Studying the GLP-1 response to a 75 grams oraal glucose load in 10 ZA and 10 WE healthy lean males to see whether GLP-1 is involved in the pathogenesis of T2D in ZA. 1. To investigate whether young lean healthy SA males without a family history of…
ID
Source
Brief title
Condition
- Glucose metabolism disorders (incl diabetes mellitus)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- AUC GLP-1 in SA versus WE
- peak GLP-1 level in SA versus WE
- time to peak GLP-1 in SA versus WE
- iinsulin sensitivity by Matsuda-index in SA versus WE
Secondary outcome
- does peak GLP-1 in plasma precede the peak of plasma insulin?
- insulin sensitivity by Matsuda-index in SA versus WE
- is metabolic flexibility in SA impaired (switch from glucose to lipid
metabolism and vice versa)
Background summary
People of South-Asian (SA) descent, such as the Surinamese-Hindostani
population in the Netherlands (especially the Hague) have a greater risk for
type 2 diabetes (T2D) than people of Western-European (white) decent. In
addition, T2D develops at younger age and lower BMI than in WE. Furthermore,
the disease is accompanied by more and grave cardiovasculair complications in
SA. The underlying cause for this increased risk is still not completely
elucidated.
In a previous investigation we found that healthy lean young men of SA descent
had higher GLP-1 levels following an oral glucose load as compared to matched
WE.
GLP-1 is a hormone secreted by the gut that has positive influences on insulin
secretion and insulin sensitivity and that delays gastric emptying and
decreases appetite. As such it improves glucose metabolisme and induces weight
loss. Therapies have been developed that increase plasma GLP-1 levels and by
that improve glucose levels and lead to some (average 3-4 kg) bodyweight loss.
In the above mentioned study (Metabolism 2014 Feb;63(2):226-32) we investigated
healthy lean men with a positive family history for T2D. It might very well be
possible however that because of that, the SA already had a little insulin
resistance and that the increased GLP-1 levels were a compensatory response.
Hence we would now like to study young lean healthy men of SA and WE descent
WITHOUT first degree relatives. If then, GLP-1 levels are still higher in SA it
is plausible that GLP-1 plays a role in the pathogenesis of T2D in SA.
We will then proceed by investigating whether the increased levels are due to
insulin resistance or incretin resistance (OGTT versus isoglycemic [to the
OGTT], IVGTT) and the glucose-lowering effect of GLP-1 in SA. In addition, we
will study the GLP-1 response in different age and different insulin resistant
populations. Furthermore it is worth investigating whether or not GLP-1
suppletion is a worthwhile preventive strategy in SA.
Indeed, in mouse models exogenous GLP-1 also has beneficial effects on the
endothelium. In addition, intracerbroventricular injection of GLP-1 in mice
activated brown fat activity (BAT). BAT burns triglycerides and glucose and is
importantly involved in energy homeostasis. Activating BAT is currently under
investigation for the treatment and prevention of obesity and associated
metabolic disorders.
Hence if, (shortage of) GLP-1 is involved in the pathogenesis of insulin
resistance/T2D in SA we will certainly also investigate the effect of supplying
GLP-1 in vascular function and BAT activation.
Study objective
Studying the GLP-1 response to a 75 grams oraal glucose load in 10 ZA and 10 WE
healthy lean males to see whether GLP-1 is involved in the pathogenesis of T2D
in ZA.
1. To investigate whether young lean healthy SA males without a family history
of
T2D also have increased GLP-1 levels following an OGTT
2. To investigate whether the GLP-1 peak indeed precedes the start of the
insulin
secretion
3. To investigate whether or not young lean healthy SA males without a
family history of T2D already have impaired metabolic flexibility
Study design
non-randomised observational controlled study
Study burden and risks
Procedure:
Medical history and physical examination: bodyweight, length, waist
circumference, fat mass by BIA.
Indirect calorimetry before and 30 min after ingestion of oral glucose solution
Intraveneus catheter for blood drawings during 75 grams OGTT of 210 minutes
time frame: 5 hours
Burden: overnight fast, blood drawing from intravenous catheter during study
day.
Risks: none
Albinusdreef 2
Leiden 2333ZA
NL
Albinusdreef 2
Leiden 2333ZA
NL
Listed location countries
Age
Inclusion criteria
- 10 Male healthy volunteers of South Asian descent and 10 male healthy volunteers of western- european descent, born in the Netherlands
- Age > 18 years and * 25 years
- BMI > 20 kg/m2 and < 25 kg/m2
Exclusion criteria
- A first degree (parent or sibling) relative with T2D
- Diabetes mellitus as defined by ADA criteria{2014 12 /id}
- Any significant chronic disease
- Renal, hepatic or endocrine disease
- Clinical cardiovascular disease, including complaints of angina pectoris or intermittend claudicatio
- Smoking
- Use of medication known to influence glucose and/or lipid metabolism
- Recent weight changes or attempts to loose weight (> 3 kg weight gain or loss, within the last 3 months)
- Difficulties to insert an intravenous catheter
- Recent blood donation (within the last 3 months)
- Recent participation in other research projects (within the last 3 months), participation in 2 or more projects in one year
Design
Recruitment
metc-ldd@lumc.nl
Followed up by the following (possibly more current) registration
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Other (possibly less up-to-date) registrations in this register
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In other registers
| Register | ID |
|---|---|
| CCMO | NL49651.058.14 |
| Other | TC 2473 |