Relationship Between Macular Thickness and Visual Acuity in the Treatment of Diabetic Macular Edema With Anti-VEGF Therapy: Systematic Review.

Purpose: To examine the relationship between central macular thickness (CMT) measured by optical coherence tomography (OCT) and visual acuity (VA) in patients with center-involving diabetic macular edema (DME) receiving antivascular endothelial growth factor (anti-VEGF) treatment. Methods: Peer-reviewed articles from 2016 to 2020 reporting intravitreal injections of bevacizumab, ranibizumab, or aflibercept that provided data on pretreatment (baseline) and final retinal thickness (CMT) and visual acuity (VA) were identified. The relationship between relative changes was assessed via a linear random-effects regression model controlling for treatment group. Results: No significant association between the logarithm of the minimum angle of resolution (logMAR) VA and CMT was found in 41 eligible studies evaluating 2667 eyes. The observed effect estimate was a 0.12 increase (95% CI, -0.124 to 2.47) in logMAR VA per 100 µm reduction in CMT after treatment change. There were no significant differences in logMAR VA between the anti-VEGF treatment groups. Conclusions: There was no statistically significant relationship between the change in logMAR VA and change in CMT as well as no significant effect of the type of anti-VEGF treatment on the change in logMAR VA. Although OCT analysis, including measurements of CMT, will continue to be an integral part of the management of DME, further exploration is needed on additional anatomic factors that might contribute to visual outcomes.

Global Prevalence of Diabetic Retinopathy in Pediatric Type 2 Diabetes: A Systematic Review and Meta-analysis.

Importance: Type 2 diabetes (T2D) is increasing globally. Diabetic retinopathy (DR) is a leading cause of blindness in adults with T2D; however, the global burden of DR in pediatric T2D is unknown. This knowledge can inform retinopathy screening and treatments to preserve vision in this population. Objective: To estimate the global prevalence of DR in pediatric T2D. Data Sources: MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), the Cochrane Library, the Web of Science, and the gray literature (ie, literature containing information that is not available through traditional publishing and distribution channels) were searched for relevant records from the date of database inception to April 4, 2021, with updated searches conducted on May 17, 2022. Searches were limited to human studies. No language restrictions were applied. Search terms included diabetic retinopathy; diabetes mellitus, type 2; prevalence studies; and child, adolescent, teenage, youth, and pediatric. Study Selection: Three teams, each with 2 reviewers, independently screened for observational studies with 10 or more participants that reported the prevalence of DR. Among 1989 screened articles, 27 studies met the inclusion criteria for the pooled analysis. Data Extraction and Synthesis: This systematic review and meta-analysis followed the Meta-analysis of Observational Studies in Epidemiology (MOOSE) and the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines for systematic reviews and meta-analyses. Two independent reviewers performed the risk of bias and level of evidence analyses. The results were pooled using a random-effects model, and heterogeneity was reported using χ2 and I2 statistics. Main Outcomes and Measures: The main outcome was the estimated pooled global prevalence of DR in pediatric T2D. Other outcomes included DR severity and current DR assessment methods. The association of diabetes duration, sex, race, age, and obesity with DR prevalence was also assessed. Results: Among the 27 studies included in the pooled analysis (5924 unique patients; age range at T2D diagnosis, 6.5-21.0 years), the global prevalence of DR in pediatric T2D was 6.99% (95% CI, 3.75%-11.00%; I2 = 95%; 615 patients). Fundoscopy was less sensitive than 7-field stereoscopic fundus photography in detecting retinopathy (0.47% [95% CI, 0%-3.30%; I2 = 0%] vs 13.55% [95% CI, 5.43%-24.29%; I2 = 92%]). The prevalence of DR increased over time and was 1.11% (95% CI, 0.04%-3.06%; I2 = 5%) at less than 2.5 years after T2D diagnosis, 9.04% (95% CI, 2.24%-19.55%; I2 = 88%) at 2.5 to 5.0 years after T2D diagnosis, and 28.14% (95% CI, 12.84%-46.45%; I2 = 96%) at more than 5 years after T2D diagnosis. The prevalence of DR increased with age, and no differences were noted based on sex, race, or obesity. Heterogeneity was high among studies. Conclusions and Relevance: In this study, DR prevalence in pediatric T2D increased significantly at more than 5 years after diagnosis. These findings suggest that retinal microvasculature is an early target of T2D in children and adolescents, and annual screening with fundus photography beginning at diagnosis offers the best assessment method for early detection of DR in pediatric patients.

