Determining Serum and Urinary Levels of miRNA 192 and miRNA 25 in Patients With and Without Type 2 Diabetes.

Association Between Urinary and Serum Levels of miRNA 192 and miRNA 25 and Glomerular Filtration and Albuminuria in Patients With and Without Type 2 Diabetes.

Diabetes kidney disease (DKD) is the leading cause of end stage renal disease (ESRD) in western countries and its incidence is worryingly increasing worldwide. Cardiovascular disease shows a continuous relationship with declining of renal function in type 2 diabetes patients. Moreover, there is a strong evidence of all-cause mortality risk excess even in patients with early stages kidney disease.

MicroRNA (miRNA) are small non-coding RNA molecules, containing 21-25 nucleotides, that modulate post-transcriptional gene expressions. In the past years many human miRNAs involved in the pathogenesis of renal disease have been discovered, such as miR-192, miR-194, miR-204 and miR-25. Among these, miR-192 and miR-25, are receiving greater attention while it seems that they play a role in glomerulosclerosis and renal fibrosis. However too few data are available in large publish trials among patients with renal impairment and the role of serum and urinary levels of miR-192 and miR-25 in people with preserved renal function remain unclear.

To evaluate the association between serum and urinary expression of miR-192 and miR-25 and renal function (according to different extent of renal impairment) in patients with or without type 2 diabetes.

Study Overview

• Status: Completed
• Conditions: Diabetic Kidney Disease; Type2 Diabetes
• Intervention / Treatment: Other: no interventions required.

Detailed Description

The day of the study patients undergo a routine clinical evaluation. Whole blood samples are collected from an antecubital vein to assess serum/plasma aliquots of 200 μl each (frozen at -80°C until required for quantitation) for evaluation of biochemical parameters (fasting glucose, HbA1c, lipid profile, serum creatinine, uric acid, electrolytes, liver function enzymes, albumin) and determination of serum miR-192 and miR-25.

Two urine samples will be also collected to assess aliquots of 200 μl each (frozen at -80°C until required for quantitation) for determination of albumin:creatinine ratio and urine expression of miR-192 and miR-25.

• Study Type: Observational
• Enrollment (Actual): 300

Contacts and Locations

Study Locations

• Italy
  • Pisa, Italy, 56125
    • University of Pisa

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The study will consecutively enrolled 300 patients (200 patients with type 2 diabetes and 100 patients without diabetes) among those referring to the Departiment of Diabetes and Metabolic disease, Santa Chiara Hospital, Pisa.

Description

Inclusion Criteria (Group 1, Diabetic patients):

• age ≥ 18 years and ≤ 75 years
• male or female patients with type 2 diabetes treated with life style modification only or any OAD or insulin
• BMI ≥ 20 e ≤ 40 Kg/m2
• patients able to consent

Exclusion Criteria (Group 1, Diabetic patients):

• personal history of current or previous cancer or chemotherapy in the past 5 years
• personal history of alcohol and/or drugs abuse in the previous 3 months
• pregnancy

Inclusion Criteria (Group 2, Non-diabetic patients):

• age ≥ 18 years and ≤ 75 years
• BMI ≥ 20 e ≤ 40 Kg/m2
• patients able to consent

Exclusion Criteria (Group 2, Non-diabetic patients):

• diagnosis of type 2 or type 1 diabetes
• personal history of current or previous cancer or chemotherapy in the past 5 years
• personal history of alcohol and/or drugs abuse in the previous 3 months
• pregnancy

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients with Type2 Diabetes; 200 patients with type 2 diabetes consecutively enrolled among those referring to our Diabetes outpatient clinic.	Other: no interventions required.; The study does not require any interventions.
Patients without Type2 Diabetes; 100 patients without diabetes among those referring to our outpatient clinic most of them affected by hypercholesterolemia, obesity or CV disease.	Other: no interventions required.; The study does not require any interventions.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum expression of miR-192	Levels of miR-192 will be assessed on serum and will be related to glomerular filtration rate and presence or absence of albuminuria (expressed as albumine:creatinine ratio).	Each patients will be assessed at baseline.
Serum expression of miR-25	Levels of miR-25 will be assessed on serum and will be related to glomerular filtration rate and presence or absence of albuminuria (expressed as albumine:creatinine ratio).	Each patients will be assessed at baseline.
Urine expression of miR-192	Levels of miR-192 will be assessed on urine and will be related to glomerular filtration rate and presence or absence of albuminuria (expressed as albumine:creatinine ratio).	Each patients will be assessed at baseline.
Urine expression of miR-25	Levels of miR-25 will be assessed on urine and will be related to glomerular filtration rate and presence or absence of albuminuria (expressed as albumine:creatinine ratio).	Each patients will be assessed at baseline.

Collaborators and Investigators

• Sponsor: University of Pisa

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 1, 2018
• Primary Completion (ACTUAL): December 31, 2019
• Study Completion (ACTUAL): March 1, 2020

Study Registration Dates

• First Submitted: November 21, 2019
• First Submitted That Met QC Criteria: November 21, 2019
• First Posted (ACTUAL): November 25, 2019

Study Record Updates

• Last Update Posted (ACTUAL): June 5, 2020
• Last Update Submitted That Met QC Criteria: June 4, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: DKD; miRNA-25; miRNA-192
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Urologic Diseases; Endocrine System Diseases; Diabetes Complications; Diabetes Mellitus; Diabetes Mellitus, Type 2; Kidney Diseases; Diabetic Nephropathies
• Other Study ID Numbers: AS0004

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No