Diabetes Mellitus, Gastroparesis
Conditions
Keywords
gastric emptying, glycemia, appetite, incretin hormones
Brief summary
The purpose of this study is to evaluate the acute effects of sitagliptin on postprandial glycemia, incretin hormones and blood pressure, and the relationship to gastric emptying, after a mashed potato meal in patients with type 2 diabetes.
Detailed description
The purpose of this study is to (i) evaluate the acute effects of the dipeptidyl peptidase-4 (DPP-4) inhibitor, sitagliptin (100mg once daily for two days), on gastric emptying, postprandial plasma glucose, insulin, glucagon and 'incretin' hormones (ie. glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP)), blood pressure and heart rate after a high carbohydrate meal, and (ii) to determine whether the magnitude of the effects of sitagliptin on postprandial glycaemia and blood pressure is related to the rate of gastric emptying, in patients with type 2 diabetes. The rate of entry of carbohydrate into the small intestine is especially important in patients with diabetes mellitus. Sitagliptin is an orally administered inhibitor of dipeptidyl-peptidase-IV (DPP-IV), the enzyme responsible for the degradation of GLP-1. It is hypothesized that sitagliptin will increase the GLP-1 response to, and thereby slow gastric emptying and diminish the glycaemic and blood pressure response to, a carbohydrate-containing meal. Twenty healthy subjects (male and female) will be studied. Each subject will be studied on two occasions following treatment for 2 days with sitagliptin (100mg once daily) or matching placebo in a randomized, double blind, crossover design. Measurements of gastric emptying, intragastric meal distribution, blood glucose concentrations, gut hormones, blood pressure, splanchnic flow and appetite will be measured for 4 hours following ingestion of a mashed potato meal.
Interventions
DRUGSitagliptin
100mg mane for 2 days
DRUGPlacebo
Inactive drug (Placebo)
Sponsors
Royal Adelaide Hospital
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Type 2 diabetes (World Health Organisation (WHO) criteria), managed by diet or metformin alone * Body mass index (BMI) 20 - 40 kg/m2 * Males and females (females of reproductive potential must be using an appropriate contraceptive method) * Glycated haemoglobin (HbA1c) ≤ 8.5% * Haemoglobin above the lower limit of the normal range (i.e. \>135g/L for men and 115g/L for women), and ferritin above the lower limit of normal (i.e. \>10mcg/L)
Exclusion criteria
* Subjects with gastrointestinal disease, significant upper or lower gastrointestinal symptoms, or previous gastrointestinal surgery (other than uncomplicated appendicectomy or cholecystectomy) * Other significant illness, including epilepsy, cardiovascular or respiratory disease. * History of unexplained pancreatitis, chronic pancreatitis, pancreatectomy. * Impaired renal or liver function (as assessed by calculated creatinine clearance \< 50 mL/min using the Cockroft-Gault equation (27) or abnormal liver function tests (\> 2 times upper limit of normal range)). * Requirement for medication known to influence blood pressure and/or heart rate and/or gastrointestinal function, drugs with anticholinergic effects * Alcohol consumption \> 20 g per day * Smoking \> 10 cigarettes per day * Pregnancy or lactation. * Vegetarian * Allergy to sitagliptin or any other 'gliptin'. * Donation of blood within the previous 3 months * Participation in any other research studies within the previous 3 months * Exposure to ionising radiation for research purposes in the previous 12 months * Inability to give informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Gastric emptying | 3 hours per gastric emptying study (i.e. 6 hours) | Gastric retention (percent in the total stomach) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Gastrointestinal hormone release | 4 hours during each gastric empty study (i.e. 8 hours) | GLP-1, GIP, C-peptide, 3-OMG |
| Intragastric meal distribution | 3 hours during each gastric empty study (i.e. 6 hours) | percent retention in the proximal and distal stomach |
| Blood pressure | 4.5 hours during each gastric empty study (i.e. 9 hours) | systolic and diastolic blood pressure (mmHg) |
| Heart rate | 4.5 hours during each gastric empty study (i.e. 9 hours) | Heart rate (beats per minute) |
| Glycaemia | 4 hours during each gastric empty study (i.e. 8 hours) | blood glucose (mmol/L) and plasma insulin (mU/L) |
| Cardiac output | 4 hours during each gastric empty study (i.e. 8 hours) | Finapres (L) |
| Stroke volume | 4 hours during each gastric empty study (i.e. 8 hours) | Finapres (mL) |
| Appetite | 4 hours during each gastric empty study (i.e. 8 hours) | visual analogue questionnaire to assess hunger, fullness, desire to eat (mm) |
| Splanchnic blood flow | 4 hours during each gastric empty study (i.e. 8 hours) | Doppler ultrasound of superior mesenteric artery flow (ml/min) |
Countries
Australia
Outcome results
None listed