Epidemiology/Health Services/Psychosocial Research O R I G I N A L
A R T I C L E
Development of Diabetes in Chinese With the Metabolic Syndrome A 6-year prospective study BERNARD M.Y. CHEUNG, PHD1 NELSON M.S. WAT, FRCP1 YU BUN MAN, MPHIL 1 SIDNEY TAM, FACB2 G. NEIL THOMAS, PHD3 GABRIEL M. LEUNG, MD3
CHUN HO CHENG, FRCP1 JEAN WOO, MD4 EDWARD D. JANUS, MD5 CHU PAK LAU, MD1 TAI HING LAM, MD3 KAREN S.L. LAM, MD1
OBJECTIVE — We investigated the association of the metabolic syndrome with new-onset diabetes in the Hong Kong Cardiovascular Risk Factor Prevalence Study cohort. RESEARCH DESIGN AND METHODS — We followed up on 1,679 subjects without diabetes at baseline. Those with a previous diagnosis of diabetes or those who were receiving drug treatment were considered to be diabetic. The remaining subjects underwent a 75-g oral glucose tolerance test (OGTT). Diabetes was defined by plasma glucose ⱖ7.0 mmol/l with fasting and/or ⱖ11.1 mmol/l at 2 h. RESULTS — The prevalences of the metabolic syndrome at baseline were 14.5 and 11.4%, respectively, according to U.S. National Cholesterol Education Program (NCEP) and International Diabetes Federation (IDF) criteria. After a median of 6.4 years, there were 66 and 54 new cases of diabetes in men and women, respectively. The metabolic syndrome at baseline predicted incident diabetes. Hazard ratios (HRs) for the NCEP and IDF definitions of the syndrome were 4.1 [95% CI 2.8 – 6.0] and 3.5 [2.3–5.2], respectively. HRs for fasting plasma glucose (FPG) ⱖ6.1 or 5.6 mmol/l were 6.9 [4.1–11.5] and 4.1 [2.8 – 6.0], respectively. The NCEP and IDF criteria had 41.9 and 31.7% sensitivity and 87.5 and 90.2% specificity, respectively. Their positive predictive values were low, ⬃20%, but their negative predictive values were ⬃95%. CONCLUSIONS — The metabolic syndrome, particularly its component, elevated FPG, predicts diabetes in Chinese. An individual without the metabolic syndrome is unlikely to develop diabetes, but one who has it should practice therapeutic lifestyle changes and have periodic FPG measurements to detect new-onset diabetes. Diabetes Care 30:1430–1436, 2007
T
he metabolic syndrome has been promoted as a clinical tool for identifying individuals predisposed to diabetes and/or adverse cardiovascular outcomes (1–7). Attempts have been made by different consensus groups to
produce diagnostic criteria for the syndrome, but there is still some controversy. The pathogenetic mechanism underlying the metabolic syndrome remains uncertain, although central obesity and insulin resistance have been proposed to play a
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From 1Department of Medicine, University of Hong Kong, Hong Kong, China; 2Department of Clinical Biochemistry Unit, Queen Mary Hospital, Hong Kong, China; 3Department of Community Medicine, University of Hong Kong, Hong Kong, China; 4Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong, China; and 5Department of Medicine, University of Melbourne, Western Hospital, Footscray, Victoria, Australia. Address correspondence and reprint requests to Prof. Bernard M.Y. Cheung, University Department of Medicine, Queen Mary Hospital, Pokfulam, Hong Kong, China. E-mail:
[email protected]. Received for publication 30 August 2006 and accepted in revised form 18 February 2007. Published ahead of print at http://care.diabetesjournals.org on 2 March 2007. DOI: 10.2337/dc06-1820. Abbreviations: CRISPS, Hong Kong Cardiovascular Risk Factor Prevalence Study; FPG, fasting plasma glucose; IDF, International Diabetes Federation; IFG, impaired fasting glucose; HOMA-IR, homeostasis model assessment estimate of insulin resistance; NCEP, National Cholesterol Education Program; OGTT, oral glucose tolerance test; ROC, receiver operating characteristic. A table elsewhere in this issue shows conventional and Syste`me International (SI) units and conversion factors for many substances. © 2007 by the American Diabetes Association.
