Is COVID-19 to Blame? Trends of Incidence and Sex Ratio in Youth-Onset Type 2 Diabetes in Germany.

OBJECTIVE: We investigated the incidence of pediatric type 2 diabetes (T2D) in Germany during 2 years of the coronavirus disease 2019 (COVID-19) pandemic (2020-2021) compared with the control period 2011-2019. RESEARCH DESIGN AND METHODS: Data on T2D in children (aged 6 to <18 years) were obtained from the DPV (German Diabetes Prospective Follow-up) Registry. Poisson regression was used to estimate incidences for 2020 and 2021 based on data from 2011 to 2019, and these were compared with observed incidences in 2020 and 2021 by estimating incidence rate ratios (IRRs) with 95% CIs. RESULTS: Incidence of youth-onset T2D increased from 0.75 per 100,000 patient-years (PYs) in 2011 (95% CI 0.58, 0.93) to 1.25 per 100,000 PYs in 2019 (95% CI 1.02, 1.48), an annual increase of 6.8% (95% CI 4.1, 9.6). In 2020, T2D incidence increased to 1.49 per 100,000 PYs (95% CI 1.23, 1.81), which was not significantly higher than predicted (IRR 1.15; 95% CI 0.90, 1.48). In 2021, the observed incidence was significantly higher than expected (1.95; 95% CI 1.65, 2.31 vs. 1.38; 95% CI 1.13, 1.69 per 100,000 PYs; IRR 1.41; 95% CI 1.12, 1.77). Although there was no significant increase in incidence in girls in 2021, the observed incidence in boys (2.16; 95% CI 1.73, 2.70 per 100,000 PYs) significantly exceeded the predicted rate (IRR 1.55; 95% CI 1.14, 2.12), leading to a reversal of the sex ratio of pediatric T2D incidence. CONCLUSIONS: In Germany, incidence of pediatric T2D increased significantly in 2021. Adolescent boys were more affected by this increase, resulting in a reversal of the sex ratio of youth-onset T2D.

Incidence of Type 1 Diabetes in Children and Adolescents During the COVID-19 Pandemic in Germany: Results From the DPV Registry.

OBJECTIVE: The aim of this study was to investigate the incidence of type 1 diabetes in children and adolescents during the coronavirus disease 2019 (COVID-19) pandemic in Germany compared with previous years. RESEARCH DESIGN AND METHODS: Based on data from the multicenter German Diabetes Prospective Follow-up Registry, we analyzed the incidence of type 1 diabetes per 100,000 patient-years in children and adolescents from 1 January 2020 through 30 June 2021. Using Poisson regression models, expected incidences for 2020/21 were estimated based on the data from 2011 to 2019 and compared with observed incidences in 2020/21 by estimating incidence rate ratios (IRRs) with 95% CIs. RESULTS: From 1 January 2020 to 30 June 2021, 5,162 children and adolescents with new-onset type 1 diabetes in Germany were registered. The observed incidence in 2020/21 was significantly higher than the expected incidence (24.4 [95% CI 23.6-25.2] vs. 21.2 [20.5-21.9]; IRR 1.15 [1.10-1.20]; P < 0.001). IRRs were significantly elevated in June 2020 (IRR 1.43 [1.07-1.90]; P = 0.003), July 2020 (IRR 1.48 [1.12-1.96]; P < 0.001), March 2021 (IRR 1.29 [1.01-1.65]; P = 0.028), and June 2021 (IRR 1.39 [1.04-1.85]; P = 0.010). CONCLUSIONS: A significant increase in the incidence of type 1 diabetes in children was observed during the COVID-19 pandemic, with a delay in the peak incidence of type 1 diabetes by ∼3 months after the peak COVID-19 incidence and also after pandemic containment measures. The underlying causes are yet unknown. However, indirect rather than direct effects of the pandemic are more likely to be the cause.

Relation of health-related quality of life to near final height and body composition in adolescents with chronic endocrinopathies during transition period.

