The incidence of type 1 diabetes (T1D) in children increased significantly during the COVID-19 pandemic (1,2). However, it is not known whether this increase is a persistent phenomenon, which would have significant implications for future patient care. The aim of this study was to investigate the long-term incidence of childhood T1D in Germany during the nine years before and four years after the emergence of COVID-19.

Gold standard for immunohistochemical analyses is the manual assessment by two specialist pathologists. This process is time-consuming, highly dependent on the respective evaluator and often difficult to reproduce. The use of image analysis software, such as ImageJ, QuPath, or CellProfiler, which employ machine learning and/or deep learning mechanisms to perform biomarker analyses, offers a potential solution to these problems. The objective of our study is to evaluate whether digital assessment using the open-source software QuPath is comparable to manual evaluation and to examine the inter-evaluator variability between the two manual evaluators and two software-based evaluations. Six tissue microarrays (TMAs) were constructed for a cohort of 309 patients with primary oral squamous cell carcinoma (OSCC). The tumor tissue and corresponding non-lesional squamous epithelial mucosa specimen were immunohistochemically stained for the biomarkers Ki67, as a nuclear marker; the epidermal growth factor receptor (EGF-R), as a membranous marker; and the major histocompatibility complex class I (MHC-I) heavy chain (HC) expressed on the membrane and in the cytoplasm. The staining pattern was analyzed by two experienced, independent manual evaluators and by QuPath. The percentage of positive cells, for Ki67, and the histoscore (H-score) based on the percentage of positive cells and their staining intensity, for EGF-R and MHC-I, were determined as final values. The results yielded high to excellent spearman correlation coefficients for all three biomarkers (p<0.001) in lesional and non-lesional tissues. The Bland-Altman plots demonstrated a high degree of agreement between manual and software-based analysis, as well as inter-evaluator variability demonstrating a high comparability of the evaluation methods. However, a prerequisite for a proper software-based analysis is an accurate, time-consuming annotation of the single specimen, which requires users with a comprehensive understanding of histology and extensive training in QuPath. Once these requirements are met, the software-based analysis offers advantages for large-scale biomarker studies due to objective and reproducible comparability of the stainings leading to a greater accuracy as well as the reuse of established conditions across similar analyses without requiring further operator input.

Patients with type 1 diabetes mellitus must be substituted with insulin for the rest of their lives. The appropriate insulin dosage is chosen for each individual or calculated by complex algorithms of the AID (Automatic Insulin Dosing) systems. It is noticeable that there are children and adolescents with increasing insulin doses requirement or insulin resistance. The occurrence of insulin resistance in children and adolescents with type 1 diabetes mellitus - defined in our publication as an insulin dosage of more than 1U/kg/d - is apparently related to various factors such as the therapeutic regimen or the type of insulin, physical activity, obesity and use of hormonal contraception. The aim of the present study is to analyze data from the DPV registry. For this purpose, data from 48,357 children and adolescents with T1D were used to demonstrate a relationship between insulin resistance and various influencing factors as described above. Our results should help to understand patients with high insulin requirement, and give indications how to reduce insulin resistance in children and adolescents with T1D by appropriate therapeutic approaches.

Hintergrund: Die Inzidenz des Diabetes mellitus Typ 2 bei Kindern und Jugendlichen steigt in Deutschland kontinuierlich an [1]. Daten US-amerikanischer Kohortenstudien zeigen, dass arterielle Hypertension, diabetische Nephropathie, Retinopathie und Neuropathie bei Jugendlichen mit Typ-2-Diabetes (T2D) früher und häufiger als bei Jugendlichen mit Typ-1-Diabetes auftreten (T1D) [2] [3]. Ob diese Beobachtungen auch für Kinder und Jugendliche mit T2D in Deutschland zutreffen, ist derzeit unbekannt.

Fragestellung: Wie haben sich die Anzahl der Krankenhausaufnahmen und der Anteil der Fälle mit Diabetes zwischen 2015 und 2022 entwickelt?

