Correction: Using financial incentives to promote physical activity in American Indian adolescents: A randomized controlled trial.

[This corrects the article DOI: 10.1371/journal.pone.0198390.].

Changes in Visceral and Subcutaneous Fat in Youth With Type 2 Diabetes in the TODAY Study.

OBJECTIVE: In the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study, metformin plus rosiglitazone (M + R) maintained glycemic control better than metformin alone (M) or metformin plus lifestyle (M + L) in youth with type 2 diabetes (T2D). We hypothesized that changes in visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) would explain the differential treatment effects on glycemia. RESEARCH DESIGN AND METHODS: In 626 youth ages 11-17 years with T2D duration <2 years, VAT and SAT were estimated by DXA at baseline and at 6 and 24 months. Changes from baseline were analyzed in linear mixed models. RESULTS: Baseline mean age was 13.9 years, 66.4% were female, 72.2% were Hispanic/non-Hispanic black, and 20.3% were non-Hispanic white (NHW). Mean BMI was 33.7 kg/m2. VAT increased more in M + R (13.1%) than M + L (3.9%, P = 0.0006) or M (6.5%, P = 0.0146). SAT also increased more in M + R (13.3%) than in M + L (5.4%, P < 0.0001) or M (6.4%, P = 0.0005), indicating no significant fat redistribution in M + R. In NHWs, VAT increased more in M + R than M (P = 0.0192) and M + L (P = 0.0482) but did not explain the race-ethnicity differences in treatment effects on glycemic control among treatment groups. VAT and SAT increases correlated with higher HbA1c, lower insulin sensitivity, and lower oral disposition index (all P < 0.05), but associations did not differ by treatment group. CONCLUSIONS: In contrast to the existing reports in adults with T2D, in TODAY, M + R resulted in the most VAT accumulation compared with M + L or M. Differential effects on depot-specific indirect measures of adiposity are unrelated to treatment effects in sustaining glycemic control. Additional studies are needed to understand the clinical markers of metabolic risk profile in youth with T2D on rosiglitazone.

Effect of Obesity and Exercise Training on Plasma Amino Acids and Amino Metabolites in American Indian Adolescents.

CONTEXT: Amino acids (AAs) and their metabolites are altered with obesity and may be predictive of future diabetes in adults, but there are fewer studies on AAs, as well as conflicting findings on how they vary with obesity, in adolescents. OBJECTIVE: To determine whether plasma AAs vary with body composition and insulin sensitivity and are altered in response to exercise training. DESIGN: Cross-sectional, and an exercise intervention. SETTING: Tribal wellness center. PARTICIPANTS: American Indian boys and girls, 11 to 17 years of age with obesity (Ob, n = 58) or normal weight (NW, n = 36). INTERVENTION: The Ob group completed 16 weeks of aerobic exercise training. MAIN OUTCOME MEASURE: A panel of 42 plasma AAs. RESULTS: Compared with the NW group, the Ob group had lower aerobic fitness and insulin sensitivity (interactive homeostasis model assessment 2), 17 AAs that were higher, and 7 AAs that were lower. Branched-chain AAs (+10% to 16%), aromatic AAs (+15% to 32%), and glutamate were among the higher AAs; all were positively correlated with body fat and negatively correlated with insulin sensitivity. The lysine metabolite 2-aminoadipic acid (2-AAA) and the valine metabolite ß-aminoisobutyric acid (BAIBA) were 47% higher and 29% lower, respectively, in the Ob group, and were positively (2-AAA) and negatively (BAIBA) correlated with insulin sensitivity. Exercise training increased aerobic fitness by 10%, but body composition, insulin sensitivity, and AAs were not significantly changed. CONCLUSIONS: Several plasma AAs are altered in American Indian adolescents with obesity and are associated with insulin sensitivity, but they were not altered with this exercise intervention.

Genomic Research and American Indian Tribal Communities in Oklahoma: Learning From Past Research Misconduct and Building Future Trusting Partnerships.

