Aims/hypothesis
While the use of insulin pumps in paediatrics has expanded dramatically, there is still considerable variability among countries in the use of pump technology. The present study ...sought to describe differences in metabolic control and pump use in young people with type 1 diabetes using data collected in three multicentre registries.
Methods
Data for the years 2011 and 2012 from 54,410 children and adolescents were collected from the Prospective Diabetes Follow-up Registry (DPV;
n
= 26,198), T1D Exchange (T1DX;
n
= 13,755) and the National Paediatric Diabetes Audit (NPDA;
n
= 14,457). The modality of insulin delivery, based on age, sex and ethnic minority status, and the impact of pump use on HbA
1c
levels were compared.
Results
The overall mean HbA
1c
level was higher in the NPDA (8.9 ± 1.6% 74 ± 17.5 mmol/mol) than in the DPV (8.0 ± 1.6% 64 ± 17.0 mmol/mol,
p <
0.001) and T1DX (8.3 ± 1.4% 68 ± 15.4 mmol/mol,
p <
0.001). Conversely, pump use was much lower in the NPDA (14%) than in the DPV (41%,
p <
0.001) and T1DX (47%,
p <
0.001). In a pooled analysis, pump use was associated with a lower mean HbA
1c
(pump: 8.0 ± 1.2% 64 ± 13.3 mmol/mol vs injection: 8.5 ± 1.7% 69 ± 18.7 mmol/mol,
p <
0.001). In all three registries, those with an ethnic minority status were less likely to be treated with a pump (
p <
0.001) and boys were treated with a pump less often compared with girls (
p <
0.001).
Conclusions/interpretation
Despite similar clinical characteristics and proportion of minority participants, substantial differences in metabolic control exist across the three large transatlantic registries of paediatric patients with type 1 diabetes, which appears to be due in part to the frequency of insulin pump therapy.
We compared the glucose management indicator (GMI) calculated using 14 days of continuous glucose monitor (CGM) data with GMI calculated using <14 days. Analysis included 581 individuals with type 1 ...diabetes or type 2 diabetes from five clinical trials. The correlation between the 14- and 7-day GMI was 0.95 and the correlation between 14 days versus 10, 5, and 3 days GMI was 0.98, 0.91, and 0.86, respectively. The percentages of GMI values within 0.3% of the 14-day GMI were 98% with 10-day GMI, 87% with 7-day GMI, 77% with 5-day GMI, and 60% with 3-day GMI. Minimal differences were observed between GMI computed using 14 days of data compared with GMI computed with 7 days. Although 10-14 days of CGM data are preferred for computing GMI, for most patients a satisfactory estimate of HbA1c can be obtained with 7 days of data.
Previous research has documented racial/ethnic disparities in diabetes treatments and outcomes. It remains controversial whether these disparities result from differences in socioeconomic status ...(SES) or other factors. We examined racial/ethnic disparities in therapeutic modalities and diabetes outcomes among the large number of pediatric participants in the T1D Exchange Clinic Registry.
The cohort included 10 704 participants aged <18 years with type 1 diabetes for ≥1 year (48% female; mean age: 11.9 ± 3.6 years; diabetes duration: 5.2 ± 3.5 years). Diabetes management and clinical outcomes were compared among 8841 non-Hispanic white (white) (83%), 697 non-Hispanic black (black) (7%), and 1166 Hispanic (11%) participants. The population included 214 high-income black and Hispanic families.
Insulin pump use was higher in white participants than in black or Hispanic participants (61% vs 26% and 39%, respectively) after adjusting for gender, age, diabetes duration, and SES (P < .001). Mean hemoglobin A1c was higher (adjusted P < .001) in black participants than in white or Hispanic participants (9.6%, 8.4%, and 8.7%). More black participants experienced diabetic ketoacidosis and severe hypoglycemic events in the previous year than white or Hispanic participants (both, P < .001). There were no significant differences in hemoglobin A1c, diabetic ketoacidosis, or severe hypoglycemia between white and Hispanic participants after adjustment for SES.
Even after SES adjustment, marked disparities in insulin treatment method and treatment outcomes existed between black versus Hispanic and white children within this large pediatric cohort. Barriers to insulin pump use and optimal glycemic control beyond SES should be explored in all ethnic groups.
To determine whether the use of continuous glucose monitoring (CGM) without confirmatory blood glucose monitoring (BGM) measurements is as safe and effective as using CGM adjunctive to BGM in adults ...with well-controlled type 1 diabetes (T1D).
