Effects of dapagliflozin on serum and urinary uric acid levels in patients with type 2 diabetes: a prospective pilot trial

Abstract Background: We aimed to evaluate the effects of short-term therapy with dapagliflozin on serum uric acid (SUA) and urinary uric acid (UUA) levels in patients with type 2 diabetes.Methods: In this prospective pilot trial, 8 patients with type 2 diabetes mellitus were assigned to the treatment group with dapagliflozin 10 mg once daily for one week, and 7 subjects with normal glucose tolerance were recruited into the control group. Data of anthropometric measurements, SUA, 24-hour UUA, fractional excretion of UA (FEUA), serum lipid parameters and 3-hour oral glucose tolerance test (OGTT) were collected in both treatment and control groups; all examinations were repeated after treatment. The area under the curve of glucose (AUCGlu) was calculated to reflect the general glucose levels, while insulin resistance and islet β-cell function were reflected by indexes calculated according to the data obtained from the OGTT.Results: The weight and serum lipid parameters showed no differences before and after treatment with dapagliflozin for one week. We found SUA levels decreased from 347.75 ± 7.75 μmol/L before treatment to 273.25 ± 43.18 μmol/L after treatment, with a statistically significant difference (P=0.001) and was accompanied by a significant increase in FEUA from 0.009 to 0.029 (P=0.035); there was a linear correlation between SUA and FEUA levels. Glucose control, insulin sensitivity and islet β-cell function were improved to a certain extent. We also found a positive correlation between the decrease in glucose levels and the improvement in islet β-cell function.Conclusions: The SUA-lowering effect of dapagliflozin could be driven by increasing UA excretion within one week of treatment, and a certain degree of improvement in glucose levels and islet β-cell function were observed.

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Effects of dapagliflozin on serum and urinary uric acid levels in patients with type 2 diabetes: a prospective pilot trial

10.21203/rs.3.rs-41361/v3 ◽

2020 ◽

Author(s):

Tao Yuan ◽

Shixuan Liu ◽

Yingyue Dong ◽

Yong Fu ◽

Yan Tang ◽

...

Keyword(s):

Type 2 Diabetes ◽

Uric Acid ◽

Serum Lipid ◽

Cell Function ◽

Pilot Trial ◽

Β Cell ◽

Glucose Levels ◽

Β Cell Function ◽

Lipid Parameters

Abstract Background: We aimed to evaluate the effects of short-term therapy with dapagliflozin on serum uric acid (SUA) and urinary uric acid (UUA) levels in patients with type 2 diabetes.Methods: In this prospective pilot trial, 8 patients with type 2 diabetes mellitus were assigned to the treatment group with dapagliflozin 10 mg once daily for one week, and 7 subjects with normal glucose tolerance were recruited into the control group. Data of anthropometric measurements, SUA, 24-hour UUA, fractional excretion of UA (FEUA), serum lipid parameters and 3-hour oral glucose tolerance test (OGTT) were collected in both treatment and control groups; all examinations were repeated after treatment. The area under the curve of glucose (AUCGlu) was calculated to reflect the general glucose levels, while insulin resistance and islet β-cell function were reflected by indexes calculated according to the data obtained from the OGTT.Results: The weight and serum lipid parameters showed no differences before and after treatment with dapagliflozin for one week. We found SUA levels decreased from 347.75 ± 7.75 μmol/L before treatment to 273.25 ± 43.18 μmol/L after treatment, with a statistically significant difference (P=0.001) and was accompanied by a significant increase in FEUA from 0.009 to 0.029 (P=0.035); there was a linear correlation between SUA and FEUA levels. Glucose control, insulin sensitivity and islet β-cell function were improved to a certain extent. We also found a positive correlation between the decrease in glucose levels and the improvement in islet β-cell function.Conclusions: The SUA-lowering effect of dapagliflozin could be driven by increasing UA excretion within one week of treatment, and a certain degree of improvement in glucose levels and islet β-cell function were observed. Trial registration: ClinicalTrials.gov identifier, NCT04014192. Registered 12 July 2019, https://www.clinicaltrials.gov/ct2/show/NCT04014192?term=NCT04014192&draw=2&rank=1. Yes.

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Regulation of serum uric acid with canagliflozin monotherapy in type 2 diabetes: A potential link between uric acid and pancreatic β-cell function

International Journal of Clinical Pharmacology and Therapeutics ◽

10.5414/cp203513 ◽

2019 ◽

Vol 57 (12) ◽

pp. 590-595 ◽

Cited By ~ 3

Author(s):

Eiji Kutoh ◽

Asuka Wada ◽

Alexandra N. Kuto ◽

Jyunka Hayashi

Keyword(s):

Type 2 Diabetes ◽

Uric Acid ◽

Serum Uric Acid ◽

Cell Function ◽

Pancreatic Β Cell ◽

Β Cell ◽

Β Cell Function ◽

Potential Link

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Pathogenetic substantiation and effectiveness of vildagliptin use inpatients with diabetes mellitus type 2

Obesity and metabolism ◽

10.14341/2071-8713-5241 ◽

2009 ◽

Vol 6 (3) ◽

pp. 16-26 ◽

Cited By ~ 1

Author(s):

T I Romantsova

Keyword(s):

