Skin collagen glycation, glycoxidation, and crosslinking are lower in subjects with long-term intensive versus conventional therapy of type 1 diabetes - Relevance of glycated collagen products versus HbA1c as markers of diabetic complications
Skin collagen glycation, glycoxidation, and crosslinking are lower in subjects with long-term intensive versus conventional therapy of type 1 diabetes - Relevance of glycated collagen products versus HbA1c as markers of diabetic complications
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DOI：
10.2337/diabetes.48.4.870
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发表时间：
1999-04-01
期刊：
影响因子：
7.7
通讯作者：
Genuth, S
中科院分区：
文献类型：
--
作者：
Monnier, VM;Bautista, O;Genuth, S
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(呋喃)、糖氧化(戊糖苷和N-epsilon-[羧甲基]-赖氨酸[CML])和交联体(酸和胃蛋白酶溶解度)指标的关系。与常规治疗相比，强化治疗5年后呋喃西林降低30%~32%，戊二醛降低9%，慢性粒细胞白血病降低9%~13%，酸溶胶原升高24%，胃酶溶解胶原升高50%。除慢性粒细胞白血病和酸溶胶原蛋白外，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)受试者中均有统计学意义。年龄和持续时间调整的胶原蛋白变量与离活检最近的HbA(1c)值和先前累积的HbA(1c)值显著相关。以6个非冗余胶原参数为自变量，以视网膜病变、肾病和神经病变结果的不同表达为因变量的多元Logistic回归分析显示，并发症与全套胶原变量显著相关。令人惊讶的是，用胶原蛋白变量解释的并发症的总变异百分比(R-2)在强化治疗中为19%至36%，在常规治疗中为14%至51%。即使在对糖化血红蛋白(1c)进行调整后，这些相关性通常仍然显著，最出人意料的是，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，特别是早期的Amadori产物(呋喃)，是否有可能成为未来发生并发症的风险的预测因子，甚至可能比糖化血红蛋白(HBA(1c))更好的预测因子。
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 HbA(1c) value nearest the biopsy and with cumulative prior HbA(1c) 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 (R-2) 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 HbA(1c), 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 (HbA(1c)).