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Objective: This study aims to (1) build and validate model-based case definitions for multiple sclerosis (MS) that use trends (ie, trend-based case definitions) and (2) to apply dynamic classification to identify the average number of data years needed for classification (ie, average trend needed)., Design: Retrospective cohort study design., Participants: 608 MS cases and 59 620 MS non-cases., Setting: Data from 1 April 2004 to 31 March 2022 were obtained from the Manitoba Population Research Data Repository. MS case status was ascertained from homecare records and linked to health data. Trend-based case definitions were constructed using multivariate generalised linear mixed models applied to annual numbers of general and specialist physician visits, hospitalisations and MS healthcare contacts or medication dispensations. Dynamic classification, which ascertains cases and non-cases annually, was used to estimate mean classification time. Classification accuracy performance measures, including sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), proportion correctly classified (PCC) and F1-scores, were compared for trend-based case definitions and a deterministic case definition of 3+MS healthcare contacts or medication dispensations., Results: When applied to the full study period, classification accuracy performance measure estimates for all case definitions exceeded 0.90, except sensitivity and PPV for the trend-based dynamic case definition (0.88, 0.64, respectively). PCC was high for all case definitions (0.94-0.99); F1-scores were lower for the trend-based case definitions compared with the deterministic case definition (0.74-0.93 vs 0.96). Dynamic classification identified 5 years as the average trend needed. When applied to the average trend windows, accuracy estimates for trend-based case definitions were lower than the estimates from the full study period (sensitivity: 0.77-0.89; specificity: 0.90-0.97; PPV: 0.54-0.81; NPV: 0.97-0.99; F1-score: 0.64-0.84). Accuracy estimates for the deterministic case definition remained high, except sensitivity (0.42-0.80). F1-score was variable (0.59-0.89)., Conclusions: Trend-based and deterministic case definitions classifications were similar to a population-based clinician assessment reference standard for multiple measures of classification accuracy. However, accuracy estimates for both trend-based and deterministic case definitions varied as the years of data used for classification were reduced. Dynamic classification appears to be a viable option for identifying the average trend needed for trend-based case definitions., Competing Interests: Competing interests: RAM receives research funding from: CIHR, Research Manitoba, Multiple Sclerosis Society of Canada, Multiple Sclerosis Scientific Foundation, Crohn’s and Colitis Canada, National Multiple Sclerosis Society, CMSC and the US Department of Defense, and is a co-investigator on studies receiving funding from Biogen Idec and Roche Canada. LL receives research funding from CIHR, Canada Research Chairs Programme, Natural Sciences and Engineering Research Council of Canada, National Institutes of Health, and the Canadian Agency for Drugs and Technologies in Health., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Objectives: To highlight the potential of multiple file record linkage. Linkage increases the value of existing information by supplying missing data or correcting errors in existing data, through generating important covariates, and by using family information to control for unmeasured variables and expand research opportunities., Methods: Recent Manitoba papers highlight the use of linkage to produce better studies. Specific ways in which linkage helps deal with different substantive issues are described., Results: Wide data files-files containing considerable amounts of information on each individual-generated by linkage improve research by facilitating better design. Nonexperimental work in particular benefits from such linkages. Population registries are especially valuable in supplying family data to facilitate work across different substantive fields., Conclusion: Several examples show how record linkage magnifies the value of information from individual projects. The results of observational studies become more defensible through the better designs facilitated by such linkage., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Algorithms used to identify disease cases in administrative health data may be sensitive to changes in the data over time. Control charts can be used to assess how variations in administrative health data impact the stability of estimated trends in incidence and prevalence for administrative data algorithms. We compared the stability of incidence and prevalence trends for multiple juvenile diabetes algorithms using observed-expected control charts., Methods: Eighteen validated algorithms for juvenile diabetes were applied to administrative health data from Manitoba, Canada between 1975 and 2018. Trends in disease incidence and prevalence for each algorithm were modelled using negative binomial regression and generalized estimating equations; model-predicted case counts were plotted against observed counts. Control limits were set as predicted case count ±0.8*standard deviation. Differences in the frequency of out-of-control observations for each algorithm were assessed using McNemar's test with Holm-Bonferroni adjustment., Results: The proportion of out-of-control observations for incidence and prevalence ranged from 0.57 to 0.76 and 0.45 to 0.83, respectively. McNemar's test revealed no difference in the frequency of out-of-control observations across algorithms. A sensitivity analysis with relaxed control limits (2*standard deviation) detected fewer out-of-control years (incidence 0.19 to 0.33; prevalence 0.07 to 0.52), but differences in stability across some algorithms for prevalence., Conclusions: Our study using control charts to compare stability of trends in incidence and prevalence for juvenile diabetes algorithms found no differences for disease incidence. Differences were observed between select algorithms for disease prevalence when using wider control limits., (© 2022. The Author(s).)

