Risk of Breast Cancer After Diabetes in Pregnancy: A Population-based Cohort Study.

OBJECTIVES: Diabetes is associated with an increased risk of several cancers, including postmenopausal breast cancer. The evidence for higher breast cancer risk after diabetes in pregnancy is conflicting. We compared the incidence of breast and other cancers between pregnant women with and without diabetes. METHODS: This work was a propensity-matched, retrospective cohort study using population-based health-care databases from Ontario, Canada. Those deliveries with gestational diabetes mellitus (GDM) and pregestational diabetes mellitus (pregestational DM) were identified and matched to deliveries without diabetes mellitus (non-DM). Deliveries from each diabetes cohort were matched 1:2 on age, parity, year of delivery, and propensity score to non-DM deliveries. Matched subjects were followed from delivery for incidence of breast cancer as a primary outcome, and other site-specific cancers as secondary outcomes. We performed Cox proportional hazards regression to compare rates of breast cancer between matched groups. RESULTS: Over a median of 8 (interquartile range 4 to 13) years of follow-up, compared with non-DM deliveries, the incidence of breast cancer was significantly lower for GDM but similar for pregestational DM deliveries (hazard ratio [HR] 0.90, 95% confidence interval [CI] 0.82 to 0.98; and HR 0.92, 95% CI 0.80 to 1.07, respectively). GDM was associated with a significantly higher incidence of pancreatic and hepatocellular cancer, and pregestational DM was associated with a higher incidence of thyroid, hepatocellular, and endometrial cancers. CONCLUSIONS: Diabetes in pregnancy does not have a higher short-term risk of subsequent breast cancer, but there may be a higher incidence of other cancers.

Salpingectomy and the Risk of Ovarian Cancer in Ontario.

Importance: A body of pathological and clinical evidence supports the position that the fallopian tube is the site of origin for a large proportion of high-grade serous ovarian cancers. Consequently, salpingectomy is now considered for permanent contraception (in lieu of tubal ligation) or ovarian cancer prevention (performed opportunistically at the time of surgical procedures for benign gynecologic conditions). Objective: To evaluate the association between salpingectomy and the risk of invasive epithelial ovarian, fallopian tube, and peritoneal cancer. Design, Setting, and Participants: This population-based retrospective cohort study included all women aged 18 to 80 years who were eligible for health care services in Ontario, Canada. Participants were identified using administrative health databases from Ontario between January 1, 1992, and December 31, 2019. A total of 131 516 women were included in the primary (matched) analysis. Women were followed up until December 31, 2021. Exposures: Salpingectomy (with and without hysterectomy) vs no pelvic procedure (control condition) among women in the general population. Main Outcomes and Measures: Women with a unilateral or bilateral salpingectomy in Ontario between April 1, 1992, and December 31, 2019, were matched 1:3 to women with no pelvic procedure from the general population. Cox proportional hazards regression models were used to estimate the hazard ratios (HRs) and 95% CIs for ovarian, fallopian tube, and peritoneal cancer combined. Results: Among 131 516 women (mean [SD] age, 42.2 [7.6] years), 32 879 underwent a unilateral or bilateral salpingectomy, and 98 637 did not undergo a pelvic procedure. After a mean (range) follow-up of 7.4 (0-29.2) years in the salpingectomy group and 7.5 (0-29.2) years in the nonsurgical control group, there were 31 incident cancers (0.09%) and 117 incident cancers (0.12%), respectively (HR, 0.82; 95% CI, 0.55-1.21). The HR for cancer incidence was 0.87 (95% CI, 0.53-1.44) when comparing those with salpingectomy vs those with hysterectomy alone. Conclusions and Relevance: In this cohort study, no association was found between salpingectomy and the risk of ovarian cancer; however, this observation was based on few incident cases and a relatively short follow-up time. Studies with additional years of follow-up are necessary to define the true level of potential risk reduction with salpingectomy, although longer follow-up will also be a challenge unless collaborative efforts that pool data are undertaken.

Fracture risk among patients with cancer compared to individuals without cancer: a population-based study.

