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DOI 10.1007/s10654-010-9540-7
DIABETES
Received: 18 June 2010 / Accepted: 15 December 2010 / Published online: 28 December 2010
The Author(s) 2010. This article is published with open access at Springerlink.com
Introduction
The concept of metabolic syndrome was introduced to
improve identification of risk of cardiovascular disease
(CVD) [1], but has failed to improve the detection of
cardiovascular risk beyond ordinary risk scores [2]. As a
predictor of type 2 diabetes, metabolic syndrome has
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J. Joseph et al.
Risk factors for type 2 diabetes in groups stratified according to metabolic syndrome
(NCEP) Adult Treatment Panel III [9], in which the metabolic syndrome is present when three or more of the
following criteria are fulfilled.
1.
2.
3.
4.
5.
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Results
In the total study population aged 2598 years and without
diabetes at baseline (n = 26,093), 492 new cases of type 2
diabetes were identified during follow up, 294 in men and
198 in women.
Table 1 shows age adjusted baseline characteristics of
those who remained free of diabetes and those who
developed type 2 diabetes during follow-up and who were
with or without metabolic syndrome at baseline. Of the
26,093 subjects, 3,684 had a high metabolic score, i.e.
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J. Joseph et al.
Table 1 Baseline characteristics in men and women initially free from diabetes, by future diabetes and metabolic status
Variables
Men
Age (years)
Women
Non
diabetics
(n = 12,104)
High metabolic
score (n = 137)
46.1 0.13
58.1 0.85***
54.1 0.89***
137 0.15
145 1.55
153 1.62***
79.7 0.11
86.1 0.94
91 1.11***
BMI (kg/m )
25.5 0.03
27.5 0.31***
30.8 0.28***
Non
diabetics
(n = 13,497)
High metabolic
score (n = 122)
46.5 0.13
59.1 1.59***
57.6 1.02***
131 0.18
146 2.67
158 2.14***
76.1 0.11
82.5 1.54
87.3 1.69***
24.6 0.03
27.2 0.57***
31.3 0.45***
6.03 0.01
6.5 0.09
6.7 0.09***
5.94 0.12
6.65 0.14
6.86 0.11**
1.35 0.02
1.35 0.02
1.07 0.21***
1.64 0.01
1.69 0.04
1.24 0.03***
1.31 0.01
1.46 0.07*
2.81 0.11***
Triglycerides (mmol/l)
1.75 0.01
1.82 0.09*
3.42 0.18***
1,372 (11.3)
39 (24.8)***
32 (23.4)***
1,804 (13.4)
25 (32.9)***
39 (31.7)***
Current
658 (5.4)
25 (15.9)*
40 (29.2)***
743 (5.5)
11 (14.5)*
29 (23.7)***
Previous
268 (2.3)
6 (3.8)
2 (1.5)
358 (2.7)
5 (6.6)
13 (10.7)**
Never
11,178 (92.3)
126 (80.3)
95 (69.3)
12,396 (91.8)
60 (78.9)
80 (65.6)
Education n (%)
Primary/secondary
5,961 (49.2)
94 (59.9)*
73 (53.3)
6,546 (48.5)
48 (63.2)*
72 (59.0)
High school
1,526 (12.7)
18 (11.5)
21 (15.3)
2,301 (17.1)
10 (13.2)
15 (12.3)
College/university \ 4 years
2,256 (18.6)
21 (13.4)
20 (14.6)
2,489 (18.4)
10 (13.2)
17 (13.9)
College/university C 4 years
2,361 (19.5)
24 (15.2)
23 (16.8)
2,161 (16.0)
8 (10.4)
18 (14.8)
1,828 (15.1)
16 (10.2)
16 (11.7)
1,998 (14.8)
6 (7.9)
15 (12.3)
Moderate
6,781 (56.0)
53 (33.7)
70 (51.1)
6,305 (46.7)
19 (25.0)
35 (28.7)
3,495 (28.9)
88 (56.1)**
51 (37.2)
5,194 (38.5)
51 (67.1)*
72 (59.0)
Current
4,593 (37.9)
92 (58.6)***
65 (47.4)
5,027 (37.2)
39 (51.3)***
45 (36.9)
Previous
3,756 (31.1)
40 (25.5)
40 (29.2)
2,944 (21.8)
13 (17.1)
19 (15.6)
Never
3,755 (31.0)
25 (15.9)
32 (23.4)
5,526 (41.0)
24 (31.6)
58 (47.5)
Inactive
Daily smoking n (%)
P for differences between low and high metabolic score, obtained by age adjusted analysis of covariance or logistic regression where
appropriate
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Risk factors for type 2 diabetes in groups stratified according to metabolic syndrome
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Table 2 Risk factors for type 2 diabetes by low and high metabolic score
Variables
Low metabolic
score
HR (95% CI)
n = 10,426
High metabolic
score
HR (95% CI)
n = 1,972
P value for
difference in
HR between
groups
Low metabolic
score
HR (95% CI)
n = 11,983
High metabolic
score
HR (95% CI)
n = 1,712
157
137
0.000
BMI (1SD)
Triglycerides (1SD)
P value for
difference in
HR between
groups
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122
0.003
0.000
0.007
0.000
0.000
0.000
Hypertension (yes)
0.001
1.86 (1.05,3.30)
0.004
2.54 (1.57,4.12)
College/university C 4 years
1.00
1.00
1.00
1.00
College/university \ 4 years
High school
Hard
1.00
1.00
1.00
1.00
Moderate
Inactive
Never
1.00
1.00
1.00
1.00
Previous
Current
Education
Smoking
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J. Joseph et al.
