Relation Between Plasma Apelin Level and Diabetic Nephropathy in Type 2 Diabetes Patients.

May 7, 2020 updated by: Mona Youssry Helmy, Cairo University

Relation Between Plasma Apelin Level and Diabetic Nephropathy in Type 2 Diabetic Patients

Diabetic nephropathy (DN) is the commonest cause of chronic kidney disease, and proteinuria isn't determent factor for the end stage renal disease in diabetics. Apelin is adipokine and have a beneficial role in early prediction of diabetic nephropathy. Few studies were done about apelin in diabetes. Purpose of the study: to investigate the association between the apelinergic system and diabetic nephropathy.

Study Overview

Status

Completed

Detailed Description

Introduction Type 2 Diabetes Mellitus is a metabolic syndrome associated with hyperglycemia due to defect in secretion or action of insulin or both. Long term hyperglycemia leads to complications of microvasculature involving the eyes, kidneys and nerves.

Diabetic nephropathy (DN) is the commonest cause of end-stage renal disease that may need hemodialysis up to renal transplantation with increased incidence of mortality. Without management, patients with diabetes worsen from micro albuminuria to frank proteinuria with more impairment of kidney functions. This worsening develops in both type 1 and type 2 diabetes.Previous studies have revealed major roles of different inflammatory molecules in the development of diabetic nephropathy, including acute phase reactants, inflammatory cytokines, adhesion molecules, and chemokines.

Previous studies have revealed major roles of different inflammatory molecules in the development of diabetic nephropathy, including acute phase reactants, inflammatory cytokines, adhesion molecules.

Apelin (APLN) is the endogenous ligand peptide which is encoded in humans by the APLN gene. It is presented widely in different organs as the heart, kidney, liver, fatty tissue, endothelium, plasma, gastrointestinal tract, brain and adrenals .Apelin has a major role in the pathophysiology of hypertension, heart failure, cardio-vascular disease, DM, and obesity. Apelin is found to be higher in type 2 diabetic patients than healthy subjects. It inhibits insulin secretion, so it may precipitates impaired metabolism of glucose.

Also, Apelin present in omental fat is higher than its presence in subcutaneous fat suggesting its contribution to central obesity which is an important risk factor for type 2 DM.

In diabetic nephropathy, the apelin-13 level is markedly higher in than non-diabetic organs. Apelin mediates podocyte apoptosis,that is inversely related with podocyte autophagy in nephropathic diabetic mice. In addition, the mTOR pathway is supposed to have responsibility for inhibiting podocyte autophagy by apelin.

Apelin participates in the pathology of glomerular angiogenesis by affecting the permeability in glomeruli and glomerular endothelial cells proliferation of diabetics. So, playing a role in DN pathogenesis. Also, administration of apelin-13 diabetic rats restored the down regulation of the antioxidant catalase, revealing its renal protective effect via antioxidant pathways.

We aimed from this work to evaluate the relation between plasma Apelin level and diabetic nephropathy in Egyptian Type 2 diabetic patients.

Materials and methods After approval by the research ethical committee of Kasr El Ainy faculty of medicine, Cairo University on research protocols. A case control study including 90 patients aged 20 to 65 years, 30 healthy subjects as a control group and 60 patients with type 2 DM .Patients were collected from the endocrinology outpatient clinic, Kasr El Ainy, Cairo university. It was conducted from November 2019 to march 2020.

Oral consent was obtained from patients before inclusion after explaining the study protocol. Patients were divided into 3 groups, (group I) 30 patients with type 2 DM with nephropathy, (group II) 30 type 2 DM without nephropathy and (group III) 30 non DM as control group. Exclusion criteria included Patients with nephropathy due to other causes than diabetes, hepatic, intrinsic renal or coronary artery disease, patients with diabetic neuropathy and retinopathy and hypertensive patient on angiotensin receptor blockers (ARBS) or angiotensin converting enzyme inhibitors (ACEI) treatment as it affect Apelin level.

Full medical history was taken from all subjects, emphasizing on age , duration of diabetes mellitus, complications specially nephropathy and other co-morbid conditions and full clinical examination including blood pressure measurement, weight, height, Body Mass Index (BMI) (kg/m2) and waist circumference .

