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.

The association between offspring birthweight and future risk of maternal diabetes: A population-based study.

AIMS: As an indicator of maternal cardiometabolic health, newborn birthweight may be an important predictor of maternal type 2 diabetes mellitus (diabetes). We evaluated the relation between offspring birthweight and onset of maternal diabetes after pregnancy. METHODS: This retrospective cohort study used linked population-based health databases from Ontario, Canada. We included women aged 16-50 years without pre-pregnancy diabetes, and who had a live birth between 2006 and 2014. We used Cox proportional hazard regression to evaluate the association between age- and sex-standardized offspring birthweight percentile categories and incident maternal diabetes, while adjusting for maternal age, parity, year, ethnicity, gestational diabetes (GDM) and hypertensive disorders of pregnancy (HDP). Results were further stratified by the presence of GDM in the index pregnancy. RESULTS: Of 893,777 eligible participants, 14,329 (1.6%) women were diagnosed with diabetes over a median (IQR) of 4.4 (1.5-7.4) years of follow-up. There was a continuous positive relation between newborn birthweight above the 75th percentile and maternal diabetes. Relative to a birthweight between the 50th and 74.9th percentiles, women whose newborn had a birthweight between the 97th and 100th percentiles had an adjusted hazards ratio (aHR) of diabetes of 2.30 (95% CI 2.16-2.46), including an aHR of 2.01 (95% CI 1.83-2.21) among those with GDM, and 2.59 (2.36-2.84) in those without GDM. CONCLUSIONS: A higher offspring birthweight signals an increased risk of maternal diabetes, offering another potentially useful way to identify women especially predisposed to diabetes.

The association between immigration status and the development of type 2 diabetes in women with a prior diagnosis of gestational diabetes: A population-based study.

AIMS: The aim of this study was to examine the influence of immigration status and region of origin on the risk of type 2 diabetes in women with prior gestational diabetes (GDM). METHODS: This retrospective population-based cohort study included women with gestational diabetes (GDM) aged 16 to 50 years in Ontario, Canada, who gave birth between 2006 and 2014. We compared the incidence of type 2 diabetes after delivery between long-term residents and immigrants-overall, by time since immigration and by region of-using Cox regression adjusted for age, year, neighbourhood income, rurality, infant birth weight and presence of hypertensive disorders of pregnancy (HDP). RESULTS: Among 38,515 women with prior GDM (42% immigrants), immigrants had a significantly higher risk of type 2 diabetes compared with long-term residents (adjusted hazard ratio [HR] 1.19, 95% confidence interval [CI] 1.13-1.26), with no meaningful difference based on time since immigration. The highest adjusted relative risks of type 2 diabetes compared with long-term residents were found for immigrants from Sub-Saharan Africa (HR 1.63, 95% CI 1.40-1.90), Latin America/Caribbean (HR 1.44, 95% CI 1.28-1.62) and South Asia (HR 1.34, 95% CI 1.25-1.44). CONCLUSIONS: Immigration is associated with a significantly higher risk of type 2 diabetes after GDM, particularly for women from certain low- and middle-income countries. Diabetes prevention strategies will need to consider the unique needs of immigrants from these regions.

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.

In persons with obesity, exercise plus liraglutide improved weight-loss maintenance vs. exercise or placebo.

SOURCE CITATION: Lundgren JR, Janus C, Jensen SBK, et al. Healthy weight loss maintenance with exercise, liraglutide, or both combined. N Engl J Med. 2021;384:1719-30. 33951361.

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.

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.

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.

Potential diabetes overtreatment and risk of adverse events among older adults in Ontario: a population-based study.

AIMS/HYPOTHESIS: More than 25% of older adults (age ≥75 years) have diabetes and may be at risk of adverse events related to treatment. The aim of this study was to assess the prevalence of intensive glycaemic control in this group, potential overtreatment among older adults and the impact of overtreatment on the risk of serious events. METHODS: We conducted a retrospective, population-based cohort study of community-dwelling older adults in Ontario using administrative data. Participants were ≥75 years of age with diagnosed diabetes treated with at least one anti-hyperglycaemic agent between 2014 and 2015. Individuals were categorised as having intensive or conservative glycaemic control (HbA1c <53 mmol/mol [<7%] or 54-69 mmol/mol [7.1-8.5%], respectively), and as undergoing treatment with high-risk (i.e. insulin, sulfonylureas) or low-risk (other) agents. We measured the composite risk of emergency department visits, hospitalisations, or death within 30 days of reaching intensive glycaemic control with high-risk agents. RESULTS: Among 108,620 older adults with diagnosed diabetes in Ontario, the mean (± SD) age was 80.6 (±4.5) years, 49.7% were female, and mean (± SD) diabetes duration was 13.7 (±6.3) years. Overall, 61% of individuals were treated to intensive glycaemic control and 21.6% were treated to intensive control using high-risk agents. Using inverse probability treatment weighting with propensity scores, intensive control with high-risk agents was associated with nearly 50% increased risk of the composite outcome compared with conservative glycaemic control with low-risk agents (RR 1.49, 95% CI 1.08, 2.05). CONCLUSIONS/INTERPRETATION: Our findings underscore the need to re-evaluate glycaemic targets in older adults and to reconsider the use of anti-hyperglycaemic medications that may lead to hypoglycaemia, especially in setting of intensive glycaemic control.

