atriuresis following an acute oral versus IV sodium load in type 2 diabetes patients with and without DKD: an incretin effect?
- Conditions
- Chronic Kidney Disease, T2DM
- Registration Number
- NL-OMON27521
- Lead Sponsor
- one
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 33
Group 1: T2DM patients with DKD
•Male between 40 and 75 years old
•Caucasian
•Average daily sodium intake of 150 mmol/day
•Known with Diabetes Mellitus - type 2, according to the ADA criteria
•One of the following criteria:
oMicroalbuminuria defined as either albuminuria >20 mg/L in a morning urine sample or albuminuria >30 mg/24 hrs collected in a 24-hours urine collection or albumin-to-creatinine ratio >3 mg/mmol in a morning urine sample
oCreatinine clearance <50 ml/min
•Stable renal function (< 6 ml/min per year decline) with or without stable therapy with RAAS inhibiting agents
•HbA1c levels between 6.0 and 10.0% (42-86 mmol/mol) during the 6 months preceding the study
•Hypertension should be controlled, i.e. = 140/90 mmHg.
•Able to provide written informed consent
Group 2: T2DM patients without DKD
•Male between 40 and 75 years old
•Caucasian
•Average daily sodium intake of 150 mmol/day
•Known with Diabetes Mellitus - type 2, according to the ADA criteria
•Without microalbuminuria defined as albumin-to-creatinine ratio < 3 mg/mmol in a morning urine sample.
•Stable renal function (creatinine clearance > 75 ml/min and < 6 ml/min per year decline) with or without stable therapy with RAAS inhibiting agents
•HbA1c levels between 6.0 and 10.0% (42-86 mmol/mol) during the 6 months preceding the study
•Hypertension should be controlled, i.e. = 140/90 mmHg.
•Able to provide written informed consent
Group 3: Healthy subjects
•Male, age between 40 and 75 years of age
•Caucasian
•Average daily sodium intake of 150 mmol/day
•Healthy, as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination (PE) and laboratory tests carried out in the screening visit.
•eGFR > 75 ml/min, without microalbuminuria
•Non-treated office blood pressure = 140/90 mmHg
•Normal glucose tolerance as assessed by a 75-g oral glucose tolerance test (OGTT) according to ADA criteria
•Capable of giving written informed consent and able to comply with the requirements and restrictions listed in the informed consent form
A potential subject of any of the three groups who meets one or more of the following criteria will be excluded from participation in this study:
•An office blood pressure >160/90 mmHg
•A major illness in the past 3 months or any significant chronic medical illness that the Investigator would deem unfavourable for enrolment, including chronic inflammatory diseases
•Current use of the following medication: thiazolidinediones, GLP-1 receptor agonists, DPP-4 inhibitors, oral glucocorticoids, immune suppressants, antimicrobial agents, chemotherapeutics, antipsychotics, tricyclic antidepressants, diuretics and monoamine oxidase inhibitors
•A history of any type of malignancy within the past 5 years with the exception of successfully treated basal cell cancer of the skin
•A history of cardiovascular disease (in the past 6 months) defined as documented coronary artery disease including myocardial infarction, (un-)stable angina pectoris or acute coronary syndrome, percutaneous transluminal coronary angioplasty, coronary artery bypass grafting, cerebrovascular disease including ischemic and hemorrhagic stroke or a subarachnodial bleeding, or peripheral artery disease including aortic aneurysmata
•A history of coagulation disorders
•A history, within 3 years, of drug abuse (including benzodiazepines, opioids, amphetamine, cocaine, THC, methamphetamine)
•A history of alcoholism and/or is drinking more than 3 units of alcohol per day. Alcoholism is defined as an average weekly intake of >21 units for males. One unit is equivalent to 8 g of alcohol: a half-pint (~240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits
•Difficulty in donating blood or limited accessibility of a vein in left and right arm
•Subject has donated blood in last 3 months
•Use of tobacco products
•Any other issue that, in the opinion of the Investigator, could be harmful to the subject or compromise interpretation of the data
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method To assess the timed effects of a matched acute oral sodium load (in the absence or presence of GLP-1 receptor agonist) or an acute intravenous sodium load in healthy individuals and T2DM patients with/without renal impairment on urinary sodium excretion after 24h, determined by the cumulative sodium balance.
- Secondary Outcome Measures
Name Time Method The most important secondary efficacy parameters include the effect of an acute oral versus intravenous sodium load on:<br>•Variation in blood pressure, determined by a non-invasive, automated, beat-to-beat blood pressure monitor (Nexfin®) measurements and 24h ABPM device <br>•Differences in total and fractional urinary sodium excretion after 2,4 and 6 hours<br>•Differences in plasma, urine and systemic hemodynamic markers<br>