Care for diabetes with COVID-19: Advice from China
糖尿病合并COVID-19的管理:来自中国的建议
The epidemic of the coronavirus disease 2019 (COVID-19) has expanded from Wuhan throughout China and is being exported to a growing number of countries outside of China.1 The growing epidemic of COVID-19 is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).2 The potential public health threat posed by COVID-19 is very high, both to China and globally. By 9 March 2020, 80 904 cases of COVID-19, including more than 3123 deaths, had been confirmed in China, mainly in Hubei province.3 A further 28 673 laboratory confirmed cases have been reported across 104 other countries/territories/areas.3 Considering the high proportion of critically ill patients with diabetes or hyperglycemia, the difficulty for treatment and high mortality rate, effective diabetes management under epidemic conditions is extremely important. In order to increase disease awareness and improve the prognosis and outcome of patients with diabetes, better understanding of the etiological associations between COVID-19 and diabetes, the clinical impact of COVID-19 on diabetes, and proposing detailed recommendations for prevention and treatment are needed.4, 5
1 ASSOCIATIONS BETWEEN COVID-19 AND DIABETES
Epidemiologic evidences suggest that diabetes is associated with high risk of infectious diseases. People with diabetes are at increased risk for the bacteremic form of pneumococcal infection and have been reported to have a high risk of nosocomial bacteremia, with a mortality rate as high as 50%.6 In the nationwide China Cardiometabolic and Cancer Cohort (4C) study, compared to those with normal glucose tolerance, individuals with impaired glucose tolerance or diabetes had high risk of pulmonary infection with multivariable-adjusted odds ratios (OR; 95% CI) of 1.56 (1.02-2.37) and 1.63 (1.01-2.61), respectively. In this epidemic of COVID-19, the affected population had higher prevalence of diabetes, especially in critically ill patients. The first study published on 41 cases of COVID-19-infected people in Wuhan reported that in 32% of cases COVID-19 was combined with other diseases, including diabetes (20%), hypertension (15%), and cardiovascular disease (CVD; 15%).7 Subsequently, another study of a total of 99 infected persons showed that 52% of the infected persons had increased glucose levels.8 A retrospective study of 138 patients with COVID-19 published on 7 February 2020 showed that 64 (46.4%) had one or more underlying diseases, of which 10% (14/138) had diabetes, whereas in intensive care units (ICU), 22.2% (8/36) patients had diabetes.9
Metabolic disorders further influence the severity of COVID-19. It is noted that, compared to subjects with no comorbidities, severe pandemic influenza cases are significantly elevated with obesity (OR for mortality 2.74, 95% CI, 1.56-4.80).10 Similar findings were reported in other respiratory illnesses such as Middle East respiratory syndrome coronavirus (MERS-CoV) and swine influenza (H1N1). From current clinical reports, COVID-19-affected patients with diabetes are at high risk of becoming critically ill and of death. The findings from Wuhan Jin Yin Tan Hospital demonstrated that in ICU, 17% patients were reported to have chronic medical illnesses, including diabetes (17%), cerebrovascular diseases (13.5%), chronic cardiac diseases (10%), etc. During ICU treatment, 35% patients were reported to have hyperglycemia as comorbidity. More strikingly, the mortality in diabetics was as high as 77.7% (7/9) among critically ill patients. Evaluating the prevalence of these chronic conditions is fundamental to mitigate COVID-19 complications.11, 12 Early identification of individuals who are at risk of becoming critically ill and who are most likely to benefit from ICU is of considerable value.
Metabolic syndrome-related conditions such as diabetes, hypertension, CVD, and obesity together with their predisposing conditions can be etiologically linked to COVID-19 pathogenesis. During infection, the coronavirus may destroy islets through its functional receptor angiotensin-converting enzyme 2 (ACE2) in islets and make diabetes progress. The SARS-CoV-2 virus can also effectively use ACE2 to enter cells to infect humans.2 No direct evidence was identified genetically supporting the existence of coronavirus S-protein binding-resistant ACE2 mutants in different populations.13 Dysglycemia is known to downregulate key mediators of host innate immune response to pathogenesis. In patients with diabetes, hyperglycemia and insulinopenia attenuate the synthesis of pro-inflammatory cytokines and their downstream acute phase reactant to functionally impair the innate and humoral immune systems of the host. Furthermore, metabolic disorders reduce immune response by impairing macrophage and lymphocyte functions,14 which might subsequently render individuals more susceptible to infectious disease complications.
