IMPORTANCE: Panretinal photocoagulation (PRP) is the standard treatment for reducing severe visual loss from proliferative diabetic retinopathy. However, PRP can damage the retina, resulting in ...peripheral vision loss or worsening diabetic macular edema (DME). OBJECTIVE: To evaluate the noninferiority of intravitreous ranibizumab compared with PRP for visual acuity outcomes in patients with proliferative diabetic retinopathy. DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial conducted at 55 US sites among 305 adults with proliferative diabetic retinopathy enrolled between February and December 2012 (mean age, 52 years; 44% female; 52% white). Both eyes were enrolled for 89 participants (1 eye to each study group), with a total of 394 study eyes. The final 2-year visit was completed in January 2015. INTERVENTIONS: Individual eyes were randomly assigned to receive PRP treatment, completed in 1 to 3 visits (n = 203 eyes), or ranibizumab, 0.5 mg, by intravitreous injection at baseline and as frequently as every 4 weeks based on a structured re-treatment protocol (n = 191 eyes). Eyes in both treatment groups could receive ranibizumab for DME. MAIN OUTCOMES AND MEASURES: The primary outcome was mean visual acuity change at 2 years (5-letter noninferiority margin; intention-to-treat analysis). Secondary outcomes included visual acuity area under the curve, peripheral visual field loss, vitrectomy, DME development, and retinal neovascularization. RESULTS: Mean visual acuity letter improvement at 2 years was +2.8 in the ranibizumab group vs +0.2 in the PRP group (difference, +2.2; 95% CI, −0.5 to +5.0; P < .001 for noninferiority). The mean treatment group difference in visual acuity area under the curve over 2 years was +4.2 (95% CI, +3.0 to +5.4; P < .001). Mean peripheral visual field sensitivity loss was worse (−23 dB vs −422 dB; difference, 372 dB; 95% CI, 213-531 dB; P < .001), vitrectomy was more frequent (15% vs 4%; difference, 9%; 95% CI, 4%-15%; P < .001), and DME development was more frequent (28% vs 9%; difference, 19%; 95% CI, 10%-28%; P < .001) in the PRP group vs the ranibizumab group, respectively. Eyes without active or regressed neovascularization at 2 years were not significantly different (35% in the ranibizumab group vs 30% in the PRP group; difference, 3%; 95% CI, −7% to 12%; P = .58). One eye in the ranibizumab group developed endophthalmitis. No significant differences between groups in rates of major cardiovascular events were identified. CONCLUSIONS AND RELEVANCE: Among eyes with proliferative diabetic retinopathy, treatment with ranibizumab resulted in visual acuity that was noninferior to (not worse than) PRP treatment at 2 years. Although longer-term follow-up is needed, ranibizumab may be a reasonable treatment alternative, at least through 2 years, for patients with proliferative diabetic retinopathy. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01489189
This study evaluated a new insulin delivery system designed to reduce insulin delivery when trends in continuous glucose monitoring (CGM) glucose concentrations predict future hypoglycemia.
...Individuals with type 1 diabetes (
= 103, age 6-72 years, mean HbA
7.3% 56 mmol/mol) participated in a 6-week randomized crossover trial to evaluate the efficacy and safety of a Tandem Diabetes Care t:slim X2 pump with Basal-IQ integrated with a Dexcom G5 sensor and a predictive low-glucose suspend algorithm (PLGS) compared with sensor-augmented pump (SAP) therapy. The primary outcome was CGM-measured time <70 mg/dL.
Both study periods were completed by 99% of participants; median CGM usage exceeded 90% in both arms. Median time <70 mg/dL was reduced from 3.6% at baseline to 2.6% during the 3-week period in the PLGS arm compared with 3.2% in the SAP arm (difference PLGS - SAP = -0.8%, 95% CI -1.1 to -0.5,
< 0.001). The corresponding mean values were 4.4%, 3.1%, and 4.5%, respectively, represent-ing a 31% reduction in the time <70 mg/dL with PLGS. There was no increase in mean glucose concentration (159 vs. 159 mg/dL,
= 0.40) or percentage of time spent >180 mg/dL (32% vs. 33%,
= 0.12). One severe hypoglycemic event occurred in the SAP arm and none in the PLGS arm. Mean pump suspension time was 104 min/day.
The Tandem Diabetes Care Basal-IQ PLGS system significantly reduced hypoglycemia without rebound hyperglycemia, indicating that the system can benefit adults and youth with type 1 diabetes in improving glycemic control.
