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Our aim in this study was to determine the test characteristics of algorithms using hospitalization and physician claims data to predict gestational diabetes (GDM).Using population-level health-care administrative data, we identified all pregnant women in Ontario in 2019. The presence of GDM was determined based on glucose screening laboratory results. Algorithms using hospitalization records and/or physician claims were tested against this "gold standard." The selected algorithm was applied to administrative data records from 1999 to 2019 to determine GDM prevalence in each year.Identifying GDM based on either a diabetes mellitus code on the delivery hospitalization record, OR at least 1 physician claim with a diabetes diagnosis code with a 90-day lookback before delivery yielded a sensitivity of 95.9%, a specificity of 99.2% and a positive predictive value of 87.6%. The prevalence of GDM increased from 4.2% of pregnancies in 1999 to 12.0% in 2019.Algorithms using hospitalization or physician claims administrative data can accurately identify GDM.

The ISCHEMIA trial showed similar cardiovascular outcomes of an initial conservative strategy as compared with invasive management in patients with stable ischemic heart disease without left main stenosis. We aim to assess the feasibility of predicting significant left main stenosis using extensive clinical, laboratory and non-invasive tests data.All adult patients who had stress testing prior to undergoing an elective coronary angiography for stable ischemic heart disease in Ontario, Canada, between April 2010 and March 2019, were included. Candidate predictors included comprehensive demographics, comorbidities, laboratory tests, and cardiac stress test data. The outcome was stenosis of 50% or greater in the left main coronary artery. A traditional model (logistic regression) and a machine learning algorithm (boosted trees) were used to build prediction models.Among 150,423 patients included (mean age: 64.2 ± 10.6 years; 64.1% males), there were 9,225 (6.1%) with left main stenosis. The final logistic regression model included 24 predictors and 3 interactions, had an optimism-adjusted c-statistic of 0.72 and adequate calibration (optimism-adjusted Integrated Calibration Index 0.0044). These results were consistent in subgroups of males and females, diabetes and non-diabetes, and extent of ischemia. The boosted tree algorithm had similar accuracy, also resulting in a c-statistic of 0.72 and adequate calibration (Integrated Calibration Index 0.0054).In this large population-based study of patients with stable ischemic heart disease using extensive clinical data, only modest prediction of left main coronary artery disease was possible with traditional and machine learning modelling techniques.

OBJECTIVE Cardiovascular risk reduction is an important focus in the management of people with diabetes. Although event rates have been declining over the long term, they have been observed to plateau or reverse in recent years. Furthermore, the impact of income-related disparities in cardiovascular events is unknown. The objective of this study is to evaluate age-, sex-, and income-related trends in cardiovascular hospitalization rates among people with diagnosed diabetes. RESEARCH DESIGN AND METHODS We calculated rates of hospitalization for acute myocardial infarction, stroke, heart failure, and lower-extremity amputation in annual cohorts of the entire population of Ontario, Canada, with diagnosed diabetes, from 1995 to 2019. Event rates were stratified by age, sex, and income level. RESULTS We studied nearly 1.7 million people with diabetes. The rate of acute myocardial infarction declined throughout the 25-year study period (P < 0.0001), such that the rate in 2019 was less than half the rate in 1995. Rates of stroke (P < 0.0001), heart failure (P < 0.0001), and amputation (P < 0.0001) also changed over time, but hospitalization rates stabilized through the 2010s. This apparent stabilization concealed a growing income-related disparity: wealthier patients showed continued declines in rates of these outcomes during the decade, whereas rates for lower-income patients increased (P for interaction < 0.0001 for all four outcomes). CONCLUSIONS During a quarter-century of follow-up, cardiovascular hospitalization rates among people with diabetes fell. However, the apparent stabilization in rates of stroke, heart failure, and amputation in recent years masks the fact that rates have risen for lower-income individuals.

OBJECTIVE Type 2 diabetes (T2D) increases dementia risk, but clear evidence to recommend interventions that can mitigate that risk remains lacking. This population-based retrospective cohort study aimed to determine whether new use of sodium–glucose cotransporter 2 (SGLT2) inhibitors compared with dipeptidyl peptidase 4 (DPP-4) inhibitors was associated with lower dementia risk. RESEARCH DESIGN AND METHODS Ontario residents aged ≥66 years who were new users of an SGLT2 inhibitor or a DPP-4 inhibitor from 1 July 2016 to 31 March 2021 entered the cohort. Incident dementia was identified using a validated algorithm for Alzheimer’s disease and related dementias. Propensity score–weighted Cox proportional hazards models were used to obtain adjusted hazard ratios (aHR) and CIs for time to incident dementia. To address reverse causality and disease latency, the observation window started at 1-year lag time from cohort entry. The primary analysis followed intention-to-treat exposure definition, and a secondary as-treated analysis was performed. RESULTS Among 106,903 individuals, SGLT2 inhibitors compared with DPP-4 inhibitors were associated with lower risk of dementia (14.2/1,000 person-years; aHR 0.80 [95% CI 0.71–0.89]) over a mean follow-up of 2.80 years from cohort entry. When stratified by different SGLT2 inhibitors, dapagliflozin exhibited the lowest risk (aHR 0.67 [95% CI 0.53–0.84]), followed by empagliflozin (aHR 0.78 [95% CI 0.69–0.89]), whereas canagliflozin showed no association (aHR 0.96 [95% CI 0.80–1.16]). The as-treated analysis observed a larger association (aHR 0.66 [95% CI 0.57–0.76]) than the intention-to-treat analysis. CONCLUSIONS SGLT2 inhibitors showed an association with lower dementia risk in older people with T2D. Randomized controlled trials are warranted.

