Bone health in young adults with type 1 diabetes and progressive eGFR decline.

BACKGROUND: Type 1 Diabetes (T1D) is associated with increased risk of fractures, worsened by presence of microvascular complications. This study's objective is to determine the impact of progressive decline in estimated glomerular filtration rate (eGFR) on bone biomarkers and bone microarchitecture in youth with T1D. METHODS: Slopes of eGFR were calculated using measures obtained at four timepoints from adolescence to young adulthood. Participants were identified as eGFR decliners if eGFR decreased ≥ 3ml/min/1.73m2/year. Bone health was assessed in young adulthood by high resolution peripheral quantitative computed tomography (HRpQCT Xtreme CTII) and bone biomarkers; osteocalcin, procollagen 1 intact n-terminal pro-peptide (P1NP), c-terminal telopeptide (CTX), and bone specific alkaline phosphatase. The relationship between diabetes duration, glycated hemoglobin, body mass index (BMI) and vitamin D level on bone biomarkers and microarchitecture was evaluated. Linear regression analysis was used for the statistical analysis in this study. RESULTS: Ninety-nine study participants were studied with longitudinal evaluation of eGFR over 7.4 ± 1.0 years with mean age of 14.7 ± 1.7 years at baseline. Cross sectional evaluation of bone was performed at 21.3 ± 2.1 years. 44% participants had eGFR decline and showed 5% higher cortical porosity diameter than non-decliners (p = 0.035). Greater diabetes duration was associated with higher trabecular separation (p = 0.004) and lower trabecular number (p = 0.01). Higher level of 25 hydroxy-vitamin D was associated with lower trabecular separation (p = 0.01). Elevated glycated hemoglobin (p = 0.0008) and BMI (p = 0.009), were associated with lower markers of bone formation. CONCLUSION: Mild increase in cortical porosity diameter was found in youth with T1D and eGFR decline, however, overall measures of bone microarchitecture on HR-pQCT were similar between both groups and there were no statistically significant changes in bone biomarkers. Hence, skeletal impairments were limited in youth with different eGFR trajectories near peak bone mass. Longitudinal HR-pQCT studies are needed to further understand the impact of eGFR decline on bone microarchitecture. Optimal glycemic control, normal BMI and vitamin D status were supported by this study as important markers for good bone health.

Association of School Instructional Mode with Community COVID-19 Incidence during August-December 2020 in Cuyahoga County, Ohio.

Remote and hybrid modes of instruction were employed as alternatives to in-person instruction as part of early mitigation efforts in response to the COVID-19 pandemic. We investigated the impact of a public school district's instructional mode on cumulative incidence and transmission in the surrounding community by employing a generalized estimating equations approach to estimate the association with weekly COVID-19 case counts by zip code in Cuyahoga County, Ohio, from August to December 2020. Remote instruction only (RI) was employed by 7 of 20 school districts; 13 used some non-remote instruction (NRI) (2-15 weeks). Weekly incidence increased in all zip codes from August to peak in late fall before declining. The zip code cumulative incidence within NRI school districts was higher than in those offering only RI (risk ratio = 1.12, p = 0.01; risk difference = 519 per 100,000, 95% confidence interval (123-519)). The mean effect for NRI on emergent cases 2 weeks after mode exposure, controlling for Social Vulnerability Index (SVI), was significant only for high SVI zip codes 1.30, p < 0.001. NRI may be associated with increased community COVID-19 incidence, particularly in communities with high SVI. Vulnerable communities may need more resources to open schools safely.

Association of Fructosamine Levels With Glycemic Control in Children With Type 1 Diabetes as Determined by Continuous Glucose Monitoring: Results From the CGM TIME Trial.

OBJECTIVE: Our aim in this study was to determine the correlation between serum fructosamine and average blood glucose, as measured by continuous glucose monitoring (CGM) in children with type 1 diabetes. METHODS: Ninety-seven blood samples were collected from 70 participants in the Timing of Initiation of continuous glucose Monitoring in Established pediatric diabetes (CGM TIME) Trial. Each eligible participant had 3 weeks of CGM data with at least 60% CGM adherence before blood collection. Ordinary least-squares linear regression incorporating restricted cubic splines was used to determine the association between fructosamine levels and mean blood glucose. RESULTS: An association was found between fructosamine and mean blood glucose, with an F statistic of 9.543 (p<0.001). Data were used to create a formula and conversion chart for calculating mean blood glucose from fructosamine levels for clinical use. CONCLUSIONS: There is a complex relationship between average blood glucose, as determined by CGM and fructosamine. Fructosamine levels may be clinically useful for assessing short-term glycemic control when CGM is not available.

