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Diabetes Care 29:2515-2517, 2006
DOI: 10.2337/dc06-0330
© 2006 by the American Diabetes Association
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Cardiovascular and Metabolic Risk
Brief Report

Is the Third Component of Metabolic Syndrome Really Predictive of Outcomes in Type 2 Diabetic Patients?

Matteo Monami, MD, Lorella Lambertucci, MD, Andrea Ungar, MD, Maria Pieri, MD, Giulio Masotti, MD, Niccolò Marchionni, MD and Edoardo Mannucci, MD

From the Department of Critical Care Medicine and Surgery, Unit of Gerontology and Geriatrics, University of Florence, Florence, Italy

Address correspondence and reprint requests to Edoardo Mannucci, MD, Department of Critical Care Medicine and Surgery, Unit of Gerontology and Geriatrics, University of Florence and Azienda Ospedaliera Careggi, Via delle Oblate 4, 50134 Florence, Italy. E-mail: edmannu{at}tin.it or mmonami{at}libero.it

Abbreviations: ATP, Adult Treatment Panel


   INTRODUCTION
TOP
 INTRODUCTION
RESEARCH DESIGN AND METHODS--
 RESULTS--
 CONCLUSIONS--
 References
 
The use of the category of metabolic syndrome in patients with type 2 diabetes has been questioned by many authors (1,2). In fact, in most studies performed in the general population, the diagnosis of metabolic syndrome is associated with increased risk of diabetes (3–5) and, to a lesser extent, of cardiovascular disease (6); however, data on the impact of metabolic syndrome on cardiovascular morbidity and mortality in type 2 diabetic patients are inconclusive (7–11). Some authors found that, in type 2 diabetes, the presence of one further component of metabolic syndrome beyond diabetes confers a risk profile similar to that of full metabolic syndrome (12). Furthermore, the Adult Treatment Panel (ATP)-III definition of metabolic syndrome considers five parameters (fasting hyperglycemia, high blood pressure, low HDL cholesterol, hypertriglyceridemia, and high waist circumference) equally relevant for diagnosis, although each one of them is associated to a different extent with insulin resistance (13) and cardiovascular disease (14).


   RESEARCH DESIGN AND METHODS—
TOP
 INTRODUCTION
 RESEARCH DESIGN AND METHODS--
RESULTS--
 CONCLUSIONS--
 References
 
An observational cohort study was performed on four consecutive series of type 2 diabetic patients resident in the city of Florence, Italy, with elevated blood pressure (sample A), hypertriglyceridemia (sample B), low HDL cholesterol (sample C), and elevated waist circumference (sample D), as defined by ATP-III criteria for metabolic syndrome (15), who were visited at the Diabetes and Metabolic Diseases Clinic of the Geriatric Unit of the University of Florence between 1 January 2000 and 31 December 2002. The four samples (A, B, C, and D), which were consecutively enrolled one after another (each during a period of 6 months) are described in Table 1.


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  		Table 1— Baseline characteristics of the four samples

 
All patients underwent a physical examination; weight and height were measured without shoes and in light clothing, while waist circumference (16) and blood pressure (17) were measured according to current recommendations. Laboratory determinations were performed in the central laboratory of Careggi Hospital, Florence, Italy, on blood samples drawn in the morning after an overnight fast. Total cholesterol, HDL cholesterol, and triglycerides were determined by an automated enzymatic method (Beckman, Brea, CA). Diagnosis of metabolic syndrome was performed using ATP-III criteria (15).

Information on all-cause mortality over 3 years after the first visit was obtained by the City of Florence Registry Office, which contains complete and updated records of all individuals living within city boundaries. For those who had moved away, queries were sent to the registry office of the new city of residence.

Statistical analysis
Normally and nonnormally distributed parameters were expressed as means ± SD and median (quartile range), respectively. {chi}2 test was used for comparisons of categorical variables. Relative risk with 95% CIs were calculated, and a Cox regression was performed for multivariate analysis. All statistical analysis was performed with SPSS 12.0.1.


