The conserved oligomeric Golgi (COG) complex is involved in intracellular vesicular transport, and is composed of eight subunits distributed in two lobes, lobe A (COG1-4) and lobe B (COG5-8). We describe fourteen individuals with Saul-Wilson syndrome, a rare form of primordial dwarfism with characteristic facial and radiographic features. All affected subjects harbored heterozygous de novo variants in COG4, giving rise to the same recurrent amino acid substitution (p.Gly516Arg). Affected individuals' fibroblasts, whose COG4 mRNA and protein were not decreased, exhibited delayed anterograde vesicular trafficking from the ER to the Golgi and accelerated retrograde vesicular recycling from the Golgi to the ER. This altered steady-state equilibrium led to a decrease in Golgi volume, as well as morphologic abnormalities with collapse of the Golgi stacks. Despite these abnormalities of the Golgi apparatus, protein glycosylation in sera and fibroblasts from affected subjects was not notably altered, but decorin, a proteoglycan secreted into the extracellular matrix, showed altered Golgi-dependent glycosylation. In summary, we define a specific heterozygous COG4 substitution as the molecular basis of Saul-Wilson syndrome, a rare skeletal dysplasia distinct from biallelic COG4-CDG.
OBJECTIVE Insulin delivery methods, glucose-monitoring modalities, and related outcomes were examined in a large, international, diverse cohort of children and adolescents with type 1 diabetes from the Better Control in Pediatric and Adolescent Diabetes: Working to Create Centers of Reference (SWEET) -Registry. RESEARCH DESIGN AND METHODS Participants with type 1 diabetes of ≥1 year, aged ≤18 years, and who had documented pump or sensor usage during the period August 2017–July 2019 were stratified into four categories: injections–no sensor (referent); injections + sensor; pump–no sensor; and pump + sensor. HbA1c and proportion of patients with diabetic ketoacidosis (DKA) or severe hypoglycemia (SH) were analyzed; linear and logistic regression models adjusted for demographics, region, and gross domestic product per capita were applied. RESULTS Data of 25,654 participants were analyzed. The proportions of participants (adjusted HbA1c data) by study group were as follows: injections–no sensor group, 37.44% (8.72; 95% CI 8.68–8.75); injections + sensor group, 14.98% (8.30; 95% CI 8.25–8.35); pump–no sensor group, 17.22% (8.07; 95% CI 8.03–8.12); and pump + sensor group, 30.35% (7.81; 95% CI 7.77–7.84). HbA1c was lower in all categories of participants who used a pump and/or sensor compared with the injections–no sensor treatment method (P < 0.001). The proportion of DKA episodes was lower in participants in the pump + sensor (1.98%; 95% CI 1.64–2.48; P < 0.001) and the pump–no sensor (2.02%; 95% CI 1.64–2.48; P < 0.05) groups when compared with those in the injections–no sensor group (2.91%; 95% CI 2.59–3.31). The proportion of participants experiencing SH was lower in pump–no sensor group (1.10%; 95% CI 0.85–1.43; P < 0.001) but higher in the injections + sensor group (4.25%; 95% CI 3.65–4.95; P < 0.001) compared with the injections–no sensor group (2.35%; 95% CI 2.04–2.71). CONCLUSIONS Lower HbA1c and fewer DKA episodes were observed in participants using either a pump or continuous glucose monitoring (CGM) or both. Pump use was associated with a lower rate of SH. Across SWEET centers, use of pumps and CGM is increasing. The concomitant use of pump and CGM was associated with an additive benefit.
