Fear of hypoglycemia

Our doubts are traitors, and make us lose the good we oft might win, by fearing to attempt. William Shakespeare, Measure for Measure Few people with diabetes have lasting ill effects of hypoglycemia on cognitive function,1, 2 and hypoglycemic encephalopathy appears to occur quite infrequently,3, 4 but there is no doubt that hypoglycemia is a common, and costly, complication of treatment of type 1 diabetes (T1D).5 Hypoglycemia is uncomfortable and tracks with anxiety, in both experimental models6 and clinical settings.7, 8 Thus, despite strong evidence that tight glycemic control reduces long-term complications of diabetes, such control may have a "dark side", with a substantial number of people with T1D developing an understandable, but ultimately counterproductive, cycle of fear of hypoglycemia (FoH) leading to anxiety, with a consequent reduction in quality of life as well as worsening control and complication rates.9 Not all studies have shown a correlation of greater degrees of FoH with higher HbA1c,10 but this association has been noted by a number of authors. In a survey of 485 French T1D patients,11 only 28.3% reached their target HbA1c value, with 40.3% not reaching their target because of FoH. In that survey, both patients and their diabetologists felt that hypoglycemia impaired their quality of life, with hypoglycemia "…the most disturbing trouble for a diabetic patient" in 68.8% of those over 50 years of age and in 43.5% of those below 18 years of age.11 Hypoglycemia fears among patients included loss of glycemic control, particularly at older age (60%), embarrassing relatives (59%), avoiding driving (27%), avoiding physical exercise (39%), and refusing some professional tasks (25%).11 Because of FoH, 23.0% of patients reduced their insulin dose, 20.1% consumed more sugar than required for the degree of hypoglycemia, and 12.1% regularly ate more (8% doing so at bedtime); greater FoH was correlated with all these "counteractive behaviors".11 Fear of hypoglycemia has been reported to occur more commonly among women than men with T1D, despite women's lower likelihood in another survey of having severe hypoglycemia and of requiring emergency services.12 In a survey of 764 Swedes with T1D, both symptoms of being worried and fear in situations of being alone were associated with frequency of severe hypoglycemia and with the number of symptoms during mild hypoglycemia.13 Again, FoH was greater among women than men.13 A similar survey of 229 people with T1D showed FoH again occurred to a greater extent among women than men, particularly with hypoglycemia unawareness, with greater FoH among those performing more frequent home glucose monitoring and among those not having support from friends, healthcare providers, or at their workplace.14 Another survey, of 288 Dutch people with T1D, showed FoH to be associated with depressive symptoms as well as with a prior history of hypoglycemia.15 Fear of hypoglycemia is associated with excessive food intake, particularly carbohydrates. Education aimed at avoidance of overtreatment of hypoglycemia with excessive ingestion of simple sugars has been found to be of limited benefit, perhaps because the symptoms of panic, disorientation, hunger, and anxiety make following such approaches quite difficult.16 Fear of hypoglycemia is also a major barrier to regular physical activity and, in some studies, tracks with lower daily mean glucose levels and increased glucose variability.16 Another analysis observed that women with T1D often experience feelings of failure, being