BACKGROUND: Patients with cancer may be at increased risk of osteoporosis and fracture; however, gaps exist in the existing literature and the association between cancer and fracture requires further examination. METHODS: We conducted a population-based cohort study of Ontario patients with cancer (breast, prostate, lung, gastrointestinal, haematologic) diagnosed between January 2007 to December 2018 and 1:1 matched non-cancer controls. The primary outcome was incident fracture (end of follow-up December 2019). Multivariable Cox regression analysis was used to estimate the relative fracture risk with sensitivity analysis accounting for competing risk of death. RESULTS: Among 172,963 cancer patients with non-cancer controls, 70.6% of patients with cancer were <65 years old, 58% were female, and 9375 and 8141 fracture events were observed in the cancer and non-cancer group, respectively (median follow-up 6.5 years). Compared to non-cancer controls, patients with cancer had higher risk of fracture (adjusted HR [aHR] 1.10, 95% CI 1.07-1.14, p < 0.0001), which was also observed for both solid (aHR 1.09, 95% CI 1.05-1.13, p < 0.0001) and haematologic cancers (aHR 1.20, 95% CI 1.10-1.31, p < 0.0001). Sensitivity analysis accounting for competing risk of death did not change these findings. CONCLUSIONS: Our study indicates that patients with cancer are at modest risk of fractures compared to non-cancer controls.

Risk of Adverse Cardiovascular Outcomes in Differentiated Thyroid Cancer Survivors: A Systematic Review and Meta-Analysis.

Introduction: Long-term cardiovascular (CV) risk is a concern for differentiated thyroid cancer (DTC) survivors. Methods: We performed a systematic review and meta-analysis evaluating the risks of CV mortality and morbidity in DTC survivors compared with the general population. Respective meta-analyses were conducted for data that were adjusted for relevant confounders and crude data. We searched five electronic databases from inception to October 2021, supplemented with a hand search. Two reviewers independently screened citations, reviewed full text articles, extracted data, and critically appraised the studies, with discrepancies resolved by a third reviewer. The primary outcome was CV mortality. Secondary outcomes included atrial fibrillation, ischemic heart disease, stroke, and heart failure. We estimated the relative risk (RR) and confidence intervals [CI] of outcomes using random-effects models (adjusted for age and gender), compared with the general population. Results: We reviewed 3409 unique citations, 65 full text articles, and included 7 studies. CV mortality risk was significantly increased in DTC survivors in one study adjusted for confounders-adjusted RR (aRR) 3.35 ([CI 1.66-6.67]; 524 DTC, 1572 controls). The risk of CV morbidity in DTC survivors, adjusted for risk factors, was estimated as follows: atrial fibrillation-aRR 1.66 [CI 1.22-2.27] (3 studies, 4428 DTC, I2 = 75%), ischemic heart disease-aRR 0.97 [CI 0.84-1.13] (2 studies, 3910 DTC, I2 = 0%), stroke-aRR 1.14 [CI 0.84-1.55] (2 studies, 3910 DTC, I2 = 69%), and heart failure-aRR 0.98 [CI 0.60-1.59] (2 studies, 3910 DTC, I2 = 79%). In meta-analyses of unadjusted data, the risks of CV mortality were not significantly increased but the CV morbidity risks were similar to adjusted data. Conclusions: There is limited evidence suggesting that DTC survivors may be at an increased risk of CV death and atrial fibrillation (after adjustment for confounders). We did not observe a significantly increased risk of ischemic heart disease, stroke, or heart failure. Most analyses were subject to significant heterogeneity and further research, with careful attention to CV risk factors, is needed to clarify CV risk in DTC survivors. Registration: PROSPERO CRD42021244743.

Associations Among Biomarkers of Inflammation, Tubular Injury and Lipid Metabolism With Gestational Diabetes Mellitus Status, Microalbuminuria and Retinopathy in the Microalbuminuria and Retinopathy in Gestational Diabetes Study.

