Mykkänen L, Haffner S M, Kuusisto J, Pyörälä K, Hales C N, Laakso M
Department of Medicine, University of Kuopio, Finland.
Diabetologia. 1995 Oct;38(10):1176-82. doi: 10.1007/BF00422366.
Insulin resistance and impaired insulin secretion are thought to be the primary defects in the pathogenesis of non-insulin-dependent diabetes mellitus (NIDDM). Disproportionately increased proinsulin relative to insulin levels are suggested to be an early indicator of a failing pancreas. We examined the relationship of fasting specific insulin, proinsulin, and 32, 33 split proinsulin concentrations, and the proinsulin: insulin ration to the risk of developing NIDDM 3.5 years later in 65-74-year-old non-diabetic Finnish subjects participating in a population-based study (n=892) on diabetes and heart disease. Altogether 69 subjects developed NIDDM over a 3.5-year follow-up (cases). The cases were compared to randomly-selected gender-matched control subjects (n=69) and control subjects matched for gender, glucose tolerance status (normal or impaired), and body mass index (n=69). There were no differences in insulin concentrations between cases and random or matched control subjects [median and interquartile range: 123 (77-154), 108 (74-143), 118 (83-145) pmol/l, p=0.271]. Random control subjects had lower proinsulin and 32, 33 split proinsulin concentrations and split proinsulin: insulin ratios compared to cases [5.7 (3.8-9.0) vs 7.3 (4.8-10.0) pmol/l, p=0.005; 7.3 (4.5-13.0 vs 10.4 (7.1-18.0) pmol/l, p=0.002; 0.073 (0.057-0.110) vs 0.097 (0.060- 0.135), p=0.003]. Matched control subjects had lower proinsulin concentrations and proinsulin: insulin ratios compared to cases [5.9 (4.0-7.7) vs 7.3 (4.8-10.0) pmol/l, p=0.019; 0.048 (0.035-0.071) vs 0.064 (0.045-0.100), p=0.008]. When cases were compared to matched control subjects a 1 SD increase in baseline proinsulin: insulin ratio was associated with a 1.37-fold risk (p=0.020) of developing diabetes. Moreover, this association was independent of fasting glucose concentration at baseline. Thus, in elderly prediabetic subjects disproportionately increased proinsulin concentration, an indicator of defective insulin secretion, is associated with conversion to diabetes over a short time period.
胰岛素抵抗和胰岛素分泌受损被认为是非胰岛素依赖型糖尿病（NIDDM）发病机制中的主要缺陷。相对于胰岛素水平，胰岛素原不成比例地增加被认为是胰腺功能衰退的早期指标。我们在一项基于人群的糖尿病和心脏病研究（n = 892）中，研究了65至74岁非糖尿病芬兰受试者的空腹特异性胰岛素、胰岛素原和32,33裂解胰岛素原浓度，以及胰岛素原与胰岛素比值与3.5年后发生NIDDM风险的关系。在3.5年的随访中，共有69名受试者患上了NIDDM（病例组）。将病例组与随机选择的性别匹配对照组受试者（n = 69）以及根据性别、糖耐量状态（正常或受损）和体重指数匹配的对照组受试者（n = 69）进行比较。病例组与随机或匹配对照组受试者之间的胰岛素浓度没有差异[中位数和四分位间距：123（77 - 154）、108（74 - 143）、118（83 - 145）pmol/l，p = 0.271]。与病例组相比，随机对照组受试者的胰岛素原和32,33裂解胰岛素原浓度以及裂解胰岛素原与胰岛素比值较低[5.7（3.8 - 9.0）对7.3（4.8 - 10.0）pmol/l，p = 0.005；7.3（4.5 - 13.0）对10.4（7.1 - 18.0）pmol/l，p = 0.002；0.073（0.057 - 0.110）对0.097（0.060 - 0.135），p = 0.003]。与病例组相比，匹配对照组受试者的胰岛素原浓度和胰岛素原与胰岛素比值较低[5.9（4.0 - 7.7）对7.3（4.8 - 10.0）pmol/l，p = 0.019；0.048（0.035 - 0.071）对0.064（0.045 - 0.100），p = 0.008]。当将病例组与匹配对照组受试者进行比较时，基线胰岛素原与胰岛素比值每增加1个标准差，患糖尿病的风险增加1.37倍（p = 0.020）。此外，这种关联独立于基线空腹血糖浓度。因此，在老年糖尿病前期受试者中，胰岛素原浓度不成比例地增加，这是胰岛素分泌缺陷的一个指标，与短时间内转变为糖尿病有关。
