Ward W K, Beard J C, Halter J B, Pfeifer M A, Porte D
Diabetes Care. 1984 Sep-Oct;7(5):491-502. doi: 10.2337/diacare.7.5.491.
The pathogenesis of the abnormal metabolic state in patients with non-insulin-dependent diabetes (NIDDM) is controversial. Even the term NIDDM stirs controversy because of the easily drawn inference that individuals with this form of diabetes do not need insulin treatment. Yet many patients with NIDDM are treated with insulin; some even develop hyperosmolar coma if not given insulin. Ketoacidosis, however, is very infrequent in this syndrome, implying that these patients are not dependent on insulin treatment to prevent mass mobilization of fatty acids and ketone bodies. The phrase noninsulin-dependent is therefore appropriate when used in this restricted fashion but inappropriate when used to imply adequacy of insulin secretion. The evaluation of the adequacy of islet function in this syndrome has been complex, since there is no standard of insulin output that can be defined for normal islets without specifying the physiologic setting under which the assessment has been made. For example, individuals with normal glucose levels but variable degrees of obesity have widely varying insulin secretion rates. Thus, the choice of controls is critical when comparing islet function in NIDDM to normal. In addition, the efficiency of the B-cell response to a challenge (e.g., oral glucose tolerance test) can markedly influence the magnitude of the stimulatory glucose level during the period of testing. For example, a subject with some impairment of insulin output will tend to become more hyperglycemic during the test. The hyperglycemia may then stimulate more insulin secretion so that the overall insulin output may appear equal to or even greater than that of a normal individual. In such a closed-loop system, strict control of input variables is necessary to evaluate whether or not insulin secretion is normal. As will be discussed, control of glucose level and other variables is seldom accomplished in dynamic glucose tolerance tests. As will be presented in this review, the development of appropriately controlled studies of islet function has provided convincing evidence that islet B-cell function is abnormal in patients with NIDDM. Since these studies are based on an understanding of normal islet function, normal islet B-cell physiology is discussed before pathophysiology. Finally, the implications of this analysis for the treatment of NIDDM with diet, hypoglycemic sulfonylureas, and insulin will be discussed.
非胰岛素依赖型糖尿病（NIDDM）患者异常代谢状态的发病机制存在争议。甚至“NIDDM”这个术语也引发了争议，因为人们很容易推断出患有这种糖尿病的个体不需要胰岛素治疗。然而，许多NIDDM患者接受胰岛素治疗；有些人如果不使用胰岛素甚至会发展为高渗性昏迷。然而，在这种综合征中酮症酸中毒非常罕见，这意味着这些患者不依赖胰岛素治疗来防止脂肪酸和酮体的大量动员。因此，“非胰岛素依赖型”这个短语在以这种受限方式使用时是合适的，但用于暗示胰岛素分泌充足时则不合适。评估该综合征中胰岛功能是否充足一直很复杂，因为在不指定评估所依据的生理背景的情况下，无法为正常胰岛定义胰岛素输出标准。例如，血糖水平正常但肥胖程度不同的个体胰岛素分泌率差异很大。因此，在比较NIDDM患者与正常人的胰岛功能时，对照的选择至关重要。此外，B细胞对刺激（如口服葡萄糖耐量试验）的反应效率会显著影响测试期间刺激血糖水平的幅度。例如，胰岛素输出有一定损害的受试者在测试期间往往会出现更高的血糖水平。然后高血糖可能会刺激更多胰岛素分泌，从而使总体胰岛素输出可能看起来等于甚至大于正常个体。在这样一个闭环系统中，严格控制输入变量对于评估胰岛素分泌是否正常是必要的。正如将要讨论的，在动态葡萄糖耐量试验中很少能实现对血糖水平和其他变量的控制。正如本综述中将阐述的，对胰岛功能进行适当对照研究的开展提供了令人信服的证据，表明NIDDM患者的胰岛B细胞功能异常。由于这些研究基于对正常胰岛功能的理解，在讨论病理生理学之前先讨论正常胰岛B细胞生理学。最后，将讨论这种分析对NIDDM饮食治疗、降糖磺脲类药物治疗和胰岛素治疗的意义。
