Design and Psychometrics for New Measures of Health-Related Quality of Life in Adults with Type 1 Diabetes: Type 1 Diabetes and Life (T1DAL)

AIMS: To use a three-phase process to develop and validate new self-report measures of diabetes-specific health-related quality of life (HRQOL) for adults with type 1 diabetes. We report on four versions of the Type 1 Diabetes and Life (T1DAL) measure for people age 18-25, 26-45, 46-60, and over 60 years. METHODS: We first conducted qualitative interviews to guide measure creation, then piloted the draft measures. We evaluated psychometric properties at six T1D Exchange Clinic Network sites via completion of T1DAL and validated measures of related constructs. Participants completed the T1DAL again in 4-6 weeks. We used psychometric data to reduce each measure to 23-27 items in length. Finally, we obtained participant feedback on the final measures. RESULTS: The T1DAL-Adult measures demonstrated good internal consistency (α=0.85-0.88) and test-retest reliability (r=0.77-0.87). Significant correlations with measures of general quality of life, generic and diabetes-specific HRQOL, diabetes burden, self-management, and glycemic control demonstrated validity. Factor analyses yielded 4-5 subscales per measure. Participants were satisfied with the final measures and reported they took 5-10 minutes to complete. CONCLUSIONS: The strong psychometric properties of the newly developed self-report T1DAL measures for adults with type 1 diabetes make them appropriate for use in clinical research and care

Targeting effector memory T cells with alefacept in new onset type 1 diabetes: 12 month results from the T1DAL study

Background Type 1 diabetes (T1D) results from autoimmune targeting of the pancreatic beta cells, likely mediated by effector memory T cells (Tems). CD2, a T cell surface protein highly expressed on Tems, is targeted by the fusion protein alefacept, depleting Tems and central memory T cells (Tcms). We hypothesized that alefacept would arrest autoimmunity and preserve residual beta cells in newly diagnosed T1D. Methods The T1DAL study is a phase II, double-blind, placebo-controlled trial that randomised T1D patients 12-35 years old within 100 days of diagnosis, 33 to alefacept (two 12-week courses of 15 mg IM per week, separated by a 12-week pause) and 16 to placebo, at 14 US sites. The primary endpoint was the change from baseline in mean 2-hour C-peptide area under the curve (AUC) at 12 months. This trial is registered with ClinicalTrials.gov, number NCT00965458. Findings The mean 2-hour C-peptide AUC at 12 months increased by 0.015 nmol/L (95% CI -0.080 to 0.110 nmol/L) in the alefacept group and decreased by 0.115 nmol/L (95% CI -0.278 to 0.047) in the placebo group, which was not significant (p=0.065). However, key secondary endpoints were met: the mean 4-hour C-peptide AUC was significantly higher (p=0.019), and daily insulin use and the rate of hypoglycemic events were significantly lower (p=0.02 and p<0.001, respectively) at 12 months in the alefacept vs. placebo groups. Safety and tolerability were comparable between groups. There was targeted depletion of Tems and Tcms, with sparing of naïve and regulatory T cells (Tregs). Interpretation At 12 months, alefacept preserved the 4-hour C-peptide AUC, lowered insulin use, and reduced hypoglycemic events, suggesting a signal of efficacy. Depletion of memory T cells with sparing of Tregs may be a useful strategy to preserve beta cell function in new-onset T1D

Alefacept provides sustained clinical and immunological effects in new-onset type 1 diabetes patients

BACKGROUND. Type 1 diabetes (T1D) results from destruction of pancreatic β cells by autoreactive effector T cells. We hypothesized that the immunomodulatory drug alefacept would result in targeted quantitative and qualitative changes in effector T cells and prolonged preservation of endogenous insulin secretion by the remaining β cells in patients with newly diagnosed T1D

Assessing Health-Related Quality of Life in Children and Adolescents with Diabetes: Development and Psychometrics of the Type 1 Diabetes and Life (T1DAL) Measures.