OBJECTIVES: Pregnancy may be complicated by gestational diabetes mellitus (GDM) and/or microvascular complications like albuminuria, retinopathy and pre-eclampsia. In this study we aimed to identify whether mechanistic pathways associated with microvascular complications are active in pregnant women with GDM or microvascular disease. METHODS: Urinary albumin excretion and biomarkers of inflammation, lipoprotein metabolism and tubular injury were quantified in 355 pregnant women with and without GDM. Participants underwent fundus photography graded for retinopathy. Adjusted associations between individual biomarkers and each outcome variable of interest, including GDM status, albuminuria and retinopathy, were performed using logistic regression. RESULTS: After adjusting for age, systolic blood pressure, body mass index and ethnicity, significant associations between GDM status and apolipoprotein A1, interleukin (IL)-6, IL-8, soluble tumour necrosis factor receptor-I and -II (sTNFR-I and -II), vascular endothelial growth factor and von Willebrand factor were observed. Increased high-sensitivity C-reactive protein (hsCRP) and sTNFR-II were associated with higher levels of albuminuria. hsCRP and previous GDM were associated with retinopathy. CONCLUSION: Mechanistic pathways associated with microvascular complications appear to be active in pregnant women with GDM or microvascular disease.

Access to diagnostic imaging and incidental detection of differentiated thyroid cancer in Ontario: A population-based retrospective cohort study.

Global increases in thyroid cancer incidence (≥90% differentiated thyroid cancers; DTC) are hypothesized to be related to increased use of pre-diagnostic imaging. These procedures can detect DTC during imaging for conditions unrelated to the thyroid (incidental detection). The objectives were to evaluate incidental detection of DTC associated with standardized, regional imaging capacity and drivetime from patient residence to imaging facility (the exposures). We conducted a population-based retrospective cohort study of 32,097 DTC patients in Ontario, 2003-2017. We employed sex-specific spatial Bayesian hierarchical models to evaluate the exposures and examine the adjusted odds of incidental detection by administrative regions. Regional capacities of computed tomography and magnetic resonance imaging scanners are positively associated with incidental detection, but vary by sex. Contrary to hypothesis, drivetimes in urban areas are positively associated with incidental detection. Access to primary care may play a role in several administrative regions with higher adjusted odds of incidental detection.

Effect of Chronic Comorbidities on Follow-up Colonoscopy After Positive Colorectal Cancer Screening Results: A Population-Based Cohort Study.

INTRODUCTION: Fecal occult blood tests (FOBTs) are colorectal cancer screening tests used to identify individuals requiring further investigation with colonoscopy. Delayed colonoscopy after positive FOBT (FOBT+) is associated with poorer cancer outcomes. We assessed the effect of comorbidity on colonoscopy receipt within 12 months after FOBT+. METHODS: Population-based healthcare databases from Ontario, Canada, were linked to assemble a cohort of 50-74-year-old individuals with FOBT+ results between 2008 and 2017. The associations between comorbidities and colonoscopy receipt within 12 months after FOBT+ were examined using multivariable cause-specific hazard regression models. RESULTS: Of 168,701 individuals with FOBT+, 80.5% received colonoscopy within 12 months. In multivariable models, renal failure (hazard ratio [HR] 0.71, 95% confidence interval [CI] 0.62-0.82), heart failure (HR 0.77, CI 0.75-0.80), and serious mental illness (HR 0.88, CI 0.85-0.92) were associated with the lowest colonoscopy rates, compared with not having each condition. The number of medical conditions was inversely associated with colonoscopy uptake (≥4 vs 0: HR 0.64, CI 0.58-0.69; 3 vs 0: HR 0.75, CI 0.72-0.78; and 2 vs 0: HR 0.87, CI 0.85-0.89). Having both medical and mental health conditions was associated with a lower colonoscopy uptake relative to no comorbidity (HR 0.88, CI 0.87-0.90). DISCUSSION: Persons with medical and mental health conditions had lower colonoscopy rates after FOBT+ than those without these conditions. Better strategies are needed to optimize colorectal cancer screening and follow-up in individuals with comorbidities.

Periodic screening for breast and cervical cancer in women with diabetes: a population-based cohort study.