IMPORTANCE: Adolescents and young adults with type 1 diabetes exhibit the worst glycemic control among individuals with type 1 diabetes across the lifespan. Although continuous glucose monitoring ...(CGM) has been shown to improve glycemic control in adults, its benefit in adolescents and young adults has not been demonstrated. OBJECTIVE: To determine the effect of CGM on glycemic control in adolescents and young adults with type 1 diabetes. DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial conducted between January 2018 and May 2019 at 14 endocrinology practices in the US including 153 individuals aged 14 to 24 years with type 1 diabetes and screening hemoglobin A1c (HbA1c) of 7.5% to 10.9%. INTERVENTIONS: Participants were randomized 1:1 to undergo CGM (CGM group; n = 74) or usual care using a blood glucose meter for glucose monitoring (blood glucose monitoring BGM group; n = 79). MAIN OUTCOMES AND MEASURES: The primary outcome was change in HbA1c from baseline to 26 weeks. There were 20 secondary outcomes, including additional HbA1c outcomes, CGM glucose metrics, and patient-reported outcomes with adjustment for multiple comparisons to control for the false discovery rate. RESULTS: Among the 153 participants (mean SD age, 17 3 years; 76 50% were female; mean SD diabetes duration, 9 5 years), 142 (93%) completed the study. In the CGM group, 68% of participants used CGM at least 5 days per week in month 6. Mean HbA1c was 8.9% at baseline and 8.5% at 26 weeks in the CGM group and 8.9% at both baseline and 26 weeks in the BGM group (adjusted between-group difference, −0.37% 95% CI, −0.66% to −0.08%; P = .01). Of 20 prespecified secondary outcomes, there were statistically significant differences in 3 of 7 binary HbA1c outcomes, 8 of 9 CGM metrics, and 1 of 4 patient-reported outcomes. The most commonly reported adverse events in the CGM and BGM groups were severe hypoglycemia (3 participants with an event in the CGM group and 2 in the BGM group), hyperglycemia/ketosis (1 participant with an event in CGM group and 4 in the BGM group), and diabetic ketoacidosis (3 participants with an event in the CGM group and 1 in the BGM group). CONCLUSIONS AND RELEVANCE: Among adolescents and young adults with type 1 diabetes, continuous glucose monitoring compared with standard blood glucose monitoring resulted in a small but statistically significant improvement in glycemic control over 26 weeks. Further research is needed to understand the clinical importance of the findings. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03263494
Our objective was to characterize diabetes-specific health-related quality of life (D-HRQOL) in a global sample of youth and young adults with type 1 diabetes (T1D) and to identify the main factors ...associated with quality of life.
The TEENs study was an international, cross-sectional study of youth, 8-25 years of age, with T1D. Participants (
= 5,887) were seen in clinical sites in 20 countries across 5 continents enrolled for 3 predetermined age groups: 8-12, 13-18, and 19-25 years of age. To assess D-HRQOL, participants completed the PedsQL Diabetes Module 3.0 and were interviewed about family-related factors. Specifics about treatment regimen and self-management behaviors were collected from medical records.
Across all age groups, females reported significantly lower D-HRQOL than did males. The 19-25-year age group reported the lowest D-HRQOL. Multivariate linear regression analyses revealed that D-HRQOL was significantly related to HbA
; the lower the HbA
, the better the D-HRQOL. Three diabetes-management behaviors were significantly related to better D-HRQOL: advanced methods used to measure food intake; more frequent daily blood glucose monitoring; and more days per week that youth had ≥30 min of physical activity.
In all three age groups, the lower the HbA
, the better the D-HRQOL, underscoring the strong association between better D-HRQOL and optimal glycemic control in a global sample of youth and young adults. Three diabetes-management behaviors were also related to optimal glycemic control, which represent potentially modifiable factors for clinical interventions to improve D-HRQOL as well as glycemic control.
To determine the optimal duration of a run-in period for initiation of real-time continuous glucose monitoring (CGM) before the start of a randomized controlled trial (RCT) in type 1 diabetes (T1D) ...or type 2 diabetes (T2D).
Data sets were pooled from 8 RCTs, which had a blinded CGM wear period followed by at least 3 months of unblinded CGM use. Across all participants, mean time in range 70-180 mg/dL (TIR) and mean time <54 mg/dL (
< 54) as well as other key CGM metrics were computed for the initial period of blinded CGM wear and from the subsequent 13 weeks of unblinded CGM use.
The analysis cohort included data from 485 participants: 348 with T1D and 137 with T2D, ranging in age from 2 to 82 years. Mean TIR was 49% with blinded CGM before initiation of unblinded CGM use, increased to 55% by the end of the first week of unblinded CGM use, and then showed little change through 13 weeks. Mean
< 54 decreased from 1.4% with blinded CGM to 0.8% 1 week and 0.6% 2 weeks after initiating unblinded CGM use, which matched the value in month 3. Similar results were obtained for mean glucose, time >180 mg/dL, time >250 mg/dL, and time <70 mg/dL, with the mean improvement in hyperglycemia metrics plateauing slightly faster than hypoglycemia metrics. Findings were largely similar for T1D and T2D.
