Nishizawa Keitaro, Tanaka Marenao, Sato Tatsuya, Gohda Tomohito, Kamei Nozomu, Murakoshi Maki, Akiyama Yukinori, Kawaharata Wataru, Aida Hiroki, Kouzu Hidemichi, Yama Naoya, Kubota Mitsunobu, Sanuki Michiyoshi, Suzuki Yusuke, Furuhashi Masato
Division of Cardiovascular-Kidney-Metabolic Medicine, Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
Division of Cardiovascular-Kidney-Metabolic Medicine, Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan; Division of Cellular Physiology and Signal Transduction, Department of Physiology, Sapporo Medical University School of Medicine, Sapporo, Japan.
J Diabetes Complications. 2025 Oct;39(10):109146. doi: 10.1016/j.jdiacomp.2025.109146. Epub 2025 Jul 30.
Cardiovascular-kidney-metabolic (CKM) syndrome is a recently defined systemic condition linking cardiovascular disease, chronic kidney disease and metabolic disorders including type 2 diabetes (T2D). Although the CKM staging has been proposed for integrated risk assessment, its association with all-cause mortality in patients with T2D remains unclear. We investigated the prognosis in patients with T2D assigned by the CKM health stage.
A total of 632 Japanese patients with T2D were enrolled. The primary endpoint was all-cause death.
The numbers of the recruited patients with stages 2, 3 and 4 were 353 (55.9 %), 116 (18.3 %) and 163 (25.8 %), respectively. During a median follow-up of 64 months (35,327 person-months), 62 patients (9.8 %) died. Kaplan-Meier survival curves analysis showed significant differences in cumulative mortality among CKM health stages (log-rank test: P < 0.001) with higher cumulative mortality in stages 3 and 4 than in stage 2. Multivariable Cox proportional hazard models after adjustment of age, sex, body mass index, current smoking habit, cancer, relevant medications and hemoglobin A1c showed that adjusted hazard ratios (HRs) [95 % confidence intervals] for all-cause death were significantly higher in patients with stages 3 (2.25[1.08-4.69]) and those with stage 4 (2.87[1.41-5.84]) than in those with stage 2 as the reference. After additional adjustment of N-terminal pro-brain natriuretic peptide and estimated glomerular filtration rate among definition criteria for staging, the association of stages with all-cause death remained statistically significant in only stage 4 (2.16[1.02-4.56]).
The CKM health staging is useful for predicting all-cause mortality in Japanese patients with T2D.
心血管-肾脏-代谢(CKM)综合征是一种最近定义的全身性疾病,它将心血管疾病、慢性肾脏病和包括2型糖尿病(T2D)在内的代谢紊乱联系在一起。尽管已提出CKM分期用于综合风险评估,但其与T2D患者全因死亡率的关联仍不明确。我们研究了根据CKM健康分期分类的T2D患者的预后情况。
共纳入632例日本T2D患者。主要终点为全因死亡。
招募的2期、3期和4期患者人数分别为353例(55.9%)、116例(18.3%)和163例(25.8%)。在中位随访64个月(35327人月)期间,62例患者(9.8%)死亡。Kaplan-Meier生存曲线分析显示,CKM健康分期之间的累积死亡率存在显著差异(对数秩检验:P<0.001),3期和4期的累积死亡率高于2期。在调整年龄、性别、体重指数、当前吸烟习惯、癌症、相关药物和糖化血红蛋白后,多变量Cox比例风险模型显示,3期患者(2.25[1.08 - 4.69])和4期患者(2.87[1.41 - 5.84])的全因死亡调整后风险比(HRs)[95%置信区间]显著高于作为参照的2期患者。在分期定义标准中额外调整N末端脑钠肽前体和估算肾小球滤过率后,分期与全因死亡的关联仅在4期仍具有统计学意义(2.16[1.02 - 4.56])。
CKM健康分期有助于预测日本T2D患者的全因死亡率。