causative role. Because insulin resistance, together with hyperinsulinemia, is a fundamental metabolic abnormality in type 2 diabetes, the metabolic syndrome may be expected to be a good predictor of the development of the latter. Asians are thought to have a higher body fat percentage and cardiovascular risks than Caucasians at a given BMI (8). These factors raise concerns that definitions of the metabolic syndrome for Caucasians, when applied to Asian populations, would underestimate the population at risk of developing adverse outcomes such as type 2 diabetes, cardiovascular disease, and mortality. Therefore, validation of the predictive value of the metabolic syndrome needs to be established in population-based cohorts of different ethnicities. The International Diabetes Federation (IDF) proposed a new definition of the metabolic syndrome, which uses ethnicspecific central obesity criteria as a prerequisite for diagnosis of the syndrome (4). The American Heart Association/ National Heart, Lung, and Blood Institute update of the U.S. National Cholesterol Education Program (NCEP) Adult Treatment Panel III guidelines also recommended similar criteria for central obesity in Asians (3). In the present study, we sought to examine the predictive ability of the metabolic syndrome for the development of diabetes in a population-based cohort of nondiabetic Chinese men and women, who were followed-up for a median of 6.4 years. We compared two definitions of the metabolic syndrome: the updated NCEP definition (3) and the IDF definition (4). We also sought to identify the components of the metabolic syndrome that were predictive of the development of diabetes.
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RESEARCH DESIGN AND METHODS — The Hong Kong Cardiovascular Risk Factor Prevalence Study (CRISPS) was a cohort study of cardiovascular risk factors in Hong Kong Chinese. In 1995–1996, a random sample of 2,895 Hong Kong Chinese (1,412 men and 1,483 women, aged 25–74 years) was recruited from the general population using
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Cheung and Associates
Figure 1—Flow of study subjects.
random telephone numbers (9 –14). This method had been validated locally; those enrolled at baseline were representative of the general population (12). In 2000 – 2004, the subjects in this cohort were invited for follow-up in the Hong Kong CRISPS2. Completion of enrollment was delayed because of the outbreak of severe acute respiratory syndrome in 2003. The study protocol was approved by the Ethics Committee of the University of Hong Kong. All subjects gave written consent. The flow of subjects is shown in Fig. 1. Of the 2,895 subjects who initially participated (CRISPS1), 1,944 (901 men and 1,043 women; aged 52 ⫾ 12 years; response rate ⫽ 67.2%) enrolled in the follow-up study (CRISPS2). The baseline characteristics of the 1,944 participants in CRISPS2 were comparable to those of the 951 nonparticipants in terms of age, BMI, LDL cholesterol, drinking habits, and the frequency of hypertension, stroke, and ischemic heart disease. However, those subjects who reenrolled were more likely to be female (54% vs. 47% in nonparticipants), married (85% vs. 77%), and nonDIABETES CARE, VOLUME 30, NUMBER 6, JUNE 2007
