Standardized Incidence Rates for the 10 Most Common Cancers Stratified by Diabetes Status | Female Breast, Diabetes Status: Yes | 287.9 Incidence per 100,000 person-years |
| Survey Responders Cohort | Age and Sex-Standardized Incidence Rates for the 10 Most Common Cancers Stratified by Diabetes Status | Melanoma, Diabetes Status: Yes | 31.7 Incidence per 100,000 person-years |
| Survey Responders Cohort | Age and Sex-Standardized Incidence Rates for the 10 Most Common Cancers Stratified by Diabetes Status | Lung/Bronchus, Diabetes Status: No | 116.1 Incidence per 100,000 person-years |
| Survey Responders Cohort | Age and Sex-Standardized Incidence Rates for the 10 Most Common Cancers Stratified by Diabetes Status | Pancreas, Diabetes Status: No | 18.5 Incidence per 100,000 person-years |
| Survey Responders Cohort | Age and Sex-Standardized Incidence Rates for the 10 Most Common Cancers Stratified by Diabetes Status | Lung/Bronchus, Diabetes Status: Yes | 105.9 Incidence per 100,000 person-years |
| Survey Responders Cohort | Age and Sex-Standardized Incidence Rates for the 10 Most Common Cancers Stratified by Diabetes Status | Rectal, Diabetes Status: No | 26.7 Incidence per 100,000 person-years |
| Survey Responders Cohort | Age and Sex-Standardized Incidence Rates for the 10 Most Common Cancers Stratified by Diabetes Status | Colon, Diabetes Status: No | 75.5 Incidence per 100,000 person-years |
| Survey Responders Cohort | Age and Sex-Standardized Incidence Rates for the 10 Most Common Cancers Stratified by Diabetes Status | Pancreas, Diabetes Status: Yes | 37.1 Incidence per 100,000 person-years |
| Survey Responders Cohort | Age and Sex-Standardized Incidence Rates for the 10 Most Common Cancers Stratified by Diabetes Status | Colon, Diabetes Status: Yes | 97.3 Incidence per 100,000 person-years |
| Survey Responders Cohort | Age and Sex-Standardized Incidence Rates for the 10 Most Common Cancers Stratified by Diabetes Status | Melanoma, Diabetes Status: No | 55.8 Incidence per 100,000 person-years |
| Survey Responders Cohort | Age and Sex-Standardized Incidence Rates for the 10 Most Common Cancers Stratified by Diabetes Status | Non-Hodgkin lymphoma, Diabetes: No | 40.6 Incidence per 100,000 person-years |
| Survey Responders Cohort | Age and Sex-Standardized Incidence Rates for the 10 Most Common Cancers Stratified by Diabetes Status | Kidney/Renal Pelvis, Diabetes Status: No | 21.5 Incidence per 100,000 person-years |
| Survey Responders Cohort | Age and Sex-Standardized Incidence Rates for the 10 Most Common Cancers Stratified by Diabetes Status | Non-Hodgkin lymphoma, Diabetes: Yes | 43.2 Incidence per 100,000 person-years |
Primary
Hazard Ratio for Risk of 10 Common Cancers Associated With Diabetes
The association between diabetes and risk of each of the 10 most common cancers was assessed by calculating hazard ratio using Cox proportional hazards regression models with control for available potential confounders: age, gender and calendar years. Cox regression techniques was used to examine the association between DM status and cancer risk with adjustment for potential confounding variables in the survey respondent cohort.
Time frame: 15 years
Population: Analysis population included participants from KPNC registry (with or without diabetes) and had completed the MHS in the epidemiology study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Full KPNC Cohort | Hazard Ratio for Risk of 10 Common Cancers Associated With Diabetes | Prostate, Diabetes Status | 0.81 Ratio |
| Full KPNC Cohort | Hazard Ratio for Risk of 10 Common Cancers Associated With Diabetes | Female Breast, Diabetes Status | 1.01 Ratio |
| Full KPNC Cohort | Hazard Ratio for Risk of 10 Common Cancers Associated With Diabetes | Lung/Bronchus, Diabetes Status | 0.99 Ratio |
| Full KPNC Cohort | Hazard Ratio for Risk of 10 Common Cancers Associated With Diabetes | Colon, Diabetes Status | 1.36 Ratio |
| Full KPNC Cohort | Hazard Ratio for Risk of 10 Common Cancers Associated With Diabetes | Non-Hodgkin lymphoma, Diabetes | 1.14 Ratio |
| Full KPNC Cohort | Hazard Ratio for Risk of 10 Common Cancers Associated With Diabetes | Corpus uteri, Diabetes Status | 1.82 Ratio |
| Full KPNC Cohort | Hazard Ratio for Risk of 10 Common Cancers Associated With Diabetes | Pancreas, Diabetes Status | 2.50 Ratio |
| Full KPNC Cohort | Hazard Ratio for Risk of 10 Common Cancers Associated With Diabetes | Kidney/Renal Pelvis, Diabetes Status | 1.56 Ratio |
| Full KPNC Cohort | Hazard Ratio for Risk of 10 Common Cancers Associated With Diabetes | Rectal, Diabetes Status | 1.25 Ratio |
| Full KPNC Cohort | Hazard Ratio for Risk of 10 Common Cancers Associated With Diabetes | Melanoma, Diabetes Status | 0.73 Ratio |
| Survey Responders Cohort | Hazard Ratio for Risk of 10 Common Cancers Associated With Diabetes | Kidney/Renal Pelvis, Diabetes Status | 1.37 Ratio |
| Survey Responders Cohort | Hazard Ratio for Risk of 10 Common Cancers Associated With Diabetes | Prostate, Diabetes Status | 0.77 Ratio |
| Survey Responders Cohort | Hazard Ratio for Risk of 10 Common Cancers Associated With Diabetes | Corpus uteri, Diabetes Status | 1.67 Ratio |
| Survey Responders Cohort | Hazard Ratio for Risk of 10 Common Cancers Associated With Diabetes | Female Breast, Diabetes Status | 0.98 Ratio |
| Survey Responders Cohort | Hazard Ratio for Risk of 10 Common Cancers Associated With Diabetes | Melanoma, Diabetes Status | 0.69 Ratio |
| Survey Responders Cohort | Hazard Ratio for Risk of 10 Common Cancers Associated With Diabetes | Lung/Bronchus, Diabetes Status | 0.84 Ratio |
| Survey Responders Cohort | Hazard Ratio for Risk of 10 Common Cancers Associated With Diabetes | Pancreas, Diabetes Status | 2.38 Ratio |
| Survey Responders Cohort | Hazard Ratio for Risk of 10 Common Cancers Associated With Diabetes | Colon, Diabetes Status | 1.18 Ratio |
| Survey Responders Cohort | Hazard Ratio for Risk of 10 Common Cancers Associated With Diabetes | Rectal, Diabetes Status | 1.41 Ratio |
| Survey Responders Cohort | Hazard Ratio for Risk of 10 Common Cancers Associated With Diabetes | Non-Hodgkin lymphoma, Diabetes | 1.06 Ratio |