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Diabetes and COVID-19: Risks, Management, and Learnings From Other National Disasters Diabetes Care 2020;43:16951703 | https://doi.org/10.2337/dc20-1192 Evidence relating to the impact of COVID-19 in people with diabetes (PWD) is limited but continuing to emerge. PWD appear to be at increased risk of more severe COVID- 19 infection, though evidence quantifying the risk is highly uncertain. The extent to which clinical and demographic factors moderate this relationship is unclear, though signals are emerging that link higher BMI and higher HbA 1c to worse outcomes in PWD with COVID-19. As well as posing direct immediate risks to PWD, COVID-19 also risks contributing to worse diabetes outcomes due to disruptions caused by the pandemic, including stress and changes to routine care, diet, and physical activity. Countries have used various strategies to support PWD during this pandemic. There is a high potential for COVID-19 to exacerbate existing health disparities, and research and practice guidelines need to take this into account. Evidence on the management of long-term conditions during national emergencies suggests various ways to mitigate the risks presented by these events. People with diabetes (PWD) have been identied as being at increased risk of serious illness from COVID-19. COVID-19 also presents substantial indirect risks to PWD through disruptions in health care and lifestyle factors. Understanding these risks and best ways to mitigate them in the short and longer term is key to facilitating informed decision-making during and after the COVID-19 pandemic. Evidence relating to COVID-19 and diabetes is limited but continuing to emerge. In this Perspective, we summarize evidence identied through rapid reviews. We consider direct and indirect risks posed to PWD by COVID-19 and management considerations for PWD both with and without COVID-19 infection. Recognizing limitations in evidence related to COVID-19, we also bring together leaders in diabetes care from countries with high rates of COVID-19, highlighting experiences from the most affected countries including Italy, France, China, the U.K., and the U.S. DIABETES AND RISKS FROM COVID-19 COVID-19 Infection: Contracting the Disease It is unclear if PWD are more likely to contract COVID-19. PWD are considered at increased risk of infection generally, which has been extended to COVID-19 (1). Community testing for COVID-19 remains limited; hence, data predominantly come from hospitalized cohorts. Systematic reviews primarily consisting of data from China have estimated rates of 8% (95% CI 611%) (2), 7.87% (95% CI 6.579.28%) (3), and 9.7% (95% CI 6.912.5%) (4) of diabetes in people hospitalized with COVID-19. The percentage hospitalization appears higher in the U.S., where from February 12 to 28 March 2020, PWD accounted for 10.9% of all COVID-19 patients (similar to the proportion of the U.S. population with diabetes), 24% of hospitalized cases (nonintensive care unit 1 Centre for Evidence-Based Medicine, Nufeld Department of Primary Care Health Sciences, University of Oxford, Oxford, U.K. 2 Nufeld Department of Primary Care Health Sciences, University of Oxford, Oxford, U.K. 3 Medical Sciences Division, University of Oxford, Oxford, U.K. 4 University of North Carolina School of Medicine, Chapel Hill, NC 5 Department of Clinical and Experimental Med- icine, Section of Metabolic Diseases and Diabe- tes, University of Pisa, Pisa, Italy 6 Peking University Diabetes Center, Peking Uni- versity Peoples Hospital, China 7 Federation de Diabetologie, Bichat Hospital, As- sistance PubliqueHˆ opitaux de Paris, Paris, France 8 INSERM, UMR_S 1138, Centre de Recherche des Cordeliers, Paris, France 9 UFR de M´ edecine, Universit´ e de Paris, Paris, France 10 Diabetes Research Centre, University of Leices- ter, Leicester, U.K. Corresponding author: Jamie Hartmann-Boyce, [email protected] Received 19 May 2020 and accepted 19 May 2020 This article is part of a special article collection available at https://care.diabetesjournals.org/ collection/diabetes-and-COVID19. © 2020 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for prot, and the work is not altered. More infor- mation is available at https://www.diabetesjournals .org/content/license. Jamie Hartmann-Boyce, 1 Elizabeth Morris, 2 Clare Goyder, 2 Jade Kinton, 3 James Perring, 3 David Nunan, 1 Kamal Mahtani, 1 John B. Buse, 4 Stefano Del Prato, 5 Linong Ji, 6 Ronan Roussel, 7,8,9 and Kamlesh Khunti 10 Diabetes Care Volume 43, August 2020 1695 DIABETES AND COVID-19

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Page 1: Diabetes and COVID-19: Risks, Management, and Learnings From … · 2020. 7. 10. · TworecentU.K.studies(bothpreprint) reported that diabet es was independently associated with a

Diabetes and COVID-19: Risks,Management, and Learnings FromOther National DisastersDiabetes Care 2020;43:1695–1703 | https://doi.org/10.2337/dc20-1192

