Asunto(s)
Automonitorización de la Glucosa Sanguínea , Glucemia , Diabetes Mellitus Tipo 1 , Hemoglobina Glucada , Humanos , Hemoglobina Glucada/análisis , Hemoglobina Glucada/metabolismo , Estudios Retrospectivos , Automonitorización de la Glucosa Sanguínea/métodos , Glucemia/análisis , Glucemia/metabolismo , Adolescente , Masculino , Femenino , Niño , Diabetes Mellitus Tipo 1/sangre , Control Glucémico/estadística & datos numéricosRESUMEN
OBJECTIVE: Hybrid diabetes (HD); ie, insulin resistance with positive diabetes-associated autoantibodies (DAAs) is increasing in children. We aimed to compare the characteristics of children with HD with those with type 1 diabetes (T1DM) and type 2 diabetes (T2DM) at diagnosis and after 2 years. METHODS: A retrospective review of patients aged 0 to 19 years, with C-peptide and 4 DAA measurements available, who were diangosed with new-onset diabetes from 2016 to 2020 were included in the analysis. RESULTS: Overall, 102 subjects were included, 32 with T1DM, 21 with HD, and 49 with T2DM. Amongst the groups (T1DM vs HD vs T2DM), there were differences in the proportion of non-Hispanic Whites (81.3% vs 47.6% vs 16.4%, P < .001), frequency of family history of T2DM (37.5% vs 100% vs 85.4%, P < .001), acanthosis nigricans (0% vs 42.9% vs 93.9%, P <.001), median body mass index z-score (-0.55 vs 1.8 vs 2.4, P <.001), and median C-peptide (0.4 ng/mL vs 0.9 ng/mL vs 2.4 ng/mL, P <.001). At 2 years, differences were seen in median body mass index z-scores (0.3 vs 1.9 vs 2.3, P <.001), mean HDL-cholesterol (58.0 mg/dL vs 48.2 mg/dL vs 39.5 mg/dL, P <.001), and the use of basal insulin (100% vs 100% vs 74.4%, P <.001). CONCLUSION: Phenotypic and metabolic differences were seen in youth with T1DM, HD, and T2DM at diagnosis and follow-up. At 2 years, all subjects with HD remained insulin dependent whereas some with T2DM were not, indicating the need for targeted interventions to address the etiopathogenesis.
Asunto(s)
Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Niño , Humanos , Adolescente , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 1/complicaciones , Péptido C , Antivirales/uso terapéutico , Insulina/uso terapéuticoRESUMEN
CONTEXT: There is concern that the growing incidence of pediatric type 2 diabetes (T2D) may have been further exacerbated by the COVID-19 pandemic. OBJECTIVE: To examine whether trends in new-onset pediatric T2D-inclusive of patients requiring hospitalization and patients managed as outpatients-were impacted during the COVID-19 pandemic, and to compare patient characteristics prior to and during COVID-19. METHODS: A retrospective single-center medical record review was conducted in a hospital which cares for 90% of Alabama's pediatric T2D patients. Patients with new-onset T2D referred from March 2017 to March 2021 were included. Counts of patients presenting per month ("monthly rates") were computed. Linear regression models were estimated for the full sample and stratified by Medicaid and non-Medicaid insurance status. Patient characteristics prior to vs during COVID-19 were compared. RESULTS: A total of 642 patients presented with new-onset T2D over this period. Monthly rates were 11.1â ±â 3.8 prior to COVID-19 and 19.3â ±â 7.8 during COVID-19 (Pâ =â .004). Monthly rates for Medicaid patients differed prior to and during COVID-19 (7.9â ±â 3.4 vs 15.3â ±â 6.6, Pâ =â .003) but not for non-Medicaid patients (3.3â ±â 1.7 vs 4.0â ±â 2.4, Pâ =â .33). Regression results showed significant increases in monthly rates during COVID-19 for the full sample (ß= 5.93, Pâ <â .05) and for Medicaid enrollees (ß= 5.42, Pâ <â .05) Hospitalization rate, severity of obesity, and hemoglobin A1c remained similar prior to and during COVID-19, though the proportion of male patients increased from 36.8% to 46.1% (Pâ =â .021). CONCLUSIONS: A rise in new-onset T2D was observed among Alabama's youth during the COVID-19 pandemic, a burden that disproportionately affected Medicaid enrollees and males. Future research should explore the pathways through which the pandemic impacted pediatric T2D.
Asunto(s)
COVID-19 , Diabetes Mellitus Tipo 2 , Adolescente , COVID-19/epidemiología , Niño , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/terapia , Femenino , Hemoglobina Glucada , Humanos , Masculino , Pandemias , Estudios Retrospectivos , Estados Unidos/epidemiologíaRESUMEN
Aurora-A differs from Aurora-B/C at three positions in the ATP-binding pocket (L215, T217, and R220). Exploiting these differences, crystal structures of ligand-Aurora protein interactions formed the basis of a design principle for imidazo[4,5-b]pyridine-derived Aurora-A-selective inhibitors. Guided by a computational modeling approach, appropriate C7-imidazo[4,5-b]pyridine derivatization led to the discovery of highly selective inhibitors, such as compound 28c, of Aurora-A over Aurora-B. In HCT116 human colon carcinoma cells, 28c and 40f inhibited the Aurora-A L215R and R220K mutants with IC50 values similar to those seen for the Aurora-A wild type. However, the Aurora-A T217E mutant was significantly less sensitive to inhibition by 28c and 40f compared to the Aurora-A wild type, suggesting that the T217 residue plays a critical role in governing the observed isoform selectivity for Aurora-A inhibition. These compounds are useful small-molecule chemical tools to further explore the function of Aurora-A in cells.