Ketosis Proneness and Insulin Dependency in Diabetes Mellitus

使用我们报道的方法测定酮体的空腹血清水平（Harano等人，Clin. Chim. Acta 22：327，1983）在超过300名患有胰岛素依赖型糖尿病（IDDM）以及非胰岛素依赖型糖尿病（NIDDM）的受试者中进行。结果表明，胰岛素依赖型糖尿病（IDDM）患者血清胰岛素水平明显高于非胰岛素依赖型糖尿病（NIDDM）患者，并建立了IDDM与NIDDM的判别方程。需要胰岛素治疗的NIDDM患者中的浓度也高于不需要胰岛素治疗的患者，尽管两组中血糖水平控制的标志物相似，表明血清酮水平可用作NIDDM患者胰岛素治疗（胰岛素依赖性）适应症的标志物。本实验从新生期腹腔注射链脲佐菌素（STZ）建立的NIDDM大鼠模型中分离肝细胞，研究血酮体水平升高的机制。酮体压 ...更多信息 NIDI）M大鼠肝细胞的诱导率受激素调节，明显高于正常大鼠，但低于酮症大鼠。这些数据表明，在非肥胖NIDDM的肝脏kotogenesis是由于胰岛素缺乏升高，而胰岛素拮抗剂和底物（游离脂肪酸）的血浆水平的升高也有助于增加浓度的ketobodies. Diabeticcoma分为两种类型;糖尿病酮症酸中毒和非酮症高渗性昏迷。然而，这两种状态的病理生理机制尚未明确。我们观察到静脉输注抗利尿激素（ADH）可降低血浆酮体水平，而不改变血浆游离脂肪酸浓度。由于血浆ADH水平在非酮症高渗性昏迷中升高，该激素可能通过抑制肝脏的生酮作用在疾病状态中发挥作用。在离体大鼠肝细胞中对ADH作用的研究表明，蛋白激酶C在生酮中起作用。我们还发现，肉碱棕榈酰转移酶的磷酸化;脂肪酸氧化的限速酶，当酶被激素激活时发生。一种新的肉毒碱类似物本发明公开了一种用于快速测定主要血浆酮体3-羟基丁酸酯（3-OHBA）的新系统，并已应用于临床。该系统由含有3-OHBA脱氢酶和染料的膜和反射率计组成。即使是患有胰岛素依赖型糖尿病的儿童，也可以在3分钟内准确测量血酮体水平。在家监测血糖水平发现，尽管血糖水平没有显著变化，但在病假和运动期间，血糖浓度会增加。我们认为，自我监测血糖和酮体水平将降低酮症酸中毒的发生率，并将改善糖尿病控制不仅对葡萄糖，而且脂肪酸代谢。少

Fasting serum levels of ketone bodies were determind using a method reported by us(Harano et al, Clin. Chim. Acta 22:327, 1983) in more than 300 subjects with insulin-dependent diabetes mellitus(IDDM) as well as non-insulin-dependent diabetes mellitus(NIDDM). The levels were higher in subjects with IDDM than in those with NIDDM, and the discriminant equation between IDDM and NIDDM has been developed. The concentrations were also higher in NIDDM patients who required insulin therapy than in the patients who did not require the insulin therapy even though markers for the control of blood glucose levels were similar in both groups, indicating that the serum ketone levels may be used as a marker for the indication of insulin therapy(insulin dependency) in NIDDM patients. The mechanisms of the elevated blood ketone body levels were studied in hepatocytes isolated from NIDDM model rats which were made diabetic by inpraperitoneal injection of streptozotocin at neonatal periods. Ketone body pr … More oduction rates in the hepatocytes from NIDI)M rats were regulated by hormones, and were significantly increased than in those from normal rats, but lower than in those from ketotic rats. These data indicate that the kotogenesis of the liver in non-obese NIDDM is elevated due to insulin deficiency, and that the elevation of plasma levels of insulin antagonists and substrate(free fatty acids) also contributes to the increased concentrations of ketone bodies.Diabetic coma is classified into two types; diabetic ketoacidosis and non-ketotic hyperosmolar coma. However, the pathophysiological mechanisms of these two states have not been clearly known. We have observed that intravenous infusion of anti-ditiretic hormone(ADH) decreased the plasma ketone body levels without changing the plasma concentrations of free fatty acids. Since plasma ADH levels are elevated in non-ketotic hyperosmolar coma, the hormone may play a role in the disease states through depressing the ketogenesis of the liver. A study of the ADH actions in isolated rat hepatocytes revealed that protein kinase C plays a role in ketogenesis. We have also found that the phosphorylation of carnitine-palmitoyl transferase; the rate limiting enzyme of fatty acid oxidation has taken place when the enzyme is activated by hormones. A new carnitine analogue; emeriamine was shown to reverse diabetic ketoacidosis and to have organ specificty; less effective in heart and other organs than in the liver.A new system for the rapid determination of a major plasma ketone body; 3-hydroxybutyrate(3-OHBA) has been developed and applied to a clinical use. The system consists with a film, containing 3-OHBA dehydrogenase and dye, and a reflectance meter. The blood ketone body levels can be measured within 3 minutes accurately even by children with IDDM. Monitoring of the levels at home revealed that the con centrations were increased on sick days as well as during exercise even though the blood glucose levels were not changed in a considerable magnitude. We believe that the self-monitoring of blood glucose and ketone body levels will decrease the incidence of ketoacidosis and will improve the diabetic control not only over glucose but also fatty acid metabolism. Less