Response to Comment on: Greenbaum et al. Fall in C-Peptide During First 2 Years From Diagnosis: Evidence of at Least Two Distinct Phases From Composite Type 1 Diabetes TrialNet Data. Diabetes 2012;61:2066–2073

Greenbaum, Carla J.; Beam, Craig A.

doi:10.2337/db13-0115

Cited by 52 publications

(92 citation statements)

References 2 publications

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“…Peak CP and CP AUC remained stable in this period after the intervention with HbA1c within target and low insulin requirements. Although these findings could represent a honeymoon state, previous data from the Trialnet and others indicate that there is a decrease in CP AUC and peak CP in patients with similar ages in the first 6-12 months of T1D (26,27). However, most patients included in Trialnet were Caucasian, and there is scarce information about the progression of the β-cell function in T1D from multiethnic populations.…”

Section: Discussionmentioning

confidence: 86%

Adipose tissue-derived stromal/stem cells + cholecalciferol: a pilot study in recent-onset type 1 diabetes patients

Dantas¹,

Araújo²,

Silva³

et al. 2021

Archives of Endocrinology and Metabolism

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Objective: Adipose tissue-derived stromal/stem cells (ASCs) and vitamin D have immunomodulatory actions that could be useful for type 1 diabetes (T1D). We aimed in this study to investigate the safety and efficacy of ASCs + daily cholecalciferol (VIT D) for 6 months in patients with recent-onset T1D. Materials and methods: In this prospective, dual-center, open trial, patients with recent onset T1D received one dose of allogenic ASC (1 x 10 6 cells/kg) and cholecalciferol 2,000 UI/day for 6 months (group 1). They were compared to patients who received chol-ecalciferol (group 2) and standard treatment (group 3). Adverse events were recorded; C-peptide (CP), insulin dose and HbA1c were measured at baseline (T0), after 3 (T3) and 6 months (T6). Results: In group 1 (n = 7), adverse events included transient headache (all), mild local reactions (all), tachycardia (n = 4), abdominal cramps (n = 1), thrombophlebitis (n = 4), scotomas (n = 2), and central retinal vein occlusion at T3 (n = 1, resolution at T6). Group 1 had an increase in basal CP (p = 0.018; mean: 40.41+/-40.79 %), without changes in stimulated CP after mixed meal (p = 0.62), from T0 to T6. Basal CP remained stable in groups 2 and 3 (p = 0.58 and p = 0.116, respectively). Group 1 had small insulin requirements (0.31+/-0.26 UI/kg) without changes at T6 (p = 0.44) and HbA1c decline (p = 0.01). At T6, all patients (100%; n = 7) in group 1 were in honeymoon vs 75% (n = 3/4) and 50% (n = 3/6) in groups 2 and 3, p = 0.01. Conclusions: Allogenic ASC + VIT D without immunosuppression was safe and might have a role in the preservation of β-cells in patients with recent-onset T1D. ClinicalTrials.gov: NCT03920397.

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Section: Discussionmentioning

confidence: 86%

Adipose tissue-derived stromal/stem cells + cholecalciferol: a pilot study in recent-onset type 1 diabetes patients

Dantas¹,

Araújo²,

Silva³

et al. 2021

Archives of Endocrinology and Metabolism

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“…V0: the 0th visit; V4: the 4th visit; V8: the 8th visit. [5]. Another assumption was the association of autoantibodies and human leukocyte antigen (HLA) genotypes.…”

Section: Discussionmentioning

confidence: 99%

“…The Joslin 50-year medalist study found that most of the T1DM participants with a duration of 50 years or more reached endogenous clinical insulin secretion (random C − peptide ≥ 0:03 pmol/mL ) [4], and 2.6% had random serum C − peptide ≥ 0:20 pmol/ mL. Recently, the pancreatic β-cell function in T1DM had been investigated in the TrialNet Study [5], Search Study [6], and European multicenter clinical study [7]. However, the natural history of β-cell function is still ambiguity, especially in longduration patients, and the related factors of the decline of β-cell function are controversial.…”