OBJECTIVES:Recent studies have suggested a link between type 1 diabetes mellitus (T1D) and metabolic dysfunction associated steatotic liver disease (MASLD) in children and adolescent, but longitudinal evidence is lacking. This study aimed to investigate the potential association between poorly controlled T1D and elevated alanine aminotransferase (ALT), serving as a proxy for MASLD in children and adolescents over time. METHODS:The study included 32,325 children aged 2-17 years with T1D from Germany, Austria, and Switzerland who had undergone at least one assessment of liver enzyme levels recorded in the Diabetes-Patienten- Verlaufsdokumentation registry. Multivariable logistic and Cox regression models were calculated to show possible associations between T1D and elevated ALT values (>26 U/L in males, >22 U/L in females) as a proxy for MASLD. RESULTS:Children with poorly controlled T1D (HbA1c > 11%) exhibited increased odds of elevated ALT values, after adjustment for age, sex, diabetes duration and overweight (odds ratio [OR] 2.54; 95% confidence interval [CI], 2.10-3.10; p < 0.01). This finding is substantiated by a longitudinal analysis, which reveals that inadequately controlled T1D was associated with a higher hazard ratio (HR) of elevated ALT values compared to children with controlled T1D over an observation period extending up to 5.5 (HR: 1.54; 95% CI, 1.19-2.01; p < 0.01). CONCLUSION:In conclusion, the current study strongly links poorly controlled T1D in children and adolescents to MASLD irrespective of overweight. This association is not only present cross-sectionally but also increases over time. The study underscores the critical role of effective diabetes management in reducing the risk of MASLD in this population.

Zusammenfassung Patienten mit Diabetes mellitus Typ 1 müssen lebenslang mit Insulin substituiert werden. Dabei wird für jede Einzelne und jeden Einzelnen die passende Insulindosierung gewählt bzw. durch komplexe Algorithmen der AID-Systeme (Automatische Insulindosierung) berechnet. Hierbei fällt auf, dass es immer wieder Kinder und Jugendliche gibt, die einen steigenden Bedarf an Insulin bzw. eine Insulinresistenz aufzeigen. Das Auftreten einer Insulinresistenz bei Kindern und Jugendlichen mit Diabetes mellitus Typ1 – in unserer Publikation definiert als Insulindosierung von über 1U/kg/d – steht augenscheinlich in Zusammenhang mit verschiedenen Einflussgrößen wie u.a. Therapieform und Insulinart, sportlicher Betätigung, Übergewicht, Einnahme einer hormonellen Kontrazeption. Das Ziel der vorliegenden Arbeit ist die Analyse von Daten aus dem DPV-Register. Hierzu wurden die Daten von 48.357 Kindern und Jugendlichen mit T1D herangezogen, um einen Zusammenhang zwischen dem Auftreten einer Insulinresistenz und verschiedenen Einflussfaktoren nachzuweisen. Die Ergebnisse sollen dazu beitragen, Patienten mit ungewöhnlich hohem Insulinbedarf besser beraten zu können und gegebenenfalls durch entsprechende Therapiemaßnahmen zu versuchen, die Insulinresistenz bei Kindern und Jugendlichen mit T1D zu verringern.

Hintergrund: Die Häufigkeit der diabetischen Ketoazidose (DKA) bei Manifestation eines Typ-1-Diabetes (T1D) im Kindesalter ist in den vergangenen Jahren angestiegen. Es gibt Hinweise, dass T1D-Früherkennungsprogramme und/oder Aufklärungskampagnen die DKA-Rate senken können. Unklar ist, ob bzw. wann dadurch eine relevante Reduktion der DKA-Rate auf Populationsebene erreicht werden kann. Dies sollte anhand von bundesweiten Daten des DPV-Registers untersucht werden.

Aims: Diabetic foot ulcer (DFU) is a leading cause of lower limb amputations in people with diabetes. This study was aimed to retrospectively analyze factors affecting DFU using real-world data from a large, prospective central-European diabetes registry (DPV [Diabetes-Patienten-Verlaufsdokumentation]). Materials and Methods: We matched adults with type 1 (T1D) or type 2 diabetes (T2D) and DFU to controls without DFU by diabetes type, age, sex, diabetes duration, and treatment year to compare possible risk factors. Cox regression was used to calculate hazard ratios for amputation among those with DFU. Results: In our cohort (N = 63 464), male sex, taller height, and diabetes complications such as neuropathy, peripheral artery disease, nephropathy, and retinopathy were associated with DFU (all p < .001). Glycated hemoglobin (HbA1c) was related to DFU only in T1D (mean with 95% confidence interval [CI]: 7.8 [6.9-9.0] % vs 7.5 [6.8-8.5] %, p < .001). High triglycerides and worse low-density lipoprotein/high-density lipoprotein ratio were also associated with DFU in T1D, whereas smoking (14.7% vs 13.1%) and alcohol abuse (6.4% vs 3.8%, both p < .001) were associated with DFU in T2D. Male sex, higher Wagner grades, and high HbA1c in both diabetes types and insulin use in T2D were associated with increased hazard ratios for amputations. Conclusions: Sex, body height, and diabetes complications were associated DFU risk in adults with T1D and T2D. Improvement in glycemic control and lipid levels in T1D and reduction of smoking and drinking in T2D may be appropriate interventions to reduce the risk for DFU or amputations.

