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.

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.

More pilot trials could plan to use qualitative data: a meta-epidemiological study.

BACKGROUND: Pilot trials often use quantitative data such as recruitment rate and retention rate to inform the design and feasibility of a larger trial. However, qualitative data such as patient, healthcare provider, and research staff perceptions of an intervention may also provide insights for a larger trial. METHODS: As part of a larger study investigating the reporting of progression criteria in pilot studies, we sought to determine how often pilot studies planned to use qualitative data to inform the design and feasibility of a larger trial and the factors associated with plans to use qualitative data. We searched for protocols of pilot studies of randomized trials in PubMed between 2013 and 2017. RESULTS: We included 227 articles. Only 92 (40.5%; 95% confidence interval [CI] 34.1-47.2) reported plans to collect qualitative data. The factors associated with collecting qualitative data were large studies (defined as sample size ≥ 60; adjusted odds ratio [aOR] 2.77; 95% CI 1.47-5.23; p = 0.002) and studies from Europe (aOR 3.86; 95% CI 1.68-8.88; p = 0.001) compared to North America and the rest of the world. Pilot trials with pharmacological interventions were less likely to plan to collect qualitative data (aOR 0.20; 95% CI 0.07-0.58; p = 0.003). CONCLUSIONS: Qualitative data is not used enough in pilot trials. Large pilot trials, pilot trials from Europe, and pilot trials of non-pharmacological interventions are more likely to plan for qualitative data.

The efficacy and safety of insulin pump therapy with predictive low glucose suspend feature in decreasing hypoglycemia in children with type 1 diabetes mellitus: A systematic review and meta-analysis.

BACKGROUND: Automated insulin delivery with predictive low glucose suspend (PLGS) feature has the potential to reduce risk of hypoglycemia in patients with type 1 diabetes mellitus (T1DM). We aim to systematically synthesize the evidence on the efficacy and safety of PLGS in children and adolescents with T1DM. METHODS: We performed a systematic search through Ovid/MEDLINE, Ovid/Embase, and other search engines. We included randomized controlled trials (RCTs) evaluating the effect of sensor augmented pump (SAP) with PLGS feature compared to SAP or insulin pump therapy without SAP in decreasing hypoglycemia in children and adolescents aged 2 to 18 years with T1DM, with at least 2 weeks of follow-up. Two reviewers independently selected studies, extracted data, and evaluated the risk of bias (ROB). RESULTS: Five RCTs with total sample size of 493 children aged 6 to 18 years met the inclusion criteria. The overall ROB of included studies was low. There is high quality evidence that PLGS is superior to SAP in decreasing time spent in hypoglycemia (sensor glucose [SG] <3.9 mmol/L [<70 mg/dL]/24 h) and nocturnal hypoglycemia (SG <3.9 mmol [<70 mg/dL]/L/night) with an absolute mean difference of 17.4 min/d (95% CI: -19.2, -15.5) and 26.3 min/night (95% CI: -35.5, -16.7), respectively, without increasing percentage of time spent in hyperglycemia or episodes of diabetic ketoacidosis (DKA). There was insufficient evidence for the impact of PLGS on health related quality of life (HRQL). CONCLUSIONS: PLGS is superior to SAP in decreasing daytime and nocturnal hypoglycemia without increasing the risk of DKA or hyperglycemia. Future studies should address the impact of PLGS on children younger than 6-years-old and HRQL.

The reporting of progression criteria in protocols of pilot trials designed to assess the feasibility of main trials is insufficient: a meta-epidemiological study.

INTRODUCTION: Pilot and feasibility trials are conducted to determine feasibility or to collect information that would inform the design of a larger definitive trial. Clear progression criteria are required to determine if a definitive or main trial is feasible and how it should be designed. We sought to determine how often progression criteria are reported and the associated factors. METHODS: We conducted a methodological review of protocols for pilot randomised trials published in three journals that publish research protocols (BMJ Open, Trials, Pilot and Feasibility Studies), using a PubMed search (2013-2017). We extracted bibliometric information including the country in which the study was conducted, source of funding, type of intervention, use of a primary feasibility outcome, sample size reporting, and justification. We used generalised linear models to determine the factors associated with reporting progression criteria. RESULTS: Our search retrieved 276 articles, of which 49 were not eligible. We included 227 articles. Overall, 45/227 (19.8%; 95% confidence interval [CI] 14.8-25.6) reported progression criteria. Protocols published in more recent years were significantly associated with higher odds of reporting progression criteria (adjusted odds ratio [aOR] 1.40; 95% CI 1.03-1.92; p = 0.034). Pilot trials from Europe (aOR 0.19; 95% CI 0.08-0.48; p < 0.001) and the rest of the world (aOR 0.05; 95% CI 0.01-0.18; p < 0.003) compared to North America were significantly associated with lower odds of reporting progression criteria. Journal, source of funding, sample size, intervention type, and having a primary outcome related to feasibility were not significantly associated with reporting progression criteria. CONCLUSION: Progression criteria are not often explicitly stated in protocols of pilot trials leaving room for varied interpretation of findings. The development of formal guidance for progression criteria in protocols of pilot trials is warranted.