Early identification of people with diabetes or prediabetes enables greater opportunities for glycemic control and management strategies to prevent related complications. To identify gaps in screening for these conditions, we examined population trends in receipt of timely glucose testing overall and in specific clinical subgroups.Using linked administrative databases, we conducted a retrospective cohort study of people aged 40 years and older without diabetes at baseline. Our primary outcome was up-to-date glucose testing, defined as having received testing at least once in the 3 years before each index year from 2010 to 2017, using linked administrative databases of people residing in Ontario, Canada. We calculated rates of up-to-date testing by age group, sex, ethnicity (South Asian, Chinese, general population) and comorbidities (hypertension, hyperlipidemia, cardiovascular disease).Over the 8-year study period, up-to-date glucose testing rates were stable at 67% for men and 77% for women (both relative risk 1.00 per year; 95% confidence interval 1.00-1.00). Testing rates were significantly lower in men than in women (all age groupsWe found lower glucose testing rates in younger men and people with hypertension. Our findings reinforce the need for initiatives to increase awareness of glycemic testing.

In Table 2 of the article cited above, the univariable MR analyses for microalbuminuria were erroneously cited as inverse variance weighted analyses. The row headings in Table 2 have been revised to show the correct analyses performed: MR-Egger, weighted median and mode, and simple mode analyses. In Fig. 3, the confidence intervals were erroneously plotted as error bars. Fig. 3 has been updated with the correct confidence intervals from the text. The revised online version of the article can be accessed at https://doi.org/10.2337/db22-0696.

Background Heterogeneous studies have demonstrated ethnic inequalities in the risk of SARS-CoV-2 infection and adverse COVID-19 outcomes. This study evaluates the association between ethnicity and COVID-19 outcomes in two large population-based cohorts from England and Canada and investigates potential explanatory factors for ethnic patterning of severe outcomes. Methods We identified adults aged 18 to 99 years in the QResearch primary care (England) and Ontario (Canada) healthcare administrative population-based datasets (start of follow-up: 24th and 25th Jan 2020 in England and Canada, respectively; end of follow-up: 31st Oct and 30th Sept 2020, respectively). We harmonised the definitions and the design of two cohorts to investigate associations between ethnicity and COVID-19-related death, hospitalisation, and intensive care (ICU) admission, adjusted for confounders, and combined the estimates obtained from survival analyses. We calculated the ‘percentage of excess risk mediated’ by these risk factors in the QResearch cohort. Results There were 9.83 million adults in the QResearch cohort (11,597 deaths; 21,917 hospitalisations; 2932 ICU admissions) and 10.27 million adults in the Ontario cohort (951 deaths; 5132 hospitalisations; 1191 ICU admissions). Compared to the general population, pooled random-effects estimates showed that South Asian ethnicity was associated with an increased risk of COVID-19 death (hazard ratio: 1.63, 95% CI: 1.09-2.44), hospitalisation (1.53; 1.32-1.76), and ICU admission (1.67; 1.23-2.28). Associations with ethnic groups were consistent across levels of deprivation. In QResearch, sociodemographic, lifestyle, and clinical factors accounted for 42.9% (South Asian) and 39.4% (Black) of the excess risk of COVID-19 death. Conclusion International population-level analyses demonstrate clear ethnic inequalities in COVID-19 risks. Policymakers should be cognisant of the increased risks in some ethnic populations and design equitable health policy as the pandemic continues.

Objective: Cardiovascular risk reduction is an important focus in the management of people with diabetes. Although event rates have been declining over the long-term, they have been observed to plateau or reverse in recent years. Furthermore, the impact of income-related disparities in cardiovascular events is unknown. The objective of this study was to evaluate age-, sex- and income-related trends in cardiovascular hospitalization rates among people with diagnosed diabetes. Research Design and Methods: We calculated rates of hospitalization for acute myocardial infarction, stroke, heart failure and lower extremity amputation in annual cohorts of the entire population of Ontario, Canada with diagnosed diabetes, from 1995 to 2019. Event rates were stratified by age, sex and income level. Results: We studied nearly 1.7 million people with diabetes. The rate of acute myocardial infarction declined throughout the 25-year study period (p Conclusions: During a quarter-century of follow-up, cardiovascular hospitalization rates among people with diabetes fell. However, the apparent stabilization in rates of stroke, heart failure and amputation in recent years masks the fact that rates have risen for lower-income individuals.

