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Context The clinical utility and implications of continuous glucose monitoring (CGM) in cystic fibrosis (CF) are unclear. Objective We examined the correlation between CGM measures and clinical outcomes in adults with CF, investigated the relationship between hemoglobin A1c (HbA1c) and CGM-derived average glucose (AG), and explored CGM measures that distinguish cystic fibrosis–related diabetes (CFRD) from normal and abnormal glucose tolerance. Methods This prospective observational study included 77 adults with CF who had CGM and HbA1c measured at 2 to 3 time points 3 months apart. Results Thirty-one of the 77 participants met American Diabetes Association–recommended diagnostic criteria for CFRD by oral glucose tolerance testing and/or HbA1c. In all participants, CGM measures of hyperglycemia and glycemic variability correlated with nutritional status and pulmonary function. HbA1c was correlated with AG (R2 = 0.71, P < 0.001), with no significant difference between this regression line and that previously established in type 1 and type 2 diabetes and healthy volunteers. Cutoffs of 17.5% time > 140 mg/dL and 3.4% time > 180 mg/dL had sensitivities of 87% and 90%, respectively, and specificities of 95%, for identifying CFRD. Area under the curve and percent of participants correctly classified with CFRD were higher for AG, SD, % time > 140, > 180, and > 250 mg/dL than for HbA1c. Conclusion CGM measures of hyperglycemia and glycemic variability are superior to HbA1c in distinguishing those with and without CFRD. CGM-derived AG is strongly correlated with HbA1c in adults with CF, with a similar relationship to other diabetes populations. Future studies are needed to investigate CGM as a diagnostic and screening tool for CFRD.

Background Cystic fibrosis related diabetes (CFRD) is associated with pulmonary decline and compromised nutritional status. Emerging data suggest that CFTR dysfunction may play a direct role in the pathogenesis of CFRD; however, studies investigating the effect of CFTR modulators on glycemic outcomes in patients with cystic fibrosis (CF) have shown mixed results. The impact of elexacaftor-tezacaftor-ivacaftor (ETI) on glycemic control is currently unknown. Our objective was to investigate the effect of ETI initiation on glycemia in adults with CF using continuous glucose monitoring (CGM). Methods In this prospective observational study, 34 adults with CF and at least one F508del CFTR mutation wore CGM sensors for 14 days prior to starting ETI and again 3-12 months after ETI initiation. Hypoglycemia symptoms were queried at each visit, and most recent anthropometric measures and spirometry data were obtained by chart review. Results Twenty-three participants completed the study. Compared to baseline, average glucose (AG), standard deviation (SD), % time >200 mg/dL, and peak sensor glucose decreased with ETI treatment, and % time in target range 70-180 mg/dL increased. Improvements in glycemic parameters were most notable in individuals with CFRD. There was no significant change in CGM-measured or self-reported hypoglycemia before and after ETI initiation. Conclusion Initiation of ETI in adults with CF was associated with improvement CGM-derived measures of hyperglycemia and glycemic variability with no effect on hypoglycemia. Further studies are needed to investigate underlying etiology of these changes and the long-term impact of ETI on glycemic control in patients with CF.

Background: Wolfram syndrome is a rare neurodegenerative disorder, characterized by the presence of diabetes insipidus, diabetes mellitus, optic atrophy, and sensorineural deafness. The majority of cases are due to autosomal recessive biallelic variants in the WFS1 gene; however, pathogenic autosomal dominant (AD) mutations have also been described. Glucagon-like peptide (GLP-1) agonists have been studied in both animal models and humans with classic Wolfram syndrome. Case: We present a 15-year-old female with a personal and family history of congenital strabismus, bilateral cataracts, low-frequency sensorineural hearing loss, and diabetes mellitus. Trio whole exome sequencing revealed a previously unknown maternally inherited heterozygous variant in exon 8 of the WFS1 gene c.2605_2616del12 p.Ser869_His872del, leading to the diagnosis of AD WFS1-related disorder. Treatment with a GLP-1 agonist resulted in marked improvement in glycemic control and discontinuation of insulin therapy. This patient’s response to a GLP-1 agonist provides suggestive indirect evidence for a role of WFS1 on β-cell endoplasmic reticulum stress and suggests that treatment with a GLP-1 agonist should be considered in patients with dominant forms of WS.

Fanconi-Bickel syndrome (FBS) is a rare autosomal recessive disease, resulting from mutations in the SLC2A2 gene, causing impaired glucose transporter 2 protein transporter protein function, impaired glucose and galactose utilisation, hepatorenal glycogen accumulation and organ dysfunction. Clinical features include failure to thrive, hepatomegaly, rickets, short stature and delayed puberty. Therapy includes electrolyte supplementation and uncooked cornstarch. We present a 15-year-old boy diagnosed with FBS in infancy. Growth velocity was normal on standard treatment until age 8.5 years, at which time growth failure led to a diagnosis of acquired growth hormone (GH) deficiency. Initiation of recombinant human GH (rhGH) replacement of 0.25 μg/kg/week resulted in marked improvement in growth velocity and height. While short stature is expected in FBS, growth velocity that falls below the normal range despite adequate therapy should prompt further evaluation. Our case suggests that acquired GH deficiency can arise in FBS and benefits from rhGH therapy.

The value of physical examination findings in the diagnosis of pneumonia in children may be limited, and the accuracy of physicians in predicting pneumonia is not known.We sought to determine the correlation between physicians' assessment of the likelihood of pneumonia and radiographic presence of pneumonia.Prospective observational study of children 21 years or younger presenting to a pediatric emergency department, who had a chest radiography performed for suspicion of pneumonia. Physicians recorded clinical findings and likelihood of pneumonia before obtaining the radiograph. Definite and probable pneumonia was defined by a radiologist's interpretation of the radiograph.Of 2071 children, 147 (7%) had definite radiographic pneumonia, whereas 321 (15%) had probable or definite pneumonia. Among patients perceived to be at lowest risk for pneumonia (5% prediction), 4.3% (95% confidence interval [CI], 2.9%-5.7%) had definite pneumonia, and 10.0% (95% CI, 8.3%-12.5%) had probable or definite pneumonia. Among children perceived to be at highest risk for pneumonia (75% prediction), 30.6% (95% CI, 15.5%-45.6%) had definite pneumonia, and 52.8% (95% CI, 37.7%-70.3%) had probable or definite pneumonia. Physicians' estimates of the likelihood of pneumonia were positively correlated with the rate of definite (Spearman ρ = 0.15, P0.001) and probable or definite radiographic pneumonia (Spearman ρ = 0.19, P0.001).With some overestimation, physicians' assessment of the likelihood of pneumonia correlates well with radiographic diagnosis of pneumonia.