smokers (77% vs. 70%) (P ⬍ 0.001). They were less likely to be diabetic at baseline (9% vs. 12%, P ⫽ 0.04). The follow-up visits took place in the morning after overnight fasting. Demographic data, including sex, age, occupation, smoking and drinking habits, and history of cardiovascular diseases, hypertension, and diabetes, were recorded. Subjects underwent a brief physical examination that included measurement of height, weight, and waist and hip circumference. Height was measured to the nearest 0.5 cm and weight to the nearest 0.1 kg (Detecto Instrument, Webb City, MO). BMI was calculated as weight in kilograms divided by the square of height in centimeters (2). Waist and hip circumferences were measured twice to the nearest 0.5 cm, and the arithmetic means were used. Waist circumference was measured halfway between the xiphisternum and the umbilicus, whereas hip circumference was measured at the level of the greater trochanters. Blood pressure was measured using a mercury sphygmomanometer according
to a standardized protocol. Subjects were seated at rest for at least 10 min, and three measurements were taken at 5-min intervals. The Korotkoff V sound was used to determine diastolic blood pressure. Venous blood (20 ml) was taken for blood biochemistry and lipid profile analysis. Lipids were measured on a Hitachi 912 analyzer as described previously (12). LDL cholesterol was calculated using Friedewald’s equation if the total triglyceride concentration was not ⬎4.5 mmol/l. Otherwise, LDL was determined by a direct assay using selective micellar solubilization of LDL by a nonionic detergent in an enzyme-coupled colorimetric assay automated on the Hitachi 912 analyzer. Glucose was measured by the hexokinase method on the Hitachi 912 analyzer. Insulin was measured by microparticle enzyme immunoassay (Abbott Laboratories, Tokyo, Japan). The homeostasis model assessment estimate of insulin resistance (HOMA-IR), a simple assessment of insulin sensitivity, was calculated using the following formula: fasting plasma glucose (FPG) (millimoles per liter) ⫻ fasting insulin (microunits per milliliter)/22.5 (15). Diabetes was defined as FPG ⱖ7.0 mmol/l (126 mg/dl) or 2-h plasma glucose ⱖ11.1 mmol/l (200 mg/dl) or both (16). Impaired fasting glucose (IFG) was defined as FPG of 5.6 – 6.9 mmol/l (100 – 125 mg/dl) (16). For comparison, the cut point of 6.1 mmol/l (110 mg/dl) for IFG was also analyzed. The NCEP criteria for the metabolic syndrome are fulfilled if an Asian individual has three or more of the following: 1) waist circumference ⱖ90 cm (35 inches) in men and ⱖ80 cm (31 inches) in women, 2) triglyceride concentration ⱖ150 mg/dl (1.7 mmol/l), 3) HDL cholesterol ⬍40 mg/dl (1.03 mmol/l) in men and ⬍50 mg/dl (1.29 mmol/l) in women, 4) blood pressure ⱖ130/85 mmHg, or 5) fasting glucose ⱖ100 mg/dl (5.6 mmol/l) (3,17). Receiving specific treatment for a criterion is counted as fulfilling the criterion. In the original NCEP Adult Treatment Panel III definition, the fasting glucose cut point was ⱖ110 mg/dl (ⱖ6.1 mmol/l) (1). This was later revised to ⱖ100 mg/dl (5.6 mmol/l) (2). The IDF criteria for the metabolic syndrome are similar to the NCEP criteria except that central obesity, defined using sex- and ethnic-specific criteria (waist circumference ⱖ90 cm in Chinese men and ⱖ80 cm in Chinese women), is a prerequisite (4). 1431
Diabetes in Chinese with metabolic syndrome Table 1—Baseline characteristics of subjects with no history of diabetes stratified by metabolic syndrome status Metabolic syndrome, NCEP criteria (3)
n Age (years) Male (%) Diabetes in either parent (%) BMI (kg/m2) Waist circumference (cm) Waist-to-hip ratio Systolic blood pressure (mmHg) Diastolic blood pressure (mmHg) Fasting glucose (mmol/l) OGTT 2-h glucose (mmol/l) Total cholesterol (mmol/l) Triglycerides (mmol/l) HDL cholesterol (mmol/l) HOMA-IR Fasting insulin (mIU/l) Tobacco use† Male (%) Female (%) Regular alcohol consumption‡ Male (%) Female (%) Physically active§