The Prevalence of Obesity Among Children With Type 2 Diabetes: A Systematic Review and Meta-analysis.

Importance: The childhood obesity epidemic is presumed to drive pediatric type 2 diabetes (T2D); however, the global scale of obesity in children with T2D is unknown. Objectives: To evaluate the global prevalence of obesity in pediatric T2D, examine the association of sex and race with obesity risk, and assess the association of obesity with glycemic control and dyslipidemia. Data Sources: MEDLINE, Embase, CINAHL, Cochrane Library, and Web of Science were searched from database inception to June 16, 2022. Study Selection: Observational studies with at least 10 participants reporting the prevalence of obesity in patients with pediatric T2D were included. Data Extraction and Synthesis: Following the Meta-analysis of Observational Studies in Epidemiology reporting guideline, 2 independent reviewers in teams performed data extraction and risk of bias and level of evidence analyses. The meta-analysis was conducted using a random-effects model. Main Outcomes and Measures: The primary outcomes included the pooled prevalence rates of obesity in children with T2D. The secondary outcomes assessed pooled prevalence rates by sex and race and associations between obesity and glycemic control and dyslipidemia. Results: Of 57 articles included in the systematic review, 53 articles, with 8942 participants, were included in the meta-analysis. The overall prevalence of obesity among pediatric patients with T2D was 75.27% (95% CI, 70.47%-79.78%), and the prevalence of obesity at diabetes diagnosis among 4688 participants was 77.24% (95% CI, 70.55%-83.34%). While male participants had higher odds of obesity than female participants (odds ratio, 2.10; 95% CI, 1.33-3.31), Asian participants had the lowest prevalence of obesity (64.50%; 95% CI, 53.28%-74.99%), and White participants had the highest prevalence of obesity (89.86%; 95% CI, 71.50%-99.74%) compared with other racial groups. High heterogeneity across studies and varying degrees of glycemic control and dyslipidemia were noted. Conclusions and Relevance: The findings of this systematic review and meta-analysis suggest that obesity is not a universal phenotype in children with T2D. Further studies are needed to consider the role of obesity and other mechanisms in diabetes genesis in this population.

Insulin pump complications among children with diabetes.

QUESTION: Several children with diabetes in our clinic use continuous subcutaneous insulin infusion therapy. Recently a 5-year-old presented with a dysfunctional pump, and it took 2 days to identify the problem and resolve it. What are the potential pitfalls of insulin pumps in children and how can these be prevented? ANSWER: The use of continuous subcutaneous insulin infusion pumps has increased considerably during the past decade. Adverse events can range from mild events that can be resolved by troubleshooting at home, to severe incidents that necessitate admission to the hospital. Adverse events include technical issues, skin complications that can lead to infection, and metabolic imbalances that can lead to hospitalization. Long-term monitoring and targeted education are needed for children and their families to ensure early identification of problems with the pump and to avoid diabetic ketoacidosis or hypoglycemia.

Prevalence of Polycystic Ovary Syndrome in Patients With Pediatric Type 2 Diabetes: A Systematic Review and Meta-analysis.