100 years after using insulin therapy for the very first time, pharmacological advances in medicine - especially in terms of insulin preparations with different kinetics, but also different methods of application and glucose self measurement - have brought about quite drastic changes, particularly within the last 20 years. Today, the use of insulin analogues has become far more common, in particular for patients with T1DM. For patients with T2DM there now is a broad spectrum of different forms of insulin therapy: BOT, BOTplus, SIT, various pre-mixtures of insulin, conventional or intensive conventional insulin therapy, or even the use of insulin pumps for few patients. The numerous different insulins and methods of application have led to a small but quite significant improvement in the blood-sugar levels of patients and have further advanced the individuality in patient care.

AIMS/HYPOTHESIS:The diagnosis of type 2 diabetes is increasing in young people worldwide. This study evaluated the frequency and clinical characteristics of young people presenting with type 2 diabetes from the multinational SWEET e.V Registry 2012-2021, including the first years of the COVID-19 pandemic. METHODS:This is a longitudinal observational study based on the SWEET Registry, which collects demographic and clinical data on children and adolescents with diabetes from centres worldwide, with the diagnosis and classification of diabetes provided locally by each centre according to International Society for Paediatric and Adolescent Diabetes definitions. By July 2022, the SWEET Registry included 96,931 individuals from 130 centres with a total of 1,154,555 visits. Data were analysed by region: Europe (EU), Australia and New Zealand (AU/NZ), South America (SA), North America (NA) and Asia/Middle East and Africa (AS/AF). Trends in proportions for the two-year periods, calculated as cases with type 2 diabetes diagnoses over all cases with diabetes diagnoses, were estimated using logistic regression models adjusted for age at onset and sex. RESULTS:Overall, there were 2819 of 58,170 new cases (4.8%) with type 2 diabetes: 614 in EU, 293 in AU/NZ, 79 in SA, 1211 in NA and 622 in AS/AF. The proportion of type 2 diabetes increased from 3.2% to 6.0% from 2012/2013 to 2020/2021, a relative rate of increase of 9% per two-year period (95% CI 5.9, 12.3; p<0.001). In the two-year period of the COVID-19 pandemic, type 2 diabetes continued to follow the observed trend, with a proportion of 6.0% in 2020-2021 compared with 5.4% in 2018-2019. High variability in the proportion of type 2 diabetes was observed across regions, with the lowest values observed in EU and the highest in NA. A significant increase in the proportion of type 2 diabetes was observed in EU, AU/NZ and NA. The median HbA1c was not uniform and was highest in AS/AF (85 mmol/mol [9.9%]; IQR 55-111 [7.2-12.3%]) and lowest in EU (63 mmol/mol [7.9%]; IQR 48-99 [6.5-11.2%]), and the difference between EU and NA (median value 73 mmol/mol [8.8%]; IQR 50-105 [6.7-11.8%]) was statistically significant (p=0.047). There was also a difference in BMI SD score by region: the lowest median BMI SD score was 2.2 (IQR 1.4-2.7) in AS/AF and the highest was 3.1 (IQR 2.5-3.6) in AU/NZ. CONCLUSIONS/INTERPRETATION:The multinational SWEET data from the years 2012 to 2021 inclusive support recent findings of a worldwide increase in type 2 diabetes in young people, albeit with regional differences. This increase highlights the need for ongoing preventive measures and available advanced treatment modalities worldwide.

