DNA methylation signatures of youth-onset type 2 diabetes and exposure to maternal diabetes.

OBJECTIVE: Youth-onset type 2 diabetes (T2D) is physiologically distinct from adult-onset, but it is not clear how the two diseases differ at a molecular level. In utero exposure to maternal type 2 diabetes (T2D) is known to be a specific risk factor for youth-onset T2D. DNA methylation (DNAm) changes associated with T2D but which differ between youth- and adult-onset might delineate the impacts of T2D development at different ages and could also determine the contribution of exposure to in utero diabetes. METHODS: We performed an epigenome-wide analysis of DNAm on whole blood from 218 youth with T2D and 77 normoglycemic controls from the iCARE (improving renal Complications in Adolescents with type 2 diabetes through REsearch) cohort. Associations were tested using multiple linear regression models while adjusting for maternal diabetes, sex, age, BMI, smoking status, second-hand smoking exposure, cell-type proportions and genetic ancestry. RESULTS: We identified 3830 differentially methylated sites associated with youth T2D onset, of which 3794 were moderately (adjusted p-value < 0.05 and effect size estimate > 0.01) associated and 36 were strongly (adjusted p-value < 0.05 and effect size estimate > 0.05) associated. A total of 3725 of these sites were not previously reported in the EWAS Atlas as associated with T2D, adult obesity or youth obesity. Moreover, three CpGs associated with youth-onset T2D in the PFKFB3 gene were also associated with maternal T2D exposure (FDR < 0.05 and effect size > 0.01). This is the first study to link PFKFB3 and T2D in youth. CONCLUSION: Our findings support that T2D in youth has different impacts on DNAm than adult-onset, and suggests that changes in DNAm could provide an important link between in utero exposure to maternal diabetes and the onset of T2D.

Incidence and prevalence of type 2 diabetes in Manitoba children 2009-10 to 2017-18: First Nation versus all other Manitobans.

AIM: To describe the incidence and prevalence of type 2 diabetes in children in Manitoba over a ten-year period. METHODS: Population-based, provincial databases were linked to calculate the incidence and prevalence of type 2 diabetes in children < 18 years of age in Manitoba from 2009-10 to 2017-18. First Nation and all other Manitoban children are described separately. RESULTS: The incidence of type 2 diabetes increased from 16.0/100,000/year in 2009-10 to 31‧1/100,000/year in 2017-18 (p < 0.001). For First Nation children, the incidence increased from 73‧4 to 121‧2/100,000/year (p < 0.001). For all other Manitoban children, the incidence increased from 3‧3 to 10‧7/100,000/year (p < 0.001). The prevalence of type 2 diabetes rose from 66‧4 to 124‧2/100,000/year between 2009 -10 and 2017-18 (<0.001). The prevalence in First Nation children rose from 282‧8 to 517‧9/100,000/year (p < 0.001) and in all other Manitoban children from 18‧4 to 35.0/100,000/year (p < 0.001). CONCLUSIONS: The incidence and prevalence of type 2 diabetes is increasing in Manitoban children. While the greatest increase is seen in all other Manitoban children, type 2 diabetes disproportionally affects First Nation children. Understanding the prevalence and incidence of type 2 diabetes in children is necessary for resource allocation and to inform program planning, aimed at both prevention and management.

Factors Affecting Quality of Life in Adolescents Living With Type 2 Diabetes: A Substudy of the Improving Renal Complications in Adolescents With Type 2 Diabetes Through REsearch (iCARE) Cohort.

