International Journal of Diabetes Mellitus 2 (2010) 3842

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International Journal of Diabetes Mellitus

journal homepage: ees.elsevier.com/locate/ijdm

Original Article

Metabolic syndrome in type 1 diabetes

Sujoy Ghosh a,*, Andrew Collier a, Mario Hair b, Iqbal Malik a, Tarik Elhadd a
a
b

Diabetes Day Centre, The Ayr Hospital, Dalmellington Road, Ayr, Scotland KA6 6DX, United Kingdom
Department of Physical Sciences, University of the West of Scotland, United Kingdom

a r t i c l e

i n f o

Article history:
Received 28 July 2009
Accepted 24 October 2009

Keywords:
Type 1 diabetes
Metabolic syndrome
Hypertension
Dyslipidaemia
Obesity
Macro-vascular complications
Micro-vascular complications
Medication

a b s t r a c t
Objectives: The aim of this study was to assess the prevalence and effects of the presence of metabolic
syndrome in patients with type 1 diabetes.
Research design and methods: Retrospective analysis of data from a one year period of patients attending
annual review clinic was undertaken. Body weight, height and blood pressure were measured along with
assessment of micro-/macro-vascular complications. HbA1c, urea, cholesterol, triglyceride, urinary albumin: creatinine ratios were also measured. Patients were divided into those with and those without metabolic syndrome.
Results: Data from 365 type 1 diabetic patients was analysed. Hundred and twelve had metabolic syndrome. There was no difference according to gender or smoking. Type 1 diabetic patients with metabolic
syndrome had longer duration of diabetes, were signicantly older, heavier, had higher blood pressure,
higher triglyceride and lower HDL cholesterol levels. There were signicant increases in mean BMI, urea,
serum creatinine, urinary albumin: creatinine ratio, cholesterol and triglyceride in the group with metabolic syndrome even after controlling for both age and duration of diabetes. Neuropathy and macro-vascular complications were commoner in patients with metabolic syndrome. Patients with metabolic
syndrome were more likely to be on statins, ACE inhibitors and angiotensin receptor blockers and had
a signicantly higher mean insulin dosage requirement per kg.
Conclusions: This study highlights the importance of the presence of the metabolic syndrome in patients
with type 1 diabetes. It shows that metabolic syndrome is associated with a higher incidence of diabetesrelated complications, a need for higher insulin doses and a more aggressive multifactorial intervention.
2009 International Journal of Diabetes Mellitus. Published by Elsevier Ltd.
Open access under CC BY-NC-ND license.

1. Background
Metabolic syndrome, for which there are multiple denitions,
consists of a clustering of cardiovascular risk factors. The most
recent denition is the consensus document from the International
Diabetes Federation (IDF) [1]. The World Health Organisation
(WHO), National Cholesterol Education Program (NCEP) and the
Adult Treatment Panel (ATP) III have each proposed different criteria for the diagnosis of the metabolic syndrome [25].
The presence of metabolic syndrome is considered to be an
important risk factor for cardiovascular disease and mortality in patients with type 2 diabetes and non-diabetic subjects [69]. The
phrase double diabetes has recently been coined for those patients
who have type 1 diabetes and insulin resistance [10,11]. Recent
studies suggest that these patients appear to be at increased risk of
developing macro- and micro-vascular complications [1215].
The aim of this study was to assess the prevalence and effects of
metabolic syndrome in type 1 diabetic patients in a Scottish popu-

* Corresponding author. Tel.: +44 1292 610555; fax: +44 1292 614538.
E-mail address: drsujoyghosh@rediffmail.com (S. Ghosh).

lation. The study also reviewed the prevalence of macro- and micro-vascular complications, differences in metabolic parameters
and the types of medications that these patients received. Statistical analysis was carried out to determine whether the prevalence
of complications and the differences in the clinical and biochemical
parameters were signicantly different between those with and
without metabolic syndrome.

2. Research design and methods

The study was undertaken at the Diabetes Day Centre, The Ayr
Hospital, which is a District General Hospital in Scotland, UK. A
comprehensive annual review is undertaken on all diabetic
patients attending the clinic. Body weights of patients are recorded
(in kg) using electronic scales (SECA, Birmingham, UK). Height was
measured in meters using a (?) Harpenden Stadiometer. Blood
pressure was recorded using a standard sphygmomanometer.
Fundal photography was undertaken with pupils dilated (TopconTRC-NW6 Digital Retinal Camera (www.topcon.co.uk) tted
with a Nikon D70 (www.nikon.co.uk)) and formally assessed by
trained graders.

