Meal-related hypertriglyceridaemia and low-grade inflammation in relation to beta-cell function in the general population
11 / 2004 - 02 / 2008
OBJECTIVES: Beta-cell dysfunction is the key component of hyperglycaemia in the aetiology of type 2 diabetes. Little is known about determinants of beta-cell function in the general adult population. Exposure to high levels of free fatty acids and ectopic intracellular storage of triglycerides may result in insulin resistance and oxidative stress. It is hypothesised that chronic exposure to high levels of free fatty acids also contribute to beta-cell dysfunction. Since physical inactivity and nutritional habits are strong determinants of obesity and ectopic triglyceride accumulation, these lifestyle characteristics are also hypothesised to be associated with beta-cell function. So far, beta-cell function in population studies has mostly been measured with the oral glucose tolerance test (OGTT). The metabolic response to a normal physiological mixed meal is expected to produce a more reliable marker of beta-cell function than the standard OGTT. We hypothesize that indicators of glucose metabolism, derived from the physiological response following a normal mixed meal (insulin secretion rate and insulin sensitivity index), are better predictors of future diabetes and cardiovascular disease than those from the 75g glucose tolerance test. We expect that triglyceride concentrations following a normal standardised breakfast are associated with insulin sensitivity and beta-cell function and with components of the metabolic syndrome. METHODS: The study, started in June 2005 at the Diabetes Research Centre in Hoorn, will draw from Hoorn s municipal registry a random sample of 300 men and women, aged 40 65, 200 of whom are expected to be included in the study. All participants will have a standard 75g OGTT and a standardised mixed meal test, on separate days, to assess both beta-cell function and insulin sensitivity. T he tests will characterise the relationship between measures of insulin sensitivity and insulin secretion (beta-cell function), as well as associations with fasting and postprandial triglyceride and free fatty acid levels. C-reactive protein will be determined as a measure of chronic low-grade inflammation. A standard 12-lead electrocardiogram and ankle-arm blood pressure ratio will measure prevalent cardiovascular disease. Anthropometric and blood-pressure measurements will be performed. Questionnaires will determine habitual physical activity, food consumption, smoking, alcohol intake, employment, education, current medication, disease history, family history of disease, and self-reported birth weight.