Family health history is a well-established risk factor for many health conditions but the systematic collection of health histories, particularly for multiple generations and multiple family members, can be challenging. Routinely-collected electronic databases in a select number of sites worldwide offer a powerful tool to conduct multigenerational health research for entire populations. At these sites, administrative and healthcare records are used to construct familial relationships and objectively-measured health histories. We review and synthesize published literature to compare the attributes of routinely-collected, linked databases for three European sites (Denmark, Norway, Sweden) and three non-European sites (Canadian province of Manitoba, Taiwan, Australian state of Western Australia) with the capability to conduct population-based multigenerational health research. Our review found that European sites primarily identified family structures using population registries, whereas non-European sites used health insurance registries (Manitoba and Taiwan) or linked data from multiple sources (Western Australia). Information on familial status was reported to be available as early as 1947 (Sweden); Taiwan had the fewest years of data available (1995 onwards). All centres reported near complete coverage of familial relationships for their population catchment regions. Challenges in working with these data include differentiating biological and legal relationships, establishing accurate familial linkages over time, and accurately identifying health conditions. This review provides important insights about the benefits and challenges of using routinely-collected, population-based linked databases for conducting population-based multigenerational health research, and identifies opportunities for future research within and across the data-intensive environments at these six sites., Competing Interests: Statement on conflicts of interest: The authors have no conflicts of interest to declare that are relevant to the content of this article.

Introduction: Health insurance registries, which capture insurance coverage and demographic information for entire populations, are a critical component of population health surveillance and research when using administrative data. Lack of standardization of registry information across Canada's provinces and territories could affect the comparability of surveillance measures. We assessed the contents of health insurance registries across Canada to describe the populations covered and document registry similarities and differences., Methods: A survey about the data and population identifiers in health insurance registries was developed by the study team and representatives from the Public Health Agency of Canada. The survey was completed by key informants from most provinces and territories and then descriptively analyzed., Results: Responses were received from all provinces; partial responses were received from the Northwest Territories. Demographic information in health insurance registries, such as primary address, date of birth and sex, were captured in all jurisdictions. Data captured on familial relationships, ethnicity and socioeconomic status varied among jurisdictions, as did start and end dates of coverage and frequency of registry updates. Identifiers for specific populations, such as First Nations individuals, were captured in some, but not all jurisdictions., Conclusion: Health insurance registries are a rich source of information about the insured populations of the provinces and territories. However, data heterogeneity may affect who is included and excluded in population surveillance estimates produced using administrative health data. Development of a harmonized data framework could support timely and comparable population health research and surveillance results from multi-jurisdiction studies., Competing Interests: The authors have no conflicts of interest to declare.

Objectives: Few adults participate in enough physical activity for health benefits. The workplace provides a unique environment to deliver heath interventions and can be beneficial to the employee and the employer. The purpose of the study was to explore the use of a physical activity counseling (PAC) program and a fitness-based health risk assessment (fHRA) in the hospital workplace., Methods: A workplace-based intervention was developed utilizing a PAC program and an fHRA to improve physical activity levels of employees. Hospital employees were enrolled in a 4-month PAC program and given the option to also enroll in an fHRA program (PAC + fHRA). Physical activity was assessed by accelerometry and measured at baseline, 2 months, and 4 months. Changes in musculoskeletal fitness for those in the fHRA program were assessed at baseline and 2 months., Results: For both groups (PAC n = 22; PAC + fHRA n = 16), total and moderate to vigorous physical activity in bouts of 10 minutes or more increased significantly by 18.8 ( P = .004) and 10.2 ( P = .048) minutes per week at each data collection point, respectively. Only participants with gym memberships demonstrated increases in light physical activity over time. Those in the fHRA group significantly increased their overall musculoskeletal fitness levels from baseline levels (18.2 vs 21.7, P < .001). There was no difference in the change in physical activity levels between the groups., Conclusions: A PAC program in the workplace may increase physical activity levels within 4 months. The addition of an fHRA does not appear to further increase physical activity levels; however, it may improve overall employee musculoskeletal fitness levels., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2019.)

