Association of HbA1C and comfort with diabetes self-management among adolescents and young adults with type 1 diabetes.

Introduction: Adolescents and young adults (AYA) living with type 1 diabetes (T1D) are a vulnerable demographic at risk for sub-optimal glycemic outcomes at a time when they are taking over their diabetes management. The purposes of this study were to examine levels of self-reported comfort with diabetes management tasks among AYA living with T1D and to describe the relationships among comfort levels, sociodemographic factors, and HbA1c. Methods: During a routine diabetes care visit, AYA aged 15-23 years old living with T1D received a transition survey to self-assess their comfort level with different diabetesmanagement tasks. Results: Among 161 participants who completed the survey (median age 17 years, median diabetes duration 7 years, 82.3% White, 40.9% female, 66.5% with private insurance, and median HbA1c 8.8%), comfort with diabetes management tasks was generally rated highly (median overall comfort level of 4.5 out of 5), irrespective of race or insurance type. Regression analysis revealed that higher self-reported comfort level with diabetes management tasks was associated with a higher HbA1c (p = 0.006), after controlling for age, sex, race, insurance type, and diabetes duration. Discussion: These findings suggest that self-reported comfort with independently managing T1D may not be a sufficient metric in assessing AYA patients' need for further intervention to optimize glycemic outcomes as they transition from pediatric to adult diabetes care, and highlights the importance of continuity of care to support diabetes management during this transitional period.

Novel therapeutic approaches to preserve the right ventricle.

The right ventricle (RV) is increasingly recognized for its role in heart disease. In fact, RV function is a strong predictor of outcome in patients with cardiovascular disease. Although the focus in heart failure has been on the left ventricle (LV), recently the spotlight has been shifting to include the RV. The RV and LV have different embryological origins and respond differently to stressors and to therapies. Newer therapies targeting the RV have been investigated in an attempt to improve right-ventricular adaptation to cardiovascular diseases. In this review, we summarize the differences between the RV and LV and focus on novel therapies that target the RV.

Novel compound heterozygous LRBA deletions in a 6-month-old with neonatal diabetes.

We report a 6-month-old boy with antibody-positive insulin-dependent diabetes mellitus. Sequencing identified compound heterozygous deletions of exon 5 and exons 36-37 in LRBA. At three years, he has yet to exhibit any other immune symptoms. Genetic testing of LRBA is warranted in patients with neonatal diabetes, even without immune dysregulation.

The Berkeley Dry Eye Flow Chart: A fast, functional screening instrument for contact lens-induced dryness.

PURPOSE: In this article, we introduce a novel flow chart-based screening tool for the categorization of contact lens-induced dryness (CLIDE) and its impact on daily visual activities: the Berkeley Dry Eye Flow Chart (DEFC). METHODS: One hundred thirty (130) experienced soft contact lens wearers discontinued lens wear for 24 hrs, passed a baseline screening and eye health examination, completed the Ocular Surface Disease Index (OSDI) then were dispensed fresh pairs of their habitual lenses. After 6 hrs of wear, subjects were administered a battery of symptom questionnaires, and underwent non-invasive tear breakup time (NITBUT) measurement, grading of distortion in reflected topographer mires, grading of lens surface wettability, and a fluorescein examination of the ocular surface. Subjects returned after at least 48 hrs and repeated all assessments after 6 hrs of wear of a second fresh pair of habitual lenses. RESULTS: The repeatability of the DEFC between visits was within 1%, and Limits of Agreement and Coefficient of Repeatability were comparable to those of the other CLIDE assessments. Higher DEFC score was significantly related to shorter pre-lens NITBUT, higher OSDI score, and higher Visual Analog Scale (VAS) ratings of average and end-of-day severity and frequency of dryness (all p < 0.001). For CLIDE as diagnosed based on DEFC score, the highest sensitivities and specificities were achieved by the OSDI and VAS ratings; pre-lens NITBUT exhibited good sensitivity but poor specificity. The optimum pre-lens NITBUT diagnostic threshold was found to be ≤ 2.0 sec for debilitating CLIDE, and the OSDI threshold was ≥ 11.4. CONCLUSIONS: The DEFC provides a means of quickly categorizing CLIDE patients based on severity and frequency of symptoms, and on the degree to which symptoms impact daily life. The DEFC has several potential advantages as a CLIDE screening and monitoring tool, has good repeatability, and is significantly related to commonly employed clinical assessments for CLIDE.