OBJECTIVES: Type 2 diabetes (T2D) disproportionately impacts adolescents living in challenging socioeconomic conditions. However, the impacts of T2D on quality of life (QOL) in this context are unknown. Our aim in this study was to evaluate QOL and identify its biological, psychological, and social determinants among adolescents living with and without T2D from similar sociodemographic backgrounds. Relationships between glycemic stability, early complications, and treatments of T2D and QOL were also examined. METHODS: Ninety-two adolescents with T2D and 59 at-risk controls were included from the Improving Renal Complications in Adolescents With Type 2 Diabetes Through Research (iCARE) cohort. The main outcome was QOL (Pediatric QOL Inventory [PedsQL]). Biological covariates included age, sex, body mass index z score, glycated hemoglobin, estimated glomerular filtration rate, and urine albumin:creatinine ratio. Psychological factors included perceived stress (14-item Perceived Stress Scale) and mental distress (6-item Kessler scale). Social factors included food security (Household Food Security Survey Module) and income quintile. Multivariate linear regression analyses were used to identify factors associated with QOL between adolescents with and without T2D, and within the T2D cohort. RESULTS: Mean total QOL scores among adolescents with T2D were lower than in controls (67.0±14.8 vs 71.7±16.2, p=0.04). Age, sex, and percent Indigenous ethnicity were not significantly different between groups. Mean duration of T2D was 2.3±2.0 years. In the multivariate analysis, QOL was not associated with diabetes status, but negative associations were seen between mental distress (ß=-1.46, p<0.001) and food insecurity QOL (ß=-6.26, p=0.037). No differences were seen between biological factors and QOL in either analysis. CONCLUSIONS: Significant factors associated with decreased QOL in adolescents living with T2D include mental distress and food insecurity, indicating areas for targeted intervention.

24-h ambulatory blood pressure readings and associations with albuminuria in youth with type 2 diabetes: A cross sectional analysis from the iCARE cohort.

AIMS: To evaluate associations between 24-h ambulatory blood pressure monitor (ABPM) data vs. single casual blood pressure (BP) and albuminuria in youth with type 2 diabetes. METHODS: A cross-sectional analysis of youth with type 2 diabetes 10-<18 yrs. from the iCARE cohort. MAIN EXPOSURES: daytime HTN (+/- nocturnal), isolated nocturnal HTN and single casual BP. MAIN OUTCOME: non-orthostatic urine albumin: creatinine ratio (ACR) ≥ 3 mg/mmol and log-transformed urine ACR. Regressions evaluated associations between 1. HTN status based on ABPM and log-transformed urine ACR (continuous) and 2. ABPM-derived BP z-scores and casual BPcentiles and albuminuria status (categorical). RESULTS: Of 281 youth included, 19.6 % had daytime HTN (+/- nocturnal), and 28.5 % isolated nocturnal HTN on 24-h ABPM. In multivariate linear regression, HTN (ABPM) (ß = 0.553; p = 0.001), duration of diabetes (ß = 0.857; p = 0.02), HbA1c (ß = 1.172; p ≤0.0001) and ACEI/ARB use (ß = 3.94; p < 0.0001) were positively associated with log-transformed ACR; (R2 = 0.184). In logistic regression analysis, all ABPM LMS z-scores were positively associated with albuminuria; casual BPcentile was not significant. CONCLUSIONS: Youth with type 2 diabetes have high rates of HTN based on 24-ABPM data. ABPM-derived measures of BP are associated with albuminuria. These data support the routine use of ABPM devices to diagnose hypertension in youth with type 2 diabetes.

Changes in Prevalence and Incidence at the Population Level of Type 2 Diabetes in First Nations and All Other Adults in Manitoba.