Levothyroxine dose and risk of atrial fibrillation: A nested case-control study.

Contemporary data on the effect of levothyroxine dose on the occurrence of atrial fibrillation (AF) are lacking, particularly in the older population. Our objective was to determine the effect of cumulative levothyroxine exposure on risk of AF and ischemic stroke in older adults. METHODS: We conducted a population-based observational study using health care databases from Ontario, Canada. We identified adults aged ≥66 years without a history of AF who filled at least 1 levothyroxine prescription between April 1, 2007, and March 31, 2016. Cases were defined as cohort members who had incident AF (emergency room visit or hospitalization) between the date of first levothyroxine prescription and December 31, 2017. Index date was date of AF. Cases were matched with up to 5 controls without AF on the same index date. Secondary outcome was ischemic stroke. Cumulative levothyroxine exposure was estimated based on total milligrams of levothyroxine dispensed in the year prior to index date. Using nested case-control approach, we compared outcomes between older adults who received high (≥0.125 mg/d), medium (0.075-0.125 mg/d), or low (0-0.075 mg/d) cumulative levothyroxine dose. We compared outcomes between current, recent past, and remote past levothyroxine use. RESULTS: Of 183,360 older adults treated with levothyroxine (mean age 82 years; 72% women), 30,560 (16.1%) had an episode of AF. Compared to low levothyroxine exposure, high and medium exposure was associated with significantly increased risk of AF after adjustment for covariates (adjusted odds ratio [aOR] 1.29, 95% CI 1.23-1.35; aOR 1.08, 95% CI 1.04-1.11; respectively). No association was observed between levothyroxine exposure and ischemic stroke. Compared with current levothyroxine use, older adults with remote levothyroxine use had lower risks of AF (aOR 0.56, 95% CI 0.52-0.59) and ischemic stroke (aOR 0.61, 95% CI 0.56-0.67). CONCLUSIONS: Among older persons treated with levothyroxine, levothyroxine at doses >0.075 mg/d is associated with an increased risk of AF compared to lower exposure.

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.

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.

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.

Prepregnancy Diabetes and Perinatal Mental Illness: A Population-Based Latent Class Analysis.

We examined the risk of any perinatal mental illness associated with prepregnancy diabetes and identified how diabetes duration, complexity, and intensity of care affect this risk. We performed a population-based study of women aged 15-49 years with (n = 14,186) and without (n = 843,818) prepregnancy diabetes who had a singleton livebirth (Ontario, Canada, 2005-2015) and no recent mental illness. Modified Poisson regression estimated perinatal mental illness risk between conception and 1 year postpartum in women with versus without diabetes and in diabetes groups, defined by a latent class analysis of diabetes duration, complexity, and intensity-of-care variables, versus women without diabetes. Women with diabetes were more likely than those without to develop perinatal mental illness (18.1% vs. 16.0%; adjusted relative risk = 1.11, 95% confidence interval: 1.07, 1.15). Latent classes of women with diabetes were: uncomplicated and not receiving regular care (59.7%); complicated, with longstanding diabetes, and receiving regular care (16.4%); and recently diagnosed, with comorbidities, and receiving regular care (23.9%). Perinatal mental illness risk was elevated in all classes versus women without diabetes (adjusted relative risks: 1.09-1.12), but results for class 2 were nonsignificant after adjustment. Women with diabetes could benefit from preconception and perinatal strategies to reduce their mental illness risk.

The Association Between Insulin Initiation and Adverse Outcomes After Hospital Discharge in Older Adults: a Population-Based Cohort Study.

