Extrait

Background and study aims Type 2 diabetes mellitus (type 2 DM) is well known to be associated with increased risks of high blood pressure, angina, heart attack and stroke. Polycystic ovary syndrome (PCOS) is a common hormone problem in young women and, as a result of it, they can experience irregular periods, reduced fertility, acne and increased body hair. Research suggests that they could have a high risk of diabetes and cardiovascular disease such as high blood pressure, angina, heart attack and stroke. One of the reasons for the increased cardiovascular risk in these patients is the presence of high bad cholesterol and low good cholesterol levels in the circulation, and insulin resistance. The fat from the diet is transported from the stomach into the blood and then cleared up by the liver, muscles and fat tissues to store or use as an energy source. Delayed removal of fat from the blood after a meal has been known to happen in diabetes and PCOS patients. According to previous studies, high fat level in the blood after a meal is an independent risk factor for cardiovascular disease. In addition, the high fat level may worsen insulin resistance and glucose levels. However why this happens in patients with type 2 DM and with PCOS, and whether lowering fat level improves insulin resistance are still not known. That is why we plan to do this research study. Who can participate? This study will recruit 10 premenopausal healthy women, 10 premenopausal women with polycystic ovary syndrome and 10 premenopausal women with type 2 diabetes mellitus. What does the study involve? The study includes 4 visits to the Diabetes centre, Hull Royal Infirmary (UK). Screening visit (Visit 1): Visit 1 is designed to obtain informed consent from you and to find out if you are eligible for the study. The screening includes a brief medical history (including pre-existing medical conditions, medicines you are currently taking, smoking status and alcohol intake), physical examination (measurement of height, weight, hip and waist circumference and blood pressure), the baseline blood tests and an oral glucose tolerance test if participants are not known to have diabetes and wish to enter the study in control arm or PCOS arm. An oral glucose tolerance test involves measuring the blood sugar level at baseline and at 120 minute after taking 75g of glucose solution following overnight fasting. Visit 2: A meal test to determine fat clearance after a meal will be done in this visit. Participant will be asked to fast overnight from 1900 hour (7pm) the day before this visit, though water is allowed. A meal made of milk, cereals, cream, cheese and bread, and an emulsion with carbon labelled fat will be provided. Blood samples will be taken half hourly for the first 3 hours and hourly for 3 hours through the inserted cannula at the forearm. Breath samples will be taken every hour for 6 hours and 4 more breath samples at home. The breath test is simple and it is basically exhaling breath for a few seconds into a test tube using a plastic straw. Total amount of blood taken will be about 40-50ml. The meal test will take 6 hours. Visit 3: Acipimox tablet is known to lower the fat level in the blood. You will be advised to take acipimox 250mg at 2000 hour, 2300 hour and 0600 hour with water only. You will be asked to fast since 1900 hour except water on the day before the meal test. The meal test will be done at 0800 hour in the next morning. The procedure for the meal test is same as that for visit 2. Then you will be asked to take a week’s course of acipimox 250mg three times a day to be taken with food starting from next day before the third meal test. Visit 4 (a week after visit 3): The visit is for the third meal test following a week’s course of one acipimox tablet three times per day. Then the meal test will be performed following overnight fasting using the same meal protocol. What are the possible benefits and risks of participating? There is no immediate benefit to the participants but the findings would be very useful to find a way to improve insulin resistance and cardiovascular risk. Possible adverse effects are hot flushes and skin rash which are common side effects of acipimox. The study doctor will look after the study participants throughout the study. Detailed information will be provided in the participant information sheet. Inserting the cannulas and taking blood samples may well cause discomfort and risks of inflammation/ infection/ bruising at the needle site. The risk will be minimised as the cannulation will be performed by experienced study doctors in accordance with the local guidelines. Where is the study run from? The study will be run at the Diabetes centre, Hull Royal Infirmary. When is the study starting and how long is it expected to run for? December 2009 to December 2013. Who is funding the study? The study is funded by the diabetes charitable fund, The Hull and East Yorkshire hospital NHS Trust and the University of Hull (UK). Who is the main contact? Prof Stephen Atkin [email protected]

Critère d'inclusion

• Type 2 diabetes mellitus, polycystic ovary syndrome

Liens

• isrctn
• ictrp