Sepsis‐induced activation of endogenous GLP‐1 system is enhanced in type 2 diabetes

Perl, Sivan; Bloch, Olga; Zelnic-Yuval, Dana; Love, Itamar Y; Mendel-Cohen, Lior; Flor, Herta; Rapoport, Micha J.

doi:10.1002/dmrr.2982

Cited by 23 publications

(31 citation statements)

References 29 publications

(69 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Elevated GLP-1 levels during critical illness have been reported by previous studies [10,11,18]. These studies reported a 1.4- to 8-fold increase in GLP-1 levels and a 2- to 10-fold increase in IL-6 levels within 30 minutes to 6 hours depending on the study design [10,11,18].…”

Section: Discussionmentioning

confidence: 73%

Mechanisms of early glucose regulation disturbance after out-of-hospital cardiopulmonary resuscitation: An explorative prospective study

et al. 2019

View full text Add to dashboard Cite

BackgroundHyperglycemia is common and associated with increased mortality after out-of-hospital cardiac arrest (OHCA) and return of spontaneous circulation (ROSC). Mechanisms behind ultra-acute hyperglycemia are not well known. We performed an explorative study to describe the changes in glucose metabolism mediators during the prehospital postresuscitation phase.MethodsWe included patients who were successfully resuscitated from out-of-hospital cardiac arrest in two physician-staffed units. Insulin, glucagon, and glucagon-like peptide 1 (GLP-1) were measured in prehospital and hospital admission samples. Additionally, interleukin-6 (IL-6), cortisol, and HbA1c were measured at hospital admission.ResultsThirty patients participated in the study. Of those, 28 cases (71% without diabetes) had sufficient data for analysis. The median time interval between prehospital samples and hospital admission samples was 96 minutes (IQR 85–119). At the time of ROSC, the patients were hyperglycemic (11.2 mmol/l, IQR 8.8–15.7), with insulin and glucagon concentrations varying considerably, although mostly corresponding to fasting levels (10.1 mU/l, IQR 4.2–25.2 and 141 ng/l, IQR 105–240, respectively). GLP-1 increased 2- to 8-fold with elevation of IL-6. The median glucose change from prehospital to hospital admission was -2.2 mmol/l (IQR -3.6 to -0.2). No significant correlations between the change in plasma glucose levels and the changes in insulin (r = 0.30, p = 0.13), glucagon (r = 0.29, p = 0.17), or GLP-1 levels (r = 0.32, p = 0.15) or with IL-6 (r = (-0.07), p = 0.75), cortisol (r = 0.13, p = 0.52) or HbA1c levels (r = 0.34, p = 0.08) were observed. However, in patients who did not receive exogenous epinephrine during resuscitation, changes in blood glucose correlated with changes in insulin (r = 0.59, p = 0.04) and glucagon (r = 0.65, p = 0.05) levels, demonstrating that lowering glucose values was associated with a simultaneous lowering of insulin and glucagon levels.ConclusionsHyperglycemia is common immediately after OHCA and cardiopulmonary resuscitation. No clear hormonal mechanisms were observed to be linked to changes in glucose levels during the postresuscitation phase in the whole cohort. However, in patients without exogenous epinephrine treatment, the correlations between glycemic and hormonal changes were more obvious. These results call for future studies examining the mechanisms of postresuscitation hyperglycemia and the metabolic effects of the global ischemic insult and medical treatment.

show abstract

Section: Discussionmentioning

confidence: 73%

Mechanisms of early glucose regulation disturbance after out-of-hospital cardiopulmonary resuscitation: An explorative prospective study

et al. 2019

View full text Add to dashboard Cite

show abstract

“…The significantly reduced sDPP4 level in all ischaemic heart disease (IHD) patients suggests the existence of incretin dependent and independent adaptive mechanisms to cardiac ischemia which attenuate endothelial dysfunction, inflammation and atherosclerotic process . This is supported by our recent demonstration of sepsis‐associated reduced sDPP4 levels . However, loss of DPP4 activity has been linked to a pro‐thrombogenic status of endothelial cells and may negatively affect the coronary microvasculature of patients with myocardial infarction and reduced formation of cardio‐protective GLP‐1 metabolites .…”

Section: Discussionmentioning

confidence: 89%

“…12 This is supported by our recent demonstration of sepsisassociated reduced sDPP4 levels. 13 However, loss of DPP4 activity has been linked to a pro-thrombogenic status of endothelial cells and may negatively affect the coronary microvasculature of patients with myocardial infarction 7 and reduced formation of cardio-protective GLP-1 metabolites. 6 Therefore, the exact role of DPP4 reduction in IHD remains to be elucidated.…”

Section: Discussionmentioning

confidence: 99%

Endogenous glucagon‐like peptide‐1 system response is impaired during ST‐elevation myocardial infarction in type 2 diabetes patients