Type 2 Diabetes ◽

Cell Function ◽

Glucagon Secretion ◽

Β Cell ◽

Dipeptidyl Peptidase 4 ◽

Glucose Levels ◽

Β Cell Function ◽

Control Of Diabetes ◽

Glucagon Like Peptide 1

Insulin resistance in muscle and liver and β-cell failure represent the core pathophysiologic defects in type 2 diabetes. Now it isrecognized that the β-cell failure occurs much earlier and is more severe than previously thought. As a result, earlier and more aggressive new therapy is needed to achiev e better control of diabetes and to prev ent/slow the progressive B-cell failure that already is w ell established in IGT subjects. One approach is to target the incretin mimetic hormone glucagon-like peptide-1 (GLP-1). When blood glucose levels are elevated, GrP-1 stimulates insulin secretion, decreases glucagon secretion, impro ves β-cell function, and slows gastric emptying. GrP-1 production is reduced in patients with type 2 diabetes. Furthermore, GrP-1 is rapidly degraded by the dipeptidyl peptidase 4 (DPP-4) enzyme. Trials have showed, that new inhibitor DPP-4 vildagliptin (Galvus) hav e been demonstrated to significantly reduce HbA lc, fasting and prandial glucose levels when used as monotherapy and in соmbination with traditional agents. Advantages of vildagliptin include few adverse events, low risk of hypoglycemia, neutral effect on body weight, and a once-daily oral dosing regimen. Inaddition, vildagliptin may preserve the decline in β-cell function. Hence, vildagliptin may modify the natural progressive course of diabetes; this however, must be confirmed with longer-term controlled studies

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A Brief Review of the Mechanisms of β-Cell Dedifferentiation in Type 2 Diabetes

Nutrients ◽

10.3390/nu13051593 ◽

2021 ◽

Vol 13 (5) ◽

pp. 1593

Author(s):

Phyu-Phyu Khin ◽

Jong-Han Lee ◽

Hee-Sook Jun

Keyword(s):

Type 2 Diabetes ◽

Cell Function ◽

Cell Mass ◽

Cell Loss ◽

Β Cell ◽

Cell Dedifferentiation ◽

Glucose Levels ◽

Β Cell Function ◽

Dedifferentiation Process

Diabetes is a metabolic disease characterized by hyperglycemia. Over 90% of patients with diabetes have type 2 diabetes. Pancreatic β-cells are endocrine cells that produce and secrete insulin, an essential endocrine hormone that regulates blood glucose levels. Deficits in β-cell function and mass play key roles in the onset and progression of type 2 diabetes. Apoptosis has been considered as the main contributor of β-cell dysfunction and decrease in β-cell mass for a long time. However, recent studies suggest that β-cell failure occurs mainly due to increased β-cell dedifferentiation rather than limited β-cell proliferation or increased β-cell death. In this review, we summarize the current advances in the understanding of the pancreatic β-cell dedifferentiation process including potential mechanisms. A better understanding of β-cell dedifferentiation process will help to identify novel therapeutic targets to prevent and/or reverse β-cell loss in type 2 diabetes.

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Effects of Dapagliflozin on Serum and Urinary Uric Acid Levels in Type 2 Diabetic Patients: a Prospective Pilot Trial

10.21203/rs.3.rs-41361/v1 ◽

2020 ◽

Author(s):

Tao Yuan ◽

Shixuan Liu ◽

Yingyue Dong ◽

Yong Fu ◽

Yan Tang ◽

...

Keyword(s):

Uric Acid ◽

Pilot Trial ◽

Diabetic Patients ◽

Cell Secretion ◽

Β Cell ◽

Type 2 Diabetic Patients ◽

Glucose Levels ◽

Lipid Parameters ◽

Type 2 Diabetic

Abstract Background We aimed to evaluate the effects of dapagliflozin short-term therapy on serum uric acid (SUA) and urinary uric acid (UUA) levels in type 2 diabetic patients. Methods In this prospective pilot trial, 8 patients with type 2 diabetes mellitus were assigned to the treatment group with dapagliflozin 10 mg once daily for one week, and 7 subjects with normal glucose tolerance were recruited in the control group. Data of anthropometric measurements, SUA, 24-hour UUA, the fractional excretion of UA (FEUA), serum lipid parameters and 3-hour oral glucose tolerance test (OGTT) were collected in both treatment and control groups, also repeated after treatment. Area under curve of glucose (AUCGlu) was calculated to reflect the general glucose levels, insulin resistance and islet β-cell secretion function were reflected by indices calculated according to the data obtained from OGTT. Results The weight and serum lipid parameters showed no differences before and after dapagliflozin treatment for one week. We found SUA levels reduced from 347.75 ± 7.75 µmol/L before treatment to 273.25 ± 43.18 µmol/L after treatment with a significant difference (p = 0.001), accompanying with a significant increase in FEUA from 0.009 to 0.029 (p = 0.035), and there was a linear correlation between SUA and FEUA levels. The glucose control, insulin sensitivity and islet β-cell secretion function were improved to a certain extent. We also found the decrease in glucose levels were positively correlated with the improvement of islet β-cell secretion function. Conclusions Dapagliflozin can present the effect on reducing SUA by increasing UA excretion within one-week treatment, a certain degree of improvement in glucose levels and islet β-cell function were observed. Trial registration: ClinicalTrials.gov identifier, NCT04014192. Registered 12 July 2019, https://www.clinicaltrials.gov/ct2/show/NCT04014192?term=NCT04014192&draw=2&rank=1. Yes.

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