Evidence relating to the impactof COVID-19 inpeoplewithdiabetes (PWD) is limitedbut continuing toemerge.PWDappear tobeat increased riskofmoresevereCOVID-19 infection, though evidence quantifying the risk is highly uncertain. The extent towhichclinical anddemographic factorsmoderate this relationship isunclear, thoughsignals are emerging that link higher BMI and higher HbA1c to worse outcomes inPWDwithCOVID-19.Aswell asposingdirect immediate risks toPWD,COVID-19alsorisks contributing to worse diabetes outcomes due to disruptions caused by thepandemic, including stress and changes to routine care, diet, and physical activity.Countries have used various strategies to support PWDduring this pandemic. Thereis a high potential for COVID-19 to exacerbate existing health disparities, andresearch and practice guidelines need to take this into account. Evidence on themanagement of long-termconditions during national emergencies suggests variousways to mitigate the risks presented by these events.

People with diabetes (PWD) have been identified as being at increased risk of seriousillness from COVID-19. COVID-19 also presents substantial indirect risks to PWDthrough disruptions in health care and lifestyle factors. Understanding these risks andbest ways tomitigate them in the short and longer term is key to facilitating informeddecision-making during and after the COVID-19 pandemic.Evidence relating to COVID-19 and diabetes is limited but continuing to emerge.

In this Perspective, we summarize evidence identified through rapid reviews. Weconsider direct and indirect risks posed to PWD by COVID-19 and managementconsiderations for PWD both with and without COVID-19 infection. Recognizinglimitations in evidence related to COVID-19, we also bring together leaders in diabetescare from countries with high rates of COVID-19, highlighting experiences from themost affected countries including Italy, France, China, the U.K., and the U.S.

DIABETES AND RISKS FROM COVID-19

COVID-19 Infection: Contracting the DiseaseIt is unclear if PWD are more likely to contract COVID-19. PWD are considered atincreased risk of infection generally, which has been extended to COVID-19 (1).Community testing for COVID-19 remains limited; hence, data predominantly comefromhospitalized cohorts. Systematic reviews primarily consisting of data fromChinahave estimated rates of 8% (95% CI 6–11%) (2), 7.87% (95% CI 6.57–9.28%) (3), and9.7% (95% CI 6.9–12.5%) (4) of diabetes in people hospitalized with COVID-19. Thepercentage hospitalization appears higher in the U.S., where from February 12 to 28March2020, PWDaccounted for 10.9%of all COVID-19patients (similar to theproportionof the U.S. population with diabetes), 24% of hospitalized cases (non–intensive care unit

1Centre for Evidence-Based Medicine, NuffieldDepartment of Primary Care Health Sciences,University of Oxford, Oxford, U.K.2Nuffield Department of Primary Care HealthSciences, University of Oxford, Oxford, U.K.3Medical Sciences Division, University of Oxford,Oxford, U.K.4University of North Carolina School of Medicine,Chapel Hill, NC5Department of Clinical and Experimental Med-icine, Section of Metabolic Diseases and Diabe-tes, University of Pisa, Pisa, Italy6Peking University Diabetes Center, Peking Uni-versity People’s Hospital, China7Federation de Diabetologie, Bichat Hospital, As-sistance Publique–Hopitaux de Paris, Paris, France8INSERM, UMR_S 1138, Centre de Recherche desCordeliers, Paris, France9UFR de Medecine, Universite de Paris, Paris,France10Diabetes Research Centre, University of Leices-ter, Leicester, U.K.

Corresponding author: Jamie Hartmann-Boyce,[email protected]

Received19May2020andaccepted19May2020

This article is part of a special article collectionavailable at https://care.diabetesjournals.org/collection/diabetes-and-COVID19.

© 2020 by the American Diabetes Association.Readersmayuse this article as longas thework isproperly cited, the use is educational and not forprofit, and the work is not altered. More infor-mation is availableathttps://www.diabetesjournals.org/content/license.

Jamie Hartmann-Boyce,1 ElizabethMorris,2

Clare Goyder,2 Jade Kinton,3

James Perring,3 David Nunan,1

Kamal Mahtani,1 John B. Buse,4

Stefano Del Prato,5 Linong Ji,6

Ronan Roussel,7,8,9 and Kamlesh Khunti10

Diabetes Care Volume 43, August 2020 1695

DIABETES

ANDCOVID-19

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[ICU]), and 32% of ICU admissions (5). Arecent (preprint) U.K. study found uncom-plicated diabetes to be the second mostcommon comorbidity (19%) in patientshospitalized with COVID-19; complicateddiabetes is reported in a figure only butprevalence looks to be approximately6.5% (6).

