Differences in COVID-19 Outcomes Among Patients With Type 1 Diabetes: First vs Later Surges

Background Outcomes of the novel coronavirus SARS-CoV-2 (COVID-19) have improved throughout the pandemic. However, whether outcomes of COVID-19 in the type 1 diabetes (T1D) population improved over time is unknown. Therefore, we aim to investigate differences in COVID-19 outcomes for patients with T1D in the US. Method We analyzed data collected via a registry of patients with T1D and COVID-19 from 56 sites between April 2020 and January 2021. First, we grouped cases into First Surge (04/09/2020 - 07/31/2020, n=188) and Late Surge (08/01/2020 - 01/31/2021, n=410). Then, we compared outcomes between both groups using descriptive statistics and logistic regression models. Results Adverse outcomes were more frequent during the first surge including Diabetic Ketoacidosis (32% versus 15%, p<0.001), severe hypoglycemia (4% versus 1%, p=0.04) and hospitalization (52% versus 22%, p<0.001). The First surge cases were older (28 +/- 18.8 years versus 18.8 +/- 11.1 years, p<0.001), had higher hemoglobin A1c (HbA1c) levels (Median (IQR): 9.3 (4.0) versus 8.4(2.8), <0.001) and use public insurance (n(%): 107 (57) versus 154 (38), p <0.001). There were five times increased odds of hospitalization for adults (OR 5.01 (2.11,12.63) in the first surge compared to the late surge. Conclusion COVID-19 cases among patients with T1D reported during the first surge had a higher proportion of adverse outcomes than those presented in a later surge

Cell transplantation therapies for diabetes mellitus: developing unlimited quantites of beta cells how solution of shortage of pancreatic tissue available

Um dos maiores obstaculos ao sucesso do transplante celular como opcao terapeutica para o diabetes mellitus refere-se 'a escassez de celulas R funcionais disponiveis. A expansao in vitro de celulas O humanas ou de seus precursores, permitira a obtencao de grandes quantidades de celulas com a capacidade de secretar insulina em resposta a glicose. Estas celulas potencialmente poderao ser utilizadas para o transplante em pacientes portadores de diabetes. A expancao de celulas b humanas e de seus precursores in vitro pode ser alcancada com a utilizacao de dois metodos distintos. O primeiro refere-se a cultura de celulas primarias na presenca de matrizes extracelulares e fatores de crescimento. Como precursores da celulas b, as celulas pancreaticas endocrinas fetais representam uma fonte potencial de celulas para transplante. O estudo dos fatores que influenciam o crescimento e a diferenciacao destas celulas podera contribuir para a identificacao das condicoes mais apropriadas para sua cultura in vitro. Neste estudo nos demonstramos que a ativina A, membro da familia dos transforming growth factos b induz a diferenciacao endocrina, enquanto que a betacelulina, membro da familia dos epidermal growth factors, possui um efeito mitogenico nas celulas humanas pancreaticas epiteliais indiferenciadas. O segundo metodo para o desenvolvimento de quantidades ilimitadas de celulas bhumanas baseia-se na expressao de oncogenes dominantes nas celulas, a qual promove a expansao celular in vitro independentemente do uso de matrizes extracelulares ou de fatores de crescimento. As linhagens celulares apresentam uma maior capacidade de replicacao quando comparadas 'as celulas primarias, sendo que a posterior inducao da atividade da telomerase nestas celulas resulta em sua total imortalizacao. Embora os oncogenes confiram 'as celulas a propriedade de se mutiplicarem indefinidamente, estes exercem efeitos negativos na sua capacidade de diferenciacao. Entretanto, neste estudo demonstramos que a imagem celular TRM-6, derivada de ilhotas pancreaticas fetais humanas, e capaz de ser diferenciadas das celulas d, dependendo da expressao do fator de transicao PDX-1 e da promocao do contato intercelular. Da mesma forma, demonstramos que blox5, uma linhagem celular derivada de celulas b humanas purificadas, pode ser induzida a exibir secrecao de insulina em resposta ao estimulo com glicose in vitro e in vivo. Este e o primeiro relato de uma...(au)BV UNIFESP: Teses e dissertaçõe

