Munich Diabetes Research Group e.V. at Helmholtz Centre, Neuherberg, Germany
Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC.
Diabetes Care. 2018 Mar;41(3):596-603. doi: 10.2337/dc17-1778. Epub 2018 Jan 8.
Severe hypoglycemic events (SHEs) in type 2 diabetes are associated with subsequent cardiovascular (CV) event risk. We examined whether CV events were associated with subsequent SHE risk.
Time-dependent associations between SHEs and a composite CV end point (fatal/nonfatal myocardial infarction or stroke, hospitalization for unstable angina, hospitalization for heart failure [hHF]) were examined post hoc in 14,671 TECOS (Trial Evaluating Cardiovascular Outcomes With Sitagliptin) participants with type 2 diabetes and CV disease followed for a median of 3.0 years.
SHEs were uncommon and unassociated with sitagliptin therapy ( = 160 [2.2%], 0.78/100 patient-years vs. = 143 [1.9%], 0.70/100 patient-years for placebo; hazard ratio [HR] 1.12 [95% CI 0.89, 1.40], = 0.33). Patients with (versus without) SHEs were older with longer diabetes duration, lower body weight, and lower estimated glomerular filtration rate; were more frequently women, nonwhite, and insulin treated; and more often had microalbuminuria or macroalbuminuria. Analyses adjusted for clinical factors showed SHEs were associated with increased risk of the primary composite CV end point (1.55 [1.06, 2.28], = 0.025), all-cause death (1.83 [1.22, 2.75], = 0.004), and CV death (1.72 [1.02, 2.87], = 0.040). Conversely, nonfatal myocardial infarction (3.02 [1.83, 4.96], < 0.001), nonfatal stroke (2.77 [1.36, 5.63], = 0.005), and hHF (3.68 [2.13, 6.36], < 0.001) were associated with increased risk of SHEs. Fully adjusted models showed no association between SHEs and subsequent CV or hHF events, but the association between CV events and subsequent SHEs remained robust.
These findings, showing greater risk of SHEs after CV events and greater risk of CV events after SHEs, suggest a common at-risk type 2 diabetes frail patient phenotype.
2 型糖尿病严重低血糖事件（SHEs）与随后的心血管（CV）事件风险相关。我们研究了 CV 事件是否与随后的 SHE 风险相关。
在 TECOS（西格列汀评估心血管结局试验）的 14671 名 2 型糖尿病合并 CV 疾病的参与者中，对 SHEs 与复合 CV 终点（致命/非致命性心肌梗死或中风、不稳定型心绞痛住院、心力衰竭住院[hHF]）之间的时间依赖性关联进行了事后分析，中位随访时间为 3.0 年。
SHEs 并不常见，与西格列汀治疗无关（=160[2.2%]，0.78/100 患者年；=143[1.9%]，0.70/100 患者年，安慰剂；风险比[HR]1.12[95%CI0.89，1.40]，=0.33）。与无 SHEs 患者相比，有 SHEs 患者年龄较大，糖尿病病程较长，体重较低，估算肾小球滤过率较低；更常见的是女性、非裔美国人、胰岛素治疗者；且更常伴有微量白蛋白尿或大量白蛋白尿。经临床因素调整的分析表明，SHEs 与主要复合 CV 终点（1.55[1.06，2.28]，=0.025）、全因死亡（1.83[1.22，2.75]，=0.004）和 CV 死亡（1.72[1.02，2.87]，=0.040）风险增加相关。相反，非致命性心肌梗死（3.02[1.83，4.96]，<0.001）、非致命性中风（2.77[1.36，5.63]，=0.005）和 hHF（3.68[2.13，6.36]，<0.001）与 SHEs 风险增加相关。完全调整的模型显示，SHEs 与随后的 CV 或 hHF 事件之间无关联，但 CV 事件与随后的 SHEs 之间的关联仍然存在。
这些发现表明，CV 事件后 SHEs 风险增加，而 CV 事件后 SHEs 风险增加，提示存在 2 型糖尿病脆弱患者表型。