Metabolic and other morbid complications in congenital generalized lipodystrophy type 4.

Morbidity and mortality rates in patients with autosomal recessive, congenital generalized lipodystrophy type 4 (CGL4), an ultra-rare disorder, remain unclear. We report on 30 females and 16 males from 10 countries with biallelic null variants in CAVIN1 gene (mean age, 12 years; range, 2 months to 41 years). Hypertriglyceridemia was seen in 79% (34/43), hepatic steatosis in 82% (27/33) but diabetes mellitus in only 21% (8/44). Myopathy with elevated serum creatine kinase levels (346-3325 IU/L) affected all of them (38/38). 39% had scoliosis (10/26) and 57% had atlantoaxial instability (8/14). Cardiac arrhythmias were detected in 57% (20/35) and 46% had ventricular tachycardia (16/35). Congenital pyloric stenosis was diagnosed in 39% (18/46), 9 had esophageal dysmotility and 19 had intestinal dysmotility. Four patients suffered from intestinal perforations. Seven patients died at mean age of 17 years (range: 2 months to 39 years). The cause of death in four patients was cardiac arrhythmia and sudden death, while others died of prematurity, gastrointestinal perforation, and infected foot ulcers leading to sepsis. Our study highlights high prevalence of myopathy, metabolic abnormalities, cardiac, and gastrointestinal problems in patients with CGL4. CGL4 patients are at high risk of early death mainly caused by cardiac arrhythmias.

Using spatial video geonarratives to improve nursing care for people who use drugs and experience homelessness: A methodology for nurses.

BACKGROUND: People who are insecurely housed and use drugs are disproportionately affected by drug poisonings. Nurses are uniquely positioned to utilize harm reduction strategies to address the needs of the whole person. Needle debris encompasses drug paraphernalia discarded in public spaces. Studying needle debris provides a strategic opportunity to identify where drugs are being used and target public health strategies accordingly. AIM: Our aim in this article is to illustrate how spatial video geonarratives (SVG) combined GPS technology interviews, and videos of locations with needle debris, can elicit valuable data for nursing research. METHODS: Using SVG required knowledge of how to collect data wearing cameras and practice sessions were necessary. A Miufly camera worn at waist height on a belt provided the stability to walk while interviewing stakeholders. We wore the cameras and conducted go-along interviews with outreach workers, while filming the built environment. Upon completion of data collection, both the interview and GPS information were analysed using Wordmapper software. CONCLUSIONS: This methodology resulted in data presented uniquely in both a visual map and narrative. These data were richer than if a single modality had been used. These data highlighted specific contextual factors that were related to the location of needle debris, which created opportunities for nursing interventions to support people experiencing vulnerability.

Socioeconomic representativeness of Australian, Canadian and British cohorts from the paediatric diabetes AdDIT study: comparisons to regional and national data.

BACKGROUND: Given limited data regarding the involvement of disadvantaged groups in paediatric diabetes clinical trials, this study aimed to evaluate the socioeconomic representativeness of participants recruited into a multinational clinical trial in relation to regional and national type 1 diabetes reference populations. METHODS: Retrospective, cross-sectional evaluation of a subset of adolescent type 1 diabetes cardiorenal intervention trial (AdDIT) participants from Australia (n = 144), Canada (n = 312) and the UK (n = 173). Validated national measures of deprivation were used: the Index of Relative Socioeconomic Disadvantage (IRSD) 2016 (Australia), the Material Resources (MR) dimension of the Canadian Marginalisation index 2016 (Canada) and the Index of Multiple Deprivation (IMD) 2015 (UK). Representativeness was assessed by comparing the AdDIT cohort's distribution of deprivation quintiles with that of the local paediatric type 1 diabetes population (regional), and the broader type 1 diabetes population for which the trial's intervention was targeted (national). RESULTS: Recruited study cohorts from each country had higher proportions of participants with higher SES, and significant underrepresentation of lower SES, in relation to their national references. The socioeconomic make-up in Australia mirrored that of the regional population (p = 0.99). For Canada, the 2nd least deprived (p = 0.001) and the most deprived quintiles (p < 0.001) were over- and under-represented relative to the regional reference, while the UK featured higher regional and national SES bias with over-representation and under-representation from the least-deprived and most-deprived quintiles (p < 0.0001). CONCLUSIONS: Significant national differences in trial participation of low SES participants were observed, highlighting limitations in access to clinical research and the importance of reporting sociodemographic representation in diabetes clinical trials. TRIAL REGISTRATION: NCT01581476. Registered on 20 April 2012.