1877-5934 2009 International Journal of Diabetes Mellitus. Published by Elsevier Ltd. Open access under CC BY-NC-ND license.
doi:10.1016/j.ijdm.2009.10.005

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S. Ghosh et al. / International Journal of Diabetes Mellitus 2 (2010) 3842

Assessment for peripheral neuropathy was performed by testing using a 10 g nylon monolament, and ankle reexes were
checked. Peripheral vascular disease was considered to be present
if pedal pulses were non-palpable or undetectable by a hand held
Doppler or if there was history of claudication and/or rest pain.
Ischaemic heart disease was documented as the presence of a history of angina, myocardial infarction or coronary revascularisation
procedures. This was conrmed from history, clinical notes or
investigations (such as ECG/ETT/Angiography). Similarly, history
of stroke or Transient Ischaemic Attack was conrmed from history, clinical notes or investigations (such as neuroimaging).
Venous blood was taken for the measurement of HbA1c using
HPLC (MenariniArkray HA 8140 haemoglobin A1c analyzer,
Menarini diagnostics, Wokingham, UK; intra-assay CV 1.9%). Blood
urea, serum creatinine, urinary albumin and creatinine, cholesterol
and triglyceride were measured using Roche Modular Analyzer
(Basel, Switzerland). Urine albumin concentration was measured
by radioimmunoassay, CV < 9%. Urinary creatinine concentration
was measured by an end point Jaffe reaction, CV < 6%.
Data was entered into the hospital-based SCI-DC database
(Scottish Care Information Diabetes Collaboration, www.DiabetesInScotland.org).We performed a retrospective analysis of our Diabetes Centre Database. For the purposes of this study, the
computerised database was used to retrieve the data obtained for
all patients attending the diabetes clinic for the year 2007. The
database contains information on patient demography, diabetic
complications, metabolic parameters and medications. Patients in
whom the diagnosis of type 1 diabetes was uncertain and in whom
data collection was incomplete were excluded from the study.
We used the WHO Criteria for the denition of the metabolic
syndrome. The WHO criterion uses either Body Mass index (BMI)
P30 kg/m2 to dene obesity, or waist circumference for the diagnosis of metabolic syndrome [16]. We used BMI data for the diagnosis
of obesity as this was the recording available from the database.
As all our patients were diabetic, patients were classied as
having metabolic syndrome if two or more of the following criteria
were present:
 Obesity as dened by BMI P30 kg/m2.
 Dyslipidaemia: triglyceride P1.7 mmol/l or HDL cholesterol
<0.9 in males or <1.0 in females (mmol/l).

 Hypertension: BP P140/90 mm Hg or on treatment.

 Microalbuminuria: (albumin:creatinine ratio) male
female P3.5 (mg/mmol).

P2.5;

Using the above criterion the patients, were divided into those
with and those without metabolic syndrome.
3. Statistical analysis
SPSS (Social Package for Statistical Sciences) version 15 was
used to analyse the data obtained.
As both age and duration of diabetes are important extraneous
variables, the analysis of the effect of metabolic syndrome on interval level variables was carried out using analysis of covariance
(ANCOVA) with group membership as the xed factor with age
and duration as covariates.
For categorical variables, hierarchical logistic regression was
carried out to assess the effect of metabolic syndrome. In the
regression models, age and duration are added as independent
variables in the rst block and metabolic syndrome is added in
the second block in order to determine the incremental improvement in t when adding group membership after the effects of
age and duration are taken into account.
4. Results
4.1. Comparison of baseline data (Table 1)
Data from 365 type 1 diabetic patients was analysed. 9.3% patients were obese, 34.0% had dyslipidaemia, 27.4% had hypertension and 21.4% had microalbuminuria. Hundred and twelve
patients fullled the criteria for metabolic syndrome. There was
no difference according to gender or smoking status. Type 1 diabetic patients with metabolic syndrome were signicantly older
and had a signicantly longer duration of diabetes. They were also
heavier, had higher blood pressure, higher triglyceride and lower
HDL cholesterol levels than their non-metabolic syndrome
counterparts.
Analysis of covariance showed that there were signicant increases in mean BMI and triglyceride in the group with metabolic
syndrome after controlling for both age and duration.

Table 1
Baseline and demographic data of the two groups of patients in terms of gender, age, duration of diagnosis, plus Body Mass index (BMI), triglycerides, High Density Lipoprotein
(HDL) and hypertension.

