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Skin Collagen Glycation Glycoxidation and Crosslinking Are Lower in Subjects With Long-Term Intensive Versus Conventional Therapy of Type 1 Diabetes

机译:长期密集治疗与1型糖尿病常规治疗相比皮肤胶原蛋白的糖基化糖基氧化和交联降低

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摘要

The relationships between long-term intensive control of glycemia and indicators of skin collagen glycation (furosine), glycoxidation (pentosidine and N-[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).
机译:长期强化血糖控制与皮肤胶原糖基化(速尿),糖氧化(戊糖苷和N -[羧甲基]-赖氨酸[CML])和交联(酸和胃蛋白酶)之间的关系从糖尿病控制和并发症试验的一级预防和二级干预队列中对216名1型糖尿病患者进行了检查。与常规治疗相比,经过5年的强化治疗后,肌酐降低了30–32%,戊糖苷降低了9%,CML降低了9–13%,酸溶性胶原蛋白增加了24%,胃蛋白酶溶性胶原蛋白增加了50%。所有这些差异在一级预防人群(P <0 .006-0.001)和二级干预人群(P <0.015-0.001)中均具有统计学意义,CML和酸溶性胶原除外。年龄和持续时间调整后的胶原蛋白变量与最接近活检的HbA1c值和累积的先前HbA1c值显着相关。多项逻辑回归分析以六个非冗余胶原参数作为自变量,以视网膜病变,肾病和神经病变结果的各种表达作为因变量,表明并发症与全套胶原变量显着相关。出乎意料的是,在强化治疗中,由胶原蛋白变量解释的并发症中总方差(R 2 )的百分比范围为19%至36%,而传统疗法为14%至51%。即使在调整了HbA1c之后,这些关联通常仍然很明显,而且最出乎意料的是,在常规治疗的受试者中,糖化胶原蛋白是与糖尿病并发症最一致相关的参数。持续监测这些受试者可能会确定皮肤中的糖基化产物,尤其是早期的Amadori产物(呋喃西林)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)更好。

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