QJM Advance Access originally published online on March 19, 2008
QJM 2008 101(6):487-491; doi:10.1093/qjmed/hcn034
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Diagnosing metabolic syndrome in type 2 diabetes: does it matter?
From the 1Diabetes Centre, Northern General Hospital and 2Diabetes Centre, Royal Hallamshire Hospital, Sheffield, UK
Address correspondence to Dr Soon H Song, Diabetes Centre, Northern General Hospital, Herries Road, Sheffield S5 7AU, UK. email: soon_song{at}hotmail.com
Received 28 October 2007 and in revised form 18 February 2008
 |
Summary |
|---|
 Top Summary IntroductionMethodsResultsDiscussionReferences |
|---|
Background: Metabolic syndrome (MetS) is used as a clinical tool to identify individuals at risk of cardiovascular disease (CVD) but its clinical value in the management of type 2 diabetes mellitus (T2DM) remains uncertain.
Aim: To determine the prevalence and clinical usefulness of MetS among patients with T2DM attending diabetes clinics in a large teaching hospital.
Design: Prospective observational study.
Methods: Prevalence of MetS was determined by using International Diabetes Federation (IDF) and National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATPIII) definitions in relation to age, sex, diabetes duration and history of CVD.
Results: A total of 390 patients were included in this study. Both IDF and NCEP-ATPIII definitions identified high prevalence of MetS in male and female patients (IDF: male vs. female, 91.7 vs. 94.8% and NCEP-ATPIII: male vs. female, 87.6 vs. 94.2%) regardless of age (below vs. above 40 yrs, 
70–75 vs. 90–95% with both definitions), diabetes duration (below vs. above 5 yrs, 85–90 vs. 90–95% with both definitions) and history of CVD (without vs. with CVD, 90 vs. 95% with both definitions). Central obesity was common reflected by mean waist circumference of 113 cm regardless of age and gender. Among those who did not have IDF-defined MetS, 60% had at least two CVD risk factors. Both definitions similarly classified 94% of the patients as either having or not having MetS.
Discussion: Both definitions can be used interchangeably to diagnose MetS. However, the clinical usefulness of MetS is debatable given the very high prevalence of this condition in T2DM.
|
Introduction |
|---|
|
TopSummaryIntroductionMethodsResultsDiscussionReferences |
|---|
Metabolic syndrome (MetS) refers to clustering of risk factors that promote the development of atherosclerotic cardiovascular disease (CVD) and its clinical role is to identify individuals at risk of this complication. Although there is general consensus regarding the main components of the syndrome (glucose intolerance, obesity, hypertension and dyslipidaemia), various definitions of MetS have been proposed.1–3 As a consequence, no standard definition was routinely used and this has led to absence of comparability between studies in different populations. The latest definition proposed by the International Diabetes Federation (IDF) was intended to be applicable to various ethnic populations worldwide.4 Apart from the IDF diagnostic criteria, the other definition most commonly used in clinical practice is National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATPIII).2 These two definitions incorporated clinically relevant and pragmatic measurements including waist circumference (WC) to determine central obesity in their diagnostic criteria. However, the IDF definition has significant differences from NCEP-ATPIII in three key aspects. First, the IDF definition emphasized the importance of central obesity as defined by WC in the diagnosis of MetS and made WC a mandatory rather than an optional diagnostic component; secondly, the threshold for WC was lowered and thirdly, ethnic-specific WC thresholds to diagnose central obesity were added.