Metabolic syndrome, IDF criteria (4)
Total
Without
With
Without
With
1,679 45.1 ⫾ 11.9 46.6 16.4 24.0 ⫾ 3.5 78.2 ⫾ 9.7 0.83 ⫾ 0.08 117.8 ⫾ 18.5 74.1 ⫾ 10.4 5.1 ⫾ 0.5 6.1 ⫾ 1.6 5.0 ⫾ 0.9 1.1 ⫾ 0.7 1.3 ⫾ 0.3 1.1 (0.7–1.7) 4.8 (3.1–7.1)
1,511 43.6 ⫾ 11.4 45.9 15.7 23.3 ⫾ 3.2 76.4 ⫾ 8.7 0.82 ⫾ 0.08 114.6 ⫾ 15.7 72.6 ⫾ 9.2 5.0 ⫾ 0.5 5.9 ⫾ 1.5 4.9 ⫾ 0.9 1.0 ⫾ 0.5 1.3 ⫾ 0.3 1.0 (0.7–1.5) 4.4 (3.0–6.7)
168 51.2 ⫾ 11.1* 50.6 20.1 27.6 ⫾ 3.5* 88.6 ⫾ 8.7* 0.90 ⫾ 0.07* 137.6 ⫾ 20.4* 84.3 ⫾ 10.9* 5.5 ⫾ 0.5* 7.4 ⫾ 1.7* 5.5 ⫾ 1.0* 2.0 ⫾ 0.9* 1.0 ⫾ 0.2* 1.9 (1.3–2.7)* 7.9 (5.7–11.2)*
1,488 44.1 ⫾ 11.6 46.6 15.9 23.4 ⫾ 3.2 76.5 ⫾ 8.5 0.82 ⫾ 0.08 115.4 ⫾ 16.7 72.9 ⫾ 9.8 5.1 ⫾ 0.5 6.0 ⫾ 1.6 5.0 ⫾ 0.9 1.0 ⫾ 0.6 1.3 ⫾ 0.3 1.0 (0.7–1.5) 4.4 (3.0–6.5)
191 53.2 ⫾ 11.5* 46.6 20.0 28.6 ⫾ 3.0* 91.7 ⫾ 7.1* 0.92 ⫾ 0.07* 136.6 ⫾ 21.2* 83.5 ⫾ 10.7* 5.4 ⫾ 0.5* 7.4 ⫾ 1.7* 5.4 ⫾ 0.9* 1.9 ⫾ 0.8* 1.0 ⫾ 0.2* 2.0 (1.3–2.7)* 8.2 (5.8–11.0)*
46.2 3.7
46.1 3.4
46.7 5.0
45.4 3.5
52.8 4.9
28.5 5.3 36.7
28.9 5.7 36.5
26.5 2.3 36.8
28.9 5.7 36.5
27.4 2.5 38.2
Data are shown as means ⫾ SD, median (interquartile range), or %. Student’s unpaired t test, Mann-Whitney test, and Fisher’s exact test were used as appropriate. *P ⬍ 0.001. †Ever been a smoker. ‡At least once a week. §Taking exercise at least once a week in the past month.
Statistical analysis Baseline characteristics were compared between groups using Student’s unpaired t test, Mann-Whitney test, McNemar test, or Fisher’s exact test. Of the 1,944 sub-
jects who participated in the follow-up study (CRISPS2), there were 1,679 subjects who did not have type 2 diabetes initially and were thus included in the present analysis. Incidence rates of diabe-
tes in subjects with or without the metabolic syndrome at baseline with 95% CIs were assessed. Cox proportional hazards regression was used to estimate the ageadjusted hazard ratios (HRs) and 95% CI
Table 2—Association of the metabolic syndrome and its components with the risk of incident diabetes
Prevalence at baseline (%) Metabolic syndrome (original NCEP criteria) (1) Metabolic syndrome (FPG ⱖ5.6 mmol/l) (2) Metabolic syndrome (FPG ⱖ5.6 mmol/l and Asian cut points for waist circumference) (3) Metabolic syndrome (IDF criteria) (4) Central obesity (original NCEP criteria) (1) Central obesity (Asian criteria) (3,4) High blood pressure Hyperglycemia (ⱖ5.6 mmol/l) Hyperglycemia (ⱖ6.1 mmol/l) Hypertriglyceridemia Low HDL cholesterol
Incidence of diabetes per 1,000 person-years (%) Without
With
Adjusted HR (95% CI) for incident diabetes*
7.5 10.0 14.5
8.9 8.1 7.3
42.2 41.0 31.3
4.2 (2.7–6.5) 4.5 (3.0–6.8) 4.1 (2.8–6.0)
11.4 4.8 22.6 25.6 15.0 3.2 15.1 39.4
8.6 9.7 7.2 7.8 7.5 9.6 9.0 8.1
29.2 43.8 25.6 21.9 33.2 66.8 24.4 16.0
3.5 (2.3–5.2) 5.1 (3.0–8.7) 3.3 (2.2–4.8) 2.3 (1.6–3.5) 4.1 (2.8–6.0) 6.9 (4.1–11.5) 2.6 (1.7–3.8) 2.0 (1.4–2.9)
Components of the metabolic syndrome are defined as follows: central obesity (original NCEP criteria): waist circumference ⬎102 cm in men or ⬎88 cm in women; central obesity (Asian criteria): waist circumference ⱖ90 cm in men or ⱖ80 cm in women; high blood pressure: systolic/diastolic blood pressure ⱖ130/85 mmHg or taking blood pressure–lowering medication; hyperglycemia: FPG ⱖ5.6 mmol/l; hypertriglyceridemia: fasting triglycerides ⱖ1.69 mmol/l; low HDL cholesterol: fasting HDL cholesterol ⬍1.03 or ⬍1.29 mmol/l in men and women, respectively. *HRs are adjusted for age, sex, tobacco use (never/ever), alcohol consumption (never/occasional/at least once a week), and physical activity (⬍1 episode/at least 1 episode a week in the past month).
