Tumors overcome the action of the wasting factor ImpL2 by locally elevating Wnt/Wingless.

Tumors often secrete wasting factors associated with atrophy and the degeneration of host tissues. If tumors were to be affected by the wasting factors, mechanisms allowing tumors to evade the adverse effects of the wasting factors must exist, and impairing such mechanisms may attenuate tumors. We use Drosophila midgut tumor models to show that tumors up-regulate Wingless (Wg) to oppose the growth-impeding effects caused by the wasting factor, ImpL2 (insulin-like growth factor binding protein [IGFBP]-related protein). Growth of Yorkie (Yki)-induced tumors is dependent on Wg while either elimination of ImpL2 or elevation of insulin/insulin-like growth factor signaling in tumors revokes this dependency. Notably, Wg augmentation could be a general mechanism for supporting the growth of tumors with elevated ImpL2 and exploited to attenuate muscle degeneration during wasting. Our study elucidates the mechanism by which tumors negate the action of ImpL2 to uphold their growth during cachexia-like wasting and implies that targeting the Wnt/Wg pathway might be an efficient treatment strategy for cancers with elevated IGFBPs.

Lesion-to-anal-verge distance in rectosigmoid endometriosis on transvaginal sonography vs magnetic resonance imaging: prospective study.

OBJECTIVES: To compare transvaginal sonography (TVS) and magnetic resonance imaging (MRI) with intraoperative measurement (IOM) using a rectal probe in the estimation of the location of rectosigmoid endometriotic lesions, i.e. lesion-to-anal-verge distance (LAVD), and to compare two different MRI techniques for measuring LAVD. METHODS: This was a prospective single-center observational study that included women undergoing surgery for symptomatic rectosigmoid endometriosis by discoid (DR) or segmental (SR) resection from December 2018 to December 2019. TVS and MRI were performed presurgically for each participant to evaluate LAVD, and the measurements on imaging were compared with IOM using a rectal probe. Clinically acceptable difference and limits of agreement (LoA) between TVS and MRI compared with IOM were set at ± 20 mm. Two different measuring methods for MRI, MRICenter and MRIDirect , were proposed and evaluated, as there is currently no guideline to describe deep endometriosis on MRI. Bland-Altman plots and LoA were used to assess agreement of TVS and both MRI methods with IOM. Systematic and proportional biases were assessed using paired t-test and Bland-Altman plots. RESULTS: Seventy-five women were eligible for inclusion. Twenty-eight women were excluded, leaving 47 women for the analysis. Twenty-three DR and 26 SR procedures were performed, with both procedures performed in two women. The Bland-Altman plots showed that there were no systematic differences between TVS or MRICenter when compared with IOM for all included participants. MRIDirect systematically underestimated LAVD for lesions located further from the anal verge. TVS, MRICenter and MRIDirect had LoA outside the preset clinically acceptable difference when compared with IOM. LAVD was within the clinically acceptable difference from IOM of ± 20 mm in 70% (33/47) of women on TVS, 72% (34/47) of women on MRICenter and 47% (22/47) of women on MRIDirect . CONCLUSIONS: TVS should be the preferred method to estimate the location of a rectosigmoid endometriotic lesion, i.e. LAVD, as it is more available, less expensive and has a similar accuracy to that of MRI. Estimating LAVD can be relevant for planning colorectal surgery for rectosigmoid endometriosis. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Wear and tear of the intestinal visceral musculature by intrinsic and extrinsic factors.

BACKGROUND: The gut visceral musculature plays essential roles in not only moving substances through the lumen but also maintaining the function and physiology of the gut. Although the development of the visceral musculature has been studied in multiple model organisms, how it degenerates is poorly understood. RESULTS: Here, we employ the Drosophila midgut as a model to demonstrate that the visceral musculature is disrupted by intrinsic and extrinsic factors, such as aging, feeding, chemical-induced tissue damage, and oncogenic transformation in the epithelium. Notably, we define four prominent visceral musculature disruption phenotypes, which we refer as "sprout," "discontinuity," "furcation," and "crossover" of the longitudinal muscle. Given that the occurrence of these phenotypes is increased during aging and under various stresses, we propose that these phenotypes can be used as quantitative readouts of deterioration of the visceral musculature. Intriguingly, administration of a tissue-damaging chemical dextran sulfate sodium (DSS) induced similar visceral musculature disruption phenotypes in zebrafish larvae, indicating that ingestion of a tissue-damaging chemical can disrupt the visceral musculature in a vertebrate as well. CONCLUSIONS: Our study provides insights into the deterioration of the gut visceral musculature and lays a groundwork for investigating the underlying mechanisms in Drosophila as well as other animals.