Research misconduct and consequential harms have been inflicted upon American Indian/Alaska Native communities for decades. To protect their people and culture and to retain oversight over research, many Native communities have established tribal health research and institutional review boards. The Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) Study showcases a successful, trusting research collaboration with tribal nations and academic investigators in Oklahoma. In 2006, the TODAY Study investigators proposed a modification of the study protocol to collect biological specimens from participants for genomic analyses and indefinite storage. Partnering American Indian tribal nations elected not to participate in the genomics collection and repository proposal. Reasons included 1) protection of cultural values, 2) concerns regarding community anonymity, 3) a potential threat to tribal services eligibility, 4) broad informed consent language, and 5) vague definitions of data access and usage. The nations believed the proposed genomics analyses presented a risk of harm to their people and nations without clear benefit. Since the 2006 proposal and the advancement of genomics research, many tribal communities in Oklahoma, appreciating the potential benefits of genomic research, are developing policies regarding oversight of/access to data and biological specimens to mitigate risks and provide members and communities with opportunities to participate in safe and meaningful genomic research.

Collaborative implementation of a community-based exercise intervention with a partnering rural American Indian community.

BACKGROUND: The prevalence and socioeconomic burden of childhood obesity and diabetes has increased rapidly in the United States in the last 30 years. American Indians have the highest prevalence of type 2 diabetes among newly diagnosed youth in the country. Contributing factors include environmental, behavioral, and genetic components. Some American Indian tribal communities have explored innovative ways to combat this epidemic including collaborations with academic centers on community-based research. METHOD: From 2012 to 2017, the University of Oklahoma Health Science Center and the Choctaw Nation of Oklahoma partnered on a National Institutes of Health-funded project to determine if financial incentives would elicit an increase in physical activity in Native youth. This was a community-based behavioral intervention for overweight or obese American Indian youth ages 11-20 living in a rural community at risk for developing diabetes. RESULTS: Tribal leaders and staff identified culturally appropriate strategies to aid implementation of the trial in their community. Their identified implementation strategies helped standardize the study in order to maintain study integrity. The mutually agreed strategies included co-review of the study by tribal and University research review boards (but designation of the Choctaw Nation review board as the "Board of Record"), training of community-based staff on research ethics and literacy, standardization of the informed consent process by videotaping all study information, creation of a viable and culturally appropriate timeline for study implementation, adapting tribal wellness center operations to accommodate youth, and development of effective two-way communication through training sessions, on-site coordination, and bi-monthly conference calls. CONCLUSION: In an effort to partner collectively on a randomized clinical research trial to combat childhood diabetes, tribal leaders and staff implemented strategies that resulted in a culturally appropriate and organized community-based behavioral intervention research project.

Using financial incentives to promote physical activity in American Indian adolescents: A randomized controlled trial.

American Indians (AI) have high prevalence of diabetes in youth and may benefit from increasing physical activity as a strategy to improve metabolic health. We tested whether financial incentives would elicit greater frequency and/or duration of exercise in AI youth at high risk for developing diabetes. Overweight/obese AI boys and girls, 11-20 years old, were instructed to exercise on 3 days/week for 48 weeks at a tribal wellness center. The program was divided into three, 16-week-long phases to test different financial incentive strategies. Within each phase participants were randomly assigned to one of two groups that received different payments for exercise. Phase 1 was designed to test whether the size of the incentive would affect exercise frequency. In Phase 1, the number of exercise sessions did not differ between the group receiving a modest fixed-value payment per exercise session and the group receiving enhanced incentives to exercise more frequently (26 ± 3 versus 28 ± 2 sessions, respectively, p = 0.568). In Phase 2, the provision of an enhanced financial incentive to increase exercise duration resulted longer sessions, as the incentivized and standard payment groups exercised 38 ± 2 versus 29 ± 1 minutes per session (p = 0.002), respectively. In Phase 3, the effect of reducing the incentives on maintenance of exercise behaviors was inconclusive due to high participant withdrawal. Aerobic fitness increased 10% during Phase 1 but was unchanged thereafter. Insulin sensitivity and body composition were unchanged during the study. In conclusion, enhanced financial incentives increased the duration of exercise sessions, but had minimal effects on exercise participation. These results indicate that financial incentives hold promise in motivating previously sedentary, overweight/obese adolescents to exercise longer, but motivating them to sustain an exercise program remains the major challenge. TRIAL REGISTRATION: ClinicalTrials.gov NCT01848353.