BACKGROUND: Starting insulin therapy in hospitalized patients may be associated with an increase in serious adverse events after discharge. OBJECTIVE: Determine whether post-discharge risks of death and rehospitalization are higher for older hospitalized patients prescribed new insulin therapy compared with oral hypoglycemic agents (OHAs). DESIGN: Retrospective population-based cohort study including hospital admissions in Ontario, Canada, between April 1, 2004, and Nov 30, 2013. PATIENTS: Persons aged 66 and over discharged after a hospitalization and dispensed a prescription for insulin and/or an OHA within 7 days of discharge. We included 104,525 individuals, subcategorized into four mutually exclusive exposure groups based on anti-hyperglycemic drug use in the 7 days post-discharge and the 365 days prior to the index admission. MAIN MEASURES: Prescriptions at discharge were categorized as new insulin (no insulin before admission), prevalent insulin (prescribed insulin before admission), new OHA(s) (no OHA or insulin before admission), and prevalent OHA (prescribed OHA only before admission) as the referent category. The primary and secondary outcomes were 30-day deaths and emergency department (ED) visits or readmissions respectively. KEY RESULTS: Of 104,525 patients, 9.2% were initiated on insulin, 4.1% died, and 26.2% had an ED visit or readmission within 30 days of discharge. Deaths occurred in 7.14% of new insulin users, 4.86% of prevalent insulin users, 3.25% of new OHA users, and 3.45% of prevalent OHA users. After adjustment for covariates, new insulin users had a significantly higher risk of death (adjusted hazard ratio (aHR) 1.59, 95% confidence interval (CI) 1.46 to 1.74) and ED visit/readmissions (aHR 1.17, 95% CI 1.12 to 1.22) than prevalent OHA users. CONCLUSIONS: Initiation of insulin therapy in older hospitalized patients is associated with a higher risk of death and ED visits/readmissions after discharge, highlighting a need for better transitional care of insulin-treated patients.

Association between allopurinol and cardiovascular outcomes and all-cause mortality in diabetes: A retrospective, population-based cohort study.

AIM: To assess the association between allopurinol and mortality and cardiovascular outcomes in an allopurinol-treated diabetes cohort. MATERIALS AND METHODS: We conducted a population-based retrospective cohort study in Ontario, Canada. Eligible subjects were ≥ 66 years old with diabetes and a first prescription for allopurinol between 1 April, 2002 and 31 March, 2012 and were followed until 31 March, 2016. The primary outcome was a composite: all-cause mortality, non-fatal cardiovascular event (myocardial infarction, revascularization procedure, or stroke) or congestive heart failure (CHF). Secondary outcomes were components of the primary outcome and pneumonia as a negative tracer. Allopurinol was modelled as time-varying exposed versus unexposed, daily dose category and cumulative dose using sex-specific multivariable Cox proportional hazards models. RESULTS: Over a median follow-up of 4.65 years (interquartile range 1.79-7.81), 16 266/23 103 males and 10 571/15 313 females experienced the primary outcome. Allopurinol was associated with a reduction in the primary outcome [adjusted hazard ratios (aHR) 0.77 (95% confidence interval 0.75-0.80) and 0.81 (0.78-0.84) for males and females, respectively], driven by marked reductions in all-cause mortality and modest reductions in cardiovascular events/CHF. There was no effect of cumulative allopurinol dose on any outcome, and allopurinol was also associated with reduced risk of pneumonia in males [aHR 0.88 (0.83, 0.93)]. CONCLUSIONS: Allopurinol was associated with reduced mortality and cardiovascular outcomes. However, lack of cumulative dose effect and a positive tracer outcome in males suggests residual bias. Future research assessing whether allopurinol prevents vascular complications in diabetes requires a clinical trial.

Identifying diabetes cases from administrative data: a population-based validation study.

BACKGROUND: 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. METHODS: 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. RESULTS: 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%). CONCLUSIONS: 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.

Trends in the Association Between Diabetes and Cardiovascular Events, 1994-2019.

This study uses administrative health care data from Ontario, Canada, to assess whether changes in diabetes management practices have affected trends in the association between diabetes vs prior cardiovascular disease and risk of cardiovascular events from 1994 to 2019 among adults aged 20 to 84 years.

The temporal relationship between diabetes and cancer: A population-based study.

BACKGROUND: Diabetes is associated with an increased risk of several cancers; however, greater detection of cancer around the time of diabetes diagnosis may partly contribute to this relationship. The goal of the current study was to explore the temporal relationship between diabetes and cancer incidence. METHODS: The authors conducted a retrospective, population-based cohort study of >1 million adults living in Ontario, Canada to evaluate the association between diabetes diagnosis and the incidence of cancer in 3 time periods: within the 10 years before a diabetes diagnosis, within the first 3 months after a diabetes diagnosis, and from 3 months to 10 years after a diabetes diagnosis. RESULTS: Individuals with diabetes were significantly more likely to have been diagnosed with cancer within the 10 years before a diabetes diagnosis compared with individuals without diabetes (odds ratio, 1.23; 95% confidence interval [95% CI], 1.19-1.27). Cancer incidence also was found to be significantly higher in individuals with diabetes within the 3-month period after a diabetes diagnosis (hazard ratio, 1.62; 95% CI, 1.52-1.74), whereas the risk was not found to be elevated in the later period (hazard ratio, 0.97; 95% CI, 0.95-0.98). Similar trends were noted for individual cancers. CONCLUSIONS: The results demonstrated that individuals with diabetes had a significantly higher risk of most cancers, which was limited to the time periods before and immediately after a diabetes diagnosis. The highest risk period was observed within the first 3 months after a diabetes diagnosis, suggesting a partial role of detection bias in the apparent relationship between diabetes and cancer. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2731-2738. © 2016 American Cancer Society.