   RESULTS—
TOP
 INTRODUCTION
 RESEARCH DESIGN AND METHODS--
 RESULTS--
CONCLUSIONS--
 References
 
The mean duration of follow-up was 32.9 ± 8.1, 32.5 ± 8.8, 33.6 ± 7,1, and 33.0 ± 8.2 months, in sample A, B, C, and D, respectively. Ninenteen (3.4%), 22 (3.7%), 22 (4.1%), and 18 (3.6%) patients of sample A, B, C, and D, respectively, were lost at follow-up; their characteristics were not significantly different from those of the rest of the samples (data not shown). Forty (7.6%), 67 (11.8%), 76 (14.6%), and 61 (11.2%) deaths were recorded among patients enrolled in sample A, B, C, and D, respectively.

Among patients of sample A, those with metabolic syndrome at baseline did not show a significantly higher mortality than those without metabolic syndrome (7.9 vs. 6.4%); similar results were obtained in sample B (12.0 vs. 10.7%), C (19.0 vs. 14.0%), and D (11.9 vs. 11.1%). Diagnosis of metabolic syndrome was not associated with increased mortality in any of the samples studied, even after adjustment for age and sex at Cox regression analysis (data not shown).

In diabetic patients with elevated blood pressure (sample A), after adjustment for age and sex, separate Cox regression analyses showed that low HDL cholesterol (adjusted odds ratio [OR] 2.6 [95% CI 1.2–5.5]), but not hypertriglyceridemia and high waist circumference, was associated with higher mortality. Among diabetic patients with hypertriglyceridemia (sample B), low HDL cholesterol (sample C), and elevated waist circumference (sample D), mortality was associated with high blood pressure (2.7 [1.4–5.1], 1.4 [1.1–2.4], and 2.3 [1.3–4.2], respectively). No other component of metabolic syndrome was significantly associated with mortality in these samples. Similar results were obtained after adjustment for duration of diabetes and medication, i.e., insulin, insulin sensitizers, insulin secretagogues, ACE inihibitors/angiotensin receptor blockers, and statins (data not shown). Combinations of any two metabolic syndrome components were not significantly associated with higher mortality in any of the four samples (data not shown).


   CONCLUSIONS—
TOP
 INTRODUCTION
 RESEARCH DESIGN AND METHODS--
 RESULTS--
 CONCLUSIONS--
References
 
The diagnosis of metabolic syndrome in patients with diabetes plus one more risk factor does not add any prognostic value in type 2 diabetic patients, in accordance with previous studies (12).

Hypertension is known as a major determinant of micro- and macrovascular disease in type 2 diabetes; in fact, treatment of elevated blood pressure substantially improves long-term morbidity and mortality (18). In diabetic patients with hypertriglyceridemia, low HDL cholesterol, or elevated waist circumference, hypertension was significantly associated with increased mortality. These data suggest that high blood pressure is a relevant independent risk factor. Conversely, the other components of metabolic syndrome do not seem to confer additional risk when two other ATP-III criteria for the syndrome are fulfilled. The notable exception is represented by low HDL cholesterol, which is associated with increased mortality in type 2 diabetic hypertensive patients only. These results need to be confirmed by further studies exploring cardiovascular morbidity.

The current ATP-III criteria for diagnosis of metabolic syndrome attribute the same relevance and diagnostic value to all the five parameters of the syndrome (5). The present analysis confirms that a different risk profile is determined by different combinations of metabolic alterations. For this reason, a diagnosis of metabolic syndrome based only on the unweighed number of components present in each patient, without considering each specific combination, could be inadequate for the prediction of risk level. This could explain the relatively unsatisfactory performance of diagnosis of metabolic syndrome in the prediction of cardiovascular morbidity and mortality in long-term epidemiological studies in type 2 diabetic patients.


   Footnotes
 
A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received for publication February 9, 2006. Accepted for publication July 16, 2006.


