The main objective of this study is to investigate the effects of a glucagon challenge on hepatic glucose production, abdominal subcutaneous glucose levels in type 2 diabetes patients with and without oral antidiabetics. In addition, endothelial…
ID
Source
Brief title
Condition
- Glucose metabolism disorders (incl diabetes mellitus)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- Hepatic glucose production
- Plasma glucagon, glucose and insulin concentrations
- Subcutaneous glucose concentrations
- Endothelial function
- Ex vivo cytokine responses in whole blood stimulated with LPS & SEB
Secondary outcome
N/A
Background summary
Patients with type 2 diabetes mellitus exhibit several abnormalities in
hormones involved in glucose homeostasis. Elevated glucagon levels play an
important role in the maintenance of increased basal hepatic glucose production
and fasting hyperglycemia, demonstrating the possibility of the glycogenolytic
pathway as therapeutic target.
The glucagon challenge, allowing assessment of hepatic glucose production, can
be used as a tool to assess the anti-glucagonaemic effect of a pharmacological
or dietary intervention. In a previous study we evaluated the glucagon
challenge as a method to investigate the glycogenolytic pathway in healthy
volunteers. In this study we will investigate the glucagon challenge in T2D
patients. In addition, the influence of use of oral antidiabetics on the
response to glucagon challenge will be investigated. This study integrates
investigation of glucose metabolism, endothelial function, and inflammatory
state, and allows investigation of the effect of therapeutic intervention on
these processes.
Study objective
The main objective of this study is to investigate the effects of a glucagon
challenge on hepatic glucose production, abdominal subcutaneous glucose levels
in type 2 diabetes patients with and without oral antidiabetics. In addition,
endothelial function and possible acute effects of hyperglucagonemia on
inflammatory response on a variety of stimuli will be investigated.
Study design
Two-way crossover, intervention study in which subjects will continue (Period
A) or discontinue (Period B) their oral antidiabetic agents two weeks before
the study day.
Study burden and risks
In this study subjects will participate in two occasions of approximately 20
hours. Especially during the glucagon challange the number of measurements is
extensive. Subjects will be asked to stay in bed for six hours. There is a
possibility that the glucagon challenge will lead to hyperglycemia during the
glucagon challenge or a rebound hypoglycemia afterwards. Therefore, glucose
levels will be monitored frequently during and after the challenge.
Furthermore, during the wash-out period of oral antidiabetics, hyperglycemia
may occur. For that reason, subjects will be emphatically instructed about
hyperglycemic symptoms. Please note that based on earlier findings in subjects
with T2D, withdrawal of oral antidiabetic medication is not expected to induce
severe hyperglycaemia, as participating patients are not insulin dependent.
Zernikedreef 10
2333 CL Leiden
Nederland
Zernikedreef 10
2333 CL Leiden
Nederland
Listed location countries
Age
Inclusion criteria
- Type 2 diabetes mellitus controlled by oral antidiabetics (except for PPAR-gamma agents) for at least one year;
- Age 18 to 65 years;
- Males or females (with regular menstrual cycles if premenopausal);
- Able and willing to provide written informed consent.
Exclusion criteria
- Use of insulin or PPAR-gamma agents;
- Glycated hemoglobin (HbA1c) > 8%;
- BMI <= 22 kg/m2 and >= 35 kg/m2;
- Any evidence of cardiovascular, pulmonary, renal, hepatic or other major organ system disease as determined by history, physical examination, and routine laboratory tests;
- Uncontrolled hypertension (systolic blood pressure >= 150 mm Hg or a diastolic blood pressure >= 95 mm Hg);
- Use of medication known to affect glucose homeostasis (except for biguanides and sulphonylureas), anti-inflammatory drugs, non-selective beta blockers such as propranolol, oral anticoagulants, systemic glucocorticoids or other immunosuppressive drugs;
- Use of prescription or over-the-counter drug(s) to promote weight loss;
- Pregnancy or breastfeeding;
- Not able or willing to use an acceptable contraceptive method for study duration for females (hormonal contraceptives, intra-uterine device or condom/pessary);
- Not able and willing to refrain from smoking and/or xanthine use on study day;
- Positive test result for HIV, hepatitis B virus, and/or hepatitis C virus;
- History of alcohol or drug abuse;
- Undergoing or have undergone treatment with an investigational drug, biologic agent or device within 90 days prior to screening
- Blood donation within three months and plasma donation within two weeks of screening.
Design
Recruitment
Medical products/devices used
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 |
|---|---|
| EudraCT | EUCTR2009-014847-36-NL |
| CCMO | NL29286.058.09 |