COMMENTARIES

Clinical Value of Diagnosing Metabolic Syndrome in Type 2 Diabetes Mellitus

Soon H. Song, M.D., FRCP¹ and Colin A. Hardisty, M.D., FRCP², ¹Consultant Physician, Diabetes Centre, Northern General Hospital, Herries Road, Sheffield S5 7AU, U.K., Email: soon_song@hotmail.com and ²Consultant Physician, Diabetes Centre, Royal Hallamshire Hospital, Glossop Road, Sheffield S10 2JF, U.K.

The concept of metabolic syndrome (MetS) conferring increased risk for type 2 diabetes mellitus (T2DM) and cardiovascular disease has been around for more than a couple of decades. Recent publications of clinical definitions have transformed MetS from a physiological curiosity to a major focus of research and clinical and public health interest. The MetS refers to the co-occurrence of obesity (in particular central obesity), dysglycemia, dyslipidemia (raised triglyceride and low HDL cholesterol), and hypertension and in many cases, this phenomenon signifies underlying insulin resistance. As a clinical tool, MetS has been promoted as a means to identify individuals at increased risk for cardiovascular disease for lifestyle and therapeutic interventions to intensively treat the atherogenic risk factors and reduce incident cardiovascular complications.

          Although there is general consensus on the main components of this syndrome, various definitions have been proposed with different inclusion criteria and associated thresholds. As a consequence, no standard definition has been routinely used resulting in absence of comparability between studies in various populations. The prevalence of MetS is also known to vary even within the same population depending on the chosen definition. A universally accepted working definition of MetS was therefore needed. The latest definition proposed by the International Diabetes Federation (IDF) was intended to be applicable to various ethnic groups worldwide [1]. This new definition is similar to National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATPIII) by incorporating identical, clinically relevant, and pragmatic measurements including waist circumference (WC) to quantify central obesity in their diagnostic criteria but with some notable differences – namely, WC as a mandatory component for diagnosis with lower and ethnic-specific WC thresholds in the IDF criteria.

          However, the concept of MetS has been received with some degree of skepticism and criticism for a variety of reasons [2,3]. Insulin resistance as the fundamental unifying cause for the clustering of cardiovascular risk factors remains uncertain because it is inconsistently related to the individual features of the syndrome. Establishing the working definition for MetS is complicated by uncertainty about which features to include and the associated thresholds to set. Its predictive ability for cardiovascular events has been questioned as the cardiovascular risk associated with the syndrome is no greater than the sum of its parts. From the perspective of clinical management, treatment of the syndrome is no different from treatment for each of its components. Inclusion of diabetes in its definition is questionable. In another words, the clinical value of diagnosing the syndrome is in serious doubt.

          In the background of raging debate about the controversy of MetS, we performed this study to evaluate the clinical usefulness of diagnosing MetS in T2DM using IDF and NCEP-ATPIII criteria [4]. The objective of this work was to address the existing gaps in current literature in this area. In contrast to non-diabetic population, few studies have examined the role of the new IDF definition on the diagnosis of MetS in T2DM including its clinical robustness compared to the NCEP-ATPIII criteria. In addition, the clinical usefulness of measuring WC as a surrogate marker for central obesity in cardiovascular risk management among patients with T2DM in the U.K. remains unknown. This issue needs an objective and practical assessment as there is a proposal recommending routine diagnosis of MetS to guide cardiovascular risk management [1].

          In our cohort of patients with T2DM who attended hospital clinics, MetS was extremely common with prevalence of ~ 75-95% irrespective of age (including early-onset T2DM below 40 years of age), gender, and diabetes duration. Those without cardiovascular disease had similar MetS prevalence as those with cardiovascular disease. Presence of central obesity was extremely common with the mean WC of ~ 113 cm regardless of age and gender. Among those who did not have IDF-defined MetS, approximately 60% possessed at least two cardiovascular risk factors (low HDL, elevated triglyceride, or hypertension). There was a high degree of concordance between IDF and NCEP-ATPIII definitions with both criteria similarly classified ~ 94% of the patients as either having or not having MetS.

          These results are important for several reasons. First, the IDF definition was not better than NCEP-ATPIII criteria in identifying MetS despite making central obesity a mandatory component and lowering the diagnostic WC threshold suggesting these changes would not make any significant difference to diagnosing the syndrome in T2DM. Second, our observation adds to the variation in the prevalence of IDF-defined MetS reported in different T2DM populations highlighting the importance of ethnicity-related differences in central obesity [5-9] which has been the focus of debate regarding the appropriate level of WC to define central obesity for different ethnic groups [5,8,10]. Third, it highlights that early-onset T2DM subjects do not possess a benign cardiovascular risk profile, reflected by the high tendency to multiple risk factor clustering [11], suggesting age is not a good indicator of cardiovascular risk in T2DM. As there is paucity of clinical trial evidence in this young cohort, clinical judgment is often required to initiate cardio-protective therapies and the strategy of risk stratification by determining the presence of additional atherogenic risk factors as a guide to lipid-lowering therapy for primary prevention as recommended by Joint British Societies-2 guidelines seems reasonable [12]. Fourth, the IDF criteria failed to identify all high risk T2DM patients despite making central obesity a mandatory component to diagnose MetS. Majority of those deemed not to have IDF-defined MetS had adverse risk factors. The indispensability of central obesity in the IDF definition has been previously questioned [5] and our observation lends further support to this argument. Fifth, the high prevalence of MetS casts doubt on its clinical value in the cardiovascular risk management of T2DM. It is questionable whether diagnosing MetS is necessary to identify high risk individuals especially above 40 years of age when almost everyone has this syndrome. Finally, it is redundant to measure central obesity as most if not all T2DM subjects have it. It is now a routine practice to look for adverse risk factors as part of the multi-factorial intervention, an approach with robust clinical evidence in reducing diabetes-related macro- and microvascular complications and recommended by national guidelines as an integral component in the clinical management of T2DM [12]. In another words, looking for MetS is not going to change the current practice of cardiovascular risk management.

          Further evidence has cast more doubt on the clinical value of MetS in T2DM. One of the contentious issues surrounding the concept of MetS relates to its ability to predict cardiovascular events. Current evidence suggests it does not perform very well in this area. A recent study based on U.K. population demonstrated that MetS is a poor discriminator of cardiovascular outcome in individual T2DM patients and hence, of limited clinical value for risk stratification in this condition [13]. Other studies have shown that diabetes alone conveyed greater risk for coronary heart disease and cardiovascular disease than presence of MetS [14,15].

          However, all is not lost. The concept of MetS has not been a fruitless effort despite being showered with criticisms for its limitations. Tremendous amounts of intense and productive research and discussion among scientists, clinicians, and public health sectors has been generated globally and as a consequence, it has brought positive influence to the clinical practice of cardiovascular risk management. More importantly, it has helped to focus one’s mind and priorities especially those of family physicians on the importance of looking for clustering of adverse risk factors in predisposed nondiabetic and diabetic individuals in the community where most clinical care is delivered.

References

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