The role of translationally controlled tumor protein in proliferation of Drosophila intestinal stem cells.

Translationally controlled tumor protein (TCTP) is a highly conserved protein functioning in multiple cellular processes, ranging from growth to immune responses. To explore the role of TCTP in tissue maintenance and regeneration, we employed the adult Drosophila midgut, where multiple signaling pathways interact to precisely regulate stem cell division for tissue homeostasis. Tctp levels were significantly increased in stem cells and enteroblasts upon tissue damage or activation of the Hippo pathway that promotes regeneration of intestinal epithelium. Stem cells with reduced Tctp levels failed to proliferate during normal tissue homeostasis and regeneration. Mechanistically, Tctp forms a complex with multiple proteins involved in translation and genetically interacts with ribosomal subunits. In addition, Tctp increases both Akt1 protein abundance and phosphorylation in vivo. Altogether, Tctp regulates stem cell proliferation by interacting with key growth regulatory signaling pathways and the translation process in vivo.

Collagenase Clostridium Histolyticum-aaes for the Treatment of Cellulite in Women: Results From Two Phase 3 Randomized, Placebo-Controlled Trials.

BACKGROUND: Fibrous septae play a role in contour alterations associated with cellulite. OBJECTIVE: To assess collagenase clostridium histolyticum-aaes (CCH) for the treatment of cellulite. MATERIALS AND METHODS: Two identically designed phase 3, double-blind, randomized studies (RELEASE-1 and RELEASE-2) were conducted. Adult women with moderate/severe cellulite (rating 3-4 on the Patient Reported Photonumeric Cellulite Severity Scale [PR-PCSS] and Clinician Reported PCSS [CR-PCSS]) on the buttocks received up to 3 treatment sessions of subcutaneous CCH 0.84 mg or placebo per treatment area. Composite response (≥2-level or ≥1-level improvement from baseline in both PR-PCSS and CR-PCSS) was determined at Day 71. RESULTS: Eight hundred forty-three women received ≥1 injection (CCH vs placebo: RELEASE-1, n = 210 vs n = 213; RELEASE-2, n = 214 vs n = 206). Greater percentages of CCH-treated women were ≥2-level composite responders versus placebo in RELEASE-1 (7.6% vs 1.9%; p = .006) and RELEASE-2 (5.6% vs 0.5%; p = .002) and ≥1-level composite responders in RELEASE-1 (37.1% vs 17.8%; p < .001) and RELEASE-2 (41.6% vs 11.2%; p < .001). Most adverse events (AEs) in the CCH group were injection site related; few CCH-treated women discontinued because of an AE (≤4.3%). CONCLUSION: Collagenase clostridium histolyticum-aaes significantly improved cellulite appearance and was generally well tolerated.

Wnt-Signaling Inhibitor Wnt-C59 Suppresses the Cytokine Upregulation in Multiple Organs of Lipopolysaccharide-Induced Endotoxemic Mice via Reducing the Interaction between ß-Catenin and NF-κB.

Sepsis is characterized by multiple-organ dysfunction caused by the dysregulated host response to infection. Until now, however, the role of the Wnt signaling has not been fully characterized in multiple organs during sepsis. This study assessed the suppressive effect of a Wnt signaling inhibitor, Wnt-C59, in the kidney, lung, and liver of lipopolysaccharide-induced endotoxemic mice, serving as an animal model of sepsis. We found that Wnt-C59 elevated the survival rate of these mice and decreased their plasma levels of proinflammatory cytokines and organ-damage biomarkers, such as BUN, ALT, and AST. The Wnt/ß-catenin and NF-κB pathways were stimulated and proinflammatory cytokines were upregulated in the kidney, lung, and liver of endotoxemic mice. Wnt-C59, as a Wnt signaling inhibitor, inhibited the Wnt/ß-catenin pathway, and its interaction with the NF-κB pathway, which resulted in the inhibition of NF-κB activity and proinflammatory cytokine expression. In multiple organs of endotoxemic mice, Wnt-C59 significantly reduced the ß-catenin level and interaction with NF-κB. Our findings suggest that the anti-endotoxemic effect of Wnt-C59 is mediated via reducing the interaction between ß-catenin and NF-κB, consequently suppressing the associated cytokine upregulation in multiple organs. Thus, Wnt-C59 may be useful for the suppression of the multiple-organ dysfunction during sepsis.

