Arterial Hypertension, Body Weight Changes, Diabetes Mellitus, Type 2
Conditions
Keywords
Sodium-Glucose Transporter 2 Inhibitors, Renin-Angiotensin System, Vasopressin, Natriuretic Peptide, Brain, Blood Pressure, Body Composition, Diabetes Mellitus, Type 2
Brief summary
Subjects treated with Canagliflozin, Dapagliflozin and Empagliflozin obtained improvement on blood pressure values, body weight and cardiovascular mortality but pathophysiological explanations of these effects are not yet known.
Detailed description
The pathophysiological explanations of the cardiovascular improvement of patients treated with SGLT2i are not yet known: osmotic diuresis and natriuresis, direct effects of weight reduction, increased in nitric oxide release, oxidative stress reduction, local renin-angiotensin-aldosterone system (RAAS) inhibition are the supposed mechanism. In the Literature the diuretic effect of SGLT2i therapy seems to be even stronger than thiazide or thiazide-like drugs. However, it is not defined the role of SGLT2i on antidiuretic function (RAAS, brain natriuretic peptide-BNP and antidiuretic hormone-ADH). Defining this relation could be important for: * knowing effect of SGLT2i on RAAS (drugs interferences are important particularly during case detection of primary aldosteronism); * discovering antidiuretic response to SGLT2i treatment and interactions between RAAS, BNP and ADH on the volume improvement induced by this new antidiabetic drugs. In addition the aim of the study is to define effect of treatment on blood pressure and body composition.
Interventions
DRUGSGLT2 inhibitor
Start of the treatment with SGLT2i.
Sponsors
University of Turin, Italy
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* diabetic patients; * clinical indication to SGLT2i therapy.
Exclusion criteria
* signs and symptoms of poor glycemic control (polydipsia, polyuria and weight loss); * HbA1c \>10% or 86 mmol/mol; * Body Mass Index (BMI) \> 40 Kg/m2; * personal history of primary and secondary aldosteronism; * personal history of heart failure; * personal history of acute kidney injury; * personal history of chronic kidney disease; * personal history of liver cirrhosis; * personal history of protein-wasting syndrome; * personal history of renin secreting tumor; * personal history of diabetes insipidus; * personal history of syndrome of inappropriate antidiuresis (SIAD); * personal history of hypocortisolism and hypercortisolism; * therapy with Angiotensin Converting Enzyme inhibitors; * therapy with Angiotensin Receptor Blockers; * therapy with renin inhibitors; * therapy with beta-blockers; * therapy with alfa2-receptors agonists; * therapy with Calcium Channel Blockers; * therapy with diuretics; * therapy with mineralocorticoid receptor antagonists; * therapy with non steroidal and steroidal anti-inflammatory drugs.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Long term changes from baseline of renin-angiotensin-aldosterone system parameters | 90 days after starting SGLT2i therapy | Blood samples for plasma renin activity (ng/mL/h) and aldosterone (pg/mL) |
| Changes from baseline of antidiuretic function parameters (sodium balance) | Before starting SGLT2i and 30 days the starting SGLT2i therapy | Samples for serum sodium (mmol/L). |
| Changes from baseline of antidiuretic function parameters (potassium balance) | Before starting SGLT2i and 30 days the starting SGLT2i therapy | Samples for serum potassium (mmol/L). |
| Changes from baseline of renin-angiotensin-aldosterone system parameters (renin) | Before starting SGLT2i and 30 days the starting SGLT2i therapy | Blood samples for plasma renin activity (ng/mL/h). |
| Long term changes from baseline of renin-angiotensin-aldosterone system parameters aldosterone) | Before starting SGLT2i and 30 days the starting SGLT2i therapy | Blood samples for aldosterone (pg/mL). |
| Changes from baseline of antidiuretic function parameters (BNP) | Before starting SGLT2i and 30 days the starting SGLT2i therapy | Blood samples for BNP (pg/mL). |
| Changes from baseline of antidiuretic function parameters (vasopressin) | Before starting SGLT2i and 30 days the starting SGLT2i therapy | Blood samples for Copeptin (pmol/L). |
| Changes from baseline of antidiuretic function parameters (osmolality) | Before starting SGLT2i and 30 days the starting SGLT2i therapy | Samples for plasma osmolality (mOsm/Kg). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes from baseline of body composition | Before starting SGLT2i and 90 days after the starting | Variation of parameters of Bioelectrical Impedance Analysis (BIA) |
| Changes in basal glicemic control | Before starting SGLT2i and 90 days after the starting | Blood samples for basal glucose (mg/dL). |
| Changes in long term glicemic control | Before starting SGLT2i and 90 days after the starting | Blood samples for Glycated albumin (mmol/mol). |
| Changes from baseline of blood pressure values (ABPM) | Before starting SGLT2i and 90 days after the starting | Mean Systolic and Diastolic Blood Pressure (mmHg) |
Countries
Italy
Contacts
Primary ContactMauro M Maccario, MD
Backup ContactMirko M Parasiliti Caprino, MD, PhD
Outcome results
None listed