Farelo de arroz como suplemento alimentar : avaliação da ação sobre insulin-like growth factor-I e oligoelementos

Orientador: Luiz de Lacerda FilhoDissertação (mestrado) - Universidade Federal do Paraná, Setor de Ciências da Saúde, Programa de Pós-Graduação em PediatriaResumo: A utilização do farelo de arroz como suplemento alimentar em crianças carentes em várias localidades do país, levou ao delineamento deste trabalho, que tem como objetivo verificar a interferência do farelo no estado nutricional de crianças, mediante a dosagem de marcadores nutricionais de alta sensibilidade : IGF-I, IGFBP- 2, IGFBP-3. Realizou-se um estudo prospectivo em 47 crianças de baixo nível sócio-econômico, pertencentes a uma creche municipal de Curitiba, entre 2 e 5 anos, cujo peso e ou estatura estivessem até o percentil 30. Mediante processo de randomização determinaram-se 2 grupos denominados de Controle e Farelo, com 23 e 24 crianças respectivamente. Ambos receberam a dieta habitual da creche com 1115,4 ± 118 kcal e 28,8 ± 7,7 g de proteínas diárias; o Grupo Farelo recebeu uma suplementação de 5,8 ± 0,11 g de farelo de arroz, acrescentados às refeições do almoço e jantar, durante um período de 4 meses. O farelo foi submetido às análises físico-química, microbiológica e toxicológica. Obtiveram-se medidas do peso e estatura, assim como amostras de sangue (basal, mês 1 e mês 4), para a determinação do IGF-I, IGFBPs, albumina, magnésio, fósforo, cobre, zinco, hematócrito e volume corpuscular médio. Os dados foram submetidos à análise da variância. Observou-se um decréscimo da concentração sérica de magnésio no grupo Farelo em relação ao Controle (F<0,01), no primeiro mês de estudo. Por outro lado houve um aumento do zinco sérico no grupo que recebeu o farelo (F<0,05), verificado no quarto mês de estudo. Não se observaram diferenças significativas entre os grupos quanto ao peso, estatura, IGF-I, IGFBPs, albumina, fósforo, cobre, hematócrito ou volume corpuscular médio. Conclui-se que o farelo de arroz não foi capaz de interferir de forma significativa no estado nutricional deste grupo de crianças, embora tenha contribuído para o aumento da concentração sérica de zinco.Abstract: In Brazil, rice bran has been used as dietary supplement to hasten the nutricional recovery of children from lower socioeconomic classes. The aim of this study was to ascertain whether rice bran changes nutricional markers (IGF-I, IGFBP- 2, IGFBP-3) 47 children, ages 2-5 years, with height at or below 30th centile (NCHS) were ramdonly assigned to either Control or Bran group (23 and 24 children respectively). They attended a public nursery; their daily caloric and protein intake were 1115,4±118 kcal and 28,8±7,7 g respectively. Bran group aditionally received 5,8 ± 0,1 lg of rice bran twice a day. Physiochemical, toxicological and microbiological analysis were performed before its utilization. Height, weight, Cu, Zn, Mg, Pi, hematocrit, IGF-I, IGFBPs were obtained before and at 4 months.Data were treated by ANOVA. Bran group showed a decreased on Mg levels at the first month (F<0,01). On the other hand, there was a increase on zinc levels at the fourth month in this group (F<0,05). Height, weight, Cu, Mg, Pi, hematocrit, IGF-I and IGFBPs did not show significant difference between the groups along the study. In conclusion : our data suggest that rice bran supplementation does not hasten recovery of growth related indices in this group of children, although it promotes increment on Zn levels

909-P: Telemedicine Visits Attendance and Perception among Pediatric Patients with Type 1 Diabetes

