美国Jaeb健康研究中心Roy Beck团队研究了严格控制血糖对新诊断的青少年1型糖尿病患者胰腺β细胞功能的影响。2023年2月24日出版的《美国医学会杂志》发表了这项成果。

1型糖尿病诊断后立即开始葡萄糖水平接近正常化，已被认为可通过降低糖毒性来保护胰腺β细胞功能。先前的研究因无法实现严格的血糖目标而受阻。

该研究旨在确定强化糖尿病管理对新诊断为1型糖尿病的青年患者维持胰腺β细胞功能的有效性，以实现血糖水平接近正常。这项随机、双盲、临床试验在美国的6个中心进行（从2020年7月20日至2021年10月13日进行随机分组；2022年9月15日完成随访），包括7至17岁新诊断的1型糖尿病青少年。

对强化糖尿病管理进行随机分配，包括使用自动胰岛素输送系统（n = 61），或标准护理，包括使用连续血糖监测仪（n = 52），作为析因设计的一部分，体重为30公斤及以上的参与者也被分配接受口服维拉帕米或安慰剂。主要结局是在诊断52周后进行混合膳食耐受试验——刺激曲线下的C肽面积（胰腺β细胞功能的测量）。

113名参与者（平均年龄11.8岁；49名为女性[43%]；从诊断到随机分组的平均时间为24天）中，108名（96%）完成了试验。在强化管理组，曲线下的平均C-肽面积从基线时的0.57 pmol/mL下降到52周时的0.45 pmol/mL，在标准护理组从0.60 pmol/mL降至0.50 pmol/mL。在连续血糖监测的情况下，52周时，强化管理组在70至180 mg/dL的目标范围内的平均时间为78%，而标准护理组为64%（校正后的差异为16%）。每组发生1例严重低血糖事件和1例糖尿病酮症酸中毒事件。

研究结果表明，在新诊断为1型糖尿病的年轻人中，强化糖尿病管理（包括自动胰岛素输送）实现了良好的血糖控制，但不能阻止52周时胰腺C肽分泌的下降。

附：英文原文

Title: Effect of Tight Glycemic Control on Pancreatic Beta Cell Function in Newly Diagnosed Pediatric Type 1 Diabetes: A Randomized Clinical Trial

Author: Jennifer McVean, Gregory P. Forlenza, Roy W. Beck, Colleen Bauza, Ryan Bailey, Bruce Buckingham, Linda A. DiMeglio, Jennifer L. Sherr, Mark Clements, Anna Neyman, Carmella Evans-Molina, Emily K. Sims, Laurel H. Messer, Laya Ekhlaspour, Ryan McDonough, Michelle Van Name, Diana Rojas, Shannon Beasley, Stephanie DuBose, Craig Kollman, Antoinette Moran, CLVer Study Group, Antoinette Moran, Jennifer McVean, Shannon Beasley, Beth Pappenfus, Anne Street, Brittney Nelson, Janice Leschyshyn, Jane Kennedy, Ihsan Rizky, Gregory Forlenza, Erin Cobry, Laurel Messer, Robert Slover, Paul Wadwa, Lindsey Towers, Angela Karami, Emily Fivekiller, Emily Boranian, Estella Escobar, Emily Jost, Samantha Lange, Cari Berget, Luke Geiser, Mark Clements, Wayne Moore, Ryan McDonough, Emily Paprocki, Kelsee Halpin, Yun Yan, Erica Livingston, Kelsye Howell, Barbara Seuferling, Susan Parish, Stephen Orlich, Rachel Goff, Anna Neyman, Linda DiMeglio, Stephanie Woerner, Carmella Evans-Molina, Emily Sims, Megan Kirchner, Dana Chatila, Bruce Buckingham, Laya Ekhlasour, Lisa Norlander, Eliana Frank, Bailey Suh, Marci Morgan, Ryan Kingman, Liana Hsu, Jennifer Sherr, Kate Weyman

Issue&Volume: 2023-02-24

Abstract:

Importance  Near normalization of glucose levels instituted immediately after diagnosis of type 1 diabetes has been postulated to preserve pancreatic beta cell function by reducing glucotoxicity. Previous studies have been hampered by an inability to achieve tight glycemic goals.

Objective  To determine the effectiveness of intensive diabetes management to achieve near normalization of glucose levels on preservation of pancreatic beta cell function in youth with newly diagnosed type 1 diabetes.

Design, Setting, and Participants  This randomized, double-blind, clinical trial was conducted at 6 centers in the US (randomizations from July 20, 2020, to October 13, 2021; follow-up completed September 15, 2022) and included youths with newly diagnosed type 1 diabetes aged 7 to 17 years.

Interventions  Random assignment to intensive diabetes management, which included use of an automated insulin delivery system (n=61), or standard care, which included use of a continuous glucose monitor (n=52), as part of a factorial design in which participants weighing 30 kg or more also were assigned to receive either oral verapamil or placebo.

Main Outcomes and Measures  The primary outcome was mixed-meal tolerance test–stimulated C-peptide area under the curve (a measure of pancreatic beta cell function) 52 weeks from diagnosis.

Results  Among 113 participants (mean [SD] age, 11.8 [2.8] years; 49 females [43%]; mean [SD] time from diagnosis to randomization, 24 [5] days), 108 (96%) completed the trial. The mean C-peptide area under the curve decreased from 0.57 pmol/mL at baseline to 0.45 pmol/mL at 52 weeks in the intensive management group, and from 0.60 to 0.50 pmol/mL in the standard care group (treatment group difference, 0.01 [95% CI, 0.11 to 0.10]; P=.89). The mean time in the target range of 70 to 180 mg/dL, measured with continuous glucose monitoring, at 52 weeks was 78% in the intensive management group vs 64% in the standard care group (adjusted difference, 16% [95% CI, 10% to 22%]). One severe hypoglycemia event and 1 diabetic ketoacidosis event occurred in each group.

Conclusions and Relevance  In youths with newly diagnosed type 1 diabetes, intensive diabetes management, which included automated insulin delivery, achieved excellent glucose control but did not affect the decline in pancreatic C-peptide secretion at 52 weeks.

DOI: 10.1001/jama.2023.2063

Source: https://jamanetwork.com/journals/jama/fullarticle/2801975