Risk Factors

Because of the well-documented genetic predisposition for diabetes/insulin resistance, hypertension, dyslipidemia, and obesity—all key components of MetSx—it is clear that MetSx also has some genetic cause. In addition, the genetic theory is supported by the fact that some ethnic groups, such as Asians and Latin people with Native American ancestors, are more likely to develop diabetes at milder degrees of abdominal obesity than Caucasians. However, the increased prevalence of MetSx in recent decades cannot be explained by genes alone, and environmental factors that lead to obesity can probably take most of the blame for the MetSx epidemic.

It has been extensively documented that obesity is arguably the most important risk factor for MetSx. Excess body fat is indeed a major risk factor for insulin resistance, a factor considered by many as the underlying disease mechanism of MetSx. When the deposits of fat in the body increase, the turnover of free fatty acids also increases, acting as a potent inhibitor of the insulin effect at the cellular level. The second mechanism to explain why obesity promotes insulin resistance is that the former induces a leptinresistance state with subsequent increase in the levels of leptin, which is also a potential inhibitor of the insulin receptor.

MetSx has been linked to a systemic inflammatory state. Obesity increases the production of proinflammatory cytokines by the adipose tissue and the liver. Animal models have shown that markers of inflammation such as C-reactive protein may cause insulin resistance, suggesting that systemic inflammation may be both a cause and a consequence of impaired insulin sensitivity. However, the way in which obesity predisposes to MetSx is not simple because, as mentioned before, some populations develop MetSx at lower levels of obesity and some people can indeed develop MetSx even with normal body weight.

Other documented risk factors for MetSx include a sedentary lifestyle and a diet high in refined carbohydrates and saturated fat. These factors are independent of the risk for MetSx attributed to obesity, even though a sedentary lifestyle and a poor diet predispose to obesity. This can be illustrated by the results of the Diabetes Prevention Program trial, where patients with impaired fasting glucose levels assigned to an exercise program that included nutritional counseling reduced the risk of developing diabetes mellitus by more than 50%, despite a quite modest weight loss of <5lb.

The strong association between lifestyle and MetSx has motivated some clinicians to call it the ‘lifestyle syndrome.’ Indeed, changes in the level of physical activity and improvements in the diet have shown to improve all of the components of MetSx in different trials.

Clinical Implications of the Metabolic Syndrome

Each of the components of MetSx has been independently associated with cardiovascular disease, including myocardial infarction, the need for coronary revascularization, and stroke. Therefore, it is not surprising that MetSx is also associated with a higher rate of cardiovascular disease and death. The presence of MetSx gives a two- to four-fold greater risk for cardiovascular death compared with those who have none of the MetSx components. This risk estimate is equivalent to having a total cholesterol >300mmHg or to the risk of smoking two packs of cigarettes a day. The risk is proportional to the number of positive criteria for MetSx and appears to be slightly higher in men than in women. The second major clinical implication of MetSx is an almost eight-fold greater risk of developing diabetes mellitus compared with those without MetSx. Diabetes mellitus represents a leading cause of death and disability in the world, even beyond the consequences of diabetes on the heart. Diabetes mellitus is the most common cause of end-stage renal disease and blindness in many countries and a leading cause of inferior limb amputation due to vascular insufficiency.

Because of the prevalence of MetSx and the strength of the association to cardiovascular disease and diabetes, MetSx represents a major public health threat. Indeed, recent data from the Inter-Heart study demonstrated that components of MetSx have the highest putative risk for ischemic heart disease in Latin America, meaning that more new cases of myocardial infarction in that region of the world can be attributed to components of MetSx than to any other cardiovascular risk factor.

Treatment

Focus on Lifestyle

The cornerstone of the management of MetSx is lifestyle change. Because most patients with MetSx are sedentary and have poor dietary patterns, there is usually enormous room for improvement. Since changing behavior is not simple, healthcare providers should avoid a minimalist approach of simply telling the patient “You need to exercise and lose weight”—a recommendation that takes less than 20 seconds. Significant and sustainable behavioral change requires the use of basic techniques mastered by psychologists and those working on the treatment of people with addictions. The basic principles for behavioral change include: motivation— fear, desire for a good health state, competitiveness, vanity, etc.; tools to facilitate the change—learning material, equipment, facilities, etc.; and tools to facilitate the maintenance of a healthy behavior.