Baron A D, Laakso M, Brechtel G, Edelman S V
Department of Medicine, Indiana University School of Medicine, Indianapolis 46202-5124.
J Clin Invest. 1991 Apr;87(4):1186-94. doi: 10.1172/JCI115117.
We have estimated the capacity and affinity of insulin-mediated glucose uptake (IMGU) in whole body and in leg muscle of obese non-insulin-dependent diabetics (NIDDM, n = 6) with severe hyperglycemia, glycohemoglobin (GHb 14.4 +/- 1.2%), lean controls (ln, n = 7) and obese nondiabetic controls (ob, n = 7). Mean +/- SEM weight (kg) was 67 +/- 2 (ln), 100 +/- 7 (ob), and 114 +/- 11 (NIDDM), P = NS between obese groups. NIDDM were also studied after 3 wk of intensive insulin therapy, GHb post therapy was 10.1 +/- 0.9, P less than 0.01 vs. pretherapy. Insulin (120 mu/m2 per min) was infused and the arterial blood glucose (G) sequentially maintained at approximately 4, 7, 12, and 21 mmol/liter utilizing the G clamp technique. Leg glucose uptake (LGU) was calculated as the product of the femoral arteriovenous glucose difference (FAVGd) and leg blood flow measured by thermodilution. Compared to ln, ob and NIDDM had significantly lower rates of whole body IMGU and LGU at all G levels. Compared to ob, the NIDDM exhibited approximately 50% and approximately 40% lower rates of whole body IMGU over the first two G levels (P less than 0.02) but did not differ at the highest G, P = NS. LGU was 83% lower in NIDDM vs. ob, P less than 0.05 at the first G level only. After insulin therapy NIDDM were indistinguishable from ob with respect to whole body IMGU or LGU at all G levels. A significant correlation was noted between the percent GHb and the EG50 (G at which 1/2 maximal FAVGd occurs) r = 0.73, P less than 0.05. Thus, (a) insulin resistance in NIDDM and obese subjects are characterized by similar decreases in capacity for skeletal muscle IMGU, but differs in that poorly controlled NIDDM display a decrease in affinity for skeletal muscle IMGU, and (b) this affinity defect is related to the degree of antecedent glycemic control and is reversible with insulin therapy, suggesting that it is an acquired defect.
我们评估了患有严重高血糖（糖化血红蛋白，GHb 14.4±1.2%）的肥胖非胰岛素依赖型糖尿病患者（NIDDM，n = 6）、瘦体型对照者（ln，n = 7）和肥胖非糖尿病对照者（ob，n = 7）全身及腿部肌肉中胰岛素介导的葡萄糖摄取（IMGU）的能力和亲和力。平均±标准误体重（kg）分别为67±2（ln）、100±7（ob）和114±11（NIDDM），肥胖组之间P值无统计学意义。还对NIDDM患者进行了为期3周的强化胰岛素治疗，治疗后糖化血红蛋白为10.1±0.9，与治疗前相比P<0.01。输注胰岛素（每分钟120μU/m²），并采用葡萄糖钳夹技术将动脉血糖（G）依次维持在约4、7、12和21mmol/L。腿部葡萄糖摄取（LGU）通过股动脉-静脉葡萄糖差值（FAVGd）与通过热稀释法测量的腿部血流量的乘积来计算。与ln相比，ob和NIDDM在所有血糖水平下全身IMGU和LGU的速率均显著降低。与ob相比，NIDDM在前两个血糖水平下全身IMGU的速率分别低约50%和约40%（P<0.02），但在最高血糖水平时无差异，P值无统计学意义。仅在第一个血糖水平时，NIDDM的LGU比ob低83%，P<0.05。胰岛素治疗后，NIDDM在所有血糖水平下的全身IMGU或LGU与ob无差异。糖化血红蛋白百分比与EG50（出现最大FAVGd的一半时的血糖值）之间存在显著相关性，r = 0.73，P<0.05。因此，（a）NIDDM和肥胖受试者的胰岛素抵抗表现为骨骼肌IMGU能力的类似降低，但不同之处在于血糖控制不佳的NIDDM对骨骼肌IMGU的亲和力降低，（b）这种亲和力缺陷与先前血糖控制的程度有关，并且可通过胰岛素治疗逆转，表明这是一种后天获得的缺陷。