COVID-19 Infection: Disease SeverityThough issues with study quality andimprecision make it extremely difficultto quantify, current data suggest thatCOVID-19 is associated with worse out-comes in PWD. Reports that aggregatedata frommultiple centers are summarizedinTable1.There isanotablepaucityofdataon what moderates the relationship be-tween diabetes and COVID-19 severity.Increased age, being male, hyperten-sion, and cardiovascular comorbidities

are associated with increased risks forCOVID-19 severity (7) and are likely tobe closely related to diabetes status. It isplausible that BMI (8), ethnicity (9), typeof diabetes, diabetes control, and cer-tain medications (10) all may also play arole. In twocohort studies (FranceandtheU.K., U.K. study preprint) in PWD hospital-ized with COVID-19, higher BMI was pos-itively associated with worse COVID-19outcomes when compared with peoplewith BMI 25–29.9 kg/m2 (11,12). Data ondiabetes type and COVID-19 outcomesare only beginning to emerge, but pre-liminary (not yet peer reviewed) datafrom England (see Table 1) suggest risksmay be higher in people with type 1diabetes compared with type 2 (thoughrisk was increased in all PWD regardlessof type) (12). Data on glucose control andCOVID-19 outcomes are discussed below.

Association Between Blood GlucoseControl and COVID-19 Outcomes

There are limited data to date on theassociation between blood glucose con-trol and COVID-19 outcomes. A retro-spective studyof 451peoplewithCOVID-19with diabetes and/or hyperglycemiafrom the U.S. reported that people withuncontrolled hyperglycemia had longerlength of stay and higher mortality com-pared with people without diabetes oruncontrolledhyperglycemia (13).Anotherretrospective study of people with type 2diabetes from China reported that well-controlled blood glucose correlated withimproved outcomes in infected patients(14). Worse infection may predispose tomore difficulty managing blood glucose,so the causal mechanism behind correla-tions between glucose control and worseCOVID-19 outcomes is unclear.

Table 1—Aggregated data (across studies or centers) on COVID-19 severity in PWD*

Study design CountryNumberof studies

Number ofparticipants Outcome measure Risk estimate

Systematic review andmeta-analysis (2)

Multiple 8 3,076 Risk of diabetes in severe patientscompared with nonsevere patients

OR 2.07, 95% CI 0.89–4.82

Systematic review andmeta-analysis (63)**

Multiple 9 2,103 Risk of diabetes in severe patientscompared with nonsevere patients

OR 2.67, 95% CI 1.91–3.7

Systematic review andmeta-analysis (4)

Multiple 6 1,527 Risk of diabetes in severe/ICU patientscompared with nonsevere (non-ICU)patients

RR 2.21, 95% CI 0.88–5.57

Meta-analysis (64) China 12 2,018 Diabetes rate ratio among patients withmore severe versus those with lesssevere infection

Rate ratio 2.26, 95% CI1.47–3.49

Chinese Centers forDisease Control andPrevention report (65)

China n/a 72,314 Case fatality rate 7.3% in PWD (comparedwith 2.3% overall)

U.S. Centers for DiseaseControl and Preventionreport (5)

U.S. n/a 74,439 Not hospitalized PWD5 6% of all COVID-19 casesHospitalized, not in ICU PWD524%of all COVID-19 casesAdmitted to ICU PWD532%of all COVID-19 cases

Multicenter cohort study(66)

China n/a 191 Risk of in-hospital death in PWDcompared with those without(unadjusted)

OR 2.85, 95% CI 1.35–6.05

Retrospective review (67) China n/a 1,590 Likelihood of reaching composite endpoint (admission to ICU, intensiveventilation,ordeath) inPWDcomparedwith those without (age- and smokingstatus–adjusted)

HR 1.59, 95% CI 1.03–2.45

Retrospective cohortstudy (15)**

U.K. n/a 17,425,445(5,683 deathsattributed toCOVID-19)

Risk of in-hospital death in PWDcompared with those without (age-,sex-, and comorbidities-adjusted)

HbA1c ,7.5% (58 mmol/mol);HR 1.50, 95% CI 1.40–1.60.HbA1c $7.5% (58 mmol/mol);2.36 (2.18–2.56)

Population cohort study(12)**

U.K. n/a 61,414,470(23,804 COVID-19–relateddeaths)

Risk of in-hospital death in PWDcompared with those without(adjusted for age, sex, deprivation,ethnicity, geographical region)

Type 1 diabetes OR 3.50 (95%CI 3.15–3.89); type 2 diabetesOR 2.03 (95% CI 1.97–2.09)

HR, hazard ratio; OR, odds ratio; RR, risk ratio. *Definition of severe disease was often not clear; we report here what was reported in the primaryliterature.Many of the systematic reviews include overlapping studies and have issueswith quality and reporting. **Preprintdmethods and data havenot been subject to peer review.

