Van Dalem Annelien, Demeester Simke, Balti Eric V, Decochez Katelijn, Weets Ilse, Vandemeulebroucke Evy, Van de Velde Ursule, Walgraeve An, Seret Nicole, De Block Christophe, Ruige Johannes, Gillard Pieter, Keymeulen Bart, Pipeleers Daniel G, Gorus Frans K
Diabetes Research Center, Vrije Universiteit Brussel, Laarbeeklaan 100, 1090, Brussels, Belgium.
Department of Clinical Chemistry and Radio-immunology, University Hospital Brussels, Brussels, Belgium.
Diabetologia. 2015 Dec;58(12):2753-64. doi: 10.1007/s00125-015-3761-y. Epub 2015 Sep 26.
AIMS/HYPOTHESIS: We examined whether measures of glycaemic variability (GV), assessed by continuous glucose monitoring (CGM) and self-monitoring of blood glucose (SMBG), can complement or replace measures of beta cell function and insulin action in detecting the progression of preclinical disease to type 1 diabetes.
Twenty-two autoantibody-positive (autoAb(+)) first-degree relatives (FDRs) of patients with type 1 diabetes who were themselves at high 5-year risk (50%) for type 1 diabetes underwent CGM, a hyperglycaemic clamp test and OGTT, and were followed for up to 31 months. Clamp variables were used to estimate beta cell function (first-phase [AUC5-10 min] and second-phase [AUC120-150 min] C-peptide release) combined with insulin resistance (glucose disposal rate; M 120-150 min). Age-matched healthy volunteers (n = 20) and individuals with recent-onset type 1 diabetes (n = 9) served as control groups.
In autoAb(+) FDRs, M 120-150 min below the 10th percentile (P10) of controls achieved 86% diagnostic efficiency in discriminating between normoglycaemic FDRs and individuals with (impending) dysglycaemia. M 120-150 min outperformed AUC5-10 min and AUC120-150 min C-peptide below P10 of controls, which were only 59-68% effective. Among GV variables, CGM above the reference range was better at detecting (impending) dysglycaemia than elevated SMBG (77-82% vs 73% efficiency). Combined CGM measures were equally efficient as M 120-150 min (86%). Daytime GV variables were inversely correlated with clamp variables, and more strongly with M 120-150 min than with AUC5-10 min or AUC120-150 min C-peptide.
CONCLUSIONS/INTERPRETATION: CGM-derived GV and the glucose disposal rate, reflecting both insulin secretion and action, outperformed SMBG and first- or second-phase AUC C-peptide in identifying FDRs with (impending) dysglycaemia or diabetes. Our results indicate the feasibility of developing minimally invasive CGM-based criteria for close metabolic monitoring and as outcome measures in trials.
目的/假设：我们研究了通过持续葡萄糖监测（CGM）和自我血糖监测（SMBG）评估的血糖变异性（GV）指标，是否可以在检测临床前期疾病进展为1型糖尿病的过程中补充或替代β细胞功能和胰岛素作用的指标。
22名1型糖尿病患者的自身抗体阳性（autoAb(+)）一级亲属（FDRs），他们自身患1型糖尿病的5年风险较高（50%），接受了CGM、高血糖钳夹试验和口服葡萄糖耐量试验（OGTT），并随访了长达31个月。钳夹变量用于估计β细胞功能（第一阶段[AUC5 - 10分钟]和第二阶段[AUC120 - 150分钟]C肽释放）以及胰岛素抵抗（葡萄糖处置率；M 120 - 150分钟）。年龄匹配的健康志愿者（n = 20）和近期发病的1型糖尿病患者（n = 9）作为对照组。
在autoAb(+) FDRs中，M 120 - 150分钟低于对照组第10百分位数（P10）在区分血糖正常的FDRs和有（即将发生的）血糖异常的个体时，诊断效率达到86%。M 120 - 150分钟优于对照组P10以下的AUC5 - 10分钟和AUC120 - 150分钟C肽，其诊断效率仅为59% - 68%。在GV变量中，CGM高于参考范围在检测（即将发生的）血糖异常方面比SMBG升高更有效（效率分别为77% - 82%和73%）。联合CGM指标与M 120 - 150分钟的效率相同（86%）。日间GV变量与钳夹变量呈负相关，且与M 120 - 150分钟的相关性比与AUC5 - 10分钟或AUC120 - 150分钟C肽的相关性更强。
结论/解读：源自CGM的GV和葡萄糖处置率，反映了胰岛素分泌和作用，在识别有（即将发生的）血糖异常或糖尿病的FDRs方面优于SMBG以及第一阶段或第二阶段AUC C肽。我们的结果表明，制定基于CGM的微创标准用于密切代谢监测并作为试验中的结局指标是可行的。