Introduction: Lifestyle factors, such as diet, physical activity and sleep, are associated with the development of many chronic diseases. The objective of The Manitoba Personalized Lifestyle Research study is to understand how these lifestyle factors interact with each other and with other factors, such as an individual's genetics and gut microbiome, to influence health., Methods: An observational study of adults, with extensive phenotyping by objective health and lifestyle assessments, and retrospective assessment of early life experiences, with retrospective and prospective utilisation of secondary data from administrative health records., Study Population: A planned non-random convenience sample of 840 Manitobans aged 30-46 recruited from the general population, stratified by sex (equal men and women), body mass index (BMI; 60% of participants with a BMI>25 kg/m 2 ) and geography (25% from rural areas). These stratifications were selected based on Manitoba demographics., Measurements: Lifestyle factors assessed will include dietary pattern, physical activity, cardiovascular fitness, and sleep. Factors such as medical history, socioeconomic status, alcohol and tobacco consumption, cognition, stress, anxiety, and early life experiences will also be documented. A maternal survey will be performed. Body composition and bone density will be measured by dual energy X-ray absorptiometry. Blood pressure, pulse wave velocity, and augmentation index will be measured on two consecutive days. Chronic disease risk biomarkers will be measured in blood and urine samples. DNA will be extracted for genetic analysis. A faecal sample will be collected for microbiome analysis. Participants may provide their Manitoba personal health information number to link their study data with administrative health records., Ethics and Dissemination: Ethics approval has been obtained from the University of Manitoba Health Research Ethics Board (protocol # HS18951; 05/01/2016). Data analysis, release of results and publication of manuscripts are scheduled to start in early 2019. Additional information at www.TMPLR.ca., Trial Registration Number: NCT03674957; Pre-results., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: The Public Health Agency of Canada's Canadian Chronic Disease Surveillance System (CCDSS) produces population-based estimates of chronic disease prevalence and incidence using administrative health data. Our aim was to assess trends in incidence rates over time, trends are essential to understand changes in population risk and to inform policy development., Methods: Incident cases of diagnosed asthma, chronic obstructive pulmonary disease (COPD), diabetes, hypertension, ischemic heart disease (IHD), and stroke were obtained from the CCDSS online infobase for 1999 to 2012. Trends in national and regional incidence estimates were tested using a negative binomial regression model with year as a linear predictor. Subsequently, models with year as a restricted cubic spline were used to test for departures from linearity using the likelihood ratio test. Age and sex were covariates in all models., Results: Based on the models with year as a linear predictor, national incidence rates were estimated to have decreased over time for all diseases, except diabetes; regional incidence rates for most diseases and regions were also estimated to have decreased. However, likelihood ratio tests revealed statistically significant departures from a linear year effect for many diseases and regions, particularly for hypertension., Conclusion: Chronic disease incidence estimates based on CCDSS data are decreasing over time, but not at a constant rate. Further investigations are needed to assess if this decrease is associated with changes in health status, data quality, or physician practices. As well, population characteristics that may influence changing incidence trends also require exploration., Competing Interests: JMP reports that his employer, ICES, received funding from the Public Health Agency of Canada to provide data to the Canadian Chronic Disease Surveillance System during the conduct of this study. KAMP was supported by funding from the Public Health Agency of Canada during the conduct of this study.

