Zeitler Phil, Hirst Kathryn, Copeland Kenneth C, El Ghormli Laure, Levitt Katz Lorraine, Levitsky Lynne L, Linder Barbara, McGuigan Paul, White Neil H, Wilfley Denise
Section of Endocrinology, Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO.
George Washington University Biostatistics Center, Rockville, MD
Diabetes Care. 2015 Dec;38(12):2285-92. doi: 10.2337/dc15-0848. Epub 2015 Nov 4.
To determine whether clinically accessible parameters early in the course of youth-onset type 2 diabetes predict likelihood of durable control on oral therapy.
TODAY was a randomized clinical trial of adolescents with type 2 diabetes. Two groups, including participants from all three treatments, were defined for analysis: (1) those who remained in glycemic control for at least 48 months of follow-up and (2) those who lost glycemic control before 48 months. Outcome group was analyzed in univariate and multivariate models as a function of baseline characteristics (age, sex, race/ethnicity, socioeconomic status, BMI, waist circumference, Tanner stage, disease duration, depressive symptoms) and biochemical measures (HbA1c, C-peptide, lean and fat body mass, insulin inverse, insulinogenic index). Receiver operating characteristic curves were used to analyze HbA1c cut points.
In multivariate models including factors significant in univariate analysis, only HbA1c and insulinogenic index at randomization remained significant (P < 0.0001 and P = 0.0002, respectively). An HbA1c cutoff of 6.3% (45 mmol/mol) (positive likelihood ratio [PLR] 3.7) was identified that optimally distinguished the groups; sex-specific cutoffs were 6.3% (45 mmol/mol) for females (PLR 4.4) and 5.6% (38 mmol/mol) for males (PLR 2.1).
Identifying youth with type 2 diabetes at risk for rapid loss of glycemic control would allow more targeted therapy. HbA1c is a clinically accessible measure to identify high risk for loss of glycemic control on oral therapy. Adolescents with type 2 diabetes unable to attain a non-diabetes range HbA1c on metformin are at increased risk for rapid loss of glycemic control.
确定青少年起病的2型糖尿病病程早期临床可获取的参数是否能预测口服治疗持久控制的可能性。
TODAY是一项针对2型糖尿病青少年的随机临床试验。为进行分析定义了两组,包括来自所有三种治疗方法的参与者:(1)在至少48个月的随访中保持血糖控制的患者,以及(2)在48个月前失去血糖控制的患者。将结局组作为基线特征(年龄、性别、种族/民族、社会经济地位、体重指数、腰围、坦纳分期、病程、抑郁症状)和生化指标(糖化血红蛋白、C肽、瘦体重和脂肪量、胰岛素抵抗、胰岛素生成指数)的函数,在单变量和多变量模型中进行分析。采用受试者工作特征曲线分析糖化血红蛋白切点。
在包含单变量分析中有显著意义因素的多变量模型中,仅随机分组时的糖化血红蛋白和胰岛素生成指数仍具有显著意义(分别为P<0.0001和P = 0.0002)。确定糖化血红蛋白临界值为6.3%(45 mmol/mol)(阳性似然比[PLR] 3.7)时能最佳区分两组;女性的性别特异性临界值为6.3%(45 mmol/mol)(PLR 4.4),男性为5.6%(38 mmol/mol)(PLR 2.1)。
识别有快速失去血糖控制风险的2型糖尿病青少年将有助于进行更有针对性的治疗。糖化血红蛋白是一种临床可获取的指标,用于识别口服治疗中失去血糖控制的高风险。使用二甲双胍无法使糖化血红蛋白达到非糖尿病范围的2型糖尿病青少年快速失去血糖控制的风险增加。