摘要
近年来,有人将2型糖尿病(T2DM)定义为由胰岛素抵抗引起的一种疾病,作为代谢综合征的一部分。胰岛素抵抗确实存在于T2DM,但同时也以同样程度存在于许多并无糖尿病的人群中,这些人可有或无代谢综合征。因而单独胰岛素抵抗不可能是T2DM的决定性致病因素。T2DM从其最早的阶段包括糖耐量受损(IGT)及空腹血糖受损(IFG),甚或在可测出的这些血糖变化之前的“糖尿病前期”就出现胰岛素释放动力学的障碍;其主要特征是对葡萄糖反应的胰岛素释放第一相丧失,随之而来的是逐渐加重的第二相胰岛素和总胰岛素分泌的受损。第一相胰岛素反应丧失的后果为肝脏未能迅速胰岛素化,延迟了对肝葡萄糖输出的抑制,从而引起餐后高血糖。在某些研究中,确已发现T2DM时β细胞量总体的减少,但并非所有研究中都有此同样结果,故对此尚须进一步证实。现已明确,糖尿病易发人群的β细胞的分泌适应能力是有限的,在胰岛素抵抗或热量负荷对胰岛素释放要求增加时,就难以胜任。此外,即使轻度的高血糖也会严重影响胰岛素的分泌并减少胰岛素原的合成,从而使代谢所需的胰岛素进一步减少。转录因子PDX-1在此损伤过程中起关键作用。因而,及早并有效地将T2DM血糖控制于接近正常水平至关重要,尤其是对胰岛素一相分泌的恢复更是如此。
Over the past years, type 2 diabetes mellitus (T2DM) has been defined as a disease caused by insulin resistance, as part of the metabolic syndrome. Insulin resistance does exist in T2DM; however, it exists to the same extent in many more persons without diabetes, whether with or without other features of the metabolic syndrome. Therefore, insulin resistance alone can not be the determining pathogenic factor in T2DM.From its earliest stages, including impaired glucose tolerance (IGT) and impaired fasting glucose (IFG), but perhaps even before these measurable changes, at the “prediabetic” period, T2DM shows derangements in the kinetics of insulin release. Its main characteristic is the loss of first-phase insulin response to glucose, with gradual impairment of also second-phase or overall insulin secretion. Loss of first-phase response has metabolic consequences: lack of rapid insulinization of the liver delays the suppression of hepatic glucose output and causes therefore postprandial hyperglycemia. β-Cell mass has been found to be reduced in T2DM in some but not all studies; therefore this necessitates further confirmation. Nevertheless, it is clear that the diabetes-prone β-cell has limited capacity to adapt cell function to increased secretory demand in insulin resistance or caloric load. Furthermore, even mild hyperglycemia dramatically impairs insulin secretion and proinsulin biosynthesis, thus further reducing the availability of insulin for metabolic needs. The transcription factor PDX-1 plays a central role in this context. Therefore, early and effective induction of near-normoglycemia in T2DM is of paramount importance, especially with restoration of first-phase insulin secretion.
出处
《中华内分泌代谢杂志》
CAS
CSCD
北大核心
2005年第3期194-198,共5页
Chinese Journal of Endocrinology and Metabolism