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Cheung and Associates Table 3—Sensitivity, specificity, and positive and negative predictive value of the different definitions of the metabolic syndrome and components with respect to the incidence of diabetes over the follow-up period
Sensitivity (%)
Specificity (%)
Positive predictive value (%)
Negative predictive value (%)
25.8 34.2 41.9
93.9 91.9 87.5
24.6 24.4 20.5
94.3 94.8 95.1
31.7
90.2
19.9
94.5
16.7 49.2 47.5 42.5 16.7 31.7 55.8
96.2 79.5 76.1 87.1 97.8 86.2 61.8
25 15.6 13.3 20.2 37.0 15.0 10.1
93.8 95.3 95.0 95.2 93.9 94.2 94.8
Definitions of metabolic syndrome Metabolic syndrome (original NCEP criteria) (1) Metabolic syndrome (FPG ⱖ5.6 mmol/l) (2) Metabolic syndrome (FPG ⱖ5.6 mmol/l and Asian cut points for waist circumference) (3) Metabolic syndrome (IDF criteria) (4) Components of metabolic syndrome Central obesity (original NCEP criteria) (1) Central obesity (Asian criteria) (3,4) High blood pressure Hyperglycemia (ⱖ5.6 mmol/l) Hyperglycemia (ⱖ6.1 mmol/l) Hypertriglyceridemia Low HDL cholesterol See Table 2 for definitions of components of the metabolic syndrome.
for the development of diabetes associated with the metabolic syndrome. Sensitivities, specificities, and positive and negative predictive values for the different definitions of the metabolic syndrome were determined. Receiver-operating characteristic (ROC) curves were drawn for the predictors of diabetes. Analyses were performed with SPSS 11.0 for Windows (SPSS, Chicago, IL); P ⬍ 0.05 (twosided) was considered statistically significant. RESULTS — Baseline characteristics of the 1,679 subjects who had no history of diabetes at baseline are shown in Table 1. At baseline, 168 and 191 subjects had the metabolic syndrome according to the NCEP and IDF criteria, respectively. As expected, subjects with the metabolic syndrome were more obese, had higher blood pressure, FPG, and plasma triglycerides, and had lower HDL cholesterol. They also tended to be older. However, there were no significant differences in sex ratio, tobacco use, alcohol use, or exercise habit. Insulin resistance, as indicated by HOMAIR, was significantly associated with the metabolic syndrome. The prevalences of the metabolic syndrome defined by the NCEP criteria were 15.6 and 13.4% for nondiabetic men and women, respectively, and were 11.3 and 11.4% (McNemar test P ⬍ 0.001), respectively, if the IDF definition was applied. During a median follow-up of 6.4 years, there were 66 and 54 new cases of DIABETES CARE, VOLUME 30, NUMBER 6, JUNE 2007
diabetes in men and women, respectively. The incidence of diabetes was markedly higher in subjects with the metabolic syndrome at baseline than in those without the syndrome (Table 2). The incidence rate was similar for either the NCEP (3) or the IDF (4) definition of the metabolic syndrome. The HRs associated with the NCEP and the IDF definitions of the metabolic syndrome were 4.1 [95% CI 2.8 – 6.0] and 3.5 [2.3–5.2], respectively. HRs for diabetes associated with the components of the metabolic syndrome are shown in Table 2. Among the individual components of the metabolic syndrome, hyperglycemia and central obesity were more strongly associated with incident diabetes than the other components. The HRs for an