ZUSAMMENFASSUNGIn der vorliegenden Auswertung aus dem DPV-Register wird der Einsatz von unterschiedlichen Antidiabetika zwischen den Jahren 2005 bis 2021 ausgewertet und analysiert. Es konnten Daten von insgesamt 405 790 Menschen mit Diabetes ausgewertet werden (2 464 078 Beobachtungsjahre). Die Population (53,4 % männlich) war im Median 70,91 Jahre alt bei einer medianen Diabetesdauer von ca. 9 Jahren. Im Laufe des Auswertungszeitraumes nahm der Anteil der über 80-Jährigen kontinuierlich zu.Seitens der Therapie nahm der Anteil der lediglich mit Insulin behandelten Patienten ebenso ab wie der Anteil der lediglich mit Lebensstil behandelten Patienten. Metformin wurde tendenziell zunehmend häufiger eingesetzt. Für Sulfonlyharnstoffe zeigte sich eine komplette gegensätzliche Entwicklung gegenüber den DPP-IV-Inhibitoren mit einer Zunahme dieser seit 2007 etablierten Substanzgruppe. Seit ungefähr 2015 zeigen sich deutlich zunehmende Verordnungshäufigkeiten für SGLT-2-Inhibitoren sowie GLP-1-Rezeptoragonisten bei gleichzeitig zu erkennendem allmählichem Rückgang der DPP-IV-Inhibitorverordnungen.Während der Anteil der Metformin-Verordnungen im Beobachtungszeitraum in allen Altersgruppen kontinuierlich und weitgehend parallel anstieg, sind für SGLT-2-Inhibitoren und GLP-1-Rezeptoragonisten anfänglich bei der Gruppe der unter 60-jährigen und erst zeitversetzt auch der älteren Patienten eingesetzt worden. Seitens der Geschlechterunterschiede in den Verordnungen gibt es für GLP-1-Rezeptoragonisten quasi keine Unterschiede, bei Metformin gibt es ein ganz leichtes Überwiegen der männlichen Patienten, welches bei SGLT-2-Inhibitoren deutlicher wird.Die mittlere glykämische Kontrolle ausgedrückt durch den HbA1c-Wert liegt in der gesamten Kohorte im Median bei 7,11 % (54,2 mmol/Mol) mit einem weitgehend unveränderten Verlauf über den Beobachtungszeitraum und einer klaren Differenzierung dahingehend, dass jüngere Patienten den höchsten medianen HbA1c aufweisen und die älteste Kohorte den niedrigsten.Die Daten werden im Kontext sich ändernder Leitlinien und Empfehlungen diskutiert und analysiert.

Zusammenfassung In der vorliegenden Auswertung aus dem DPV-Register wird der Einsatz von unterschiedlichen Antidiabetika zwischen den Jahren 2005 bis 2021 ausgewertet und analysiert. Es konnten Daten von insgesamt 405790 Menschen mit Diabetes ausgewertet werden (2464078 Beobachtungsjahre). Die Population (53,4 % männlich) war im Median 70,91 Jahre alt bei einer medianen Diabetesdauer von ca. 9 Jahren. Im Laufe des Auswertungszeitraumes nahm der Anteil der über 80-jährigen kontinuierlich zu. Seitens der Therapie nahm der Anteil der lediglich mit Insulin behandelten Patienten ebenso ab wie der Anteil der lediglich mit Lebensstil behandelten Patienten. Metformin wurde tendenziell zunehmend häufiger eingesetzt. Für Sulfonlyharnstoffe zeigte sich eine komplette gegensätzliche Entwicklung gegenüber den DPP-IV-Inhibitoren mit einer Zunahme dieser seit 2007 etablierten Substanzgruppe. Seit ungefähr 2015 zeigen sich deutlich zunehmende Verordnungshäufigkeiten für SGLT-2-Inhibitoren sowie GLP-1-Rezeptoragonisten bei gleichzeitig zu erkennendem allmählichem Rückgang der DPP-IV-Inhibitorverordnungen. Während der Anteil der Metformin-Verordnungen im Beobachtungszeitraum in allen Altersgruppen kontinuierlich und weitgehend parallel anstieg, sind für SGLT-2-Inhibitoren und GLP-1-Rezeptoragonisten anfänglich bei der Gruppe der unter 60-jährigen und erst zeitversetzt auch der älteren Patienten eingesetzt worden. Seitens der Geschlechterunterschiede in den Verordnungen gibt es für GLP-1-Rezeptoragonisten quasi keine Unterschiede, bei Metformin gibt es ein ganz leichtes Überwiegen der männlichen Patienten, welches bei SGLT-2-Inhibitoren deutlicher wird. Die mittlere glykämische Kontrolle ausgedrückt durch den HbA1c-Wert liegt in der gesamten Kohorte im Median bei 7,11 % (54,2 mmol/Mol) mit einem weitgehend unveränderten Verlauf über den Beobachtungszeitraum und einer klaren Differenzierung dahingehend, dass jüngere Patienten den höchsten medianen HbA1c aufweisen und die älteste Kohorte den niedrigsten. Die Daten werden im Kontext sich ändernder Leitlinien und Empfehlungen diskutiert und analysiert.

