ADA2019

One of the delightful aspects of the annual American Diabetes Association (ADA) meetings is the way in which multiple sessions overlap, such as the sessions addressing varied psychosocial considerations. Frank Snoek, from the VU University Medical Center, Amsterdam, Netherlands, received the Robert Rubin award for his lecture entitled, “#DiabetesPsychologyMatters”. He pointed out that despite the profound influence of psychological factors on diabetes outcome, most people with diabetes do not see a psychologist, so that other healthcare professionals must be able to offer assessment, counseling, and “psychoeducation”. Snoek recommended an organized approach to periodic assessment and discussion of well-being, to increase detection rates of distress and increase satisfaction with care, acknowledging that this approach may not improve glycemic control per se. He distinguished between “mere depression screening”, which in itself may not be helpful (he suggested it may even be harmful) and focusing on “diabetes-related emotional distress”, particularly when persistent at a high level, or when levels of distress are in transition from moderate to high. Intensification of medical treatment, may, for example, worsen distress, and intervention at a time when the person is receptive is crucial. Snoek suggested that development of Internet or mobile app-based interventions needs to be readily scalable to address the needs of large numbers of patients. An interesting recent meta-analysis of this topic concluded that depression is associated with an increased risk of developing complications and, conversely, although to a somewhat lesser degree, that the development of complications of diabetes is associated with subsequent development of depression.1 William Polonsky (University of California, San Diego, California) reviewed what he termed “psychological insulin resistance”. Snoek cited a study of more than 3000 insulin-naïve people with type 2 diabetes (T2D) for whom initiation of insulin was recommended, in which nearly one-third declined and, of these, fewer than half eventually started insulin, citing concern about side effects, particularly hypoglycemia, and the sense that the risks and benefits were not explained, or that they were uncertain about adjusting doses or did not have adequate training. Injection-related anxiety, a perceived lack of control, a low sense of self-efficacy, and a sense of personal failure all are factors, along with what Polonsky termed the “enormous obstacle, and getting worse” of cost. The notion that people starting insulin have worse outcome represents a confusion of cause and effect, and the common and unfortunate use of insulin treatment as a “threat” by some providers in endeavoring to improve lifestyle adherence is another factor. Polonsky proposed five healthcare provider actions that can be used in “solving” psychological insulin resistance: (a) demonstration of the injection process, which he considered the single most helpful approach and lack of which most strongly tracks with delay; (b) explanation of the benefits of insulin; (c) the use of a “collaborative” style of provider-patient interaction, perhaps by asking the patient to “try insulin for a limited period of time”; (d) dispelling of insulin myths; and (e) being sure to avoid use of “authoritarian” approaches to the recommendation.2 The period between 12 and 15 years of age is one particularly associated with difficulty in glycemic control, as the child strives to assert autonomy before development of competency. Olga Gupta (University of Texas Southwestern Medical Center, Dallas, Texas) described an elegant and simple intervention to improve adherence