Obesity is postulated to independently increase chronic kidney disease (CKD), even after adjusting for type 2 diabetes (T2D) and hypertension. Dysglycemia below T2D thresholds, frequently seen with obesity, also increases CKD risk. Whether obesity increases CKD independent of dysglycemia and hypertension is unknown and likely influences the optimal weight loss (WL) needed to reduce CKD. T2D remission rates plateau with 20–25% WL after bariatric surgery (BS), but further WL increases normoglycemia and normotension. We undertook bidirectional inverse variance weighted Mendelian randomization (IVWMR) to investigate potential independent causal associations between increased BMI and estimated glomerular filtration rate (eGFR) in CKD (CKD(eGFR)) (50% decline in eGFR (primary outcome) or CKD hospitalization (secondary outcome), using

Objective Type 2 diabetes increases dementia risk, but clear evidence to recommend interventions that can mitigate that risk remains lacking. This population-based retrospective cohort study aimed to determine whether new use of sodium-glucose cotransporter-2 (SGLT2) inhibitors compared to dipeptidyl peptidase-4 (DPP4) inhibitors was associated with lower dementia risk. Research Design and Methods Ontario residents aged ≥66 years who were new users of an SGLT2 inhibitor or a DPP4 inhibitor from July 1st, 2016 to March 31st, 2021 entered the cohort. Incident dementia was identified using a validated algorithm for Alzheimer’s disease and related dementias. Propensity-score weighted Cox proportional hazards models were used to obtain adjusted hazard ratios (aHR) and confidence intervals (CI) for time to incident dementia. To address reverse causality and disease latency, the observation window started at 1-year lag-time from cohort entry. The primary analysis followed intention-to-treat exposure definition, and a secondary as-treated analysis was performed. Results Among 106,903 individuals, SGLT2 inhibitors compared with DPP4 inhibitors were associated with lower risk of dementia (14.2/1000 person-years; aHR [95% CI]=0.80 [0.71-0.89]) over a mean follow-up of 2.80 years from cohort entry. When stratified by different SGLT2 inhibitors, dapagliflozin exhibited the lowest risk (aHR [95% CI]=0.67 [0.53-0.84]), followed by empagliflozin (aHR [95% CI]=0.78 [0.69-0.89]), whereas canagliflozin showed no association (aHR [95% CI]=0.96 [0.80-1.16]). The as-treated analysis observed a larger association (aHR [95% CI]=0.66 [0.57-0.76]) than the intention-to-treat analysis. Conclusions SGLT2 inhibitors showed an association with lower dementia risk in older people with type 2 diabetes. Randomized controlled trials are warranted.

Jasbir Dhaliwal,1– 6 Meltem Tuna,1 Baiju R Shah,1,7,8 Sanjay Murthy,1,9,10 Emily Herrett,4 Anne M Griffiths,2,3 Eric I Benchimol1– 3,8 1ICES, Toronto, ON, Canada; 2SickKids Inflammatory Bowel Disease Centre, Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, ON, Canada; 3Department of Paediatrics, University of Toronto, Toronto, ON, Canada; 4London School of Hygiene and Tropical Medicine, London, UK; 5Cincinnati Children’s Hospital Medical Center, Division of Gastroenterology, Hepatology and Nutrition, Cincinnati, OH, USA; 6Department of Pediatrics, University of Cincinnati, Cincinnati, OH, USA; 7Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, ON, Canada; 8Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada; 9The Ottawa Hospital IBD Centre, The Ottawa Hospital and Ottawa Hospital Research Institute, Ottawa, ON, Canada; 10Department of Medicine and School of Epidemiology and Public Health, University of Ottawa, Ottawa, ON, CanadaCorrespondence: Jasbir DhaliwalPediatrics, University of Cincinnati, Cincinnati Children’s Hospital Medical Center, Division of Gastroenterology, Hepatology and Nutrition, Secondary Appointments in Division of Biomedical Informatics and James M Anderson Center for Health Systems Excellence, 3333 Burnet Avenue, Cincinnati, OH, 45229, USATel +15133789468Email Jasbir.dhaliwal@cchmc.orgBackground: Inflammatory bowel disease (IBD) is now a global disease with incidence increasing throughout Asia.Aim: To determine the incidence of IBD among South Asians and Chinese people residing in Ontario, Canada’s most populous province.Methods: All incident cases of IBD in children (1994– 2015) and adults (1999– 2015) were identified from population-based health administrative data. We classified South Asian and Chinese ethnicity using immigration records and surnames. We determined standardized incidence of IBD and adjusted incidence rate ratio (aIRR) in South Asians and Chinese compared to the general population.Results: Among 16,230,638 people living in Ontario, standardized incidence of IBD per 100,000 person-years was 24.7 (95% CI 24.4– 25.0), compared with 14.6 (95% CI 13.7– 15.5) in 982,472 South Asians and with 5.4 (95% CI 4.8– 5.9) in 764,397 Chinese. The risk of IBD in South Asians was comparable to the general population after adjusting for immigrant status and confounders (aIRR 1.03, 95% CI 0.96– 1.10). South Asians had a lower risk of Crohn’s disease (CD) (aIRR 0.66, 95% CI 0.60– 0.77), but a higher risk of ulcerative colitis (UC) (aIRR 1.47, 95% CI 1.34– 1.61). Chinese people had much lower rates of IBD (aIRR 0.24, 95% CI 0.20– 0.28), CD (aIRR 0.21, 95% CI 0.17– 0.26), and UC (aIRR 0.28, 95% CI 0.23– 0.25).Conclusion: Canadians of South Asian ethnicity had a similarly high risk of developing IBD compared to other Canadians, and a higher risk of developing UC, a finding distinct from the Chinese population. Our findings indicate the importance of genetic and environmental risk factors in people of Asian origin who live in the Western world.Keywords: inflammatory bowel disease, ulcerative colitis, Crohn’s disease, incidence, ethnicity, epidemiology, South Asian, Chinese

