糖尿病的现代认知与SGLT2抑制剂的作用机制.ppt

* This graph then summarizes the anticipated effect of 30 to 50% blockade of the proximal tubular glucose reabsorption capacity using chemicals that promote competitive inhibition of the SGLT-2 specific in the kidney. ? Again, the y axis represents the rate of filtration, reabsorption and excretion of glucose by the kidney versus plasma glucose concentration in the x axis. The blockade shifts the curve to your left and the new threshold is reached when plasma glucose is at or around 100-140 glucose. Thus, glucose is lost in the urine at a lower concentration level [Tm]. Note that the starting threshold is shown at a higher value since these are diabetic conditions. The selective inhibition of SGLT-2 lowers plasma glucose in an insulin-independent manner without the risk of hypoglycemia and accomplishes body weight loss due to an average urinary loss of 600- 800 calories per day. * individuals stratified based on having hyperfiltration (T1D-H, GFR ≥ 135 mL/min/1.73m2, n=27) or normal GFR (T1D-N, GFR 90–134 mL/min/1.73m2, n=13) 1型糖尿病高滤过组：GFR ≥ 135 mL/min/1.73m2 1型糖尿病正常GFR组： GFR 90–134 mL/min/1.73m2 * 肾糖阈指血糖逐渐升高时引起糖尿现象时的血糖浓度，正常值为8.88mmol/L(160-190mg/dL)血糖超出肾糖阈，肾葡萄糖转运体饱和导致糖尿 Chao EC, et al. Nat Rev Drug Discov 2010;9:551-559; Marsenic O. Am J Kidney Dis 2009;53:875-883. 0 8.3 mmol/L 排泄阈 13.3 饱和阈 25 0 1 2 葡萄糖的过滤率/重吸收 / 排泄 (mmol/min) 3 葡萄糖的最大转运值(TmG) 开始出现糖尿 葡萄糖滤过率通常与血糖浓度成正比 过滤的葡萄糖 没有排泄 排泄的葡萄糖 重吸收的葡萄糖 斜偏 血糖 0 149.6 mg/dL 239.6 450.5 肾脏葡萄糖最大重吸收量取决于肾糖阈 八重奏—肾脏 2型糖尿病患者肾糖阈和TmG均升高 2型糖尿病患者 葡萄糖重吸收率(mg/dL) 血糖 (mmol/L) 健康受试者 阈值 斜偏 TmG =317 血糖 (mmol/L) 葡萄糖重吸收率(mg/dL) 阈值 TmG =420 肾糖阈：2型糖尿病患者较健康受试者升高15% 葡萄糖的最大转运值（TmG ）：2型糖尿病患者较健康受试者升高32%* * P0.001 Defronzo RA , et al. Diabetes Care. 2013; 36(10):3169-76. 细实线：葡萄糖滤过率 粗实线：预测的重吸收率 虚横线：TmG的几何平均数 圆圈：实际重吸收率 八重奏—肾脏 肾糖阈升高导致葡萄糖重吸收增加，可引起高血糖 肾糖阈升高葡萄糖重吸收和再循环增加，引起高血糖 Chao EC, et al. Nat Rev Drug Discov 2010;9:551-559;Marsenic O. Am J Kidney Dis 2009;53:875-883. Gerich JE. Diabet Med 2010;27:136–42; Abdul-Ghani MA, DeFronzo RA. Endocr