The ACT-OUT Trial: ACTivity OUTcomes Based on the Consumption of a High Carbohydrate or High Fat Diet in Patients With Metabolic Syndrome

1. BACKGROUND AND RATIONALE:

Current obesity prevention emphasizes increasing physical activity and a low-fat, calorie restricted diet to produce a negative caloric balance. Caloric restriction is associated with decreases in energy expenditure. The other mainstay of obesity prevention increasing levels of physical activity is associated with greater caloric intake. Failure of the eat less-exercise more strategy is evident with epidemic of obesity, metabolic syndrome (MetS) and type II diabetes. Moreover, the displacement of dietary fat in the diet has led to compensatory increases in carbohydrate intake that is associated with untoward metabolic effects.

Carbohydrate restricted diets are controversial despite benefits of this approach. The controversy stems from a compensatory increase in dietary fat intake associated with carbohydrate restriction and fears that greater fat intake increases risk of cardiovascular disease. Carbohydrate restriction decreases insulin resistance and ameliorates MetS. This protocol aims to establish a greater evidence base for carbohydrate restricted diets as a therapeutic option for MetS. The investigators will review current knowledge with respect to: (i) obesity and insulin resistance in Canada, (ii) positions of major medical organizations (iii) shortcomings of the current obesity prevention paradigm (iv) why carbohydrate restricted diets work.

1.1) Obesity and insulin resistance in Canada In the 1980s low fat, caloric restricted diets became the cornerstone of dietary advice to reduce obesity. This approach successfully reduced the percent of calories from fat with a consequential increase in carbohydrate consumption. In the ensuing years, obesity become epidemic. In Canada, the prevalence of obesity (BMI ≥ 30 kg/m2) increased from 10% in 1970s to 23% in 2004 with an additional 36% considered overweight (BMI 25-29.9). As obesity is a risk factor for MetS and type II diabetes, the prevalence of these disorders has also reached epidemic proportions. Approximately 2 million Canadians were living with diabetes in 2007 and by 2012 it is estimated that 2.8 million Canadians will be living with diabetes. First Nations communities have been especially hard hit, with a prevalence 3-4 times higher and a younger age of onset than non-First Nations individuals. Novel chronic disease prevention strategies are needed to address this crisis.

Insulin resistance underpins the pathophysiology of obesity, Insulin resistance is a condition in which normal amounts of insulin are inadequate to produce a normal insulin response from fat, muscle and liver cells. As a result, insulin resistant individuals have both elevated blood glucose, fasting insulin and secrete greater amounts of insulin in response to dietary carbohydrate. This compensatory hyperinsulinemia is associated with adverse effects in tissues which retain their sensitivity to insulin. Elevated blood glucose levels are associated with advanced glycation end products, reactive oxygen species and low grade inflammation. These exposures are associated with increased risk of cardiovascular disease & diabetes. Despite the evidence associating elevated insulin levels to atherogenic changes in the vasculature, it remains a matter of controversy as to whether persistently elevated insulin levels are pathogenic.