in type 1 diabetes (T1D): 28 adolescents with T1D with HbA1c >8.5% were given a fish tank and fish, and asked to feed the fish twice daily, to change the water in the tank and review glucose logs at intervals. The strategy of fostering self-efficacy to facilitate gradual transition of diabetes care was highly successful, with HbA1c decreasing by 0.5%, compared with an increase of 0.8% in the control group (whose members received their own fish at the end of the study).3 The topic of adherence in diabetes overlaps with psychology, with Niteesh Choudry (Department of Medicine, Division of Pharmacoepidemiology & Pharmacoeconomics, Brigham & Women's Hospital, Boston, Massachusetts) pointing out that more than 25% of patients fail to fill prescriptions given during physician visits.4 In studies of statins over a longer term, only half of patients take the prescriptions.5 Adherence is, in turn, associated with outcome, as shown in a study comparing non-adherent, partially adherent, and fully adherent patients.6 Non-adherence, then, is a public health problem, accounting, Choudry said, for 125 000 deaths per year, and for 11% of hospitalizations, as well as threatening the huge amounts spent on identifying, evaluating, and prescribing effective new medicines. However, non-adherence should be seen as a complex behavioral issue, involving poor provider-patient communication and a host of psychological factors.7 Socioeconomic factors associated with adherence include membership in an ethnic minority, sex (women being approximately 10% less adherent), and employment or other activity of the patient themselves as a caregiver, but Choudry noted that the “chaos of our healthcare system leads to non-adherence as well”, citing requirements for insurance preauthorization, necessitating more pharmacy visits, further reducing adherence. Complex dosing regimens,8 higher costs,9 changes in pill color and shape when generics are prescribed, and printed rather than electronically delivered prescriptions all are associated with reduced rates of adherence. Larry Garber (Reliant Medical Group, Worcester, Massachusetts) reviewed approaches to improving adherence by teaching patients, prescribers, and staff to appreciate the value of prescribed medicines by influencing behavior through reminding or rewarding patients, fitting adherence support into real-world workflows, and by developing social and family support strategies to increase communication and trust among stakeholders, helping all involved to share in decision making. Another related topic is that of transitions in diabetes care, encompassing a variety of circumstances leading patients with diabetes to have difficulty in continuing an appropriate regimen of care. Katharine Garvey (Department of Pediatrics, Boston Children's Hospital, Boston, Massachusetts) discussed the transition to adult care for youth with diabetes. Young adults need to think about their blood glucose levels all the time, Garvey observed, asking a crucial question pertaining to emerging adulthood and the individual's acceptance of responsibility: “How do we teach them to succeed on their own?” Young adulthood in T1D and type 2 diabetes (T2D) is associated with increased mortality rates, and with an increased prevalence of nephropathy, retinopathy, and neuropathy.10 The ADA guidelines include recommendations that pediatric diabetes providers need to prepare patients by scheduling visits without the parent, discussion of screening tests, and of independent management.11 Such high-quality, developmentally appropriate care is certainly not always provided. In surveys reported in 2012 and 2016, only two-thirds of young adults were referred to an