OBJECTIVES: The prevalence of type 2 diabetes (T2D) is increasing and Indigenous populations are at highest risk. Canadian data are crucial for health planning. METHODS: Population-based, de-identified, linked databases were used to calculate the incidence and prevalence of T2D for registered adult First Nations Manitobans and all other adult Manitobans from 2011-2012 to 2016-2017. RESULTS: The crude prevalence of T2D increased over the 6-year study period. The crude incidence of T2D for First Nations Manitobans dropped from 11.02 to 9.74 per 1,000 person-years at risk and the crude incidence for all other Manitobans did not change; in the last 2-year period, it was 6.53 per 1,000 person-years at risk. When incidence was stratified by age, the results differed between the younger and older age groups. For First Nations individuals, the adjusted incidence of T2D for those <30 years old increased over time, with no change in those ≥30 years old. For all other Manitobans, crude incidence increased over time in the young and middle age ranges (i.e. 18 to 29 years and 35 to 44 years, respectively). Both age- and sex-adjusted relative prevalence (adjusted rate ratio [aRR], 3.47; 95% confidence interval [CI], 2.56 to 4.70) and incidence (aRR, 1.97; 95% CI, 1.51 to 2.56) were higher for First Nations Manitobans. CONCLUSIONS: The prevalence of T2D continues to increase and disproportionately affects First Nations populations. Furthermore, the incidence is increasing in the younger age groups. Prevention and screening programs must include younger age groups and partner with First Nations communities.

High prevalence of periodontitis in children and adolescents with type 2 diabetes.

BACKGROUND: The aim of the present study was to determine the prevalence of periodontitis in children and adolescents with type 2 diabetes, and if poor glycemic control is associated with increasing prevalence of the disease. METHODS: This is a cross-sectional study involving children and adolescents with type 2 diabetes. A questionnaire related to oral health care history and oral health behaviors was administered to each participant and they then underwent a full-mouth oral evaluation. In addition, clinical and metabolic parameters were extracted from the clinical chart. RESULTS: One hundred and twenty one children and adolescents (8-17 years, 11 months) participated. Overall, 45.5% presented some degree of periodontitis, with 10 (8.3%) mild, 36 (29.8%) moderate, and nine (7.4%) severe. The periodontitis group (PD-group) had higher mean gingival and plaque indexes, periodontal probing depth, and clinical attachment loss than the group without periodontitis (NoPD-group) (p<0.05). A statistically significant relationship between the prevalence of periodontitis and glycosylated hemoglobin (HbA1c) was verified in the bivariate (odds ratio [OR] 1.31 [95% CI, 1.13-1.53], p = 0.001) and multivariate (OR, 1.29 [95% CI, 1.03-1.61], p = 0.03) analysis. For the adjustment variables, associations were verified for duration of diabetes, age, body mass index z-score, lack of running water, insulin use, and acanthosis nigricans. CONCLUSIONS: Children and adolescents with type 2 diabetes presented high rates of periodontitis comparable with that seen in previous studies in youth with diabetes. Uncontrolled HbA1c influences prevalence of periodontal disease. The lack of matched control group and radiographs are limitations of the study. Comprehensive periodontal examination is essential for children and adolescents with type 2 diabetes to prevent, identify, and treat periodontitis early.

Maternal and neonatal outcomes in pregnancies with type 2 diabetes in First Nation and other Manitoban people: a population-based study.

BACKGROUND: First Nation people living in Canada experience a high prevalence of type 2 diabetes in pregnancy. In this study, we aimed to describe maternal and neonatal outcomes in First Nation and all other females with type 2 diabetes living in Manitoba, Canada. METHODS: This was a population-level retrospective cohort study using linked administrative data from Manitoba (2012-2017). We compared First Nation females with type 2 diabetes with all other Manitoban females with type 2 diabetes, using relative risks (RRs) and 95% confidence intervals (CIs). RESULTS: A total of 2181 females with type 2 diabetes were included, and 1218 (55.8%) were First Nation. First Nation females with type 2 diabetes were significantly more likely to experience stillbirth (RR 2.14, 95% CI 1.11-4.13) and perinatal death (RR 2.39, 95% CI 1.37-4.17) than all other Manitoban females with type 2 diabetes. Offspring of First Nation females with type 2 diabetes had a higher risk of most neonatal complications than offspring of all other Manitoban females with type 2 diabetes, including a higher risk of congenital malformations (RR 1.97, 95% CI 1.30-2.99), but First Nation people did not have a higher risk of most maternal complications. INTERPRETATION: First Nation pregnant individuals living with type 2 diabetes experienced a higher risk for adverse pregnancy outcomes than all other Manitoban females with type 2 diabetes. Additional studies are needed to identify both high-risk and protective factors for pregnancy complications in First Nation people living with type 2 diabetes in pregnancy.