In contrast to non-diabetic populations, few studies have examined the clinical relevance of the new IDF definition on the diagnosis of MetS in type 2 diabetes mellitus (T2DM). In the UK, only one study has been performed to examine the clinical significance of MetS in T2DM.5 In this study, MetS was defined by using the modified NCEP-ATPIII definition in which the WC was not measured and was substituted by body mass index as a measure of central adiposity. At present, the clinical significance and relevance of IDF and NCEP-ATPIII-defined MetS using WC as a measure of central obesity in the CVD risk management among patients with T2DM in the UK remains unknown. This issue requires an objective and practical assessment as there is a proposal recommending routine diagnosis of MetS to guide CVD risk management.4 The aims of this study are (i) to estimate the prevalence of MetS using IDF definition among T2DM patients who attended diabetes clinics in a UK teaching hospital; (ii) to compare the prevalence of MetS with those based on NCEP-ATPIII definition; (iii) to assess the concordance between these two definitions and (iv) to determine the clinical usefulness of MetS.
|
Methods |
|---|
|
TopSummaryIntroductionMethodsResultsDiscussionReferences |
|---|
Patients with T2DM who attended hospital diabetes clinics for their clinical care were included in this study. For each patient, the following data were collected: age, sex, ethnicity, diabetes duration, weight, body mass index, WC, blood pressure, HDL cholesterol, triglyceride, total cholesterol, HbA1c and history of CVD defined by presence of ischaemic heart disease, cerebrovascular disease and peripheral vascular disease. The lipid profile was performed on fasting samples. MetS was defined using the IDF and NCEP-ATPIII definitions as detailed subsequently.
NCEP-ATPIII definition
Diagnosis is based on the presence of three or more of these risk factors: abdominal obesity defined by WC >102 cm in men and >88 cm in women, serum triglyceride >1.7 mmol/l, HDL cholesterol <1.03 mmol/l in men and <1.29 mmol/l in women, blood pressure >130/85 and a fasting glucose >6.1 mmol/l. T2DM patients with at least two other risk factors are deemed to have MetS.
IDF definition
The new diagnostic criteria are central obesity, defined as WC >94 cm and >80 cm for Caucasian male and female, respectively or >90 cm and >80 cm for Asian male and female, respectively; together with two of the following: raised triglycerides >1.7 mmol/l or specific treatment for this lipid abnormality; reduced HDL-cholesterol (<1.03 mmol/l in males and <1.29 mmol/l in females) or specific treatment for this lipid abnormality; blood pressure >130/85 mm Hg; and fasting hyperglycaemia, defined as glucose >5.6 mmol/l or previous diagnosis of diabetes or impaired glucose tolerance. T2DM patients with at least one other risk factor after fulfilling the WC threshold are deemed to have MetS.
Statistical analysis was performed using either Students t-test or chi-square. Test of concordance between IDF and NCEP-ATPIII definitions were analysed by the kappa test. P-value <0.05 were considered significant. Data are expressed as mean and standard deviation.
|
Results |
|---|
|
TopSummaryIntroductionMethodsResultsDiscussionReferences |
|---|
Baseline clinical characteristics
A total of 390 patients with T2DM were included in this study. Baseline clinical characteristics of these patients are shown in Table 1. Mean age was
61 years with diabetes duration of 10.6 years. A total of 37.7% of these patients had CVD complications. Majority of these patients were Caucasians (83.6%) with the remaining patients of Asian origin.
|
Concordance between IDF and NCEP-ATPIII definitions
There was good concordance between the two definitions (
= 0.60, P < 0.0001). Both definitions identified 346 (88.7%) and 20 (5.1%) patients with and without MetS respectively. There was no difference in the clinical characteristics among patients with MetS identified by either IDF or NCEP-ATPIII definition (Table 2). Among those patients who did not have MetS according to IDF definition (n = 27), 59.2% had at least two other MetS risk factors (low HDL, elevated triglyceride or hypertension).
|
Prevalence of MetS
Both definitions identified high prevalence of MetS (IDF vs. NCEP-ATPIII, 93.1 vs. 90.5%) regardless of gender (IDF: male vs. female, 91.7 vs. 94.8% and NCEP-ATPIII: male vs. female, 87.6 vs. 94.2%). Among those below 40 years of age,
70–75% had MetS. After the age of 40, the proportion of patients with MetS increased to 90–95% and remained static across different age groups (Table 3). In parallel with the high MetS prevalence, a high degree of central obesity was also observed regardless of age and gender. Mean WC was 113 cm across all age groups in male and female patients (Table 3). Prevalence of MetS was high regardless of diabetes duration (Table 4). Only 10 out of 390 (2.5%) patients were treated with fibrate and despite this, all of these patients had MetS with both criteria. None of the patients in this study cohort was treated with nicotinic acid.