Comparison of Cellulite Severity Scales and Imaging Methods.

Cellulite is characterized by dimpled contour alterations of the skin and is present in approximately 85% to 90% of postpubertal females. Although the pathophysiology of cellulite remains to be fully elucidated, experimental evidence indicates a multifactorial process involving the number and types of fibrous septae, microvascular dysfunction, subcutaneous inflammation, decreased dermal thickness with age, and fat deposition. Cellulite is a major cosmetic concern for many women, and a number of both noninvasive (eg, massage, cosmeceuticals, laser therapy) and minimally invasive techniques (eg, subcision, collagenase injection) have been evaluated to improve the appearance of the affected skin. However, evidence for many of these treatments is limited, largely due to the lack of a validated, convenient tool for the standardized evaluation of cellulite severity. Various imaging modalities have been employed to characterize cellulite severity and the impact of treatment, but only 2-dimensional and 3-dimensional digital photography have been adequately validated. However, in many cases, imaging findings do not correlate with subjective measures of cellulite severity. A number of cellulite rating scales have been developed; some provide only a qualitative measure, whereas others do not fully capture all clinically relevant aspects of cellulite, including the perspective of the patient. There remains an unmet need for global adoption of a validated scale that can be utilized easily by clinicians and patients in clinical and research settings. We propose features that should be included in an ideal rating scale for assessment of cellulite severity.

Analytical Validation of HEARTBiT: A Blood-Based Multiplex Gene Expression Profiling Assay for Exclusionary Diagnosis of Acute Cellular Rejection in Heart Transplant Patients.

BACKGROUND: HEARTBiT is a whole blood-based gene profiling assay using the nucleic acid counting NanoString technology for the exclusionary diagnosis of acute cellular rejection in heart transplant patients. The HEARTBiT score measures the risk of acute cellular rejection in the first year following heart transplant, distinguishing patients with stable grafts from those at risk for acute cellular rejection. Here, we provide the analytical performance characteristics of the HEARTBiT assay and the results on pilot clinical validation. METHODS: We used purified RNA collected from PAXgene blood samples to evaluate the characteristics of a 12-gene panel HEARTBiT assay, for its linearity range, quantitative bias, precision, and reproducibility. These parameters were estimated either from serial dilutions of individual samples or from repeated runs on pooled samples. RESULTS: We found that all 12 genes showed linear behavior within the recommended assay input range of 125 ng to 500 ng of purified RNA, with most genes showing 3% or lower quantitative bias and around 5% coefficient of variation. Total variation resulting from unique operators, reagent lots, and runs was less than 0.02 units standard deviation (SD). The performance of the analytically validated assay (AUC = 0.75) was equivalent to what we observed in the signature development dataset. CONCLUSION: The analytical performance of the assay within the specification input range demonstrated reliable quantification of the HEARTBiT score within 0.02 SD units, measured on a 0 to 1 unit scale. This assay may therefore be of high utility in clinical validation of HEARTBiT in future biomarker observational trials.

Collagenase Clostridium Histolyticum for the Treatment of Edematous Fibrosclerotic Panniculopathy (Cellulite): A Randomized Trial.

BACKGROUND: Edematous fibrosclerotic panniculopathy (EFP; cellulite) is associated with thickening and contraction of collagen-rich subdermal septae. Collagenase clostridium histolyticum (CCH) may disrupt collagen-rich septae. OBJECTIVE: To evaluate the safety and efficacy of CCH for treatment of EFP. MATERIALS AND METHODS: In a randomized, double-blind study, women with moderate or severe EFP of the buttocks or posterolateral thighs (i.e., Clinician Reported Photonumeric Cellulite Severity Scale [CR-PCSS] and Patient Reported Photonumeric Cellulite Severity Scale [PR-PCSS] ratings of 3 to 4, and Hexsel Cellulite Severity Scale score ≤13) received up to 3 treatment sessions (Days 1, 22, and 43) of subcutaneous CCH 0.84 mg or placebo injections. End points included the percentage of 2-level and 1-level composite responders (i.e., had ≥2-level or ≥1-level improvement in CR-PCSS and PR-PCSS) at Day 71. RESULTS: Three hundred seventy-five women (mean age, 46.5 years; 86.4% white) were randomly assigned to CCH (n = 189) or placebo (n = 186). At Day 71, the percentages of 2-level and 1-level composite responders were greater with CCH (10.6% and 44.6%, respectively) versus placebo (1.6% and 17.9%; p < .001 for both). The most common adverse events were injection-site related. CONCLUSION: CCH significantly improved EFP appearance versus placebo; further evaluation of CCH for EFP (cellulite) is warranted.