The utility of Zip4 codes in spatial epidemiological analysis.

There are many public health situations within the United States that require fine geographical scale data to effectively inform response and intervention strategies. However, a condition for accessing and analyzing such data, especially when multiple institutions are involved, is being able to preserve a degree of spatial privacy and confidentiality. Hospitals and state health departments, who are generally the custodians of these fine-scale health data, are sometimes understandably hesitant to collaborate with each other due to these concerns. This paper looks at the utility and pitfalls of using Zip4 codes, a data layer often included as it is believed to be "safe", as a source for sharing fine-scale spatial health data that enables privacy preservation while maintaining a suitable precision for spatial analysis. While the Zip4 is widely supplied, researchers seldom utilize it. Nor is its spatial characteristics known by data guardians. To address this gap, we use the context of a near-real time spatial response to an emerging health threat to show how the Zip4 aggregation preserves an underlying spatial structure making it potentially suitable dataset for analysis. Our results suggest that based on the density of urbanization, Zip4 centroids are within 150 meters of the real location almost 99% of the time. Spatial analysis experiments performed on these Zip4 data suggest a far more insightful geographic output than if using more commonly used aggregation units such as street lines and census block groups. However, this improvement in analytical output comes at a spatial privy cost as Zip4 centroids have a higher potential of compromising spatial anonymity with 73% of addresses having a spatial k anonymity value less than 5 when compared to other aggregations. We conclude that while offers an exciting opportunity to share data between organizations, researchers and analysts need to be made aware of the potential for serious confidentiality violations.

Prevalence and geographic features of patients eligible for extracorporeal cardiopulmonary resuscitation.

OBJECTIVE: This study sought to identify Out of Hospital Cardiac Arrests (OHCA) eligible for Extracorporeal Cardiopulmonary Resuscitation (ECPR), use Geographic Information Systems (GIS) to investigate geographic patterns, and investigate if correlation between ECPR candidacy and Social Determinants of Health (SDoH) exist. METHODS: This study is of emergency medical service (EMS) runs for OHCA to an urban medical center from January 1, 2016 to December 31, 2020. All runs were filtered to inclusion criteria for ECPR: age 18-65, initial shockable rhythm, and no return of spontaneous circulation within initial defibrillations. Address level data were mapped in a GIS. Cluster detection assessed for granular areas of high concentration. The Center for Disease Control and Prevention (CDC) Social Vulnerability Index (SVI) was overlaid. The SVI ranges from 0-1 with higher values indicating increasing social vulnerability. RESULTS: There were 670 EMS transports for OHCA during the study period. 12.7% (85/670) met inclusion criteria for ECPR. 90% (77/85) had appropriate addresses for geocoding. Three geographic clusters of events were detected. Two were residential areas and one was concentrated over a public use area of downtown Cleveland. The SVI for these locations was 0.79, indicative of high social vulnerability. Nearly half (32/77, 41.5%) occurred in neighborhoods with the highest level of social vulnerability (SVI ≥ 0.9). CONCLUSION: A significant proportion of OHCAs were eligible for ECPR based on prehospital criteria. Utilizing GIS to map and analyze ECPR patients provided insights into the locations of these events and the SDoH that may be driving risk in these places.

The Geographic Context of Racial Disparities in Aggressive Endometrial Cancer Subtypes: Integrating Social and Environmental Aspects to Discern Biological Outcomes.

