Consequences of (recurrent) hypoglycaemia on cardiovascular and inflammatory responses in patients with diabetes mellictus type 1, type 2 and healthy volunteers
- Conditions
- sugar disease100146991001265310003216
- Registration Number
- NL-OMON49321
- Lead Sponsor
- Radboud Universitair Medisch Centrum
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 56
Overall inclusion criteria
* Ability to provide written informed consent
* Must be able to speak and read Danish (for Hillerød-site) and Dutch (for
Nijmegen-site)
* Insulin treatment according to basal-bolus insulin regimen (injections or
insulin pump) (except for group 5)
* Body-Mass Index: 19-40 kg/m2
* Age *18 years, * 75 years
* Blood pressure: <140/90 mmHg
* Duration of diabetes > 1 year (except for group 5)
* HbA1c < 100 mmol/mol, Group specific
* Group 1: HbA1c >64 mmol/mol
* Group 2: IAH as assessed by a score of *3 on the modified Clarke
questionnaire, *4 on the Gold questionnaires and a positive score on the
Pedersen-Bjergaard questionnaire.
* Group 3: NAH as assessed by a score of <3 on the modified Clarke
questionnaire, <4 on the Gold questionnaire and a negative score on the
Pedersen-Bjergaard.
* Group 4: Insulin treatment for at least 1 year and age*18 years, * 80 years
* Group 5: HbA1c <42 mmol/mol and age*18 years, * 80 years
Recurrent hypoglycaemia study
Healthy participants
- Ability to provide written informed consent
- Body-Mass Index: 19-40 kg/m2
- Age *16 years, * 75 years
- Blood pressure: <140/90 mmHg
- Severe medical or psychological conditions interfering with the perception of
hypoglycaemia other than IAH such as brain injuries, epilepsy, a major
cardiovascular disease event or anxiety disorders
- Use of immune-modifying drugs or antibiotics
- Treatment with glucose-modifying (other than insulin, SGLT-2 inhibitors and
methformin) agents (e.g. prednisolon)
- Use of anti-depressive drugs
- Pregnancy or breastfeeding or unwillingness to undertake measures for birth
control
- Use of statins (e.g. stop statins >2 weeks before performing blood sampling.
This can be safely done in the context of primary prevention)
- Any event of cardiovascular disease in the past 5 years (e.g. myocardial
infarction, stroke, heart failure, symptomatic peripheral arterial disease)
- Auto-inflammatory or auto-immune diseases
- Any infection in past three months
- Previous vaccination in the past three months
- Laser coagulation for proliferative retinopathy in the past six months
- Proliferative retinopathy
- Diabetic nephropathy as reflected by an albumin-creatinine ratio * 30 mg/gor
an estimated glomerular filtration rate (by MDRD) *60ml/min/1.73m2
- History of pancreatitis (acute or chronic) or pancreatic cancer
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The main study endpoint is the ex vivo production of pro- and anti-inflammatory<br /><br>cytokines and chemokines after ex vivo stimulation of isolated monocytes. </p><br>
- Secondary Outcome Measures
Name Time Method <p>Furthermore we will measure the following parameters in circulating monocytes<br /><br>isolated from the blood:<br /><br>* Monocyte foam cell formation<br /><br>* Distribution of pro- and anti-inflammatory monocyte subsets using FACS<br /><br>(Fluorescence-activated Cell Sorting).<br /><br>* Gene expression of circulating monocytes using mRNA-sequencing assays.<br /><br>* Chromatin accessibility of circulating monocytes using ATAC-seq. (Assay for<br /><br>Transposase-Accessible Chromatin sequencing)<br /><br>* Epigenetic signature of circulating monocytes using DNA-methylation.<br /><br>* Characterization of intracellular metabolism of isolated innate immune cells<br /><br>by ex vivo Sea HorseTM respirometer<br /><br>* Metabolomics<br /><br>* Oxidative stress measured in urine<br /><br>* MicroRNA using PCR on plasma<br /><br>* Examine the changes in cardiac function with echocardiography </p><br>