Abstract
Obesity and diabetes have both been associated with an increased risk of cancer. In the face of increasing obesity and diabetes rates worldwide, this is a worrying trend for cancer rates. ...Factors such as hyperinsulinemia, chronic inflammation, antihyperglycemic medications, and shared risk factors have all been identified as potential mechanisms underlying the relationship. The most common obesity- and diabetes-related cancers are endometrial, colorectal, and postmenopausal breast cancers. In this review, we summarize the existing evidence that describes the complex relationship between obesity, diabetes, and cancer, focusing on epidemiological and pathophysiological evidence, and also reviewing the role of antihyperglycemic agents, novel research approaches such as Mendelian Randomization, and the methodological limitations of existing research. In addition, we also describe the bidirectional relationship between diabetes and cancer with a review of the evidence summarizing the risk of diabetes following cancer treatment. We conclude this review by providing clinical implications that are relevant for caring for patients with obesity, diabetes, and cancer and provide recommendations for improving both clinical care and research for patients with these conditions.
Graphical Abstract
Graphical Abstract
Health care data allow for the study and surveillance of chronic diseases such as diabetes. The objective of this study was to identify and validate optimal algorithms for diabetes cases within ...health care administrative databases for different research purposes, populations, and data sources.
We linked health care administrative databases from Ontario, Canada to a reference standard of primary care electronic medical records (EMRs). We then identified and calculated the performance characteristics of multiple adult diabetes case definitions, using combinations of data sources and time windows.
The best algorithm to identify diabetes cases was the presence at any time of one hospitalization or physician claim for diabetes AND either one prescription for an anti-diabetic medication or one physician claim with a diabetes-specific fee code sensitivity 84.2%, specificity 99.2%, positive predictive value (PPV) 92.5%. Use of physician claims alone performed almost as well: three physician claims for diabetes within one year was highly specific (sensitivity 79.9%, specificity 99.1%, PPV 91.4%) and one physician claim at any time was highly sensitive (sensitivity 93.6%, specificity 91.9%, PPV 58.5%).
This study identifies validated algorithms to capture diabetes cases within health care administrative databases for a range of purposes, populations and data availability. These findings are useful to study trends and outcomes of diabetes using routinely-collected health care data.
Because individuals with osteoarthritis (OA) avoid physical activities that exacerbate symptoms, potentially increasing risk for cardiovascular disease (CVD) and death, we assessed the relationship ...between OA disability and these outcomes.
In a population cohort aged 55+ years with at least moderately severe symptomatic hip and/or knee OA, OA disability (Western Ontario McMaster Universities (WOMAC) OA scores; Health Assessment Questionnaire (HAQ) walking score; use of walking aids) and other covariates were assessed by questionnaire. Survey data were linked to health administrative data to determine the relationship between baseline OA symptom severity to all-cause mortality and occurrence of a composite CVD outcome (acute myocardial infarction, coronary revascularization, heart failure, stroke or transient ischemic attack) over a median follow-up of 13.2 and 9.2 years, respectively.
Of 2156 participants, 1,236 (57.3%) died and 822 (38.1%) experienced a CVD outcome during follow-up. Higher (worse) baseline WOMAC function scores and walking disability were independently associated with a higher all-cause mortality (adjusted hazard ratio, aHR, per 10-point increase in WOMAC function score 1.04, 95% confidence interval, CI 1.01-1.07, p = 0.004; aHR per unit increase in HAQ walking score 1.30, 95% CI 1.22-1.39, p<0.001; and aHR for those using versus not using a walking aid 1.51, 95% CI 1.34-1.70, p<0.001). In survival analysis, censoring on death, risk of our composite CVD outcome was also significantly and independently associated with greater baseline walking disability ((aHR for use of a walking aid = 1.27, 95% CI 1.10-1.47, p = 0.001; aHR per unit increase in HAQ walking score = 1.17, 95% CI 1.08-1.27, p<0.001).
Among individuals with hip and/or knee OA, severity of OA disability was associated with a significant increase in all-cause mortality and serious CVD events after controlling for multiple confounders. Research is needed to elucidate modifiable mechanisms.
Summary Background The prevalence of diabetes has been increasing greatly, but WHO's predicted 39% rise in the global rate of diabetes from 2000 to 2030 might be an underestimate. We aimed to assess ...diabetes trends in Ontario, Canada. Methods Using population-based data, including a validated diabetes database from the province of Ontario, Canada, we examined trends in diabetes prevalence and mortality from 1995 to 2005, and incidence from 1997 to 2003, in adults aged 20 years or older. Findings Age-adjusted and sex-adjusted diabetes prevalence increased by 69%, from 5·2% in a population of 7 908 562 in 1995 to 8·8% of 9 276 945 in 2005. Prevalence increased by 27% from 6·9% in a population of 8 457 720 in 2000 to 8·8% of 9 276 945 in 2005. Although prevalence rates have remained higher in people aged 50 years or older (7·1% of 3 675 554) than in those aged 20–49 years (3·5% of 5 601 391), rates increased to a greater extent in the younger population (94% vs 63%, p<0·0001). A 31% increase occurred in yearly incidence over 6 years, from 6·6 per 1000 in 1997 to 8·2 per 1000 in 2003. The adjusted mortality rate in people with diabetes fell by 25% from 1995 to 2005. Interpretation The prevalence of diabetes in Ontario, Canada increased substantially during the past 10 years, and by 2005 already exceeded the global rate that was predicted for 2030. This increase in prevalence is attributable to both rising incidence and declining mortality. Effective public-health interventions aimed at diabetes prevention are needed, as well as improved resources to manage the greater number of people living longer with the disease.