Background An increased prevalence of diabetic ketoacidosis at diagnosis of type 1 diabetes in children was observed in various diabetes centres worldwide during the COVID-19 pandemic. We aimed to evaluate trends in the prevalence of diabetic ketoacidosis at diagnosis of paediatric type 1 diabetes before and during the COVID-19 pandemic, and to identify potential predictors of changes in diabetic ketoacidosis prevalence during the pandemic.Methods For this international multicentre study, we used data from 13 national diabetes registries (Australia, Austria, Czechia, Denmark, Germany, Italy, Luxembourg, New Zealand, Norway, Slovenia, Sweden, USA [Colorado], and Wales). The study population comprised 104 290 children and adolescents aged 6 months to younger than 18 years, who were diagnosed with type 1 diabetes between Jan 1, 2006, and Dec 31, 2021. The observed diabetic ketoacidosis prevalence in 2020 and 2021 was compared to predictions based on trends over the pre-pandemic years 2006-19. Associations between changes in diabetic ketoacidosis prevalence and the severity of the COVID-19 pandemic and containment measures were examined with excess all-cause mortality in the whole population and the Stringency Index from the Oxford COVID-19 Government Response Tracker.Findings 87 228 children and adolescents were diagnosed with type 1 diabetes between 2006 and 2019, 8209 were diagnosed in 2020, and 8853 were diagnosed in 2021. From 2006 to 2019, diabetic ketoacidosis at diagnosis of type 1 diabetes was present in 23 775 (27middot3%) of 87 228 individuals and the mean annual increase in the prevalence of diabetic ketoacidosis in the total cohort from 2006 to 2019 was 1middot6% (95% CI 1middot3 to 1middot9). The adjusted observed prevalence of diabetic ketoacidosis at diagnosis of type 1 diabetes was 39middot4% (95% CI 34middot0 to 45middot6) in 2020 and 38middot9% (33middot6 to 45middot0) in 2021, significantly higher than the predicted prevalence of 32middot5% (27middot8 to 37middot9) for 2020 and 33middot0% (28middot3 to 38middot5) for 2021 (p<0middot0001 for both years). The prevalence of diabetic ketoacidosis was associated with the pandemic containment measures, with an estimated risk ratio of 1middot037 (95% CI 1middot024 to 1middot051; p<0middot0001) per ten-unit increase in the Stringency Index for 2020 and 1middot028 (1middot009 to 1middot047; p=0middot0033) for 2021, but was not significantly associated with excess all-cause mortality.Interpretation During the COVID-19 pandemic, there was a marked exacerbation of the pre-existing increase in diabetic ketoacidosis prevalence at diagnosis of type 1 diabetes in children. This finding highlights the need for early and timely diagnosis of type 1 diabetes in children and adolescents.Funding German Federal Ministry for Education and Research, German Robert Koch Institute, German Diabetes Association, German Diabetes Foundation, Slovenian Research Agency, Welsh Government, Central Denmark Region, and Swedish Association of Local Authorities and Regions.Copyright (c) 2022 Elsevier Ltd. All rights reserved.