adult provider, gaps in care exceeding 6 months occurred in 35% and 21% of patients, respectively, and there was little communication between the adult and pediatric diabetes care providers.12, 13 Such care requires intensive time and care coordination, and the divergence between adult and pediatric approaches, with the former perhaps more focused on glycemic control and less on hypoglycemia avoidance, may be another barrier.14 Garvey noted that young adults may find the adult provider to be stricter and less friendly. As a consequence, the likelihood of poor glycemic control at follow-up more than doubles after the transition period.15 Office visits decrease, whereas emergency room visits and hospitalizations increase during the first 2 years after transition.16 Another transition is that between the hospital and outpatient setting. Daniel Rubin (Division of Endocrinology, Diabetes and Metabolism, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania) stressed the importance of avoiding medication errors and miscommunications, of patients being unable to obtain medications, of lack of preparation and unwillingness to continue injected medications, and of clinical inertia in continuing prior treatment although glucose levels are not well controlled,17 or of continuing insulin administered in hospital when it is not actually needed. These issues can be addressed by medication reconciliation and adjustment, by diabetes education, by better communication with outpatient providers, and particularly with early post-hospital follow-up.18 Development of strategies for adjusting diabetes regimens on discharge may be an important component of the transition. An HbA1c-based diabetes discharge treatment algorithm19 suggested that resuming outpatient treatment if HbA1c was below 7%, adding basal insulin at 50% to 80% of the dose used in hospital for HbA1c between 7% and 9%, and either basal-bolus or resumption of outpatient treatment along with basal insulin glargine for HbA1c exceeding 9%, although in a study of this approach nearly half of those discharged on basal-bolus insulin developed hypoglycemia.19 The use of a dipeptidyl peptidase (DPP)-4 inhibitor with a similar regimen appeared to lead to less hypoglycemia.20 Avoiding rehospitalization is crucial. Rubin observed that as many as one-fifth of patients are readmitted within 30 days of discharge, at a total cost of US$123 billion/year. Risk factors for readmission include greater numbers of prior hospitalizations, comorbidities, length of stay, insulin use, and abnormal levels of sodium, creatinine, hemoglobin, and hypoglycemia within the 24 hours before discharge.21, 22 In addition, various psychosocial factors contribute to readmission, including lack of knowledge about diabetes and discharge instructions, and patients' “loss of control” of their illness.23 Guillermo Umpierez (Division of endocrinology and metabolism, Grady Memorial Hospital, Atlanta, Georgia) discussed the reverse transition, from outpatient to inpatient care. In general, he pointed out, discontinuation of oral hypoglycemia agents and the use of basal-bolus insulin is preferable in the hospital setting, certainly when compared with the “sliding scale” approach commonly used in hospitals in the US and worldwide. A study of the basal-bolus approach showed improved glycemia and lower rates of wound infection and acute renal insufficiency, although hypoglycemia remained an issue.24 Studies of the use of newer agents, including DPP-4 and sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists, may help establish their indications and contraindications, and could be particularly appropriate for subsequent transition to outpatient treatment. 