Primary Objective:To investigate whether arterial microcalcification (18F-NaF-PET detected) and macrocalcification (CT detected) are increased in patients with T2D who have macroalbuminuria as compared to patients with normoalbuminuria.Secondary…
ID
Source
Brief title
Condition
- Diabetic complications
- Nephropathies
- Arteriosclerosis, stenosis, vascular insufficiency and necrosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Vascular 18F-NaF uptake (proxy for vascular macrocalcification) is quantified
by using target-to-background ratios (TBRs).
Secondary outcome
* CT assessed arterial macrocalcification using measurement of hounds field
units.
* Albuminuria assessed in 2 separate 24-hours urine samples
* Carotid-femoral PWV assessed arterial stiffness
* C-reactive protein (CRP) assessed systemic inflammation
* VAT volume assessed with CT
* SAT volume assessed with CT
* Body weight, length, BMI
* Adipokines: adiponectin and leptin
* Glycemic indices: HbA1c, insulin, HOMA-IR, fasting glucose
* Lipid parameters: total cholesterol, LDL-cholesterol, HDL-cholesterol,
triglycerides, apo-B, PCSK9 levels
* Systolic and diastolic blood pressure
* Kidney function and degree of albuminuria assessed using 24-hours urine
creatinine clearance and albumin-to-creatinine ratio (ACR)
* Plasma calcium phosphate metabolism plasma markers, including calcium,
albumin, phosphate, vitamin D3, fetuin A, klotho, fibroblast growth factor 23,
parathormone, serum calcification propensity score (T50).
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. Expected is that
vascular ageing is more pronounced in T2D patients who are also suffering from
macroalbuminuria. 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. VAT is distributed through the
abdominal cavity and is present surrounding the abdominal organs and the
vasculature.
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. The intensity of vascular
calcification on PET will be compared with CT assessed macrocalcification and
vascular ageing markers such as vascular stiffness and calcium phosphate
metabolism. Besides that, the role of adipose tissue will be studied. Adipose
tissue volumes of VAT and subcutaneous adipose tissue (SAT) will be ranked and
compared to vascular calcification. This clinical project will supply insight
information of the additional risk of macroalbuminuria in the accelerated
vascular ageing of T2D patients.
Study objective
Primary Objective:
To investigate whether arterial microcalcification (18F-NaF-PET detected) and
macrocalcification (CT detected) are increased in patients with T2D who have
macroalbuminuria as compared to patients with normoalbuminuria.
Secondary Objectives:
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 components of the
metabolic syndrome, including adipose tissue volumes (visceral and
subcutaneous), adipokines, insulin resistance index (HOMA-IR), and 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 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).
Study design
Single center, cross-sectional, observational, case-control study in het UMCG
Study burden and risks
Small, slight radiationload and bruising of venapuncture.
Hanzeplein 1
Groningen 9700RB
NL
Hanzeplein 1
Groningen 9700RB
NL
Listed location countries
Age
Inclusion criteria
Inclusion criteria T2D patients:
* Men and women, age above 18 years
* Written informed consent
* Using RAAS inhibitors
* 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 ml/min/175m2 (CKD-EPI formula)
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
* 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
* Systolic blood pressure > 200 mmHg,
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
* 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
* Systolic blood pressure > 200 mmHg
Design
Recruitment
Medical products/devices used
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 |
|---|---|
| EudraCT | EUCTR2018-002347-28-NL |
| CCMO | NL66049.042.18 |