GLUCOSE FLUXES AND OXIDATION AFTER AN ORAL GLUCOSE-LOAD IN PATIENTS WITH NON-INSULIN-DEPENDENT DIABETES-MELLITUS OF VARIABLE SEVERITY
GLUCOSE FLUXES AND OXIDATION AFTER AN ORAL GLUCOSE-LOAD IN PATIENTS WITH NON-INSULIN-DEPENDENT DIABETES-MELLITUS OF VARIABLE SEVERITY
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DOI：
10.1016/0026-0495(93)90113-3
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发表时间：
1993-04-01
影响因子：
9.8
通讯作者：
BALASSE, EO
中科院分区：
文献类型：
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作者：
FERY, F;MELOT, C;BALASSE, EO
研究人员对19名肥胖非胰岛素依赖型糖尿病（NIDDM）患者和11名匹配的非糖尿病对照者进行了5小时口服葡萄糖耐量试验（OGTT），试验负荷为75 g，相当于约67 g 1.73 m2，研究了肝脏和外周组织对餐后葡萄糖反应的相对贡献。双示踪技术分别测量外源性和内源性葡萄糖通量。葡萄糖氧化用间接量热法测定。根据吸收后血糖浓度，以140 mg/dL为临界值，将糖尿病患者分为“轻度”（n= 7）和“重度”（n= 12）两组。在基础状态下，对照组和两个糖尿病亚组的葡萄糖浓度分别为99、117和194 mg/dL，但胰岛素浓度在组间无显著差异。与对照组相比，轻度糖尿病患者的基础高血糖完全由代谢清除率降低引起（118 v 144 mL/min； P< 0.05）。而在严重糖尿病患者中，基础高血糖是由肝糖输出量增加引起的（187v 139mg /min； P< 0.05）。代谢清除率降低（97 v 144 mL/min； P< 0.001）。001)。在葡萄糖摄入后的最初2小时内也出现了类似的情况。在轻度NIDDM患者中，葡萄糖浓度比对照组的36±7 mg/dL升高了121±10 mg/dL （P< 0.05）。001)。这种差异完全是由于组织葡萄糖摄取减少(31±2 v 42±3 g 2小时；P<。005)，两组总葡萄糖出现率（R a）几乎相同（43±2 v 46±3 g 2小时；NS）。糖尿病患者与对照组平均0 ~ 2小时胰岛素水平（73±16 v 92±10 μU/mL； NS）无显著差异。另一方面，重度糖尿病患者0 ~ 2小时综合胰岛素水平明显降低（36±3 v 92±10 μU/mL； P< 0.05）。001)，血糖的过度增加（2小时+ 158 mg/dL）与较高的总葡萄糖进入率(53±2 v 46±3 g 2小时；P<。P< 0.01)和减少组织处置(33±2 v 42±3 g 2 h；005)。总葡萄糖进入率升高仅与肝剩余葡萄糖输出率升高有关(15±1 v 8±1 g 2小时；P<。001)，外源性葡萄糖的R a不受糖尿病的影响。由于氧化和非氧化处理的损害，摄取减少的比例大致相等。糖尿病患者血糖和胰岛素水平持续升高超过2小时，使他们在摄入葡萄糖后5小时内葡萄糖处理和氧化率恢复正常。这些数据表明，在从正常状态过渡到明显的NIDDM期间，葡萄糖耐量降低最初是由于主要与外周胰岛素抵抗相关的外周葡萄糖处理受损。在异常的血糖反应中，肝脏葡萄糖输出抑制受损的额外参与只能在与严重缺乏胰岛素反应相关的更严重的糖尿病状态中确定。
The retative contribution of liver and peripheral tissues to the postprandial glucose response has been examined in 19 obese non-insulin-dependent diabetes mellitus (NIDDM) patients and 11 matched nondiabetic control subjects during a 5-hour oral glucose tolerance test (OGTT) performed with a load of 75 g, corresponding to approximately 67 g 1.73 m 2. A dual-tracer technique was used to measure exogenous and endogenous glucose fluxes separately. Glucose oxidation was measured by indirect calorimetry. Diabetic patients were subdivided into two subgroups designated as “mild”(n= 7) and “severe”(n= 12) NIDDM according to postabsorptive glucose concentration with a cut-off point of 140 mg/dL. In the basal state, glucose concentrations averaged 99, 117, and 194 mg/dL, respectively, in control subjects and in the two diabetic subgroups, but insulin concentrations were not significantly different between groups. In comparison to control subjects, the basal hyperglycemia of mildly diabetic patients was entirely caused by a reduced metabolic clearance rate (118 v 144 mL/min; P<. 05), whereas in severely diabetic patients basal hyperglycemia resulted from a combination of increased hepatic glucose output (187 v 139 mg/min; P<. 001) and decreased metabolic clearance rate (97 v 144 mL/min; P<. 001). A similar situation prevailed during the initial 2 hours after glucose ingestion. In patients with mild NIDDM, glucose concentration increased by 121±10 mg/dL as compared with 36±7 mg/dL in control subjects (P<. 001). This difference was entirely due to a reduction in tissue glucose uptake (31±2 v 42±3 g 2 hours; P<. 005), with the rates of total glucose appearance (R a) being almost identical in the two groups (43±2 v 46±3 g 2 hours; NS). Average 0 to 2-hour insulin levels were not significantly different between diabetic and control subjects (73±16 v 92±10 μU/mL; NS). On the other hand, in severely diabetic patients in whom the integrated 0-to 2-hour insulin levels were markedly decreased (36±3 v 92±10 μU/mL; P<. 001), the excessive increase in glycemia (+ 158 mg/dL at 2 hours) was accounted for in similar proportions by higher rates of total glucose entry (53±2 v 46±3 g 2 hours; P<. 01) and decreased tissular disposal (33±2 v 42±3 g 2 hours; P<. 005). The elevated total glucose entry rate was solely related to higher rates of residual hepatic glucose output (15±1 v 8±1 g 2 hours; P<. 001), with the R a of exogenous glucose not being affected by the presence of diabetes. The reduction in uptake resulted in approximately equal proportion from an impairment in oxidative and nonoxidative disposal. The persistence of elevated levels of glucose and insulin in the diabetic patients beyond 2 hours allowed them to normalize their rates of glucose disposal and oxidation within the 5 hours following glucose ingestion. It is suggested from these data that during the transition from the normal state to overt NIDDM, reduced glucose tolerance is due initially to an impaired peripheral glucose disposal related mainly to peripheral insulin resistance. The additional participation of an impaired suppression of hepatic glucose output in the abnormal glycemic response could only be identified in a more severe diabetic state associated with a grossly deficient insulin response.