Objective: Evidence suggests the increased prevalence of diabetes among South Asian (SA) adolescents is due to their genetic risk profile. The South Asian Adolescent Diabetes Awareness Program (SAADAP) is a pilot intervention for SA youth in Canada with a family history of type 2 diabetes mellitus (T2DM). We sought to investigate changes in (1) diabetes knowledge and associated risk factors, (2) risk perception and (3) health behaviours among adolescents participating in SAADAP. Design: One-group pre-test, post-test design informed by a commitment to community-based participatory research (CBPR). Setting: Sixty-eight adolescents aged 13–17 years with a family history of T2DM participated in SAADAP in a clinical-community setting in Canada. Method: Pre–post questionnaires were administered to evaluate diabetes knowledge and associated risk factors, risk perceptions and health behaviours. Analyses were restricted to 49 participants who attended at least four diabetes education sessions. Results: The mean age of adolescents was 14.5 years, and 57.1% self-identified as girls. The difference in knowledge about the definition, symptoms and complications of T2DM from baseline to post-intervention was 3.32 out of 21 ( p Conclusion: SAADAP showed promising outcomes in raising knowledge and improving health behaviours in SA adolescents with a family history of diabetes. Larger controlled trials with longer follow-up are recommended to support and expand on the current findings.

BACKGROUND Pretransplant diabetes and new-onset diabetes after transplant (NODAT) are known risk factors for vascular events after kidney transplantation, but the incidence and magnitude of the risk of major adverse cardiovascular events (MACE) and cardiac deaths remain uncertain in recent era. METHODS A population cohort study of kidney transplant recipients identified using data from linked administrative healthcare databases from Ontario, Canada. The incidence rates of MACE (expressed as events with 95% confidence interval [95% CI] per 1000 person-years were reported according to diabetes status of pretransplant diabetes, NODAT, or no diabetes. Extended Cox regression model was used to examine the association between diabetes status, MACE, and cardiac death. RESULTS Of 5248 recipients, 1973 (38%) had pretransplant diabetes, and 799 (15%) developed NODAT with a median follow-up of 5.5 y. The incidence rates (95% CI) of MACE for recipients with pretransplant diabetes, NODAT, and no diabetes between 1 and 3 y posttransplant were 38.1 (32.1-45.3), 12.6 (6.3-25.2), and 11.8 (9.2-15.0) per 1000 person-years, respectively. Compared with recipients with pretransplant diabetes, recipients with NODAT experienced a lower risk of MACE (adjusted hazard ratio, 0.59; 95% CI, 0.47-0.74) but not cardiac death (adjusted hazard ratio, 0.97; 95% CI, 0.61-1.55). The rate of MACE and cardiac death was lowest in patients without diabetes. CONCLUSIONS Patients with pretransplant diabetes incur the greatest rate of MACE and cardiac deaths after transplantation. Having NODAT also bears high burden of vascular events compared with those without diabetes, but the magnitude of the increased rate remains lower than recipients with pretransplant diabetes.

Aim: Many economic evaluations used linear or log-transformed additive methods to estimate the disutility of hypoglycemic events in diabetes, both nonsevere (NSHEs) and severe (SHEs). Methods: We conducted a literature search for studies of disutility for hypoglycemia. We used additive, minimum and multiplicative methods, and the adjusted decrement estimator to estimate the disutilities of joint health states with both NSHEs and SHEs in six scenarios. Results: Twenty-four studies reported disutilities for hypoglycemia in diabetes. Based on construct validity, the adjusted decrement estimator method likely provides less biased estimates, predicting that when SHEs occur, the additional impact from NSHEs is marginal. Conclusion: Our proposed new method provides a different perspective on the estimation of quality-adjusted life-years in economic evaluations of hypoglycemic treatments.

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.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.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.A higher offspring birthweight signals an increased risk of maternal diabetes, offering another potentially useful way to identify women especially predisposed to diabetes.

Background Characteristics of patients using newer 2nd and 3rd line antidiabetic drugs in a real-world setting are poorly understood. We described the characteristics of new users of sodium-glucose co-transporter-2 inhibitors (SGLT-2i), dipeptidyl peptidase-4 inhibitors (DPP-4i), and glucagon-like peptide-1 receptor agonists (GLP-1 RA) in Canada and the United Kingdom (UK) between 2016 and 2018. Methods We conducted a multi-database cohort study using administrative health databases from 7 Canadian provinces and the UK Clinical Practice Research Datalink. We assembled a base cohort of antidiabetic drug users between 2006 and 2018, from which we constructed 3 cohorts of new users of SGLT-2i, DPP-4i, and GLP-1 RA between 2016 and 2018. Results Our cohorts included 194,070 new users of DPP-4i, 166,722 new users of SGLT-2i, and 27,719 new users of GLP-1 RA. New users of GLP-1 RA were more likely to be younger (mean ± SD: 56.7 ± 12.2 years) than new users of DPP-4i (67.8 ± 12.3 years) or SGLT-2i (64.4 ± 11.1 years). In Canada, new users of DPP-4i were more likely to have a history of coronary artery disease (22%) than new users of SGLT-2i (20%) or GLP-1 RA (15%). Conclusion Although SGLT-2i, DPP-4i, and GLP-1 RAs are recommended as 2nd or 3rd line therapy for type 2 diabetes, important differences exist in the characteristics of users of these drugs. Contrary to existing guidelines, new users of DPP-4i had a higher prevalence of cardiovascular disease at baseline than new users of SGLT2i or GLP-1RA.