Monogenic diabetes in overweight and obese youth diagnosed with type 2 diabetes: the TODAY clinical trial.

PurposeMonogenic diabetes accounts for 1-2% of diabetes cases. It is often undiagnosed, which may lead to inappropriate treatment. This study was performed to estimate the prevalence of monogenic diabetes in a cohort of overweight/obese adolescents diagnosed with type 2 diabetes (T2D).MethodsSequencing using a custom monogenic diabetes gene panel was performed on a racially/ethnically diverse cohort of 488 overweight/obese adolescents with T2D in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) clinical trial. Associations between having a monogenic diabetes variant and clinical characteristics and time to treatment failure were analyzed.ResultsMore than 4% (22/488) had genetic variants causing monogenic diabetes (seven GCK, seven HNF4A, five HNF1A, two INS, and one KLF11). Patients with monogenic diabetes had a statistically, but not clinically, significant lower body mass index (BMI) z-score, lower fasting insulin, and higher fasting glucose. Most (6/7) patients with HNF4A variants rapidly failed TODAY treatment across study arms (hazard ratio = 5.03, P = 0.0002), while none with GCK variants failed treatment.ConclusionThe finding of 4.5% of patients with monogenic diabetes in an overweight/obese cohort of children and adolescents with T2D suggests that monogenic diabetes diagnosis should be considered in children and adolescents without diabetes-associated autoantibodies and maintained C-peptide, regardless of BMI, as it may direct appropriate clinical management.

Impact of lifestyle behavior change on glycemic control in youth with type 2 diabetes.

BACKGROUND: Little is known about the feasibility and impact of lifestyle intervention, determined by change in diet and cardiovascular fitness (CRF), on glycemic control in youth who are overweight with type 2 diabetes. This was examined in the Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) clinical trial cohort from across 15 US centers. SUBJECTS: TODAY enrolled 699 youth aged 10 to 17 years with type 2 diabetes <2 years and body mass index ≥85th percentile at baseline. METHODS: Dietary data were collected by an interviewer-administered food frequency questionnaire; CRF was assessed using a submaximal cycle ergometer test. Change from baseline in these variables was analyzed using generalized linear mixed models for both continuous and categorical measures. Models were adjusted for age, baseline HbA1c, treatment group, and medication adherence. Data were collected at baseline, 6, and 24 months. Trial registration ClinicalTrials.gov NCT00081328. RESULTS: At 6 months, ~25% of females and ~33% of males improved CRF. In males, this was related to a decreased HbA1c (P = .001) and a lower percent experiencing glycemic failure (HbA1c ≥8%; P = .007). Females who decreased their saturated fat intake and/or increased their fiber intake had lower HbA1c at month 24 (P = .01 and P = .007, respectively). Males who increased their sweetened beverage intake at 6-month follow-up were at a 1.6-fold higher risk of experiencing glycemic failure (P = .04). CONCLUSIONS: Few youth improved fitness and/or diet over time, although those who did showed a beneficial impact on glycemic outcomes. Although lifestyle behaviors are difficult to change in youth with type 2 diabetes, interventions are needed that are feasible (in scope, complexity, and demands), sustainable, and clinically meaningful.

Youth-Onset Type 2 Diabetes Consensus Report: Current Status, Challenges, and Priorities.

