Monnier V M, Bautista O, Kenny D, Sell D R, Fogarty J, Dahms W, Cleary P A, Lachin J, Genuth S
Institute of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.
Diabetes. 1999 Apr;48(4):870-80. doi: 10.2337/diabetes.48.4.870.
The relationships between long-term intensive control of glycemia and indicators of skin collagen glycation (furosine), glycoxidation (pentosidine and N(epsilon)-[carboxymethyl]-lysine [CML]), and crosslinking (acid and pepsin solubility) were examined in 216 patients with type 1 diabetes from the primary prevention and secondary intervention cohorts of the Diabetes Control and Complications Trial. By comparison with conventional treatment, 5 years of intensive treatment was associated with 30-32% lower furosine, 9% lower pentosidine, 9-13% lower CML, 24% higher acid-soluble collagen, and 50% higher pepsin-soluble collagen. All of these differences were statistically significant in the subjects of the primary prevention cohort (P < 0.006-0.001) and also of the secondary intervention cohort (P < 0.015-0.001) with the exception of CML and acid-soluble collagen. Age- and duration-adjusted collagen variables were significantly associated with the HbA1c value nearest the biopsy and with cumulative prior HbA1c values. Multiple logistic regression analyses with six nonredundant collagen parameters as independent variables and various expressions of retinopathy, nephropathy, and neuropathy outcomes as dependent variables showed that the complications were significantly associated with the full set of collagen variables. Surprisingly, the percentage of total variance (R2) in complications explained by the collagen variables ranged from 19 to 36% with the intensive treatment and from 14 to 51% with conventional treatment. These associations generally remained significant even after adjustment for HbA1c, and, most unexpectedly, in conventionally treated subjects, glycated collagen was the parameter most consistently associated with diabetic complications. Continued monitoring of these subjects may determine whether glycation products in the skin, and especially the early Amadori product (furosine), have the potential to be predictors of the future risk of developing complications, and perhaps be even better predictors than glycated hemoglobin (HbA1c).
在糖尿病控制与并发症试验的一级预防和二级干预队列中，对216例1型糖尿病患者进行了长期强化血糖控制与皮肤胶原糖基化指标（糠氨酸）、糖氧化指标（戊糖苷和N-ε-（羧甲基）-赖氨酸[CML]）以及交联指标（酸溶性和胃蛋白酶溶性）之间关系的研究。与传统治疗相比，强化治疗5年使糠氨酸降低30 - 32%，戊糖苷降低9%，CML降低9 - 13%，酸溶性胶原增加24%，胃蛋白酶溶性胶原增加50%。除CML和酸溶性胶原外，所有这些差异在一级预防队列（P < 0.006 - 0.001）和二级干预队列（P < 0.015 - 0.001）的受试者中均具有统计学意义。经年龄和病程调整后的胶原变量与活检时最近的糖化血红蛋白（HbA1c）值以及累积的既往HbA1c值显著相关。以六个非冗余胶原参数作为自变量，以视网膜病变、肾病和神经病变结局的各种表达作为因变量进行的多因素逻辑回归分析表明，这些并发症与全套胶原变量显著相关。令人惊讶的是，胶原变量解释的并发症总方差百分比（R2）在强化治疗组中为19%至36%，在传统治疗组中为14%至51%。即使在调整HbA1c后，这些关联通常仍然显著，而且最出乎意料的是，在接受传统治疗的受试者中，糖基化胶原是与糖尿病并发症最始终相关的参数。对这些受试者的持续监测可能会确定皮肤中的糖基化产物，尤其是早期的阿马多里产物（糠氨酸），是否有可能成为未来发生并发症风险的预测指标，甚至可能比糖化血红蛋白（HbA1c）是更好的预测指标。