|
|
Association with macrovascular complication
Patients with MetS had higher prevalence of CVD complications (IDF; MetS vs. no MetS, 39.1 vs. 18.5%, P < 0.001 and NCEP-ATPIII; MetS vs. no MetS, 39.7 vs. 18.9%, P < 0.001). Among those with CVD (n = 147), both definitions similarly identified 139 (94.5%) patients with this complication indicating high degree of concordance in CVD identification between these two definitions (
= 0.65, P < 0.0001). A high prevalence of MetS was also observed among patients without CVD but this was slightly lower compared to those with CVD (without CVD; IDF vs. NCEP-ATPIII, 90.9 vs. 87.7% and with CVD; IDF vs. NCEP-ATPIII, 96.6 vs. 95.2%). |
Discussion |
|---|
|
TopSummaryIntroductionMethodsResultsDiscussionReferences |
|---|
To our knowledge, this is the first study to examine the prevalence and usefulness of IDF and NCEP-ATPIII-defined MetS in clinical practice among patients with T2DM in a UK population. Despite limiting the diagnosis of MetS to those with abdominal obesity and lowering WC diagnostic threshold for central obesity, the IDF definition was similar to NCEP-ATPIII in its ability to identify MetS in T2DM. The two definitions similarly classified
94% of patients as either having or not having MetS. This high degree of concordance could be explained by the fact that the two definitions use the same five diagnostic components and apart from WC, the remaining criteria are nearly identically defined. The level of WC observed in this study far exceeded the diagnostic threshold for both definitions and is likely to have contributed to the similarity in the diagnosis of MetS.
Our observation adds to the variation in the prevalence of IDF-defined MetS reported in different T2DM populations.6–10 The reported prevalence varied from 20 to 75% depending on the ethnicity of the study population with the lowest and highest prevalence in Japanese6 and Italian cohorts,7,8 respectively. In our study cohort, consisting predominantly of white Caucasian patients, a higher prevalence (90–95%) was observed. The patient characteristics in these studies may explain the variation in MetS prevalence. The Japanese,6 Italian,7,8 Chinese9 and Hong Kong10 cohorts had lower body weight, body mass index and WC with similar lipid and blood pressure profiles compared to our cohort. It is plausible that the lesser degree of central obesity leads to lower prevalence of MetS since IDF definition requires quantification of central obesity as mandatory for its diagnosis. Furthermore, the concordance between NCEP-ATPIII and IDF definitions is also much higher in our cohort (90–95%) compared to Japanese,6 Italian,7,8 Chinese9 and Hong Kong10 cohorts (up to 70%). These observations suggest that the new IDF definition varies in its ability to identify T2DM patients with MetS in different populations.