FPG ⱖ6.1 or 5.6 mmol/l (ⱖ110 or 100 mg/dl) were 6.9 [95%CI 4.1–11.5] and 4.1 [2.8 – 6.0], respectively. Sensitivity, specificity, and positive and negative predictive values for the metabolic syndrome and its components are shown in Table 3. Different definitions of the metabolic syndrome (1– 4) are shown for comparison. All the definitions were highly specific but not sensitive. The positive predictive values were low, ranging from 19.9 to 24.6%, but the negative predictive values were close to 95%. In this population, the updated NCEP definition (3) had a higher sensitivity than previous NCEP definitions (1,2) and the IDF definition (4). However, IFG alone has a similar sensitivity, but the positive predictive value tends to be higher. Two
cut points for central obesity (waist circumference) and hyperglycemia (FPG) were examined (Table 3). The Asian criteria for central obesity and FPGⱖ5.6 mmol/l had higher sensitivities but lower positive predictive values. ROC curves for the prediction of the development of diabetes using baseline parameters are shown in Fig. 2. For the sake of clarity, not all curves are plotted. For men, the areas ⫾ SE under the ROC curves were 0.67 ⫾ 0.03 for waist-to-hip ratio, 0.70 ⫾ 0.03 for waist circumference, 0.75 ⫾ 0.03 for BMI, 0.76 ⫾ 0.03 for FPG, and 0.76 ⫾ 0.03 for the plasma glucose at 2 h in an OGTT. For women, the respective areas ⫾ SE under the ROC curves were 0.74 ⫾ 0.03, 0.74 ⫾ 0.03, 0.74 ⫾ 0.03, 0.75 ⫾ 0.03, and 0.82 ⫾ 0.03. CONCLUSIONS — In recent years, there has been an alarming increase in diabetes and the metabolic syndrome in Asia (17–19). The prevalence of the metabolic syndrome (by NCEP criteria using waist circumference criteria for Asians) stands at 11% in Koreans, 14 –24% in Chinese, and 29% in Indians (9,19,20). These are not low compared with the prevalence of 33.6% in the United States (21). Our prospective study confirms that the metabolic syndrome predicts the development of diabetes in urbanized Chinese as much as in Americans (6,7). The HR for the development of diabetes associated with the metabolic syndrome is quite variable, depending on the popula1433
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Figure 2—ROC curves showing the ability of the baseline waist circumference (solid line), FPG (light dotted line), and plasma glucose at 2 h in an OGTT (dark dotted line) to predict the development of diabetes in men and women after an interval of 6.4 years. Diagonal segments are produced by ties. The values were adjusted for age, tobacco use, alcohol consumption, and physical activity. The sensitivities and specificities of the NCEP (⫹) and IDF (*) definitions of the metabolic syndrome (3,4) are shown for comparison. For men, the points on the ROC curves closest to the ideal were 79.4 cm for waist circumference (sensitivity 0.73% and specificity 0.63%), 5.2 mmol/l for FPG (sensitivity 0.72% and specificity 0.69%), and 5.8 mmol/l for the 2-h plasma glucose (sensitivity 0.77% and specificity 0.67%). For women, the points on the ROC curves closest to the ideal were 76.1 cm for waist circumference (sensitivity 0.74% and specificity 0.65%), 5.2 mmol/l for FPG (sensitivity 0.74% and specificity 0.72%), and 6.45 mmol/l for the 2-h plasma glucose (sensitivity 0.87% and specificity 0.67%).
