Martin S, Pawlowski B, Greulich B, Ziegler A G, Mandrup-Poulsen T, Mahon J
Diabetes Research Institute, Düsseldorf, Germany.
Diabetes Care. 1992 Jan;15(1):66-74. doi: 10.2337/diacare.15.1.66.
To describe the natural course of clinical remission in insulin-dependent diabetes mellitus (IDDM) when insulin dose is minimized without loss of target glycemia and to identify factors that predict clinical remission.
Ninety-five patients, who were placebo-treated control subjects in the Canadian-European multicenter randomized trial of cyclosporin A in recent-onset IDDM, were studied.
The mean insulin dose decreased during the first months after diagnosis, with a nadir at 3 mo, when 27% of the patients did not require insulin to maintain target glycemia. At 1 yr, 10% of patients still did not need insulin. Patients not receiving insulin who had glycosylated hemoglobin within the normal range were called remitters. Mean basal and glucagon-stimulated C-peptide values were significantly (P less than 0.025) higher in remitters than nonremitters at the start of the study. Therefore, all patients were divided into those with values above the mean stimulated C-peptide (0.4 nM) and those with values below the mean at entry. The probability of entering a remission with a stimulated C-peptide greater than 0.4 nM was 10 times as high (P less than 0.05) as for those with a stimulated C-peptide below this level. Surprisingly, the beginning and end of the remission were associated with neither major changes in C-peptide levels nor islet cell antibody and insulin-antibody titer. A more rapid loss of stimulated C-peptide occurred in patients who lacked HLA-DR3 and -DR4 (P less than 0.05 at mo 9).
This study shows a higher spontaneous clinical remission rate than expected during the 1st yr after diagnosis. Preserved beta-cell function at entry predicts a greater chance of entering a remission, and a more rapid loss of beta-cell function was seen in patients without HLA-DR3 and -DR4.
描述胰岛素依赖型糖尿病（IDDM）在胰岛素剂量最小化且不影响目标血糖水平时临床缓解的自然病程，并确定预测临床缓解的因素。
对95名患者进行了研究，这些患者是加拿大 - 欧洲多中心环孢素A治疗近期发病IDDM随机试验中的安慰剂对照受试者。
诊断后的头几个月平均胰岛素剂量下降，在3个月时达到最低点，此时27%的患者无需胰岛素来维持目标血糖水平。1年后，10%的患者仍不需要胰岛素。糖化血红蛋白在正常范围内且未接受胰岛素治疗的患者被称为缓解者。在研究开始时，缓解者的平均基础及胰高血糖素刺激后的C肽值显著高于未缓解者（P<0.025）。因此，将所有患者分为入组时刺激后C肽值高于平均值（0.4 nM）和低于平均值的两组。刺激后C肽大于0.4 nM的患者进入缓解期的概率是低于此水平患者的10倍（P<0.05）。令人惊讶的是，缓解期的开始和结束与C肽水平、胰岛细胞抗体及胰岛素抗体滴度的重大变化均无关。缺乏HLA - DR3和 - DR4的患者刺激后C肽下降更快（9个月时P<0.05）。
本研究显示诊断后第1年的自发临床缓解率高于预期。入组时保留的β细胞功能预示进入缓解期的机会更大，且在无HLA - DR3和 - DR4的患者中观察到β细胞功能丧失更快。