OBJECTIVE To develop and validate new measures of diabetes-specific health-related quality of life (HRQOL) for people with type 1 diabetes (T1D) that are brief, developmentally appropriate, and usable in clinical research and care. Here we report on the phases of developing and validating the self-report Type 1 Diabetes and Life (T1DAL) measures for children (age 8-11) and adolescents (age 12-17). METHODS Measure development included qualitative interviews with youth and parents (n = 16 dyads) followed by piloting draft measures and conducting cognitive debriefing with youth (n = 9) to refine the measures. To evaluate the psychometric properties, children (n = 194) and adolescents (n = 257) at three T1D Exchange Clinic Network sites completed the age-appropriate T1DAL measure and previously validated questionnaires measuring related constructs. Using psychometric data, the investigators reduced the length of each T1DAL measure to 21 and 23 items, respectively, and conducted a final round of cognitive debriefing with six children and adolescents. RESULTS The T1DAL measures for children and adolescents demonstrated good internal consistency (α = 0.84 and 0.89, respectively) and test-retest reliability (r = 0.78 and 0.80, respectively). Significant correlations between the T1DAL scores and measures of general quality of life, generic and diabetes-specific HRQOL, diabetes burden, and diabetes strengths demonstrated construct validity. Correlations with measures of self-management (child and adolescent) and glycemic control (adolescent only) demonstrated criterion validity. Factor analyses indicated four developmentally specific subscales per measure. Participants reported satisfaction with the measures. CONCLUSIONS The new T1DAL measures for children and adolescents with T1D are reliable, valid, and suitable for use in care settings and clinical research

Design and psychometrics for new measures of health-related quality of life in adults with type 1 diabetes: Type 1 Diabetes and Life (T1DAL)

Aims: To use a three-phase process to develop and validate new self-report measures of diabetes-specific health-related quality of life (HRQOL) for adults with type 1 diabetes. We report on four versions of the Type 1 Diabetes and Life (T1DAL) measure for people age 18–25, 26–45, 46–60, and over 60 years. Methods: We first conducted qualitative interviews to guide measure creation, then piloted the draft measures. We evaluated psychometric properties at six T1D Exchange Clinic Network sites via completion of T1DAL and validated measures of related constructs. Participants completed the T1DAL again in 4–6 weeks. We used psychometric data to reduce each measure to 23–27 items in length. Finally, we obtained participant feedback on the final measures. Results: The T1DAL-Adult measures demonstrated good internal consistency (α = 0.85–0.88) and test–retest reliability (r = 0.77–0.87). Significant correlations with measures of general quality of life, generic and diabetes-specific HRQOL, diabetes burden, self-management, and glycemic control demonstrated validity. Factor analyses yielded 4–5 subscales per measure. Participants were satisfied with the final measures and reported they took 5–10 min to complete. Conclusions: The strong psychometric properties of the newly developed self-report T1DAL measures for adults with type 1 diabetes make them appropriate for use in clinical research and care

Health-related quality of life in parents and partners of people with type 1 diabetes: Development and validation of type 1 diabetes and life (T1DAL) measures.

Introduction: Despite the significant impact of type 1 diabetes (T1D) on family, few instruments are available to assess health-related quality of life (HRQOL) among family members of people with T1D. This study aimed to develop and evaluate the psychometric properties of new measures of diabetes-specific HRQOL for parents and partners of people with T1D. We report on the multistep development and validation process for the self-report Type 1 Diabetes and Life (T1DAL) measures, with versions for parents of youth age <8, 8–11, 12–17, and 18–25 years, and for partners of people age ≥18 years with T1D. Method: First, we conducted qualitative interviews (total parents/partners n = 38) to develop draft measures and piloted them (total n = 20). Next, we tested the measures’ psychometric properties. Participants (total across versions n = 813) at six T1D Exchange Clinic Network sites completed the appropriate T1DAL measure and validated measures of related constructs. We then reduced each T1DAL measure to 20–30 items in length based on psychometric data and participant feedback. Eleven participants reviewed the final measures via cognitive debriefing. Results: The T1DAL measures for parents and partners demonstrated good internal consistency (α = .80–.88) and test–retest reliability (r = .73–.86). Correlations with measures of general quality of life, generic and diabetes-specific HRQOL, and diabetes burden demonstrated construct validity. Factor analyses identified 3–4 subscales/measure. Participants reported being satisfied with the shortened measures, which took 5–10 minutes to complete. Discussion: The new T1DAL measures for parents and partners of people with T1D are reliable, valid, and ready for use in research and clinical settings. (PsycInfo Database Record (c) 2021 APA, all rights reserved) Public Significance Statement—This study developed a set of validated questionnaires to measure health-related quality of life in parents and partners of people with type 1 diabetes. The experiences of family members are important and have implications for the health and well-being of people with diabetes, yet there have been few measures to accurately and reliably assess their quality of life. These new measures can be used in clinical practice and research settings. (PsycInfo Database Record (c) 2021 APA, all rights reserved