Type 2 diabetes is a significant and increasing burden in adolescents and young adults. Clear strategies for research, prevention, and treatment of the disease in these vulnerable patients are needed. Evidence suggests that type 2 diabetes in children is different not only from type 1 but also from type 2 diabetes in adults. Understanding the unique pathophysiology of type 2 diabetes in youth, as well as the risk of complications and the psychosocial impact, will enable industry, academia, funding agencies, advocacy groups, and regulators to collectively evaluate both current and future research, treatment, and prevention approaches. This Consensus Report characterizes type 2 diabetes in children, evaluates the fundamental differences between childhood and adult disease, describes the current therapeutic options, and discusses challenges to and approaches for developing new treatments.

Relationship Between Parental Diabetes and Presentation of Metabolic and Glycemic Function in Youth With Type 2 Diabetes: Baseline Findings From the TODAY Trial.

OBJECTIVE: Children whose parents have diabetes are at increased risk for developing type 2 diabetes. This report assessed relationships between parental diabetes status and baseline demographics, anthropometrics, metabolic measurements, insulin sensitivity, and ß-cell function in children recently diagnosed with type 2 diabetes. RESEARCH DESIGN AND METHODS: The sample included 632 youth (aged 10-17 years) diagnosed with type 2 diabetes for <2 years who participated in the TODAY clinical trial. Medical history data were collected at baseline by self-report from parents and family members. Youth baseline measurements included an oral glucose tolerance test and other measures collected by trained study staff. RESULTS: Youth exposed to maternal diabetes during pregnancy (whether the mother was diagnosed with diabetes prior to pregnancy or had gestational diabetes mellitus) were diagnosed at younger ages (by 0.6 years on average), had greater dysglycemia at baseline (HbA1c increased by 0.3% [3.4 mmol/mol]), and had reduced ß-cell function compared with those not exposed (C-peptide index 0.063 vs. 0.092). The effect of maternal diabetes on ß-cell function was observed in non-Hispanic blacks and Hispanics but not whites. Relationships with paternal diabetes status were minimal. CONCLUSIONS: Maternal diabetes prior to or during pregnancy was associated with poorer glycemic control and ß-cell function overall but particularly in non-Hispanic black and Hispanic youth, supporting the hypothesis that fetal exposure to aberrant metabolism may have long-term effects. More targeted research is needed to understand whether the impact of maternal diabetes is modified by racial/ethnic factors or whether the pathway to youth-onset type 2 diabetes differs by race/ethnicity.

HbA1c After a Short Period of Monotherapy With Metformin Identifies Durable Glycemic Control Among Adolescents With Type 2 Diabetes.

OBJECTIVE: To determine whether clinically accessible parameters early in the course of youth-onset type 2 diabetes predict likelihood of durable control on oral therapy. RESEARCH DESIGN AND METHODS: TODAY was a randomized clinical trial of adolescents with type 2 diabetes. Two groups, including participants from all three treatments, were defined for analysis: (1) those who remained in glycemic control for at least 48 months of follow-up and (2) those who lost glycemic control before 48 months. Outcome group was analyzed in univariate and multivariate models as a function of baseline characteristics (age, sex, race/ethnicity, socioeconomic status, BMI, waist circumference, Tanner stage, disease duration, depressive symptoms) and biochemical measures (HbA1c, C-peptide, lean and fat body mass, insulin inverse, insulinogenic index). Receiver operating characteristic curves were used to analyze HbA1c cut points. RESULTS: In multivariate models including factors significant in univariate analysis, only HbA1c and insulinogenic index at randomization remained significant (P < 0.0001 and P = 0.0002, respectively). An HbA1c cutoff of 6.3% (45 mmol/mol) (positive likelihood ratio [PLR] 3.7) was identified that optimally distinguished the groups; sex-specific cutoffs were 6.3% (45 mmol/mol) for females (PLR 4.4) and 5.6% (38 mmol/mol) for males (PLR 2.1). CONCLUSIONS: Identifying youth with type 2 diabetes at risk for rapid loss of glycemic control would allow more targeted therapy. HbA1c is a clinically accessible measure to identify high risk for loss of glycemic control on oral therapy. Adolescents with type 2 diabetes unable to attain a non-diabetes range HbA1c on metformin are at increased risk for rapid loss of glycemic control.