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Two recent U.K. studies (both preprint)reported that diabetes was independentlyassociated with a higher risk of deaththat increased with higher HbA1c (12,15).Compared with people without diabetes,one study reported that PWDwith HbA1c.7.5% (58 mmol/mol) had a higherchance of in-hospital death than thosewith HbA1c,7.5% (,7.5% HR 1.50 [95%CI 1.40–1.60], $7.5% HR 2.36 [2.18–2.56]) (15). In a separate analysis, PWDwith HbA1c .10% (86 mmol/mol) had ahigher risk of in-hospital death related toCOVID-19 than those with an HbA1c of6.5–7% (48–53mmol/mol) (HbA1c.10%compared with HbA1c 6.5–7% adjustedHR 2.19 [95% CI 1.46–3.29] for type 1diabetes, 1.62 [95% CI 1.48–1.79] fortype 2; in patients with type 2 diabetes,a significant differencewas also detectedwhen comparing HbA1c values .7.5%[59 mmol/mol] to the reference cate-gory) (12). These data suggest that di-abetes control preinfection has a role toplay in COVID-19outcomes. In contrast, aFrench observational study in PWD hos-pitalized with COVID-19 did not find anassociation between long-term glucosecontrol and COVID-19 outcomes but hada smaller sample (11).

Indirect Risks to PWD Posed byCOVID-19Health care services, and in some casesaccess to medication and supplies, havebeen disrupted by COVID-19. Evidencefrom other national emergencies showsthat such disruptions can lead to worsediabetes outcomes during and after theseevents (16–18). Diet and physical activityaremainstaysofdiabetesself-managementand can reduce risk of worse outcomes inPWDandthosewithcardiometabolicmulti-morbidities (19). Though yet to be ad-dressed by the COVID-19 literature, thepandemic presents significant disruptiontoboth: aU.S. surveyof PWD foundmorethan a third of respondents reportedtheir diet is now less healthy, and halfreport exercising less (20). The currentpandemic and social isolation are likely toincrease rates of anxiety and depression,whichmayalso lead topooradherence tomedications and worsening of risk factorcontrol (21,22).

MANAGINGDIABETES DURINGTHECOVID-19 PANDEMIC

Reducing Risk from COVID-19There is little evidence on how PWD canreduce their risk during the COVID-19

pandemic beyond following general in-fection control guidance within eachcountry. More frequent blood glucosemonitoring (in people who self-monitor)has been suggested, though it is unclearwhat evidence was used to make theserecommendations (1).

Considerations for DiabetesManagement in All PWDFigure 1 summarizes specific considera-tions for diabetes management duringnational emergencies.

Self-management

There is little information on the effective-ness of self-management/self-educationduring the pandemic. A variety of onlineservices have been implemented buthave yet to be assessed (see EXPERIENCES

FROM COUNTRIES WITH HIGH RATES OF COVID-19).Thewider literatureon care of long-termconditions during national emergenciessuggests a role for educationalmaterials(23). Evidence for interventions aimingto optimize self-management in PWDthat are potentially feasible in disastercontexts include mobile phone apps (24),web- or computer-based interventions(25), text messaging (26,27), and self-monitoring of blood glucose (28,29).The latter two show the most promisebased on the available literature. How-ever, the interventions tested may notbewidely available ormay require healthcare resources to be set up. In addition,choice of format should be tailored topatient preferences, which will vary byage and sociodemographic group (30).

Diabetes Services

Guidelines for routine diabetes care duringthe COVID-19 pandemic vary by country.Themes are summarized in Table 2. Studiesof remote consultations have generallyfound positive results, though their gen-eralizability to the current pandemicmaybe limited (31). Within diabetes, there islittle evidence to support or oppose re-mote support (32,33).

MentalHealthandDiabetes-RelatedDistress

There are overarching concerns aboutthe impact of the COVID-19 pandemic onmental health and well-being (34,35).PWD are more prone to mental healthissues than the general population (36).Adherence to treatment can worsenwhen people are distressed or have de-pression (21), as seen both during andafter disasters (37,38). We found no ev-idence directly pertaining to management

of diabetes-related anxiety or distressduring this pandemic. In the generalliterature, there is mixed evidence oninterventions to reduce diabetes-relateddistress, and the vast majority of in-terventions tested involve face-to-facecontactdan unsuitable format in thecurrent context (39).

Managing COVID-19 in PWDManagement of PWD with COVID-19generally follows standard sick-day rules.Considerations that may be specific toCOVID-19 are summarized below.

Medication

MostCOVID-19–relatedconsensus state-ments recommend stopping metforminand sodium–glucose cotransporter 2 in-hibitors (SGLT2i) during acute illness andfollowing the sick-day rules. Dipeptidylpeptidase 4 inhibitors (DPP-4i), glucagon-like peptide 1 receptor agonists (GLP-1RA),and insulinarethepreferredoptionsin particular for hospitalized patients(see Fig. 2) (40,41). There has been somediscussion regarding use of ACE inhibitorsand angiotensin receptor blockers (ARBs)being associatedwithworse outcomes inCOVID-19, particularly in PWD. However,in view of data showing potential bene-fits, the current recommendation is tocontinue with these therapies (40).