When initiating unblinded real-time CGM, improvement in key CGM metrics occurs rapidly, with maximal effect on the mean of each metric achieved within 1-2 weeks. For a randomized trial in which all participants will use real-time unblinded CGM for glucose monitoring, a run-in period should be implemented before collecting baseline data for participants who are not CGM users. For such CGM-naive individuals, a 7- to 14-day acclimation period is sufficient followed by a 14-day period for collection of baseline unblinded CGM data.
Capillary hemoglobin A1c (HbA1c) collection has grown in importance due to its convenience during situations such as the coronavirus disease 2019 (COVID-19) pandemic and virtual visits. The viability ...of capillary blood samples as an accurate alternative to venous samples has previously only been assessed in smaller sample sizes. In this brief report, 773 paired capillary and venous samples taken from 258 study participants in the Insulin-Only Bionic Pancreas Trial were analyzed at the University of Minnesota Advanced Research and Diagnostic Laboratory and assessed for HbA1c value congruency. Results showed that 97.7% of the capillary samples were within 5% of their respective venous measurement, and
between the two HbA1c sources was 0.95. These results are consistent with previous studies that also reported high concordance between capillary and venous HbA1c values using the same laboratory method, providing further evidence that capillary HbA1c measurements are an accurate alternative to venous measurements. Clinical Trial Registration number: NCT04200313.
In children 2 to younger than 6 years of age with type 1 diabetes, a closed-loop control system was associated with a greater percentage of time in the target glycemic range than standard care.
It is generally accepted that complete β-cell destruction eventually occurs in individuals with type 1 diabetes, which has implications for treatment approaches and insurance coverage. The frequency ...of residual insulin secretion in a large cohort of individuals at varying ages of diagnosis and type 1 diabetes duration is unknown.
The frequency of residual insulin secretion was determined by measurement of nonfasting serum C-peptide concentration in 919 individuals with type 1 diabetes according to prespecified groups based on age at diagnosis and duration of disease (from 3 to 81 years' duration). Stimulated C-peptide was measured in those with detectable nonfasting values and a group of those with undetectable values as control.
The overall frequency of detectable nonfasting C-peptide was 29%, decreasing with time from diagnosis regardless of age at diagnosis. In all duration groups, the frequency of C-peptide was higher with diagnosis age >18 years compared with ≤18 years. Nineteen percent of those with undetectable nonfasting C-peptide were C-peptide positive upon stimulation testing.
The American Diabetes Association's definition of type 1 diabetes as "usually leading to absolute insulin deficiency" results in clinicians often considering the presence of residual insulin secretion as unexpected in this population. However, our data suggest that residual secretion is present in almost one out of three individuals 3 or more years from type 1 diabetes diagnosis. The frequency of residual C-peptide decreases with time from diagnosis regardless of age at diagnosis, yet at all durations of disease, diagnosis during adulthood is associated with greater frequency and higher values of C-peptide.
Nocturnal hypoglycemia can cause seizures and is a major impediment to tight glycemic control, especially in young children with type 1 diabetes. We conducted an in-home randomized trial to assess ...the efficacy and safety of a continuous glucose monitor-based overnight predictive low-glucose suspend (PLGS) system.
In two age-groups of children with type 1 diabetes (11-14 and 4-10 years of age), a 42-night trial for each child was conducted wherein each night was assigned randomly to either having the PLGS system active (intervention night) or inactive (control night). The primary outcome was percent time <70 mg/dL overnight.
Median time at <70 mg/dL was reduced by 54% from 10.1% on control nights to 4.6% on intervention nights (P < 0.001) in 11-14-year-olds (n = 45) and by 50% from 6.2% to 3.1% (P < 0.001) in 4-10-year-olds (n = 36). Mean overnight glucose was lower on control versus intervention nights in both age-groups (144 ± 18 vs. 152 ± 19 mg/dL P < 0.001 and 153 ± 14 vs. 160 ± 16 mg/dL P = 0.004, respectively). Mean morning blood glucose was 159 ± 29 vs. 176 ± 28 mg/dL (P < 0.001) in the 11-14-year-olds and 154 ± 25 vs. 158 ± 22 mg/dL (P = 0.11) in the 4-10-year-olds, respectively. No differences were found between intervention and control in either age-group in morning blood ketosis.
In 4-14-year-olds, use of a nocturnal PLGS system can substantially reduce overnight hypoglycemia without an increase in morning ketosis, although overnight mean glucose is slightly higher.
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