Integrative analysis reveals novel associations between DNA methylation and the serum metabolome of adolescents with type 2 diabetes: A cross-sectional study.

Objective: Rates of type 2 diabetes (T2D) among adolescents are on the rise. Epigenetic changes could be associated with the metabolic alterations in adolescents with T2D. Methods: We performed a cross sectional integrated analysis of DNA methylation data from peripheral blood mononuclear cells with serum metabolomic data from First Nation adolescents with T2D and controls participating in the Improving Renal Complications in Adolescents with type 2 diabetes through Research (iCARE) cohort study, to explore the molecular changes in adolescents with T2D. Results: Our analysis showed that 43 serum metabolites and 36 differentially methylated regions (DMR) were associated with T2D. Several DMRs were located near the transcriptional start site of genes with established roles in metabolic disease and associated with altered serum metabolites (e.g. glucose, leucine, and gamma-glutamylisoleucine). These included the free fatty acid receptor-1 (FFAR1), upstream transcription factor-2 (USF2), and tumor necrosis factor-related protein-9 (C1QTNF9), among others. Conclusions: We identified DMRs and metabolites that merit further investigation to determine their significance in controlling gene expression and metabolism which could define T2D risk in adolescents.

Mental health comorbidity is common in children with type 2 diabetes.

OBJECTIVE: To describe the prevalence of mental health comorbidity in children with type 2 diabetes compared to a matched population without diabetes and children with type 1 diabetes. RESEARCH DESIGN AND METHODS: Population-based cohorts of 528 youth (7-18 years of age) with prevalent type 2 diabetes, 1519 matched children without diabetes and 778 youth with type 1 diabetes were identified from a clinical registry and linked to provincial health care records to assess the prevalence of mental health comorbidity using ICD-9CM, ICD-10CA and ATC codes. RESULTS: The majority of children with type 2 diabetes were of First Nations heritage. Compared to their matched peers, children with type 2 diabetes where more likely to have a mood or anxiety disorder before and after diagnosis [RR 2.38 (1.63, 3.48) p < 0.001 and 1.70 (1.39, 2.08) p < 0.001 respectively], to attempt/complete suicide [RR 3.18 (1.30, 7.81) p = 0.012 and 2.18 (1.32, 3.60) p = 0.0002 respectively] and be prescribed an antipsychotic [RR 2.33 (1.23, 4.39) p = 0.009 and 1.76 (1.23, 2.52) p = 0.002 respectively]. Following adjustment for age and sex, children with type 2 diabetes, compared to children with type 1 diabetes where more likely to have a mood or anxiety disorder and be prescribed an antipsychotic after diagnosis [RR 1.43 (1.07, 1.91) p = 0.015; RR 2.41 (1.44, 4.06) p = 0.0009 respectively]. CONCLUSIONS: Children with type 2 diabetes have high rates of comorbid mental illness. Programs to provide care, support, and education must address the mental health comorbidity in the context of the demographic, socioeconomic, and psycho-cultural characteristics of the population.

Hospitalization and comorbidity in children with type 2 diabetes.

