II型（非胰岛素依赖型）糖尿病患者死亡的危险因素：神经病变作用及HLA - DR4保护作用的证据

Risk factors for mortality in Type II (non-insulin-dependent) diabetes: evidence of a role for neuropathy and a protective effect of HLA-DR4.

作者信息

Forsblom C M, Sane T, Groop P H, Tötterman K J, Kallio M, Saloranta C, Laasonen L, Summanen P, Lepäntalo M, Laatikainen L, Matikainen E, Teppo A M, Koskimies S, Groop L

机构信息

Department of Medicine, Helsinki University Hospital, Finland.

出版信息

Diabetologia. 1998 Nov;41(11):1253-62. doi: 10.1007/s001250051062.

DOI:10.1007/s001250051062

PMID:9833930

Abstract

To test the hypothesis that interaction between genetic, immunological, clinical and metabolic risk factors influences the outcome of Type II (non-insulin-dependent) diabetes mellitus, we examined which of the above factors present at baseline were associated with mortality in 134 Type II diabetic patients followed for 9 years. Thirty-eight patients (29%) died during the follow-up period; the majority of whom (68%) died from cardiovascular disease. At baseline, the deceased patients had higher HbA1c values (p = 0.002), higher LDL-triglycerides (p = 0.007), lower HDL-cholesterol (p = 0.007), higher non-esterified fatty acid (NEFA) concentrations (p = 0.014), and higher albumin excretion rate (p < 0.0001) than the patients who survived. In addition, the frequency of HLA-DR4 (21 vs 39%, p = 0.048) and of parietal cell antibodies (5 vs 14%, p = 0.016) were decreased in the deceased as compared to the living patients. Patients who died during follow-up also had more retinopathy (42 vs 16%, p = 0.002), neuropathy (57 vs 23%, p < 0.001), microalbuminuria (45 vs 6%, p < 0.0001), coronary heart disease (50 vs 13%, p < 0.0001), and peripheral vascular disease (27 vs 9%, p = 0.005) at baseline than patients who survived. In a multiple logistic regression analysis macroangiopathy (p = 0.004), neuropathy (p = 0.007), HbA1c (p = 0.018) and albumin excretion rate (p = 0.016) were independent risk factors for death. In patients free of cardiovascular disease at baseline, conventional risk factors such as LDL-cholesterol (p = 0.005) and age (p = 0.003) were associated with subsequent development of cardiovascular disease. In conclusion, in addition to coexisting macroangiopathy, increased albumin excretion rate, poor glycaemic control and neuropathy are risk factors for cardiovascular mortality in patients with Type II diabetes. The presence of HLA-DR4 and signs of autoimmunity may be associated with decreased risk of cardiovascular disease.

摘要

为了验证基因、免疫、临床和代谢风险因素之间的相互作用会影响II型（非胰岛素依赖型）糖尿病预后这一假设，我们研究了134例随访9年的II型糖尿病患者中，哪些基线时存在的上述因素与死亡率相关。38例患者（29%）在随访期间死亡；其中大多数（68%）死于心血管疾病。基线时，死亡患者的糖化血红蛋白（HbA1c）值更高（p = 0.002），低密度脂蛋白甘油三酯更高（p = 0.007），高密度脂蛋白胆固醇更低（p = 0.007），非酯化脂肪酸（NEFA）浓度更高（p = 0.014），白蛋白排泄率更高（p < 0.0001）。此外，与存活患者相比，死亡患者中HLA - DR4的频率（21%对39%，p = 0.048）和壁细胞抗体的频率（5%对14%，p = 0.016）降低。随访期间死亡的患者在基线时也比存活患者有更多的视网膜病变（42%对16%，p = 0.002）、神经病变（57%对23%，p < 0.001）、微量白蛋白尿（45%对6%，p < 0.0001）、冠心病（50%对13%，p < 0.0001）和外周血管疾病（27%对9%，p = 0.005）。在多因素logistic回归分析中，大血管病变（p = 0.004）、神经病变（p = 0.007）、HbA1c（p = 0.018）和白蛋白排泄率（p = 0.016）是死亡的独立危险因素。在基线时无心血管疾病的患者中，常规风险因素如低密度脂蛋白胆固醇（p = 0.005）和年龄（p = 0.003）与随后心血管疾病的发生相关。总之，除了并存的大血管病变外，白蛋白排泄率增加、血糖控制不佳和神经病变是II型糖尿病患者心血管死亡的危险因素。HLA - DR4的存在和自身免疫迹象可能与心血管疾病风险降低相关。