Levy J C, Rudenski A, Burnett M, Knight R, Matthews D R, Turner R C
Diabetes Research Laboratories, Radcliffe Infirmary, Oxford, UK.
Diabetologia. 1991 Jul;34(7):488-99. doi: 10.1007/BF00403285.
The plasma insulin or C-peptide response to a 90-min constant glucose infusion 5 mg.kg ideal body weight-1.min-1 provides Beta-cell assessment comparable to more intensive methods. In 14 diet-treated Type 2 (non-insulin-dependent) diabetic subjects and 12 non-diabetic subjects, plasma insulin and C-peptide concentrations gave near linear plots against simultaneous glucose values. The 'glucose-insulin and glucose-C-peptide vectors' (G-I and G-C vectors), could be extrapolated to predict insulin and C-peptide levels during a 12 mmol/l hyperglycaemic clamp. Predicted concentrations correlated with clamp concentrations, r = 0.94 and r = 0.98 respectively, p less than 0.001, validating the vectors as empirical glucose dose-response curves. The vector slopes correlated highly with %Beta, a mathematical model-derived measure of Beta-cell function using constant infusion of glucose model assessment, Spearman r = 0.95 and 0.93 for insulin and C-peptide, respectively. G-I vector slopes in 21 diet-treated Type 2 diabetic subjects with fasting glucose (mean + 1 SD) 7.5 +/- 2.3 mmol/l, were lower than in 28 non-diabetic subjects, (geometric mean, 1 SD range, 8.4 pmol/mmol (3.3-21.0) and 25.1 pmol/mmol (14.3-44.1), p less than 0.001, respectively), indicating an impaired Beta-cell response. The G-I vector slopes correlated with obesity in both groups (r = 0.54 p less than 0.02 and 0.72, p less than 0.001 respectively), and, in 15 non-diabetic subjects, correlated inversely with insulin sensitivity as measured by a euglycaemic clamp (r = -0.66, p less than 0.01). Thus, Beta-cell function needs to be interpreted in relation to obesity/insulin resistance and, taking obesity into account, only 4 of 21 diabetic patients had Beta-cell function (G-I vector slope) in the non-diabetic range. The fasting plasma glucose in the diabetic subjects correlated inversely with the obesity-corrected G-I and G-C vector slopes (partial r = -0.57, p less than 0.01 and -0.86, p less than 0.001, respectively). The insulin or C-peptide response to the glucose infusion provides a direct empirical measure of the Beta-cell function, which can be interpreted in relation to obesity or to insulin resistance to assess underlying pancreatic responsiveness.
以5mg·kg理想体重⁻¹·min⁻¹的速率进行90分钟持续葡萄糖输注后，血浆胰岛素或C肽反应可提供与更强化方法相当的β细胞评估。在14例接受饮食治疗的2型（非胰岛素依赖型）糖尿病患者和12例非糖尿病患者中，血浆胰岛素和C肽浓度与同时测定的葡萄糖值呈近似线性关系。“葡萄糖-胰岛素和葡萄糖-C肽向量”（G-I和G-C向量）可外推以预测12mmol/l高血糖钳夹期间的胰岛素和C肽水平。预测浓度与钳夹浓度相关，r分别为0.94和0.98，p<0.001，验证了这些向量作为经验性葡萄糖剂量反应曲线的有效性。向量斜率与β细胞功能百分比高度相关，β细胞功能百分比是通过持续输注葡萄糖模型评估得出的一种数学模型衍生的β细胞功能测量指标，胰岛素和C肽的Spearman r分别为0.95和0.93。21例接受饮食治疗且空腹血糖（均值±1标准差）为7.5±2.3mmol/l的2型糖尿病患者的G-I向量斜率低于28例非糖尿病患者（几何均值，1标准差范围，分别为8.4pmol/mmol（3.3 - 21.0）和25.1pmol/mmol（14.3 - 44.1），p<0.001），表明β细胞反应受损。两组中G-I向量斜率均与肥胖相关（r分别为0.54，p<0.02和0.72，p<0.001），并且在15例非糖尿病患者中，与通过正常血糖钳夹测量的胰岛素敏感性呈负相关（r = -0.66，p<0.01）。因此，β细胞功能需要结合肥胖/胰岛素抵抗来解释，考虑到肥胖因素，21例糖尿病患者中只有4例的β细胞功能（G-I向量斜率）处于非糖尿病范围。糖尿病患者的空腹血浆葡萄糖与校正肥胖后的G-I和G-C向量斜率呈负相关（偏相关系数r分别为 -0.57，p<0.01和 -0.86，p<0.001）。葡萄糖输注后的胰岛素或C肽反应提供了β细胞功能的直接经验性测量指标，可结合肥胖或胰岛素抵抗来解释，以评估潜在的胰腺反应性。