Co-stimulation modulation with abatacept in patients with recent-onset type 1 diabetes: a randomised, double-blind, placebo-controlled trial

The immunopathogenesis of type 1 diabetes mellitus is associated with T-cell autoimmunity. To be fully active, immune T cells need a co-stimulatory signal in addition to the main antigen-driven signal. Abatacept modulates co-stimulation and prevents full T-cell activation. We evaluated the effect of abatacept in recent-onset type 1 diabetes. In this multicentre, double-blind, randomised controlled trial, patients aged 6–45 years recently diagnosed with type 1 diabetes were randomly assigned (2:1) to receive abatacept (10 mg/kg, maximum 1000 mg per dose) or placebo infusions intravenously on days 1, 14, 28, and monthly for a total of 27 infusions over 2 years. Computer-generated permuted block randomisation was used, with a block size of 3 and stratified by participating site. Neither patients nor research personnel were aware of treatment assignments. The primary outcome was baseline-adjusted geometric mean 2-h area-under-the-curve (AUC) serum C-peptide concentration after a mixed-meal tolerance test at 2 years' follow-up. Analysis was by intention to treat for all patients for whom data were available. This trial is registered at ClinicalTrials.gov, NCT00505375. 112 patients were assigned to treatment groups (77 abatacept, 35 placebo). Adjusted C-peptide AUC was 59% (95% CI 6·1–112) higher at 2 years with abatacept (n=73, 0·378 nmol/L) than with placebo (n=30, 0·238 nmol/L; p=0·0029). The difference between groups was present throughout the trial, with an estimated 9·6 months' delay (95% CI 3·47–15·6) in C-peptide reduction with abatacept. There were few infusion-related adverse events (36 reactions occurred in 17 [22%] patients on abatacept and 11 reactions in six [17%] on placebo). There was no increase in infections (32 [42%] patients on abatacept vs 15 [43%] on placebo) or neutropenia (seven [9%] vs five [14%]). Co-stimulation modulation with abatacept slowed reduction in β-cell function over 2 years. The beneficial effect suggests that T-cell activation still occurs around the time of clinical diagnosis of type 1 diabetes. Yet, despite continued administration of abatacept over 24 months, the decrease in β-cell function with abatacept was parallel to that with placebo after 6 months of treatment, causing us to speculate that T-cell activation lessens with time. Further observation will establish whether the beneficial effect continues after cessation of abatacept infusions. US National Institutes of Health

Costimulation Modulation With Abatacept in Patients With Recent-Onset Type 1 Diabetes:Follow-up 1 Year After Cessation of Treatment

OBJECTIVE: We previously reported that 2 years of costimulation modulation with abatacept slowed decline of β-cell function in recent-onset type 1 diabetes (T1D). Subsequently, abatacept was discontinued and subjects were followed to determine whether there was persistence of effect. RESEARCH DESIGN AND METHODS: Of 112 subjects (ages 6–36 years) with T1D, 77 received abatacept and 35 received placebo infusions intravenously for 27 infusions over 2 years. The primary outcome—baseline-adjusted geometric mean 2-h area under the curve (AUC) serum C-peptide during a mixed-meal tolerance test (MMTT) at 2 years—showed higher C-peptide with abatacept versus placebo. Subjects were followed an additional year, off treatment, with MMTTs performed at 30 and 36 months. RESULTS: C-peptide AUC means, adjusted for age and baseline C-peptide, at 36 months were 0.217 nmol/L (95% CI 0.168–0.268) and 0.141 nmol/L (95% CI 0.071–0.215) for abatacept and placebo groups, respectively (P = 0.046). The C-peptide decline from baseline remained parallel with an estimated 9.5 months’ delay with abatacept. Moreover, HbA(1c) levels remained lower in the abatacept group than in the placebo group. The slightly lower (nonsignificant) mean total insulin dose among the abatacept group reported at 2 years was the same as the placebo group by 3 years. CONCLUSIONS: Costimulation modulation with abatacept slowed decline of β-cell function and improved HbA(1c) in recent-onset T1D. The beneficial effect was sustained for at least 1 year after cessation of abatacept infusions or 3 years from T1D diagnosis