A randomized noninferiority clinical trial was conducted at 14 sites in the T1D Exchange Clinic Network. Participants were ≥18 years of age (mean 44 ± 14 years), had T1D for ≥1 year (mean duration 24 ± 12 years), used an insulin pump, and had an HbA
≤9.0% (≤75 mmol/mL) (mean 7.0 ± 0.7% 53 ± 7.7 mmol/mol); prestudy, 47% were CGM users. Participants were randomly assigned 2:1 to the CGM-only (
= 149) or CGM+BGM (
= 77) group. The primary outcome was time in range (70-180 mg/dL) over the 26-week trial, with a prespecified noninferiority limit of 7.5%.
CGM use averaged 6.7 ± 0.5 and 6.8 ± 0.4 days/week in the CGM-only and CGM+BGM groups, respectively, over the 26-week trial. BGM tests per day (including the two required daily for CGM calibration) averaged 2.8 ± 0.9 and 5.4 ± 1.4 in the two groups, respectively (
< 0.001). Mean time in 70-180 mg/dL was 63 ± 13% at both baseline and 26 weeks in the CGM-only group and 65 ± 13% and 65 ± 11% in the CGM+BGM group (adjusted difference 0%; one-sided 95% CI -2%). No severe hypoglycemic events occurred in the CGM-only group, and one occurred in the CGM+BGM group.
Use of CGM without regular use of confirmatory BGM is as safe and effective as using CGM with BGM in adults with well-controlled T1D at low risk for severe hypoglycemia.
Overnight hypoglycemia occurs frequently in individuals with type 1 diabetes and can result in loss of consciousness, seizure, or even death. We conducted an in-home randomized trial to determine ...whether nocturnal hypoglycemia could be safely reduced by temporarily suspending pump insulin delivery when hypoglycemia was predicted by an algorithm based on continuous glucose monitoring (CGM) glucose levels.
Following an initial run-in phase, a 42-night trial was conducted in 45 individuals aged 15-45 years with type 1 diabetes in which each night was assigned randomly to either having the predictive low-glucose suspend system active (intervention night) or inactive (control night). The primary outcome was the proportion of nights in which ≥1 CGM glucose values ≤60 mg/dL occurred.
Overnight hypoglycemia with at least one CGM value ≤60 mg/dL occurred on 196 of 942 (21%) intervention nights versus 322 of 970 (33%) control nights (odds ratio 0.52 95% CI 0.43-0.64; P < 0.001). Median hypoglycemia area under the curve was reduced by 81%, and hypoglycemia lasting >2 h was reduced by 74%. Overnight sensor glucose was >180 mg/dL during 57% of control nights and 59% of intervention nights (P = 0.17), while morning blood glucose was >180 mg/dL following 21% and 27% of nights, respectively (P < 0.001), and >250 mg/dL following 6% and 6%, respectively. Morning ketosis was present <1% of the time in each arm.
Use of a nocturnal low-glucose suspend system can substantially reduce overnight hypoglycemia without an increase in morning ketosis.
To evaluate the safety and effectiveness of the Loop Do-It-Yourself automated insulin delivery system.
A prospective real-world observational study was conducted, which included 558 adults and ...children (age range 1-71 years, mean HbA1c 6.8% ± 1.0%) who initiated Loop either on their own or with community-developed resources and provided data for 6 months.
Mean time-in-range 70-180 mg/dL (TIR) increased from 67% ± 16% at baseline (before starting Loop) to 73% ± 13% during the 6 months (mean change from baseline 6.6%, 95% confidence interval CI 5.9%-7.4%;
< 0.001). TIR increased in both adults and children, across the full range of baseline HbA1c, and in participants with both high- and moderate-income levels. Median time <54 mg/dL was 0.40% at baseline and changed by -0.05% (95% CI -0.09% to -0.03%,
< 0.001). Mean HbA1c was 6.8% ± 1.0% at baseline and decreased to 6.5% ± 0.8% after 6 months (mean difference = -0.33%, 95% CI -0.40% to -0.26%,
< 0.001). The incidence rate of reported severe hypoglycemia events was 18.7 per 100 person-years, a reduction from the incidence rate of 181 per 100 person-years during the 3 months before the study. Among the 481 users providing Loop data at 6 months, median continuous glucose monitoring use was 96% (interquartile range IQR 91%-98%) and median time Loop modulating basal insulin was at least 83% (IQR 73%-88%).
The Loop open source system can be initiated with community-developed resources and used safely and effectively by adults and children with type 1 diabetes.
To assess the proportion of youth with type 1 diabetes under the care of pediatric endocrinologists in the United States meeting targets for HbA1c, blood pressure (BP), BMI, and lipids.