COVID-19 pandemic has triggered the widespread adoption of Telemedicine (TM). As physical distancing measures were established, we rapidly shifted our outpatient appointments to TM. Here we show findings regarding patient TM perception and attendance. Patient demographics and attendance to in person and TM outpatient encounters from January to July 2020 were reviewed. A survey evaluating TM perceptions was distributed to patients and their families following an encounter between March and July 2020. Our diabetes clinic currently cares for 1504 unique patients with type 1 diabetes (T1D) with 46% being publicly insured. A total of 1,653 encounters including in person and TM were included in the analysis. TM visits became available in March 2020, with a total of 571 encounters by July 2020. There was a significantly lower number of completed TM encounters by publicly insured patients when compared with privately insured (p value=0.03523) and a threefold increase in no-shows and same day cancelations by the publicly insured group. Perception of TM was addressed with a survey completed by 40 patients. TM perception was positive with 86% of patients being very satisfied with the visit. TM encounter was thought to be the same as in person encounter by 60% and better than in person visit by 37% of patients. Reported benefits associated with TM included: overall time saved, no missed school day for the patient or workday for the parent, decreased childcare and transportation costs. In conclusion, although TM is perceived as positive by patients with T1D, low-income families showed lower TM visit attendance rate when compared to privately insured families. The COVID-19 pandemic has highlighted disparities related to access to and use of technology to improve diabetes care. More research is needed to identify the specific causes for the disparities. Patient centered approach to increase education and help navigate the processes required for utilizing TM technology may help decrease the health equity gaps. Disclosure C. Demeterco-berggren: None. M. Gottschalk: None. </jats:sec

942-P: Disparities in Telemedicine Use among Pediatric Patients with Type 1 and Type 2 Diabetes

Despite the increase in telehealth services in diabetes care during the COVID-pandemic, studies have found disparities in telemedicine (TM) use among patients. Our Diabetes Clinic currently cares for 1400 patients with type 1 diabetes (T1D) with 46% being publicly insured and for 375 patients with type 2 diabetes (T2D) , 88% being publicly insured. We have previously shown a significantly lower number of completed TM encounters between March and July 2020 by publicly insured patients when compared with privately insured and a threefold increase in no-shows and same day TM visit cancelations by the publicly insured group. Between January and March 2021 we surveyed families who had never attended a TM visit to better understand barriers to TM use. Of the 7patients who received care during this period, 162 (22.8%) had never attended a TM visit. Of the 39 surveyed patients, 84.6% had T1D and 15.4% had T2D. There were 46.2% who self-identified as Non-Hispanic White, 35.9% as Hispanic, 5.1% as Asian, 2.6% as Non-Hispanic Black, and 10.3% as Other. Additionally, 48.7% had public insurance, 23.1% had no EMR access and 15.4% did not speak English as their primary language. Out of patients with T1D, 63.6% used a CGM and 33.3% used an insulin pump. Reported reasons not to attend a TM visit included: preference for in-person care (43.6%) , not being offered a TM visit (17.9%) , technology issues (12.8%) , scheduling conflicts or forgetting about the appointment (17.9%) and 20.5% preferred not to provide a reason. In conclusion, more than half of our surveyed patients with diabetes who never attended a TM visit were from racial and ethnic minority groups. The COVID-pandemic has highlighted disparities related to access to and use of technology to improve diabetes care. Our results show the importance of ensuring all families are aware of TM options and receive support with TM technology. Further research into TM perception and adoption barriers should be conducted to prevent disparities in care and to close health equity gaps. Disclosure K.Chan: None. C.Demeterco-berggren: None. </jats:sec

SAT-057 A Novel IGSF1 Variant in a Boy with Central Hypothyroidism and Epiphyseal Dysplasia

