The main purpose of this study is to evaluate the effect of glycemic control on microvascular endothelial function in type 2 diabetes mellitus.
ID
Source
Brief title
Condition
- Glucose metabolism disorders (incl diabetes mellitus)
- Arteriosclerosis, stenosis, vascular insufficiency and necrosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To assess the relationship between glycemic control and endothelial function on
the microvascular level in diabetes mellitus type 2 (NO, ET-1, Ang II).
Secondary outcome
To assess underlying mechanisms involved in microvascular endothelial
dysfunction and possibly its improvement
Background summary
Diabetes-associated atherosclerosis is a major clinical problem. Diabetic
patients have a two- to fourfold increased incidence of coronary artery disease
and stroke and a tenfold increased incidence of lower extremity vascular
disease (1,2). Not only macrovascular, but also microvascular dysfunction is a
considerable cause of morbidity and mortality in diabetic subjects.
Microvascular dysfunction, besides leading to nephropathy and retinopathy, also
affects the microcirculation of the myocardium (3,4). Diabetes mellitus is
associated with a diminished coronary flow reserve and impaired cardiac
ischemic preconditioning (3,4). Intervention studies have shown that improved
glycemic control reduces the risk of especially microvascular complications in
diabetes (5,6).
With regard to the pathogenesis of vascular disease in diabetes endothelial
dysfunction is considered to be a critical initial event (7,8). This
endothelial dysfunction might be caused by an adverse effect of hyperglycemia
(glucotoxicity) on endothelial vascular function. However, elevated blood
pressure and dyslipidemia may be involved as well.
Study objective
The main purpose of this study is to evaluate the effect of glycemic control on
microvascular endothelial function in type 2 diabetes mellitus.
Study design
This is a prospective, non-randomized, single-center study which will evaluate
the ability of glycemic control to reverse or improve endothelium-dependent and
endothelium-independent microvascular function in patients with poorly
controlled diabetes mellitus type 2.
Study burden and risks
to undergo two skin biopsies: one at baseline and the second after 12 weeks
improved glycemic control. At the same time-points serum will be collected.
The biopsies will be used for isolation of microvascular resistance vessels.
The isolated vessels will be used in a standard microvascular functional assay
to study NO-dependent and -independent vasodilatation and endothelin-1 (ET-1)
and angiotensin II (Ang II)-induced vasoconstriction. The collected serum will
be used for experiments with cultured endothelial cells.
's Gravendijkwal 230
3015 CE
Nederland
's Gravendijkwal 230
3015 CE
Nederland
Listed location countries
Age
Inclusion criteria
Male or female type 2 diabetic patients; Documented GlycoHb > 8.5% for at least 6 weeks; Age 30-60 years; BMI 25-35 kg/m2; LDL-cholesterol concentration < 3.0 mmol/l; Blood pressure < 140/90 mmHg
Exclusion criteria
(Clinical or laboratory) evidence of atherosclerosis or cardiovascular disease; Other systemic disorder with likelihood of (micro)vascular involvement; diabetic nephropathy (albuminuria > 300 mg per day); Kidney disease other than diabetes (serum creatinine > 120 µmol/l); Alcohol abuse; Unwillingness to give written informed consent; Condition that precludes follow-up; Oral anticoagulant therapy or bleeding diathesis
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 |
|---|---|
| CCMO | NL22134.078.08 |