Bals, Robert

Jüni, Peter

Lepper, Philipp M.

von Eynatten, Maximilian

Diabetologia

English

Acronym

LETTERBlood glucose, diabetes and metabolic control in patientswith community-acquired pneumoniaPhilipp M. Lepper1 & Robert Bals1 & Peter Jüni2,3 & Maximilian von Eynatten4Received: 18 June 2020 /Accepted: 25 June 2020# The Author(s) 2020Keywords Community-acquired pneumonia . COVID-19 . Diabetesmellitus . HyperglycaemiaAbbreviationsCAP Community-acquired pneumoniaCOVID-19 Coronavirus disease-2019SARS-CoV2 Coronavirus severe acuterespiratory syndrome coronavirus 2To the Editor:We read with interest the studies by Cariou et al[1] andWang et al [2] published in the journal. Evidence so farsuggests that type 2 diabetes mellitus may not increase theoverall risk of an infection with the novel coronavirus severeacute respiratory syndrome coronavirus 2 (SARS-CoV2) [3],the causal agent of a syndrome called coronavirus disease-2019 (COVID-19); however, pre-existing type 2 diabetesappears to be associated with more severe infection [4].Moreover, recent evidence by Zhu et al [5] and data from anobservational NHS England cohort [6, 7], consistentlyshowed an increased risk for COVID-19-related death inpatients with type 2 diabetes. The study by Cariou et al [1]adds to current knowledge by reporting that higher BMI (butnot long-term glycaemic control or type of glucose-loweringtherapy used) was significantly associated with the severity ofCOVID-19 infection as studied in their cohort of 1317 patientswith pre-existing diabetes (89% with type 2 diabetes). Wangand colleagues analysed whether blood glucose taken within24 h of admission after a fasting period was a predictive mark-er for 28-day mortality in 605 COVID-19 patients withoutdiabetes [2]. They found that patients with fasting serumglucose concentrations ≥7.0 mmol/l had a significantly higherrisk of death (HR 2.30; 95% CI 1.49, 3.55; p = 0.0002).Hence, currently available evidence on clinical risk manage-ment in patients with COVID-19 strongly supports the inclu-sion of assessment of diabetes status as well as careful consid-eration of additional clinical attributes, such as BMI and bloodglucose levels.These important insights may have just recently emergedfor COVID-19; however, previous evidence in clinicalcommunity-acquired pneumonia (CAP) research has alreadyidentified the importance of pre-existing diabetes for outcomerisk assessment. We conducted a large prospective study in6891 Caucasian patients admitted for CAP due to causes otherthan SARS-CoV2 to 12 German centres [8]. We exploredwhether pre-existing diabetes would be associated with anincreased mortality risk from CAP caused by any infectiousagent [8]. The 28-day mortality risk was significantlyincreased in the 1114 participants with diabetes comparedwith that in individuals without diabetes with normal serumglucose levels (adjusted HR 1.92; 95% CI 1.34, 2.75;p < 0.001).Notably, evidence for assessing COVID-19 mortality riskhas recently expanded beyond exploring diabetes status andindicated that assessing blood glucose levels could furtheridentify at-risk individuals for adverse outcomes. Cariou andcolleagues report an age- and sex-independent associationbetween increased admission plasma glucose levels and theseverity of COVID-19, as well as early mortality at day 7,among individuals with diabetes [1]. In our previous studywe also utilised admission glucose values to further categorisepatients into normo- and hyperglycaemic subgroups [8]. This* Philipp M. Lepperphilipp.lepper@uks.eu1 Department of Internal Medicine V – Pneumology, Allergology andIntensive Care Medicine, University Hospital of Saarland, KirrbergerStrasse 100, 66421 Homburg/Saar, Germany2 Applied Health Research Centre (AHRC), Li Ka Shing KnowledgeInstitute of St. Michael’s Hospital, Toronto, ON, Canada3 Department of Medicine and Institute of Health Policy, Managementand Evaluation, University of Toronto, Toronto, ON, Canada4 Nestlé Health Science, Vevey, Switzerlandhttps://doi.org/10.1007/s00125-020-05225-1/ Published online: 17 July 2020Diabetologia (2020) 63:2488–2490glucose-based stratification allowed us to identify individuals atfurther increased risk for CAPmortality. Compared with partic-ipants with normal plasma glucose levels and without diabetesat admission, the adjusted