INTRODUCTION: The aim of the study was to assess the differences in key parameters of type 1 diabetes (T1D) control associated with treatment and monitoring modalities including newly introduced hybrid closed-loop (HCL) algorithm in children and adolescents with T1D (CwD) using the data from the population-wide pediatric diabetes registry ČENDA. METHODS: CwD younger than 19 years with T1D duration >1 year were included and divided according to the treatment modality and type of CGM used: multiple daily injection (MDI), insulin pump without (CSII) and with HCL function, intermittently scanned continuous glucose monitoring (isCGM), real-time CGM (rtCGM), and intermittent or no CGM (noCGM). HbA1c, times in glycemic ranges, and glucose risk index (GRI) were compared between the groups. RESULTS: Data of a total of 3,251 children (mean age 13.4 ± 3.8 years) were analyzed. 2,187 (67.3%) were treated with MDI, 1,064 (32.7%) with insulin pump, 585/1,064 (55%) with HCL. The HCL users achieved the highest median TIR 75.4% (IQR 6.3) and lowest GRI 29.1 (7.8), both p < 0.001 compared to other groups, followed by MDI rtCGM and CSII groups with TIR 68.8% (IQR 9.0) and 69.0% (7.5), GRI 38.8 (12.5) and 40.1 (8.5), respectively (nonsignificant to each other). These three groups did not significantly differ in their HbA1c medians (51.8 [IQR 4.5], 50.7 [4.5], and 52.7 [5.7] mmol/mol, respectively). NoCGM groups had the highest HbA1c and GRI and lowest TIR regardless of the treatment modality. CONCLUSION: This population-based study shows that the HCL technology is superior to other treatment modalities in CGM-derived parameters and should be considered as a treatment of choice in all CwD fulfilling the indication criteria.
- MeSH
- diabetes mellitus 1. typu * farmakoterapie MeSH
- dítě MeSH
- glykovaný hemoglobin MeSH
- hypoglykemika terapeutické užití MeSH
- inzulin terapeutické užití MeSH
- krevní glukóza MeSH
- lidé MeSH
- mladiství MeSH
- regulace glykemie MeSH
- selfmonitoring glykemie MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- Publikační typ
- časopisecké články MeSH
INTRODUCTION: Among children born small for gestational age, 10-15% fail to catch up and remain short (SGA-SS). The underlying mechanisms are mostly unknown. We aimed to decipher genetic aetiologies of SGA-SS within a large single-centre cohort. METHODS: Out of 820 patients treated with growth hormone (GH), 256 were classified as SGA-SS (birth length and/or birth weight <-2 SD for gestational age and life-minimum height <-2.5 SD). Those with the DNA triplet available (child and both parents) were included in the study (176/256). Targeted testing (karyotype/FISH/MLPA/specific Sanger sequencing) was performed if a specific genetic disorder was clinically suggestive. All remaining patients underwent MS-MLPA to identify Silver-Russell syndrome, and those with unknown genetic aetiology were subsequently examined using whole-exome sequencing or targeted panel of 398 growth-related genes. Genetic variants were classified using ACMG guidelines. RESULTS: The genetic aetiology was elucidated in 74/176 (42%) children. Of these, 12/74 (16%) had pathogenic or likely pathogenic (P/LP) gene variants affecting pituitary development (LHX4, OTX2, PROKR2, PTCH1, POU1F1), the GH-IGF-1 or IGF-2 axis (GHSR, IGFALS, IGF1R, STAT3, HMGA2), 2/74 (3%) the thyroid axis (TRHR, THRA), 17/74 (23%) the cartilaginous matrix (ACAN, various collagens, FLNB, MATN3), and 7/74 (9%) the paracrine chondrocyte regulation (FGFR3, FGFR2, NPR2). In 12/74 (16%), we revealed P/LP affecting fundamental intracellular/intranuclear processes (CDC42, KMT2D, LMNA, NSD1, PTPN11, SRCAP, SON, SOS1, SOX9, TLK2). SHOX deficiency was found in 7/74 (9%), Silver-Russell syndrome in 12/74 (16%) (11p15, UPD7), and miscellaneous chromosomal aberrations in 5/74 (7%) children. CONCLUSIONS: The high diagnostic yield sheds a new light on the genetic landscape of SGA-SS, with a central role for the growth plate with substantial contributions from the GH-IGF-1 and thyroid axes and intracellular regulation and signalling.