2 SPECIAL CONSIDERATIONS FOR PATIENTS WITH DIABETES DURING THE EPIDEMIC
During the outbreak of COVID-19, we recommend the “Seven Treasures” policy for diabetes management, including health education, balanced nutrition, physical activity, standardized medication, blood glucose monitoring, regular schedule, and care for mental health. “Five No” (no going out, no gatherings, no sedentariness, no stop on medications, no anxiety), “Five Keep” (keep wearing a face mask when you go out, keep hands clean, keep routine medical check if necessary, keep regular life, keep scientific attitude to COVID-19), and “Five Refuse” (refuse to visit friends, refuse group dining, refuse to taste wild animals, refuse rumors, refuse to shake hands or hug or kiss) should be advocated for patients with diabetes by endocrinologists, healthcare providers, and public health administrators.
For metabolically stable patients, a monitoring frequency for fasting and postprandial glucose levels of two to three times per week is acceptable. If marked hyperglycemia is indicated (blood glucose consistently exceeds 13.9 mmol/L) or severe symptoms (eg, thirst, dizziness, fatigue, nausea) occurred, timely hospital management is required. Two-way referral system should be established between the general practitioners and endocrinologists, and the specialists should provide training and guidance to the general practitioner during the epidemic.
3 GLYCEMIC MANAGEMENT FOR COVID-19-AFFECTED DIABETES PATIENTS
Healthcare personnel are on the front line of caring for patients with confirmed or possible infection with COVID-19. Personal protective equipment, routine cleaning, and disinfection procedures are appropriate for SARS-CoV-2 in healthcare settings, including those patient care areas in which aerosol-generating procedures are performed. Management of laundry, food service utensils, and medical waste should also be performed in accordance with routine procedures. The examination of eye diseases can be postponed due to the potential risk of COVID-19 infection through the conjunctiva, if not urgent.
3.1 Individualized glycemic recommendation
Individualized goals for blood glucose control should be recommended in the treatment. For nonsenile patients with mild or ordinary type of COVID-19, glucose targets are as follows: fasting blood glucose 4.4 ~ 6.1 mmol/L, 2-hour postprandial or random blood glucose 6.1 ~ 7.8 mmol/L. For older patients with mild or ordinary type of COVID-19 or in use of glucocorticoid, the goals are less stringent: fasting blood glucose 6.1~7.8 mmol/L, 2-hour postprandial or random blood glucose 7.8~10.0 mmol/L. In severe or critically ill cases of COVID-19, a fasting blood glucose of 7.8~10.0 mmol/L and a 2-hour postprandial or random blood glucose of 7.8~13.9 mmol/L should be achieved.
3.2 Pharmacological therapy for diabetes
A patient-centered approach should be used to guide the choice of pharmacologic agents. Considerations include age, severity of COVID-19, cardiovascular comorbidities, and hypoglycemia risk. For patients with mild COVID-19, previous medication regimens should be evaluated and followed as appropriate. For ordinary cases, subcutaneous insulin injections, including rapid-acting prandial/basal insulin or premixed insulin regimens, are recommended. For severe and critically ill patients, intravenous insulin therapy may be the preferred treatment.
The past 2 months have seen tremendous efforts of medical staff to address the condition of critically ill patients and safeguard the public health in China. With the epidemic under control, people are gradually coming back to work, and clinics are back in service to the public. We are now at a critical stage of the prevention and control of the COVID-19 epidemic. Endocrinologists should understand the impact of the epidemic on diabetic patients. It is important to follow standard hospital management and treatment regimens for COVID-19-affected patients with diabetes. Meanwhile, we should pay attention to the lifestyle and glucose management of patients with diabetes outside the hospital and provide them precise medical services. We also suggest that, if possible, global cooperation is needed in both basic and clinical research, for example the genetic, molecular, and immune mechanisms explaining the interplay between COVID-19 and diabetes, and the interplay between disease features, such as susceptibility, severity, and outcome of diabetic patients, with COVID-19 in different populations. We believe, all our efforts will finally overcome COVID-19.