HR for death within 28 days afteradmission in those with diabetes was 1.92 (95% CI 1.34, 2.75;p < 0.001) and the observed mortality risk remained largelyunchanged for up to 180 days of follow-up [8].Importantly, the clinical utility of glucose levels on admis-sion appears to extend to CAP patients without pre-existingdiabetes. The study by Wang et al [2], as well as our previousstudy [8], found a significant association between admissionglucose and CAP mortality outcome in individuals withoutknown diabetes. We reported that glucose levels on admissionin patients admitted for CAP but without pre-existing diabetes(n = 5141) were significantly associated with all-cause mortal-ity. In non-diabetic individuals 28- and 90-day mortality wasincreased whether glucose concentrations were assessed by aspecific glucose threshold level (i.e. ≥6.0 mmol/l on admis-sion; HR 1.71; 95% CI 1.22, 2.40; p for trend 0.001) or werecategorised in a stepwise manner (i.e. <4 mmol/l, 4–5.99 mmol/l [reference group], 6–10.99 mmol/l [HR 2.89;95% CI 2.27, 3.69], 11–13.99 mmol/l [HR 4.01; 95% CI2.78, 5.81], and ≥14 mmol/l [HR 6.04; 95% CI 4.18, 8.74],all p for trend <0.001). Interestingly, in our study, the almostthreefold mortality risk in individuals without diabetes butwith elevated glucose levels on admission within the moderaterange (6–10.99 mmol/l) was comparable to the HR for deathat 28 days seen for individuals with COVID-19 and an FBG≥7.0 mmol/l as reported by Wang et al of 2.30 (95% CI 1.49,3.55) [2].Thus, the available evidence shows that mortality risk fromCAP (including COVID-19) is considerably increased in indi-viduals with pre-existing diabetes, but also under conditionsof acutely elevated blood glucose levels, even in patients with-out previously diagnosed diabetes. Based on these results,clinical risk assessment based on pre-existing diabetes statusin individuals with COVID-19 is essential. If diabetes is pres-ent, BMI, as well as rigorous and serial assessments of in-hospital glucose levels (defined as at least one documented2 h post-prandial glucose value exceeding 10 mmol/l) couldadd further value for risk stratification [5]. However, it may bedifficult to obtain this information within a useful timeframefor the latter, and we suggest that a single point-of-caremeasurement of glucose, especially at standardised timepoints(i.e. at hospital admission without a fasting period) could be anattractive alternative. Notably, hospital admission glucosemay be of particular importance for people presenting withCOVID-19 without pre-existing diabetes, as this clinicalmarker could identify at-risk individuals that may easily bemissed by solely assessing diabetes status.In summary, evidence from large CAP cohorts (includingpatients with and without COVID-19) from differentgeographical regions and ethnic groups, strongly suggests thatindividuals with pre-existing diabetes and/or elevated bloodglucose levels need special attention when presenting to ahospital, as they represent a group at high risk for increasedmortality (Table 1). We believe admission glucose couldrepresent an attractive clinical tool for early and effectiveCAP risk assessment as it is readily available in daily practice.Funding Information Open Access funding provided by Projekt DEAL.COVID-19 research at the University Hospital of Saarland is funded bythe Federal State of Saarland, Saarland University and the Dr. Rolf M.Schwiete Foundation.Authors’ relationships and activities RB received funding fromAstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Grifols,Novartis, CSL Behring, German Federal Ministry of Education andResearch (BMBF) Competence Network, Sander Stiftung, Dr. Rolf M.Schwiete Foundation, German Cancer help (Krebshilfe) andMukosizidose e.V.Contribution statement PL and MvE drafted the letter, RB and PJrevised the letter for important intellectual content. All authors approvedthe final version of the manuscript.Open Access This article is licensed under a Creative CommonsAttribution 4.0 International License, which permits use, sharing, adap-tation, distribution and reproduction in any medium or format, as long asyou give appropriate credit to the original author(s) and the source,provide a link to the Creative Commons licence, and indicate if changeswere made. The images or other third