PURPOSE: Diabetes is associated with poorer cancer outcomes. Screening for breast and cervical cancer is recommended by clinical guidelines; however, utilization of these tests in people with diabetes has been unclear due to methodological limitations in the evidence base. We used administrative data to determine the association between diabetes and the rates of becoming up-to-date with periodic breast and cervical cancer screening over a 20-year period. METHODS: Healthcare databases from Ontario, Canada, were linked to assemble two population-based cohorts of 50-70 and 21-70 year-olds between 1994 and 2011, eligible for breast and cervical cancer screening, respectively. Using age as the time scale, multivariable recurrent events models were implemented to examine the association between the presence of diabetes and the rates of becoming up-to-date with the recommended cancer screenings. RESULTS: In each of the breast and cervical cancer screening cohorts, there were, respectively, 1,516,302 (16% had diabetes at baseline) and 4,751,220 (9.5% had diabetes at baseline) screen-eligible women. In multivariable models, prevalent diabetes (duration ≥ 2 years) was associated with lower rates of becoming up-to-date with cervical (hazard ratio, HR 0.85, 95% confidence interval, CI 0.84-0.85) and breast (HR 0.94, CI 0.93-0.94) cancer screening, compared to no diabetes. CONCLUSIONS: Having diabetes is associated with decreased rates of becoming up-to-date with two recommended periodic cancer screenings, with a bigger reduction in the rates of becoming up-to-date with cervical cancer screening. Greater attention to cervical cancer preventive services is needed in women with diabetes.

Allopurinol adherence, persistence and patterns of use in individuals with diabetes and gout: A retrospective, population-based cohort analysis.

OBJECTIVE: There has been growing interest in the potential role for allopurinol to reduce cardiovascular events in people with diabetes. While adherence to allopurinol is poor in those with gout, our aim was to characterize persistence, patterns of use, and predictors of allopurinol use in a population-based cohort of individuals with diabetes and gout. METHODS: Individuals with diabetes older than 66 (thus eligible for prescription medication coverage) and newly prescribed allopurinol were followed for up to three years in a retrospective cohort study. Allopurinol use patterns were categorized as adherer (used continuously throughout follow-up), interrupter (non-persistent but subsequently resumed), or discontinuer (non-persistent with no subsequent resumption). Main outcomes were allopurinol non-persistence (no subsequent prescription accounting for a grace period), and indicators of gout severity throughout follow-up (prescriptions for prednisone or colchicine, outpatient gout visits, hospitalization/emergency department visits for gout). Outcome frequencies were determined, a multivariable Cox proportional hazards model evaluated associations between predictors and non-persistence, and zero-inflated negative binomial (ZINB) models evaluated associations between allopurinol use pattern and indicators of gout severity. RESULTS: 22,056 individuals were followed for a maximum of 3.0 years (17,410 with 3 years of follow-up). 9092 (41.2%) were non-persistent with allopurinol. Higher risks of non-persistence were associated with female sex (HR, 95% CI: 1.28, 1.23-1.33), dementia (1.23, 1.11-1.35), and an outpatient visit for gout in the prior year (1.19, 1.09-1.29). There were 12,964 (58.8%) allopurinol adherers, 4618 interrupters (20.9%), and 4474 (20.3%) discontinuers. Allopurinol interrupters and discontinuers had indicators of more severe gout over time compared to adherers, including greater odds of being prescribed prednisone. CONCLUSION: Allopurinol non-persistence and interruptions were frequent in individuals with diabetes and gout and were associated with prescriptions for prednisone. Suboptimal allopurinol adherence may not only increase the risk of gout complications in this population but also potentially diabetes complications through greater prednisone use and its negative effects on glycemic control.

In obesity with T2DM, biliopancreatic diversion increased T2DM remission vs. medical and lifestyle therapy at 10 y.

SOURCE CITATION: Mingrone G, Panunzi S, De Gaetano A, et al. Metabolic surgery versus conventional medical therapy in patients with type 2 diabetes: 10-year follow-up of an open-label, single-centre, randomised controlled trial. Lancet. 2021;397:293-304. 33485454.

Allopurinol and Renal Outcomes in Adults With and Without Type 2 Diabetes: A Retrospective, Population-Based Cohort Study and Propensity Score Analysis.