ACKNOWLEDGEMENT
No funding declared.
CONFLICT OF INTEREST
None declared.
2019年, 由严重急性呼吸系统综合征冠状病毒2(severe acute respiratory syndrome coronavirus 2, SARS-CoV-2)引起2的传染性新型冠状病毒肺炎(2019 novel coronavirus infectious diseases, COVID-19)从武汉扩散至全国, 并逐渐影响到中国以外越来越多的国家1。无论对于中国还是全球的公共卫生而言, COVID-19都将带来很高的潜在威胁。至2020年3月9日, 中国已确诊80,904例COVID-19患者(大部分在湖北省), 其中包括3,123例死亡病例3; 其他104个国家/地区, 出现了28,673例实验室确诊病例3。而在感染COVID-19的患者中, 合并重症糖尿病或高血糖的患者所占比例高, 且治疗困难、死亡率高, 因此, 在当前新冠肺炎的流行条件下针对糖尿病的有效管理极为重要。为了提高对疾病的认识并改善糖尿病患者的预后和结局, 就需要我们更好地了解COVID-19与糖尿病之间的病因学联系以及COVID-19对糖尿病的临床影响, 并提出预防和治疗的详细建议4,5。
1. COVID-19与糖尿病的联系
流行病学证据表明, 糖尿病与感染传染病高风险相关。糖尿病患者感染肺炎球菌的风险增加, 据报道, 糖尿病有较高的医院内菌血症感染风险, 死亡率高达50%6。中国心脏代谢疾病及肿瘤队列研究(China Cardiometabolic and Cancer Cohort, 4C)结果表明, 与糖耐量正常的人群相比, 糖耐量受损或糖尿病的人群发生肺部感染的风险更高[多因素校正OR(95%CI)值分别为1.56(1.02-2.37)和1.63(1.01-2.61)]。COVID-19患者, 尤其是重症患者, 糖尿病患病率高。首份发表的COVID-19研究(基于41例武汉患者)显示, 32%的COVID-19感染者合并其他疾病, 包括糖尿病(20%), 高血压(15%)和心血管疾病(15%)7。随后, 另一项基于99例感染者的研究报道, 52%的感染者血糖升高8。2020年2月7日发表的一项基于138例COVID-19患者的回顾性分析显示, 64名(46.4%)患者合并有1种或多种基础疾病, 其中10%(14/138)合并糖尿病, 而在重症监护病房(ICU)的患者中, 22%(8/36)合并糖尿病9。
代谢紊乱进一步加重了COVID-19的严重程度。值得注意的是, 与没有合并症的人群相比, 肥胖人群严重大流行性流感的感染率显著增加(死亡率OR 2.74, 95%CI:1.56-4.80)10, 在其他呼吸系统疾病如MERS-CoV和H1N1中也有类似的发现。根据当前的临床报告, 合并糖尿病的COVID-19患者发展至重症甚至死亡的风险较高。武汉金银潭医院的研究结果显示, 重症监护病房中17%的患者合并有慢性病, 包括糖尿病(17%), 脑血管疾病(13.5%), 慢性心脏病(10%)等。在ICU治疗期间, 35%的患者并发高血糖。更惊人的是, 合并糖尿病的危重患者死亡率高达77.7%(7/9)。评估这些慢性病的患病率对缓解COVID-19并发症至关重要11,12。尽早发现有发展为重症风险的患者和识别最可能从ICU中受益的患者, 有重大价值。