Background: Standardizing the Fried criteria (S-FC) using cutoffs specific to the patient population improves adverse outcome prediction. However, there is limited evidence to determine if a S-FC assessment can improve discrimination of cardiovascular disease (CVD) risk in middle-aged and older women., Design: The objective of this cross-sectional analysis was to compare the ability of the Fried frailty phenotype criteria (FC) to discriminate between individuals at higher risk for CVD according to the Framingham Risk Score and Rasmussen Disease Score in comparison to the S-FC., Setting: Asper Clinical Research Institute, St. Boniface Hospital Research Centre., Participants: 985 women 55 years of age or older with no previous history of CVD., Measurements: Discrimination of individuals with high CVD risk according to the Framingham and Rasmussen Disease scores was assessed using receiver operating characteristic (ROC) curves, integrated discrimination index (IDI) and net reclassification index (NRI)., Results: The S-FC showed superior ability to discriminate CVD risk as assessed by area under the ROC curve (AUROC) based on the Framingham (0.728 vs 0.634, p < 0.001), but not for the Rasmussen (0.594 vs 0.552, p = 0.079) risk score. Net reclassification index identified improved discrimination for both the Framingham (67.9%, p < 0.001) and Rasmussen Disease scores (26.0%, p = 0.003). Integrated discrimination index also identified improved CVD risk discrimination with the Framingham (3.0%, p < 0.001) and Rasmussen Disease scores (1.5%, p < 0.001)., Conclusion: In this study, the Fried frailty phenotype better discriminated cardiovascular disease risk when standardized to the study population., (Copyright © 2019. Published by Elsevier Inc.)

While previous investigations have demonstrated the benefit of cardiac rehabilitation (CR) on outcomes after cardiac surgery, the association between pre-operative frailty and post-operative CR completion is unclear. The purpose of this retrospective cohort study was to determine if pre-operative frailty scores impacted CR completion post-operatively and if CR completion influenced frailty scores in 114 cardiac surgery patients. Frailty was assessed with the use of the Clinical Frailty Scale (CFS), the Modified Fried Criteria (MFC), the Short Physical Performance Battery (SPPB), and the Functional Frailty Index (FFI). A Mann-Whitney test was used to compare frailty scores between CR completers and non-completers and changes in frailty scores from baseline to 1-year post-operation. CR non-completers were more frail than CR completers at pre-operative baseline based on the CFS ( p = 0.01), MFC ( p < 0.001), SPPB ( p = 0.007), and the FFI ( p < 0.001). A change in frailty scores from baseline to 1-year post-operation was not detected in either group using any of the four frailty assessments. However, greater improvements from baseline to 1-year post-operation in two MFC domains (cognitive impairment and low physical activity) and the physical domain of the FFI were found in CR completers as compared to CR non-completers. These data suggest that pre-operative frailty assessments have the potential to identify participants who are less likely to attend and complete CR. The data also suggest that frailty assessment tools need further refinement, as physical domains of frailty function appear to be more sensitive to change following CR than other domains of frailty.

Objective: Lifestyle factors such as physical activity are known to reduce the risk of frailty. However, less is known about the frailty-sedentary behavior relationship. A systematic review was conducted to synthesize the available evidence concerning associations between sedentary behaviors and frailty levels in adults., Method: MEDLINE, Embase, Web of Science, CINAHL, SPORTDiscus, Scopus, and the World Health Organization Clinical Trials Registry were searched up to August 2017 for observational studies in adults >18 years for cohort studies. Included studies identified frailty as a specified outcome using a multi-component tool. Sedentary behavior was measured by self-report or objectively. Studies with statistical models adjusting for at least one covariate were included. Meta-analysis could not be performed due to the heterogeneity in frailty and sedentary behavior measures., Results: Six longitudinal and ten cross-sectional studies were identified (n = 14, 693 unique participants); sample sizes ranged from 26 to 5871. Studies were generally at a low to moderate risk of bias. Most studies (n = 9) used the Fried criteria to measure frailty. Five studies measured sedentary behavior by questionnaire, with three studies specifically measuring television viewing time. Seven studies measured sedentary time by accelerometry. Thirteen of sixteen studies observed a detrimental association between high amounts of sedentary behaviors and an increased prevalence of frailty or higher frailty levels. Six of seven studies adjusting for physical activity behaviors demonstrated an independent association between sedentary behaviors and frailty. All six longitudinal studies found a negative association between sedentary behaviors and frailty., Conclusions: Sedentary behaviors were associated with a higher prevalence of frailty or higher frailty levels. Longitudinal studies are needed that adjust for physical activity when determining the association between sedentary behaviors and frailty. The efficacy of sedentary behavior reduction outside of physical activity interventions to treat and reverse frailty should also be tested., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Chronic diseases have a major impact on populations and healthcare systems worldwide. Administrative health data are an ideal resource for chronic disease surveillance because they are population-based and routinely collected. For multi-jurisdictional surveillance, a distributed model is advantageous because it does not require individual-level data to be shared across jurisdictional boundaries. Our objective is to describe the process, structure, benefits, and challenges of a distributed model for chronic disease surveillance across all Canadian provinces and territories (P/Ts) using linked administrative data. The Public Health Agency of Canada (PHAC) established the Canadian Chronic Disease Surveillance System (CCDSS) in 2009 to facilitate standardized, national estimates of chronic disease prevalence, incidence, and outcomes. The CCDSS primarily relies on linked health insurance registration files, physician billing claims, and hospital discharge abstracts. Standardized case definitions and common analytic protocols are applied to the data for each P/T; aggregate data are shared with PHAC and summarized for reports and open access data initiatives. Advantages of this distributed model include: it uses the rich data resources available in all P/Ts; it supports chronic disease surveillance capacity building in all P/Ts; and changes in surveillance methodology can be easily developed by PHAC and implemented by the P/Ts. However, there are challenges: heterogeneity in administrative databases across jurisdictions and changes in data quality over time threaten the production of standardized disease estimates; a limited set of databases are common to all P/Ts, which hinders potential CCDSS expansion; and there is a need to balance comprehensive reporting with P/T disclosure requirements to protect privacy. The CCDSS distributed model for chronic disease surveillance has been successfully implemented and sustained by PHAC and its P/T partners. Many lessons have been learned about national surveillance involving jurisdictions that are heterogeneous with respect to healthcare databases, expertise and analytical capacity, population characteristics, and priorities., Competing Interests: Statement on conflicts of interest: The authors declare that they have no conflicts of interest.