OBJECTIVE: To describe hospitalization rates and reasons for hospitalization in children with type 2 diabetes (T2D) and to compare these rates to a matched cohort without diabetes and to children with type 1 diabetes (T1D). METHODS: Population-based cohorts of 528 children (7-18 years of age) with prevalent T2D, 1519 matched control children without diabetes and 778 children with T1D were identified from a clinical registry and linked to health care records to assess hospitalizations and reasons for hospitalizations using ICD-9CM and ICD-10CA codes. RESULTS: Children with T2D are more likely than their matched controls and children with T1D to be admitted to hospital in the year prior to diagnosis {RR 2.83 (1.77, 4.53) p < 0.0001 and 8.05 (4.05, 16.00) p < 0.0001, respectively}, in the first year post diagnosis {RR 3.19 (2.08, 4.89) p < 0.0001 and 3.04 (1.86, 4.98) p < 0.0001, respectively} and in the 5 year post diagnosis period {RR 1.99 (1.56, 2.53) p < 0.0001 and 1.91 (1.48, 2.46) p < 0.0001, respectively}. Mental illness was the most common cause for hospital admission in both children with T2D and their matched controls. CONCLUSIONS: This differs from children with T1D where endocrine causes constitute the most common reason for hospital admission. This analysis provides novel data on hospitalization rates and diagnoses in the increasing population of children with T2D. This information is important to inform health care programming and health policy planning to best meet the needs of this population.

Impact of COVID-19 Pandemic on Adolescents and Young Adults Living With Type 2 Diabetes.

OBJECTIVES: The aim of this study was to assess the impacts of the COVID-19 pandemic on adolescents and young adults living with type 2 diabetes (T2D) involved in the national Improving Renal Complications in Adolescents with T2D through REsearch (iCARE) study. METHODS: The Environmental influences on Child Health Outcomes (ECHO) COVID-19 Questionnaire developed by the National Institutes of Health ECHO COVID-19 Task Force was administered to participants (n=85) from the iCARE study between June 2020 and October 2020. Children 12 years old (via parent report) and adolescents and young adults ≥13 years old (via self-report) participated. The questionnaire assessed the impact of the pandemic on health-care appointments, lifestyle, internet use, social connections and mental health. RESULTS: Participants were 17.0±3.1 (range, 12 to 27) years of age and predominantly female (61.3%). During the pandemic, 69.4% were able to attend their health-care appointments by telephone or virtual platforms, 31.7% ate more, 45.1% slept more and 29.3% spent less time on physical activities. There was an increase in internet use for both educational (42.0%) and noneducational purposes (54.9%). Participants felt less socially connected (64.6%). Participants also felt sometimes (59.2%), often (19.7%) and very often (6.7%) satisfied with their lives. DISCUSSION: Our study revealed that the COVID-19 pandemic has had various impacts on the daily lives of adolescents and young adults living with T2D. Future research should include longitudinal studies of the health burden of the COVID-19 pandemic on this population, with a more in-depth evaluation of mental health outcomes and clinical outcomes.

Pregestational Diabetes Exposure In Utero: Validation of a Definition for Use in Administrative Data.

OBJECTIVE: Our aim in this study was to determine the best administrative data case definition for pregestational diabetes exposure. METHODS: We compared the performance of case definitions for pregestational diabetes exposure within the administrative health data housed in the Manitoba Population Health Research Repository at the Manitoba Centre for Health Policy with an identified population of women in whom the diagnosis of pregestational diabetes was known from the clinical database of the Manitoba Diabetes Education Resource for Children and Adolescents (DER-CA) (August 12, 1989 through January 28, 2015). The DER-CA database contains maternal diabetes status during pregnancy and also includes women diagnosed with type 2 diabetes in childhood whose pregnancies were thus all complicated by pregestational diabetes exposure. Linkage of mother-child dyads is possible within the Repository. Diagnosis codes from the International Classification of Diseases---ninth or tenth revision and physician tariff codes were used to identify diabetes in the biologic mothers of children with type 2 diabetes identified from the DER-CA database. The timing of the diagnosis of diabetes in the mother with respect to the gestational age of the pregnancy was determined. RESULTS: The best administrative definition of pregestational diabetes exposure was any incident code for diabetes in the mother before the pregnancy of the index child or within the first 25 weeks of pregnancy (sensitivity: 84.77%; positive predictive value: 92%). CONCLUSION: The definition cited can be used to define pregestational diabetes exposure in studies utilizing administrative data.

Service use, clinical outcomes and user experience associated with urgent care services that use telephone-based digital triage: a systematic review.

