Genes and environment in type 2 diabetes and atherosclerosis Figure 57 Not much genetic evolution has occurred in humans in the past 20,000 years. In the Palaeolithic age, our ‘thrifty genotype’ was well-adapted to the high level of physical activity associated with our hunter-gatherer existence. However, this genotype has become redundant in the presence of our sedentary lifestyle and a diet low in fibre and high in animal fats and glucides. In short, our genotype – no longer adapted to our lifestyle – has become a ‘susceptibility genotype’.

Pima Indians Thrifty genes Figure 58 Epidemiological evidence of the ‘thrifty genotype’ becoming a ‘susceptibility genotype’ comes from the study of the Pima Indians. Those maintaining a traditional way of life have little obesity or type II diabetes, while those with the newer, more sedentary way of life have developed high rates of obesity (75%) and type II diabetes (50%).

Aboriginal Canadians Oji-Cree Figure 59 Similarly, rapid change to a sedentary lifestyle in aboriginal Canadians resulted in a tripling of CHD over 20 years.

Obesity, type 2 diabetes, atherosclerosis Figure 60 Thus, the interaction between our current genotype and our present day environment places us at risk of having a phenotype that is highly susceptible to AS.

The Metabolic Syndrome Figure 61 The Metabolic Syndrome (‘Syndrome X’) is the pathological expression of the ‘susceptibility genotype’. It is a disease of the modern Western lifestyle characterized by truncal/visceral obesity, hypertension, hyperinsulinemia, reduced glucose tolerance, and a pro-coagulatory state.

Visceral obesity is associated with a cluster of metabolic abnormalities Figure 62 The Metabolic Syndrome is characterized by the following features of dyslipidemia: high TGs; increased small, dense LDL; low HDL-cholesterol; elevated apo B; pro-inflammatory profile.

The atherogenic triad Figure 63 The traditional ‘atherogenic triad’ of high TGs, high LDL and low HDL is associated with an odds ratio of 4.4 for CHD. However, the newer triad of hyperinsulinemia, elevated apo B, and increased small dense LDL is associated with an odds ratio almost five times greater. Therefore, the Metabolic Syndrome represents a virulent CHD-promoting condition.

PROCAM Study: MI-Incidence according to LDL-cholesterol and triglycerides Figure 64 The PROCAM study identified low HDL-cholesterol as an independent risk factor for MI (in addition to raised TGs and LDL).

70% of men with CHD had a low HDL ≤44mg/dL Framingham Male Offspring 35-54 Figure 65 The importance of HDL-cholesterol as a risk factor was confirmed in the Framingham Male Offspring study. The study showed that almost 70% of men with premature CAD had low HDL (<44 mg/dL) whereas almost 70% had normal or only moderately elevated LDL.