With metabolic syndrome

Without metabolic syndrome

p Value

N
Mean age in years (SD)
Mean duration of diabetes in years (SD)
Males (%)
Smoking status (%)

112
55.43 (20.35)
21.58 (13.38)
56.3
42 (37.8%)

253
38.62 (15.82)
17.92 (12.58)
56.1
92 (36.7%)

t(362) = 8.54, p < 0.01

t(356) = 2.48, p < 0.05
{2(1, N = 365) = 0.0005, p > 0.05
{2(1, N = 362) = 0.05, p > 0.05

Mean BMI (kg/m2) (SD)a

Mean triglyceride (mmol/l) (SD)a
Mean HDL (mmol/l) (SD)a
Hypertension (%)

26.74 (3.96)
2.36 (1.29)
1.45 (0.43)
72.3%

24.74 (3.23)
1.24 (0.67)
1.73 (0.46)
7.5%

F(1, 345) = 21.22, p < 0.01

F(1, 347) = 99.91, p < 0.01
F(1, 340) = 23.87, p < 0.01
{2(1) = 97.91, p < 0.01

Estimated marginal means are evaluated at the mean values for covariates of length of diagnosis and age.

Table 2
The biochemical parameters measured in the two groups.

N
Mean
Mean
Mean
Mean
Mean
a

urea (mmol/l) (SD)a

creatinine (lmol/l) (SD)a
cholesterol (mmol/l) (SD)a
LDL (mmol/l) (SD)a
albumin:creatinine (mg/mmol) (SD)a

With metabolic syndrome

Without metabolic syndrome

p Value

112
7.54 (4.19)
122.39 (61.69)
5.21 (1.09)
2.64 (0.92)
8.99 (9.46)

253
5.77 (2.01)
96.55 (15.95)
4.71 (0.95)
2.43 (0.83)
2.01 (3.86)

F(1,
F(1,
F(1,
F(1,
F(1,

Estimated marginal means are evaluated at the mean values for covariates of length of diagnosis and age.

347) = 27.06, p < 0.01

345) = 31.19, p < 0.01
347) = 15.65, p < 0.01
327) = 3.49, p = 0.06
305) = 72.94, p < 0.01

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S. Ghosh et al. / International Journal of Diabetes Mellitus 2 (2010) 3842

Table 3
Prevalence of complications in the two groups.
With metabolic Without metabolic p Value
syndrome
syndrome
N
112
Neuropathy (%) 25 (22.3%)

253
10 (4.0%)

Retinopathy (%) 12 (10.7%)

IHD/MI (%)
27 (24.1%)
Stroke (%)
6 (5.4%)

25 (9.9%)
10 (4.0%)
5 (2.0%)

{2(1) = 15.26,
p < 0.01
{2(1) = 0.15, p = 0.70
{2(1) = 4.24, p < 0.05
{2(1) = 0.06, p = 0.81

4.2. Comparison of the biochemical parameters (Table 2)

Those with metabolic syndrome had signicantly higher mean
levels of urea, serum creatinine, urinary albumin: creatinine ratio
and total cholesterol levels after controlling for both age and duration of diabetes. Patients with metabolic syndrome had a higher
mean LDL-cholesterol, but the difference was not signicant.
4.3. Comparison of prevalence of complications (Table 3)
Macro-vascular complications such as ischaemic heart disease/
myocardial infarction (IHD) was more common in patients with
metabolic syndrome as was neuropathy.
Difference in the prevalence of retinopathy or stroke in patients
with metabolic syndrome failed to reach levels of statistical
signicance.
4.4. Comparison of the use of medication in the two groups (Table 4)
Patients with metabolic syndrome were more likely to be on
statins, ACE inhibitors and angiotensin receptor blockers. Only
two patients were on brates, and while both were in the metabolic syndrome group the numbers were too small.
Finally, an analysis of covariance showed that patients with
metabolic syndrome had a signicantly higher mean insulin dose
requirement per kg after controlling for age and duration.
5. Conclusions
In our cross-sectional study, metabolic syndrome was evident
in 30% of type 1 diabetic patients, which is similar to that of
the FinnDiane Study. The FinnDiane study, which used NCEP criteria, demonstrated that 38% of men and 40% of women with type 1
diabetes had metabolic syndrome [17,18]. The DCCT Follow-up
group and the Pittsburgh Epidemiology of Diabetes Complications
study groups had a lower prevalence (between 8% and 22%). In the
Pittsburgh Epidemiology of Diabetes Complications study groups,
metabolic syndrome was most commonly found with the IDF crite-

Table 4
The comparative use of medication between the two groups.
With
metabolic
syndrome

Without
metabolic
syndrome

N
On statins (%)
On brates (%)
On ACE I (%)

112
27 (24.1%)
2 (1.8%)
45 40.2%)

253
20 (7.9%)
0 (0.0%)
9 (3.6%)

On ARB (%)
Mean insulin dose
per kg (SD)a

7 (6.3%)
0.86 (0.36)