INTRODUCTION: We evaluated sequelae of disease and therapy in adolescents with chronic endocrinopathies using a medical and psychological workup to record health-related quality of life (HRQoL), near final height (NFH) and body compositions during the transition period from paediatric to adult care. METHODS: Near final height, weight, body mass index (BMI), grip strength (GS), hip and waist circumference (HC; WC), skin folds (SF) and HRQoL T-scores by KIDSCREEN and DISABKIDS were assessed in 134 patients (70 females and 64 males) from May 2010 to March 2016 diagnosed with congenital adrenal hyperplasia (CAH; n = 22), multiple pituitary hormone deficiency (MPHD; n = 17), growth hormone deficiency (GHD; n = 37), Turner syndrome (TS; n = 27), SGA-short stature (SGA; n = 20) and Klinefelter syndrome (KS; n = 11). RESULTS: Median HRQoL T-scores for KIDSCREEN (50.6-56.5) and DISABKIDS (52.7-58.9) ranged within references with considerable variations but without significant deficit in any diagnosis. Median-corrected height SDS (CoH-SDS: NFH-SDS-TH [target height]-SDS) was >-1, except in KS (SDS + 1.3) and in TS (SDS - 1.9; P < .0001) without correlations with HRQoL. Median BMI was below 25 kg/m2 in all patients except MPHD (26.5 kg/m2 ; SDS 1.5; P = .006). BMI correlated negatively in CAH females with self-perception (rs  = -.64, P = .0338), physical well-being (rs  = -.8; P = .0086), social exclusion rs  = -.65; P = .031) and emotions (rs  = -.7; P = .0169). CONCLUSION: Health-related quality of life and body compositions were similar to those of healthy adolescents. Lower scores in HRQoL dimensions as self-perception, physical well-being, social exclusion and emotions were detected and correlated negatively with BMI. Treatment strategies and psychological support should consider HRQoL and adapted in specific treatment guidelines.

Typical characteristics of children with congenital adrenal hyperplasia due to 11ß-hydroxylase deficiency: a single-centre experience and review of the literature.

Background 11ß-hydroxylase deficiency (11ßOHD) is a rare disease representing the second most common cause of congenital adrenal hyperplasia (CAH) (5-8%) with an incidence of about 1:100,000. In contrast to 21-hydroxylase deficiency (21OHD), 11ßOHD is not included in neonatal screening programmes. The objective of this study was to demonstrate the typical features of male patients with 11ßOHD. Methods Clinical, biochemical and radiological data of patients with 11ßOHD were analysed in this retrospective single-centre analysis. Results Six male patients of four unrelated families with 11ßOHD were identified (0.1-13.5 years of chronological age [CA] at diagnosis). The predominant symptoms were arterial hypertension, tall stature and precocious pseudopuberty. Bone ages (BAs) were remarkably advanced at diagnosis in four index patients (median difference BA-CA: 5.5 years, range 1.5-9.2 years). Homozygous mutations were identified in exon 7 (c.1179_1180dupGA [p.Asn394Argfs*37]) and exon 8 (c.1398+2T>C) of the CYP11B1 gene leading both to a complete loss of function. The latter mutation has not yet been described in databases. 11ßOHD was identified by the measurement of 11-deoxycortisol in a newborn screening card of one patient retrospectively. Testicular adrenal rest tumours (TARTs) were detected in three patients at 3.7 years, 11 years and 14.4 years. Conclusion The diagnosis of CAH due to 11ßOHD is delayed and should be suspected in children with arterial hypertension, tall stature and precocious pseudopuberty. Patients may develop TARTs as early as infancy. 11ßOHD should be included in newborn screening programmes, at least in newborns of index families, to allow early diagnosis and the start of treatment to reduce morbidity.

Clinical Features and Response to Treatment of Prolactinomas in Children and Adolescents: A Retrospective Single-Centre Analysis and Review of the Literature.

BACKGROUND: Paediatric prolactinomas are rare. The aim of this study was to investigate the clinical features and outcome of paediatric patients with prolactinomas. METHODS: In this single-centre retrospective analysis, clinical, biochemical, and radiological features of all paediatric patients with pituitary adenomas diagnosed between 2000 and 2016 were evaluated. RESULTS: Among 21 patients with pituitary adenomas, 12 patients with prolactinomas (median age 14.2 years, range 11-16.6 years, 8 females, 4 males) were identified (7 macro- and 5 microprolactinomas). The most common clinical symptoms were headaches (67%) and pubertal delay (67%). All patients with macroprolactinomas with prolactin concentrations >10,000 mU/L had at least 1 pituitary hormone deficiency. Cabergoline as first-line treatment (n = 11, median follow-up of 37 months, range 12-89 months) induced normoprolactinemia (n = 8), reduced the mean tumour volume by 80%, and ameliorated headaches (p = 0.016) and pubertal delay (p = 0.031), whereas intermittent moderate side effects occurred in 55%. CONCLUSION: Adolescents with headaches and pubertal delay should be investigated for prolactinomas. Treatment with cabergoline is well tolerated and effective in reducing clinical symptoms and prolactin concentrations was well as inducing tumour shrinkage. Further clinical prospective studies are needed to standardize paediatric treatment modalities.

Understanding childhood diabetes mellitus: new pathophysiological aspects.

