Division of Metabolism, Endocrinology & Diabetes, Department of Internal Medicine, The Brehm Center for Diabetes Research, University of Michigan Medical School, Ann Arbor, Michigan 48105, USA.
Curr Opin Endocrinol Diabetes Obes. 2013 Aug;20(4):279-84. doi: 10.1097/MED.0b013e3283628610.
The assumption that patients with an extended duration of type 1 diabetes mellitus (T1D) do not retain residual functional β cells and endogenous insulin production has recently been challenged. The purpose to this review is to highlight some of the key emerging evidence supporting residual insulin and C-peptide secretion in long-standing T1D.
Recent investigations conducted in a group of type 1 diabetics of long-term duration, characterized clinically and histologically, provided solid evidence to suggest that pancreatic β cells are still present even after 50 years in a majority of these individuals. These residual β cells can secrete insulin in a physiologically regulated manner. Several published reports showed promising effects of glucagon-like peptide 1 (GLP-1) agonists on the glycemic control and residual C-peptide production in long-term T1D, although prospective studies are needed to rule out the potential long-term adverse effects of these drugs.
C-peptide is no longer considered an irrelevant by-product of insulin biosynthesis. In-depth basic and translational investigations aimed at understanding the molecular immunology and the pathophysiology are needed to elucidate the mechanisms underlying the residual insulin and C-peptide production in long-term T1D. This may shed light on to the regenerative capacity of β cells, the genetic susceptibility of the mechanisms of resistance to β-cell destruction, and possibly identifying new therapeutic strategies for T1D. Studies evaluating the long-term effects of insulin secretogogue agents along with immune intervention hold promise for their use in future clinical trials for long-term T1D.
目的综述： 人们一直认为，1 型糖尿病（T1D）病程延长的患者不再保留有功能的β细胞和内源性胰岛素分泌，但这种假设最近受到了挑战。本综述的目的是强调一些关键的新证据，这些证据支持长期 T1D 患者仍存在胰岛素和 C 肽分泌。
最新发现： 最近对一组长期 T1D 患者进行的临床和组织学特征研究提供了确凿的证据，表明即使在大多数患者中病程超过 50 年，胰腺β细胞仍存在。这些残留的β细胞可以以生理调节的方式分泌胰岛素。几项已发表的报告显示，胰高血糖素样肽 1（GLP-1）激动剂对长期 T1D 的血糖控制和残留 C 肽分泌有良好的效果，但需要前瞻性研究来排除这些药物的潜在长期不良影响。
总结： C 肽不再被认为是胰岛素生物合成的无关副产物。深入的基础和转化研究旨在阐明长期 T1D 中胰岛素和 C 肽分泌残留的分子免疫学和病理生理学机制，这可能有助于阐明β细胞的再生能力、β细胞破坏抵抗机制的遗传易感性，并可能为 T1D 确定新的治疗策略。评估胰岛素分泌刺激剂和免疫干预的长期效果的研究有望为长期 T1D 的未来临床试验提供这些药物的使用。