OBJECTIVE: To evaluate service use, clinical outcomes and user experience related to telephone-based digital triage in urgent care. DESIGN: Systematic review and narrative synthesis. DATA SOURCES: Medline, Embase, CINAHL, Web of Science and Scopus were searched for literature published between 1 March 2000 and 1 April 2020. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Studies of any design investigating patterns of triage advice, wider service use, clinical outcomes and user experience relating to telephone based digital triage in urgent care. DATA EXTRACTION AND SYNTHESIS: Two reviewers extracted data and conducted quality assessments using the mixed methods appraisal tool. Narrative synthesis was used to analyse findings. RESULTS: Thirty-one studies were included, with the majority being UK based; most investigated nurse-led digital triage (n=26). Eight evaluated the impact on wider healthcare service use following digital triage implementation, typically reporting reduction or no change in service use. Six investigated patient level service use, showing mixed findings relating to patients' adherence with triage advice. Evaluation of clinical outcomes was limited. Four studies reported on hospitalisation rates of digitally triaged patients and highlighted potential triage errors where patients appeared to have not been given sufficiently high urgency advice. Overall, service users reported high levels of satisfaction, in studies of both clinician and non-clinician led digital triage, but with some dissatisfaction over the relevance and number of triage questions. CONCLUSIONS: Further research is needed into patient level service use, including patients' adherence with triage advice and how this influences subsequent use of services. Further evaluation of clinical outcomes using larger datasets and comparison of different digital triage systems is needed to explore consistency and safety. The safety and effectiveness of non-clinician led digital triage also needs evaluation. Such evidence should contribute to improvement of digital triage tools and service delivery. PROSPERO REGISTRATION NUMBER: CRD42020178500.

Diabetic ketoacidosis at presentation of type 1 diabetes in children in Canada during the COVID-19 pandemic.

Type 1 diabetes is a common chronic illness in childhood. Diabetic ketoacidosis (DKA) is the leading cause of morbidity and mortality in children with type 1 diabetes. Early recognition of symptoms of diabetes and immediate initiation of treatment are important factors in preventing DKA at first presentation. We describe the numbers of children presenting with DKA at initial diagnosis across eight Canadian paediatric centres during the COVID-19 pandemic (March 15, 2020 to July 31, 2020) and compare this to the same time period in 2019. Comparing the pre-COVID to the COVID-19 time period, presentation in DKA increased from 36.4% to 55.0% (P<0.0001) and presentation in severe DKA from 37.0% to 48.3% (P=0.044). These findings are concerning and emphasize the importance of awareness of the signs and symptoms of diabetes. In addition, these findings raise concern about access to appropriate and timely care during the COVID-19 pandemic.

Impact of remote prenatal education on program participation and breastfeeding of women in rural and remote Indigenous communities.

BACKGROUND: First Nations (FN) women have a higher risk of diabetes than non-FN women in Canada. Prenatal education and breastfeeding may reduce the risk of diabetes in mothers and offspring. The rates of breastfeeding initiation and participation in the prenatal program are low in FN communities. METHODS: A prenatal educational website, social media-assisted prenatal chat groups and community support teams were developed in three rural or remote FN communities in Manitoba. The rates of participation of pregnant women in prenatal programs and breastfeeding initiation were compared before and after the start of the remote prenatal education program within 2014-2017. FINDINGS: The participation rate of FN pregnant women in rural or remote communities in the prenatal program and breastfeeding initiation during 1-year after the start of the community-based remote prenatal education program were significantly increased compared to that during 1-year before the start of the program (54% versus 36% for the participation rate, 50% versus 34% for breastfeeding initiation, p < 0·001). Availability of high-speed Wi-Fi and/or postpartum supporting team were associated with favorite study outcomes. Positive feedback on the remote prenatal education was received from participants. INTERPRETATION: The findings suggest that remote prenatal education is feasible and effective for improving the breastfeeding rate and engaging pregnant women to participate in the prenatal program in rural or remote FN communities. The remote prenatal education remained active during COVID-19 in the participating communities, which suggests an advantage to expand remote prenatal education in other Indigenous communities. FUNDING: Canadian Institutes of Health Research, the Lawson Foundation and University of Manitoba.

