Haffner S M, Gonzalez C, Mykkänen L, Stern M
Department of Medicine, University of Texas Health Science Center at San Antonio 78284-7873, USA.
Diabetologia. 1997 Jul;40(7):830-7. doi: 10.1007/s001250050756.
Although insulin resistance and decreased insulin secretion are characteristic of established non-insulin-dependent diabetes mellitus (NIDDM), which of these metabolic abnormalities is the primary determinant of NIDDM is still controversial. A disproportionate increase in the proinsulin to insulin ratio has been proposed as a marker of compromised insulin secretion. We examined the association of fasting immunoreactive insulin (which cross-reacts with proinsulin), specific insulin (which does not cross-react with proinsulin), total immunoreactive proinsulin (or insulin precursors), and the fasting proinsulin/specific insulin ratio to the risk of developing NIDDM in the 3.25-year follow-up of the Mexico City Diabetes Study. These measurements were made in 85 subjects who subsequently converted to NIDDM (prediabetic subjects) and in 85 age and gender matched subjects who remained non-diabetic at follow-up (control subjects). Immunoreactive insulin, proinsulin and the proinsulin/specific insulin ratio were significantly higher in prediabetic than in control subjects. However, the relation between specific insulin and the development of NIDDM was weaker than for proinsulin or immunoreactive insulin. After further adjustment for obesity, body fat distribution and glucose tolerance status, proinsulin and the proinsulin/specific insulin ratio, but not specific or immunoreactive insulin, predicted conversion to NIDDM. A high proinsulin/specific insulin ratio predicted conversion to NIDDM both in subjects with normal and those with impaired glucose tolerance at baseline. We conclude that in prediabetic subjects increased proinsulin, a marker of islet cell distress or compromised insulin secretion, is associated with rapid conversion (within 3.25 years) to NIDDM even in obese populations.
尽管胰岛素抵抗和胰岛素分泌减少是成熟的非胰岛素依赖型糖尿病（NIDDM）的特征，但这些代谢异常中哪一个是NIDDM的主要决定因素仍存在争议。胰岛素原与胰岛素的比例不成比例增加已被提议作为胰岛素分泌受损的标志物。在墨西哥城糖尿病研究的3.25年随访中，我们研究了空腹免疫反应性胰岛素（与胰岛素原交叉反应）、特异性胰岛素（与胰岛素原不交叉反应）、总免疫反应性胰岛素原（或胰岛素前体）以及空腹胰岛素原/特异性胰岛素比例与发生NIDDM风险之间的关联。对85名随后转变为NIDDM的受试者（糖尿病前期受试者）以及85名年龄和性别匹配且在随访中仍未患糖尿病的受试者（对照受试者）进行了这些测量。糖尿病前期受试者的免疫反应性胰岛素、胰岛素原和胰岛素原/特异性胰岛素比例显著高于对照受试者。然而，特异性胰岛素与NIDDM发生之间的关系比胰岛素原或免疫反应性胰岛素弱。在进一步调整肥胖、体脂分布和糖耐量状态后，胰岛素原和胰岛素原/特异性胰岛素比例而非特异性或免疫反应性胰岛素可预测向NIDDM的转变。高胰岛素原/特异性胰岛素比例在基线糖耐量正常和受损的受试者中均能预测向NIDDM的转变。我们得出结论，在糖尿病前期受试者中，胰岛素原增加，这是胰岛细胞功能障碍或胰岛素分泌受损的标志物，即使在肥胖人群中也与快速（3.25年内）转变为NIDDM相关。