Background: Maternal metabolic health during the prenatal period is an established determinant of cardiometabolic disease risk. Many studies have focused on poor offspring outcomes after exposure to poor maternal health, while few have systematically appraised the evidence surrounding the role of maternal exercise in decreasing this risk. The aim of this study is to characterize and quantify the specific impact of prenatal exercise on children's cardiometabolic health markers, at birth and in childhood., Methods: A systematic review of Scopus, MEDLINE, EMBASE, CENTRAL, CINAHL, and SPORTDiscus up to December 2017 was conducted. Randomized controlled trials (RCTs) and prospective cohort studies of prenatal aerobic exercise and/or resistance training reporting eligible offspring outcomes were included. Four reviewers independently identified eligible citations and extracted study-level data. The primary outcome was birth weight; secondary outcomes, specified a priori, included large-for-gestational age status, fat and lean mass, dyslipidemia, dysglycemia, and blood pressure. We included 73 of the 9804 citations initially identified. Data from RCTs was pooled using random effects models. Statistical heterogeneity was quantified using the I 2 test. Analyses were done between June and December 2017 and the search was updated in December 2017., Results: Fifteen observational studies (n = 290,951 children) and 39 RCTs (n = 6875 children) were included. Observational studies were highly heterogeneous and had discrepant conclusions, but globally showed no clinically relevant effect of exercise on offspring outcomes. Meta-analyzed RCTs indicated that prenatal exercise did not significantly impact birth weight (mean difference [MD] - 22.1 g, 95% confidence interval [CI] - 51.5 to 7.3 g, n = 6766) or large-for-gestational age status (risk ratio 0.85, 95% CI 0.51 to 1.44, n = 937) compared to no exercise. Sub-group analyses showed that prenatal exercise reduced birth weight according to timing (starting after 20 weeks of gestation, MD - 84.3 g, 95% CI - 142.2, - 26.4 g, n = 1124), type of exercise (aerobic only, MD - 58.7 g, 95% CI - 109.7, - 7.8 g; n = 2058), pre-pregnancy activity status (previously inactive, MD - 34.8 g, 95% CI - 69.0, - 0.5 g; n = 2829), and exercise intensity (light to moderate intensity only, MD - 45.5 g, 95% CI - 82.4, - 8.6 g; n = 2651). Fat mass percentage at birth was not altered by prenatal exercise (0.19%, 95% CI - 0.27, 0.65%; n = 130); however, only two studies reported this outcome. Other outcomes were too scarcely reported to be meta-analyzed., Conclusions: Prenatal exercise does not causally impact birth weight, fat mass, or large-for-gestational-age status in a clinically relevant way. Longer follow up of offspring exposed to prenatal exercise is needed along with measures of relevant metabolic variables (e.g., fat and lean mass)., Protocol Registration: Protocol registration number: CRD42015029163 .

