None listed
Conditions
Brief summary
Cells release diverse types of small membrane vesicles called exosomes and microvesicles and collectively are known as extracellular vesicles. Exosomes have an endocytic origin and are released upon multivesicular body fusion with the plasma membrane. Microvesicles are released from the cell surface, and are a rich source of non-conventionally secreted proteins lacking a conventional signal peptide, and thus not secreted by the classical secretory pathways. Both types of extracellular vesicles play major roles in intercellular communication by serving as vehicles for transfer between cells of membrane and cytosolic proteins, lipids and RNA. These extracellular vesicles are fragments of virtually all cell types (mainly endothelium, platelets, leukocytes) released into all types of body fluids during cell apoptosis or cell activation. They are characterised by an integral plasma membrane containing a subset of proteins, lipids and nucleic acids that are derived from the cell from which they originated. Extracellular vesicles may have important roles in intercellular communication, both locally and systemically, by transferring their contents between cells. Endothelial microvesicles play key roles in coagulation, inflammation and angiogenesis and can be quantified by flow cytometry using specific endothelial markers. Diabetic nephropathy is a prevalent major microvascular complication defined by functional, structural and clinical abnormalities of the kidney that is caused by diabetes. This complication has become the most frequent cause of end-stage renal disease. Additionally, it is strongly associated with cardiovascular morbidity and mortality. Diagnosis is usually based on the measurement of high levels of albumin in the urine and evidence of reduced kidney function.
Interventions
The study involves a screening visit to establish eligibility to the study based on presence or absence of diabetes status, renal impairment and macroalbuminia; and then a follow-up visit for blood and urine collection for isolation and characterisation of endothelial and urinary extracellular vesicles.
Comparisons will be made between three groups:
group 1 - type 2 diabetes, renal impairment [eGRF <60 ml/min] and no macroalbuminuria; group 2 - type 2 diabetes, renal impairment [eGFR <60 ml/m
The study involves a screening visit to establish eligibility to the study based on presence or absence of diabetes status, renal impairment and macroalbuminia; and then a follow-up visit for blood and urine collection for isolation and characterisation of endothelial and urinary extracellular vesicles. Comparisons will be made between three groups: group 1 - type 2 diabetes, renal impairment [eGRF <60 ml/min] and no macroalbuminuria; group 2 - type 2 diabetes, renal impairment [eGFR <60 ml/min[ and macroalbuminuria group 3 - no type 2 diabetes, no renal impairment [eGFR = to or > 60 ml/min] and no macroalbuminuria
Sponsors
Baker Heart and Diabetes Institute
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
(i) type 2 diabetes cohort 1. age 18-75 years 2. type 2 diabetes mellitus with macroalbuminuria (urinary albumin:creatine = to or > 30mg/mmol and renal impairment (eGFR < 60 ml/min) without albuminuria (urinary albumin:creatine < 3mg/mmol) but with renal impairment (eGFR < 60 ml/min) (ii) healthy cohort 1. age 18-75 years 2. no type 2 diabetes without albuminuria (urinary albumin:creatine < 3mg/mmol) but without renal impairment (eGFR = to or > 60 ml/min)
Exclusion criteria
(i) type 2 diabetes cohort 1. pregnant females 2. known renal/renal tract disease other than diabetic nephropathy (ii) healthy cohort 1. presence of any diabetes including history of gestational diabetes mellitus 2. presence renal impairment (eGFR < 60 ml/min) 3. known renal/renal tract disease other than diabetic nephropathy 4. pregnant females
Outcome results
None listed