Ketosis Proneness and Insulin Dependency in Diabetes Mellitus

空腹血清酮体水平采用我们报道的方法测定(Harano等人，临床。詹。研究人员对300多名胰岛素依赖型糖尿病（IDDM）和非胰岛素依赖型糖尿病（NIDDM）患者进行了研究。IDDM患者的水平高于NIDDM患者，并建立了IDDM与NIDDM之间的判别方程。需要胰岛素治疗的NIDDM患者的浓度也高于不需要胰岛素治疗的患者，尽管两组的血糖水平控制指标相似，这表明血清酮水平可以作为NIDDM患者胰岛素治疗指证（胰岛素依赖）的指标。以新生儿期腹腔注射链脲佐菌素致糖尿病的NIDDM模型大鼠肝细胞为样本，研究其血酮体水平升高的机制。酮体在NIDI)M大鼠肝细胞中的诱导率受激素调节，显著高于正常大鼠，但低于酮症大鼠。这些数据表明，非肥胖型NIDDM患者肝脏的生殖功能由于胰岛素缺乏而升高，血浆中胰岛素拮抗剂和底物（游离脂肪酸）水平的升高也有助于酮体浓度的增加。糖尿病昏迷分为两种类型；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不清楚。我们观察到静脉输注抗二体激素（ADH）可降低血浆酮体水平，但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在生酮过程中起作用。我们还发现肉毒碱-棕榈酰转移酶的磷酸化；脂肪酸氧化的限速酶在激素的激活下发生。一种新的肉碱类似物；研究表明，亚胺可逆转糖尿病酮症酸中毒，并具有器官特异性；对心脏和其他器官的作用不如对肝脏的有效。一种新的血浆酮体快速测定方法3-羟基丁酸酯（3-OHBA）已被开发并应用于临床。该系统由含有3-OHBA脱氢酶和染料的薄膜和反射率计组成。即使是IDDM患儿，也可在3分钟内准确测定血酮体水平。在家监测血糖水平显示，在病假和运动期间，血糖浓度会增加，尽管血糖水平没有明显变化。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，并将改善糖尿病的血糖和脂肪酸代谢控制。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