Data were ...evaluated for 13,316 participants in the T1D Exchange clinic registry younger than 20 years old with type 1 diabetes for ≥1 year.
American Diabetes Association HbA1c targets of <8.5% for those younger than 6 years, <8.0% for those 6 to younger than 13 years old, and <7.5% for those 13 to younger than 20 years old were met by 64, 43, and 21% of participants, respectively. The majority met targets for BP and lipids, and two-thirds met the BMI goal of <85th percentile.
Most children with type 1 diabetes have HbA1c values above target levels. Achieving American Diabetes Association goals remains a significant challenge for the majority of youth in the T1D Exchange registry.
IMPORTANCE: Intravitreous bevacizumab (0.25 mg to 0.625 mg) is commonly used to treat type 1 retinopathy of prematurity (ROP), but there are concerns about systemic toxicity, particularly the risk of ...neurodevelopmental delay. A much lower dose may be effective for ROP while reducing systemic risk. Previously, after testing doses of 0.25 mg to 0.031 mg, doses as low as 0.031 mg were found to be effective in small cohorts of infants. OBJECTIVE: To find the lowest dose of intravitreous bevacizumab effective for severe ROP. DESIGN, SETTING, AND PARTICIPANTS: Between April 2017 and May 2019, 59 premature infants with type 1 ROP in 1 or both eyes were enrolled in a masked, multicenter, dose de-escalation study. In cohorts of 10 to 14 infants, 1 eye per infant received 0.016 mg, 0.008 mg, 0.004 mg, or 0.002 mg of intravitreous bevacizumab. Diluted bevacizumab was prepared by individual research pharmacies and delivered using 300-µL syringes with 5/16-inch, 30-guage fixed needles. Analysis began July 2019. INTERVENTIONS: Bevacizumab intravitreous injections at 0.016 mg, 0.008 mg, 0.004 mg, or 0.002 mg. MAIN OUTCOMES AND MEASURES: Success was defined as improvement by 4 days postinjection and no recurrence of type 1 ROP or severe neovascularization requiring additional treatment within 4 weeks. RESULTS: Fifty-five of 59 enrolled infants had 4-week outcomes completed; the mean (SD) birth weight was 664 (258) g, and the mean (SD) gestational age was 24.8 (1.6) weeks. A successful 4-week outcome was achieved for 13 of 13 eyes (100%) receiving 0.016 mg, 9 of 9 eyes (100%) receiving 0.008 mg, 9 of 10 eyes (90%) receiving 0.004 mg, but only 17 of 23 eyes (74%) receiving 0.002 mg. CONCLUSIONS AND RELEVANCE: These data suggest that 0.004 mg may be the lowest dose of bevacizumab effective for ROP. Further investigation is warranted to confirm effectiveness of very low-dose intravitreous bevacizumab and its effect on plasma vascular endothelial growth factor levels and peripheral retinal vascularization.
Diabetic ketoacidosis (DKA) in children and adolescents with established type 1 diabetes is a major problem with considerable morbidity, mortality, and associated costs to patients, families, and ...health care systems. We analyzed data from three multinational type 1 diabetes registries/audits with similarly advanced, yet differing, health care systems with an aim to identify factors associated with DKA admissions.
Data from 49,859 individuals <18 years with type 1 diabetes duration ≥1 year from the Prospective Diabetes Follow-up Registry (DPV) initiative (n = 22,397, Austria and Germany), the National Paediatric Diabetes Audit (NPDA; n = 16,314, England and Wales), and the T1D Exchange (T1DX; n = 11,148, U.S.) were included. DKA was defined as ≥1 hospitalization for hyperglycemia with a pH <7.3 during the prior year. Data were analyzed using multivariable logistic regression models.
The frequency of DKA was 5.0% in DPV, 6.4% in NPDA, and 7.1% in T1DX, with differences persisting after demographic adjustment (P < 0.0001). In multivariable analyses, higher odds of DKA were found in females (odds ratio OR 1.23, 99% CI 1.10-1.37), ethnic minorities (OR 1.27, 99% CI 1.11-1.44), and HbA1c ≥7.5% (≥58 mmol/mol) (OR 2.54, 99% CI 2.09-3.09 for HbA1c from 7.5 to <9% 58 to <75 mmol/mol and OR 8.74, 99% CI 7.18-10.63 for HbA1c ≥9.0% ≥75 mmol/mol).
These multinational data demonstrate high rates of DKA in childhood type 1 diabetes across three registries/audits and five nations. Females, ethnic minorities, and HbA1c above target were all associated with an increased risk of DKA. Targeted DKA prevention programs could result in substantial health care cost reduction and reduced patient morbidity and mortality.
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