AIMS The elevated lifetime risk of cardiovascular disease in women who develop gestational diabetes mellitus (GDM) has been attributed to adverse life-course trajectories of cardiovascular risk factors that arise before pregnancy and continue thereafter. We hypothesized that pregnancy may differentially affect these trajectories in women who develop GDM and those who do not. MATERIALS AND METHODS With population-based administrative databases, we identified all nulliparous women in Ontario, Canada, who had singleton pregnancies between January 2011 and December 2016 and ≥2 measurements of the following analytes both before and after pregnancy: glycated haemoglobin (HbA1c), glucose, lipids and transaminases. In total, 39 581 women (4373 with GDM) had 3.9 ± 3.4 tests before and 4.6 ± 5.4 tests after pregnancy. RESULTS Both before and after pregnancy, women who developed GDM had higher HbA1c, fasting glucose, low-density lipoprotein (LDL)-cholesterol and triglycerides than their peers, with lower high-density lipoprotein (HDL)-cholesterol (all p

OBJECTIVE To develop twin-specific outcome-based oral glucose tolerance test (OGTT) diagnostic thresholds for GDM based on the risk of future maternal type-2 diabetes. DESIGN A population-based retrospective cohort study (2007-2017). SETTING Ontario, Canada. METHODS Nulliparous women with a live singleton (n = 55 361) or twin (n = 1308) birth who underwent testing for gestational diabetes mellitus (GDM) using a 75-g OGTT in Ontario, Canada (2007-2017). We identified the 75-g OGTT thresholds in twin pregnancies that were associated with similar incidence rates of future type-2 diabetes to those associated with the standard OGTT thresholds in singleton pregnancies. RESULTS For any given 75-g OGTT value, the incidence rate of future maternal type-2 diabetes was lower for women with a twin than women with a singleton pregnancy. Using women with a negative OGTT as reference, the risk of future maternal type-2 diabetes in twin pregnancies with a positive OGTT based on the standard OGTT thresholds (9.86 per 1000 person years, adjusted hazard ratio (aHR) 4.79, 95% CI 2.69-8.51) was lower than for singleton pregnancies with a positive OGTT (18.74 per 1000 person years, aHR 8.22, 95% CI 7.38-9.16). The twin-specific OGTT fasting, 1-hour and 2-hour thresholds identified in the current study based on correlation with future maternal type-2 diabetes were 5.8 mmol/l (104 mg/dl), 11.8 mmol/l (213 mg/dl) and 10.4 mmol/l (187 mg/dl), respectively. CONCLUSIONS We identified potential twin-specific OGTT thresholds for GDM that are associated with a similar risk of future type-2 diabetes to that observed in women diagnosed with GDM in singleton pregnancies based on standard OGTT thresholds. TWEETABLE ABSTRACT Potential twin-specific OGTT thresholds for GDM were identified.

OBJECTIVE We aimed to quantify the risk of future maternal type 2 diabetes mellitus (T2DM) in women with gestational diabetes mellitus (GDM) based on the type and number of abnormal 75-g oral glucose tolerance test (OGTT) values and the diagnostic criteria used for the diagnosis of GDM. RESEARCH DESIGN AND METHODS We conducted a population-based retrospective cohort study of all nulliparous women with a live singleton birth who underwent testing for GDM using a 75-g OGTT in Ontario, Canada (2007–2017). We estimated the incidence rate (per 1,000 person-years), overall risk (expressed as adjusted hazard ratio [aHR]), and risk at 5 years after the index pregnancy of future maternal T2DM. Estimates were stratified by the type and number of abnormal OGTT values, as well as by the diagnostic criteria for GDM (Diabetes Canada [DC] vs. International Association of the Diabetes and Pregnancy Study Groups [IADPSG] criteria). RESULTS A total of 55,361 women met the study criteria. The median duration of follow-up was 4.4 (interquartile range 2.8–6.3; maximum 10.3) years. Using women without GDM as reference (incidence rate 2.18 per 1,000 person-years), women with GDM were at an increased risk of future T2DM; this risk was greater when using the DC compared with the IADPSG criteria (incidence rate 18.74 [95% CI 17.58–19.90] vs. 14.07 [95% CI 13.24–14.91] per 1,000 person-years, respectively). The risk of future maternal T2DM increased with the number of abnormal OGTT values and was highest for women with three abnormal values (incidence rate 49.93 per 1,000 person-years; aHR 24.57 [95% CI 21.26–28.39]). The risk of future T2DM was also affected by the type of OGTT abnormality: women with an abnormal fasting value had the greatest risk, whereas women with an abnormal 2-h value had the lowest risk (aHR 14.09 [95% CI 12.46–15.93] vs. 9.22 [95% CI 8.19–10.37], respectively). Similar findings to those described above were observed when the risk of T2DM at a fixed time point of 5 years after the index pregnancy was considered as the outcome of interest. CONCLUSIONS In women with GDM, individualized information regarding the future risk of T2DM can be provided based on the type and number of abnormal OGTT values, as well as the diagnostic criteria used for the diagnosis of GDM.