Assessment of Body Mass Index, Sugar Sweetened Beverage Intake and Time Spent in Physical Activity of American Indian Children in Oklahoma.

American Indian (AI) children have a combined overweight and obesity prevalence of 53%. Behaviors that contribute to obesity, such as sugar sweetened beverage (SSB) intake and time spent in physical activity (PA), have been poorly explored in this population. The purpose of this study is to report body mass index (BMI), SSB intake, and time spent in PA of 7-to-13-year-old AI children who reside in rural and urban areas in Oklahoma. Cross-sectional survey study. Self-reported SSB intake in the last month, and time spent in PA were collected via questionnaires. Height and weight were professionally measured. The sample included 124 7-to-13-year-old AI children who attended a diabetes prevention summer camp in 2013. BMI percentile, overweight and obesity prevalence, SSB intake, time spent in PA, and number of participants meeting the Physical Activity Guidelines for Americans. Descriptive characteristics for BMI percentile, overweight and obesity, SSB intake, time spent in PA, and meeting PA recommendations were calculated using means, standard deviations, and frequencies. Independent t test and Chi square analyses were used to test for gender differences. Participants were 10.2 ± 1.5 years old and 57% female. Sixty-three percent were overweight or obese. Children consumed 309 ± 309 kcal/day of SSB and spent 4.4 ± 3.8 h per week in moderate-to-vigorous PA. Approximately 32% met the 2008 Physical Activity Guidelines for Americans. No gender differences were observed. The prevalence of overweight and obesity was higher than previously reported in a similar population, and higher than that of US children in the general population. SSB intake and physical activity levels were also found to be higher in this group than in the general population.

Clinical trials in youth-onset type 2 diabetes: needs, barriers, and options.

Youth-onset type 2 diabetes (T2D) is increasingly recognized as a disorder with substantial risk for long-term metabolic, cardiovascular, and renal morbidity and mortality, as well as individual and societal burden. Recent studies suggest that the disorder differs from adult-onset T2D in a variety of ways and that there is an urgent need for an expanded set of treatment options. However, demographic, economic, and social challenges limit the number of eligible candidates for clinical trials in youth-onset T2D, and a growing number trials mandated by regulatory agencies have created a circumstance in which too many trials are chasing too few eligible participants. A solution to this situation will require novel approaches to clinical trial design incorporating collaboration among clinical investigators, pharmaceutical sponsors, and regulatory agencies. If successful, this approach could also serve as a model for clinical trials in other rare and understudied pediatric disorders.

Partnering in research: a national research trial exemplifying effective collaboration with American Indian Nations and the Indian Health Service.

Despite the fact that numerous major public health problems have plagued American Indian communities for generations, American Indian participation in health research traditionally has been sporadic in many parts of the United States. In 2002, the University of Oklahoma Health Sciences Center (Oklahoma City, Oklahoma) and 5 Oklahoma American Indian research review boards (Oklahoma City Area Indian Health Service, Absentee Shawnee Tribe, Cherokee Nation, Chickasaw Nation, and Choctaw Nation) agreed to participate collectively in a national research trial, the Treatment Options for Type 2 Diabetes in Adolescence and Youth (TODAY) Study. During that process, numerous lessons were learned and processes developed that strengthened the partnerships and facilitated the research. Formal Memoranda of Agreement addressed issues related to community collaboration, venue, tribal authority, preferential hiring of American Indians, and indemnification. The agreements aided in uniting sovereign nations, the Indian Health Service, academics, and public health officials to conduct responsible and ethical research. For more than 10 years, this unique partnership has functioned effectively in recruiting and retaining American Indian participants, respecting cultural differences, and maintaining tribal autonomy through prereview of all study publications and local institutional review board review of all processes. The lessons learned may be of value to investigators conducting future research with American Indian communities.