A number of studies are currentlytesting chloroquine/hydroxychloroquinefor prevention ormanagement of COVID-19.Careful glucose monitoring will be re-quired in PWD due to these drugs’ anti-diabetic properties, with the potentialrisk of hypoglycemia that is associatedwith increased risk of cardiac arrhyth-mia, cardiovascular events, and mor-tality (42).

Management in Hospital

Guidance emphasizes the importance ofreferring to local specialist diabetes teamsand of managing hyperglycemia (43). Anarrative review suggests insulin is thepreferred agent for control of hypergly-cemia in this context (1). In the U.S., amajor early focus for hospital manage-mentwas tomove inpatient care for PWDto “virtual” formats where possible, toreduce the need for personal protectiveequipment. This included use of electronichealth records to interrogate data, tele-phone communication between diabetescare providers and inpatients and hospitalstaff, expanded “diabetes self-managementprotocols” allowing selected inpatients tomonitor their own glucose and self-administer

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insulin with oversight and advice fromthe virtual care team, and, in someinstitutions, initiating inpatient continuousglucose monitoring and/or flash systems.Tominimize the need for ICU beds, severalinstitutions launched subcutaneous insulinprotocols for the treatment of diabeticketoacidosis on floors with adequate nurs-ing staffing. Virtual diabetes care teamsfocused on supporting transitions to lowerlevels of care or outpatient settings.

EXPERIENCES FROM COUNTRIESWITH HIGH RATES OF COVID-19

We summarize here experiences fromfive countries that have had significantCOVID-19 outbreaks.

ChinaDuring the outbreak in China, many PWDwere unable to access health care pro-viders (HCPs) or medical supplies due tostay-at-home orders or quarantine. Hos-pitals reduced the number of appoint-ments drastically. Tomitigate the impactof those changes on diabetes manage-ment, several organizations issued guid-ance to PWD on how to cope with thesituation (44,45). The guidance devel-oped by the Chinese Geriatric EndocrineSociety mainly focused on preventionand early discovery of hyperglycemic cri-ses and management of medications andprovided detailed instructions on how toget access to certified internet-basedmedical services through smartphones(45). If PWD urgently needed to see an

HCP in hospital, detailed guidance onhow to prepare for consultations beforeleaving home and minimize exposure tothe virus were given en route and duringthe hospital visit. Guidance was pro-moted in the form of reading materialand lectures given by medical professio-nals through internet-based public mediasuch as Baidu Health (an equivalent ofGoogle in China) and theWeChat mobileapp. An expert recommendation on in-sulin treatment of hyperglycemia in patientsaffected with COVID-19 was developed(46).

FranceOn 12March, President Macron orderedmost people to stay at home, especially“at-risk” groups, including PWD. ManyPWD were struck by the announcementand were not expecting to be publiclyidentified as such, without answers tobasic questions. On 18March, a group ofHCPs and researchers from the Federa-tion of Diabetology launched a web app,CoviDIAB, to provide PWDwith diabetes-specific, scientifically based informationand to provide support. This free serviceincludes access to a frequently updatedmedia library and to live webinars withnurses, physicians, and experts. Twice aweek, registrants also receive short ques-tionnaires about COVID-19 symptoms andtests for anxiety/depression. If indicated,registrants automatically receive a no-tice suggesting medical contact, andphone calls may follow. At the time of

writing, tens of thousands of patientswere registered. Empathy was a drivingprinciple in design, and comments sug-gest that the service helps people tounderstand and self-manage their indi-vidual risk and to limit disruption inlifestyle and care. An evaluation willindicate to what extent it reduces theburden of disease. Recommendationshave been formulated by the French-speaking Diabetes Society (SocieteFrancophone du Diabete) to promotethe intensification of glycemic controlby remote support by professionalsand frequent self-monitoring. How-ever, extremely limited evidence wasavailable to guide both patients andHCPs. In response, a group of physiciansand researchers from50Frenchhospitalsdesigned and launched a large registerto collect data on PWD hospitalized withCOVID-19 and their prognosis (COVID-19and Diabetes Outcomes [CORONADO],NCT04324736, ClinicalTrials.gov). Recruit-ment has exceeded expectation; earlyresults are now available (11).