The number of Endometrial Carcinoma (EC) diagnoses is projected to increase substantially in coming decades. Although most ECs have a favorable prognosis, the aggressive, non-endometrioid subtypes are disproportionately concentrated in Black women and spread rapidly, making treatment difficult and resulting in poor outcomes. Therefore, this study offers an exploratory spatial epidemiological investigation of EC patients within a U.S.-based health system's institutional cancer registry (n = 1748) to search for and study geographic patterns. Clinical, demographic, and geographic characteristics were compared by histotype using chi-square tests for categorical and t-tests for continuous variables. Multivariable logistic regression evaluated the impact of risks on these histotypes. Cox proportional hazard models measured risks in overall and cancer-specific death. Cluster detection indicated that patients with the EC non-endometrioid histotypes exhibit geographic clustering in their home address, such that congregate buildings can be identified for targeted outreach. Furthermore, living in a high social vulnerability area was independently associated with non-endometrioid histotypes, as continuous and categorical variables. This study provides a methodological framework for early, geographically targeted intervention; social vulnerability associations require further investigation. We have begun to fill the knowledge gap of geography in gynecologic cancers, and geographic clustering of aggressive tumors may enable targeted intervention to improve prognoses.

Spatial Syndromic Surveillance and COVID-19 in the U.S.: Local Cluster Mapping for Pandemic Preparedness.

Maps have become the de facto primary mode of visualizing the COVID-19 pandemic, from identifying local disease and vaccination patterns to understanding global trends. In addition to their widespread utilization for public communication, there have been a variety of advances in spatial methods created for localized operational needs. While broader dissemination of this more granular work is not commonplace due to the protections under Health Insurance Portability and Accountability Act (HIPAA), its role has been foundational to pandemic response for health systems, hospitals, and government agencies. In contrast to the retrospective views provided by the aggregated geographies found in the public domain, or those often utilized for academic research, operational response requires near real-time mapping based on continuously flowing address level data. This paper describes the opportunities and challenges presented in emergent disease mapping using dynamic patient data in the response to COVID-19 for northeast Ohio for the period 2020 to 2022. More specifically it shows how a new clustering tool developed by geographers in the initial phases of the pandemic to handle operational mapping continues to evolve with shifting pandemic needs, including new variant surges, vaccine targeting, and most recently, testing data shortfalls. This paper also demonstrates how the geographic approach applied provides the framework needed for future pandemic preparedness.

Application of Place-Based Methods to Lung Transplant Medicine.

Lung transplantation is an increasingly common lifesaving therapy for patients with fatal lung diseases, but this intervention has a critical limitation as median survival after LT is merely 5.5 years. Despite the profound impact of place-based factors on lung health, this has not been rigorously investigated in LT recipients-a vulnerable population due to the lifelong need for daily life-sustaining immunosuppression medications. There have also been longstanding methodological gaps in transplant medicine where both time and place have not been measured; gaps which could be filled by the geospatial sciences. As part of an exploratory analysis, we studied recipients transplanted at our center over a two-year period. The main outcome was at least one episode of rejection within the first year after transplant. We found recipients averaged 1.7 unique residential addresses, a modest relocation rate. Lung rejection was associated with census tracts of predominantly underrepresented minorities or where English was not the primary language as measured by the social vulnerability index. Census tracts likely play an important role in measuring and addressing geographic disparities in transplantation. In a future paradigm, patient spatial data could become an integrated part of real time clinical care to aid in personalized risk stratification and personalized delivery of healthcare.

Do new trauma centers provide needed or redundant access? A nationwide analysis.