70
119
60
Men
Women
HR
50
73
40
30
20
10
0
0 (ref)
6.5
6.4
9.8
9.2
Metabolic score
Men
Women
0.5
0.1
1.2
0.6
3.0
2.8
Discussion
Our study shows how the metabolic syndrome, used as a
dichotomously defined exposure variablealthough identifying a high risk group, misses half of the incident cases of
type 2 diabetes. We found a significantly better detection of
cases by adding a family history of type 2 diabetes, smoking,
low education and physical inactivity to the risk assessment
especially among those with a low metabolic score.
Our study showed an increasing risk of type 2 diabetes
with increasing number of metabolic features in accordance with other prospective studies where the relationship
between similar features of metabolic syndrome and type
2 diabetes have been analysed [10, 14, 15]. In accordance with other studies, we also found that the use of
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dichotomous risk factors gave significantly weaker prediction of incident cases of type 2 diabetes than using the
metabolic risk factors as continuous variables [4, 15]. Our
study strongly indicates a continuous risk associated with
all metabolic syndrome features, also below established
cut-off values for metabolic syndrome. That those who do
not fulfil the criteria at baseline are older, and consequently
could have worsened in metabolic profile more slowly,
might indicate a need for longer exposure time for those
with lower risk factor levels. In both men and women, low
risk subjects were significantly older when they developed
diabetes compared to high risk subjects. In particular, this
was shown for women who had significantly longer follow
up time as compared to men before development of diabetes if low in metabolic score. A difference in susceptibility to changes in BMI could be the cause of these
observed gender differences. It has been shown that men
are more susceptible to an increase in blood pressure given
an increase in BMI than are women [16]. Changes in risk
factors have been shown to be independent predictors of
diabetes risk [17]. Accordingly, we also found worsening
of metabolic risk factors in 97% of low risk subjects who
subsequently developed type 2 diabetes.
Furthermore our study strongly indicates that life style
risk factors such as physical inactivity, smoking, educational level and also family history of diabetes should be
included when assessing diabetes risk. A recent review of
tools for predicting risk of type 2 diabetes in daily practice,
concluded that the Finnish Diabetes Risk Score (FINDRISC) which included all these risk factors except educational level, showed the highest ROC area (ROC 87%)
compared to metabolic syndrome which had only an ROC
of 83% [18]. Similarly our study showed that adding these
non-metabolic risk factors increased correct classification
significantly to a similar ROC (87%). Studies with a multifactorial approach to diabetes risk assessment conclude
that the concept of metabolic syndrome has a limited
practical utility as a diagnostic or management tool in case
of diabetes or CVD [6, 19].
As metabolic syndrome factors are differently distributed among men and women, we find that HDL cholesterol
is a protective factor only among women with a high
metabolic score, although earlier studies have shown a
significant lowering of risk for increasing HDL cholesterol
in both men and women [8]. We have earlier shown that
this is due to an interaction between HDL cholesterol, BMI
and triglycerides most pronounced in women where the
protective effect of HDL increased by increasing triglyceride levels and more so at high BMI levels corresponding
to the high score group as defined in the present article.
This indicates that the definition of a metabolic syndrome
does not describe a unified syndrome as such, but a complex of related risk factors.
Risk factors for type 2 diabetes in groups stratified according to metabolic syndrome
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