胰岛beta功能是2型糖尿病的初始因素

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Type 2 diabetes results from two fundamental pathogenic defects:impaired insulin secretion (or B -cell dysfunction) and insulin resistance manifested by increased hepatic glucose production and reduced peripheral glucose uptake. 2型糖尿病源于2个基本病理缺陷：不可修复的胰岛分泌（或者B细胞功能障碍）和表现为肝糖原产生增加和外周血糖摄入减少的胰岛素抵抗。
These defects are both genetically determined and influenced by environmental factors, such as physical inactivity and obesity. Preserved B -cell function to secrete sufficient insulin in response to peripheral resistance has emerged as the pivotal point in determining whether or not a patient progresses towards type 2 diabetes. 这些缺陷是由遗传决定并被如活动减少和肥胖等环境因素影响的。对外周抵抗作出反应的残存B细胞分泌功能不足的出现，是决定一个病人是否要进展到2型糖尿病的关键。
Studies in young and apparently healthy Caucasian populations with normal glucose tolerance (NGT) or impaired fasting glucose (IFG) demonstrated that the-cell--function varied quantitatively with B differences in insulin sensitivity.对年轻的和血糖正常或者空腹血糖受损看起来健康的的高加索人群的研究显示，胰岛素敏感性方面，细胞功能随着B细胞数量的不同而不同。
Analysis of first degree relatives of patients with type 2 diabetes has shown between--that the relationship -cell function is reciprocal in that changes insulin sensitivity and in one directly affect the other but not in a linear or logarithmic fashion .
对2型糖尿病患者一级相关的分析显示，细胞功能与胰岛素敏感性的关系是互反的，并且是一个直接关系而不是线性或者对数型。
The natural history has been extensively studied in the Pima Indians of Arizona who have a high percentage of their adult population developing type 2 diabetes by age 40. Further characterization of the -cell B--dysfunction have demonstrated that insulin secretion defects are indeed present prior to the progression to hyperglycemia and can predict progression from NGT to IGT to diabetes (DM) . 对于亚利桑那州的印度人的自然病史已有广泛的研究，他们40岁时以下的成人，发展为2型糖尿病的比例很高。对B细胞功能障碍特点的进一步研究显示，胰岛素分泌缺陷确实在进展到高血糖之前出现，并且能对空腹血糖正常发展到空腹血糖受损甚至糖尿病进行预测。
A longitudinal study that monitored progression at yearly intervals inpatients with initial NGT, found that transition from NGT to IGT was associated with an increase in body weight, a decline in insulin-stimulated glucose disposal, and a decline in the acute insulin secretory response to intravenous glucose (AIRglucose), but no change in endogenous glucose output .一个纵向研究，对起始血糖正常的住院病人一年一次进行监测，发现从空腹血糖正常到空腹血糖受损的转变与体重增加、胰岛素引起的血糖处理降低、静脉输入血糖急性胰岛素分泌反应降低有关，但是在内源性血糖产生上没有改变。
Longitudinal evaluation in the Mexico City study showed that beta cell function and not body weight or IR predicted progression to DM. Similarly, studies in women who have had a history of gestational diabetes shows that the progression to type 2 DM is correlated with the extent of impairment of insulin secretion.在墨西哥城研究的纵向评估显示，B细胞功能，而不是体重或者胰岛素抵抗，能预测到糖尿病的发展。相似的，对曾经有过妊娠糖尿病病史的妇女的研究，显示进展到2型糖尿病与胰岛素分泌功能损伤有关。
The role of the progressive nature of the insulin secretory defect was classically demonstrated by the UKPDS in newly diagnosed patients with Type 2 DM.胰岛素分泌缺陷的自然进展的作用，被研究新诊断2型糖尿病患者的UKPDS经典地阐释。
Beta cell function, as measured by the homeostasis model assessment method (HOMA), showed an inexorable decline over time which explains why most patients with type 2 DM will eventually necessitate insulin therapy if glycemic targets were to be achieved. B细胞功能，用HOMA测量，显示随着时间有顽固地降低，这解释了为什么大多数2型糖尿病患者最终必须使用胰岛素才能达到血糖靶目标。
