糖尿病胰岛素治疗总汇.ppt

* 1921年，1936年，1978 克隆出，1982年，第一个由基因工程生产的药物——胰岛素，在美国和英国获准使用； * Insulin detemir is an engineered analogue of insulin, produced by recombinant DNA techniques. The amino acid threonine at the B30 position has been removed, and a 14-carbon fatty acid has been attached to the amino acid lysine at position B29. These modifications to the insulin molecule radically change its properties of absorption and distribution, leading to a protracted action profile. Insulin detemir is also soluble at neutral pH. * 当发展至2型糖尿病时， ?细胞功能仅剩50%，患者从餐后高血糖进展至空腹高血糖，此时胰岛素分泌不足则更为显著，在第6年后?细胞功能减至25%。当由IGT发展至糖尿病阶段时，胰岛素抵抗并无进一步的发展，此时主要是胰岛?细胞受到损害，餐后高血糖加重胰岛素功能衰竭是疾病进展的重要驱动力。 总结从NGT ?胰岛素抵抗?IGT?糖尿病各项指标的演变过程，在所有指标中餐后高血糖是预测胰岛?细胞分泌功能的指标，餐后血糖越高，胰岛?细胞储备能力越低，越易转变为糖尿病。 * Available OADs act to modulate severe physiological or pathophysiological processes that contribute to hyperglycaemia in patients with Type 2 diabetes. Each of these treatments relies on the ability of patients’ beta cells to secrete insulin naturally or when stimulated. As previously discussed, Type 2 diabetes is characterised by a progressive decline in beta cell function. The insulin secretory capacity of the beta cell declines over time despite lifestyle and/or OAD intervention. Eventually the decline reaches a threshold where: Sulphonlyureas and prandial glucose regulators can no longer stimulate the secretion of sufficient insulin to maintain glycaemic control There will be too little circulating insulin for insulin sensitising agents (glitazones or metformin) to be effective The body will be unable to to deal with the glucose load that follows a meal, even when its absorption is slowed during alpha-glucosidase treatment. * 97、98年UKPDS总结了单一药物的应用，单用格列苯脲，氯磺丙脲、胰岛素、二甲双胍的病人HbA1c控制在8％以下。当时8％已经不错了，现在要求最好在7％以下，至少也在7.5％以下。发现3年大约只有半数病人可维持8％以下，6年大约只有35％－38％维持8％以下， 9年时大约16％－21％维持8％以下，所以单一药物治疗经过若干年（3、6、9年）效果越来越差。 * 可以预防糖尿病性合并症，这已被北美进行的 糖尿病控制和并发症试验(DCCT)这一大规模 DCCT：糖尿病控制与并发症关系的研究：它是以1441名胰岛素依赖型糖尿病患者为对象，随机分为强化胰岛素疗法 (自己测定血糖和CSn或多次注