Importance: The prevalence of pediatric type 2 diabetes (T2D) is increasing globally. Girls with T2D are at risk of developing polycystic ovary syndrome (PCOS), but the prevalence of PCOS among girls with T2D is unknown. Objective: To determine the prevalence of PCOS in girls with T2D and to assess the association of obesity and race with this prevalence. Data Sources: In this systematic review and meta-analysis, MEDLINE, Embase, CINAHL, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Web of Science: Conference Proceedings Citation Index-Science, and the gray literature were searched from inception to April 4, 2021. Study Selection: Two reviewers independently screened for studies with observational study design that recruited 10 or more participants and reported the prevalence of PCOS in girls with T2D. Data Extraction and Synthesis: Risk of bias was evaluated using a validated tool, and level of evidence was assessed using the Oxford Centre for Evidence-Based Medicine criteria. A random-effects meta-analysis was performed. This study follows the Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guideline. Main Outcomes and Measures: The main outcome of this systematic review was the prevalence of PCOS in girls with T2D. Secondary outcomes included assessing the associations of obesity and race with PCOS prevalence. Results: Of 722 screened studies, 6 studies involving 470 girls with T2D (mean age at diagnosis, 12.9-16.1 years) met the inclusion criteria. The prevalence (weighted percentage) of PCOS was 19.58% (95% CI, 12.02%-27.14%; I2 = 74%; P = .002). Heterogeneity was moderate to high; however, it was significantly reduced after excluding studies that did not report PCOS diagnostic criteria, leading to a calculated prevalence (weighted percentage) of 24.04% (95% CI, 15.07%-33.01%; I2 = 0%; P = .92). Associations with obesity and race could not be determined because of data paucity. Conclusions and Relevance: In this meta-analysis, approximately 1 in 5 girls with T2D had PCOS, but the results of this meta-analysis should be considered with caution because studies including the larger numbers of girls did not report the criteria used to diagnose PCOS, which is a challenge during adolescence. The associations of obesity and race with PCOS prevalence among girls with T2D need further evaluation to help define at-risk subgroups and implement early assessment and treatment strategies to improve management of this T2D-related comorbidity.

Prevalence of Hypertension and Albuminuria in Pediatric Type 2 Diabetes: A Systematic Review and Meta-analysis.

Importance: Hypertension and albuminuria are markers of diabetes-related nephropathy and important factors associated with kidney outcomes in pediatric type 2 diabetes. However, their prevalence in these patients is unknown. Objective: To measure the prevalence of hypertension and albuminuria in pediatric patients with type 2 diabetes and to evaluate the association of sex and race/ethnicity with these conditions. Data Sources: MEDLINE, Embase, CINAHL, Cochrane Library, Web of Science, the gray literature, and references of the screened articles were searched for human studies from date of database inception to February 20, 2020. Study Selection: Observational studies with at least 10 participants reporting the prevalence of hypertension and/or albuminuria in pediatric patients with type 2 diabetes were included. Three teams of 2 independent reviewers screened 7614 papers, of which 60 fulfilled the eligibility criteria. Data Extraction and Synthesis: Three teams of 2 independent reviewers performed data extraction, risk of bias analysis, and level of evidence analyses. The meta-analysis was conducted using a random-effects model and followed the Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines. Main Outcomes and Measures: The primary outcomes included the pooled prevalence rates (percentages with 95% CI) for hypertension and albuminuria. The secondary outcomes assessed pooled prevalence rates by sex and racial/ethnic group. Results: Sixty studies were included in the systematic review. Diabetes duration varied from inclusion at diagnosis to 15.0 years after diagnosis, and the reported mean age at diagnosis ranged from 6.5 to 21.0 years. Hypertension prevalence among 3463 participants was 25.33% (95% CI, 19.57%-31.53%). Male participants had higher hypertension risk than female participants (odds ratio [OR], 1.42 [95% CI, 1.10-1.83]), with Pacific Islander and Indigenous youth having the highest prevalence of all racial/ethnic groups (Pacific Islander youth: 26.71% [95% CI, 14.54%-40.72%]; Indigenous youth: 26.48% [95% CI, 17.34%-36.74%]; White youth: 20.95% [95% CI, 12.65%-30.57%]; African American youth: 19.04% [95% CI, 12.01%-27.23%]; Hispanic/Latino youth: 15.11% [95% CI, 6.56%-26.30%]; Asian youth: 18.37% [95% CI, 9.49%-29.23%]). Albuminuria prevalence among 2250 participants was 22.17% (95% CI, 17.34%-27.38%). Pacific Islander youth, Indigenous youth, and Asian youth had higher prevalence rates than White youth (Pacific Islander youth: 31.84% [95% CI, 11.90%-55.47%]; Indigenous youth: 24.27% [95% CI, 14.39%-35.73%]; Asian youth: 23.00% [95% CI, 18.85%-27.41%]; White youth: 12.59% [95% CI, 7.75%-18.33%]), with no sex differences (OR for male vs female participants, 0.68 [95% CI, 0.46-1.01]). Heterogeneity was high among studies, with a low to moderate risk of bias. Conclusions and Relevance: In this study, markers of diabetes-related nephropathy were commonly detected in pediatric patients with type 2 diabetes, with a disproportionate burden noted among Pacific Islander and Indigenous youth. Personalized management strategies to target kidney outcomes are urgently needed in pediatric patients with type 2 diabetes to alleviate the burden of this condition on the kidneys.