OBJECTIVE <p>This study aims to examine insulin delivery methods, glucose monitoring modalities and related outcomes in a large, international, diverse cohort of children and adolescents with type 1 diabetes from the SWEET-Registry<sub></sub></p> <p> </p> <p>RESEARCH DESIGN AND METHODS</p> <p>Participants with type 1 diabetes of <u>></u>1 year of duration, aged ≤18y and documented pump/sensor usage during the period August 2017-July 2019 were stratified into four categories: injections-no sensor (reference); injections+sensor; pump-no sensor; pump+sensor. HbA<sub>1c</sub> and proportion of patients with DKA or SH were analyzed; linear and logistic regression models adjusted for demographics, region and gross-domestic-product (GDP)-per capita were applied.</p> <p> </p> <p>RESULTS</p> <p>Data of 25,654 subjects were analyzed. Injections-no sensor: 37.44% [adjusted-HbA<sub>1c</sub> 8.72 (95%CI 8.68-8.75)]; injections+sensor: 14.98% [adjusted-HbA<sub>1c</sub> 8.30 (8.25-8.35)]; pump-no sensor: 17.22% [adjusted-HbA<sub>1c</sub> 8.07 (8.03-8.12)]; pump+sensor: 30.35% [adjusted-HbA<sub>1c</sub> 7.81 (7.77-7.84)]. HbA<sub>1c</sub> was lower in all categories of subjects using pump and/or sensor compared to injections-no sensor treatment method (p<0.001, respectively). Proportion of DKA episodes was lower in subjects with pump+sensor [1.98 (1.64-2.48); p<0.001] and pump-no sensor [2.02 (1.64-2.48); p<0.05)] when compared to injections-no sensor [2.91 (2.59-3.31)]. Proportion of SH was lower in pump-no sensor [1.10 (0.85-1.43); p<0.001] but higher in the injections+sensor [4.25 (3.65-4.95); p<0.001] compared to injections-no sensor [2.35 (2.04-2.71)].</p> <p> </p> <p>CONCLUSIONS</p> Lower HbA<sub>1c</sub> and fewer DKA episodes were observed in subjects using either a pump, CGM or both. Pump use was associated with lower rate of SH. Across SWEET centers, use of pumps and CGM is increasing. The concomitant use of pump and CGM was found to be associated with an additive benefit.
OBJECTIVE To analyze whether the coronavirus disease 2019 (COVID-19) pandemic increased the number of cases or impacted seasonality of new-onset type 1 diabetes (T1D) in large pediatric diabetes centers globally. RESEARCH DESIGN AND METHODS We analyzed data on 17,280 cases of T1D diagnosed during 2018–2021 from 92 worldwide centers participating in the SWEET registry using hierarchic linear regression models. RESULTS The average number of new-onset T1D cases per center adjusted for the total number of patients treated at the center per year and stratified by age-groups increased from 11.2 (95% CI 10.1–12.2) in 2018 to 21.7 (20.6–22.8) in 2021 for the youngest age-group, <6 years; from 13.1 (12.2–14.0) in 2018 to 26.7 (25.7–27.7) in 2021 for children ages 6 to <12 years; and from 12.2 (11.5–12.9) to 24.7 (24.0–25.5) for adolescents ages 12–18 years (all P < 0.001). These increases remained within the expected increase with the 95% CI of the regression line. However, in Europe and North America following the lockdown early in 2020, the typical seasonality of more cases during winter season was delayed, with a peak during the summer and autumn months. While the seasonal pattern in Europe returned to prepandemic times in 2021, this was not the case in North America. Compared with 2018–2019 (HbA1c 7.7%), higher average HbA1c levels (2020, 8.1%; 2021, 8.6%; P < 0.001) were present within the first year of T1D during the pandemic. CONCLUSIONS The slope of the rise in pediatric new-onset T1D in SWEET centers remained unchanged during the COVID-19 pandemic, but a change in the seasonality at onset became apparent.
BackgroundResearch studies show conflicting results regarding the association between menarche and body weight. The purpose of the present study was to investigate if anthropometric indicators of body composition, body mass index (BMI), waist circumference (WC), triceps (TSF) and subscapular skinfold (SSF) thicknesses, were differentially associated with age at menarche in Norwegian girls.MethodsThe association between menarche and BMI, WC, TSF and SSF was investigated in 1481 girls aged 8–15.5 years, and in a subgroup of 181 girls with menarche during the 12 months prior to examination. Anthropometric measures were categorized as low (< −1SDS), average (−1 ≤ SDS ≤ +1) or high (> 1SDS), and menarche according to this classification was analysed with Kaplan-Meier curves and unadjusted and adjusted Cox regression.ResultsThe median age at menarche in the total sample was 13.1 years. In the unadjusted models, low categories of all traits were associated with later menarche, and high categories with earlier menarche. When adjusted for other covariates, earlier menarche was only related with a high BMI (Hazard Ratio 1.41, 95% confidence interval (CI) 1.07, 1.85), and later menarche with a low BMI (HR 0.53, 95%CI 0.38, 0.75) and low SSF (HR 0.54, 95%CI 0.39, 0.75). In girls with recent menarche, early menarche was significantly associated with a high BMI in the final model (HR 1.79, 95%CI 1.23, 2.62).ConclusionsThe timing of menarche was associated with the BMI, WC, TSF and SSF, but more strongly so with the BMI. These associations may be related to a common tempo of growth, as the mean age at menarche has remained stable during the last decades during a time period while the prevalence of overweight and obesity has increased significantly.
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