We hypothesize that impaired insulin uptake into skeletal muscle interstitium (thus decreased transendothelial transport of insulin) is impaired in patients with type 2 diabetes mellitus. This hypothesis will be addressed in the present study.
ID
Source
Brief title
Condition
- Glucose metabolism disorders (incl diabetes mellitus)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary objective: Is insulin uptake impaired in T2DM patients as compared to
non-diabetic individuals, both in the fasted state and during postprandial
hyperinsulinemia? (Specific parameters that will be calculated are explained in
the study protocol page 7).
Secondary outcome
Secondary objectives: what are determinants of insulin uptake in T2DM patients
and in non-diabetic controls (i.e. metabolic parameters known to affect insulin
sensitivity, and hemodynamic parameters)? Are glucose uptake and insulin uptake
differentially related in T2DM patients as compared to non-diabetics? Does
insulin uptake associate with measures of glycemic control such as fasting or
postprandial glucose levels and A1C?
Background summary
Background: Impaired glucose uptake by skeletal muscle is a hallmark of type 2
diabetes mellitus (T2DM) and a significant contributor of postprandial
hyperglycemia. Glucose uptake is facilitated by insulin, which promotes glucose
transport into skeletal muscle following binding to its insulin receptor on
skeletal muscle membrane. However, insulin affects endothelial cells resulting
in increased blood flow and recruitment of capillaries, thereby increasing
surface for nutrient exchange. There is evidence that insulin uptake into
skeletal muscle interstitium is of physiological relevance, however, it is
unclear whether this process is impaired in T2DM. We hypothesize that impaired
insulin uptake into skeletal muscle interstitium (thus decreased
transendothelial transport of insulin) is impaired in patients with type 2
diabetes mellitus.
Study objective
We hypothesize that impaired insulin uptake into skeletal muscle interstitium
(thus decreased transendothelial transport of insulin) is impaired in patients
with type 2 diabetes mellitus. This hypothesis will be addressed in the present
study.
Study design
Methodology: A prospective, single center study in T2DM patients (n=50) and
non-diabetic individuals (n=50) will be performed. During elective coronary
angiography (CAG), arteriovenous (AV) balances of glucose and insulin will be
measured using the forearm balance method. In each group, 25 patients will be
measured in the fasting state, whereas 25 patients will be measured in the
postprandial state, i.e. 1 hour following ingestion of an oral glucose
tolerance test. Hormones and metabolites of interest will be obtained from
blood sampling. Hemodynamic parameters will be derived from doppler/ultra sound
measurements (limb blood flow), applanation tonometry (arterial stiffness),
continuous non-invasive arterial blood pressure measurements (cardiac index,
peripheral resistance, cardiac output and stroke volume) and heart rate
variability (autonomic nervous system balance).
Study burden and risks
There are no risks to participate in this study (see above)
Boerhaavelaan 22
Haarlem 2035RC
NL
Boerhaavelaan 22
Haarlem 2035RC
NL
Listed location countries
Age
Inclusion criteria
Inclusion criteria for all participants:
- written informed consent
- hemodynamically stable with a systolic blood pressure > 100 mmHg
Inclusion criteria for non-diabetic individuals:
- 30 years * age * 80 years (extremes included)
- fasting glucose level of < 7.0 mmol/L and HbA1C < 6.5% (<= < 48 mmol/mol)
Inclusion criteria for T2DM patients:
- 30 years * age * 80 years (extremes included)
- fasting glucose level of > 7.0 mmol/L, or HbA1C > 6.5 (<= > 48 mmol/mol) or known T2DM
Exclusion criteria
Exclusion criteria for all participants:
- ongoing myocardial infarction as determined from elevated cardiac markers
- participation in an investigational trial within 90 days prior to present study
- donation of blood (> 100 mL) within 90 days prior to present study
- serious mental impairment or language problems i.e. preventing to understand the study protocol/aim
- Use or recent use (within 3 months of study participation) of oral glucocorticoids
Exclusion criteria for non-diabetic individuals:
- known T2DM/use of glucose-lowering medication
Exclusion criteria for T2DM patients:
- treatment with insulin preparations
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 | NL45266.094.13 |