Randomized controlled trials (RCTs) have demonstrated that bariatric surgery improves glycemic control among people with diabetes. However, evidence from RCTs may not be generalizable to real-world clinical care with unselected patients in routine clinical practice.To examine long-term glycemic control and glucose-lowering drug regimens following bariatric surgery for people with type 2 diabetes (T2D) in unselected patients in routine clinical practice.Population-based cohort study using linked routinely collected real-world data from Ontario, Canada.Individuals with T2D who were assessed for bariatric surgery at any referral center in the province between February 2010 and November 2016 were identified and divided into those who received surgery within 2 years of the initial assessment and those who did not.There were 3674 people who had bariatric surgery and 1335 who did not. By 2 years, people who had undergone surgery had a significantly lower HbA1C (6.3 ± 1.2 % versus 7.8 ± 1.8 %, P.0001), and this difference persisted at 3, 4, 5, and 6 years. Even by 6 years, half of those who had undergone surgery remained on no glucose-lowering drugs, and they were nearly 6 times less likely to be on insulin than those who had not undergone surgery.In real-world clinical care, bariatric surgery was associated with large and sustained improvements in glycemic control.

Objectives Our aim in this study was to determine the distribution of glycated hemoglobin (A1C) in the Ontario diabetes population and identify subgroups with a high risk of poor glycemic control. Methods In this cross-sectional study, we used real-world clinical data linked with health-care administrative data to identify all people with prevalent diabetes on December 31, 2019. We then identified their most recent A1C result during the year. The distribution of A1C was assessed, and the proportion of those with an A1C of >8.0% was determined, stratified by various sociodemographic and clinical characteristics. Results In the population of 1,009,938 individuals with diabetes, mean ± standard deviation A1C was 7.2±1.4%, with 43.4% of them having an A1C of >7.0% and 19.0% with an A1C of >8.0%. Younger age, remote location of residence, longer diabetes duration and other surrogates for diabetes severity were associated with poor control. Conclusions The mean A1C among people with diabetes in Ontario was 7.2%, but nearly 20% had an A1C of >8%. There were notable disparities in glycemic control that identified several high-risk groups, including younger people, people with longer disease duration and people living in remote areas. Better clinical and policy approaches are needed to improve diabetes care for these populations.

To understand geographical and temporal patterns in the diabetes gap, the excess mortality risk associated with type 2 diabetes (T2D), in three high-income countries.Using databases from Canada (Ontario), Spain (Catalonia) and the UK (England), we harmonized the study design and the analytical strategy to extract information on subjects aged over 35 years with incident T2D between 1998 and 2018 matched to up to five subjects without diabetes. We used Poisson models to estimate age-specific mortality trends by diabetes status and rate ratios and rate differences associated with T2D.In more than 6 million people, 694 454 deaths occurred during a follow-up of 52 million person-years. Trends in all-cause mortality rates differed between Ontario and England; yet, the diabetes gaps were very similar in recent years: in 2018, we estimated 1.3 (95% confidence interval: 0.8, 1.8) and 0.8 (0.2, 1.5) more deaths per 1000 person-years in 50-year-old men with diabetes in Ontario and England, respectively, and 8.9 (6.1, 11.7) and 12.1 (9.1, 15.1) in 80-year-old men; between-country differences were small also in women. In Catalonia, rate ratios comparing T2D with no diabetes in men in 2018 were 1.53 (1.11, 2.11) at 50 years old, 0.88 (0.72, 1.06) at 60 years old, 0.74 (0.60, 0.90) at 70 years old and 0.81 (0.66, 1.00) at 80 years old, indicating lower mortality rates in men with T2D from the age of 60 years; rates were similar in women with and without diabetes at all ages. The diabetes gaps in cardiorenal mortality mirrored those of all-cause mortality: we observed consistent reductions in the proportions of cardiorenal deaths in subjects aged 80 years but variations in subjects aged ≤70 years, regardless of the presence of diabetes.By reducing the confounding impact of epidemiological and analytical differences, this study showed geographical similarities and differences in the diabetes gap: an excess risk of all-cause and cardiorenal mortality in subjects with T2D is still present in Ontario and England in recent years, particularly in elderly subjects. Conversely, there were very small gaps in young men with T2D or even lower mortality rates in older subjects with T2D in Catalonia.

Context The optimal 50 g-glucose challenge test (GCT) cutoff for the diagnosis of gestational diabetes mellitus (GDM) in twin pregnancies is unknown. Objective This work aimed to explore the screening accuracy of the 50 g-GCT and its correlation with the risk of large for gestational age (LGA) newborn in twin compared to singleton pregnancies. A population-based retrospective cohort study (2007-2017) was conducted in Ontario, Canada. Participants included patients with a singleton (n = 546 892 [98.4%]) or twin (n = 8832 [1.6%]) birth who underwent screening for GDM using the 50 g-GCT. Methods We compared the screening accuracy, risk of GDM, and risk of LGA between twin and singleton pregnancies using various 50 g-GCT cutoffs. Results For any given 50 g-GCT result, the probability of GDM was higher (P = .0.007), whereas the probability of LGA was considerably lower in the twin compared with the singleton group, even when a twin-specific growth chart was used to diagnose LGA in the twin group (P Conclusion The screening performance of the 50 g-GCT for GDM and its correlation with LGA differ between twin and singleton pregnancies.