BACKGROUND: Our prior research has demonstrated that increasing the number of trauma centers (TCs) in a state does not reliably improve state-level injury-related mortality. We hypothesized that many new TCs would serve populations already served by existing TCs, rather than in areas without ready TC access. We also hypothesized that new TCs would also be less likely to serve economically disadvantaged populations. METHODS: All state-designated adult TCs registered with the American Trauma Society in 2014 and 2019 were mapped using ArcGIS Pro (ESRI Inc., Redlands, CA). Trauma centers were grouped as Level 1 or 2 (Lev12) or Level 3, 4 or 5 (Lev345). We also obtained census tract-level data (73,666 tracts), including population counts and percentage of population below the federal poverty threshold. Thirty-minute drive-time areas were created around each TC. Census tracts were considered "served" if their geographic centers were located within a 30-minute drive-time area to any TC. Data were analyzed at the census tract level. RESULTS: A total of 2,140 TCs were identified in 2019, with 256 new TCs and 151 TC closures. Eighty-two percent of new TCs were Levels 3 to 5. Nationwide, coverage increased from 75.3% of tracts served in 2014 to 78.1% in 2019, representing an increased coverage from 76.0% to 79.4% of the population. New TC served 17,532 tracts, of which 87.3% were already served. New Lev12 TCs served 9,100 tracts, of which 91.2% were already served; new Lev345 TCs served 15,728 tracts, of which 85.9% were already served. Of 2,204 newly served tracts, those served by Lev345 TCs had higher mean percentage poverty compared with those served by Lev12 TCs (15.7% vs. 13.2% poverty, p < 0.05). DISCUSSION: Overall, access to trauma care has been improving in the United States. However, the majority of new TCs opened in locations with preexisting access to trauma care. Nationwide, Levels 3, 4, and 5 TCs have been responsible for expanding access to underserved populations. LEVEL OF EVIDENCE: Prognostic and Epidemiologic; Level IV.

Mapping Mobility: Utilizing Local-Knowledge-Derived Activity Space to Estimate Exposure to Ambient Air Pollution among Individuals Experiencing Unsheltered Homelessness.

Individuals experiencing homelessness represent a growing population in the United States. Air pollution exposure among individuals experiencing homelessness has not been quantified. Utilizing local knowledge mapping, we generated activity spaces for 62 individuals experiencing homelessness residing in a semi-rural county within the United States. Satellite derived measurements of fine particulate matter (PM2.5) were utilized to estimate annual exposure to air pollution experienced by our participants, as well as differences in the variation in estimated PM2.5 at the local scale compared with stationary monitor data and point location estimates for the same period. Spatial variation in exposure to PM2.5 was detected between participants at both the point and activity space level. Among all participants, annual median PM2.5 exposure was 16.22 µg/m3, exceeding the National Air Quality Standard. Local knowledge mapping represents a novel mechanism to capture mobility patterns and investigate exposure to air pollution within vulnerable populations. Reliance on stationary monitor data to estimate air pollution exposure may lead to exposure misclassification, particularly in rural and semirural regions where monitoring is limited.

Successful treatment of severe hypertriglyceridemia with icosapent ethyl in a case of congenital generalized lipodystrophy type 4.

OBJECTIVES: Congenital generalized lipodystrophy type 4 (CGL4) is a rare autosomal recessive condition with high rates of morbidity and mortality. It is a multisystem condition associated with ventricular tachyarrhythmia, congenital myopathy, hepatitis, and metabolic profile of severe hypertriglyceridemia and insulin resistance. Metreleptin is the first line treatment, however it is unavailable in several countries. Herein, we describe a unique presentation and treatment of CGL4. CASE PRESENTATION: A 16-year-old female presented with insulin resistant diabetes, and was later found to have myopathy, hypertriglyceridemia, nonalcoholic fatty liver disease, ventricular arrhythmias, and genetic confirmation of CGL4 due to homozygous change in CAVIN1 gene. She had severe hypertriglyceridemia, frequently >17 mmol/L, requiring several hospital admissions. To better control hypertriglyceridemia, in context of known congenital myopathy, we opted for treatment with icosapent ethyl, an ethyl ester of eicosapentaenoic acid (EPA), which reduces synthesis and enhances clearance of triglycerides. On this treatment, she was able to maintain stable triglyceride levels of 4 mmol/L. CONCLUSIONS: We present the first case report of a patient with CGL4, successfully treated for hypertriglyceridemia, with icosapent ethyl.

Motivational Stage at Continuous Glucose Monitoring (CGM) Initiation in Pediatric Type 1 Diabetes Is Associated With Current Glycemic Control but Does Not Predict Future CGM Adherence or Glycemic Control.