Arterial compliance is increased in children with type 2 diabetes compared with normal weight peers but not obese peers.

BACKGROUND: We reported that obesity was associated with increased arterial compliance in children, possibly due to accelerated vascular maturation. Here, we explored the additional burden of type 2 diabetes (T2DM) on vascular function in children. METHODS: Fifty normal weight [body mass index (BMI) 25-75%], 58 obese (BMI ≥ 95%), and 34 children with T2DM diagnosed by American Diabetes Association (ADA) criteria ages 10-18 yr were studied. Large and small artery elasticity (LAEI and SAEI, respectively) were measured by diastolic pulse-wave contour analysis. RESULTS: SAEI was 27% higher in children with T2DM compared to normal weight children (p = 0.005). Mean LAEI for those with T2DM not different from either group. In the group with T2DM, both SAEI and LAEI increased with age up to 16 yr, but declined thereafter. The strongest multivariable model predicting SAEI in children with T2DM combined lean mass, systolic blood pressure (SBP), and glucose (r2 = 0.59); for predicting LAEI, the strongest model included height, SBP, and low-density lipid-cholesterol (r2 = 0.61). CONCLUSION: The lower arterial compliance in older adolescents with T2DM compared to that of their peers without diabetes may indicate a premature maturation of the vascular system; however, follow-up will clarify whether these vascular changes portend an early increase in diabetes-associated cardiovascular disease risk.

Management of newly diagnosed type 2 Diabetes Mellitus (T2DM) in children and adolescents.

Over the past 3 decades, the prevalence of childhood obesity has increased dramatically in North America, ushering in a variety of health problems, including type 2 diabetes mellitus (T2DM), which previously was not typically seen until much later in life. The rapid emergence of childhood T2DM poses challenges to many physicians who find themselves generally ill-equipped to treat adult diseases encountered in children. This clinical practice guideline was developed to provide evidence-based recommendations on managing 10- to 18-year-old patients in whom T2DM has been diagnosed. The American Academy of Pediatrics (AAP) convened a Subcommittee on Management of T2DM in Children and Adolescents with the support of the American Diabetes Association, the Pediatric Endocrine Society, the American Academy of Family Physicians, and the Academy of Nutrition and Dietetics (formerly the American Dietetic Association). These groups collaborated to develop an evidence report that served as a major source of information for these practice guideline recommendations. The guideline emphasizes the use of management modalities that have been shown to affect clinical outcomes in this pediatric population. Recommendations are made for situations in which either insulin or metformin is the preferred first-line treatment of children and adolescents with T2DM. The recommendations suggest integrating lifestyle modifications (ie, diet and exercise) in concert with medication rather than as an isolated initial treatment approach. Guidelines for frequency of monitoring hemoglobin A1c (HbA1c) and finger-stick blood glucose (BG) concentrations are presented. Decisions were made on the basis of a systematic grading of the quality of evidence and strength of recommendation. The clinical practice guideline underwent peer review before it was approved by the AAP. This clinical practice guideline is not intended to replace clinical judgment or establish a protocol for the care of all children with T2DM, and its recommendations may not provide the only appropriate approach to the management of children with T2DM. Providers should consult experts trained in the care of children and adolescents with T2DM when treatment goals are not met or when therapy with insulin is initiated. The AAP acknowledges that some primary care clinicians may not be confident of their ability to successfully treat T2DM in a child because of the child's age, coexisting conditions, and/or other concerns. At any point at which a clinician feels he or she is not adequately trained or is uncertain about treatment, a referral to a pediatric medical subspecialist should be made. If a diagnosis of T2DM is made by a pediatric medical subspecialist, the primary care clinician should develop a comanagement strategy with the subspecialist to ensure that the child continues to receive appropriate care consistent with a medical home model in which the pediatrician partners with parents to ensure that all health needs are met.

