Steele Chynna, Hagopian William A, Gitelman Stephen, Masharani Umesh, Cavaghan Melissa, Rother Kristina I, Donaldson David, Harlan David M, Bluestone Jeffrey, Herold Kevan C
Department of Medicine, Division of Endocrinology, and the Naomi Berrie Diabetes Center, College of Physicians and Surgeons, Columbia University, New York, New York, USA.
Diabetes. 2004 Feb;53(2):426-33. doi: 10.2337/diabetes.53.2.426.
Type 1 diabetes, a chronic autoimmune disease, causes destruction of insulin-producing beta-cells over a period of years. Although many markers of the autoimmune process have been described, none can convincingly predict the rate of disease progression. Moreover, there is relatively little information about changes in insulin secretion in individuals with type 1 diabetes over time. Previous studies document C-peptide at a limited number of time points, often after a nonphysiologic stimulus, and under non-steady-state conditions. Such methods do not provide qualitative information and may not reflect physiologic responses. We have studied qualitative and quantitative insulin secretion to a 4-h mixed meal in 41 patients with newly diagnosed type 1 diabetes and followed the course of this response for 24 months in 20 patients. Newly diagnosed diabetic patients had an average total insulin secretion in response to a mixed meal that was 52% of that in nondiabetic control subjects, considerably higher than has been described previously. In diabetic patients there was a decline of beta-cell function at an average rate of 756 +/- 132 pmol/month to a final value of 28 +/- 8.4% of initial levels after 2 years. There was a significant correlation between the total insulin secretory response and control of glucose, measured by HbA(1c) (P = 0.003). Two persistent patterns of insulin response were seen depending on the peak insulin response following the oral meal. Patients with an early insulin response (i.e., within the first 45 min after ingestion) to a mixed meal, which was also seen in 37 of 38 nondiabetic control subjects, had a significantly accelerated loss of insulin secretion, as compared with those in whom the insulin response occurred after this time (P < 0.05), and significantly greater insulin secretory responses at 18 and 24 months (P < 0.02). These results, which are the first qualitative studies of insulin secretion in type 1 diabetes, indicate that the physiologic metabolic response is greater at diagnosis than has previously been appreciated, and that the qualitative insulin secretory response is an important determinant of the rate of metabolic decompensation from autoimmune destruction.
1型糖尿病是一种慢性自身免疫性疾病，会在数年时间里导致产生胰岛素的β细胞遭到破坏。尽管已经描述了许多自身免疫过程的标志物，但没有一个能够令人信服地预测疾病进展速度。此外，关于1型糖尿病患者胰岛素分泌随时间变化的信息相对较少。以往的研究在有限的几个时间点记录C肽，通常是在非生理性刺激后且在非稳态条件下。此类方法无法提供定性信息，可能也无法反映生理反应。我们对41例新诊断的1型糖尿病患者进食4小时混合餐后的胰岛素分泌进行了定性和定量研究，并对其中20例患者的这一反应过程进行了24个月的跟踪。新诊断的糖尿病患者对混合餐的平均总胰岛素分泌量为非糖尿病对照受试者的52%，远高于此前所描述的水平。糖尿病患者的β细胞功能平均以756±132皮摩尔/月的速度下降，两年后最终值为初始水平的28±8.4%。总胰岛素分泌反应与通过糖化血红蛋白（HbA1c）测量的血糖控制之间存在显著相关性（P = 0.003）。根据口服餐后胰岛素反应峰值，观察到两种持续的胰岛素反应模式。对混合餐有早期胰岛素反应（即摄入后前45分钟内）的患者，38例非糖尿病对照受试者中有37例也出现这种情况，与胰岛素反应在此时间之后出现的患者相比，其胰岛素分泌损失显著加速（P < 0.05），且在18个月和24个月时胰岛素分泌反应显著更大（P < 0.02）。这些结果是对1型糖尿病胰岛素分泌的首次定性研究，表明在诊断时生理代谢反应比之前认识到的更大，且定性胰岛素分泌反应是自身免疫性破坏导致代谢失代偿速度的重要决定因素。
