Variable incidence of ketoacidosis in youth with type 1 diabetes onset during Covid-19 pandemic peaks in France.
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SUBMITTER: Delpeut J
PROVIDER: S-EPMC8746844 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ImportanceThe COVID-19 pandemic has had considerable mental health consequences for children and adolescents, including the exacerbation of previously diagnosed eating disorders. Whether the pandemic is a factor associated with the concomitant increase in new-onset anorexia nervosa or atypical anorexia nervosa remains unknown.ObjectiveTo assess the incidence and severity of newly diagnosed anorexia nervosa or atypical anorexia nervosa in a national sample of youth before and during the first wave of the COVID-19 pandemic.Design, setting, and participantsThis repeated cross-sectional study analyzed new eating disorder assessments that were conducted at 6 pediatric tertiary-care hospitals in Canada between January 1, 2015, and November 30, 2020. Patients aged 9 to 18 years with a new anorexia nervosa or atypical anorexia nervosa diagnosis at the index assessment were included.ExposuresCOVID-19-associated public health confinement measures during the first wave of the pandemic (March 1 to November 30, 2020).Main outcomes and measuresPrimary outcomes were the incidence and hospitalization rates within 7 days of de novo anorexia nervosa or atypical anorexia nervosa diagnosis. Event rate trends during the first wave were compared with trends in the 5-year prepandemic period (January 1, 2015, to February 28, 2020) using an interrupted time series with linear regression models. Demographic and clinical variables were compared using a χ2 test for categorical data and t tests for continuous data.ResultsOverall, 1883 children and adolescents with newly diagnosed anorexia nervosa or atypical anorexia nervosa (median [IQR] age, 15.9 [13.8-16.9] years; 1713 female patients [91.0%]) were included. Prepandemic anorexia nervosa or atypical anorexia nervosa diagnoses were stable over time (mean [SD], 24.5 [1.6] cases per month; β coefficient, 0.043; P = .33). New diagnoses increased during the first wave of the pandemic to a mean (SD) of 40.6 (20.1) cases per month with a steep upward trend (β coefficient, 5.97; P < .001). Similarly, hospitalizations for newly diagnosed patients increased from a mean (SD) of 7.5 (2.8) to 20.0 (9.8) cases per month, with a significant increase in linear trend (β coefficient, -0.008 vs 3.23; P < .001). These trends were more pronounced in Canadian provinces with higher rates of COVID-19 infections. Markers of disease severity were worse among patients who were diagnosed during the first wave rather than before the pandemic, including more rapid progression (mean [SD], 7.0 [4.2] months vs 9.8 [7.4] months; P < .001), greater mean (SD) weight loss (19.2% [9.4%] vs 17.5% [9.6%]; P = .01), and more profound bradycardia (mean [SD] heart rate, 57 [15.8] beats per minute vs 63 [15.9] beats per minute; P < .001).Conclusions and relevanceThis cross-sectional study found a higher number of new diagnoses of and hospitalizations for anorexia nervosa or atypical anorexia nervosa in children and adolescents during the first wave of the COVID-19 pandemic in Canada. Research is needed to better understand the drivers and prognosis for these patients and to prepare for their mental health needs in the event of future pandemics or prolonged social isolation.
| S-EPMC8652595 | biostudies-literature
Project description:We assessed the incidence of diabetic ketoacidosis (DKA) in children aged <15 years with newly diagnosed type 1 diabetes mellitus (T1DM) in the Auckland Region (New Zealand) in 1999-2013, in a retrospective review of a complete regional cohort. DKA and its severity were classified according to ISPAD 2014 guidelines. Of 730 children presenting with new-onset T1DM over the 15-year time period, 195 cases had DKA of any severity (27%). There was no change in the incidence of DKA or the proportion of children with severe DKA at presentation. The incidence of DKA among children aged <2.0 years (n = 40) was 53% compared to 25% for those aged 2-14 years (n = 690; p = 0.005). In children aged 2-14 years, increasing age at diagnosis was associated with greater likelihood of DKA at presentation (p = 0.025), with the odds of DKA increasing 1.06 times with each year increase in age. Non-Europeans were more likely to present in DKA than New Zealand Europeans (OR 1.52; p = 0.048). Despite a consistent secular trend of increasing incidence of T1DM, there was no reduction in the incidence of DKA in new-onset T1DM in the Auckland Region over time. Thus, it is important to explore ways to reduce DKA risk.
