lancet-header

Preprints with The Lancet is part of SSRN´s First Look, a place where journals identify content of interest prior to publication. Authors have opted in at submission to The Lancet family of journals to post their preprints on Preprints with The Lancet. The usual SSRN checks and a Lancet-specific check for appropriateness and transparency have been applied. Preprints available here are not Lancet publications or necessarily under review with a Lancet journal. These preprints are early stage research papers that have not been peer-reviewed. The findings should not be used for clinical or public health decision making and should not be presented to a lay audience without highlighting that they are preliminary and have not been peer-reviewed. For more information on this collaboration, see the comments published in The Lancet about the trial period, and our decision to make this a permanent offering, or visit The Lancet´s FAQ page, and for any feedback please contact preprints@lancet.com.

Diabetes Increases Risk of Sepsis, But Not Mortality, Inflammatory or Lipid Responses

44 Pages Posted: 15 May 2019

See all articles by James A. Russell

James A. Russell

University of British Columbia (UBC) - Centre for Heart Lung Innovation; University of British Columbia (UBC) - Division of Critical Care Medicine

Mark Trinder

University of British Columbia (UBC) - Centre for Heart Lung Innovation

Terry Lee

University of British Columbia (UBC) - Centre for Health Evaluation and Outcome Sciences; University of British Columbia (UBC) - St. Paul's Hospital

Liam R. Brunham

University of British Columbia (UBC) - Centre for Heart Lung Innovation; University of British Columbia (UBC) - St. Paul's Hospital

Joe Hsu

Stanford University - Division of Pulmonary and Critical Care Medicine

John Boyd

University of British Columbia (UBC) - Centre for Heart Lung Innovation; University of British Columbia (UBC) - Division of Critical Care Medicine

Joel Singer

University of British Columbia (UBC) - School of Population and Public Health; University of British Columbia (UBC) - St. Paul's Hospital

Keith R. Walley

University of British Columbia (UBC) - Centre for Heart Lung Innovation; University of British Columbia (UBC) - Division of Critical Care Medicine

More...

Abstract

Background: Diabetes may increase sepsis risk, but it is unknown whether and how diabetes alters sepsis mortality. Our hypotheses were: (1) diabetes increases risk of sepsis and mortality; during sepsis (2) diabetes alters the inflammatory response; (3) hyperglycemia is associated with altered lipid levels.

Methods: We studied four cohorts (Population-based, multi-center, and single center cohorts; 2000-2016) with minimum 28-day follow-up: UK Biobank Cohort 1 (n =484,857; diabetics n = 25,430; non-diabetics n = 459,407), Single Centre Cohort 2 (n = 727; diabetics = 37; non-diabetics n = 690), Inflammation Mechanism Cohort 3 (n = 779; diabetics n = 165; non-diabetics n = 614), Lipid Mechanism Cohort 4 (n = 200; diabetics n = 49; non-diabetics n = 151). Twenty eight-day mortality and days-alive-and-free (DAF) of vasopressors, ventilation and renal replacement therapy (RRT) of diabetics and non-diabetics were compared. Hierarchical clustering was done on 39 cytokines and glucose association with HDL and triglyceride levels was evaluated early in sepsis.

Findings: Diabetics increased sepsis admission risk (n = 478/25,430 [1.89%] vs. n = 3,179/459,407 [0.70%], odds ratio (OR)[95% CI]: 2.75 [2.50 to 3.03], p<1E-15) but not mortality in UK Biobank Cohort 1 (15.8% vs. 13.7%; OR [95% CI]: 1.18 [0.91 - 1.54]], p=0.21), Single Centre Cohort 2 (24.3% vs. 19.3%, OR 1.35 [ 95% CI]: 0.63-2.92] p=0.452), Inflammation Mechanism Cohort 3 (38.8% vs. 36.9%, OR 1.09 [95%CI: 0.76, 1.55] p=0.651); or Lipid Mechanism Cohort 4 ((90-day) 17% vs. 14%, OR 1.59 [0.70-3.65], p=0.28), or in DAF vasopressors, ventilation and RRT (Cohort 3). Diabetics and non-diabetics had similar cytokine levels, hierarchical clustering and principal components analyses. There was no association of hyperglycemia with HDL or triglycerides levels.

Interpretation: Despite increased risk of sepsis, diabetic patients did not have increased 28-day mortality perhaps because inflammatory and lipid responses of diabetics and non-diabetics were similar.

Funding Statement: Support for VASST: Canadian Institutes of Health Research, Grant number: MCT 44152, Trial Registration: ISRCTN94845869. John Boyd is a recipient of a Providence Health Care Research Scholarship. Liam Brunham is supported by a Canada Research Chair in Precision Cardiovascular Disease Prevention and is a Michael Smith Foundation for Health Research Scholar. Keith Walley is supported by CIHR FDN 154311. Joe Hsu is supported by a grant from the National Institutes of Health, National Heart Lung and Blood Institute (1K08HL122528-01A1).