ItalyThe first cases COVID-19 in Italy wererecorded early in February. Tragically,Italy has suffered among the highestnumbers of deaths in the world (47). Atthe time of this writing, the death rate inItaly was estimated at 122.52 per 1,000infections, i.e., a 10-fold higher rate thanin Germany (14.14 per 1,000 infections)(48). This could be due to demographicfeatures of the Italian population, whichinclude a large proportion (23%) of peo-ple aged $65 years (49). From 9 March,social confinement rules were issued in-clud-ing restricted access to outpatientclinics. Access to diabetes clinics hasbeen limited to urgent cases, and remotecontacts via telephone or video telecon-sultation have been officially approvedand reimbursed by the National HealthSystem. Prescriptions of glucose-loweringagents requiring specialist approval(DPP-4i, SGLT2i, GLP-1RA, and new basalinsulin analogs) were automatically re-newed until the end ofMay. Special jointrecommendations have been promptlyissued by the Italian Society of Diabetes(SID), the Association of Italian Diabetol-ogists (AMD), the Italian Society of En-docrinology (SIE), and the Italian Societyof Pediatric Endocrinology (SIEDP) (50).The same organizations have opened aFacebook page entitled “One hour with

Self-/remote

Figure 1—Considerations for diabetes management during national emergencies. T1D, type 1diabetes.

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AMD, SID, and SIEDP” allowing PWD andtheir relatives to contact specialists (51).A government web page providing sim-ple and pragmatic recommendations hasbeen created focusing on disruptions tophysical activity and diet as a result ofsocial confinement (52). At the time ofwriting, discussions were ongoing re-garding restarting clinical activitiesand how to organize post-COVID dia-betes clinics.

U.K.

Over 90%of PWD in theU.K. aremanagedin primary care, by enhanced diabetes-skilled primary care physicians, nurses,and health care assistants. These modelshave shown to be effective in reducinghospitalizations, outpatient attendance,and admissions for diabetes-relatedcomplications (53). In March, the govern-ment issued guidance on social distanc-ing and self-isolation (54). In England,people considered especially clini-cally vulnerable (including some but

not all PWD) were contacted by thegovernment with advice on shielding.All people at high risk, including PWD,were advised to only leave the housefor limited periods for essential shop-ping and one form of exercise (55). ThePrimary Care Diabetes Society and theAssociation of British Clinical Diabetolo-gists have issued guidance on managingPWD in primary care (56). The nationalcharity Diabetes UK has been active ingiving advice to PWD through their web-site and social media. Both primary andsecondary care are providing emergencyand routine follow-up using telephone orvideo consultations including support formental well-being, though there are someregional variations. Social media channelshave been set up where HCPs are sharingexperience in managing people in thecommunity and hospital and exchangingnew guidance. A number of self-manage-menteducationprogramshavebeenmadefreely available. There are also discus-sions regarding longer-term plans to

phase in face-to-face consultations forroutine chronic disease management.

U.S.

The lack of universal health coverageposes additional challenges to PWD andtheir care providers during the COVID-19pandemic in the U.S. There has been analmost wholesale switch to virtual carefor outpatient appointments, but therearemany failings in this approach. Phonevisits provide a much lower rate of re-imbursement than video visits, butmanyof the most vulnerable patients haveinadequate equipment or connectivity tosupport video visits. Contacts with cer-tified diabetes educators by phone orvideo are not reimbursed. Additionalefforts have beenmade to communicatewith PWD at home to ensure that theyare safe. Laboratory and physical exammonitoring of complications has virtu-ally ceased for most patients as longas they symptomatically remain well.

Table 2—Selection of guidance and recommendations relating to routine care in PWD during COVID-19 pandemic

Service Recommendations

Inpatient diabetes services c Inpatient diabetes services will need to continue and potentially increase capacity, with need forteam approach re: glycemic control and nutritional status, and consideration of “virtual visits” forreviews (see MANAGEMENT IN HOSPITAL) (68).

Urgent/acute diabetes care (outpatient) c Face-to-face consultations should continue in the following circumstances: a new diagnosis ofT1D; urgent insulin start where symptomatic, HbA1c.10% (86 mmol/mol), or ketones detected;teaching blood glucose monitoring for urgent reasons; or in cases where physical examination isessential (e.g., foot ulcer, infection, some points in pregnancy) (69).

c Virtual (telephone, video, or e-mail) consultations should be used in the following circumstances:follow-up of new T1D diagnoses; vulnerable patients (recent hospital admission, recurrent severehypoglycemia, HbA1c.11% [99mmol/mol]); intensive follow-up in high-risk situations; or whererisk of attending an appointment face-to-face is greater than the benefits (69).*

Routine diabetes care c Consider routine diabetes care delivered virtually in the context of broader long-term conditionmanagement and prioritization, taking into account individual risk factors and clinical needs (68).

c The following should be deferred: routine appointments where diabetes is stable and well-managed; face-to-face structured group education courses; flash glucose monitoring startsessions; where the risk of attending an appointment is greater than the benefits; and wheredeferring appointments will not compromise clinical care (69).

Foot services for PWD c Mayneedtocontinueat full capacitywithconsiderationofmovingsupport to remote formswherepossible (68); many of these services are essential (70).

c Access to in-person support should continue for those with acute or limb-threatening problems(70) or where physical examination is essential (69).

c All new referrals should ideally be reviewed within 24 h (70).

