Cardiovascular Diabetology
BioMed Central
Open Access
Original investigation
Metabolic syndrome and risk of incident diabetes: findings from the European Prospective Investigation into Cancer and Nutrition-Potsdam Study Earl S Ford*1, Matthias B Schulze2, Tobias Pischon3, Manuela M Bergmann3, Hans-Georg Joost4 and Heiner Boeing3 Address: 1Division of Adult and Community Health, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia, USA, 2Public Health Nutrition Unit, Technische Universität München, Center of Life and Food Sciences, Freising, Germany, 3Department of Epidemiology, German Institute for Human Nutrition (DIfE), Potsdam-Rehbrücke, Nuthetal, Germany and 4Department of Pharmacology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany Email: Earl S Ford* -
[email protected]; Matthias B Schulze -
[email protected]; Tobias Pischon -
[email protected]; Manuela M Bergmann -
[email protected]; Hans-Georg Joost -
[email protected]; Heiner Boeing -
[email protected] * Corresponding author
Published: 12 December 2008 Cardiovascular Diabetology 2008, 7:35
doi:10.1186/1475-2840-7-35
Received: 8 October 2008 Accepted: 12 December 2008
This article is available from: http://www.cardiab.com/content/7/1/35 © 2008 Ford et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract Background: Several aspects concerning the relationship between the metabolic syndrome and incident diabetes are incompletely understood including the magnitude of the risk estimate, potential gender differences in the associations between the metabolic syndrome and incident diabetes, the associations between the components of the metabolic syndrome and incident diabetes, and whether the metabolic syndrome provides additional prediction beyond its components. To shed light on these issues, we examined the prospective association between the metabolic syndrome defined by the National Cholesterol Education Program (NCEP) and International Diabetes Federation (IDF) and diabetes. Methods: We used data for 2796 men and women aged 35–65 years from the European Prospective Investigation into Cancer and Nutrition-Potsdam Study followed for an average of 6.9 years. This analysis employed a case-cohort design that included 697 participants who developed diabetes and 2099 participants who did not. Incident diabetes was identified on the basis of self-reports and verified by contacting the patient's attending physician. Results: The adjusted hazard ratio for the NCEP definition was 4.62 (95% confidence interval [CI]: 3.90– 5.48) and that for the IDF definition was 4.59 (95% CI: 3.84–5.50). The adjusted hazard ratios for the NCEP but not IDF definition were higher for women than men. When participants who had no cardiometabolic abnormalities were used as the reference group for the NCEP definition, the adjusted hazard ratio for having 3 or more abnormalities increased to 22.50 (95% CI: 11.21–45.19). Of the five components, abdominal obesity and hyperglycemia were most strongly associated with incident diabetes. Conclusion: In this study population, both definitions of the metabolic syndrome provided similar estimates of relative risk for incident diabetes. The increase in risk for participants with the metabolic syndrome according to the NCEP definition was very large when contrasted with the risk among those who had no cardiometabolic abnormalities.
Page 1 of 8 (page number not for citation purposes)
Cardiovascular Diabetology 2008, 7:35
Introduction The concept of the metabolic syndrome can be traced back to as early as 1923 when an association between hypertension, uric acid, and hyperglycemia was reported [1]. Since major organizations started formulating definitions for this syndrome in 1998, it has been the object of intense research. Although it has been shown to be a significant predictor of diabetes, cardiovascular disease, and all-cause mortality [2], controversy about its importance as a risk factor remains [3]. The most recent definition of the metabolic syndrome was developed by the International Diabetes Federation (IDF) in 2005 [4]. This definition places a major emphasis on central obesity. Since that time, several reports have examined the associations between the metabolic syndrome as defined by the IDF and incident diabetes and compared these risk estimates to those calculated using other definitions [5-13]. However, several issues remain unresolved including the presence of potential gender differences in the risk for incident diabetes associated with the metabolic syndrome and whether the metabolic syndrome offers additional prediction beyond its components. To examine these issues and to compare the ability of the metabolic syndrome to predict the risk of developing diabetes using two definitions, namely those of the National Cholesterol Education Program (NCEP) and IDF, we used data from a large prospective German study.