Introduction: Efforts to identify individuals at a higher risk for adverse cardiovascular outcomes focus on traditional risk factors, such as age, sex, smoking status, blood pressure and and cholesterol; however, this approach does not directly assess cardiovascular function and may underestimate the risk of experiencing adverse cardiovascular outcomes in women. This prospective, observational cohort study will examine the ability of the Heart Attack Prevention Program for You (HAPPY) Hearts screening protocol, a series of non-invasive procedures to identify middle-aged and older women who are at an elevated risk for experiencing an adverse cardiovascular event in the 5-year period after screening. The predictive value of the HAPPY Hearts protocol will also be compared with the Framingham Risk Score to determine the sensitivity for estimating risk for an adverse cardiovascular outcome., Methods and Analysis: One thousand women 55 years of age or older will be recruited to be screened by the HAPPY Hearts protocol. This involves the cardiovascular assessment of resting blood pressure, blood pressure response to 3 min of moderate intensity exercise and large and small arterial elasticity. The participants will be classified into risk categories based on these measures. The incidence of the following adverse cardiovascular outcomes will be assessed in the 5-year period after screening in both groups: ischaemic heart disease, acute myocardial infarction, stroke, percutaneous coronary intervention, coronary bypass surgery, congestive heart failure and new hypertension., Ethics and Dissemination: Information gathered in this research will be published in peer-reviewed journals and presented in a programme evaluation report to inform Manitoba Health and key stakeholders about the outcomes of the study. The University of Manitoba Health Research Ethics Board has approved the study protocol V.2.0, dated 29 September 2014 (H2014:224)., Trial Registration Number: NCT02863211., Competing Interests: Competing interests: The 4-Test Rasmussen cardiovascular screening program protocol is protected by intellectual property owned by the University of Minnesota and licensed to CVC-HEARTSAVERS LLC. St. Boniface General Hospital has a service agreement to utilize the methodology., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

The sarco(endo)plasmic reticulum calcium ATPase (SERCA) is responsible for transporting calcium (Ca(2+)) from the cytosol into the lumen of the sarcoplasmic reticulum (SR) following muscular contraction. The Ca(2+) sequestering activity of SERCA facilitates muscular relaxation in both cardiac and skeletal muscle. There are more than 10 distinct isoforms of SERCA expressed in different tissues. SERCA2a is the primary isoform expressed in cardiac tissue, whereas SERCA1a is the predominant isoform expressed in fast-twitch skeletal muscle. The Ca(2+) sequestering activity of SERCA is regulated at the level of protein content and is further modified by the endogenous proteins phospholamban (PLN) and sarcolipin (SLN). Additionally, several novel mechanisms, including post-translational modifications and microRNAs (miRNAs) are emerging as integral regulators of Ca(2+) transport activity. These regulatory mechanisms are clinically relevant, as dysregulated SERCA function has been implicated in the pathology of several disease states, including heart failure. Currently, several clinical trials are underway that utilize novel therapeutic approaches to restore SERCA2a activity in humans. The purpose of this review is to examine the regulatory mechanisms of the SERCA pump, with a particular emphasis on the influence of exercise in preventing the pathological conditions associated with impaired SERCA function.

The prevalence of type 2 diabetes mellitus (T2DM) in youth has increased dramatically over the past decades. The literature also suggests that the progression from an impaired glucose tolerance state to established T2DM is more rapid in youth, compared to adults. The presence of significant cardiovascular complications in youth with T2DM, including cardiac, macrovascular, and microvascular remodeling, is another major issue in this younger cohort and poses a significant threat to the healthcare system. However, this issue is only now emerging as a major public health concern, with few data to support optimal treatment targets and strategies to reduce cardiovascular disease (CVD) risk in youth with T2DM. Accordingly, the purpose of this minireview is to better understand the cardiovascular complications in youth with T2DM. We briefly describe the pathophysiology from youth studies, including oxidative stress, inflammation, renin-angiotensin aldosterone system, and epigenetics, which link T2DM and CVD. We also describe the literature concerning the early signs of CVD in youth and potential treatment options to reduce cardiovascular risk.