Role of endogenous GLP-1 on arterial stiffness and renal haemodynamics following bariatric surgery.

BACKGROUND: Cardiovascular trials have revealed the positive impact of GLP-1 receptor agonists (GLP-1 RAs) on cardiovascular outcomes in type 2 diabetes (T2D). However, the specific effects of endogenous GLP-1 on arterial stiffness and renal function remain understudied. This study aimed to explore the influence of endogenous GLP-1 response post-bariatric surgery on arterial stiffness and renal haemodynamic. METHODS: Thirty individuals with morbid obesity and without T2D, scheduled for Roux-en-Y Gastric Bypass (RYGB), were included. Clinical parameters, 3-hour oral glucose tolerance test (OGTT) with serial sampling for glycaemia, GLP-1 and insulin, carotid-femoral pulse wave velocity (cf-PWV), carotid distensibility coefficient (carotid-DC) and renal resistive index (RRI) measurements were conducted pre-surgery and 1-year post-surgery. Participants were categorized into high-response and low-response groups based on their post-surgery increase in GLP-1 (median increase of 104% and 1%, respectively, pre- vs. post-surgery). RESULTS: Post-surgery, high-response group demonstrated a greater reduction in cf-PWV (p = .033) and a greater increase (p = .043) in carotid DC compared to low-response group. These enhancements were observed independently of weight loss or blood pressure changes. High-response group exhibited a reduction in RRI (p = .034), although this association was influenced by improvement in pulse pressure. Finally, a multivariate stepwise regression analysis indicated that the percentage increase of GLP1, Δ-GLP1(AUC)%, was the best predictor of percentage decrease in cf-PWV (p = .014). CONCLUSIONS: Elevated endogenous GLP-1 response following RYGB was associated with improved arterial stiffness and renal resistances, suggesting potential cardio-renal benefits. The findings underscore the potential role of endogenous GLP-1 in influencing vascular and renal haemodynamics independent of traditional weight loss.

Severe and fatal COVID-19 is characterised by increased circulating glucagon like peptide 1 and procalcitonin modulated by type 2 diabetes.

AIMS: Endotoxemia commonly occurs in severe and fatal COVID-19, suggesting that concomitant bacterial stimuli may amplify the innate immune response induced by SARS-CoV-2. We previously demonstrated that the endogenous glucagon like peptide 1 (GLP-1) system in conjunction with increased procalcitonin (PCT) is hyperactivated in patients with severe Gram-negative sepsis and modulated by type 2 diabetes (T2D). We aimed to determine the association of COVID-19 severity with endogenous GLP-1 activation upregulated by increased specific pro-inflammatory innate immune response in patients with and without T2D. MATERIALS AND METHODS: Plasma levels of total GLP-1, IL-6, and PCT were estimated on admission and during hospitalisation in 61 patients (17 with T2D) with non-severe and severe COVID-19. RESULTS: COVID-19 patients demonstrated ten-fold increase of IL-6 levels regardless of disease severity. Increased admission GLP-1 levels (p = 0.03) accompanied by two-fold increased PCT were found in severe as compared with non-severe patients. Moreover, GLP-1 and PCT levels were significantly increased in non-survived as compared with survived patients at admission (p = 0.01 and p = 0.001, respectively) and at 5 to 6 days of hospitalisation (p = 0.05). Both non-diabetic and T2D patients demonstrated a positive correlation between GLP-1 and PCT response (r = 0.33, p = 0.03, and r = 0.54, p = 0.03, respectively), but the intensity of this joint pro-inflammatory/GLP-1 response was modulated by T2D. In addition, hypoxaemia down-regulated GLP-1 response only in T2D patients with bilateral lung damage. CONCLUSIONS: The persistent joint increase of endogenous GLP-1 and PCT in severe and fatal COVID-19 suggests a role of concomitant bacterial infection in disease exacerbation. Early elevation of endogenous GLP-1 may serve as a new biomarker of COVID-19 severity and fatal outcome.

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

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.

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

BACKGROUND: High levels of circulating GLP-1 are associated with severity of sepsis in critically ill nondiabetic patients. Whether patients with type 2 diabetes (T2D) display different activation of the endogenous GLP-1 system during sepsis and whether it is affected by diabetes-related metabolic parameters are not known. METHODS: Serum levels of GLP-1 (total and active forms) and its inhibitor enzyme sDPP-4 were determined by ELISA on admission and after 2 to 4 days in 37 sepsis patients with (n = 13) and without T2D (n = 24) and compared to normal healthy controls (n = 25). Correlations between GLP-1 system activation and clinical, inflammatory, and diabetes-related metabolic parameters were performed. RESULTS: A 5-fold (P < .001) and 2-fold (P < .05) increase in active and total GLP-1 levels, respectively, were found on admission as compared to controls. At 2 to 4 days from admission, the level of active GLP-1 forms in surviving patients were decreased significantly (P < .005), and positively correlated with inflammatory marker CRP (r = 0.33, P = .05). T2D survivors displayed a similar but more enhanced pattern of GLP-1 response than nondiabetic survivors. Nonsurvivors demonstrate an early extreme increase of both total and active GLP-1 forms, 9.5-fold and 5-fold, respectively (P < .05). The initial and late levels of circulating GLP-1 inhibitory enzyme sDPP-4 were twice lower in all studied groups (P < .001), compared with healthy controls. CONCLUSIONS: 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.