Diabetes mellitus (DM) is not a single disease, but several pathophysiological conditions where synthesis, release, and/or action of insulin are disturbed. A progressive autoimmune/autoinflammatory destruction of islet cells is still considered the main pathophysiological event in the development of T1DM, but there is evidence that T1DM itself is a heterogeneous disease. More than 50 gene regions are closely associated with T1DM and a variety of epigenetic factors and metabolic patterns have been characterized, which may play a role in the development of T1DM. The pathogenesis and genetics of type 2 DM (T2DM) are distinct from T1DM. Genes associated with T2DM are distinct from those in T1DM. Characteristic metabolic patterns, different from those in T1DM were reported in T2DM, and some children with T2DM also express islet-antibodies. Huge progress has been made in the characterization of other specific types of DM, which had been considered very rare before. The molecular clarification of maturity-onset diabetes of the young (MODY) has greatly improved our understanding of the pathophysiology of DM. There are genetic overlaps between T2DM and monogenetic DM. Neonatal DM has been shown to be monogenetic in most cases, and genetic elucidation leads to more precise and individualized therapies. Cystic fibrosis related DM (CFRDM) should be considered a genuine part of cystic fibrosis, and not a complication, since pancreatic fibrosis does not sufficiently explain the pathophysiology of CFRDM. Disturbances of cystic fibrosis transmembrane conductance regulator (CFTR) as well as autoimmunity are involved in the pathogenesis of CFRDM.

Frequencies of inherited organic acidurias and disorders of mitochondrial fatty acid transport and oxidation in Germany.

UNLABELLED: The lack of epidemiological data on the frequency and/or burden of organic acidurias (OA) and mitochondrial fatty acid transport and oxidation disorders (mtFATOD) is one reason for hesitation to expand newborn screening (NBS) by tandem mass spectrometry (MS-MS). From 1999 to 2000, the frequency of ten potentially treatable OA and mtFATOD was assessed by active nation-wide surveillance on cases presenting with clinical symptoms using the German Paediatric Surveillance Unit (ESPED) system. Case ascertainment was complemented by a second independent source: 3-monthly inquiries in the metabolic laboratories performing secondary selected screening for OA and mtFATOD. Frequency estimates for clinically symptomatic cases older than 7 days in a birth cohort of 844,575 conventionally screened children was compared to the frequency found in a cohort of 382,247 screened by MS-MS in Bavaria and Baden-Württemberg. The overall frequency of the ten conditions considered was 1:8,000 (95% CI 1:11,000-1:6,000) by MS-MS as compared to 1:23,000 (95% CI 1:36,000-1:17,000) in symptomatic cases presenting mainly with metabolic crisis. The contributions of medium-chain acyl-CoA dehydrogenase deficiency (MCADD), other mtFATOD and OA were 29, 4 and 13 among the 46 cases identified by MS-MS, and 19, 1 and 13 among the 33 clinically symptomatic cases, respectively. Acute metabolic crisis, with a lethal outcome in four patients, was reported for 22/33 clinically symptomatic cases. No clinically symptomatic cases were reported from cohorts with screened by MS-MS. CONCLUSION: ten potentially treatable organic acidurias and mitochondrial fatty acid transport and oxidations disorders were more common than phenylketonuria with organic acidurias accounting for 28% of the cases detected by newborn screening and 39% of the cases identified on high risk screening. These conditions were related to considerable morbidity and mortality. Considerations for their inclusion in expanded newborn screening programmes might be warranted.

Incidence and short-term outcome of children with symptomatic presentation of organic acid and fatty acid oxidation disorders in Germany.

OBJECTIVE: To determine the incidence of symptomatic children with inherited organic acid disorders (OADs) and fatty acid oxidation disorders (FAODs) in Germany. METHODS: An active surveillance of symptomatic children with inherited OADs and FAODs was conducted during a time period of 24 months (1999-2000) in Germany. Monthly inquiries were sent to all Departments of Pediatrics by the German Pediatric Surveillance Unit (ESPED) and quarterly to all specialized metabolic laboratories. Newly diagnosed patients were added to the database, recording clinical and biochemical information via a standardized questionnaire. RESULTS: Prospective surveillance enrolling 844 575 children identified a total of 57 symptomatic children with newly diagnosed OADs or FAODs in states with conventional neonatal screening, resulting in an estimated cumulative incidence of 1:14 800. The most frequent diagnosis among these children was medium-chain acyl-CoA dehydrogenase deficiency (n = 20). The majority of symptomatic children revealed clinical symptoms during the first year of life (n = 36), frequently presenting with acute metabolic crises (n = 31). Eight children died during these crises. Notably, 47 of the symptomatic children suffered from diseases potentially detectable by expanded neonatal screening programs. This subgroup included 29 children presenting with metabolic crises and 7 of the 8 deaths. CONCLUSIONS: Despite increased clinical awareness of OADs and FAODs, the mortality and morbidity for these children remains high, if they are diagnosed after manifestation of clinical disease. An introduction of nationwide neonatal screening programs would change the focus for organic acid analysis from patients presenting with acute metabolic crises to more chronic clinical presentations, especially the cerebral organic acid disorders.