Feasibility of measuring memory response to increasing dexmedetomidine sedation in children.

BACKGROUND: The memory effect of dexmedetomidine has not been prospectively evaluated in children. We evaluated the feasibility of measuring memory and sedation responses in children during dexmedetomidine sedation for non-painful radiological imaging studies. Secondarily, we quantified changes in memory in relation to the onset of sedation. METHODS: A 10 min bolus of dexmedetomidine (2 mcg kg-1) was given to children as they named simple line drawings every five s. The absence of sedation was identified as any verbal response, regardless of correctness. After recovery, recognition memory was tested with correct Yes/No recognitions (50% novel pictures) and was matched to sedation responses during the bolus period (subsequent memory paradigm). RESULTS: Of 64 accruals, 30 children (mean [SD]6.1 (1.2) yr, eight male) received dexmedetomidine and completed all study tasks. Individual responses were able to be modelled successfully in the 30 children completing all the study tasks, demonstrating feasibility of this approach. Children had 50% probability of verbal response at five min 40 s after infusion start, whereas 50% probability of subsequent recognition memory occurred sooner at four min five s. CONCLUSIONS: Quantifying memory and sedation effects during dexmedetomidine infusion in verbal children was possible and demonstrated that memory function was present until shortly before verbal unresponsiveness occurred. This is the first study to investigate the effect of dexmedetomidine on memory in children. CLINICAL TRIAL REGISTRATION: NCT 02354378.

Differences in Blood Pressure in Infants After General Anesthesia Compared to Awake Regional Anesthesia (GAS Study-A Prospective Randomized Trial).

BACKGROUND: The General Anesthesia compared to Spinal anesthesia (GAS) study is a prospective randomized, controlled, multisite, trial designed to assess the influence of general anesthesia (GA) on neurodevelopment at 5 years of age. A secondary aim obtained from the blood pressure data of the GAS trial is to compare rates of intraoperative hypotension after anesthesia and to identify risk factors for intraoperative hypotension. METHODS: A total of 722 infants ≤60 weeks postmenstrual age undergoing inguinal herniorrhaphy were randomized to either bupivacaine regional anesthesia (RA) or sevoflurane GA. Exclusion criteria included risk factors for adverse neurodevelopmental outcome and infants born at <26 weeks of gestation. Moderate hypotension was defined as mean arterial pressure measurement of <35 mm Hg. Any hypotension was defined as mean arterial pressure of <45 mm Hg. Epochs were defined as 5-minute measurement periods. The primary outcome was any measured hypotension <35 mm Hg from start of anesthesia to leaving the operating room. This analysis is reported primarily as intention to treat (ITT) and secondarily as per protocol. RESULTS: The relative risk of GA compared with RA predicting any measured hypotension of <35 mm Hg from the start of anesthesia to leaving the operating room was 2.8 (confidence interval [CI], 2.0-4.1; P < .001) by ITT analysis and 4.5 (CI, 2.7-7.4, P < .001) as per protocol analysis. In the GA group, 87% and 49%, and in the RA group, 41% and 16%, exhibited any or moderate hypotension by ITT, respectively. In multivariable modeling, group assignment (GA versus RA), weight at the time of surgery, and minimal intraoperative temperature were risk factors for hypotension. Interventions for hypotension occurred more commonly in the GA group compared with the RA group (relative risk, 2.8, 95% CI, 1.7-4.4 by ITT). CONCLUSIONS: RA reduces the incidence of hypotension and the chance of intervention to treat it compared with sevoflurane anesthesia in young infants undergoing inguinal hernia repair.

Spinal dopaminergic projections control the transition to pathological pain plasticity via a D1/D5-mediated mechanism.