OBJECTIVES: The Timing of Initiation of Continuous Glucose Monitoring in Established Pediatric Diabetes (CGM TIME) Trial is a multicenter, randomized controlled trial in children with type 1 diabetes, comparing simultaneous pump and CGM with CGM initiation 6 months later (Paradigm, Veo, Enlite Sensor, Medtronic Canada). This study addresses the ability of SOCRATES (Stages Of Change Readiness And Treatment Eagerness Scale) to classify children and parents into distinct motivational stages and identify the stages' association with glycated hemoglobin (A1C) at trial entry and outcomes 6 months after CGM initiation. METHODS: Ninety-eight of 99 eligible children 10 to 18 years of age and 137 of 141 eligible parents completed SOCRATES at trial entry and 6 months later. Parent-child agreement for motivational stage was determined by weighted kappa. Linear regression was used to examine association between motivational stage and i) A1C at trial entry and ii) change in A1C and CGM adherence 6 months after CGM initiation. RESULTS: More than 87% of children and 88% of parents were classified into distinct motivational stages, with weak parent-child agreement. At trial entry, motivational stage was associated with A1C, which was 1.02% higher for children in the Action stage than in the Precontemplation stage (p<0.0001). When compared with children of parents in Precontemplation, A1C for children of parents in the Maintenance and Action stages were 0.83% (p=0.02) and 0.36% (p=0.048) higher, respectively. Precontemplation was associated with shorter diabetes duration. Motivational stage at CGM initiation did not predict change in A1C or CGM adherence 6 months later. CONCLUSIONS: SOCRATES can categorize children with type 1 diabetes and their parents into motivational stages. Although motivational stage was associated with glycemic control at trial entry, it did not predict future diabetes-related behaviour or A1C.

Is more better? Do statewide increases in trauma centers reduce injury-related mortality?

OBJECTIVES: Trauma centers are inconsistently distributed throughout the United States. It is unclear if new trauma centers improve care and decrease mortality. We tested the hypothesis that increases in trauma centers are associated with decreases in injury-related mortality (IRM) at the state level. METHODS: We used data from the American Trauma Society to geolocate every state-designated or American College of Surgeons-verified trauma center in all 50 states and the District of Columbia from 2014 to 2018. These data were merged with publicly available IRM data from the Centers for Disease Control and Prevention. We used geographic information systems methods to map and study the relationships between trauma center locations and state-level IRM over time. Regression analysis, accounting for state-level fixed effects, was used to calculate the effect of total statewide number of trauma center on IRM and year-to-year changes in statewide trauma center with the IRM (shown as deaths per additional trauma center per 100,000 population, p value). RESULTS: Nationwide between 2014 and 2018, the number of trauma center increased from 2,039 to 2,153. Injury-related mortality also increased over time. There was notable interstate variation, from 1 to 284 trauma centers. Four patterns in statewide trauma center changes emerged: static (12), increased (29), decreased (5), or variable (4). Of states with trauma center increases, 26 (90%) had increased IRM between 2014 and 2017, while the remaining 3 saw a decline. Regression analysis demonstrated that having more trauma centers in a state was associated with a significantly higher IRM rate (0.38, p = 0.03); adding new trauma centers was not associated with changes in IRM (0.02, p = 0.8). CONCLUSION: Having more trauma centers and increasing the number of trauma center within a state are not associated with decreases in state-level IRM. In this case, more is not better. However, more work is needed to identify the optimal number and location of trauma centers to improve IRM. LEVEL OF EVIDENCE: Epidemiologic, level III; Care management, level III.

Comparison of Clinical and Social Characteristics of Canadian Youth Living With Type 1 and Type 2 Diabetes.

OBJECTIVES: Our aim in this study was to describe the clinical and social characteristics of 2 Canadian cohorts of adolescents with diabetes. METHODS: Participants from the Improving renal Complications in Adolescents with type 2 diabetes through REsearch (iCARE) study (n=322) and the Early Determinants of Cardio-Renal Disease in Youth With Type 1 Diabetes (n=199) study were compared. RESULTS: Adolescents were 10 to 18 years of age (mean ± standard deviation: 14.8±2.4 years). The T2DM cohort had a shorter duration of diabetes. Both groups had glycated hemoglobin levels above target. The type 2 diabetes (T2D) cohort was comprised of predominantly Indigenous youth. The type 1 diabetes (T1D) cohort was 58.3% European/Caucasian, with a high proportion (41.7%) of visible minority groups (Afro-Caribbean, Asian/Pacific Islander, Hispanic). The prevalence of obesity, hypertension, left ventricular hypertrophy, albuminuria and hyperfiltration was higher in the T2D cohort. The T1D cohort was more socially and economically advantaged in all 4 dimensions of health inequality. CONCLUSIONS: There are significant differences in clinical and social characteristics of adolescents with T2D and T1D in Canada. Both have inadequate glycemic control with evidence of onset and progression of diabetes-related complications.