Objective: To investigate the frequency, treatment, and outcome of patients with diabetes due to severe insulin resistance syndromes (SIRS). Research Design and Methods: Based on data from the multicenter prospective Diabetes Registry DPV, we analyzed diagnosis, treatment, and outcome of 636,777 patients with diabetes from 1995 to 2022. Results: Diabetes due to SIRS was documented in 67 cases (62.7% females), 25 (37%) had lipodystrophies (LD) and 42 (63%) had congenital defects of insulin signaling. The relative frequency compared to type 1 diabetes (T1D) was about 1:2300. Median age at diabetes diagnosis in patients with SIRS was 14.8 years (interquartile range (IQR) 12.8-33.8). A total of 38 patients with SIRS (57%) received insulin and 34 (51%) other antidiabetics, mostly metformin. As high as 16% of patients with LD were treated with fibrates. Three out of eight patients with generalized LD (37.5%) were treated with metreleptin and one patient with Rabson-Mendenhall syndrome was treated with recombinant insulin-like growth factor 1.The median glycated hemoglobin level at follow-up was 7.1% (54 mmol/mol). Patients with LD had higher triglycerides than patients with T1D and T2D (P < 0.001 and P = 0.022, respectively), and also significantly higher liver enzymes and lower high-density lipoprotein cholesterol than patients with T1D (P < 0.001). Patients with insulin receptor disorders were significantly less likely to be treated with antihypertensive medication than patients with T2D (P = 0.042), despite having similar levels of hypertension. Conclusions: Diabetes due to SIRS is rarely diagnosed and should be suspected in lean children or young adults without classical T1D. Awareness of cardiovascular risk factors in these patients should be raised.

In the present study with data of the DPV registry the usage of different antidiabetic agents in the observation period from 2005 to 2021 has been analyzed. Among 405 790 people with diabetes mellitus (type 2 greater or equal 18 years of age) 2 464 078 patient years could be analyzed. 53,4% were men, the median age was 70,91 years with median diabetes duration slightly above 9 years. The proportion of people over 80 years increased continuously.There was a slightly, but continuously decrease of only with Insulin treated as well as only with lifestyle treated patients. Overall, the prescription of metformin increased through the whole period. While the proportion of the usage of sulfonylureas decreased constantly, the usage of DPP-IV-inhibitors increased almost reciprocal. Since approximately 2015 there is a marked increase of the usage as well of SGLT-2 inhibitors as well as for GLP-1 receptor agonists with a gradually flattening and decreasing proportion of DPP-IV-inhibitors in the same period.While Metformin was used more and more parallel in all investigated age groups there was an increase of the usage of of SGLT-2 inhibitors and GLP-1 receptor agonists primarly in the younger age groups and with time shift even in older age groups.There was no gender difference in the use of GLP-1 receptor agonists, for the Metformin use there was a slight difference with preponderance in the male group, more pronounced in the proportion of SGLT-2 inhibitor use.The glycemic control in terms of median HbA1c is 7,11 % (54,2 mmol/Mol) throughout the whole cohort with an almost unchanged trajectory from 2005 to 2021. There was a clear difference with the lowest HbA1c values in the oldest group and highest in the youngest group.The data were analyzed and discussed on the background of changing guidelines and statement papers.

CONTEXT:Treatment of children with classical congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is challenging. Linear growth and adult height are compromised according to recent publications. However, most of these data were obtained in the era before CAH newborn screening.DESIGN:Body height of patients with classical CAH diagnosed before and after the establishment of newborn screening were analyzed retrospectively.PATIENTS AND METHODS:We identified 600 patients with classical CAH (227 male) with data on near-adult height (NAH), target height (TH), and information on newborn screening from the electronic German CAH registry (German Society for Paediatric Endocrinology and Diabetology). Newborn screening was performed in 101 (16.8%) patients. All patients received hydrocortisone with or without fludrocortisone.To assess the effects of newborn screening, a linear regression model adjusted/stratified for sex and phenotype was used (SAS 9.4).RESULTS:TH corrected NAH (mean; 95% confidence interval) was closer to 0 in patients with CAH and newborn screening [-0.25 standard deviation score (SDS); -0.44 to -0.06] than in patients without newborn screening (-0.44 SDS; -0.52 to -0.36) (P = .069). Screening had no effect on NAH in female patients. In male patients, NAH was significantly better (P = .033) with screening than without screening. After stratifying for CAH phenotype, screening did not affect the NAH of patients with salt-wasting CAH. Patients with simple-virilizing CAH had a significantly better cNAH (P = .034) with screening (0.15 SDS; -0.28-0.59) than without screening (-0.35 SDS; -0.52 to -0.18).CONCLUSIONS:Our data suggest that newborn screening might be associated with improved NAH in male CAH patients and in patients with simple-virilizing CAH.