The mechanisms that lead to the maintenance of chronic pain states are poorly understood, but their elucidation could lead to new insights into how pain becomes chronic and how it can potentially be reversed. We investigated the role of spinal dorsal horn neurons and descending circuitry in plasticity mediating a transition to pathological pain plasticity suggesting the presence of a chronic pain state using hyperalgesic priming. We found that when dorsal horn neurokinin 1 receptor-positive neurons or descending serotonergic neurons were ablated before hyperalgesic priming, IL-6- and carrageenan-induced mechanical hypersensitivity was impaired, and subsequent prostaglandin E2 (PGE2) response was blunted. However, when these neurons were lesioned after the induction of priming, they had no effect on the PGE2 response, reflecting differential mechanisms driving plasticity in a primed state. In stark contrast, animals with a spinally applied dopaminergic lesion showed intact IL-6- and carrageenan-induced mechanical hypersensitivity, but the subsequent PGE2 injection failed to cause mechanical hypersensitivity. Moreover, ablating spinally projecting dopaminergic neurons after the resolution of the IL-6- or carrageenan-induced response also reversed the maintenance of priming as assessed through mechanical hypersensitivity and the mouse grimace scale. Pharmacological antagonism of spinal dopamine D1/D5 receptors reversed priming, whereas D1/D5 agonists induced mechanical hypersensitivity exclusively in primed mice. Strikingly, engagement of D1/D5 coupled with anisomycin in primed animals reversed a chronic pain state, consistent with reconsolidation-like effects in the spinal dorsal horn. These findings demonstrate a novel role for descending dopaminergic neurons in the maintenance of pathological pain plasticity.

MRI differential diagnosis of suspected multiple sclerosis.

Diagnosing multiple sclerosis (MS) can be very challenging owing to its variable clinical features and lack of a definitive test. Magnetic resonance imaging (MRI) is a core diagnostic tool in the detection of MS lesions and demonstration of spatial and temporal distribution of disease. Moreover, MRI plays a crucial role in the exclusion of alternative diagnoses of MS. The aim of this review is to describe the typical MRI features of MS and to present a series of common mimics of MS with emphasis on their distinguishing features from MS.

Impact of a hormone-releasing intrauterine system on the vaginal microbiome: a prospective baboon model.

BACKGROUND: Use of a levonorgestrel-releasing intrauterine system (LNG-IUS) in humans may alter vaginal microbial populations and susceptibility to pathogens. This study evaluated the time-dependent effects of an LNG-IUS on the vaginal microbiome of the baboon, a useful animal model for reproductive studies. METHODS: Levonorgestrel-releasing intrauterine systems were inserted into three reproductively mature, female baboons. The animals were evaluated for 6 months by physical examination and Gram-stained cytology. The vaginal microbiota was characterized at each timepoint by culture-independent analysis of the 16S rRNA-encoding gene. RESULTS: Each baboon harbored a diverse vaginal microbiome. Interindividual variation exceeded intra-individual variation. Diversity declined over time in one baboon and showed mild fluctuations in the other two. There were no significant community differences from early to late post-LNG-IUS placement. CONCLUSIONS: The baboon vaginal microbiome is unique to each individual and is polymicrobial. In this pilot study, the vaginal microbiome remained stable from early to late post-LNG-IUS placement.

The role of the humoral immune response to Clostridium difficile toxins A and B in susceptibility to C. difficile infection: a case-control study.

Antibody levels to Clostridium difficile toxin A (TcdA), but not toxin B (TcdB), have been found to determine risk of C. difficile infection (CDI). Historically, TcdA was thought to be the key virulence factor; however the importance of TcdB in disease is now established. We re-evaluated the role of antibodies to TcdA and TcdB in determining patient susceptibility to CDI in two separate patient cohorts. In contrast to earlier studies, we find that CDI patients have lower pre-existing IgA titres to TcdB, but not TcdA, when compared to control patients. Our findings suggest that mucosal immunity to TcdB may be important in the early stages of infection and identifies a possible target for preventing CDI progression.

Protocol to analyze Drosophila intestinal tumor cellular heterogeneity using immunofluorescence imaging and nuclear size quantification.

Drosophila intestinal tumors show an extended cellular heterogeneity. We devise a protocol to assess tumor cell heterogeneity by employing nuclear size measurement and immunofluorescence-based cell lineage analysis. We describe steps for intestinal dissection, staining, and imaging, followed by detailed procedures for nuclear size analysis. This approach detects overall heterogeneity across the entire tumor cell population and deviations within specific cell populations. The procedure is also applicable for analyzing the heterogeneity of wild-type intestinal cells in various contexts. For complete details on the use and execution of this protocol, please refer to Pranoto et al.1.

Comparative interactome analysis of α-arrestin families in human and Drosophila.

