Clinical effects of high-fat meals and weight gain due to high-fat feeding.

Overfeeding high-fat (HF) meals results in both short-term and long-term effects that vary depending upon adiposity status (obese vs nonobese) and family history of type 2 diabetes. Although more than 4 weeks of overeating produces mild insulin resistance, whether the same is true of a single, HF meal is not clear. We reviewed overfeeding studies of 4-8 weeks duration, studies of single HF meals and our own (unpublished) plasma insulin and glucose concentration data from 59 nonobese and 15 overweight/obese volunteers who consumed either a normal-fat (NF) breakfast or a breakfast matched for carbohydrate and protein, but with an additional 80 g of monounsaturated fat (HF). Four to eight weeks of overfeeding a HF diet causes an ∼10% reduction in insulin sensitivity. Some authors report that a single HF meal is associated with greater postprandial insulin concentrations, whereas other investigators have not confirmed such a response. We found that plasma glucose concentrations peaked later following a HF breakfast than a NF breakfast in both obese and nonobese adults and that daytime plasma insulin concentrations were not uniformly increased following a HF breakfast. We conclude that a single HF meal delays the postprandial peak in glucose concentrations, likely due to delayed gastric emptying. This will confound attempts to use insulinemia as a marker of insulin resistance. After 4-8 weeks of overeating a HF diet accompanied by 2-4 kg of fat gain, insulin sensitivity decreases by ∼10%. Although we could not demonstrate that baseline insulin resistance predicts visceral fat gain with overfeeding, normal-weight relatives of type 2 diabetes mellitus do tend to gain more weight and become more insulin resistant than those without a positive family history of type 2 diabetes mellitus. In summary, short-term weight gain from HF diets induces relatively mild metabolic disorders.