Metabolic Syndrome and Type 2 Diabetes/CVD Risk

The recognition of the metabolic syndrome as a risk factor for type 2 diabetes and cardiovascular disease (CVD) in the NCEP-ATP III and IDF guidelines has had important clinical/public health ramifications. Gaining ground is the notion that the most prevalent form of the metabolic syndrome is associated with abdominal obesity, especially when accompanied by excess visceral fat. This form of adiposity has been strongly linked to a cluster of diabetogenic and atherogenic metabolic abnormalities known as the metabolic syndrome, which substantially increases CVD risk, even in the absence of traditional risk factors. Because abdominal adiposity can be assessed through simple anthropometric measurements such as waist circumference, this approach is often used to identify abdominally obese patients with the most prevalent form of the metabolic syndrome. The current debate about the relevance of considering the metabolic syndrome in clinical practice highlights the fact that pathophysiology and clinical screening tools have often been confused. Much additional research will be needed to determine which key features of the metabolic syndrome further contribute to global CVD risk (as assessed by classical risk factors). Moreover, simple and effective tools must be developed for health professionals as there is an urgent need to identify these high-risk abdominally obese patients. So far, several organizations and groups have proposed clinical tools to identify patients likely to have features of the metabolic syndrome (hypertriglyceridemic waist, NCEP-ATP III, IDF, WHO, EGIR, AACE). Regardless of whether one recognizes that this syndrome really exists, there is compelling evidence that the abdominal obesity and type 2 diabetes epidemics represent a major threat to the cardiovascular health of most populations worldwide.

Key Points

• Hypertriglyceridemic waist (elevated waist girth and triglyceride concentrations) could be a simple and inexpensive way to identify individuals with high levels of visceral fat and the features of the metabolic syndrome.
• The simultaneous presence of an elevated waist circumference and high triglyceride levels increases relative risk of CHD.
• Hypertriglyceridemic waist increases the risk of type 2 diabetes.
• A diagnosis of hypertriglyceridemic waist is not sufficient, however, to assess global CHD risk.

Read more on Usefulness of Hypertriglyceridemic Waist.

Key Points

• NCEP-ATP III guidelines have emphasized that the metabolic syndrome is a secondary target of therapy beyond elevated LDL cholesterol.
• NCEP-ATP III guidelines have also singled out excess abdominal adipose tissue as a key feature of the metabolic syndrome.
• Other elements of the metabolic syndrome include atherogenic dyslipidemia, insulin resistance, a pro-inflammatory and pro-thrombotic profile, and high blood pressure.
• To date, numerous prospective studies have shown that the metabolic syndrome predicts CVD risk, with very few exceptions.
• Overall CVD risk related to the metabolic syndrome has been evaluated in meta-analyses, which have concluded that the metabolic syndrome increases relative risk of CVD.
• The metabolic syndrome is a stronger predictor of type 2 diabetes than CVD risk.

Read more on NCEP-ATP III.

Key Points

• Waist girth is a mandatory feature of IDF clinical criteria for diagnosing the metabolic syndrome.
• For the first time, population-specific cutoffs have been proposed to consider ethnic differences in the relationship between abdominal obesity and incidence of CHD and type 2 diabetes.
• IDF clinical criteria are similar to those proposed by the NCEP-ATP III regarding metabolic markers used to diagnose the metabolic syndrome.
• When managing the metabolic syndrome, the first step should be to reduce visceral adipose tissue through lifestyle modification.
• Most prospective studies have found a positive relationship between the metabolic syndrome (IDF criteria) and CVD.
• Further research is required to establish specific waist circumference cutoffs for all regions of the world.

Read more on IDF.

Key Points

• WHO was the first major organization to produce a definition of the metabolic syndrome that focused mainly on insulin resistance, whose diagnosis requires an oral glucose tolerance test.
• WHO criteria also proposed that microalbuminuria as a marker to identify high-risk patients with the metabolic syndrome.
• In response to WHO, EGIR sought to establish criteria that would be easier to use in clinical practice. EGIR makes measuring insulin resistance mandatory.
• The AACE position does not provide a specific scoring system for diagnosing the “insulin resistance syndrome”. Insulin resistance is at the core of AACE criteria, while waist circumference is not considered a diagnosis criterion.
• These organizations acknowledge that their diagnosis tools can be refined and that further research is needed to improve diagnosis of the metabolic syndrome in clinical practice.

Read more on Other Tools (WHO, EGIR AND AACE).

Key Points

• WHO and EGIR clinical criteria rely mainly on insulin resistance. IDF criteria rely on abdominal obesity, while NCEP-ATP III gives equal weight to each clinical criterion of the metabolic syndrome.
• The IDF and NCEP-ATP III approaches use the same cutoff values for lipids, fasting glucose, and blood pressure. However, the IDF has proposed ethnic-specific cutoffs for waist circumference. Waist circumference is also a mandatory IDF criterion.
• A few prospective studies have compared metabolic syndrome criteria in assessing CVD risk. Although most criteria have a similar relationship to CVD risk, NCEP-ATP III criteria seem to have the strongest ties to CVD.
• Independent of the clinical criteria studied, the metabolic syndrome better predicts type 2 diabetes risk than CVD risk.
• Further studies are needed to compare various metabolic syndrome clinical criteria using different statistical models and in all populations of the world.

Read more on Comparison of Screening Tools.

Key Points

• The underlying cause(s) of the metabolic syndrome are not fully understood. Visceral obesity and insulin resistance are thought to be the driving forces behind the development of the metabolic syndrome.
• Although the metabolic syndrome is associated with incident CVD and diabetes, it is not clear whether it enhances CVD and diabetes risk on top of currently available algorithms for assessing CVD and diabetes risk.
• Further research and work is needed to eventually harmonize metabolic syndrome diagnosis criteria and develop new modelling approaches to take into account the linear relationship between the features of the metabolic syndrome and CVD and diabetes risk.
• For the moment, it is unclear whether the metabolic syndrome is a clinical entity that increases CVD and diabetes risk more than the sum of its individual components. It is also unclear whether the metabolic syndrome should be treated differently than its individual components.

Read more on Limitations.