OBJECTIVES: Elevated uric acid (UA) is common in diabetes and is implicated in the pathogenesis of chronic kidney disease (CKD). Lowering UA with allopurinol may delay CKD progression. We assessed the association between allopurinol and renal outcomes in older adults both with and without diabetes, and whether this differed by diabetes status. METHODS: We conducted a population-based, retrospective cohort study of older adults ≥66 years of age with a gout flare using administrative data from Ontario, Canada. The primary outcome was doubling of creatinine or kidney failure. Secondary outcomes were a composite of death or kidney failure, decline in estimated glomerular filtration rate by >30%, death and kidney failure. New allopurinol users were compared with nonusers using Cox proportional hazards models and inverse probability of treatment weighting (IPTW). An interaction between allopurinol use and presence or absence of diabetes was assessed. RESULTS: Among 5,937 older adults with a gout flare (1,911 with diabetes), 1,304 (22%) were newly treated with allopurinol. Median follow-up time was 1.11 (interquartile range, 0.33 to 3.21) years for allopurinol users and 3.38 (interquartile range, 1.42 to 4.43) years for nonusers. There was no association between allopurinol use and the primary outcome (IPTW-adjusted hazard ratio, 0.97; 95% confidence interval, 0.72 to 1.31), and this did not differ by diabetes status. Allopurinol use was not associated with any of the secondary outcomes. CONCLUSIONS: Allopurinol use was not associated with renal outcomes in older adults with or without diabetes. This supports the interpretation of UA as a biomarker of CKD risk rather than a modifiable target for prevention or treatment of CKD.

Influence of chronic comorbidities on periodic colorectal cancer screening participation: A population-based cohort study.

Guidelines recommend regular screening for colorectal cancer (CRC). We examined the effects of chronic comorbidities on periodic CRC testing. Using linked healthcare databases from Ontario, Canada, we assembled a population-based cohort of 50-74-year olds overdue for guideline-recommended CRC screening between April 1, 2004 and March 31, 2016. We implemented multivariable recurrent events models to determine the association between comorbidities and the rate of becoming up-to-date with periodic CRC tests. The cohort included 4,642,422 individuals. CRC testing rates were significantly lower in persons with renal disease on dialysis (hazard ratio, HR 0.66, 95% confidence interval, CI 0.63 to 0.68), heart failure (HR 0.75, CI 0.75 to 0.76), respiratory disease (HR 0.84, CI 0.83 to 0.84), cardiovascular disease (HR 0.85, CI 0.84 to 0.85), diabetes (HR 0.86, 95% CI 0.86 to 0.87) and mental illness (HR 0.88, CI 0.87 to 0.88). There was an inverse association between the number of medical conditions and the rate of CRC testing (5 vs. none: HR 0.30, CI 0.25 to 0.36; 4 vs. none: HR 0.48, CI 0.47 to 0.50; 3 vs. none: HR 0.59, CI 0.58 to 0.60; 2 vs. none: HR 0.72, CI 0.71 to 0.72; 1 vs. none: HR 0.85, CI 0.84 to 0.85). Having both medical and mental comorbidities was associated with lower testing rates than either type of comorbidity alone (HR 0.72, CI 0.71 to 0.72). In summary, chronic comorbidities present a barrier to periodic guideline-recommended CRC testing. Exploration of cancer prevention gaps in these populations is warranted.

BMI and risk of gestational diabetes among women of South Asian and Chinese ethnicity: a population-based study.

AIMS/HYPOTHESIS: The aim of this study was to examine how BMI influences the association between Asian ethnicity and risk of gestational diabetes (GDM). METHODS: This population-based cohort study included pregnant women without pre-existing diabetes mellitus in Ontario, Canada between 2012 and 2014. Women of Chinese and South Asian ethnicity were identified using a validated surname algorithm. GDM was ascertained using hospitalisation codes. The relationship between ethnicity and GDM was modelled using modified Poisson regression, adjusted for maternal age, pre-pregnancy BMI, parity, previous GDM, long-term residency status, income quintile and smoking status. An interaction term between ethnicity and pre-pregnancy BMI was tested. RESULTS: Of 231,618 pregnant women, 9289 (4.0%) were of South Asian ethnicity and 12,240 (5.3%) were of Chinese ethnicity. Relative to women from the general population, in whom prevalence of GDM was 4.3%, the adjusted RR of GDM was higher among those of South Asian ethnicity (1.81 [95% CI 1.64, 1.99]) and Chinese ethnicity (1.66 [95% CI 1.53, 1.80]). The association between GDM and Asian ethnicity remained significant across BMI categories but differed according to BMI. The prevalence of GDM exceeded 5% at an estimated BMI of 21.5 kg/m2 among South Asian women, 23.0 kg/m2 among Chinese women and 29.5 kg/m2 among the general population. CONCLUSIONS/INTERPRETATION: The risk of GDM is significantly higher in South Asian and Chinese women, whose BMI is lower than that of women in the general population. Accordingly, targeted GDM prevention strategies may need to consider lower BMI cut-points for Asian populations.

