Whitmer Rachel A, Karter Andrew J, Yaffe Kristine, Quesenberry Charles P, Selby Joseph V
Kaiser Permanente, Division of Research, Section of Etiology and Prevention, 2000 Broadway, Oakland, CA 94612, USA.
JAMA. 2009 Apr 15;301(15):1565-72. doi: 10.1001/jama.2009.460.
Although acute hypoglycemia may be associated with cognitive impairment in children with type 1 diabetes, no studies to date have evaluated whether hypoglycemia is a risk factor for dementia in older patients with type 2 diabetes.
To determine if hypoglycemic episodes severe enough to require hospitalization are associated with an increased risk of dementia in a population of older patients with type 2 diabetes followed up for 27 years.
DESIGN, SETTING, AND PATIENTS: A longitudinal cohort study from 1980-2007 of 16,667 patients with a mean age of 65 years and type 2 diabetes who are members of an integrated health care delivery system in northern California.
Hypoglycemic events from 1980-2002 were collected and reviewed using hospital discharge and emergency department diagnoses. Cohort members with no prior diagnoses of dementia, mild cognitive impairment, or general memory complaints as of January 1, 2003, were followed up for a dementia diagnosis through January 15, 2007. Dementia risk was examined using Cox proportional hazard regression models, adjusted for age, sex, race/ethnicity, education, body mass index, duration of diabetes, 7-year mean glycated hemoglobin, diabetes treatment, duration of insulin use, hyperlipidemia, hypertension, cardiovascular disease, stroke, transient cerebral ischemia, and end-stage renal disease.
At least 1 episode of hypoglycemia was diagnosed in 1465 patients (8.8%) and dementia was diagnosed in 1822 patients (11%) during follow-up; 250 patients had both dementia and at least 1 episode of hypoglycemia (16.95%). Compared with patients with no hypoglycemia, patients with single or multiple episodes had a graded increase in risk with fully adjusted hazard ratios (HRs): for 1 episode (HR, 1.26; 95% confidence interval [CI], 1.10-1.49); 2 episodes (HR, 1.80; 95% CI, 1.37-2.36); and 3 or more episodes (HR, 1.94; 95% CI, 1.42-2.64). The attributable risk of dementia between individuals with and without a history of hypoglycemia was 2.39% per year (95% CI, 1.72%-3.01%). Results were not attenuated when medical utilization rates, length of health plan membership, or time since initial diabetes diagnosis were added to the model. When examining emergency department admissions for hypoglycemia for association with risk of dementia (535 episodes), results were similar (compared with patients with 0 episodes) with fully adjusted HRs: for 1 episode (HR, 1.42; 95% CI, 1.12-1.78) and for 2 or more episodes (HR, 2.36; 95% CI, 1.57-3.55).
Among older patients with type 2 diabetes, a history of severe hypoglycemic episodes was associated with a greater risk of dementia. Whether minor hypoglycemic episodes increase risk of dementia is unknown.
尽管急性低血糖可能与1型糖尿病儿童的认知障碍有关，但迄今为止尚无研究评估低血糖是否为老年2型糖尿病患者患痴呆症的危险因素。
确定在随访27年的老年2型糖尿病患者群体中，严重到需要住院治疗的低血糖发作是否与痴呆症风险增加有关。
设计、地点和患者：一项1980年至2007年的纵向队列研究，研究对象为16667名平均年龄65岁的2型糖尿病患者，他们是北加利福尼亚综合医疗服务系统的成员。
收集并审查1980年至2002年期间的低血糖事件，依据医院出院诊断和急诊科诊断进行。截至2003年1月1日，无痴呆症、轻度认知障碍或一般记忆问题既往诊断的队列成员，随访至2007年1月15日以诊断痴呆症。使用Cox比例风险回归模型检查痴呆症风险，并对年龄、性别、种族/族裔、教育程度、体重指数、糖尿病病程、7年平均糖化血红蛋白、糖尿病治疗、胰岛素使用时长、高脂血症、高血压、心血管疾病、中风、短暂性脑缺血和终末期肾病进行校正。
随访期间，1465名患者（8.8%）至少被诊断出1次低血糖发作，1822名患者（11%）被诊断出痴呆症；250名患者同时患有痴呆症和至少1次低血糖发作（16.95%）。与无低血糖发作的患者相比，有单次或多次发作的患者风险呈分级增加，完全校正后的风险比（HRs）为：1次发作（HR，1.26；95%置信区间[CI]，1.10 - 1.49）；2次发作（HR，1.80；95% CI，1.37 - 2.36）；3次或更多次发作（HR，1.94；95% CI，1.42 - 2.64）。有低血糖病史和无低血糖病史个体之间痴呆症的归因风险为每年2.39%（95% CI，1.72% - 3.01%）。当将医疗利用率、健康计划会员时长或自首次诊断糖尿病以来的时间添加到模型中时，结果并未减弱。在检查因低血糖导致的急诊科入院与痴呆症风险的关联（535次发作）时，结果相似（与0次发作的患者相比），完全校正后的HRs为：1次发作（HR，1.42；95% CI，1.12 - 1.78），2次或更多次发作（HR，2.36；95% CI，1.57 - 3.55）。
在老年2型糖尿病患者中，严重低血糖发作史与痴呆症风险增加有关。轻微低血糖发作是否会增加痴呆症风险尚不清楚。