Elbaz‐Greener

Bloch

Kumets

et al. 2018

Diabetes Obesity Metabolism

Self Cite

View full text Add to dashboard Cite

We previously demonstrated increased glucagon-like peptide-1 (GLP-1) secretion during acute ST elevation myocardial infarction (STEMI) in non-diabetic (ND) patients. Whether the endogenous GLP-1 system response is different in patients with type 2 diabetes (T2D) during STEMI is unknown. Patients with STEMI (20 ND, 13 T2D) and 3 control groups (non-STEMI [14 ND, 13 T2D], stable angina pectoris [SAP] [8 ND, 10 T2D] patients and healthy subjects) (n = 25) were studied. Plasma levels of total and active GLP-1 and soluble dipeptidyl peptidase-4 (sDPP4) were estimated by enzyme-linked immunosorbent assay on admission and at 24 and 48 hours after percutaneous coronary intervention in all patients. Sharply elevated levels of total and active GLP-1 were found in ND STEMI patients at 24 h (P < 0.05 and P < 0.005, respectively), but not in T2D STEMI patients. All patients demonstrated decreased sDPP4 levels compared with healthy controls (P < 0.0005) accompanied by increased active/total GLP-1 ratio regardless of their ischemic state. These data demonstrate that T2D patients fail to further upregulate their endogenous GLP-1 system during STEMI. This may underlie their worse cardiovascular outcome.

show abstract

“…GLP-1 agonists have beneficial effects on cardiovascular mortality and ameliorate kidney injury in diabetics [17], possibly by protecting the endothelium. Also, GLP-1 secretion is increased in the presence of acute inflammation [18] and in critically ill diabetic patients [13], which might be an adaptive physiologic response to stress. GLP-1 improves vascular dysfunction in sepsis [19], but Perl et al found that diabetic patients with sepsis who showed an extremely early increase in the GLP-1 level had a poor prognosis, suggesting that severe acidemia activates endogenous GLP-1 [13].…”

Section: Discussionmentioning

confidence: 99%

“…The levels of several biomarkers, including GLP-1, are increased in septic patients [13]. Renal tubular epithelial cells contribute to the inflammatory response in ischemic kidney injury by producing inflammatory cytokines [14].…”

Section: Introductionmentioning

confidence: 99%

Renal Tubular Glucagon-Like Peptide-1 Receptor Expression Is Increased in Early Sepsis but Reduced in Chronic Kidney Disease and Sepsis-Induced Kidney Injury

Choi

Kim

Kwon

et al. 2019

IJMS

View full text Add to dashboard Cite

Acute kidney injury (AKI) is common in patients with sepsis and causes renal ischemia. Glucagon-like peptide-1 (GLP-1) protects the vascular system and the kidney, and GLP-1 receptor (GLP-1R) is expressed in the kidney. Renal GLP-1R activity is decreased in chronic kidney disease (CKD), but is increased by the inflammatory response; however, the effect of AKI on GLP-1R expression is unknown. We investigated the role of GLP-1 by assessing GLP-1R expression in the renal cortex in animals with AKI-related sepsis, CKD, and CKD-with-sepsis. We generated a model of CKD by 5/6 nephrectomy, and sepsis induced by cecal perforation, in male Sprague–Dawley rats. We compared renal GLP-1R expression at 3, 6, 12, 24, and 72 h after cecal perforation, and in CKD and CKD-with-sepsis. We performed blood and urine tests, western blotting (WB), and immunohistochemistry (IHC) to assay GLP-1R expression in renal tubules. The CKD-with-sepsis group showed the lowest kidney function, urine volume, and serum glucose and albumin levels. GLP-1R expression in renal tubules was decreased at 3 h, increased at 24 h, and decreased at 72 h after sepsis induction. GLP-1R expression was decreased at 8 weeks after CKD and was lowest in the CKD-with-sepsis group. The WB results were verified against those obtained by IHC. GLP-1R expression in renal tubules is increased in early sepsis, which may explain the protective effect of endogenous GLP-1 against sepsis-related inflammation.

show abstract

Sepsis‐induced activation of endogenous GLP‐1 system is enhanced in type 2 diabetes

Abstract: Taken together, these data indicate that endogenous GLP-1 system is activated during sepsis. Patients with T2D display an enhanced and prolonged activation as compared to nondiabetic patients. Extreme early increased GLP-1 levels during sepsis indicate poor prognosis.

Cited by 23 publications

References 29 publications

Mechanisms of early glucose regulation disturbance after out-of-hospital cardiopulmonary resuscitation: An explorative prospective study

Mechanisms of early glucose regulation disturbance after out-of-hospital cardiopulmonary resuscitation: An explorative prospective study

Endogenous glucagon‐like peptide‐1 system response is impaired during ST‐elevation myocardial infarction in type 2 diabetes patients

Renal Tubular Glucagon-Like Peptide-1 Receptor Expression Is Increased in Early Sepsis but Reduced in Chronic Kidney Disease and Sepsis-Induced Kidney Injury

Contact Info

Product

Resources

About