Search

Objectives: Data regarding atherogenic dyslipidemia and the inflammation profile in youth with type 2 diabetes is limited and the effect of insulin therapy on these variables has not previously been studied in youth. We determined the impact of insulin therapy on lipid and inflammatory markers in youth with poorly controlled type 2 diabetes.Study Design: In the Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) multicenter trial, 285 participants failed to sustain glycemic control on randomized treatment (primary outcome, glycated hemoglobin A1c [HbA1c] at ≥8% for 6 months); 363 maintained glycemic control (never reached primary outcome). Statins were used for a low-density lipoprotein cholesterol of ≥130 mg/dL. Upon reaching the primary outcome, insulin was started. Changes in lipids and inflammatory markers (slopes over time) were examined.Results: Progression of dyslipidemia was related to glycemic control. In those with the primary outcome, insulin therapy impacted HbA1c modestly, and dampened the increase in total cholesterol, low-density lipoprotein cholesterol, and total apolipoprotein B, although statin use increased from 8.6% to 22% year after the primary outcome. The increase in triglycerides and plasma nonesterified fatty acids stabilized after insulin was started, independent of HbA1c. There was an increase in high-sensitivity C-reactive protein that continued after insulin initiation, related to HbA1c and percent overweight.Conclusions: Worsening dyslipidemia and inflammation over time raise concern regarding premature development of atherosclerosis in youth with type 2 diabetes. Insulin therapy has a limited benefit in the absence of glycemic control. Strategies to achieve better glycemic control are needed.Trial Registration: ClinicalTrials.gov: NCT00081328. [ABSTRACT FROM AUTHOR]

Objectives: To characterize, during a 2-year period, the proportion of youth with type 2 diabetes (T2D) enrolled in the Treatment Options for Type 2 Diabetes in Adolescents and Youth study that reported ever at least trying smoking cigarettes and/or drinking alcohol.Study Design: Longitudinal data were examined for participants with T2D ages 10-18 years at baseline. Youth psychosocial, parent/family, environmental, and biological correlates of trying health risk behaviors were tested via cross-sectional multivariate models at each time point. Longitudinal models were explored for selected factors.Results: Data were obtained from the Treatment Options for Type 2 Diabetes in Adolescents and Youth study's ethnically diverse participants at baseline (N=644), 6-month (N=616), and 24-month (N=543) assessments. The percentage of youth ever trying only smoking remained stable at 4%; only drinking alcohol increased from 17% to 26%, and both smoking and drinking increased from 10% to 18% during the 2-year period. Factors related to trying health risk behaviors were older age, male sex, non-Hispanic white race-ethnicity, lower grades, more depressive symptoms, and stressful life events. Depressive symptoms, stressful life events, and body mass index Z-score (the latter with smoking only) were related to engagement in health risk behaviors over time.Conclusions: Youth with T2D who are already at risk for health complications and who reported engaging in activities that further increase the likelihood of life-threatening morbidities were characterized. Although most correlates of trying these risk behaviors are nonmodifiable, intervention efforts may need to focus on potentially modifiable factors, such as depressive symptoms and lower grades. [ABSTRACT FROM AUTHOR]

Objectives: To examine cardiac biomarkers over time in youth-onset type 2 diabetes, and relate serum concentrations to cardiovascular disease risk factors, and left ventricular structure and function.Study Design: TODAY (Treatment Options for type 2 Diabetes in Adolescents and Youth) was a multicenter randomized trial of 3 treatments including 521 participants with type 2 diabetes, aged 10-17 years, and with 2-6 years of follow-up. Participants were 36% male, obese, and ethnically diverse. Annual serum concentrations of brain natriuretic peptide, troponin, tumor necrosis factor (TNF)-α, receptors 1 and 2 were related to blood pressure, body mass index, hemoglobin A1c, and left ventricular ejection fraction, diastolic function, relative wall thickness, and mass.Results: Elevated concentrations of brain natriuretic peptide (≥100 pg/mL), TNF-α (≥5.6 pg/mL) and troponin (≥0.01 ng/mL), were present in 17.8%, 18.3%, and 34.2% of the cohort, respectively, at baseline, and in 15.4%, 17.1%, and 31.1% at the end of the study, with wide variability over time, without persistence in individuals or clear relationship to glycemia or cardiovascular structure/function. TNF receptors concentrations were increased at baseline and not significantly different from end-of-study concentrations. Adverse echocardiographic measures were more likely in the highest TNF receptor tertile (all P < .05): higher left ventricular mass (39.3 ± 9.0 g/m2.7), left atrial internal dimension (3.7 ± 0.4 cm) and E/Em ratio, a measure of diastolic dysfunction (6.2 ± 1.9). After adjustment for body mass index, these relationships were no longer significant.Conclusions: Elevated serum concentrations of cardiac biomarkers were common in youth with type 2 diabetes, but their clinical significance is unclear and will require further long-term study.Trial Registration: ClinicalTrials.govNCT00081328. [ABSTRACT FROM AUTHOR]

