Twenty-four middle-aged healthy men were given a low-fat high-carbohydrate (5.5 g fat; L), or a moderately-fatty, (25.7 g fat; M) breakfast of similar energy contents for 28 d. Other meals were under less control. An oral glucose tolerance test (OGTT) was given at 09.00 hours on day 1 before treatment allocation and at 13.30 hours on day 29. There were no significant treatment differences in fasting serum values, either on day 1 or at the termination of treatments on day 29. The following was observed on day 29: (1) the M breakfast led to higher OGTT C-peptide responses and higher areas under the curves (AUC) of OGTT serum glucose and insulin responses compared with the OGTT responses to the L breakfast (P < 0.05); (2) treatment M failed to prevent OGTT glycosuria, eliminated with treatment L; (3) serum non-esterified fatty acid (NEFA) AUC was 59% lower with treatment L than with treatment M, between 09.00 and 13.20 hours (P <0.0001), and lower with treatment L than with treatment M during the OGTT (P = 0.005); (4) serum triacylglycerol (TAG) concentrations were similar for both treatments, especially during the morning, but their origins were different during the afternoon OGTT when the Svedberg flotation unit 20–400 lipid fraction was higher with treatment L than with treatment M (P = 0.016); plasma apolipoprotein B-48 level with treatment M was not significantly greater than that with treatment L (P = 0.086); (5) plasma tissue plasminogen-activator activity increased after breakfast with treatment L (P = 0.0008), but not with treatment M (P = 0.80). Waist:hip circumference was positively correlated with serum insulin and glucose AUC and with fasting LDL-cholesterol. Waist:hip circumference and serum TAG and insulin AUC were correlated with factors of thrombus formation; and the OGTT NEFA and glucose AUC were correlated. A small difference in fat intake at breakfast has a large influence on circulating diurnal NEFA concentration, which it is concluded influences adversely glucose tolerance up to 6 h later.

Dietary and pharmacological approaches to slowing the rate of glucose absorption and blunting the insulin response show promise in the treatment of diabetes and hyperlipidaemia. These approaches include dietary fibre, low-glycaemic-index foods and gastrointestinal digestive enzyme inhibitors. One common feature is that they spread the nutrient load over time. A potentially simpler approach is to take more frequent smaller meals over a longer period of the day. Early studies suggested that frequent glucose and insulin administration to diabetic patients improved diabetes control. More recent acute studies of one test meal or 1 d blood metabolite profiles have identified a significant economy in insulin secretion when glucose is sipped or when meal frequency is increased in both diabetic or non-diabetic subjects. In diabetic subjects improvement in mean blood glucose levels has also been reported. However, despite the demonstration of an alteration in response over time in glucose tolerance in healthy volunteers, no longer-term improvement in glycaemic control was reported in the only study in diabetes to examine a change from three to nine meals daily over a 1- month period. The disparity between longer-term and acute studies requires further investigation. At present, although this nutritional approach holds considerable theoretical promise, specific advice is premature.