Maruyama Taro, Tanaka Shoichiro, Shimada Akira, Funae Osamu, Kasuga Akira, Kanatsuka Azuma, Takei Izumi, Yamada Satoru, Harii Norikazu, Shimura Hiroki, Kobayashi Tetsuro
Third Department of Internal Medicine, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi, Japan.
J Clin Endocrinol Metab. 2008 Jun;93(6):2115-21. doi: 10.1210/jc.2007-2267. Epub 2008 Apr 8.
We tested the hypothesis that insulin therapy rather than sulfonylurea (SU) treatment is preferable to reverse or preserve beta-cell function among patients with slowly progressive insulin-dependent (type 1) diabetes (SPIDDM) or latent autoimmune diabetes in adults.
This multicenter, randomized, nonblinded clinical study screened 4089 non-insulin-dependent diabetic patients for glutamic acid decarboxylase autoantibodies (GADAb). Sixty GADAb-positive non-insulin-requiring diabetic patients with a 5-yr duration or shorter of diabetes were assigned to either the SU group (n = 30) or the insulin group (n = 30). Serum C-peptide responses to annual oral glucose tolerance tests were followed up for a mean of 57 months. The primary endpoint was an insulin-dependent state defined by the sum of serum C-peptide values during the oral glucose tolerance test (SigmaC-peptide) less than 4 ng/ml (1.32 nmol/liter).
The progression rate to an insulin-dependent state in the insulin group (three of 30, 10%) was lower than that in the SU group (13 of 30, 43%; P = 0.003, log-rank). Longitudinal analysis demonstrated that SigmaC-peptide values were better preserved in the insulin group than in the SU group. Multiple regression analysis demonstrated that insulin treatment, a preserved C-peptide response, and a low GADAb titer at entry were independent factors in preventing progression to an insulin-dependent state. Subgroup analysis suggested that insulin intervention was highly effective for SPIDDM patients with high GADAb titers [> or =10 U/ml (180 World Health Organization U/ml)] and preserved beta-cell function [SigmaC-peptide > or = 10 ng/ml (3.31 nmol/liter)] at entry. No severe hypoglycemic episodes occurred during the study.
Insulin intervention to preserve beta-cell function is effective and safe for patients with SPIDDM or latent autoimmune diabetes in adults.
我们检验了这样一个假设，即在缓慢进展的胰岛素依赖型（1型）糖尿病（SPIDDM）或成人隐匿性自身免疫性糖尿病患者中，胰岛素治疗而非磺脲类药物（SU）治疗更有利于逆转或保留β细胞功能。
这项多中心、随机、非盲的临床研究对4089例非胰岛素依赖型糖尿病患者进行了谷氨酸脱羧酶自身抗体（GADAb）筛查。60例GADAb阳性、糖尿病病程为5年或更短且不需要胰岛素治疗的糖尿病患者被分为SU组（n = 30）或胰岛素组（n = 30）。对年度口服葡萄糖耐量试验的血清C肽反应进行了平均57个月的随访。主要终点是由口服葡萄糖耐量试验期间血清C肽值总和（SigmaC肽）小于4 ng/ml（1.32 nmol/升）定义的胰岛素依赖状态。
胰岛素组进展至胰岛素依赖状态的发生率（30例中的3例，10%）低于SU组（30例中的13例，43%；P = 0.003，对数秩检验）。纵向分析表明，胰岛素组的SigmaC肽值比SU组保存得更好。多元回归分析表明，胰岛素治疗、保存的C肽反应以及入组时较低的GADAb滴度是预防进展至胰岛素依赖状态的独立因素。亚组分析表明，胰岛素干预对入组时GADAb滴度高[≥10 U/ml（180世界卫生组织U/ml）]且β细胞功能保存良好[SigmaC肽≥10 ng/ml（3.31 nmol/升）]的SPIDDM患者非常有效。研究期间未发生严重低血糖事件。
对于成人SPIDDM或隐匿性自身免疫性糖尿病患者，采用胰岛素干预来保留β细胞功能是有效且安全的。