Pregnancy services for PWD c Mayneedtocontinueat full capacitywithconsiderationofmovingsupport to remote formswherepossible (68).

c In-person support will be essential for physical examinations and/or teaching blood glucosemonitoring at some points in pregnancy (69).

Blood tests for PWD c Urgentbloodtestmonitoringshouldcontinue(e.g., decliningrenal function, raisedpotassium, lowsodium) (69).

Eye screening for PWD c This was not mentioned in the guidance reviewed but we understand in most affected countrieseye screening has been halted in view of high risk of transfer. Of note, evidence indicates that riskstratifying is possible (71).

*PWD may be concerned about the need to visit hospital; they should be encouraged to contact their physician in case of any signs or symptomsrelated to acute diabetes complications.

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Many patients have lost insurance cov-erage. Prescription fills for diabetesmed-ications are down 10%; a survey of PWDfound one in six respondents needinginsulin experienced a problem. A similarproportion reported issues with obtain-ing test strips, and a quarter of respond-ents reported issues with obtainingpump or continuous glucose monitoringsupplies (20). Many pharmaceuticalcompanies have stepped in to increaseaccess to otherwise unaffordable med-ications. In data available through theend of March, relatively early in the U.S.COVID-19 course, approximately 80% ofclinicians reported serious strain andnearly two-thirds were uncertain whetherthey would be able to keep their practicesopen due to insufficient financial resourcesand low volume of reimbursable work.Overall visits (virtual and face-to-face) forchronic asymptomatic care were down;50% (57). As the future course of theepidemic in theU.S. isuncertainandseemslikely to persist formanyweeks, the threatto PWD is grave. The hope is that newgovernment initiatives and innovation onthe part of stakeholders will fill the

emerging cracks in an already frag-mented system.

CONSIDERATIONS FORMANAGEMENT OF LONG-TERMCONDITIONS DURING NATIONALEMERGENCIES

Evidence on the management of long-term conditions during national emer-gencies suggests variousways tomitigatethe risks presented by these events,which predominantly fall under two phases:planning and response (23). These strate-gies are outlined in Table 3.

AFTER COVID-19

There is much uncertainty as to how theCOVID-19 pandemic will end and whatwill be left in its wake. Disruptions thatarise due to national emergencies canlead to increased HbA1c in those affectedup to 16 months later, with some evi-dence that this is particularly the case forpeople of lower socioeconomic statusand those treated with insulin (18,23). Alack of access to routine health care is aleading cause of morbidity and mortality

after disasters; stroke, acute myocardialinfarctions, and diabetes complica-tions are all shown to increase after theimmediate threat has dissipated (26,58).Services such as diabetes clinics may alsorethink their organization to minimize riskof ongoing transmission.

CONCLUSIONS

The need for decisive action creates animportant tension when evidence is lim-ited. An example here is the classificationof PWD as being at increased risk fromCOVID-19 and therefore subject to in-creased preventive measures. Thoughrisk is clearly increased, quantification isscant. There is little to no evidence onpotentially moderating factors, despitethe fact that these data are routinelycollected in data sets used for existinganalyses; the results presented are oftenunadjusted and use single disease cate-gories, ignoring potential differences be-tween type 1 and type 2 diabetes andmultimorbidities, which are associatedwith worse outcomes (59).

In the face of a limited evidence baserelating directly to COVID-19, decisions

Figure 2—Possible flowchart for management of people hospitalized with diabetes and COVID-19, adapted with permission from Ceriello et al. (49).ACEi, ACE inhibitors; AGIs,a-glucosidase inhibitors; BNP, brain natriuretic peptide; CAD, coronary artery disease; CGM, continuous glucosemonitoring;CK, creatine kinase; CKD, chronic kidney disease; CRP, C-reactive protein; eGFR, estimated glomerular filtration rate (mL/min/ 1.73m2);MI, myocardialinfarction; NT-proBNP, N-terminal prohormone of brain natriuretic peptide; OADs; oral antidiabetes drugs; PAD, peripheral arterial disease; RF, riskfactor; SUs, sulfonylureas; TIA, transient ischemic attack.

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can be informed by international expe-riences to date and, to someextent, fromthe literature as it relates to other na-tional emergencies. This latter source ofevidence shows the toll of disruptions todiabetes care is often most pronouncedafter the acute phase of the emergencyor disaster has passed. In some cases, theexcess morbidity and mortality in theaftermath of national emergencies ishigher than the toll during the emer-gency itself. History issues a stark warn-ing here when considering the balancebetween diverting resources toward theacute COVID-19 crisis and maintainingroutine care for people living with long-term conditions.Finally, in reviewing what has been

written on the topic of diabetes andCOVID-19, we have been struck by twonoticeable absences. The first is theabsence of literature on wider contextualfactors. PWD are likely to be impacted byCOVID-19 just asmuchoutside thehealthcare setting as within it, with particularconcerns relating to disruptions to dietand physical activity, increased stress,and burdens on mental health andwell-being, yet the literature to date fo-cuses almost exclusively on clinicalmanage-ment. The other unspoken issue in theliterature we reviewed is that of inequality.COVID-19 is not an equal-opportunity dis-ease. The burden will disproportionally beborne by people from less-advantagedgroups (60). Emerging data also suggestthat COVID-19 may pose more of a riskto nonwhite ethnic groups (9). Diabetesdiscriminates in similar ways, and the

intersection of diabetes and COVID-19creates a maelstrom in which existinghealth disparities risk exacerbation withprofound and long-lasting consequences.COVID-19 holds a mirror to our health caresystems and care of PWD; may we do allwe can now to make that reflection favor-able in hindsight.