Levels of hyperglycemia below those for diagnosis of diabetes are associated with microvascular injury, though the duration required to induce these complications remains poorly understood. This is especially relevant in patients with GDM due to its transient nature, which can nevertheless predispose to microvascular disease. Our aim was to assess whether mechanistic pathways associated with microvascular complications are upregulated in pregnant women with GDM or microvascular disease. In this analysis, urinary albumin excretion and biomarkers of inflammation, lipoprotein metabolism, and tubular injury were quantified in 355 women at 32-40 weeks of gestation, with and without GDM. Adjusted associations between all biomarkers and each outcome variable - GDM status, microalbuminuria, and retinopathy - were performed using logistic regression. Significant associations between GDM status and ApoA1, Il-6, IL-8, sTNFR I/II, NGAL, VEGF and vWF were observed (Figure 1A) . Increased CRP and sTNFR-II were associated with higher levels of albuminuria (Figure 1B) . CRP (Figure 1C) and previous GDM were associated with retinopathy. In conclusion, GDM and its relatively short-term exposure to hyperglycemia are associated with pathways involved in diabetes and microvascular complications. Disclosure H.Liu: None. B.R.Shah: None. V.S.Sridhar: None. L.Lovblom: None. D.Feig: Advisory Panel; Novo Nordisk, Research Support; Apotex. E.Herer: None. A.Kiss: None. L.Lipscombe: n/a. P.M.Yip: None. D.Cherney: Other Relationship; AbbVie Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Janssen Research & Development, LLC, Lilly, Maze, BMS, CSL-Behring, Merck, Otsuka, Novartis and Novo-Nordisk , Mitsubishi Tanabe Pharma Corporation, Sanofi, Research Support; Boehringer Ingelheim-Lilly, Merck, Janssen, Sanofi, AstraZeneca and Novo-Nordisk.

Objective: We assessed long-term incidence and prevalence trends of dementia and parkinsonism across major ethnic and immigrant groups in Ontario. Methods: Linking administrative databases, we established two cohorts (dementia 2001–2014 and parkinsonism 2001–2015) of all residents aged 20 to 100 years with incident diagnosis of dementia (N = 387,937) or parkinsonism (N = 59,617). We calculated age- and sex-standardized incidence and prevalence of dementia and parkinsonism by immigrant status and ethnic groups (Chinese, South Asian, and the General Population). We assessed incidence and prevalence trends using Poisson regression and Cochran–Armitage trend tests. Results: Across selected ethnic groups, dementia incidence and prevalence were higher in long-term residents than recent or longer-term immigrants from 2001 to 2014. During this period, age- and sex-standardized incidence of dementia in Chinese, South Asian, and the General Population increased, respectively, among longer-term immigrants (by 41%, 58%, and 42%) and long-term residents (28%, 7%, and 4%), and to a lesser degree among recent immigrants. The small number of cases precluded us from assessing parkinsonism incidence trends. For Chinese, South Asian, and the General Population, respectively, prevalence of dementia and parkinsonism modestly increased over time among recent immigrants but significantly increased among longer-term immigrants (dementia: 134%, 217%, and 117%; parkinsonism: 55%, 54%, and 43%) and long-term residents (dementia: 97%, 132%, and 71%; parkinsonism: 18%, 30%, and 29%). Adjustment for pre-existing conditions did not appear to explain incidence trends, except for stroke and coronary artery disease as potential drivers of dementia incidence. Conclusion: Recent immigrants across major ethnic groups in Ontario had considerably lower rates of dementia and parkinsonism than long-term residents, but this difference diminished with longer-term immigrants.

Background and Purpose: Many patients with ischemic stroke present with multiple comorbidities that threaten survival and recovery. This study sought to determine the risks of adverse long-term stroke outcomes associated with multimorbid diabetes mellitus and depression. Methods: Retrospective analysis of prospectively collected data on consecutive patients without premorbid dementia admitted from the community for a first-ever acute ischemic stroke to comprehensive stroke centers across Ontario, Canada (2003–2013). Premorbid histories of diabetes mellitus and depression were ascertained within 5 years before stroke admission. Adjusted hazard ratios (aHR [95% CI]) of admission to long-term care, incident dementia, readmission for stroke or transient ischemic attack and all-cause mortality, over time among those discharged back into the community poststroke. Results: Among 23 579 stroke admissions, n=20 201 were discharged back into the community. Diabetes mellitus and depression were associated with synergistic hazards of admission to long-term care (X 2 =5.4; P =0.02) over a median follow-up of 5.6 years. This interaction was observed among women specifically; depression multimorbidity showed particularly high hazards of admission to long-term care (aHR Depression =1.57 [1.24–1.98]) and incident dementia (aHR Depression =1.85 [1.40–2.44]) among women with diabetes mellitus. In the whole cohort, diabetes mellitus and depression were associated individually with long-term care admission (aHR Diabetes =1.20 [1.12–1.29]; aHR Depression =1.19 [1.04–1.37]), incident dementia (aHR Diabetes =1.14 [1.06–1.23]; aHR Depression =1.27 [1.08–1.49]), stroke/transient ischemic attack readmission (aHR Diabetes =1.18 [1.10–1.26]; aHR Depression =1.24 [1.07–1.42]), and all-cause mortality (aHR Diabetes =1.29 [1.23–1.36]; aHR Depression =1.16 [1.05–1.29]). Conclusions: The risks of dementia and needing long-term care in the years after surviving a stroke were particularly elevated among women when premorbid diabetes mellitus and depression occurred together. Long-term stroke recovery strategies might target high-risk patients with mood and metabolic multimorbidity.