Timing of CGM initiation in pediatric diabetes: The CGM TIME Trial.

OBJECTIVE: To determine whether timing of CGM initiation offering low glucose suspend (LGS) affects CGM adherence in children and youth starting insulin pump therapy. METHODS: A 5-site RCT of pump-naïve subjects (aged 5-18 years) with type 1 diabetes (T1D) for at least 1 year compared simultaneous pump and CGM initiation offering LGS vs standard pump therapy with CGM initiation delayed for 6 months. Primary outcome was CGM adherence (hours per 28 days) (MiniMed™ Paradigm™ Veo™ system; CareLink Pro™ software) over 6 months after CGM initiation. Secondary outcome HbA1c was measured centrally. Linear mixed-models and ordinary least squares models were fitted to estimate effect of intervention, and covariates baseline age, T1D duration, HbA1c, gender, ethnicity, hypoglycemia history, clinical site, and association between CGM adherence and HbA1c. RESULTS: The trial randomized 144/152 (95%) eligible subjects. Baseline mean age was 11.5 ± 3.3(SD) years, T1D duration 3.4 ± 3.1 years, and HbA1c 7.9 ± 0.9%. Six months after CGM initiation, adjusted mean difference in CGM adherence was 62.4 hours per 28 days greater in the Simultaneous Group compared to Delayed Group (P = .007). There was no difference in mean HbA1c at 6 months. However, for each 100 hours of CGM use per 28-day period, HbA1c was 0.39% (95% CI 0.10%-0.69%) lower. Higher CGM adherence was associated with reduced time with glucose >10 mmol/L (P < .001). CONCLUSION: CGM adherence was higher after 6 months when initiated at same time as pump therapy compared to starting CGM 6 months after pump therapy. Greater CGM adherence was associated with improved HbA1c.

Fear of hypoglycemia in children with type 1 diabetes and their parents: Effect of pump therapy and continuous glucose monitoring with option of low glucose suspend in the CGM TIME trial.

To determine if pump therapy with continuous glucose monitoring offering low glucose suspend (LGS) decreases fear of hypoglycemia among children with type 1 diabetes and their parents. The CGM TIME trial is a multicenter randomized controlled trial that enrolled 144 children with type 1 diabetes for at least 1 year (mean duration 3.4 ± 3.1 years) starting pump therapy (MiniMed™ Veo™, Medtronic Canada). CGM (MiniMed™ Enlite™ sensor) offering LGS was introduced simultaneously or delayed for 6 months. Hypoglycemia Fear Scale (HFS) was completed by children ≥10 years old and all parents, at study entry and 12 months later. Simultaneous and Delayed Group participants were combined for all analyses. Subscale scores were compared with paired t-tests, and individual items with paired Wilcoxon tests. Linear regression examined association with CGM adherence. 121/140 parents and 91/99 children ≥10 years had complete data. Mean Behavior subscale score decreased from 21.1 (SD 5.9) to 17.2 (SD 6.1) (p < .001) for children, and 20.7 (SD 7.5) to 17.4 (7.4) (p < .001) for parents. Mean Worry subscale score decreased from 17.9 (SD 11.9) to 11.9 (SD 11.4) (p < .001) for children, and 23.1 (SD 13.2) to 17.6 (SD 10.4) (p < .001) for parents. Median scores for 10/25 child items and 12/25 parent items were significantly lower at 12 months (p < .001). Linear regression found no association between HFS scores and CGM adherence. Insulin pump therapy with CGM offering LGS significantly reduced fear of hypoglycemia not related to CGM adherence in children with type 1 diabetes and their parents.