Objective: To investigate the relationships of cardiac structure and function with body composition and cardiorespiratory fitness (CRF) among adolescents with type 2 diabetes in the Treatment Options for Type 2 Diabetes in Adolescents and Youth study.Study Design: Cross-sectional evaluation of 233 participants (median age 18.3 [min-max 12.4-24.2] years, 63% females, median hemoglobin A1c 6.8%) who had echocardiography measurements of left ventricular (LV) mass, ejection fraction, left atrial dimensions, LV diastolic function (early transmitral flow velocity to early mitral annular velocity ratio from tissue Doppler imaging), and right ventricular function (tricuspid annular plane systolic excursion [TAPSE]) and body composition (dual-energy x-ray absorptiometry) and CRF (cycle ergometry determination of physical work capacity at heart rate of 170 beats per minute).Results: LV mass correlated positively with CRF (r = 0.5, P < .0001), lean body mass (LBM) (r = 0.7, P < .0001), and fat mass (FM) (r = 0.2, P = .00047); LV ejection fraction did not. Early transmitral flow velocity to early mitral annular velocity was positively related to FM (r = 0.14, P = .03) and % body fat (r = 0.18, P = .007), and left atrial internal diameter correlated with FM (r = 0.4, P < .0001), LBM (r = 0.3, P < .001), and CRF (r = 0.2, P = .0033). TAPSE weakly correlated with CRF (r = 0.2, P = .0014) and LBM (r = 0.13, P < .05) but not with FM. In multivariable regression analyses, LBM (β = 2.13, P < .0001) and CRF (β = 0.023, P = .008) were related to LV mass independent of race, sex, age, hemoglobin A1c, hypertension, smoking, and diabetes medications. CRF (β = 0.0002, P = .0187) and hemoglobin A1c (β = -0.022, P = .0142) were associated with TAPSE.Conclusions: In youth with type 2 diabetes, LV size is related to physical fitness. LV ejection fraction is within normal limits. LV diastolic function is inversely related to FM. Greater fitness may counteract adverse effects of poor glycemic control on right ventricular function.Trial Registration: ClinicalTrials.gov:NCT00081328. [ABSTRACT FROM AUTHOR]

Objective: To examine the relationships between stressful life events and physiological measures, adherence to prescribed oral medication regimens, depressive symptoms, and impaired quality of life (QoL) in adolescents with recent-onset type 2 diabetes (T2D).Study Design: Data were collected from 497 ethnically diverse participants (66% female) in the final year of the Treatment Options for Type 2 Diabetes in Adolescents and Youth multicenter clinical trial. Exposure to 32 possible events over the previous year and rating of subsequent distress were collected by self-report and summarized as a major stressors score. This score was analyzed for relationship to glycemic control (hemoglobin A1c and treatment failure), body mass index, diagnosis of hypertension or triglyceride dyslipidemia, adherence to a prescribed oral medication regimen, presence of depressive symptoms, and impaired QoL.Results: The total number of major stressful life events in the adolescents with T2D was calculated, with 33% reporting none, 67% reporting ≥ 1, 47% reporting ≥ 2, 33% reporting ≥ 3, and 20% reporting ≥ 4. There were no associations between the major stressors score and physiological measures or diagnosis of comorbidities. The odds of medication nonadherence increased significantly from those reporting ≥ 1 major stressor (OR, 1.58; P = .0265) to those reporting ≥ 4 major stressors (OR, 2.70; P = .0009). Significant odds of elevated depressive symptoms and impaired QoL were also found with increased reporting of major stressors.Conclusion: Exposure to major stressful life events is associated with lower adherence to prescribed oral medication regimens and impaired psychosocial functioning in adolescents with T2D. [ABSTRACT FROM AUTHOR]