scholarly journals Decrease of dipeptidyl peptidase 4 activity is associated with weight loss after bariatric surgery

2021 ◽  
Author(s):  
Carsten T. Herz ◽  
Johanna M. Brix ◽  
Bernhard Ludvik ◽  
Guntram Schernthaner ◽  
Gerit-Holger Schernthaner

Abstract Purpose Dipeptidyl peptidase 4 (DPP4) is expressed and secreted by adipocytes. DPP4 induces insulin resistance independently of its effect on glucagon-like peptide 1, thus it is conceivable that DPP4 directly contributes to metabolic dysfunction in patients with morbid obesity. The aim of this study was to investigate the impact of weight loss induced by bariatric surgery on DPP4 activity, and whether these changes are associated with improvements in markers of metabolic dysfunction and fatty liver disease. Materials and Methods We included 68 non-diabetic patients who underwent bariatric surgery. Serum DPP4 activity was measured using a fluorogenic substrate before and after surgery. Results Results: After a median follow-up period of 12 (IQR 11-17) months, median serum DPP4 activity decreased from 230 (IQR: 194-273) to 193 (164-252) pmol/min (p=0.012). The decrease in DPP4 activity was significantly correlated with decreases in BMI, improved cholesterol levels, reduced hepatic injury markers as well as improved post-prandial insulin sensitivity. After multivariable adjustment, ΔDPP4 activity remained significantly associated with Δcholesterol (beta=0.341, p=0.025), ΔLDL cholesterol (beta=0.350, p=0.019), Δgamma-glutamyltransferase (beta=0.323, p=0.040) and ΔMatsuda index (beta=-0.386, p=0.045). Conclusion We demonstrated that weight loss induced by bariatric surgery results in decreased circulating DPP4 activity beyond the initial phase of weight loss. The associations between decreased DPP4 activity and improved cholesterol levels as well as hepatic injury markers point towards pleiotropic effects of DPP4 beyond glucose metabolism which warrant further investigation.

2017 ◽  
pp. E188-E199
Author(s):  
Abdulhalim Senyigit ◽  
Omur Tabak ◽  
Timur Orhanoglu ◽  
Aytac Karadag ◽  
Serdal Ugurlu ◽  
...  

Purpose: Hyperglycemia is the major risk factor for microvascular complications in type 2 diabetes mellitus (T2DM) patients. This randomized controlled clinical trial aimed to investigate T2DM patients with microvascular complications with regard to possible relations among serum clusterin (CLU), amylin, secreted frizzled-related protein-4 (SFRP-4), glucagon-like peptide-1 (GLP-1) and dipeptidyl peptidase-4 (DPP-4) activities. Methods: Subject groups were defined as follows: T2DM without complications (n=25, F/M=9/16, age 53.9±11.1 years); T2DM+Retinopathy (n=25, F/M=13/12, age 63.8±7.1 years); T2DM+Nephropathy (n=25, F/M=13/12, age 58.7±14.4 years); T2DM+Neuropathy (n=25, F/M=15/10, age 63.2±9.6 years); and healthy control subjects (HC) (n=25). CLU, amylin, SFRP-4, DPP-4 and GLP-1 (total and active) activities were measured and compared in blood samples from type 2 diabetic patients with and without microvascular complications. Results: Significantly lower levels of DPP-4 and GLP-1total (P


Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Jessica K Devin ◽  
Mias Pretorius ◽  
Frederic T Billings ◽  
Hui Nian ◽  
Nancy J Brown

Glucagon-like peptide 1 (GLP-1) causes direct vasodilation in animal models. Dipeptidyl peptidase 4 (DPP4) inhibitors improve glycemic control in diabetic patients by preventing the degradation of GLP-1. The direct effect of GLP-1 in the human vasculature, and how it is altered by DPP4 inhibition, has not been reported. This study tested the hypothesis that intra-arterial infusion of GLP-1 causes dose-dependent vasodilation, and that DPP4 inhibition potentiates the forearm blood flow (FBF) response to GLP-1 by decreasing its degradation. Eight healthy, non-obese (BMI<30 kg/m 2 ) subjects, age 28-54 years old (3 female) participated in this double-blind, placebo-controlled crossover study. On study days separated by at least one week subjects received DPP4 inhibitor (sitagliptin 200 mg p.o.) or placebo, followed by infusion of GLP-1 in the brachial artery at graded doses (0.45-3.60 pmol/min) for 5 minutes per dose. Sitagliptin significantly decreased plasma DPP4 activity (p<0.001 vs. placebo). Sitagliptin did not significantly affect baseline heart rate or baseline FBF. Baseline mean arterial pressure was significantly higher during sitagliptin than during placebo [87.13 ± 2.10 mmHg versus 84.75 ± 3.28 mmHg, p=0.037]. GLP-1 concentrations were significantly higher after sitagliptin (Left Figure; N=5). There was no effect of GLP-1 on FBF either in the presence or absence of sitagliptin. Moreover, there was no interactive effect of GLP-1 and sitagliptin on FBF (Right Figure). GLP-1 does not cause vasodilation in healthy humans even when its degradation is inhibited. These data have implications for the cardiovascular effects of DPP4 inhibitors and GLP-1 receptor agonists.