Association between diabetes and haematological malignancies: a population-based study.

AIMS/HYPOTHESIS: Contemporary data for the association of diabetes with haematological malignancies are lacking. We evaluated the risk of developing haematological malignancies and subsequent mortality in individuals with diabetes compared with those without diabetes. METHODS: We conducted a population-based observational study using healthcare databases from Ontario, Canada. All Ontario residents 30 years of age or older free of cancer and diabetes between 1 January 1996 and 31 December 2015 were eligible for inclusion. Using Cox regression analyses, we explored the association between diabetes and the risk and mortality of haematological malignancies (leukaemia, lymphoma, multiple myeloma). The impact of timing on associations was evaluated with analyses stratified by time since diabetes diagnosis (<3 months, 3 months to 1 year, ≥1 year). RESULTS: We identified 1,003,276 individuals with diabetes and age and sex matched these to 2,006,552 individuals without diabetes. Compared with individuals without diabetes, those with diabetes had a modest but significantly higher risk of a haematological malignancy (adjusted HR 1.10 [95% CI 1.08, 1.12] p < 0.0001). This association persisted across all time periods since diabetes diagnosis. Among those with haematological malignancies, diabetes was associated with a higher all-cause mortality (HR 1.36 [95% CI 1.31, 1.41] p < 0.0001) compared with no diabetes, as well as cause-specific mortality. CONCLUSIONS/INTERPRETATION: Diabetes is associated with a higher risk of haematological malignancies and is an independent risk factor of all-cause and cause-specific mortality. Greater efforts for lifestyle modification may not only reduce diabetes burden and its complications but may also potentially lower risk of malignancy and mortality. Graphical abstract.

Incidental detection, imaging modalities and temporal trends of differentiated thyroid cancer in Ontario: a population-based retrospective cohort study.

BACKGROUND: Incidence rates of thyroid cancer in Ontario have increased more rapidly than those of any other cancer, whereas mortality rates have remained relatively stable. We evaluated the extent to which incidental detection of differentiated thyroid cancer during unrelated prediagnostic imaging procedures contributed to Ontario's incidence rates. METHODS: We conducted a retrospective cohort study involving Ontarians who received a diagnosis of differentiated thyroid cancer from 1998 to 2017 using linked health care administrative databases. We classified cases as incidentally detected if a nonthyroid diagnostic imaging test (e.g., computed tomography [CT]) preceded an index event (e.g., prediagnostic fine-needle aspiration biopsy); all other cases were nonincidentally detected cases. We used Joinpoint and negative binomial regressions to characterize sex-specific rates of differentiated thyroid cancer by incidentally detected status and to quantify potential age, diagnosis period and birth cohort effects. RESULTS: The study included 36 531 patients with differentiated thyroid cancer, of which 78.7% were female. Incidentally detected cases increased from 7.0% to 11.0% of female patients and from 13.5% to 18.2% of male patients over the study period. Age-standardized incidence rates increased more rapidly for incidentally detected cases (4.2-fold for female and 3.7-fold for male patients) than for nonincidentally detected cases (2.6-fold for female and 3.0-fold for male patients; p < 0.001). Diagnosis period was the primary factor associated with increased incidence rates of differentiated thyroid cancer, adjusting for other factors. Within each period, incidentally detected rates increased faster than nonincidentally detected rates, adjusting for age. Our results showed that CT was the most common imaging procedure preceding incidentally detected diagnoses. INTERPRETATION: Incidentally detected cases represent a large and increasing component of the observed increases in differentiated thyroid cancer in Ontario over the past 20 years, and CT scans are primarily associated with these cases despite the modality having similar, increasing rates of use compared with magnetic resonance imaging (1993-2004). Recent increases in rates of differentiated thyroid cancer among males and incidentally detected cases among females in Ontario appear to be unrelated to birth cohort effects.

Impact of diabetes on colorectal cancer stage and mortality risk: a population-based cohort study.