To evaluate the association between cumulative duration of metformin use after prostate cancer (PC) diagnosis and all-cause and PC-specific mortality among patients with diabetes.
We used a ...population-based retrospective cohort design. Data were obtained from several Ontario health care administrative databases. Within a cohort of men older than age 66 years with incident diabetes who subsequently developed PC, we examined the effect of duration of antidiabetic medication exposure after PC diagnosis on all-cause and PC-specific mortality. Crude and adjusted hazard ratios (HRs) were calculated by using a time-varying Cox proportional hazard model to estimate effects.
The cohort consisted of 3,837 patients. Median age at diagnosis of PC was 75 years (interquartile range IQR, 72 to 79 years). During a median follow-up of 4.64 years (IQR, 2.7 to 7.1 years), 1,343 (35%) died, and 291 patients (7.6%) died as a result of PC. Cumulative duration of metformin treatment after PC diagnosis was associated with a significant decreased risk of PC-specific and all-cause mortality in a dose-dependent fashion. Adjusted HR for PC-specific mortality was 0.76 (95% CI, 0.64 to 0.89) for each additional 6 months of metformin use. The association with all-cause mortality was also significant but declined over time from an HR of 0.76 in the first 6 months to 0.93 between 24 and 30 months. There was no relationship between cumulative use of other antidiabetic drugs and either outcome.
Increased cumulative duration of metformin exposure after PC diagnosis was associated with decreases in both all-cause and PC-specific mortality among diabetic men.
Aims/hypothesis
Individuals with diabetes are at increased risk of developing and dying from cancer. Evidence-based guidelines recommend universal screening for breast, cervical and colorectal ...cancer; however, evidence on the uptake of these tests in individuals with diabetes is mixed. We conducted a meta-analysis to quantify the association between diabetes and participation in breast, cervical and colorectal cancer screening.
Methods
MEDLINE, EMBASE and CINAHL were searched systematically for publications between 1 January 1997 and 18 July 2018. The search was supplemented by handsearching of reference lists of the included studies and known literature reviews. Abstracts and full texts were assessed in duplicate according to the following eligibility criteria: study conducted in the general population; diabetes included as a predictor vs a comparison group without diabetes; and breast (mammography), cervical (Papanicolaou smear) or colorectal (faecal and endoscopic tests) cancer screening uptake included as an outcome. Random-effects meta-analyses were performed using the most-adjusted estimates for each cancer site.
Results
Thirty-seven studies (25 cross-sectional, 12 cohorts) were included, with 27 studies on breast, 19 on cervical and 18 on colorectal cancer screening. Having diabetes was associated with significantly lower likelihood of breast (adjusted OR 0.83 95% CI 0.77, 0.90) and cervical (OR 0.76 95% CI 0.71, 0.81) cancer screening, relative to not having diabetes. Colorectal cancer screening was comparable across groups with and without diabetes (OR 0.95 95% CI 0.86, 1.06); however, women with diabetes were less likely to receive a colorectal cancer screening test than women without diabetes (OR 0.86 95% CI 0.77, 0.97).
Conclusions/interpretation
Our findings suggest that women with diabetes have suboptimal breast, cervical and colorectal cancer screening rates, compared with women without diabetes, although the absolute differences might be modest. Given the increased risk of cancer in this population, higher quality prospective evidence is necessary to evaluate the contribution of diabetes to cancer screening disparities in relation to other patient-, provider- and system-level factors.
Registration
PROSPERO registration ID CRD42017073107.
Women with preeclampsia (PEC) and gestational hypertension (GH) exhibit insulin resistance during pregnancy, independent of obesity and glucose intolerance. Our aim was to determine whether women ...with PEC or GH during pregnancy have an increased risk of developing diabetes after pregnancy, and whether the presence of PEC/GH in addition to gestational diabetes (GDM) increases the risk of future (postpartum) diabetes.
We performed a population-based, retrospective cohort study for 1,010,068 pregnant women who delivered in Ontario, Canada between April 1994 and March 2008. Women were categorized as having PEC alone (n=22,933), GH alone (n=27,605), GDM alone (n=30,852), GDM+PEC (n=1,476), GDM+GH (n=2,100), or none of these conditions (n=925,102). Our main outcome was a new diagnosis of diabetes postpartum in the following years, up until March 2011, based on new records in the Ontario Diabetes Database. The incidence rate of diabetes per 1,000 person-years was 6.47 for women with PEC and 5.26 for GH compared with 2.81 in women with neither of these conditions. In the multivariable analysis, both PEC alone (hazard ratio HR=2.08; 95% CI 1.97-2.19) and GH alone (HR=1.95; 95% CI 1.83-2.07) were risk factors for subsequent diabetes. Women with GDM alone were at elevated risk of developing diabetes postpartum (HR=12.77; 95% CI 12.44-13.10); however, the co-presence of PEC or GH in addition to GDM further elevated this risk (HR=15.75; 95% CI 14.52-17.07, and HR=18.49; 95% CI 17.12-19.96, respectively). Data on obesity were not available.
Women with PEC/GH have a 2-fold increased risk of developing diabetes when followed up to 16.5 years after pregnancy, even in the absence of GDM. The presence of PEC/GH in the setting of GDM also raised the risk of diabetes significantly beyond that seen with GDM alone. A history of PEC/GH during pregnancy should alert clinicians to the need for preventative counseling and more vigilant screening for diabetes. Please see later in the article for the Editors' Summary.
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