闭环治疗与 1 型糖尿病患者 C 肽分泌的保存。

Closed-Loop Therapy and Preservation of C-Peptide Secretion in Type 1 Diabetes.

机构信息

From the Wellcome-Medical Research Council Institute of Metabolic Science (C.K.B., J.M.A., J.W., M.E.W., R.H.) and the Department of Paediatrics (J.M.A., J.W., M.E.W., A.T., R.H.), University of Cambridge, and Wolfson Diabetes and Endocrine Clinic, Cambridge University Hospitals NHS Foundation Trust (C.K.B., S.H.), Cambridge, the Department of Paediatric Diabetes and Endocrinology, Nottingham Children's Hospital, Nottingham (T.R.), the Department of Diabetes, Alder Hey Children's NHS Foundation Trust, Liverpool (A.G.), the Department of Paediatrics, University of Oxford, and the National Institute for Health and Care Research Oxford Biomedical Research Centre, John Radcliffe Hospital, Oxford (R.E.J.B.), the Department of Diabetes, Royal Hospital for Sick Children, Edinburgh (D.E.), the Department of Paediatric Diabetes, Southampton Children's Hospital, Southampton (N.T.), the Department of Paediatric Diabetes, Leeds Children's Hospital, Leeds (F.M.C.), and the Diabetes Research Group, Swansea University, Swansea (G.D.) - all in the United Kingdom; and Jaeb Center for Health Research, Tampa, FL (J.S., P.C., R.B.).

出版信息

N Engl J Med. 2022 Sep 8;387(10):882-893. doi: 10.1056/NEJMoa2203496.

DOI:10.1056/NEJMoa2203496

PMID:36069870

Abstract

BACKGROUND

Whether improved glucose control with hybrid closed-loop therapy can preserve C-peptide secretion as compared with standard insulin therapy in persons with new-onset type 1 diabetes is unclear.

METHODS

In a multicenter, open-label, parallel-group, randomized trial, we assigned youths 10.0 to 16.9 years of age within 21 days after a diagnosis of type 1 diabetes to receive hybrid closed-loop therapy or standard insulin therapy (control) for 24 months. The primary end point was the area under the curve (AUC) for the plasma C-peptide level (after a mixed-meal tolerance test) at 12 months after diagnosis. The analysis was performed on an intention-to-treat basis.

RESULTS

A total of 97 participants (mean [±SD] age, 12±2 years) underwent randomization: 51 were assigned to receive closed-loop therapy and 46 to receive control therapy. The AUC for the C-peptide level at 12 months (primary end point) did not differ significantly between the two groups (geometric mean, 0.35 pmol per milliliter [interquartile range, 0.16 to 0.49] with closed-loop therapy and 0.46 pmol per milliliter [interquartile range, 0.22 to 0.69] with control therapy; mean adjusted difference, -0.06 pmol per milliliter [95% confidence interval {CI}, -0.14 to 0.03]). There was not a substantial between-group difference in the AUC for the C-peptide level at 24 months (geometric mean, 0.18 pmol per milliliter [interquartile range, 0.06 to 0.22] with closed-loop therapy and 0.24 pmol per milliliter [interquartile range, 0.05 to 0.30] with control therapy; mean adjusted difference, -0.04 pmol per milliliter [95% CI, -0.14 to 0.06]). The arithmetic mean glycated hemoglobin level was lower in the closed-loop group than in the control group by 4 mmol per mole (0.4 percentage points; 95% CI, 0 to 8 mmol per mole [0.0 to 0.7 percentage points]) at 12 months and by 11 mmol per mole (1.0 percentage points; 95% CI, 7 to 15 mmol per mole [0.5 to 1.5 percentage points]) at 24 months. Five cases of severe hypoglycemia occurred in the closed-loop group (in 3 participants), and one occurred in the control group; one case of diabetic ketoacidosis occurred in the closed-loop group.

CONCLUSIONS

In youths with new-onset type 1 diabetes, intensive glucose control for 24 months did not appear to prevent the decline in residual C-peptide secretion. (Funded by the National Institute for Health and Care Research and others; CLOuD ClinicalTrials.gov number, NCT02871089.).

摘要

背景

新诊断为 1 型糖尿病的患者，采用混合闭环疗法改善血糖控制，与标准胰岛素疗法相比，是否可以保留 C 肽分泌，目前尚不清楚。

方法

在一项多中心、开放标签、平行组、随机试验中，我们将发病后 21 天内年龄为 10.0 至 16.9 岁的青少年患者随机分为接受混合闭环治疗或标准胰岛素治疗（对照组）的两组，进行 24 个月的治疗。主要终点是诊断后 12 个月时混合餐耐量试验后血浆 C 肽水平的曲线下面积（AUC）。分析基于意向治疗。

结果

共有 97 名参与者（平均[±标准差]年龄，12±2 岁）进行了随机分组：51 名参与者接受闭环治疗，46 名参与者接受对照组治疗。12 个月时 C 肽水平的 AUC（主要终点）在两组间无显著差异（几何均数，闭环治疗组为 0.35 pmol/ml[四分位距，0.16 至 0.49]，对照组为 0.46 pmol/ml[四分位距，0.22 至 0.69]；平均调整差异，-0.06 pmol/ml[95%置信区间{CI}，-0.14 至 0.03]）。24 个月时 C 肽水平的 AUC 两组间也无明显差异（几何均数，闭环治疗组为 0.18 pmol/ml[四分位距，0.06 至 0.22]，对照组为 0.24 pmol/ml[四分位距，0.05 至 0.30]；平均调整差异，-0.04 pmol/ml[95%CI，-0.14 至 0.06]）。12 个月时，闭环组的平均糖化血红蛋白水平比对照组低 4 mmol/mol（0.4 个百分点；95%CI，0 至 8 mmol/mol[0.0 至 0.7 个百分点]），24 个月时低 11 mmol/mol（1.0 个百分点；95%CI，7 至 15 mmol/mol[0.5 至 1.5 个百分点]）。闭环组发生 5 例严重低血糖（3 名参与者），对照组发生 1 例；闭环组发生 1 例糖尿病酮症酸中毒。