Planta Medica ◽  
2019 ◽  
Vol 85 (11/12) ◽  
pp. 825-839 ◽  
Author(s):  
José-Luis Ríos ◽  
Isabel Andújar ◽  
Guillermo R. Schinella ◽  
Flavio Francini

AbstractIncretins are metabolic hormones released after a meal that increase insulin secretion from pancreatic β-cells. The two main incretins are the intestinal peptides glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide. Both induce a decrease in glycemia, slow down the absorption of nutrients, and are inactivated by the enzyme dipeptidyl peptidase-4. Recently, incretin-based therapies have become a useful tool to treat diabetic patients, and different studies have focused on the identification of glucagon-like peptide-1 receptor agonists, including those of natural origin. This review focuses on the new findings of medicinal plants and natural products as possible active agents on the potentiation of incretin receptor signaling. Among these, soluble fiber from species of Plantago and guar gum show promising effects, iridoid derivatives are relevant activators of incretin receptors, and derivatives of cyanidin, especially diglycosylated ones, are an interesting source of dipeptidyl peptidase-4 inhibitors.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1250.2-1251
Author(s):  
W. S. Chen ◽  
Y. S. Chang ◽  
C. Y. Tsai ◽  
C. C. Chang

Background:The risk of psoriasis in diabetic patients has rarely been explored.Objectives:This study aimed to investigate the association between dipeptidyl peptidase-4 (DPP4) inhibitors and the risk of psoriasis in type 2 diabetes mellitus (T2DM) patients.Methods:We conducted a population-based propensity score-matched cohort study on the basis of Taiwan’s National Health Insurance Research Database that included initiators of combination therapy with DPP4i (DPP4i plus metformin) and sulfonylurea (sulfonylurea plus metformin). Psoriasis (PSO) was identified with ≥2 diagnoses. Diabetes complications severity index (DCSI) was calculated. A total of 22721 DPP4 initiator and 227684 sulfonylurea initiator were identified. A 1:10 matched-pair cohort based on propensity score(PS) was created. PS-stratified Cox proportional hazards models compared the risk of PSO in DPP4i versus sulfonylurea initiator within 2 years, controlling for potential confounders.Results:After propensity score matching, 9962 patients with T2DM starting DPP4i combination therapy and 39848 starting sulfonylurea combination therapy were selected. The incidence rate of PSO was lower in DPP4i group (188/100000 person- years) than in sulfonylurea group (467/100000 person-years). Risks of incident psoriasis were significantly lower in the DPP4i group versus sulfonylurea with the PS-stratified HR of 0.422 (95% CI 0.273 to 0.716).Conclusion:DPP4i plus metformin was associated with a reduced risk of psoriasis than sulfonylurea plus metformin. These findings merit further investigation.Disclosure of Interests:None declared


Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000012534
Author(s):  
Seong Ho Jeong ◽  
Hye Ryun Kim ◽  
Jeonghun Kim ◽  
Hankyeol Kim ◽  
Namki Hong ◽  
...  

Objectives:To investigate whether dipeptidyl peptidase-4 inhibitors (DPP-4i) have beneficial effects on amyloid aggregation and longitudinal cognitive outcome in diabetic Alzheimer’s disease-related cognitive impairment (ADCI).Methods:We retrospectively reviewed 282 patients with ADCI who had positive scan of 18F-florbetaben amyloid PET images were classified into three groups according to a prior diagnosis of diabetes and DPP-4i use: diabetic patients being treated with (ADCI-DPP-4i+, n=70) or without DPP-4i (ADCI-DPP-4i-, n=71), and non-diabetic patients (n=141). Multiple linear regression analyses were performed to determine inter-group differences in global and regional amyloid retention using standardized uptake value ratios calculated from cortical areas. We assessed the longitudinal changes in Mini-Mental State Examination (MMSE) score using a linear mixed model.Results:The ADCI-DPP-4i+ group had lower global amyloid burden than the ADCI-DPP-4i− group (β = 0.075, SE = 0.024, p = 0.002) and the non-diabetic ADCI group (β = 0.054, SE = 0.021, p = 0.010) after adjusting for age, sex, education, cognitive status, and APOE ε4 carrier status. Additionally, the ADCI-DPP-4i+ group had lower regional amyloid burden in temporo-parietal areas than either the ADCI-DPP-4i− group or the non-diabetic ADCI group. The ADCI-DPP-4i+ group showed a slower longitudinal decrease in MMSE score (β = 0.772, SE = 0.272, p = 0.005) and memory recall sub-score (β = 0.291, SE = 0.116, p = 0.012) than the ADCI-DPP-4i− group.Conclusions:These findings suggest that DPP-4i use is associated with low amyloid burden and favorable long-term cognitive outcome in diabetic patients with ADCI.


2019 ◽  
Vol 6 (2) ◽  
pp. 264
Author(s):  
Deniz Avci ◽  
Ali Cetinkaya

Background: The aim of this study was to determine how HbA1c, lipid, renal functions and such parameters were affected in the long term by adding dipeptidyl peptidase-4 inhibitors to the ongoing treatment regimens of patients with Type 2 diabetes mellitus.Methods: The study was conducted in diabetes mellitus outpatient clinic of Kayseri Training and Research Hospital between February 2012 and May 2017, with patients who did not achieve the sufficient success in diabetes their controls at the time of admission. From these patients, those who added (dipeptidyl peptidase-4 inhibitors) to their treatments were selected. Patients were followed up as long as they continued to these new treatments and the parameters at the baseline were compared with final values.Results: A total of 80 diabetic patients were followed in the study. The median age of the patients was 56.08±9.71 years. During this follow-up, an average decrease of 1.03% was noted when patients were compared with 9.53±1.87% of the initial hemoglobin A1c, and 8.50±1.48% of the Hemoglobin A1c values at the end of follow-up. This decrease was statistically significant (p <0.001). However, differences in the initial and final values of the lipid parameters of the patients were not statistically significant.Conclusions: Addition of dipeptidyl peptidase-4 inhibitors to patients' treatments causes significant decreases in Hemoglobin A1c mean values. This decline is long lasting. However, there are no positive or negative effects on biochemical parameters such as lipids, kidney and liver functions.


Sign in / Sign up

Export Citation Format

Share Document