Bonfanti R, Bazzigaluppi E, Calori G, Riva M C, Viscardi M, Bognetti E, Meschi F, Bosi E, Chiumello G, Bonifacio E
Department of Paediatrics, Scientific Institute H San Raffaele, University of Milan, Italy.
Diabet Med. 1998 Oct;15(10):844-50. doi: 10.1002/(SICI)1096-9136(199810)15:10<844::AID-DIA679>3.0.CO;2-A.
Factors associated with residual insulin secretion and spontaneous remission in Type 1 diabetic patients are important in the evaluation of treatment aimed at modifying the natural history of Type 1 DM. We investigated the effect of parameters at onset on residual beta cell function in 215 Type 1 DM children and adolescents. Blood gas analysis, HLA, GAD and IA-2 antibodies before the start of insulin treatment were recorded for each patient. Residual C-peptide secretion was assessed by the glucagon test, and parameters of metabolic control (HbA1c and insulin dose U kg(-1) day(-1)) were examined at disease onset and after 3, 6, and 12 months. Residual C-peptide secretion throughout the first year of disease was significantly reduced in patients with disease onset before age 5. Multiple regression analysis showed that low pH at onset showed a significant and independent association with reduced C-peptide at 3 months (p = 0.02) and that the detection of GAD antibodies had a significant independent association with decreased C-peptide secretion at 6 months of follow-up (p = 0.02). Insulin requirement was higher in the youngest patients group and in patients with GAD antibodies. Spontaneous insulin remission (HbA1c <6% and insulin <0.3 U kg(-1) day(-1)) occurred in 22/192 (11%) patients at 3 months of follow-up, in 15/190 (8%) patients at 6 months and in 8/169 (5%) patient at 12 months. Remission was more prevalent in older patients (p = 0.01) and in patients without detectable GAD antibodies: (14/64 vs 8/128, p = 0.001). Sex, IA-2 antibodies and HLA DR were not independently associated with C-peptide secretion, insulin requirement or remission in the first year of Type 1 DM. This study confirms the association of young age, severe acidosis at disease onset, and GAD antibodies with decreased residual beta-cell function and spontaneous remission during the first year of insulin treatment. These factors should be considered in trials evaluating therapies to retain beta-cell function and induce remission at and after disease onset.
1型糖尿病患者残余胰岛素分泌及自发缓解的相关因素在评估旨在改变1型糖尿病自然病程的治疗中具有重要意义。我们研究了起病时各参数对215例1型糖尿病儿童及青少年残余β细胞功能的影响。记录了每位患者胰岛素治疗开始前的血气分析、HLA、GAD和IA - 2抗体情况。通过胰高血糖素试验评估残余C肽分泌，并在疾病起病时以及3、6和12个月后检查代谢控制参数（糖化血红蛋白HbA1c和胰岛素剂量U kg(-1) 天(-1)）。5岁前起病的患者在疾病第一年的残余C肽分泌显著减少。多元回归分析显示，起病时低pH值与3个月时C肽减少存在显著独立关联（p = 0.02），且随访6个月时GAD抗体检测与C肽分泌减少存在显著独立关联（p = 0.02）。最年轻患者组和有GAD抗体的患者胰岛素需求量更高。随访3个月时，22/192（11%）的患者出现自发胰岛素缓解（糖化血红蛋白HbA1c <6%且胰岛素<0.3 U kg(-1) 天(-1)），6个月时为15/190（8%），12个月时为8/169（5%）。缓解在年龄较大的患者中更常见（p = 0.01），且在未检测到GAD抗体的患者中更常见：（14/64 vs 8/128，p = 0.001）。性别、IA - 2抗体和HLA DR与1型糖尿病第一年的C肽分泌、胰岛素需求或缓解无独立关联。本研究证实了年龄小、疾病起病时严重酸中毒以及GAD抗体与胰岛素治疗第一年残余β细胞功能降低和自发缓解之间的关联。在评估旨在保留β细胞功能并在疾病起病时及之后诱导缓解的治疗试验中应考虑这些因素。