Our observation of the high prevalence of MetS raises debate in relation to its clinical value in the CVD risk management of T2DM. It supports the concept of T2DM as a condition at risk of cardiovascular complications characterized by clustering of multiple risk factors. However, it is questionable whether diagnosing MetS is necessary for identification of high risk individuals above 40 years of age where its prevalence exceeds 90%. The prognostic role of MetS, defined by measuring WC as a surrogate for central obesity with either IDF or NCEP-ATPIII definitions, in predicting future CVD events remains unproven in UK population. On the other hand, multi-factorial intervention, in which there is strong clinical evidence for its role in reducing CVD and diabetes-related microvascular complications,11 is now a recognized approach in the clinical management of T2DM endorsed by national guideline.12
Among young T2DM subjects aged below 40 years, our previous work demonstrated that multiple risk factor clustering is common.13 This present study, by measuring WC to determine the presence of central obesity and quantifying the prevalence of MetS as a marker of risk factor clustering, confirms our previous observation. Young T2DM patients are increasingly recognized to be at risk of CVD complications as manifested by greater reduction in life expectancy compared to those diagnosed at later life with major cause of mortality due to CVD,14 higher relative risk of developing myocardial infarction15 and possessing adverse CVD risk profile.13,16 Preventing cardiovascular complication is therefore important. The strategy of risk stratification by determining the presence of additional cardiovascular risk factors as a guide to initiate lipid-lowering therapy for primary prevention of CVD as recommended by Joint British Societies-2 guideline12 may be a reasonable approach for T2DM subjects below 40 years. As there is paucity of clinical trial evidence in this young cohort, clinical judgement is required to initiate cardio-protective therapies and the observation from this study supports the Joint British Societies-2 recommendation.
The concept of MetS has been questioned including its ability to predict CVD complications.17 The IDF definition is no exception. In comparison to NCEP-ATPIII, the IDF definition was not a better predictor of CVD event and all-cause mortality in some T2DM populations.6,8,10 Various factors could have contributed to these observations including inaccurate WC threshold to define central obesity in certain ethnic groups,6,9,18 ethnic differences in the pathophysiology of diabetes19 and exclusion of CVD risk factors (such as LDL cholesterol) unrelated to insulin resistance from the MetS definition. Indispensability of central obesity in the IDF definition has also been questioned.6 This issue was illustrated in our cohort where almost 60% of patients deemed not to have IDF-defined MetS by failure to fulfil the mandatory WC threshold had multiple CVD risk factors.
There are limitations to this study. First, there is no prospective data on the development of CVD events and hence, the prognostic implications of the IDF and NCEP-ATPIII definitions could not be determined. In the UK, there is only one study performed in T2DM on the prognostic impact of MetS but it utilized modified NCEP-ATPIII definition where WC was substituted with body mass index as a measure of central obesity.5 Secondly, as this is a hospital clinic rather than population based, our observations may not be extrapolated to the majority of T2DM patients whose care is delivered in the community. It is possible that higher risk patients are preferentially referred to hospital clinics.
In conclusion, MetS is extremely common in a hospital population of T2DM regardless of age, sex, diabetes duration and prior history of CVD. Despite changes in the diagnostic criteria, the IDF definition is not better than NCEP-ATPIII in identifying T2DM patients with MetS. Both definitions could be used interchangeably for diagnostic purpose in this sample of UK population. However, the clinical value of diagnosing MetS in the CVD risk management of T2DM is debatable. From a pragmatic perspective, T2DM can be regarded as a high risk condition with multiple CVD risk factors. These individual risk factors should be actively searched for and intensively treated including among young patients (<40 years of age).
Conflict of interest: None declared.
|
References |
|---|
|
TopSummaryIntroductionMethodsResultsDiscussionReferences |
|---|
1. Alberti K, Zimmett P. Definition, diagnosis and classification of diabetes mellitus and its complication: Part 1: diagnosis and classification of diabetes mellitus. Report of a WHO consultation. Diabet Med (1998) 15:539–53.[CrossRef][Web of Science][Medline]
2. Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection. Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA (2001) 285:2486–97.
3. Balkau B, Charles MA. Comment on the provisional report from the WHO consultation. European Group for the Study of Insulin Resistance (EGIR). Diabet Med (1999) 16:442–43.[CrossRef][Web of Science][Medline]
4. Alberti KG, Zimmet P, Shaw J. The IDF Epidemiology Task Force Consensus Group. The metabolic syndrome: a new worldwide definition. Lancet (2005) 366:1059–62.[CrossRef][Web of Science][Medline]
5. Guzder RN, Gatling W, Mullee MA, Byrne CD. Impact of metabolic syndrome criteria on cardiovascular disease risk in people with newly diagnosed type 2 diabetes. Diabetologia (2006) 49:49–55.[CrossRef][Medline]
6. Sone H, Tanaka S, Ishibashi S, Yamasaki Y, Oikawa S, Ito H, et al. The new worldwide definition of metabolic syndrome is not a better diagnostic predictor of cardiovascular disease in Japanese diabetic patients than the existing definitions. Diabetes Care (2006) 29:145–47.