Section: Introductionmentioning

confidence: 99%

Residual β-Cell Function in Type 1 Diabetes Followed for 2 Years after 3C Study

Lin

Yang

et al. 2021

Journal of Diabetes Research

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Objective. To investigate the natural history and related factors of the pancreatic β-cell function in Chinese type 1 diabetic patients from 3C study Shantou center. Method. Stimulated C-peptide levels from follow-up data of 201 individuals in 3C study Shantou subgroup starting in 2012 were used. Residual β-cell function was defined as stimulated C − peptide level ≥ 0.2 pmol / mL , on the basis of cut-points derived from the Diabetes Control and Complications Trial (DCCT). Results. 36.8% of patients had residual β-cell function, and the percentage was 68.2% in newly diagnosed diabetic patients. COX regression analysis indicated that the age of diagnosis, HbA1C level, and duration were independent factors of residual β-cell function in individuals with ≤5 years duration, but in those with duration ≥5 years, only the age of diagnosis was a predictor. The pancreatic β-cell function mainly declined in the first 5 years of the duration, and the rate of decline was correlated negatively with the duration and age of diagnosis. Receiver operating characteristic (ROC) analysis indicated that the cut-off point of stimulated C-peptide was 0.615 pmol/mL in patients with <5 years duration to have 7% HbA1c. Conclusion. Age at diagnosis was the strongest predictor for residual C-peptide. There was a more rapid decline of stimulated C-peptide in duration ≤5 years and younger patients. Therefore, intervention therapies of β-cells should start from the early stage, and the recommended target goal of stimulated C-peptide is 0.615 pmol/mL or above.

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“…The rate of β-cell loss occurs slower in adults than in children, and some fundamental differences in the disease process might be associated with age of type 1 diabetes presentation. 32 As suggested with other drugs, including CTLA4-Ig, anti-CD20, and anti-CD3 monoclonal antibodies, 3,4,7 imatinib might prove to be more efficacious in children with recent-onset type 1 diabetes than in adults. The ideal dose and duration of imatinib therapy requires further evaluation.…”

Section: B Discussionmentioning

confidence: 96%

Imatinib therapy for patients with recent-onset type 1 diabetes: a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial

Gitelman¹,

Bundy²,

Ferrannini³

et al. 2021

The Lancet Diabetes & Endocrinology

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Background Type 1 diabetes results from autoimmune-mediated destruction of β cells. The tyrosine kinase inhibitor imatinib might affect relevant immunological and metabolic pathways, and preclinical studies show that it reverses and prevents diabetes. Our aim was to evaluate the safety and efficacy of imatinib in preserving β-cell function in patients with recent-onset type 1 diabetes. MethodsWe did a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. Patients with recentonset type 1 diabetes (<100 days from diagnosis), aged 18-45 years, positive for at least one type of diabetesassociated autoantibody, and with a peak stimulated C-peptide of greater than 0•2 nmol L -¹ on a mixed meal tolerance test (MMTT) were enrolled from nine medical centres in the USA (n=8) and Australia (n=1). Participants were randomly assigned (2:1) to receive either 400 mg imatinib mesylate (4 × 100 mg film-coated tablets per day) or matching placebo for 26 weeks via a computer-generated blocked randomisation scheme stratified by centre. Treatment assignments were masked for all participants and study personnel except pharmacists at each clinical site. The primary endpoint was the difference in the area under the curve (AUC) mean for C-peptide response in the first 2 h of an MMTT at 12 months in the imatinib group versus the placebo group, with use of an ANCOVA model adjusting for sex, baseline age, and baseline C-peptide, with further observation up to 24 months. The primary analysis was by intention to treat (ITT). Safety was assessed in all randomly assigned participants. This study is registered with ClinicalTrials.gov, NCT01781975 (completed).Findings Patients were screened and enrolled between Feb 12, 2014, and May 19, 2016. 45 patients were assigned to receive imatinib and 22 to receive placebo. After withdrawals, 43 participants in the imatinib group and 21 in the placebo group were included in the primary ITT analysis at 12 months. The study met its primary endpoint: the adjusted mean difference in 2-h C-peptide AUC at 12 months for imatinib versus placebo treatment was 0•095 (90% CI -0•003 to 0•191; p=0•048, one-tailed test). This effect was not sustained out to 24 months. During the 24-month follow-up, 32 (71%) of 45 participants who received imatinib had a grade 2 severity or worse adverse event, compared with 13 (59%) of 22 participants who received placebo. The most common adverse events (grade 2 severity or worse) that differed between the groups were gastro intestinal issues (six [13%] partici pants in the imatinib group, primarily nausea, and none in the placebo group) and additional laboratory investigations (ten [22%] participants in the imatinib group and two [9%] in the placebo group). Per the trial protocol, 17 (38%) participants in the imatinib group required a temporary modification in drug dosing and six (13%) permanently discontinued imatinib due to adverse events; five (23%) participants in the placebo group had temporary modifications in dosing and none had a permanent discontinuation du...

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Response to Comment on: Greenbaum et al. Fall in C-Peptide During First 2 Years From Diagnosis: Evidence of at Least Two Distinct Phases From Composite Type 1 Diabetes TrialNet Data. Diabetes 2012;61:2066–2073

Cited by 52 publications

References 2 publications

Adipose tissue-derived stromal/stem cells + cholecalciferol: a pilot study in recent-onset type 1 diabetes patients

Adipose tissue-derived stromal/stem cells + cholecalciferol: a pilot study in recent-onset type 1 diabetes patients

Residual β-Cell Function in Type 1 Diabetes Followed for 2 Years after 3C Study

Imatinib therapy for patients with recent-onset type 1 diabetes: a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial

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