A meta-epidemiological study of subgroup analyses in cochrane systematic reviews of atrial fibrillation.

BACKGROUND: Information on subgroup assessments in systematic reviews (SR) of atrial fibrillation (AF) is limited. This review aims to describe subgroup analyses in AF SRs to inform the design of SRs and randomized trials as well as clinical practice. METHODS: We conducted a cross sectional meta-epidemiological study of Cochrane AF reviews by searching AF (including variants) in the title, abstract, or keyword field without date or language restrictions (Issue 9; September 2018). Two reviewers independently extracted study characteristics to summarize frequency of subgroups pre-specified and conducted and report credibility of subgroup effects claimed. RESULTS: Of 39 Cochrane reviews identified, 17 met inclusion criteria (including 168 reports of 127 randomized trials) and the majority (16; 94.1%) conducted meta-analysis of outcomes. Most (13; 76.5%) planned pre-specified subgroup analyses; 7 of which (41.2%) conducted subgroups. In these 7 reviews, 56 subgroups were planned, 17 (30.4%) conducted and 6 (10.7%) yielded subgroup effects. Variables such as co-morbid disease, stroke risk factors, prior stroke/transient ischemic attack, age, race, and sex represented 44% (24 subgroups) of all planned subgroups (8 conducted; 14.3%); however, information on covariate selection was lacking. Overall, more subgroups were planned than conducted (mean difference (95% CI) 2.3 (1.2-3.5, p < 0.001)). Of all subgroups conducted, anticoagulant characteristics comprised a third of all subgroup effects (n = 5, 35.7%). The credibility of subgroups identified (n = 14) was assessed and less than half (43%) represented one of a small number of pre-specified hypothesis and rarely were effects seen within studies (7%). Of 5 reviews that reported subgroup effects, only 3 discussed subgroup effects as part of the overall conclusions; none discussed credibility of subgroup effects. CONCLUSIONS: This meta-epidemiological review of a subset of Cochrane AF reviews suggests that planning and reporting of subgroup analyses in AF reviews can be improved to better inform clinical management. Most pre-specified subgroup analyses were not performed, important variables (such as stroke, bleeding risk, and other comorbidities) were rarely examined and credibility of subgroup effects claimed was low. Future reviews should aim to identify important subgroups in their protocols and use recommended approaches to test subgroup effects in order to better support clinical decision-making.

Exploring the outcome of multiple sclerosis among Saudi adult patients. A single-centered cross-sectional study at King Abdulaziz Medical City in Riyadh, Saudi Arabia.

OBJECTIVE: To assess the outcome and impact of multiple sclerosis (MS) using validated Arabic versions of the Barthel index (BI) multiple sclerosis impact scale (MSIS-29), the modified Rankin scale (mRS), and the expanded disability status scale (EDSS). METHODS: A cross-sectional study conducted at King Abdulaziz Medical City in Riyadh, Kingdom of Saudi Arabia, during July-November 2017. All Saudi adult patients diagnosed with MS between 2000-2016 (269 patients) were included. Patients were contacted via phone calls and were assessed using a newly developed and validated multi-component questionnaire that included demographic data, disease course, and Arabic versions of the scales RESULTS: Out of 269 patients, 210 (78.2%) responded. The average patient age was 37.44+/-10.3 years. The majority were females (69.5%). Only, 51 (24.3%) patients reported worsening conditions. Annually, the average relapse rate was 2.28+/-1.91. In regard to patient outcomes, 120 (57.1%) showed no significant disability in mRS, 146 (69.5%) were ambulatory without aid in EDSS, and 185 (89.4%) were independent in BI scores. The average MSIS-29-PHYS score was 33.6+/-27.6 and MSIS-29-PSYCH score was 38.2+/-25.8. Modified Rankin scale and EDSS were significantly associated with the current use of disease-modifying therapy (DMT). Modified Rankin scale was negatively associated with delayed diagnosis. Barthel index showed significant association with medication compliance and the absence of attacks. CONCLUSION: Majority of patients had a favorable outcome that was linked with the use of DMT, compliance, early diagnosis, and absence of attacks.