AIMS/HYPOTHESIS: Diabetes is associated with an increased incidence of colorectal cancer (CRC). There exists conflicting evidence regarding the impact of diabetes on CRC-specific mortality (herein also referred to as cancer-specific mortality). The objectives of this study were to determine whether diabetes is associated with a more advanced CRC stage at diagnosis and with higher all-cause and cancer-specific mortality. METHODS: This retrospective cohort study used linked, population-based health databases from Ontario, Canada. Among individuals diagnosed with CRC from 2007 to 2015, we compared the likelihood of presenting with later- (III or IV) vs early- (I or II) stage CRC between patients with and without diabetes adjusting for relevant covariates. We then determined the association between diabetes and all-cause and CRC-specific mortality, after adjusting for CRC stage at diagnosis and other covariates. RESULTS: Of the 44,178 individuals with CRC, 11,822 (26.7%) had diabetes. After adjustment for CRC screening and other covariates, individuals with diabetes were not more likely to present with later-stage CRC (adjusted OR 0.97, 95% CI 0.93, 1.01). Over a median follow-up of 2.63 (interquartile range [IQR] 0.97-5.10) years, diabetes was associated with higher all-cause mortality (adjusted HR 1.08, 95% CI 1.04, 1.12) but similar cancer-specific survival (adjusted HR 1.0, 95% CI 0.95, 1.06). CONCLUSIONS/INTERPRETATION: Individuals with diabetes who develop CRC are not more likely to present with a later stage of CRC and have similar cancer-specific mortality compared with those without diabetes. Diabetes was associated with higher all-cause mortality in CRC patients, indicating that greater attention to non-cancer care is needed for CRC survivors with diabetes.

Association between diabetes, obesity, aging, and cancer: review of recent literature.

Rates of obesity and diabetes have risen significantly in recent years and are projected to increase even further in the coming decades. Obesity and diabetes are associated with increased risk of certain tumours, with the strongest relationships demonstrated for colorectal, post-menopausal breast, and endometrial cancer. Another important risk factor for cancer development is aging. Aging is characterized by chronic inflammation and immunosenescence, and accelerated by obesity, which may further stimulate the development of cancer. In this review, we summarize recent literature on the complex interactions between obesity, diabetes, aging, and cancer risk and mortality. We will also provide an overview of both epidemiological as well as pathophysiologic data and their clinical implications. In the context of an aging population and anticipated rise in rates of obesity and diabetes, a better understanding of how these factors interact and impact on cancer risk and prognosis will be important in helping to guide therapeutic interventions.

Review: Diabetes, Obesity, and Cancer-Pathophysiology and Clinical Implications.

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.

Breast, cervical and colorectal cancer screening in adults with diabetes: a systematic review and meta-analysis.

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.

Characteristics of Women With Gestational Diabetes From Non-Caucasian Compared With Caucasian Ethnic Groups.

OBJECTIVES: Short- and long-term outcomes in women after gestational diabetes mellitus (GDM) vary by ethnicity. Understanding differences in baseline diabetes risk factors is important for informing choice of risk-reducing interventions. We aimed to compare maternal and pregnancy-related characteristics in Caucasian and non-Caucasian women with GDM. METHODS: Using a large multicentre Canadian cohort of women diagnosed with GDM and recruited between 2009 and 2013, we compared demographic, clinical and behavioural characteristics in women with GDM across 7 ethnic groups. Data were obtained from chart reviews and surveys, and logistic and linear regression models were used to compare binary and continuous variables, respectively, between Caucasian and non-Caucasian ethnic groups. RESULTS: Of the 1,332 women with GDM, 911 were eligible for inclusion. Of these, 41.4% were white Caucasian, 17.1% were South Asian, 18.4% were East Asian, 5.8% were black, 8.8% were Filipina, 5.2% were Middle Eastern and 3.3% were Hispanic. Non-Caucasian women were diagnosed with GDM at a younger age and were more likely to have a family history of diabetes compared with Caucasian women. With the exception of East Asians, non-Caucasian women were more likely to be overweight using ethnicity-specific body mass index cutoffs and have higher oral glucose tolerance test values than Caucasian women. Prepregnancy smoking and alcohol consumption prevalence were highest in Caucasian women. CONCLUSIONS: Several important ethnicity-specific differences in clinical and behavioural characteristics of women with GDM were identified. These differences need to be considered when offering interventions for reducing risk of adverse perinatal outcomes and subsequent type 2 diabetes.