- MeSH
- dítě MeSH
- gestační stáří MeSH
- hypotrofický novorozenec MeSH
- insulinu podobný růstový faktor I MeSH
- lidé MeSH
- lidský růstový hormon * genetika MeSH
- nanismus * MeSH
- novorozenec MeSH
- poruchy růstu genetika diagnóza MeSH
- protein SHOX MeSH
- Silverův-Russellův syndrom * genetika MeSH
- tělesná výška genetika MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- novorozenec MeSH
- Publikační typ
- časopisecké články MeSH
AIMS: To evaluate glucose control non-inferiority and time benefits of telemedicine follow-up in children with type 1 diabetes (CwD). METHODS: In a single-center 9-month-long randomized controlled study (clinicaltrials.gov NCT05484427), 50 children were randomized to either telemedicine group (TG) followed-up distantly by e-mail, or to face-to-face group (FFG) attending standard personal visits. The primary endpoint was non-inferiority of HbA1c at final visit (level of non-inferiority was set at 5 mmol/mol). The secondary endpoints were subcutaneous glucose monitoring parameters and time consumption from both study subjects' and the physicians' point of view. RESULTS: Non-inferiority of HbA1c in the TG was proven (mean HbA1C 45.8 ± 7.3 [TG] vs. 50.0 ± 12.6 [FFG] mmol/mol, 6.3 vs. 6.7 % DCCT, p = 0.17; between groups HbA1C difference 95 % CI -10.2 to 1.9 mmol/mol). Telemedicine saved time for participants (mean visit duration [MVD] 50 [TG] vs. 247 min [FFG], p < 0.001). There were no other differences between groups neither in CGM parameters nor physician's time consumption (MVD 19 [TG] vs. 20 min [FFG], p = 0.58). CONCLUSIONS: Nine-month telemedicine follow-up of the children with well-controlled T1D is not inferior to standard face-to-face visits. Telemedicine visits saved time for the participants but not for their diabetologists.
OBJECTIVE: To compare parameters of glycemic control among three types of hybrid closed loop (HCL) systems in children with T1D (CwD) using population-wide data from the national pediatric diabetes registry ČENDA. METHODS: CwD aged <19 years treated with Medtronic MiniMed 780G (780G), Tandem t:slim X2 (Control-IQ) or do-it-yourself AndroidAPS (AAPS) systems for >12 months and monitored by CGM >70% of the time were included. HbA1c, times in glycemic ranges, and Glycemia Risk Index (GRI) were used for cross-sectional comparison between the HCL systems. RESULTS: Data from 512 CwD were analyzed. 780G, Control-IQ and AAPS were used by 217 (42.4%), 211 (41.2%), and 84 (16.4%) CwD, respectively. The lowest HbA1c value was observed in the AAPS group (44 mmol/mol; IQR 8.0, p<0.0001 vs any other group), followed by Control-IQ and 780G groups (48 (IQR 11) and 52 (IQR 10) mmol/mol, respectively). All of the systems met the recommended criteria for time in range (78% in AAPS, 76% in 780G, and 75% in Control-IQ users). CwD using AAPS spent significantly more time in hypoglycemia (5% vs 2% in 780G and 3% in Control-IQ) and scored the highest GRI (32, IQR 17). The lowest GRI (27, IQR 15) was seen in 780G users. CONCLUSION: Although all HCL systems proved effective in maintaining recommended long-term glycemic control, we observed differences that illustrate strengths and weaknesses of particular systems. Our findings could help in individualizing the choice of HCL systems.
