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ID
Source
Brief title
Health condition
Accelerated vascular ageing
Type 2 diabetes
Diabetic nephropathy/macroalbuminuria
Sponsors and support
Intervention
Outcome measures
Primary outcome
To investigate whether arterial microcalcification (18F-NaF-PET detected) and macrocalcification (CT detected) are increased in patients with T2D with preserved renal function who have macroalbuminuria as compared to patients with normoalbuminuria.
Secondary outcome
1. To investigate whether arterial microcalcification (18F-NaF-PET detected) and macrocalcification (CT detected) are associated with vascular stiffness (assessed by PWV).
2. To investigate whether arterial microcalcification (18F-NaF-PET detected) and macrocalcification (CT detected) are associated with markers of the metabolic syndrome, including adipose tissue volumes (visceral and subcutaneous), adipokines, insulin resistance index (HOMA-IR), and clinical components (HbA1c, fasting glucose, lipid metabolism, and blood pressure).
3. To investigate whether arterial microcalcification (18F-NaF-PET detected) and macrocalcification (CT detected) are associated with markers of the calcium phosphate metabolism
4. To investigate which of the above mentioned factors (i.e. macroalbuminuria, metabolic syndrome, calcium phosphate metabolism, and kidney function) are independent determinants of arterial microcalcification (18F-NaF-PET detected) and macrocalcification (CT detected).
Background summary
Type 2 diabetes mellitus (T2D) is associated with a strong increase in cardiovascular risk, which is a consequence of accelerated vascular ageing. This process is hallmarked by vascular remodeling, chronic low-grade inflammation, calcification, and increased vascular stiffness. Vascular ageing is more pronounced in T2D patients who are also suffering from chronic kidney disease (CKD). But, the direct causality and mechanisms underpinning relationships between kidney function and accelerated vascular ageing is still incomplete. Macroalbuminuria could be a proxy for early changes to the vascular wall in T2D patients and therefore could be an early clinical indication of accelerated vascular ageing. Therefore, there is a clinical need to early identify those patients at risk and to explore new pathways on which new interventions can be developed.
In particular T2D patients are accompanied with obesity, and whereas visceral adipose tissue (VAT) is playing a central role in causing insulin resistance and metabolic syndrome.
To study whether vascular calcification in T2D subjects with or without macroalbuminuria is more prominent, the whole body, and therefore vasculature, will be imaged with 18F-NaF PET. With this nuclear tracer, microcalcification and therefore vascular ageing, will be imaged.
non-invasively assessed as aortic pulse wave velocity (PWV) will be
performed. Also, venapuncture and a positron emission tomography (PET)/computed
tomography (CT) scan will be performed with nuclear tracer 18fluor-sodiumfloride (18F-NaF).
Study objective
The hypothesis is that macroalbuminuria could be a proxy for early changes to the vascular wall in T2D patients and therefore could be an early clinical indication of accelerated vascular ageing. Therefore, there is a clinical need to early identify those patients at risk and to explore new pathways on which new interventions can be developed.
Study design
T0= informed consent
T1 = venapuncture, PWV measurement, 18F-NaF PET/CT scan
Intervention
Not applicable.
Inclusion criteria
Inclusion criteria T2D patients:
• Men and women, age above 18 years
• Written informed consent
• eGFR above 60
• Fulfils ADA criteria for diabetes
o Fasting plasma glucose ≥ 7.0 mmol/l OR
o Random plasma glucose ≥ 11.1 mmol/l OR
o HbA1C ≥ 6,5%
Inclusion criteria healthy controls:
• Men and women, age above 18 years
• Written informed consent
• eGFR above 60
Exclusion criteria
Exclusion criteria T2D patients:
• Type 1 diabetes
• Clinically significant liver disease
• Other causes for macroalbuminuria than nephropathy
• Previous cardiovascular disease, defined as stable coronary artery disease or acute coronary syndrome, stroke or transient ischemic attack, peripheral artery disease
• Known atrial fibrillation
• Patients who are mentally incompetent and cannot sign a Patient Informed Consent
• Claustrophobia
• Pregnancy or breastfeeding women.
• Current active bone malignancy or in the previous 6 months
• Disorders affecting bone metabolism, e.g. hyperparathyroidism, Paget's disease
• Using vitamin K antagonists
• Using bisphosphonates, calcium or vitamin D
Exclusion criteria healthy controls:
• Type 1 or 2 diabetes
• Micro- or macroalbuminuria
• Clinically significant liver disease
• Previous cardiovascular disease, defined as stable coronary artery disease or acute coronary syndrome, stroke or transient ischemic attack, peripheral artery disease
• Known atrial fibrillation
• Patients who are mentally incompetent and cannot sign a Patient Informed Consent
• Claustrophobia
• Pregnancy or breastfeeding women.
• Current active bone malignancy or in the previous 6 months
• Disorders affecting bone metabolism, e.g. hyperparathyroidism, Paget's disease
• Using vitamin K antagonists
• Using bisphosphonates, calcium or vitamin D
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| NTR-new | NL7444 |
| NTR-old | NTR7686 |
| Other | Research register UMCG : 201800548 |