年轻1型糖尿病患者残余β细胞功能的预测

Prediction of residual islet β-cell function in young patients with type 1 diabetes mellitus

目的 探讨影响新诊断年轻1型糖尿病患者病程进展后残余β细胞功能（RBF）的预测因素。 方法 入选110例12～35岁起病的新诊断1型糖尿病患者进行（35.1±13.8）个月的临床随访研究。记录一般资料，进行口服葡萄糖耐量试验和C肽释放试验，检测血清学指标、HbA1C和抗谷氨酸脱羧酶抗体（GAD）水平，并进行人类白细胞抗原（HLA）-Ⅱ类基因分型。根据随访终点的C肽峰值（Cmax）是否≥0.6 ng/ml将患者分成高RBF组和低RBF组。建立logistics回归模型分析预测RBF的相关因素。 结果 在随访终点，高RBF组的Cmax水平显著高于低RBF组[（1.87±1.35对0.23±0.19）ng/ml, P〈0.01]，HbA1C更低[（7.00±1.69对8.39±1.77）%, P〈0.01]，胰岛素剂量显著减低[（0.62±0.17对0.79±0.17）IU·kg-1·d-1,P〈0.01]。Logistics回归提示影响低RBF的相关因素有：起病年龄（OR＝0.82，95%CI 0.73～0.92, P＝0.001）、HLA-Ⅱ高危表型（OR＝4.73，95%CI 1.28～17.52, P＝0.020）、女性（OR＝3.39，95%CI 1.03～11.22, P＝0.045）、糖尿病酮症酸中毒起病史（OR＝8.71，95%CI 2.31～32.83, P＝0.001）以及病程进展中的HbA1C水平（OR＝2.46，95%CI 1.47～4.11, P＝0.001）。与血糖控制水平相比，起病状态的相关危险因素（起病年龄〈18岁、女性、携带高危的HLA表型、糖尿病酮症酸中毒起病）的综合预测概率值更大[（OR＝145.75，95%CI 17.30～1 228.31, P〈0.01）对（OR＝1.82，95%CI 1.24～2.69, P＝0.003）]。 结论 起病年龄小、女性、HLA-Ⅱ的高危表型、糖尿病酮症酸中毒起病史和病程中血糖控制不佳是较长病程后低RBF的影响因素；且相比于病程中HbA1C水平，起病状态对残余β细胞功能的影响作用更大。

Objective To investigate the predictive factors of residual β-cell function in young patients with newly-diagnosed type 1 diabetes mellitus. Methods After an average follow-up of （ 35.1 ± 13.8 ） months, a total of 110 young patients with type 1 diabetes mellitus were analyzed. At baseline and follow-up, oral glucose tolerance test （OGTF） and C-peptide release test were carried out, the levels of HbA1c, glutamie acid decarboxylase-antibody （ GAD ）, and the genetic polymorphisms of human leukocyte antigen （ HLA ） - Ⅱ were detected. The patients were divided into two groups： high-residual 13-cell function group （ high-RBF group） and low-residual β-cell function group （low-RBF group） , which were defined as stimulated C-peptide （ Cmax ） ≥ 0. 6 ng/ml and 〈0.6 ng/ml at endpoint, respectively. Logistic regression analyses were performed to explore the factors that influence long-term residual β-cell function. Results Compared with low-RBF group, Cmax levels were higher [ （ 1.87 ± 1.35 vs 0. 23 ±0.19 ） ng/ml, P〈0. 01 1, HbA1c levels were lower [ （7.00 ± 1.69 vs 8.39 ± 1.77 ） %, P 〈 0.01 ], insulin dosages were lower [ （0.62 ± 0.17 vs 0. 79 ± 0.17 ） IU · kg^-1 · d^-1 , P 〈0.01 ] in high-RBF group at endpoint. Logistic regression analysis suggested that factors including age of onset （years） [ OR = 0. 82, 95 % CI 0 73-0.92, P = 0. 001 ] , higher HLA risk status （ OR=4.73,95% CI 1.28-17.52, P=0. 020）, female sex （ OR=3.39, 95% CI 1.03-11.22, P= 0. 045 ）, diabetic ketoacidosis history at onset （ OR = 8.71, 95% CI 2.31-32.83, P = 0. 001 ）, and higher mean HbAlc levels （ OR=2.46, 95% CI 1.47-4.11, P=0. 001 ） were related to low residual β-cell function. Compared with mean HbAlc level during diabetes course, predicted probability value for the four baseline factors （ diagnosis age, HLA risk status, gender, and diabetic ketoacidosis history） as the onset state of type 1 diabetes patients was higher [ （ OR = 145.75,95% CI 17.30-1 228.31, P〈0.01 ） vs （ OR = 1. 82, 95% CI 1.24-2.69, P = 0.003 ） ]. Conclusion Younger age of onset, female, higher HLA risk status, diabetic ketoacidosis history at onset and poor glyeemic controlduring diabetes course were the predictive factors of low residual β-cell function in the development of the disease. Compared with mean HbA1c level during diabetes course, an onset state of type 1 diabetes mellitus patients is more valuable to predict long-term residual β-cell function.