Methods Study population The European Prospective Investigation into Cancer and Nutrition (EPIC) Potsdam study is part of the multi-centre prospective cohort study EPIC [14,15]. In Potsdam, Germany, 27,548 subjects, 16,644 women mainly aged 35– 65 years and 10,904 men mainly aged 40–65 years, from the general population were recruited between 1994 and 1998 [16]. The baseline examination included anthropometric measurements, a personal interview including questions on prevalent diseases, and a questionnaire on socio-demographic and lifestyle characteristics. Follow-up questionnaires to identify incident cases of diabetes mellitus have been administered every 2 to 3 years. Response rates for each of the three waves of follow-up were about 95%. We also considered questionnaires that were part of the ongoing fourth wave of follow-up round and were sent out until January 31st 2005. By August 31st 2005, 90% of them were returned. Consent was obtained from all participants of the study, and approval was given by the Ethical Committee of the State of Brandenburg, Germany. The conduct of the study was performed in accordance with principles of the Declaration of Helsinki.
http://www.cardiab.com/content/7/1/35
Ascertainment of incident type 2 diabetes Potentially incident cases of diabetes were those with selfreports of a diabetes diagnosis, diabetes-relevant medication, or dietary treatment due to diabetes. All potentially incident cases were verified by questionnaires mailed to the diagnosing physician asking about the date and type of diagnosis, diagnostic tests, and treatment of diabetes. Only cases with a physician diagnosis of type 2 diabetes (International Classification of Diseases, 10th Revision: E11) and a diagnosis date after the baseline examination were considered as confirmed incident cases of type 2 diabetes and were used in the analysis. Ascertainment of prevalent type 2 diabetes Self-reported diabetes mellitus at baseline was evaluated by a study physician using information on self-reported medical diagnoses, medication records and dieting behavior. Uncertainties regarding a proper diagnosis were clarified with the participant or treating physician. We also used plasma concentrations of glucose to define prevalent diabetes. Because many participants did not provide fasting blood samples, we defined diabetes as a fasting plasma glucose ≥ 126 mg/dl or a nonfasting plasma glucose of ≥ 200 mg/dl. Case-cohort construction The case-cohort consisted of a random sample of participants from the full cohort and all participants from the full cohort who developed incident diabetes. Thus, a random sample of 2,500 participants (subcohort) was drawn from the participants of the full cohort who had blood samples available (26,444 of 27,548). After excluding participants with prevalent diabetes and missing information for study covariates, the subcohort included 2,165 participants. Of the 801 participants from the full cohort with blood samples who developed incident diabetes, 697 remained for analyses after the exclusion criteria were applied. Because the subcohort is representative of the full cohort at baseline in case-cohort studies, the random sample of the full cohort included 66 of the 697 subjects who developed incident type 2 diabetes during follow-up. Metabolic syndrome According to the IDF definition, someone has the metabolic syndrome if he or she has central adiposity plus ≥ 2 of the following four factors [4]:
1. raised concentration of triglycerides: ≥ 150 mg/dl (1.7 mmol/L) or specific treatment for this lipid abnormality; 2. reduced concentration of high-density lipoprotein cholesterol: < 40 mg/dl (1.03 mmol/L) in males and < 50 mg/ dl (1.29 mmol/L) in females or specific treatment for this lipid abnormality;
Page 2 of 8 (page number not for citation purposes)
Cardiovascular Diabetology 2008, 7:35
3. raised blood pressure: systolic blood pressure ≥ 130 mmHg or diastolic blood pressure ≥ 85 mmHg or treatment of previously diagnosed hypertension; 4. raised fasting plasma glucose ≥ 100 mg/dl (5.6 mmol/ l) or previously diagnosed type 2 diabetes. For this study of German participants, we used a waist circumference threshold of ≥ 94 cm for men and ≥ 80 cm for women. Using the 2004 National Heart, Lung, and Blood Institute/American Heart Association revision of the original NCEP criteria, participants who had three or more of the following criteria were defined as having the metabolic syndrome [17,18]: 1. abdominal obesity (waist circumference >102 cm in men and >88 cm in women); 2. concentration of triglycerides ≥ 150 mg/dl (1.7 mmol/l); 3. concentration of high-density lipoprotein cholesterol