Abstract Background: IGSF1 deficiency syndrome, also known as X-linked central hypothyroidism and testicular enlargement (CHTE) syndrome, is caused by mutations in the immunoglobulin superfamily, member 1 gene. Recently recognized as the most common genetic cause of isolated central hypothyroidism (CH), its cardinal features include CH and adult macroorchidism. We describe a boy with CH and epiphyseal dysplasia found to have a novel IGSF1 variant. Clinical case: A male with attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder, obsessive compulsive disorder and obesity was evaluated at age 9y for high total and LDL cholesterol and low T4 with normal TSH. He had short stature for family, high BMI, high sitting height ratio, and short arm span. Laboratory investigation revealed persistently mildly high total and LDL cholesterol, low T4, normal cortisol response to low-dose Cortrosyn stimulation, and normal IGF-1 and IGF-BP3. Bone age at 9y1m chronological age was 8y0m. Skeletal survey showed abnormal epiphyses of the femoral heads, knees, and humeral capitella suggesting primary epiphyseal dysplasia; he was referred to genetics. Growth improved after starting levothyroxine for CH. Multiple epiphyseal dysplasia gene panel (with reflex to clinical exome) did not find any variants known to be pathogenic for his condition. He was found to be a carrier of autosomal recessive Bartter syndrome. Heterozygous variants of unknown significance were found in RMRP, FGFR1, CDT1 and APOB. Whole exome sequencing showed hemizygosity for the p.Q743X (c.2227C&amp;gt;T) variant in IGSF1. Discussion: The p.Q743X IGSF1 variant has not been reported in the literature and is not present in population databases. It is predicted to cause loss of normal protein function and is considered pathogenic. CH is found in all males with IGSF1 deficiency syndrome. Macroorchidism, another defining feature, develops in adulthood; age of testicular growth onset is normal, but pubertal testosterone rise is delayed. Our patient remains prepubertal at age 11y. Other features sometimes present include hypoprolactinemia (which was found in this child) and transient partial GHD (not seen in this case). Overweight and the metabolic syndrome are common; this child’s cholesterol abnormalities may be due to weight and/or APOB variant found on genetic testing. ADHD has been seen in some patients with this syndrome; this child also has extensive psychiatric/behavioral problems, which have not been described. The skeletal findings in this case have not been previously noted in IGSF1 deficiency syndrome; whether this is a rare feature of IGSF1 deficiency syndrome or a separate entity is unclear. This case adds to the growing list of disease-causing variants in IGSF1. Endocrinologists should consider IGSF1 deficiency syndrome when diagnosing isolated CH in boys, as the characteristic macroorchidism is not present in childhood.</jats:p

Thyrotoxic, hypokalemic periodic paralysis (THPP) in adolescents

AbstractPeriodic paralysis associated with hyperthyroidism and hypokalemia is an uncommon disorder reported primarily in Asian males and rarely in children. We report three Hispanic adolescent males who were seen with Graves’ disease (GD) and THPP.The method used was chart review.Two of these boys presented with episodes of paralysis and were diagnosed with GD. The third was initially seen with hyperthyroidism and developed weakness and paralysis when his disease progressed because of therapeutic noncompliance. Hypokalemia was documented in two of the three patients with the third not seen during paralysis. Intravenous KTHPP is considered uncommon except in Asian males and rare in childhood and adolescence. Its occurrence in these three Hispanic boys suggests that it may occur more frequently in the young and in the USA than has been suspected, especially with the changing national demographics. We believe that our experience should raise the awareness of THPP among pediatric care providers.</jats:p

Unawareness of the Effects of Soy Intake on the Management of Congenital Hypothyroidism

It has been established that soy products can interfere with thyroid hormone absorption resulting in continued hypothyroidism in individuals receiving recommended levothyroxine replacement. It has also been reported that achievement of euthyroidism in hypothyroid patients using soy products requires increased doses of levothyroxine. We have observed 2 patients with congenital hypothyroidism who continued to manifest clinical hypothyroidism while receiving recommended doses of hormone and ingesting soy products. The first patient was diagnosed by newborn screening (thyroid-stimulating hormone [TSH] =169 µIU/mL) and treated with 50 µg of levothyroxine since 6 days of age while simultaneously starting soy formula. At 3 weeks of age, she was clinically and biochemically hypothyroid (thyroxine = 4.0 µg/dL, TSH = 216 µIU/mL). We stopped her soy formula and decreased her levothyroxine dose. Three weeks later signs of hypothyroidism were resolving, and, by 10 weeks of age, she was clinically and biochemically euthyroid. Another patient was diagnosed by newborn screening, received levothyroxine, and did well. She was lost to us for 2 years. During this interval she began consuming soy milk and became profoundly hypothyroid (free thyroxine &amp;lt;0.4 ng/dL, TSH = 248 µIU/mL), even though the primary care physician had increased her levothyroxine dose to 112 µg/day. She was switched to cow milk, and her thyroid function slowly normalized with decreasing doses of levothyroxine. These 2 patients reinforce the importance of remembering that soy products interfere with levothyroxine absorption and can endanger infants and young children with congenital hypothyroidism who are at risk for developmental and growth delay.</jats:p