To assess the association between SGLT-2 inhibitors initiation and genital tract infections (GTIs) among patients with type 2 diabetes.A population-based cohort study using administrative healthcare data from Alberta, Canada, and primary care data from the UK's Clinical Practice Research Datalink (CPRD). Among new metformin users, we identified new users of SGLT-2 inhibitors and five active comparator cohorts (new users of dipeptidyl peptidase-4 (DPP-4) inhibitors, sulfonylureas (SU), glucagon-like peptide-1 receptor agonists (GLP-1 RA), thiazolidinediones (TZD) and insulin). The outcome of interest was a composite GTI outcome. In each cohort, we used high-dimensional propensity score matching to adjust for confounding and conditional Cox proportional hazards regression to estimate the hazard ratios (HR). We used random-effects meta-analysis to combine aggregate data across databases.The risk of GTI was higher for SGLT-2 inhibitors users compared with DPP4inhibitor users (pooled HR 2.68, 95% CI 2.19 3.28), SU users (3.29, 2.62-4.13), GLP1-RA users (2.51, 1.90-3.31), TZD users (4.17, 2.46-7.08) and insulin users (1.86, 1.27-2.73).In five comparative cohorts, SGLT-2 inhibitors initiation is associated with a higher risk of GTIs. These findings from real-world data are consistent with placebo-controlled randomized controlled trials.

Background Women with gestational diabetes (GDM) have an elevated lifetime incidence of cardiovascular disease (CVD), but the basis of this excess risk remains to be established. In this context, we hypothesized that chronic exposure to adverse cardiovascular risk factors may contribute to their elevated risk of CVD. We thus sought to quantify the determinants of CVD risk in women with a history of GDM by performing mediation analyses. Methods Women in Ontario, Canada, with a live-birth pregnancy between Jan 1998 and Dec 2017 (n=757,541) were followed for a median of 13.2 years and stratified into the following 4 groups: women with GDM who developed CVD (GDM+/CVD+); women without GDM who developed CVD (GDM−/CVD+); those with GDM but no CVD (GDM+/CVD−); and those with neither GDM nor CVD (GDM−/CVD−). Lipids (total cholesterol, LDL, HDL, triglycerides) and glycemic variables (A1c, fasting glucose) were measured between 4.3±3.0 and 4.8±3.4 times over follow-up. Results On successive measurements at a median of 4.8, 7.1, and 8.7 years postpartum, respectively, each lipid and glycemic measure progressively worsened from GDM−/CVD− to GDM+/CVD− to GDM−/CVD+ to GDM+/CVD+ (all ppp Conclusions Adverse glycemic and lipid measures mediate the elevated risk of CVD in women with previous GDM, with the impact of lipids particularly evident in those who do not develop diabetes. These findings thus identify potential targets for risk factor monitoring and ultimately early intervention towards the goal of primary prevention of CVD in this at-risk patient population.

Nearly half of all adults with type 2 diabetes mellitus (T2DM) live in India and China. These populations have an underlying predisposition to deficient insulin secretion, which has a key role in the pathogenesis of T2DM. Indian and Chinese people might be more susceptible to hepatic or skeletal muscle insulin resistance, respectively, than other populations, resulting in specific forms of insulin deficiency. Cluster-based phenotypic analyses demonstrate a higher frequency of severe insulin-deficient diabetes mellitus and younger ages at diagnosis, lower β-cell function, lower insulin resistance and lower BMI among Indian and Chinese people compared with European people. Individuals diagnosed earliest in life have the most aggressive course of disease and the highest risk of complications. These characteristics might contribute to distinctive responses to glucose-lowering medications. Incretin-based agents are particularly effective for lowering glucose levels in these populations; they enhance incretin-augmented insulin secretion and suppress glucagon secretion. Sodium-glucose cotransporter 2 inhibitors might also lower blood levels of glucose especially effectively among Asian people, while α-glucosidase inhibitors are better tolerated in east Asian populations versus other populations. Further research is needed to better characterize and address the pathophysiology and phenotypes of T2DM in Indian and Chinese populations, and to further develop individualized treatment strategies.

The risk of diabetes is higher in South Asians compared to the general population. As a result of migration during the twentieth-century postindependence, the South Asian diaspora is incredibly vast. We examined the diabetes prevalence between groups of the South Asian diaspora based on their distinct migration patterns. Population-based health care and immigration administrative data were used to compare crude and standardized diabetes prevalence between immigrants from nine regions of the South Asian diaspora and the non-immigrant population. Diabetes prevalence across groups were also stratified by gender. There were 199,003 South Asian immigrants; 33,882 (crude prevalence of 17.0%) of whom had a diagnosis of diabetes. The nine subgroups varied significantly in the prevalence of diabetes after adjusting for age, sex and income: Sri Lanka 24.3%, Pakistan 22.2%, Fiji 21.5%, Bangladesh 20.7%, the Caribbean 20.4%, India 16.0%, East Africa 13.8%, South Africa 10.8%, and the Middle East 9.6% in comparison to the non-immigrant population 17.8%. Higher prevalence was evident among men compared with women in each subgroup with the exception of Pakistan. Diabetes prevalence is not uniform among South Asians. Our findings highlight potential impacts of their unique migration histories on the risk and burden of diabetes, and move beyond a one size fits all approach in the South Asian population of Ontario to develop targeted interventions.