Although individuals in the UKPDS receiving sulfonylurea therapy demonstrated an early increase in B -cell function from 45% to 78% in year 1 of the study(consistent with a secretagogue effect of the sulfonylurea agent) B -cell function subsequently decreased along the same slope as the diet treated group.虽然UKPDS中接受磺脲类治疗的个体显示，在研究的最初一年B细胞功能从45％上升到78％（磺脲类制剂的持续的促分泌作用）而在饮食治疗组随后有相同坡度的降低。
This inevitable decline in B -cell function also occurred in the metformin group in which B -cell function initially increased (similar to that in the sulfonylurea group) then declined from 66% to 38% by year 6.这种不可避免的B细胞功能的降低，同样发生于二甲双胍治疗组，B细胞功能开始升高（同磺脲类治疗组相似）然后从66％到第6年降到38％。
These data suggest that a significant amount of beta cell function has typically been lost at the time of diagnosis and it continues to decrease rapidly when treated with traditional monotherapies.这些数据显示，在诊断时B细胞功能已经丢失很明显，用传统的单一疗法它会继续很快地降低。
Over time, insulin secretion declines, presumably accelerated by glucotoxicity and lipotoxicity. Any therapeutic strategy that corrects hyperglycemia and reduces free fatty acid levels can potentially improve insulin action and increase the efficiency of insulin secretion.随着时间地过去，胰岛素分泌下降，推测可能被糖毒性和酯毒性加速。任何纠正血糖、降低了游离脂肪酸水平的治疗策略能潜在改善胰岛素作用，增加胰岛素分泌效率。
It is conceivable that earlier intervention with a combination of agents that reduce insulin resistance and also promote insulin secretion may preserve B -cell functional integrity to maintain a durable glycemic response but eventually, supplemental insulin replacement will be needed to achieve near-normoglycemia.早期降低胰岛素水平、促进胰岛素分泌的药物联合干预，可能残存B细胞功能整合以维持较长的血糖反应，这是可信的，但是最终，为达到接近正常的血糖需要补充胰岛素替代品。
Insulin replacement should be considered an option as part of the initial therapy in patients with type 2 diabetes in an attempt to correct the pathogenic defects and effectively reach glycemic targets.胰岛素替代品需要被认作是，2型糖尿病患者尝试纠正病理缺陷并有效达到血糖靶目标的起始治疗的选择的一部分。
The fact that this inexorable decline could not be altered with our traditional monotherapies suggests that a new approach to diabetes is needed. Given that the hyperglycemia develops because of a relative deficiency of insulin, this raises the question as to why insulin is typically not included in the regimen from the time of diagnosis.这种顽固的降低不能被我们传统的单一疗法改变的事实，预示对于糖尿病，需要一个新的方法。假设高血糖的进展是因为胰岛素相对缺陷，这将问题上升到，为什么胰岛素从诊断时就典型地不包括在样本中。
Indeed, short-term intensive insulin therapy in type 2 diabetes has been shown to improve insulin action by reversing glucotoxicity/lipotoxicity and possibly inducing “B -cell rest” that results in improved insulin secretion. 确实，对2型糖尿病患者进行短期的强化胰岛素治疗，已经显示通过逆转血糖毒性或者脂毒性来改变胰岛素作用，并可能诱导B细胞休息以改善胰岛素分泌。
It is tempting to speculate, therefore, that much earlier insulin administration, perhaps from the outset of the disease, might be crucial for preserving B-cell Preliminary support for this “B -cell rest”-function. is provided by a small study in newly diagnosed hyperglycemic-hypothesis with type 2 diabetes subjected to a period of 2 weeks of intensive insulin-patients therapy, resulting in near-normoglycemia.尝试去推测，因此，比较早期的胰岛素注射，或许从疾病起始，可能以让B细胞休息为理由对保护B细胞功能有重要作用。
Most of the patients subsequently-sustained good glycemic control for long periods of time without-pharmacologic intervention. 多数病人随后长期维持较好的血糖控制水平，不需要药物干预。
These intriguing findings, albeit with small-numbers of patients, suggest that insulin treatment in recently diagnosed of-type 2 diabetes might halt disease progression and permit long-term maintenance agents-nearly normal blood glucose levels with better response to oral-or to simpler long-term insulin supplementation.这些吸引人的发现，虽然患者数量较少，预示，对最近诊断为2型糖尿病者行胰岛素治疗可能停止疾病的进展，并允许长效制剂维持正常血糖水平，并对口服或者更简单的长效胰岛素补充有更好的反应。