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tion studied (22–24). The hazard of developing diabetes associated with the NCEP definition of the metabolic syndrome is 4.1 in our population, comparable to the odds ratios of 3.3 and 5.0 reported for the U.S. and Finland, respectively (6,23). In the San Antonio Heart Study, which followed-up on 1,734 participants after 7– 8 years, the original NCEP definition (1) performed better than the World Health Organization definition, but lowering the FPG cutoff to 5.4 mmol/l improved the prediction further (6). Interestingly, in our population, an FPG of ⬃5.2 mmol/l had a sensitivity and specificity of ⬃70%. Thus, our results support the change in cut point for IFG from 6.1 to 5.6 mmol/l, because of the ⬎1-fold gain in sensitivity. However, this gain must be balanced against the lower cardiovascular risk of those who have the mildest hyperglycemia, the paucity of evidence of benefit in treating such individuals, and the negative consequences of labeling someone as having a disease. We compared the IDF definition of the metabolic syndrome with the NCEP criteria in terms of prediction of newonset diabetes. The IDF criteria include abdominal obesity as a prerequisite and have different cutoffs for waist circumference for different ethnic groups (4). In the Insulin Resistance Atherosclerosis Study, the predictive values of the NCEP and IDF criteria were similar (7). In our population, the updated NCEP (3) and IDF (4) criteria have similar positive and negative predictive values, but the sensitivity of the NCEP criteria tended to be higher. We investigated which component of the metabolic syndrome was more predictive of diabetes. We found that IFG conferred a high risk of subsequent development of diabetes, as in our previous observations in this cohort after 2 years of follow-up (13). Indeed, IFG was as good as any of the definitions of the metabolic syndrome in predicting the development of diabetes. However, whether IFG is as strong a predictor as the metabolic syndrome for cardiovascular mortality was not addressed in our study. In our ROC analysis, waist circumference was as good a predictor as FPG in predicting diabetes in women, but the other components of the metabolic syndrome, such as elevated blood pressure, were less predictive. In women, the 2-h plasma glucose value in an OGTT was an even better predictor of the development of diabetes. Nevertheless, FPG is easier to obtain than an OGTT DIABETES CARE, VOLUME 30, NUMBER 6, JUNE 2007
Cheung and Associates test and is therefore the measurement of choice for practical reasons. If FPG is as good as the metabolic syndrome in predicting the development of diabetes in the future, the extra effort and costs to diagnose the metabolic syndrome may need to be justified if the objective is solely to predict the development of diabetes. On the other hand, the process of diagnosing the metabolic syndrome may lead to the identification of associated cardiometabolic risk factors such as high blood pressure and dyslipidemia that are of significant magnitude to justify intervention for the prevention of cardiovascular disease. For Hong Kong Chinese, the Asian cut points for central obesity, compared with the cut points for white Americans, have higher sensitivity, but the positive predictive value is slightly lower. Results of the ROC analysis are also supportive of the use of the lower cut points for central obesity in both sexes in our Asian population. Further studies on the appropriate cut points for different parameters are needed to formulate public health policy for controlling diabetes in the community. The positive predictive value of the metabolic syndrome is low because the majority of people with it will not develop new-onset diabetes within 6 years. However, the hazard associated with it is not low, which means that an individual with the metabolic syndrome but not diabetes should have periodic measurements of FPG to detect the onset of diabetes. On the other hand, the metabolic syndrome has a very high negative predictive value for future diabetes, which means that an individual without the metabolic syndrome has a much lower chance of developing diabetes in future. Thus, it is worthwhile to prevent or reverse the metabolic syndrome. Abdominal obesity has been postulated as the leading modifiable cause of cardiovascular disease in Asia (25). Treatment to reduce obesity not only reduces body weight and plasma glucose but also decreases waist circumference, blood pressure, and lipid levels. Clinical trials in recent years have shown that lifestyle interventions accompanied by weight reduction can reduce the development of diabetes (26 –28). In summary, the metabolic syndrome predicts the development of diabetes in Hong Kong Chinese. Of the different definitions examined, the updated NCEP diagnostic criteria of the metabolic syndrome appear to be most DIABETES CARE, VOLUME 30, NUMBER 6, JUNE 2007
appropriate for the prediction of diabetes in this population. The absence of the metabolic syndrome strongly predicts the absence of future diabetes. Interventions targeted to improve FPG and central obesity will be most useful for preventing diabetes in our population. The presence of the metabolic syndrome in someone without diabetes is a strong warning signal; periodic measurement of FPG should be performed to detect progression to diabetes, and lifestyle modifications, including healthy diet, weight control, and regular physical activity, should be strongly encouraged. Acknowledgments — T h e H o n g K o n g CRISPS2 was supported by a Hong Kong Research Grants Council grant (7229/01M) and the Sun Chieh Yeh Heart Foundation. The project titled “Impaired Glucose Tolerance as a Precursor of Diabetes and Hypertension in Hong Kong Chinese” was supported by a Health Care and Promotion Fund Committee Research Grant (212907). G. Cheung, J.L.F. Lo, D.F.Y. Chau, and C.Y. Law were the research nurses involved with the clinical study of the subjects.
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DIABETES CARE, VOLUME 30, NUMBER 6, JUNE 2007
