Postprandial hyperglycemia due to paradoxical hyperglucagonemia is a major challenge of diabetes treatment despite the use of the artificial pancreas. We postulated that adjunctive therapy with pramlintide or exenatide would attenuate hyperglycemia in the postprandial phase through glucagon suppression, thereby optimizing the functioning of the closed-loop (CL) system. Subjects with type 1 diabetes (T1DM) on insulin pump therapy were recruited to participate in a 27-hour hospitalized admission on 3 occasions (2-4 weeks apart) and placed on the insulin delivery via CL system in random order to receive (1) insulin alone (control), (2) exenatide 2.5 µg + insulin, (3) pramlintide 30 µg + insulin. Medications were given prior to lunch and dinner, which was a standardized meal of 60 grams of carbohydrates. Insulin delivery was as per the ePID algorithm via the Medtronic CL system and continuous subcutaneous glucose monitoring via Medtronic Sof-sensors. Ten subjects age 23 ± 1 years with a HbA1c of 7.29 ± 0.3% (56 ± 1 mmol/mol) and duration of T1DM 10.6 ± 2.0 years participated in the 3-part study. Exenatide was found to be significantly better in attenuating postprandial hyperglycemia as compared to insulin monotherapy (P < .03) and pramlintide (P > .05). Glucagon suppression was statistically significant with exenatide (P < .03) as compared to pramlintide. Insulin requirements were lower with adjunctive therapy, but statistically insignificant. Insulin monotherapy results in postprandial hyperglycemia in T1DM in the CL setting and adjunctive therapy with exenatide reduces postprandial hyperglycemia effectively and should be considered as adjunctive therapy in T1DM.

The objective of this study was to evaluate the impact of short stature on generic health-related quality of life (HRQOL) and cognitive functioning in pediatric patients. Eighty-nine youth, 48 who were initially seen with short stature (SS group) and 41 with a history of short stature being treated with growth hormone (GHT group) and one of their legal guardians participated in the study. HRQOL and cognitive functioning were assessed using the PedsQL™ 4.0 Generic Core Scales and PedsQL™ Cognitive Functioning Scale. Comparisons were made between the study groups and with a previously obtained matched healthy sample. For the GHT group, height Z score was found to be a positive predictor of overall HRQOL while duration of GHT was found to be a predictor of physical functioning. For the SS group, the difference between midparental height Z score and height Z score was found to be a negative predictor of overall HRQOL and cognitive functioning. Comparison with the healthy sample demonstrated significant negative impact on HRQOL for child self-report and on HRQOL and cognitive functioning for parent proxy-report in both study groups. The GHT group had a significantly higher child self-reported Physical Functioning score than the SS group (effect size (ES) = 0.52, p < 0.05). In conclusion, the GHT group had slightly better HRQOL scores than the SS group, but the difference was not statistically significant. Both groups had significantly lower HRQOL and cognitive functioning scores than healthy sample. Predictors of HRQOL and cognitive functioning found in this study lend support to the use of the PedsQL™ 4.0 Generic Score Scales and PedsQL™ Cognitive Functioning Scale in routine assessment of children with short stature in order to identify children at increased risk for impaired HRQOL and cognitive functioning.

BackgroundAlong with the rise in obesity, cardiovascular disease (CVD) has become the major cause of death in developed countries. Although overt coronary heart disease rarely manifests during childhood, atherosclerosis can begin by the second decade of life. Therefore, identifying reliable risk markers of early vascular disease in childhood could be important. Alteration in endothelial function (EF) is an early preclinical marker of the atherosclerotic process and can be assessed non-invasively using reactive hyperemia peripheral arterial tonometry (RH-PAT). The purpose of this study was to investigate if obesity in children is associated with lower EF as measured with RH-PAT, and if obese children with impaired glucose regulation have further impairment in RH-PAT measured EF compared to obese children with normal glucose tolerance.MethodsCardiovascular risk factors, adipocytokines and EF using RH-PAT were evaluated in lean (n = 14) and obese (n = 37) adolescents (age 12–18 years). Based on an oral glucose tolerance test, the obese group was subdivided into: obese with normal (NGT, n = 22) and obese with impaired glucose regulation (IGR, n = 15).ResultsRH-PAT score was lower in obese subjects compared to lean controls (1.70 ± 0.02 vs. 1.98 ± 0.09, P = 0.02), indicating worse EF. This difference remained significant when adjusted for age, sex and ethnicity (P = 0.02). We observed a pattern of worsening EF with increasing metabolic burden, with RH-PAT scores of 1.98 ± 0.09,1.73 ± 0.08 and 1.65 ± 0.12 in the lean, obese-NGT and obese-IGR groups, respectively, ptrend = 0.03. Obese subjects were more insulin resistant [higher HOMA] (p = 0.03), and had higher levels of leptin (p = 0.004), hsCRP (p = 0.0004), and TNF-α (p = 0.03) compared to lean subjects. Adjusting for insulin resistance and adipocytokines substantially attenuated the obesity association with RH-PAT, suggesting that insulin resistance and inflammation may mediate the association of EF with obesity.ConclusionsRisk factors for adult cardiovascular disease, including impaired EF, insulin resistance and inflammation, are evident in obese adolescents. Whether early detection of these cardiovascular risk factors will be useful for informing interventions to prevent disease progression needs further study.Trial registrationClinical Trials Identifier: NCT01879033

Disaster preparedness still lags in families of lower socioeconomic status.