Diabetes is associated with dramatically decreased survival in female but not male subjects with cystic fibrosis
Diabetes is associated with dramatically decreased survival in female but not male subjects with cystic fibrosis
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DOI：
10.2337/diacare.28.9.2141
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发表时间：
2005-09-01
期刊：
影响因子：
16.2
通讯作者：
Moran, A
中科院分区：
文献类型：
--
作者：
Milla, CE;Billings, J;Moran, A
目的：对囊性纤维化（CF）患者的前瞻性随访队列进行生存分析，以确定糖尿病发展对生存的影响。研究设计和方法：检索1987-2002年在明尼苏达CF中心诊断为CF相关性糖尿病（CFRD）的患者的临床资料。Kaplan-Meier生存分析估计中位生存期。采用Cox回归分析资料，评价CFRD诊断时临床特征对死亡率的影响。结果：对1081例CF患者的临床信息进行了回顾。共发现123例伴有空腹高血糖的CFRD患者（男性58例）。无糖尿病男性受试者中位生存期为49.5年，有糖尿病男性受试者中位生存期为47.4年，无糖尿病女性受试者中位生存期为47.0年，有糖尿病女性受试者中位生存期为30.7年。只有女性和CFRD诊断时1 s内的用力呼气量是随后死亡风险的显著预测因子（P < 0.001）。这种强烈的相关性没有被CFTR基因型、BMI、类固醇使用、呼吸道病原体、HbA（1C）或妊娠混淆。结论：与所有患有CF的男性受试者和患有CF但无糖尿病的女性受试者相比，患有CFRD的女性受试者预后明显较差。这种性别差异的病因尚不清楚。我们推测这可能涉及女性激素和糖尿病的相互作用，促进促炎状态，或者雄激素可能保护男性受试者免受胰岛素缺乏的分解代谢影响。另外，女性CF患者出现糖尿病可能仅仅是其他生物学差异的一个标志，而这些差异并不是立即明显的。
OBJECTIVE- Survival analysis was performed on a prospectively followed cohort of patients with cystic fibrosis (CF) to determine the impact of the development of diabetes on survival.RESEARCH DESIGN AND METHODS- Clinical data were retrieved for patients diagnosed with CF-related diabetes (CFRD) at the Minnesota CF Center in 1987-2002. Kaplan-Meier survival analysis was performed to estimate median survival. Data were analyzed by Cox regression to evaluate the influence of clinical characteristics at the time of CFRD diagnosis on mortality.RESULTS- Clinical information was reviewed from 1,081 CF patients. A total of 123 patients with CFRD with fasting hyperglycemia were identified (58 males). Median survival was 49.5 years for male subjects without diabetes, 47.4 years for male subjects with diabetes, 47.0 years for female subjects without diabetes, and 30.7 years for female subjects with diabetes. Only female sex and forced expiratory volume in 1 s at the time of CFRD diagnosis were significant predictors of the subsequent risk of death (P < 0.001). This strong association was not confounded by CFTR genotype, BMI, steroid use, respiratory pathogens, HbA(1C), or pregnancy.CONCLUSIONS- Female subjects with CFRD have a remarkably poorer prognosis compared with all male subjects with CF and female subjects with CF but without diabetes. The etiology of this sex difference is not clear. We speculate it might involve the interaction of female hormones and diabetes on promotion of a proinflammatory state or that androgens might protect male subjects from the catabolic effects of insulin deficiency. Alternatively, the appearance of frank diabetes in female subjects with CF may simply be a marker for some other biological difference that is not immediately apparent.