- MeSH
- diabetes mellitus 1. typu * farmakoterapie MeSH
- dítě MeSH
- glykovaný hemoglobin MeSH
- hypoglykemie * chemicky indukované epidemiologie MeSH
- inzulin terapeutické užití MeSH
- inzulinové infuzní systémy MeSH
- krevní glukóza MeSH
- lidé MeSH
- průřezové studie MeSH
- registrace MeSH
- selfmonitoring glykemie MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Familial short stature (FSS) describes vertically transmitted growth disorders. Traditionally, polygenic inheritance is presumed, but monogenic inheritance seems to occur more frequently than expected. Clinical predictors of monogenic FSS have not been elucidated. The aim of the study was to identify the monogenic etiology and its clinical predictors in FSS children. Of 747 patients treated with growth hormone (GH) in our center, 95 with FSS met the inclusion criteria (pretreatment height ≤-2 SD in child and his/her shorter parent); secondary short stature and Turner/Prader-Willi syndrome were excluded criteria. Genetic etiology was known in 11/95 children before the study, remaining 84 were examined by next-generation sequencing. The results were evaluated by American College of Medical Genetics and Genomics (ACMG) guidelines. Nonparametric tests evaluated differences between monogenic and non-monogenic FSS, an ROC curve estimated quantitative cutoffs for the predictors. Monogenic FSS was confirmed in 36/95 (38%) children. Of these, 29 (81%) carried a causative genetic variant affecting the growth plate, 4 (11%) a variant affecting GH-insulin-like growth factor 1 (IGF1) axis and 3 (8%) a variant in miscellaneous genes. Lower shorter parent's height (P = 0.015) and less delayed bone age (BA) before GH treatment (P = 0.026) predicted monogenic FSS. In children with BA delayed less than 0.4 years and with shorter parent's heights ≤-2.4 SD, monogenic FSS was revealed in 13/16 (81%) cases. To conclude, in FSS children treated with GH, a monogenic etiology is frequent, and gene variants affecting the growth plate are the most common. Shorter parent's height and BA are clinical predictors of monogenic FSS.
- Publikační typ
- časopisecké články MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
Objective: We evaluated the safety and feasibility of open-source automated insulin delivery AndroidAPS in adolescents and young adults with type 1 diabetes (T1D) and compared its efficacy in three different scenarios: hybrid closed loop (HCL) with meal boluses, meal announcement only (MA), and full closed loop (FCL). Research Design and Methods: In an open-label, prospective, randomized crossover trial (clinicaltrials.gov NCT04835350), 16 adolescents with T1D (10 females) with mean age of 17 years (range 15-20), glycated hemoglobin 56 mmol/mol (range 43-75), and mean duration of diabetes 5.9 years (9-15) underwent three distinct 3-day periods of camp living, comparing the above-mentioned scenarios of AndroidAPS. We used modified and locked version of AndroidAPS 3.1.03, which was called Pancreas4ALL for study purposes. The order of MA and FCL periods was assigned randomly. The primary endpoints were feasibility and safety of the system represented by percentage of time of glucose control by the system and time in hypoglycemia below 3 mmol/L. Results: The glycemia was controlled by the system 95% time of the study and the proportion of time below 3 mmol/L did not exceed 1% over the whole study period (0.72%). The HCL scenario reached significantly higher percentage of time below 3 mmol/L (HCL 1.05% vs. MA 0.0% vs. FCL 0.0%; P = 0.05) compared to other scenarios. No difference was observed among the scenarios in the percentage of time between 3.9 and 10 mmol/L (HCL 83.3% vs. MA 79.85% vs. FCL 81.03%, P = 0.58) corresponding to mean glycemia (HCL 6.65 mmol/L vs. MA 7.34 mmol/L vs. FCL 7.05 mmol/L, P = 0.28). No difference was observed in the mean daily dose of insulin or in the daily carbohydrate intake. No serious adverse event occurred during the study period. Conclusions: Our pilot study showed that FCL might be a realistic mode of treatment for people with T1D.