party material in this article areincluded in the article's Creative Commons licence, unless indicatedotherwise in a credit line to the material. If material is not included inthe article's Creative Commons licence and your intended use is notpermitted by statutory regulation or exceeds the permitted use, you willneed to obtain permission directly from the copyright holder. To view acopy of this licence, visit http://creativecommons.org/licenses/by/4.0/.Table 1 HRs for selected groups of patients with CAP, including COVID-19Study Population Preexisting diabetes Patients (n) Glucose level (mmol/l) OR or HR (95% CI) for death p valueCariou et al [1] COVID-19 Yes 1317 >5.55 Increased for death on day 7 0.0059Zhu et al [5] COVID-19 Yes 952 Any HR 2.90 (2.21, 3.81) <0.001Lepper et al [8] CAP Yes 1114 Any HR: 1.92 (1.34, 2.75) <0.001No 5756 ≥6.0 HR: 1.69 (1.24, 2.30) <0.001Wang et al [2] COVID-19 No 605 ≥7.0 HR: 2.30 (1.49, 3.55) 0.00022489Diabetologia  (2020) 63:2488–2490References1. Cariou B, Hadjadj S, Wargny M et al (2020) Phenotypic character-istics and prognosis of inpatients with COVID-19 and diabetes: theCORONADO study. Diabetologia 63(8):1500–1515. https://doi.org/10.1007/s00125-020-05180-x2. Wang S, Ma P, Zhang S et al (2020) Fasting blood glucose at admis-sion is an independent predictor for 28-day mortality in patients withCOVID-19 without previous diagnosis of diabetes: a multi-centreretrospective study. Diabetologia. https://doi.org/10.1007/s00125-020-05209-13. Fadini GP, Morieri ML, Longato E, Avogaro A (2020) Prevalenceand impact of diabetes among people infected with SARS-CoV-2. JEndocrinol Investig 43:867–869. https://doi.org/10.1007/s40618-020-01236-24. Guan WJ, Ni ZY, Hu Y et al (2020) Clinical characteristics of coro-navirus disease 2019 in China. N Engl J Med 382(18):1708–1720.https://doi.org/10.1056/NEJMoa20020325. Zhu L, She ZG, Cheng X, Qin JJ et al (2020) Association of bloodglucose control and outcomes in patients with COVID-19 and pre-existing type 2 diabetes. Cell Metab S1550-S4131(20)30238-2.https://doi.org/10.1016/j.jcmgh.2020.06.0096. Barron E, Bakhai C, Kar P et al (2020) Type 1 and type 2 diabetesand COVID-19 related mortality in England: a whole populationstudy. (Preprint) 19 May 2020. Available from https://www.england.nhs.uk/publication/type-1-and-type-2-diabetes-and-covid-19-related-mortality-in-england/. Accessed 17 June 20207. Holman N, Knighton P, Kar P et al (2020) Type 1 and type 2 andCOVID-19 related mortality in England: a cohort study in peoplewith diabetes. (Preprint) 19 May 2020. Available from https://www.england.nhs.uk/publication/type-1-and-type-2-diabetes-and-covid-19-related-mortality-in-england/. Accessed 17 June 20208. Lepper PM, Ott S, Nüesch E, von Eynatten M et al (2012) Serumglucose levels for predicting death in patients admitted to hospital forcommunity acquired pneumonia: prospective cohort study. GermanCommunity Acquired Pneumonia Competence Network. BMJ 344:e3397. https://doi.org/10.1136/bmj.e3397Publisher’s note Springer Nature remains neutral with regard to jurisdic-tional claims in published maps and institutional affiliations.2490 Diabetologia  (2020) 63:2488–2490

Blood glucose, diabetes and metabolic control in patients with community-acquired pneumonia

Universaar

The discovery of insulin in 1921 has been one of greatest scientific achievements of the 20th century. Since then, the availability of insulin has shifted the focus of diabetes treatment from trying to keep patients alive to saving and improving the life of millions. Throughout this time, basic and clinical research has advanced our understanding of insulin synthesis and action, both in healthy and pathological conditions. Yet, multiple aspects of insulin production remain unknown. In this review, we focus on the most recent findings on insulin synthesis, highlighting their relevance in diabetes. Graphical abstract

Lepper, Philipp

Hochschulbibliothekszentrum des Landes Nordrhein-Westfalen (hbz)

https://publikationen.sulb.uni-saarland.de/bitstream/20.500.11880/30965/1/Lepper2020_Article_BloodGlucoseDiabetesAndMetabol.pdf

Blood glucose, diabetes and metabolic control in patients with community-acquired pneumonia

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Hochschulbibliothekszentrum des Landes Nordrhein-Westfalen (hbz)