糖尿病、高血压、CVD和肥胖等与代谢综合征相关的疾病及其诱发因素可能与COVID-19发病机制有关。冠状病毒在感染过程中可能通过其在胰岛中的功能性受体血管紧张素转换酶2(angiotensin-converting enzyme 2, ACE2)破坏胰岛细胞, 促进糖尿病进展。SARS-CoV-2病毒也可以有效地利用ACE2进入细胞并感染人类2。尚无直接证据支持不同人群中存在抵抗冠状病毒S蛋白结合的ACE2突变体13。已知血糖异常可下调宿主固有免疫应答关键介质的表达, 因此, 在糖尿病患者中, 高血糖和胰岛素缺乏会减弱促炎细胞因子及其下游急性期反应物的合成, 从而在功能上损害宿主的固有免疫和体液免疫系统。此外, 代谢紊乱会通过损害巨噬细胞和淋巴细胞功能来降低免疫应答14, 从而可能使个体更容易感染传染病。
2. COVID-19流行期间糖尿病患者的特殊注意事项
在COVID-19疫情时刻, 我们对糖尿病的管理推荐“七法宝”策略, 包括健康教育, 均衡营养, 适当运动, 规范用药, 血糖监测, 规律作息和关注心理。内分泌医生、医疗保健提供者和公共卫生管理者应向糖尿病患者提倡“五不”(不外出, 不聚会, 不久坐, 不停药, 不焦虑), “五常”(戴口罩、常洗手、常检查、常规律、常科学)和“五拒”(拒出门、拒聚餐、拒野味、拒谣言、拒握手或近距离接触)。
对于代谢稳定的患者, 应每周检测空腹和餐后血糖2-3次。如果出现明显的高血糖(血糖持续超过13.9 mmol/L)或严重症状(如口渴, 头晕, 疲劳, 恶心), 则需要及时寻求医院指导治疗。全科医生和内分泌科医生之间应建立双向转诊制度, 专家应在疫情期间为全科医生提供培训和指导。
3. COVID-19合并糖尿病患者的血糖管理
医护人员处于照顾已确诊或可疑感染COVID-19患者的第一线。个人防护设备、常规清洁和消毒程序在医疗机构, 包括在进行有气溶胶生成操作的患者护理区域中, 适用于防护SARS-CoV-2感染。医务清洗、食品用具和医疗废物的管理也应按照常规程序进行。非紧急情况下, 眼科疾病的检查应该推后, 以减低COVID-19通过结膜感染的潜在风险。
3.1 个性化血糖管理建议
在治疗中应推荐个性化血糖控制目标。对于患有轻度或普通类型COVID-19的非老年患者, 血糖控制目标为:空腹血糖4.4-6.1mmol/L, 餐后两小时或随机血糖6.1-7.8mmol/L; 对于患有轻度或普通类型COVID-19或正在使用糖皮质激素的老年患者, 血糖控制目标放宽为:空腹血糖6.1-7.8mmol/L, 餐后两小时或随机血糖7.8-10.0mmol/L; 对于重症COVID-19患者, 空腹血糖应控制在7.8-10.0mmol/L, 餐后两小时或随机血糖应控制在7.8-13.9mmol/L。
3.2 糖尿病的药物治疗
应以患者为中心的思想来指导药物的选择。考虑因素包括年龄、COVID-19的严重程度、心血管合并症和低血糖风险。对于轻度COVID-19患者, 应评估先前的用药方案并酌情遵循; 对于普通型COVID-19患者, 建议皮下注射胰岛素, 包括速效餐前/基础胰岛素或预混胰岛素; 对于重症患者, 首选静脉胰岛素治疗。
在过去的两个月中, 医务人员为治疗重症患者和维护中国的公共卫生付出了巨大的努力。随着疫情逐渐得到控制, 人们逐渐恢复工作, 医院也重新服务于大众。我们现在正处于预防和控制COVID-19流行的关键阶段。内分泌医生应了解COVID-19对糖尿病患者的影响。对于合并糖尿病的COVID-19患者, 遵循标准的医院管理和治疗方案非常重要。同时, 我们应重视医院外糖尿病患者的生活方式和血糖管理, 为他们提供精确的医疗服务。我们还建议, 在可能的情况下, 全球的基础研究和临床研究应通力合作, 例如, 阐明COVID-19与糖尿病之间相互作用的遗传, 分子和免疫机制; 阐明疾病特征之间的相互作用, 例如不同人群中合并糖尿病的COVID-19患者的易感性、严重性和结局。我们相信, 我们的所有努力终将战胜COVID-19。
