Nauck M, Stöckmann F, Creutzfeldt W
Department of Medicine, Georg-August-University, Göttingen, FRG.
Eur J Clin Invest. 1990 Feb;20(1):15-28. doi: 10.1111/j.1365-2362.1990.tb01786.x.
In 15 patients with insulinoma, six patients after successful removal of this tumour, two patients with previous pancreas resection because of hypoglycaemia elsewhere, and 10 control subjects, the diagnostic usefulness of euglycaemic clamp procedures (without exogenous insulin) was assessed in comparison with prolonged starvation. Only insulinoma patients developed sustained hypoglycaemia (less than or equal to 2.3 mmol l-1) within 2-44 h without caloric intake, because of inappropriately elevated immunoreactive insulin (IR-insulin) concentrations. IR-proinsulin values were elevated in most (7 out of 10), but not in all insulinoma patients. The steady-state glucose infusion rate necessary to maintain a stable plasma glucose concentration of 4.4-5.0 mmol l-1 was significantly (P less than or equal to 0.001) higher in insulinoma patients (2.5 +/- 0.6 mg kg-1 min-1) than in pancreas resected patients (0.6 +/- 0.2 mg kg-1 min-1), or in control subjects (0.5 +/- 0.1 mg kg-1 min-1). Due to a considerable degree of overlap, sensitivity (0.44) and specificity (0.95) were too low for such a procedure to qualify as a diagnostic test. There was no correlation of glucose infusion rates to IR-insulin values (r = 0.024, P = 0.461). One reason for this was the development of insulin resistance in some, but not in all insulinoma patients. When, in analogy to insulin/glucose ratios, a diagnostic index was derived by multiplying the steady state glucose infusion rate by the steady state IR-insulin concentration, the diagnostic accuracy was greatly increased (sensitivity and specificity 0.94, respectively), but still lower than that of 'amended' insulin/glucose ratios in fasting plasma or at the time of discontinuation of prolonged fasts (1.00). Somatostatin infusions inhibited insulin secretion (IR-C-peptide plasma concentrations) by 52-88% in subjects without insulinoma and in those insulinoma patients whose tumour cells ultrastructurally contained plenty of normal secretory granules, and to a lesser degree when only abnormal or virtually no secretory granules were present, i.e. in more de-differentiated tumours. In contrast to this significant (P = 0.036) association, malignancy, i.e. the presence of metastases, could not be predicted from whether or not insulin secretion was resistant to the inhibitory action of somatostatin. In conclusion, euglycaemic clamp experiments are less reliable for detecting or excluding a functioning insulinoma than the relation of glucose and insulin values during starvation. The inhibition of insulin secretion by somatostatin depends on the presence of normal beta-granules, and does not distinguish adenomas from carcinomas.
在15例胰岛素瘤患者中，6例成功切除肿瘤，2例因其他部位低血糖曾行胰腺切除术，10例为对照受试者。将正常血糖钳夹术（不使用外源性胰岛素）与长时间饥饿进行比较，评估其诊断价值。仅胰岛素瘤患者在无热量摄入的2 - 44小时内出现持续性低血糖（≤2.3 mmol/L），原因是免疫反应性胰岛素（IR - 胰岛素）浓度异常升高。大多数（10例中的7例）但并非所有胰岛素瘤患者的IR - 胰岛素原值升高。维持血浆葡萄糖浓度稳定在4.4 - 5.0 mmol/L所需的稳态葡萄糖输注速率，胰岛素瘤患者（2.5±0.6 mg·kg⁻¹·min⁻¹）显著高于胰腺切除患者（0.6±0.2 mg·kg⁻¹·min⁻¹）或对照受试者（0.5±0.1 mg·kg⁻¹·min⁻¹）（P≤0.001）。由于存在相当程度的重叠，该检查的敏感性（0.44）和特异性（0.95）过低，不足以作为诊断试验。葡萄糖输注速率与IR - 胰岛素值无相关性（r = 0.024，P = 0.461）。原因之一在于部分但并非所有胰岛素瘤患者出现了胰岛素抵抗。类似于胰岛素/葡萄糖比值，通过将稳态葡萄糖输注速率乘以稳态IR - 胰岛素浓度得出诊断指数时，诊断准确性大幅提高（敏感性和特异性分别为0.94），但仍低于空腹血浆或长时间禁食结束时“修正”的胰岛素/葡萄糖比值（1.00）。生长抑素输注可使无胰岛素瘤的受试者以及肿瘤细胞超微结构中含有大量正常分泌颗粒的胰岛素瘤患者的胰岛素分泌（IR - C肽血浆浓度）抑制52% - 88%，而在仅存在异常或几乎无分泌颗粒时，即肿瘤分化程度更高时，抑制程度较小。与这种显著关联（P = 0.036）相反，无法根据胰岛素分泌是否对生长抑素的抑制作用有抵抗来预测恶性肿瘤，即转移的存在情况。总之，正常血糖钳夹实验在检测或排除功能性胰岛素瘤方面不如饥饿期间葡萄糖和胰岛素值的关系可靠。生长抑素对胰岛素分泌的抑制取决于正常β颗粒的存在，且无法区分腺瘤和癌。