The α-arrestins form a large family of evolutionally conserved modulators that control diverse signaling pathways, including both G-protein-coupled receptor (GPCR)-mediated and non-GPCR-mediated pathways, across eukaryotes. However, unlike ß-arrestins, only a few α-arrestin targets and functions have been characterized. Here, using affinity purification and mass spectrometry, we constructed interactomes for 6 human and 12 Drosophila α-arrestins. The resulting high-confidence interactomes comprised 307 and 467 prey proteins in human and Drosophila, respectively. A comparative analysis of these interactomes predicted not only conserved binding partners, such as motor proteins, proteases, ubiquitin ligases, RNA splicing factors, and GTPase-activating proteins, but also those specific to mammals, such as histone modifiers and the subunits of V-type ATPase. Given the manifestation of the interaction between the human α-arrestin, TXNIP, and the histone-modifying enzymes, including HDAC2, we undertook a global analysis of transcription signals and chromatin structures that were affected by TXNIP knockdown. We found that TXNIP activated targets by blocking HDAC2 recruitment to targets, a result that was validated by chromatin immunoprecipitation assays. Additionally, the interactome for an uncharacterized human α-arrestin ARRDC5 uncovered multiple components in the V-type ATPase, which plays a key role in bone resorption by osteoclasts. Our study presents conserved and species-specific protein-protein interaction maps for α-arrestins, which provide a valuable resource for interrogating their cellular functions for both basic and clinical research.

Prevalence of depression among young people with Type 1 diabetes: a systematic review.

AIMS: To determine: (1) prevalence of depression among young people with Type 1 diabetes compared with control groups or population norms; (2) implications of depression for HbA(1c) level; and (3) the relationship between history of depressive symptoms and future depressive symptoms. BACKGROUND: Among adults with Type 1 diabetes depression is higher than the general population, and has been associated with adverse implications for self-care and HbA(1c) level. The last published review of depression among young people with Type 1 diabetes only included studies up to 1999. METHOD: Systematic searches were conducted for articles published from January 1999 to December 2011 including young people (up to 25 years old) with Type 1 diabetes. RESULTS: Twenty-three articles met the inclusion criteria. Of five studies that reported prevalence of depression compared with control groups, three found no differences. Of the three studies that investigated prevalence of depression making reference to population norms, all three showed higher rates of depressive symptoms. Fourteen of 15 studies found associations between more depressive symptoms and higher HbA(1c) level either cross-sectionally or longitudinally. Past depressive symptoms were associated with later depressive symptoms. CONCLUSIONS: Current evidence is inconclusive about whether there is increased prevalence of depression among young adults with Type 1 diabetes, as established among adults, but those who are more depressed have higher HbA(1c) level. This review is limited by methodological problems and no identified work in the UK met the inclusion criteria. Given the adverse clinical outcomes, we conclude there is a case for routine mental health screening for young adults with Type 1 diabetes.

Eating problems in adolescents with Type 1 diabetes: a systematic review with meta-analysis.

AIMS: We report a systematic review to determine (1) prevalence of eating problems compared with peers and (2) the association between eating problems and glycaemic control in young adults with Type 1 diabetes. METHOD: We conducted a systematic literature search via electronic databases and meta-analysis. Cohen's d (the mean difference score between Type 1 diabetes and comparison groups) was calculated for 13 studies that met inclusion criteria. RESULTS: Eating problems [both disordered eating behaviour (39.3 and 32.5%; d = 0.52, 95% CI 0.10-0.94) and eating disorders (7.0 and 2.8%; d = 0.46, 95% CI 0.10-0.81)] were more common in adolescents with Type 1 diabetes compared with peers and both were associated with poorer glycaemic control (d = 0.40, 95% CI 0.17-0.64). In restricted analyses involving measures adapted for diabetes, associations between eating problems and poorer glycaemic control remained (d = 0.54, 95% CI 0.32-0.76). Disordered eating behaviour (51.8 and 48.1%; d = 0.06, 95% CI -0.05 to 0.21) and eating disorders (6.4 and 3.0%; d = 0.43, 95% CI -0.06 to 0.91) were more common in adolescents with Type 1 diabetes compared with peers, but differences were non-significant. CONCLUSIONS: Eating problems are common among this age group. Future work in populations with Type 1 diabetes should develop sensitive measures of eating problems and interventions, and establish predictors of eating problems. Screening in clinics is recommended.