   References
TOP
 INTRODUCTION
 RESEARCH DESIGN AND METHODS--
 RESULTS--
 CONCLUSIONS--
 References
 

  1. 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 28:2289–2304, 2005[Abstract/Free Full Text]
  2. Reaven GM: The metabolic syndrome: requiescat in pace. Clin Chem 51:931–938, 2005[Abstract/Free Full Text]
  3. Boyko EJ, de Courten M, Zimmet PZ, Chitson P, Tuomilehto J, Alberti KG: Features of the metabolic syndrome predict higher risk of diabetes and impaired glucose tolerance: a prospective study in Mauritius. Diabetes Care 23:1242–1248, 2000[Abstract/Free Full Text]
  4. Lorenzo C, Okoloise M, Williams K, Stern MP, Haffner SM: The metabolic syndrome as predictor of type 2 diabetes: the San Antonio Heart Study. Diabetes Care 26:3153–3159, 2003[Abstract/Free Full Text]
  5. Wang JJ, Qiao Q, Miettinen ME, Lappalainen J, Hu G, Tuomilehto J: The metabolic syndrome defined by factor analysis and incident type 2 diabetes in a chinese population with high postprandial glucose. Diabetes Care 27:2429–2437, 2004[Abstract/Free Full Text]
  6. Ford ES: Risks for all-cause mortality, cardiovascular disease, and diabetes associated with the metabolic syndrome: a summary of the evidence. Diabetes Care 28:1769–1778, 2005[Abstract/Free Full Text]
  7. Isomaa B, Almgren P, Tuomi T, Forsen B, Lahti K, Nissen M, Taskinen MR, Groop L: Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care 24:683–689, 2001[Abstract/Free Full Text]
  8. Bonora E, Targher G, Formentini G, Calcaterra F, Lombardi S, Marini F, Zenari L, Saggiani F, Poli M, Perbellini S, Raffaelli A, Gemma L, Santi L, Bonadonna RC, Muggeo M: The metabolic syndrome is an independent predictor of cardiovascular disease in type 2 diabetic subjects: prospective data from the Verona Diabetes Complications Study. Diabet Med 21:52–58, 2004[Medline]
  9. Hunt KJ, Resendez RG, Williams K, Haffner SM, Stern MP: National Cholesterol Education Program versus World Health Organization metabolic syndrome in relation to all-cause and cardiovascular mortality in the San Antonio Heart Study. Circulation 110:1251–1257, 2004[Abstract/Free Full Text]
  10. Lakka HM, Laaksonen DE, Lakka TA, Niskanen LK, Kumpusalo E, Tuomilehto J, Salonen JT: The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men. JAMA 288:2709–2716, 2002[Abstract/Free Full Text]
  11. Golden SH, Chong R: Are there specific components of the insulin resistance syndrome that predict the increased atherosclerosis seen in type 2 diabetes mellitus? Curr Diab Rep 4:26–30, 2004[Medline]
  12. Bruno G, Merletti F, Biggeri A, Bargero G, Ferrero S, Runzo C, Prina CS, Pagano G, Cavallo-Perin P: Metabolic syndrome as a predictor of all-cause and cardiovascular mortality in type 2 diabetes: the Casale Monferrato Study. Diabetes Care 27:2689–2694, 2004[Abstract/Free Full Text]
  13. Hanson RL, Imperatore G, Bennett PH, Knowler WC: Components of the "metabolic syndrome" and incidence of type 2 diabetes. Diabetes 51:3120–3127, 2002[Abstract/Free Full Text]
  14. Malik S, Wong ND, Franklin SS, Kamath TV, L’Italien GJ, Pio JR, Williams GR: Impact of the metabolic syndrome on mortality from coronary heart disease, cardiovascular disease, and all causes in United States adults. Circulation 110:1245–1250, 2004[Abstract/Free Full Text]
  15. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults: 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 285:2486–2497, 2001[Free Full Text]
  16. World Health Organization: Obesity: Preventing and Managing the Global Epidemic: Report of a WHO Consultation. Geneva, World Health Org., 2000 (Tech. Rep. Ser., no. 894)
  17. Chalmers J, MacMahon S, Mancia G, Whitworth J, Beilin L, Hansson L, Neal B, Rodgers A, Ni MC, Clark T: 1999 World Health Organization-International Society of Hypertension Guidelines for the management of hypertension: guidelines sub-committee of the World Health Organization. Clin Exp Hypertens 21:1009–1060, 1999[Medline]
  18. UK Prospective Diabetes Study Group: Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38: UK Prospective Diabetes Study Group. BMJ 317:703–713, 1998[Abstract/Free Full Text]

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[Abstract] [Full Text] [PDF]

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