| S-EPMC4650806 | biostudies-other
Project description:Mutations in the human glucokinase (GK) gene are thought to cause maturity-onset diabetes of youth (MODY) by leading to the production of enzymes with reduced catalytic activities and increased glucose Km values. However, in some cases the diabetic phenotype is more severe than might be predicted from these apparent kinetic effects alone. To determine whether these mutations might also effect other characteristics of the enzyme, nine MODY-associated mutants were expressed as fusion proteins with Schistosoma japonicum glutathione S-transferase (GST) and compared with three wild-type human GK isoforms that were also expressed in the same manner. Three GST-GK isoforms (liver 1, liver 2 and islet) were kinetically indistinguishable from each other and from purified rat liver GK. Noteworthy is a glucose-induced fit effect for the interaction of trinitrophenyl (TNP)-ATP with GST-GK, whereby glucose significantly increased the affinity of TNP-ATP binding to GST-GK without changing the stoichiometry of binding. The nine MODY-associated mutations studied either showed diminished catalytic activity, substrate affinities, allosteric regulation, or stability of the fusion enzyme. We conclude that: (1) Gly261 and Lys414 are important for ATP binding; (2) Val203 may be essential for a glucose-induced fit effect; and (3) the stability of fusion protein may be significantly reduced when Glu300 is replaced by Lys. These results suggest that, in addition to effects on the Km and Vmax. of GK, a decrease in the ATP-binding affinity or stability of the mutated enzyme may also contribute to a reduction of GK activity in individuals with GK-MODY. In the B-cell this would have the effect of blunting glucose-stimulated insulin release, thereby contributing to the diabetic phenotype.
| S-EPMC1135815 | biostudies-other
Project description:PurposeWe hypothesized that the COVID-19 pandemic may have modified dispensing of colonoscopy preparations, a proxy for the number of colonoscopies performed. We therefore studied changes in dispensing of colonoscopy preparations during the pandemic in France.MethodsUsing the French national health data system, we identified colonoscopy preparations dispensed from 2018 to 2020. The expected 2020 dispensations were estimated from 2018 to 2019 dispensations.ResultsDispensing of colonoscopy preparations decreased markedly during the eight weeks of national lockdown: 83,045 colonoscopy preparations were dispensed, i.e., 181,826 (68.6%) fewer than expected. After lockdown, dispensing of colonoscopy preparations gradually returned to expected numbers. Overall, this represents an estimated decrease of roughly 250,000 colonoscopy preparations during the six-month period following onset of the pandemic. This shortfall in the dispensing of colonoscopy preparations was of the same order of magnitude in people under or over 50 years of age, in men and women, and in those in the highest and the lowest quintiles of the deprivation index.ConclusionIn conclusion, roughly 250,000 fewer colonoscopy preparations were dispensed during the first six months of the COVID-19 pandemic in France. Deleterious consequences on morbidity and mortality related to gastroenterological diseases, such as colorectal cancer, are to be feared.
| S-EPMC7787877 | biostudies-literature
Project description:BackgroundThe prevalence of type 2 diabetes in youth is increasing, but little is known regarding the occurrence of related complications as these youths transition to adulthood.MethodsWe previously conducted a multicenter clinical trial (from 2004 to 2011) to evaluate the effects of one of three treatments (metformin, metformin plus rosiglitazone, or metformin plus an intensive lifestyle intervention) on the time to loss of glycemic control in participants who had onset of type 2 diabetes in youth. After completion of the trial, participants were transitioned to metformin with or without insulin and were enrolled in an observational follow-up study (performed from 2011 to 2020), which was conducted in two phases; the results of this follow-up study are reported here. Assessments for diabetic kidney disease, hypertension, dyslipidemia, and nerve disease were performed annually, and assessments for retinal disease were performed twice. Complications related to diabetes identified outside the study were confirmed and adjudicated.ResultsAt the end of the second phase of the follow-up study (January 2020), the mean (±SD) age of the 500 participants who were included in the analyses was 26.4±2.8 years, and the mean time since the diagnosis of diabetes was 13.3±1.8 years. The cumulative incidence of hypertension was 67.5%, the incidence of dyslipidemia was 51.6%, the incidence of diabetic kidney disease was 54.8%, and the incidence of nerve disease was 32.4%. The prevalence of retinal disease, including more advanced stages, was 13.7% in the period from 2010 to 2011 and 51.0% in the period from 2017 to 2018. At least one complication occurred in 60.1% of the participants, and at least two complications occurred in 28.4%. Risk factors for the development of complications included minority race or ethnic group, hyperglycemia, hypertension, and dyslipidemia. No adverse events were recorded during follow-up.ConclusionsAmong participants who had onset of type 2 diabetes in youth, the risk of complications, including microvascular complications, increased steadily over time and affected most participants by the time of young adulthood. Complications were more common among participants of minority race and ethnic group and among those with hyperglycemia, hypertension, and dyslipidemia. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; ClinicalTrials.gov numbers, NCT01364350 and NCT02310724.).
| S-EPMC8697255 | biostudies-literature
Project description:Single cell RNA-sequencing analysis allows for a more complete cell-by-cell analysis of the effects of SGLT2 inhibitors on the kidneys of patients with youth onset type 2 diabetes.