Laboratory investigations in the form of fasting blood glucose (FBG), 2 hr- postprandial blood glucose (2 hr -PPG), fasting lipids {total cholesterol (TC), triglycerides (TAG), low densitylipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), glycosylated hemoglobin (Hb A1c), urea, creatinine, urine analysis , albumin creatinine ratio , estimated glomerular filtration rate (e GFR) , glycosylated hemoglobin (Hb A1c), and Apelin levels were assessed.

Sampling: Five ml of venous blood was collected by venipuncture was divided into 3 parts: The first part was 2 ml of blood added to a tube containing EDTA for determination of HbA1C by caution exchange resin. The 2nd part was 3 ml of blood was left in plastic serum tubes and the specimens were allowed to clot at room temperature then serum was separated from the cells as soon as by centrifugation at 3000xg for 5 minutes. The separated serum was stored at -20ºC until analysis. The 3rd part was collected in a tube containing EDTA and centrifuged for 15 min at 1000×g at 2-8℃ within 30 min of collection. The supernatant was collected and stored at -80ºC for apelin determination.

Determination of serum urea, serum creatinine, serum total cholesterol, serum triglyceride, serum LDL and serum HDL were carried out on Dimension RxL Max analyzer, (Siemens Healthcare GmbH - Henkestr. 127, 91052 Erlangen, Germany) by colorimetric techniques.

Plasma apelin was determined using competitive-ELISA kit supplied from Elabscience Biotechnology Inc., (1 Shizishan Street, Hongshan District, Wuhan, Hubei, China) , ( Estienne A et al . 2019). eGFR was estimated using Cockcroft Gault equation: Cockcroft Gault equation= 140-age x weight/72 x S.Cr mg/dl(x 0.85 in female).

Complete urine analysis was done to detect the presence of active urinary sediment (proteinuria, pyuria, RBCs or RBCs casts, granular cast).

Albumin concentrations were measured in urine using a Minineph micro albumin kit based on nephelometry method on Minineph-nephelometer. Urinary creatinine was determined on Dimension RxL Max analyzer by colorimetric technique and the ratio of urine albumin to creatinine was used to define micro albuminuria.

Study Type

Observational

Enrollment (Actual)

90

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Manial
      • Cairo, Manial, Egypt, 12511
        • Cairo University Hospitals

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years to 60 years (ADULT)

Accepts Healthy Volunteers

N/A

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

90 patients aged 20 to 65 years, 30 healthy subjects as a control group and 60 patients with type 2 DM .Patients were collected from the endocrinology 84 outpatient clinic, Kasr El Ainy, Cairo university

Description

Inclusion Criteria:

  • type 2 diabetes patients of both sexes ,20-60 years of age

Exclusion Criteria:

  • Patients with nephropathy due to other causes than diabetes, hepatic, intrinsic renal or coronary artery disease, patients with diabetic neuropathy and retinopathy and hypertensive patient on angiotensin receptor blockers (ARBS) or angiotensin converting enzyme inhibitors (ACEI)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
I
30 patients with type 2 DM with nephropathy
blood sample for detection of plasma Apelin level
II
30 type 2 DM without nephropathy
blood sample for detection of plasma Apelin level
III
30 non DM as control group
blood sample for detection of plasma Apelin level

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
prediction of diabetic nephropathy
Time Frame: 12 weeks
the use of plasma apelin level as a predictor for development of diabetic nephropathy
12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

  • 1. American Diabetes Association (ADA) .2012. Diagnosis of diabetes mellitus.2012 .Diabetes 291 Care;35. suppl S64- S71. doi: 10.2337/dc12-s064 . 292 2. Bonnet F and Cooper ME. 2000. Potential influence of lipids in diabetic nephropathy:insights 293 from experimental data and clinical studies. Diabetes Metab.;26:254-64. 294 3. Chan YH. 2003: Biostatistics102: Quantitative Data - Parametric & Non-parametric Tests. 295 Singapore Med J.;44(8): 391-396. 296 4. Chan YH. 2003: Biostatistics 104: Correlational Analysis. Singapore Med J.;44(12) : 614- 297 619.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

November 30, 2019

Primary Completion (ACTUAL)

March 20, 2020

Study Completion (ACTUAL)

March 29, 2020

Study Registration Dates

First Submitted

May 5, 2020

First Submitted That Met QC Criteria

May 5, 2020

First Posted (ACTUAL)

May 8, 2020

Study Record Updates

Last Update Posted (ACTUAL)

May 11, 2020

Last Update Submitted That Met QC Criteria

May 7, 2020

Last Verified

May 1, 2020

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

no sharing

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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