scholarly journals Renal tubular effects of prolonged therapy with the GLP-1 receptor agonist lixisenatide in patients with type 2 diabetes mellitus

2019 ◽  
Vol 316 (2) ◽  
pp. F231-F240 ◽  
Author(s):  
Lennart Tonneijck ◽  
Marcel H. A. Muskiet ◽  
Charles J. Blijdorp ◽  
Mark M. Smits ◽  
Jos W. Twisk ◽  
...  

Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) are well-established glucose-lowering drugs for type 2 diabetes mellitus (T2DM) management. Acute GLP-1RA administration increases urinary excretion of sodium and other electrolytes. However, the renal tubular effects of prolonged GLP-1RA treatment are largely unknown. In this secondary analysis of a randomized trial, we determined the renal tubular effects of 8-wk treatment with 20 μg lixisenatide, a short-acting (prandial) GLP-1RA, versus titrated once-daily insulin glulisine in 35 overweight T2DM-patients on stable insulin glargine background therapy (age: 62 ± 7 yr, glycated hemoglobin: 8.0 ± 0.9%, estimated glomerular filtration rate: >60 ml·min−1·1.73 m−2). After a standardized breakfast, lixisenatide increased absolute and fractional excretions of sodium, chloride, and potassium and increased urinary pH. In contrast, lixisenatide reduced absolute and fractional excretions of magnesium, calcium, and phosphate. At week 8, patients treated with lixisenatide had significantly more phosphorylated sodium-hydrogen exchanger isoform 3 (NHE3) in urinary extracellular vesicles than those on insulin glulisine treatment, which suggested decreased NHE3 activity in the proximal tubule. A rise in postprandial blood pressure with lixisenatide partly explained the changes in the urinary excretion of sodium, potassium, magnesium, and phosphate and the changes in urinary pH. In conclusion, lixisenatide affects postprandial urinary excretion of several electrolytes and increases urinary pH compared with insulin glulisine in T2DM patients after 8 wk of treatment. This is most likely explained by a drug-induced rise in blood pressure or direct inhibitory effects on NHE3 in the proximal tubule.

Author(s):  
Hadi Bazyar ◽  
Seyed Ahmad Hosseini ◽  
Sirous Saradar ◽  
Delsa Mombaini ◽  
Mohammad Allivand ◽  
...  

Abstract Background In patients with type 2 diabetes mellitus (T2DM) the inflammatory and metabolic responses to epigallocatechin-3-gallate (EGCG) are unknown. Objectives Evaluate the impacts of EGCG on metabolic factors and some biomarkers of stress oxidative in patients with T2DM. Methods In this randomized, double-blind, placebo-controlled trial, 50 patients with T2DM consumed either 2 tablets (300 mg) EGCG (n=25) or wheat flour as placebo (n=25) for 2 months. The total antioxidant capacity (TAC), interleukin-6 (IL-6), lipid profile, mean arterial pressure (MAP), atherogenic index of plasma (AIP) were evaluated before and after the intervention. Results The finding of present study exhibited a significant increase in the serum levels of TAC after the EGCG supplementation (p=0.001). Also, in compare with control group, the mean changes of TAC were significantly higher in supplement group (p=0.01). In intervention group, a significant decrease was observed in the mean levels of triglyceride, total cholesterol, diastolic blood pressure (DBP), AIP, and MAP (p<0.05). Taking EGCG resulted in the mean changes of total cholesterol, MAP and DBP were significantly lower in compare with control group (p<0.05). Conclusions This study recommended that EGCG supplementation may be improved blood pressure, lipid profile, AIP, and oxidative status in patients with T2DM.


2021 ◽  
pp. 1-9
Author(s):  
Ramkumar Mohan ◽  
Stefanie Wei Lynn Goh ◽  
Guan Wei Tan ◽  
Yen Pin Tan ◽  
Sameer P. Junnarkar ◽  
...  

<b><i>Background:</i></b> Acute cholangitis (AC) is a common emergency with a significant mortality risk. The Tokyo Guidelines (TG) provide recommendations for diagnosis, severity stratification, and management of AC. However, validation of the TG remains poor. This study aims to validate TG07, TG13, and TG18 criteria and identify predictors of in-hospital mortality in patients with AC. <b><i>Methods:</i></b> This is a retrospective audit of patients with a discharge diagnosis of AC in the year 2016. Demographic, clinical, investigation, management and mortality data were documented. We performed a multinomial logistic regression analysis with stepwise variable selection to identify severity predictors for in-hospital mortality. <b><i>Results:</i></b> Two hundred sixty-two patients with a median age of 75.9 years (IQR 64.8–82.8) years were included for analysis. TG13/TG18 diagnostic criteria were more sensitive than TG07 diagnostic criteria (85.1 vs. 75.2%; <i>p</i> &#x3c; 0.006). The majority of the patients (<i>n</i> = 178; 67.9%) presented with abdominal pain, pyrexia (<i>n</i> = 156; 59.5%), and vomiting (<i>n</i> = 123; 46.9%). Blood cultures were positive in 95 (36.3%) patients, and 79 (83.2%) patients had monomicrobial growth. The 30-day, 90-day, and in-hospital mortality numbers were 3 (1.1%), 11 (4.2%), and 15 (5.7%), respectively. In multivariate analysis, type 2 diabetes mellitus (OR = 12.531; 95% CI 0.354–116.015; <i>p</i> = 0.026), systolic blood pressure &#x3c;100 mm Hg (OR = 10.108; 95% CI 1.094–93.395; <i>p</i> = 0.041), Glasgow coma score &#x3c;15 (OR = 38.16; 95% CI 1.804–807.191; <i>p</i> = 0.019), and malignancy (OR = 14.135; 95% CI 1.017–196.394; <i>p</i> = 0.049) predicted in-hospital mortality. <b><i>Conclusion:</i></b> TG13/18 diagnostic criteria are more sensitive than TG07 diagnostic criteria. Type 2 diabetes mellitus, systolic blood pressure &#x3c;100 mm Hg, Glasgow coma score &#x3c;15, and malignant etiology predict in-hospital mortality in patients with AC. These predictors could be considered in acute stratification and treatment of patients with AC.


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