overwhelmed, and fatalism concerning complications, and that these women exhibit a variant of what has been termed the "external eating style", namely the tendency to eat in response to factors other than hunger, "…eating in response to insulin dose and time effects, capillary blood glucose levels, and/or planned physical activity, which have little to do with typical stimuli such as hunger and sensation".17 This critical effect of FoH on eating pattern was also noted in analysis of food intake and glucose and insulin logbooks over a 2-day period from 121 people with T1D,18 94 of whom experienced at least one hypoglycemic event (there was a total of 271 events during the period, further illustrating how commonly this issue occurs). On average, 73% of respondents overtreated their hypoglycemia with excess food ingestion.18 Similarly, FoH is a barrier to regular physical exercise.19, 20 Fear of hypoglycemia can be readily ascertained in the clinical setting. Recently, a condensed version of the Hypoglycemia Fear Survey II was published (Fig. 1),21 scored as the sum of the answers to five behavioral and six worry items, each rated from 0 (never) to 4 (almost always). More consistent use of such tools may enhance awareness of the symptom complex. Of course, the goal is to develop more effective approaches to control glycemia in T1D with lower risk of hypoglycemia. To this end, the development of continuous glucose monitoring and its integration into "closed loop" artificial pancreas insulin administration units appears increasingly close to widespread availability. However, until such time as this is truly available to all T1D patients, recognition of FoH will continue to be of clinical importance. 我们的多疑背叛了我们, 由于惧怕尝试, 它使我们失去了有可能赢得的利益。 威廉·莎士比亚, 量罪记 只有少数糖尿病患者的低血糖会对认知功能产生持续性的不良影响1,2,低血糖脑病似乎也很少发生3,4,但毫无疑问在1型糖尿病(T1D)患者中低血糖是一种常见的、代价高昂的治疗并发症5。无论是在实验模型6还是在临床环境7,8中, 低血糖都会令人不舒服并且使人焦虑不安。因此, 尽管已经有强有力的证据表明严格血糖控制可以减少糖尿病长期并发症, 但是严格控制血糖可能还有"不良的一面", 大量的T1D患者都会发生可以理解但是最终却事与愿违的周期性低血糖恐惧症(fear of hypoglycemia,FoH),导致焦虑, 随后生活质量明显下降, 除此之外血糖控制也会变差, 而且并发症的发生率也升高了9。 并不是所有的研究都能够证实FoH程度越高与HbA1c越高之间具有相关性10,但是许多作者都已经注意到了这种相关性。在一项纳入485名法国T1D患者的调查中11,只有28.3%的患者达到了HbA1c目标值, 有40.3%的患者因为FoH而没有达到目标。在那项调查中, 患者与他们的糖尿病专科医生都认为低血糖会影响患者的生活质量, 在年龄大于50岁的患者中有68.8%,在年龄小于18岁的患者中有43.5%的人认为低血糖是"…最令糖尿病患者感到不安的麻烦"11。患者对低血糖的恐惧包括血糖失控, 尤其是在老年人中(60%),令人尴尬的亲属关系(59%)、驾驶受限(27%)、体育锻炼受限(39%)、以及不能完成一些专业任务(25%)11。因为FoH,23.0%的患者减少了他们的胰岛素剂量, 20.1%的患者消耗的糖超过了与低血糖程度相匹配所需的量, 12.1%的患者经常进食过多(8%的患者在睡前这样做);FoH程度越高与所有这些"反面行为"之间具有相关性11。 与男性T1D患者相比, 女性T1D患者报告发生的低血糖恐惧更常见, 虽然在另外一项调查中发现女性患者出现严重低血糖并且需要急救服务的风险更低12。在一项纳入了764名瑞典T1D患者的调查中, 发现焦虑症状以及害怕一人独处的情况均与严重低血糖发生率以及轻度低血糖症状发生次数之间具有相关性13。并且再一次发现女性FoH比男性更多13。在一项类似的纳入了229名T1D患者的调查中再一次发现女性发生的FoH明显比男性更多, 特别是在那些使用家庭血糖监测以及不能从朋友、医疗服务机构或者他们的工作场所获得帮助的患者中出现未察觉低血糖后FoH更明显增多了14。在另外一项纳入288名荷兰T1D患者的调查中, 发现FoH与抑郁症状以及既往低血糖病史之间都有相关性15。 低血糖恐惧症与摄食过多, 特别是碳水化合物摄取过多相关。发现针对避免过量摄入单糖过度治疗低血糖的教育获益有限, 这也许是因为恐慌、迷惘、饥饿以及焦虑症状使得后续的治疗方法很难实施16。低血糖恐惧症还是患者进行规律体育活动的主要障碍, 在一些研究中, 还伴随着更低的日平均血糖水平以及更高的血糖变异性16。另外一项分析观察到了女性T1D患者经常有失败、被压垮、相关并发症宿命论的感觉, 并且这些女性患者表现出一种变异的饮食习惯被称为"外部饮食风格", 亦即患者倾向于用进食来应对除了饥饿之外的其他因素, "…以进食应对胰岛素剂量、时间效应、毛细血管血糖水平和/或计划内的体育活动, 这些因素与典型刺激如饥饿与知觉的关系不大"17。对来自121名T1D患者2日以上的食物摄入、血糖以及胰岛素日志表进行分析后也发现FoH对饮食模式具有这种重要的影响18,他们中有94名患者至少出现了1次低血糖事件(在此期间总共有271次低血糖事件, 进一步说明了这个问题是多么的普遍)。平均算来, 73%的受访者通过过量摄食来过度治疗他们的低血糖18。同样, FoH也是患者进行规律体育锻炼的障碍19,20。 低血糖恐惧症在临床环境中很容易确定。最近, 低血糖恐惧症调查报告II的精简版发表了(图1)21,得分为回答5项行为和6项焦虑问题后的总得分, 每项问题的评分范围都是从0(从不)到4(几乎总是)。持之以恒地使用这种方法可以使我们进一步意识到症状的复杂性。 当然, 我们的目标是研究出一种更加有效并且低血糖风险更低的方法来控制T1D患者的血糖。为此, 开发连续血糖监测系统并且将其纳入"闭环"人工胰腺胰岛素管理单元似乎越来越接近全面推广应用阶段。然而, 识别FoH目前仍然具有重要的临床意义, 直到这种装置能够真正地提供给所有的T1D患者。