2023-01-19 | GSE220939 | GEO
Project description:Severe hypoglycemia (SH) and diabetic ketoacidosis (DKA) are common serious acute complications of type 1 diabetes (T1D). The aim of this study was to determine the frequency of SH and DKA and identify factors related to their occurrence in the T1D Exchange pediatric and young adult cohort.The analysis included 13?487 participants in the T1D Exchange clinic registry aged 2 to <26?yr with T1D ?2?yr. Separate logistic regression models were used to evaluate the association of baseline demographic and clinical factors with the occurrence of SH or DKA in the prior 12?months.Non-White race, no private health insurance, and lower household income were associated with higher frequencies of both SH and DKA (p?<?0.001). SH frequency was highest in children <6?yr old (p?=?0.005), but across the age range, SH was not associated with hemoglobin A1c (HbA1c) levels after controlling for other factors (p?=?0.72). DKA frequency was highest in adolescents (p?<?0.001) and associated with higher HbA1c (p?<?0.001).Our data show that poor glycemic control increases the risk of DKA but does not protect against SH in youth and young adults with type 1 diabetes. The high frequencies of SH and DKA observed in disadvantaged minorities with T1D highlight the need for targeted interventions and new treatment paradigms for patients in these high risk groups.
| S-EPMC4100244 | biostudies-literature
Project description: Not available
| S-EPMC8654887 | biostudies-literature
Project description:Purpose of reviewTo provide an update on knowledge the role of genetics in youth-onset type 2 diabetes (T2D).Recent findingsThe prevalence in youth of T2D, once thought to be exclusively a disease of adults, has increased by over 35% since 2001. Youth with T2D tend to have higher rates of complications, more aggressive disease, with more rapid loss of beta-cell function and a less favorable response to treatment than adults. Obesity is the most important risk factor for T2D, and the rise in childhood overweight and obesity appears responsible for the dramatic increase in T2D in youth. However, some obese children do not develop T2D, consistent with genetic differences in susceptibility to the disease in the setting of obesity and insulin resistance, currently far less well characterized in youth than in adults. Recent studies have begun to show associations of several established adult T2D genetic risk variants with youth-onset T2D and related glycemic quantitative traits, including the strongest known cross-population T2D genetic contributor TCF7L2. Maturity-onset diabetes of the young (MODY), a diabetes subtype distinct from type 1 diabetes (T1D) and T2D, is now known to result from a highly penetrant gene mutation in one of several genes. MODY has been shown to account for or contribute to at least 4.5% of clinically diagnosed T2D, even among those who are overweight or obese, impacting treatment decisions. The recently formed ProDiGY (Progress in Diabetes Genetics in Youth) Consortium is using genome-wide association studies and whole exome sequencing to understand the genetic architecture of T2D in youth, including how it differs from that of adults. The limited amount of research conducted to date on the genetics of youth-onset T2D, which tends to be a more aggressive disease than adult T2D, suggests some overlap with genes involved in adult T2D and a sizeable influence of highly penetrant monogenic diabetes variants. The ProDiGY Consortium is expected to provide a more comprehensive understanding of youth T2D genetics.
| S-EPMC6051541 | biostudies-literature
Project description:ObjectiveIncidence of youth-onset diabetes in India has not been well described. Comparison of incidence, across diabetes registries, has the potential to inform hypotheses for risk factors. We sought to compare the incidence of diabetes in the U.S.-based registry of youth onset diabetes (SEARCH) to the Registry of Diabetes with Young Age at Onset (YDR-Chennai and New Delhi regions) in India.MethodsWe harmonized data from both SEARCH and YDR to the Observational Medical Outcomes Partnership (OMOP) Common Data Model. Data were from youth registered with incident diabetes (2006-2012). Denominators were from census and membership data. We calculated diabetes incidence by averaging the total cases across the entire follow-up period and dividing this by the estimated census population corresponding to the source population for case ascertainment. Incidence was calculated for each of the registries and compared by type and within age and sex categories using a 2-sided, skew-corrected inverted score test.ResultsIncidence of type 1 was higher in SEARCH (21.2 cases/100 000 [95% CI: 19.9, 22.5]) than YDR (4.9 cases/100 000 [95% CI: 4.3, 5.6]). Incidence of type 2 diabetes was also higher in SEARCH (5.9 cases/100 000 [95% CI: 5.3, 6.6] in SEARCH vs 0.5/cases/100 000 [95% CI: 0.3, 0.7] in YDR). The age distribution of incident type 1 diabetes cases was similar across registries, whereas type 2 diabetes incidence was higher at an earlier age in SEARCH. Sex differences existed in SEARCH only, with a higher rate of type 2 diabetes among females.ConclusionThe incidence of youth-onset type 1 and 2 diabetes was significantly different between registries. Additional data are needed to elucidate whether the differences observed represent diagnostic delay, differences in genetic susceptibility, or differences in distribution of risk factors.
| S-EPMC7748376 | biostudies-literature