Acknowledgments. Parts of this article arebased on Rapid Reviews conducted for the Centrefor Evidence-Based Medicine’s COVID-19 EvidenceService (23,61,62).Funding. This work was not funded. E.M. andC.G. are funded by Wellcome Trust fellow-ships. J.B.B. is supported by grants from theNational Institutes of Health (UL1TR002489 andP30DK124723). K.K. acknowledges support fromthe National Institute for Health Research (NIHR)Applied Research Collaboration East Midland(NIHR ARC-EM) and the NIHR Leicester Biomed-ical Research Centre.The views expressed are those of the authors

andnot thoseof the universities, theNIHR, or theU.K. Department of Health and Social Care.Duality of Interest. J.B.B. reports nonfinancialsupport and other from Adocia, AstraZeneca,Dance Biopharm, Dexcom, Eli Lilly, Fractyl, GIDynamics, Intarcia Therapeutics, Lexicon, Mann-Kind, Metavention, NovaTarg, Novo Nordisk,Orexigen, PhaseBio, Sanofi, Senseonics, vTv Ther-apeutics, and Zafgen; grants and nonfinancialsupport from AstraZeneca, Eli Lilly, Intarcia Ther-apeutics, Johnson & Johnson, Lexicon,Medtronic,NovaTarg, Novo Nordisk, Sanofi, Theracos, Toler-ion, and vTv Therapeutics; personal fees fromCirius Therapeutics Inc. and CSL Behring; andpersonal fees and other from Mellitus Health,Pendulum Therapeutics, PhaseBio, and StabilityHealth, outside the submitted work. R.R. reportsgrants, personal fees, and nonfinancial supportfrom Sanofi, personal fees and nonfinancialsupport from Merck Sharp & Dohme, personal

fees from AstraZeneca, grants and personal feesfrom Novo Nordisk, personal fees from Janssen,personal fees from Eli Lilly, personal fees fromAbbott, personal fees from Medtronic, grantsand personal fees from Diabnext, and personalfees from Mundipharma, outside the submittedwork. K.K. has received grants from BohringerIngelheim, AstraZeneca, Novartis, Novo Nordisk,Sanofi, Eli Lilly, Merck Sharp & Dohme, andServier, outside the submitted work. K.K. hasserved as a consultant, speaker, or an advisoryboard member for AstraZeneca, Bayer, NappPharmaceuticals, Eli Lilly,Merck Sharp&Dohme,Novartis, Novo Nordisk, Roche, Berlin-ChemieAG/Menarini Group, Sanofi, Servier, and Boeh-ringer Ingelheim. No other potential conflicts ofinterest relevant to this article were reported.Author Contributions. J.H.-B., E.M., C.G., D.N.,K.M., and K.K. were involved in concept anddesign. J.H.-B., E.M., C.G., J.K., and J.P. reviewedstudies for inclusion and extracted relevant data.J.B.B., S.D.P., L.J., R.R., and K.K. contributedexperiences from individual countries. J.H.-B.drafted the remainder of the article. All authorsedited and approved the finalmanuscript. J.H.-B.had full access to all data and final responsibilityfor the decision to submit for publication.

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Table 3—Strategies suggested for mitigating risks to management of long-term conditions during national emergencies (23)

Phase Suggested strategy

Planning c Collaboration, including the role of community-based partnershipsc Development of culturally adapted resources for people living with LTCs, including print and web-based educational materialsand access to support telephone lines

c Access to online self-management education programsc Monitoring for patients using prescription data on assessing adherence to medicationsc Proactive remote review of patients requiring care for LTCs and their possible needs if health care services are disruptedc Clear point of contact for patient care should disasters/emergencies occurc Improving identification and tracking mechanisms for people living with LTCs

Response c Triage and resource allocationc Transfer of care to allied HCPs including nurses and pharmacistsc Communication between different agenciesc Business continuity plans for pharmacies, and consideration of 30-day supplies from pharmacistsc Ensuring access to appropriate foods where supplies may be limited (for people with LTCs impacted by diet)c Dedicated patient transportation or mobile clinics for patients requiring in-person care who may be affected by transportdifficulties

c Continued guidance from patient support groups

LTCs, long-term conditions.

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