- MeSH
- diabetes mellitus 1. typu * farmakoterapie MeSH
- dospělí MeSH
- hypoglykemika MeSH
- inzulin lidský terapeutické užití MeSH
- inzulin * terapeutické užití MeSH
- inzulinové infuzní systémy MeSH
- klinické křížové studie MeSH
- krevní glukóza MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- pilotní projekty MeSH
- prospektivní studie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
Přibližně u 10 % dětí, které se narodily malé na svůj gestační věk (SGA; small for gestational age) s porodní hmotností a/nebo délkou nižší než −2 SD, nedojde po narození k růstovému výšvihu. Tyto děti zůstávají malé po celé dětství (s výškovým skóre směrodatné odchylky [ht-SDS] pod −2,5 SDS) a skončí jako malí dospělí. Označujeme je jako SGA-SS (small for gestational age with short stature). Evropská léková agentura schválila již v roce 2003 SGA-SS jako indikaci pro léčbu růstovým hormonem. Z 1502 dětí SGA-SS evidovaných v české národní databázi příjemců růstového hormonu REPAR již 397 dětí (221 chlapců) ukončilo růst a dosáhlo téměř finální dospělé tělesné výšky. Léčba růstovým hormonem v dávce 0,034 mg/kg/den (medián) byla zahájena u chlapců ve věku 8,5 roku (medián; P5-95: 3,2–15,0), u dívek ve věku 7,3 roku (3,9–13,5). Průměr ht-SDS při zahájení léčby byl −3,21 (SD: 0,91). Léčba byla ukončena u chlapců ve věku 16,2 roku (medián; P5-95: 14,0–18,7 roku), u dívek ve věku 14,3 roku (12,4–17,3). Léčba vedla do okamžiku ukončení léčby k průměrnému přírůstku ht-SDS o 1,59 a k dosažení téměř dospělé výšky (near-final height) ht-SDS −1,62 (SD: 0,97; p < 0,0001 proti výšce před léčbou). Při ukončení léčby tedy většina pacientů dosáhla výšky nad −2 SDS, v rozmezí hodnot běžné populace. Po adjustaci na ht-SDS v 18 letech věku tato výška odpovídá ht-SDS −2,30 (SD: 1,09; p < 0,0001 proti výšce před léčbou). I po této adjustaci, která efekt léčby mírně podhodnocuje, byla léčba růstovým hormonem úspěšná a vedla ke zlepšení v průměru o 0,91 ht-SDS. Výsledky analýzy z databáze REPAR prokazují u dětí SGA-SS účinnost léčby růstovým hormonem a její potenciál významně zlepšit dospělou tělesnou výšku.
Of children born small for gestational age (SGA) with birth weight and/or birth length below −2 SD, about 10% fail to catch-up after birth. These children remain short over childhood (with height standard deviation score [ht-SDS] below −2.5 SDS) and end up as short adults. They are assigned as SGA-SS (small for gestational age with short stature). European Medicine Agency approved growth hormone therapy in SGA-SS already in 2003. Out of 1502 SGA-SS children that are registered in the Czech national database of growth hormone recipients REPAR, 397 children (221 boys) already completed growth and achieved near-final height. Growth hormone therapy (median dose 0.034 mg/kg/day) was initiated at age 8.5 years in boys (median; P5-95: 3.2-15.0) and 7.3 years in girls (3.9-13.5). The mean ht-SDS at treatment initiation was −3.21 (SD: 0.91). Treatment was terminated at age 16.2 years in boys (median; P5-95: 14.0-18.7) and 14.3 years in girls (12.4-17.3). By treatment termination, the patients have had gained 1.59 ht-SDS (mean) and have achieved near-final height −1.62 ht-SDS (SD: 0.97; p<0.0001 if compared to pre-treatment). Thus, majority of patients exceeded −2 SDS at treatment completion and achieved height within normal limits. After adjusting for ht-SDS at age 18 years, their height corresponded to ht-SDS −2.30 (SD: 1.09; p < 0.0001 if compared to pre-treatment). Growth hormone therapy was successful even after this adjustment that mildly underestimates the treatment effect, and led to mean height increase of 0.91 ht-SDS. Analysis results of the REPAR database confirm efficacy of growth hormone therapy in SGA-SS children and its potential to significantly improve the adult height.