Support for current study: Department of Anesthesia and Department of Medicine, Division of Pulmonary and Critical Care, Stanford University; James A. Russell (overhead funds UBC/PHC); Canadian Institutes of Health Research (CIHR)(SONRIS).

Declaration of Interests: Dr. Russell reports patents owned by the University of British Columbia (UBC) that are related to the use of PCSK9 inhibitor(s) in sepsis and related to the use of vasopressin in septic shock. Dr. Russell is an inventor on these patents. Dr. Russell was a founder, Director and shareholder in Cyon Therapeutics Inc. Dr. Russell is a shareholder in Molecular You Corp. Dr. Russell reports receiving consulting fees in the last 3 years from: 1. Asahi Kesai Pharmaceuticals of America (AKPA)(developing recombinant thrombomodulin in sepsis). 2. SIB Therapeutics LLC (developing a sepsis drug). 3. Ferring Pharmaceuticals (manufactures vasopressin and developing selepressin). No longer actively consulting for the following: 4. La Jolla Pharmaceuticals (developing angiotensin II; Dr. Russell chaired the DSMB of a trial of angiotensin II from 2015 - 2017) - no longer actively consulting. 5. Cubist Pharmaceuticals (now owned by Merck; formerly was Trius Pharmaceuticals; developing antibiotics) – no longer actively consulting. 6. Grifols (sells albumin) - no longer actively consulting. 7. CytoVale Inc. (developing a sepsis diagnostic) - no longer actively consulting. 8. PAR Pharma (sells prepared bags of vasopressin) - no longer actively consulting. Dr. Russell reports having received an investigator-initiated grant from Grifols (entitled “Is HBP a mechanism of albumin’s efficacy in human septic shock?”) that was provided to and administered by UBC.

Ethics Approval Statement: UK Biobank Cohort 1 was approved by the UK Biobank (ID: 42857) and by the Clinical Research Ethics Board of the University of British Columbia. Single Centre Cohort 2 was approved by the Institutional Review Board of St. Paul’s Hospital and the University of British Columbia. The Inflammation Mechanism Cohort 3 was approved by each participating hospital. Lipid Mechanism Cohort 4 was approved by the Institutional Review Board of St. Paul’s Hospital and the University of British Columbia. For each study written informed consent was obtained from patients, next of kin or surrogate decision maker.

Suggested Citation

Russell, James A. and Trinder, Mark and Lee, Terry and Brunham, Liam R. and Hsu, Joe and Boyd, John and Singer, Joel and Walley, Keith R., Diabetes Increases Risk of Sepsis, But Not Mortality, Inflammatory or Lipid Responses (May 13, 2019). Available at SSRN: https://ssrn.com/abstract=3387518. or http://dx.doi.org/10.2139/ssrn.3387518

James A. Russell (Contact Author)

University of British Columbia (UBC) - Centre for Heart Lung Innovation ( email )

1081 Burrard Street
Room 166
Vancouver, British Columbia V6Z 1Y6
United States

University of British Columbia (UBC) - Division of Critical Care Medicine ( email )

Canada

Mark Trinder

University of British Columbia (UBC) - Centre for Heart Lung Innovation ( email )

1081 Burrard Street
Room 166
Vancouver, British Columbia V6Z 1Y6
United States

Terry Lee

University of British Columbia (UBC) - Centre for Health Evaluation and Outcome Sciences ( email )

Vancouver, BC V6T 1Z3
Canada

University of British Columbia (UBC) - St. Paul's Hospital ( email )

1081 Burrard Street
Vancouver, V6Z 1Y
Canada

Liam R. Brunham

University of British Columbia (UBC) - Centre for Heart Lung Innovation ( email )

1081 Burrard Street
Room 166
Vancouver, British Columbia V6Z 1Y6
United States

University of British Columbia (UBC) - St. Paul's Hospital ( email )

1081 Burrard Street
Vancouver, V6Z 1Y
Canada

Joe Hsu

Stanford University - Division of Pulmonary and Critical Care Medicine ( email )

Stanford, CA
United States

John Boyd

University of British Columbia (UBC) - Centre for Heart Lung Innovation ( email )

1081 Burrard Street
Room 166
Vancouver, British Columbia V6Z 1Y6
United States

University of British Columbia (UBC) - Division of Critical Care Medicine ( email )

Canada

Joel Singer

University of British Columbia (UBC) - School of Population and Public Health ( email )

Vancouver, British Columbia
Canada

University of British Columbia (UBC) - St. Paul's Hospital ( email )

1081 Burrard Street
Vancouver, V6Z 1Y
Canada

Keith R. Walley

University of British Columbia (UBC) - Centre for Heart Lung Innovation ( email )

1081 Burrard Street
Room 166
Vancouver, British Columbia V6Z 1Y6
United States

University of British Columbia (UBC) - Division of Critical Care Medicine ( email )

Canada

Click here to go to TheLancet.com

Paper statistics

Abstract Views
299
Downloads
32
PlumX Metrics