Paraspinal muscle ladybird homeobox 1 (LBX1) in adolescent idiopathic scoliosis: a cross-sectional study.

BACKGROUND CONTEXT: Adolescent idiopathic scoliosis (AIS) is the leading cause of spinal deformity in adolescents globally. Recent evidence from genome-wide association studies has implicated variants in or near the ladybird homeobox 1 (LBX1) gene, encoding the ladybird homeobox 1 transcription factor, in AIS development. This gene plays a critical role in guiding embryonic neurogenesis and myogenesis and is vital in muscle mass determination. Despite the confirmation of the role for LBX1 gene variants in the development of AIS, the biological basis of LBX1 contribution to AIS remains mostly unknown. PURPOSE: To investigate the potential role of LBX1 in driving spinal curving, curve laterality, and progression through muscle-based mechanisms in AIS patients by analyzing its gene and protein expression. STUDY DESIGN: This is a cross-sectional study using clinical data and biological samples from the Immunometabolic CONnections to Scoliosis study (ICONS study). PATIENT SAMPLE: Twenty-five patients with AIS provided informed consent. Paraspinal muscle biopsies from the maximal points of concavity and convexity for gene expression and protein analysis were obtained at the start of corrective spinal surgery. OUTCOME MEASURES: The outcome measures included the detection of paraspinal muscle LBX1 mRNA abundance and LBX1 protein expression and the correlation of the latter with age, sex, and curve severity. METHODS: The measurement of mRNA abundance was done using quantitative real-time polymerase chain reaction (qRT-PCR). Additionally, protein lysates from the biopsied muscle samples were probed with a monoclonal LBX1 antibody to compare the muscle protein levels on either side of the scoliotic curve by western blot. This study received funding from the Division of Orthopedics, Department of Surgery, McMaster University, Hamilton, Ontario, Canada ($39,900 CAN for 2 years). The authors have no conflicts of interest to disclose. RESULTS: LBX1 mRNA abundance (concave 2.98±0.87, convex 3.40±1.10, p value 0.73) and protein expression (concave 1.20±0.13, convex 1.21±0.10, p value 0.43) were detected on both sides of the scoliotic curve at equivalent levels. The expression of LBX1 protein did not correlate with age (concave: correlation coefficient 0.32, p value 0.12; convex: correlation coefficient 0.08, p value 0.69), sex (concave: correlation coefficient -0.03, p value 0.08; convex: correlation coefficient 0.07, p value 0.72), or the severity of spinal curving measured using the Cobb angle (concave: correlation coefficient -0.16, p value 0.45; convex: correlation coefficient -0.08, p value 0.69). CONCLUSIONS: LBX1 is expressed in erector spinae muscles, and its levels are equal in muscles on both sides of the scoliotic curve in AIS. The expression of LBX1 on the convex and concave sides of the scoliotic curve did not correlate with age, sex, or the severity of spinal curving. The molecular mechanisms by which LBX1contributes to the development and propagation of AIS need to be explored further in muscle and other tissues.