美国糖尿病协会(American Diabetes Association，ADA)年会上一个吸引人的地方是将多个会议重叠，例如讨论各种社会心理问题的会议。 来自荷兰阿姆斯特丹VU大学医学中心的Frank Snoek因其题为“糖尿病心理学的重要性”的演讲而获得罗伯特•鲁宾奖(Robert Rubin award)。他指出，尽管心理因素对糖尿病结局有着深刻的影响，但大多数糖尿病患者并未到心理医生处就诊，因此其他医疗专业人员必须能够为糖尿病提供心理评估、咨询以及“心理教育”。Snoek建议采用有序的方法，定期评估与讨论患者的幸福和健康感，以提高负面情绪的检出率，改善患者的治疗满意度，同时他也承认这种方法本身可能无法改善血糖控制。他将“单纯的抑郁症筛查”(他认为这种方法本身可能对患者并没有帮助，甚至可能有害)与专注于“ 糖尿病相关情感障碍”区分开来，特别是当患者的负面情绪持续处于较高水平时，或者负面情绪的程度从中度过渡到高度时。例如，强化治疗可能会导致患者的负面情绪加重，因此在患者容易接受时进行干预至关重要。Snoek建议基于互联网或者移动应用程序干预措施的发展, 需要随时扩展以满足大量患者的需求。最近一项关于这一主题的meta分析得出了以下结论:抑郁症与糖尿病并发症发生风险增加有关，而反过来说，尽管相关程度稍低，糖尿病并发症的发生与随后发生的抑郁症之间也具有相关性1。 William Polonsky(加利福尼亚大学圣地亚哥分校)对他所主张的“心理胰岛素抵抗”进行了回顾性分析。Snoek引用了一项研究，该研究纳入了超过3000例既往从未使用胰岛素治疗的2型糖尿病(type 2 diabetes，T2D)患者，这些患者均被推荐接受胰岛素治疗，其中近三分之一的患者拒绝，最终拒绝患者中只有不到一半开始胰岛素治疗，患者提及的理由包括担心副作用，特别是低血糖，以及感到(医生)没有解释风险与获益，不确定如何调整剂量，或者没有接受足够的培训。注射相关的焦虑、感觉不能控制、自我效能感低、个人挫败感，以及被Polonsky称为“巨大的障碍，而且越来越高” 的费用，都是造成不愿注射胰岛素的原因。还有一种观点认为开始使用胰岛素治疗的人结局更糟糕，这代表了对因果关系的混淆，另外一种因素就是一些医务工作者为了提高患者对生活方式治疗的依从性，普遍及不幸地将胰岛素治疗用作一种“威胁”。Polonsky提出了5种可供医务工作者用于“解决”心理胰岛素抵抗的方法:(a)演示注射过程，他认为这是唯一最有效的方法，不这样做可能会导致胰岛素治疗时机明显延迟；(b)解释胰岛素治疗的获益；(c)采用一种“协作式”的医-患互动方式，比如让患者“在有限的时间内尝试使用胰岛素治疗”；(d)消除胰岛素治疗的误传；(e) 确定避免采用“ 独裁”的方法对患者提出建议2 。 12-15岁年龄段的孩子血糖特别难控制，因为孩子在能够拥有自我控制能力之前的自主性太强。Olga Gupta(德克萨斯大学西南医学中心，达拉斯，德克萨斯州)描述了一种精巧而简单的用于改善1型糖尿病(type 1 diabetes，T1D)患者治疗依从性的干预方法:28名HbA1c>8.5%的T1D青少年患者均获赠了一个鱼缸与鱼，要求他们每天给鱼喂食两次，每隔一段时间更换鱼缸中的水并检查自己的血糖记录，以提高自我效能感，促进糖尿病治疗的逐步转变，该策略非常成功，HbA1c降低了0.5%，而对照组HbA1c上升了0.8%(对照组患者在研究结束时才收到获赠的鱼)3。 糖尿病患者的依从性与心理学问题相互重叠。Niteesh Choudry(马萨诸塞州波士顿市布莱根妇女医院药物流行病学与药物经济学系医学部)指出，超过25%的患者未能按照医生访视期间开具的处方拿药4。在长期服用他汀类药物治疗的研究中，仅一半患者能够按照处方用药5。在一项比较患者不依从、部分依从与完全依从的研究中，依从性与结局相关6。Choudry提到，不依从医嘱是一个公共卫生问题，每年有125 000例患者因此而死亡，并且因此而住院的患者占全部住院患者的11%。除此之外，在鉴定、评估与处方有效新药方面还要因此而花费巨额经费。然而，应将不依从医嘱视为一种复杂的行为问题，包括医患沟通不畅以及一系列的心理因素7。与依从性相关的社会经济因素包括少数民族成员、性别(女性的依从性大约低10%)，以及患者本身从事护理职业或者其他相关职业。但Choudry还注意到“医疗卫生系统的混乱也会导致患者不依从治疗”，因为保险预授权的要求，需要患者更多次地到药房取药，这进一步降低了依从性。复杂的用药方案8、更高的成本9、处方仿制药物时药丸的颜色和形状不同、开具打印的处方而非电子处方，这些均与依从性下降有关。Larry Garber(马萨诸塞州伍斯特市Reliant医疗集团)系统地分析了提高依从性的方法，即通过教导患者、处方医生以及员工使他们能够了解处方药物的价值，通过提醒或奖励患者来影响他们的行为，同时将依从性支持纳入实际的工作流程中，以及通过制定社会与家庭支持策略，增强利益相关者之间的沟通与信任，帮助所有相关人员共同参与决策。 另一个相关的主题就是糖尿病护理的转变，包括各种导致糖尿病患者难以继续进行适当的治疗方案的情况。Katharine Garvey(马萨诸塞州波士顿市波士顿儿童医院儿科)讨论了青少年糖尿病患者向成人护理过渡的问题。Garvey观察到，年轻人需要时时刻刻考虑自己的血糖水平，他提出了一个与即将成年和个人承担责任有关的关键问题:“我们如何教会他们自己取得成功?”成年早期的T1D或者T2D可导致死亡率增加，以及肾病、视网膜病变和神经病变的患病率增加10。ADA指南建议儿科糖尿病医务工作者需要通过安排患者在没有父母陪同的情况下就诊、讨论筛查测试以及独立的管理，为患者步入成年做好准备11。当然我们并非总能提供这种高质量的、适合发育的护理。在2012年与2016年的调查报告中，只有2/3的年轻人被转诊至成人糖尿病医务工作者，分别有35%与21%的患者护理间隔超过6个月，并且成人和儿童糖尿病医务工作者之间几乎没有交流12,13。这种护理需要密集的时间与协调护理，而成人与儿童护理方法之间的差异可能是另一个障碍，前者可能更注重血糖控制，而较少关注避免低血糖14。Garvey指出，年轻人可能会发现成人医务工作者更严格并且不那么友好。因此，在过渡期后随访时血糖控制不佳的可能性增加了一倍以上15。在过渡期后的前2年内，患者门诊访视的次数减少，而到急诊室就诊以及住院的次数均增加16。 另外一个过渡是在于医院与门诊环境之间。Daniel Rubin[宾夕法尼亚州费城坦普尔大学刘易斯•卡茨(Lewis Katz)医学院内分泌、糖尿病与代谢科]强调了要避免出现以下情况的重要性:用药错误与沟通不畅，患者无法获得药物，缺乏准备与不愿意继续注射药物，以及在血糖水平控制不佳的情况下，仍继续使用先前治疗方案的临床惯性17，或者在实际上并不需要的情况下继续住院注射胰岛素治疗。这些问题可以通过对比以往所用药物和现在医生处方药而加以调整、糖尿病教育、与门诊医务工作者进行更好的沟通、特别是出院后进行早期随访来解决18。制定一个经过调整的糖尿病患者出院治疗方案可能是过渡期的一个重要组成部分。基于HbA1c的糖尿病出院治疗策略19建议，如HbA1c<7%，则继续门诊治疗方案；如HbA1c为7%-9%，则将住院期间的基础胰岛素剂量增加50%至80%；如HbA1c>9%，则采用基础-餐时胰岛素治疗方案或者恢复门诊治疗方案加上基础甘精胰岛素一起治疗，尽管在一项针对这种方法的研究中，近一半出院后使用基础-餐时胰岛素治疗方案的患者出现了低血糖19。使用类似方案的二肽基肽酶(dipeptidyl peptidase，DPP)-4抑制剂治疗似乎可以减少低血糖20。避免再次住院至关重要。Rubin发现，多达五分之一的患者在出院后30天内再次入院，每年的总花费达1230亿美元。再入院的危险因素包括既往住院次数较多、合并症、住院时间、使用胰岛素治疗、以及血钠、肌酐、血红蛋白水平异常、出院前24小时内出现低血糖21,22。此外，各种心理社会因素也会导致患者再次入院，包括缺乏糖尿病相关知识与出院指导，以及患者“没有控制”自己的疾病23。Guillermo Umpierez(佐治亚州亚特兰大市格雷迪纪念医院内分泌与代谢科)讨论了从门诊到住院治疗的逆向过渡。他指出，总的来说，与美国以及世界各地医院普遍采用的“可以灵活调整”的治疗方法相比较，在医院环境中更倾向于停用口服降糖药物，使用基础-餐时胰岛素治疗。一项使用基础-餐时胰岛素治疗的研究显示，尽管仍会引起低血糖问题，但该方案能够改善血糖水平，降低伤口感染与急性肾功能不全的发生率24。关于DPP-4抑制剂、钠-葡萄糖协同转运体2抑制剂以及胰高血糖素样肽-1受体激动剂等新型药物治疗的研究可能有助于明确这些药物的适应证与禁忌证，并且可能特别适合随后过渡到门诊治疗。