Current treatment options for type 2 diabetes mellitus in youth: today's realities and lessons from the TODAY study.

The incidence of type 2 diabetes in children and adolescents has increased over the last 2 decades, paralleled by an increase in obesity over the same time period. Although the value of lifestyle modification in obese youth is unquestioned, scant evidence for optimal treatment of type 2 diabetes in this age group exists. Despite recent therapeutic drug trials, metformin and insulin are the only medicines currently approved by the U.S. Food and Drug Administration for the treatment of type 2 diabetes in youth. Because of recently amended pharmaceutical regulations, however, it is likely that more antidiabetic medications soon will be added to the armamentarium of therapeutic options for youth with type 2 diabetes. Additionally, the recently published TODAY study comparing safety and efficacy of three treatment regimens in maintaining glycemic control in youth with type 2 diabetes has shed new light on the problem.

Sex differences in cardiovascular disease risk in adolescents with type 1 diabetes.

BACKGROUND: Cardiovascular disease is seen at a younger age and at a higher prevalence in patients with type 1 diabetes than in the general population. It is well described that women with type 1 diabetes have a higher relative risk of cardiovascular disease than men with type 1 diabetes, unlike that seen in the general population. The pathophysiology behind this is unknown. OBJECTIVE: We performed a cross-sectional study to examine sex differences in cardiovascular disease risk factors in adolescents with type 1 diabetes between ages 13 and 20 years, compared with children of a similar age without type 1 diabetes. METHODS: All patients underwent a dual energy x-ray absorptiometry scan to measure body composition and a pulse wave test measure of arterial elasticity. Fasting serum lipid levels, apolipoprotein B, and apolipoprotein C-III levels were measured in each patient. Twenty-nine children with type 1 diabetes (10 girls, 19 boys) and 37 healthy children (18 girls, 19 boys) participated. RESULTS: Although no sex differences for body mass index (P = 0.91) and glycosylated hemoglobin (P = 0.69) were seen, girls with type 1 diabetes had a significantly higher percent trunk fat compared with boys (P = 0.004). No sex differences were found (P > 0.05) for percent trunk fat in adolescents without diabetes. There was no sex difference among any other cardiovascular risk factors in either children with or without diabetes. CONCLUSIONS: Female adolescents with type 1 diabetes have more centrally distributed fat, which may contribute to their relatively higher cardiovascular disease risk. Attenuation of the central distribution of fat through exercise and dietary modifications may help ameliorate their subsequent cardiovascular disease burden.

Sex differences in vascular compliance in normal-weight but not obese boys and girls: the effect of body composition.

Objectives. To determine the effect of sex and obesity on vascular function in children and explore potential mechanisms that account for differences in vascular function. Methods. Participants were 61 (30 boys) normal-weight (BMI 25-75% ile for age and sex) and 62 (30 boys) obese (BMI ≥ 95% ile) children of ages 8-18 years. Measurements of large and small artery elastic index (LAEI and SAEI, resp.) and reactive hyperemia index (RHI) were obtained at rest, along with anthropometric and biochemical information. Results. In normal-weight children, LAEI was 16% higher in males than females (P = 0.04) with a similar trend for SAEI (13% higher in males, P = 0.067). In obese children, no sex-related differences in vascular measures were observed. In multivariable models, sex differences in arterial compliance were explained by higher lean mass in normal-weight boys. Fat mass predicted LAEI and SAEI in both normal-weight and obese females, but fat mass predicted arterial compliance in boys when fat mass exceeded 24 kg (37% of the sample). Conclusions. Normal-weight males have higher arterial compliance than normal-weight females due to increased lean mass, but sex-related differences were not observed among obese children due to a lack of sex-related differences in lean or fat mass.