Cardiovascular Comorbidity Associated With Albuminuria in Youth-Onset Type 2 Diabetes: Analyses From the iCARE Study.

OBJECTIVES: Little is known about the relationship between albuminuria in youth with type 2 diabetes (T2D) and cardiovascular risk. We aimed to determine whether youth with T2D and albuminuria have evidence of increased cardiovascular risk and/or early cardiovascular dysfunction compared with youth with T2D without albuminuria. METHODS: Youth with T2D were stratified by albuminuria status. Cardiovascular risk factors, including body mass index (BMI), 24-hour blood pressure, lipid profile, smoking and smoking exposure, habitual physical activity and screen time, were compared between groups. Left ventricular structure and function and carotid intima-media thickness (cIMT) were evaluated in participants who underwent cardiac imaging. RESULTS: Two hundred sixty-five youth participated, 83 (31.3%) of whom had albuminuria. Ethnicity, sex, BMI z score, age at diagnosis, duration of diabetes and hepatocyte nuclear factor-1alpha status did not differ between youth stratified by albuminuria. Smoking, exposure to second-hand smoke and low physical activity levels did not differ between groups. Youth with albuminuria were more likely to have hypertension, dyslipidemia and poor glycemic control. Left ventricular structure and carotid cIMT did not differ between groups, but youth with albuminuria had evidence of early left ventricular diastolic dysfunction. CONCLUSIONS: We found evidence of increased cardiovascular disease risk factors and left ventricular diastolic dysfunction in youth with T2D and albuminuria compared with those without albuminuria, despite a relatively short duration of disease. Thus, albuminuria may serve as a marker of early cardiovascular disease risk in youth with T2D.

Physical activity and cardiometabolic health in adolescents with type 2 diabetes: a cross-sectional study.

INTRODUCTION: Youth living with type 2 diabetes display increased risk of cardiovascular disease (CVD). It is unclear if regular physical activity (PA) modifies this risk. RESEARCH DESIGN AND METHODS: We compared CVD risk factors in a cross-sectional study of 164 youth with type 2 diabetes stratified according to weekly vigorous-intensity PA. Outcomes were hemoglobin A1c (HbA1c), ambulatory blood pressure (BP; ambulatory 24-hour readings), plasma lipoproteins, and albuminuria. The main exposure, vigorous-intensity PA, was quantified with the Adolescent Physical Activity Recall Questionnaire. RESULTS: Youth were 15±3 years, and 78% lived rurally and 68% were female, with a mean body mass index (BMI) Z-score of 2.4±1.1 and a mean HbA1c of 9.6% ±2.6%. Youth who participated in regular vigorous-intensity PA (40%; n=67) achieved nearly twice the dose of PA than peers who did not (62 vs 34 metabolic equivalent score-hour/week, p=0.001). After adjusting for duration of diabetes, BMI Z-score, sex, and smoking, youth who engaged in vigorous-intensity PA displayed lower HbA1c (9.1% vs 9.9%, p=0.052), diastolic BP (70 mm Hg vs 73 mm Hg, p=0.002), diastolic load (20% vs 26%, p=0.023), and mean arterial pressure (87.3 mm Hg vs 90.3 mm Hg, p<0.01), compared with youth who did not. Compared with youth who did not participate in regular vigorous-intensity PA, those who did also displayed lower odds of albuminuria after adjusting for duration of diabetes, sex, smoking, rural residence, and BMI Z-score (adjusted OR: 0.40, 95% CI 0.19 to 0.84). CONCLUSIONS: Among youth with type 2 diabetes, participation in vigorous-intensity PA is associated with lower CVD risk.