7. Targher G, Bertolini L, Tessari R, Zenari L, Arcaro G. The International Diabetes Federation definition of the metabolic syndrome independently predicts future cardiovascular events in type 2 diabetic patients. The Valpolicella Heart Diabetes Study. Diabet Med (2006) 23:1268–74.[Web of Science][Medline]
8. Monami M, Marchionni N, Masotti G, Mannucci E. IDF and ATPIII definitions of metabolic syndrome in the prediction of all-cause mortality in type 2 diabetic patients. Diabetes, Obese Metab (2007) 9:350–53.[CrossRef]
9. Lu B, Yang Y, Song X, Dong X, Zhang Z, Zhou L, et al. An evaluation of the International Diabetes Federation definition of metabolic syndrome in Chinese patients older than 30 years old and diagnosed with type 2 diabetes mellitus. Metabolism (2006) 55:1088–96.[CrossRef][Web of Science][Medline]
10. Tong PC, Kong AP, So WY, Yang X, Ho CS, Ma RC, et al. The usefulness of the International Diabetes Federation and the National Cholesterol Education Program's Adult Treatment Panel III Definitions of the metabolic syndrome in predicting coronary heart disease in subjects with type 2 diabetes. Diabetes Care (2007) 30:1206–11.
11. Gaede P, Vedel P, Larsen N, Jensen GV, Parving HH, Pedersen O. Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. N Engl J Med (2003) 348:383–93.
12. British Cardiac Society, British Hypertension Society, Diabetes UK, Heart UK, Primary Care Cardiovascular Society, Stroke Society. Joint British Societies’ guidelines on prevention of cardiovascular disease in clinical practice. Heart (2005) 91(Suppl V):v1–52.
13. Song SH, Hardisty CA. Cardiovascular risk profile of early and later onset type 2 diabetes. Practical Diabetes International (2007) 24:20–4.[CrossRef]
14. Roper NA, Bilous RW, Kelly WF, Unwin NC, Connolly VM. Excess mortality in a population with diabetes and the impact of material deprivation: longitudinal, population based study. Br Med J (2001) 322:1389–93.
15. Hillier TA, Pedula KL. Complications in young adults with early-onset type 2 diabetes: losing the relative protection of youth. Diabetes Care (2003) 26:2999–3005.
16. Hatunic M, Burns N, Finucane F, Mannion C, Nolan JJ. Contrasting clinical and cardiovascular risk status between early and later onset type 2 diabetes. Diabetes Vasc Dis Res (2005) 2:73–5.[CrossRef]
17. Kahn R, Buse J, Ferrannini E, Stern M. The metabolic syndrome: time for a critical appraisal: joint statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care (2005) 28:2289–304.
18. Hayashi T, Bokyo EJ, McNeely MJ, Leonetti DL, Kahn SE, Fujimoto WY. Minimum waist and visceral fat values for identifying Japanese Americans at risk for the metabolic syndrome. Diabetes Care (2007) 30:120–27.
19. Mitsui R, Fukushima M, Nishi Y, Ueda N, Suzuki H, Taniguchi A, et al. Factors responsible for deteriorating glucose intolerance in newly diagnosed type 2 diabetes in Japanese men. Metabolism (2006) 55:53–8.[CrossRef][Web of Science][Medline]
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  S. H Song and T. A Gray Management of type 2 diabetes and lipids: a critique of the NICE guidelines 2008 The British Journal of Diabetes & Vascular Disease, March 1, 2009; 9(2): 69 - 74. [Abstract] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||