Coenzyme Q supplementation in pulmonary arterial hypertension.

Mitochondrial dysfunction is a fundamental abnormality in the vascular endothelium and smooth muscle of patients with pulmonary arterial hypertension (PAH). Because coenzyme Q (CoQ) is essential for mitochondrial function and efficient oxygen utilization as the electron carrier in the inner mitochondrial membrane, we hypothesized that CoQ would improve mitochondrial function and benefit PAH patients. To test this, oxidized and reduced levels of CoQ, cardiac function by echocardiogram, mitochondrial functions of heme synthesis and cellular metabolism were evaluated in PAH patients (N=8) in comparison to healthy controls (N=7), at baseline and after 12 weeks oral CoQ supplementation. CoQ levels were similar among PAH and control individuals, and increased in all subjects with CoQ supplementation. PAH patients had higher CoQ levels than controls with supplementation, and a tendency to a higher reduced-to-oxidized CoQ ratio. Cardiac parameters improved with CoQ supplementation, although 6-minute walk distances and BNP levels did not significantly change. Consistent with improved mitochondrial synthetic function, hemoglobin increased and red cell distribution width (RDW) decreased in PAH patients with CoQ, while hemoglobin declined slightly and RDW did not change in healthy controls. In contrast, metabolic and redox parameters, including lactate, pyruvate and reduced or oxidized gluthathione, did not change in PAH patients with CoQ. In summary, CoQ improved hemoglobin and red cell maturation in PAH, but longer studies and/or higher doses with a randomized placebo-controlled controlled design are necessary to evaluate the clinical benefit of this simple nutritional supplement.

Fasting 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography to detect metabolic changes in pulmonary arterial hypertension hearts over 1 year.

BACKGROUND: The development of tools to monitor the right ventricle in pulmonary arterial hypertension (PAH) is of clinical importance. PAH is associated with pathologic expression of the transcription factor hypoxia-inducible factor (HIF)-1α, which induces glycolytic metabolism and mobilization of proangiogenic progenitor (CD34(+)CD133(+)) cells. We hypothesized that PAH cardiac myocytes have a HIF-related switch to glycolytic metabolism that can be detected with fasting 2-deoxy-2-[(18)F]fluoro-d-glucose positron emission tomography (FDG-PET) and that glucose uptake is informative for cardiac function. METHODS: Six healthy control subjects and 14 patients with PAH underwent fasting FDG-PET and echocardiogram. Blood CD34(+)CD133(+) cells and erythropoietin were measured as indicators of HIF activation. Twelve subjects in the PAH cohort underwent repeat studies 1 year later to determine if changes in FDG uptake were related to changes in echocardiographic parameters or to measures of HIF activation. MEASUREMENTS AND RESULTS: FDG uptake in the right ventricle was higher in patients with PAH than in healthy control subjects and correlated with echocardiographic measures of cardiac dysfunction and circulating CD34(+)CD133(+) cells but not erythropoietin. Among patients with PAH, FDG uptake was lower in those receiving ß-adrenergic receptor blockers. Changes in FDG uptake over time were related to changes in echocardiographic parameters and CD34(+)CD133(+) cell numbers. Immunohistochemistry of explanted PAH hearts of patients undergoing transplantation revealed that HIF-1α was present in myocyte nuclei but was weakly detectable in control hearts. CONCLUSIONS: PAH hearts have pathologic glycolytic metabolism that is quantitatively related to cardiac dysfunction over time, suggesting that metabolic imaging may be useful in therapeutic monitoring of patients.