4 (1.6%)
0.73 (0.35)

p Value

{2(1) = 6.03, p < 0.05

NS
{2(1) = 38.64,
p < 0.01
{2(1) = 3.89, p < 0.05
F(1, 324) = 9.01,
p < 0.01

a
Estimated marginal means are evaluated at the mean values for covariates of
length of diagnosis and age.

ria, and less so with AHA/NCEP criteria [19]. The different denitions used understandably give differing prevalence of metabolic
syndrome in type 1 diabetes [20].
The metabolic syndrome generally predicts an adverse outcome
and the risk of developing major micro- and macro-vascular complications, but the prevalence obviously varies according to the
denition used. Microalbuminuria, which is a criterion in some
denitions of the metabolic syndrome, seems to be the best marker
of prediction for the development of micro- and macro-vascular
complications [21]. Microalbuminuria appears to reect both insulin resistance, which is central to both the concept of the metabolic
syndrome, and vascular damage, as originally postulated by the
Steno Group [22].
Cardiovascular disease is one of the leading causes of morbidity and mortality in Scotland, in part due to the increasing prevalence of obesity [23]. Obesity is a major public health concern,
with more than 40% of the adult population in the industrialised
world being overweight or clinically obese [24]. The reasons for
the dramatic increase in obesity are complex, and include lifestyle changes plus demographic and political factors [25]. It
seems likely that the prevalence of obesity in type 1 diabetes
parallels the prevalence of obesity in the general population.
With this increase, there is also an increased chance of clustering
of cardiovascular risk factors including hypertension, dyslipidaemia, central obesity and low physical activity, all of which are
associated with insulin resistance and contribute to the metabolic syndrome. Hence, it comes as no surprise that a signicant
proportion of our patients with type 1 diabetes fullled the criteria for the metabolic syndrome.
In our study, patients with metabolic syndrome were older,
and had a longer duration of diabetes. As these type 1 patients
would obviously have been younger and probably also leaner
at diagnosis, our study probably under-estimates the effect of
the risk factors that make up metabolic syndrome. Despite this
under-estimation, our study clearly demonstrates a much higher
prevalence of complications in this group of patients. Even after
adjustment for age and duration of diabetes, these patients were
more likely to have hypertension, dyslipidaemia and worse glycaemic control. In addition, the risk of developing macro-vascular complications such as ischaemic heart disease, myocardial
infarction and peripheral vascular disease, along with micro-vascular complications such as nephropathy and neuropathy, were
higher in the group with metabolic syndrome, despite receiving
much greater therapeutic interventions.
Longitudinal studies, such as the Pittsburgh study and the DCCT
Follow-up, clearly showed that patients with type 1 diabetes gain
weight with time. It would seem likely that this weight gain would
be associated with an increase in the prevalence of the metabolic
syndrome [2629]. However, the DCCT Follow-up study showed
that the intensively treated group fared better with diabetes-related outcomes despite the weight gain. It would appear from this
study that the long-term benets of good glycaemic control outweigh the deleterious effects of weight gain associated with the
treatment of diabetes [30].
Even with relatively small numbers, our study demonstrates
an increase in the prevalence of neuropathy and nephropathy
in patients with metabolic syndrome conrming the ndings of
previous studies, including the Metascreen study [31]. Previous
studies have demonstrated that the risk of stroke is higher in
patients with type 1 diabetes with metabolic syndrome.[32]
Our study demonstrated that in patients with the metabolic syndrome patients there was a threefold increase in the prevalence
of stroke; however this did not reach levels of statistical
signicance.
The prevalence of retinopathy in our study was not increased
in those with metabolic syndrome. Our results are similar to the

S. Ghosh et al. / International Journal of Diabetes Mellitus 2 (2010) 3842

ndings of previous studies [33]. The reasons for this are not
clearly understood.
Our patients with metabolic syndrome were on higher doses of
insulin per kg of body weight, and yet achieved poorer glycaemic
control, implying that even higher doses of insulin would have
been required to achieve comparable glycaemic control. This is
clearly in keeping with the concept that insulin resistance being
a key feature of metabolic syndrome [34]. Other studies have also
demonstrated that patients who are overweight/obese with metabolic syndrome have higher insulin requirements [35].
In type 2 diabetic patients, metformin provides cardiovascular
protection reducing all-cause mortality by 36% and myocardial
infarction by 39% [36]. The mechanism of action is not clearly
understood, but it is suggested that metformin has signicant effects on several markers of endothelial and thrombolytic function
with reductions in vascular cell adhesion molecule, plasminogen
activator inhibitor-1 and tissue plasminogen activator [37,38]. In
addition, other studies have demonstrated that the use of metformin can improve glycaemic control, and reduce total daily insulin
dosage in overweight and adolescent type 1 diabetic patients [39].
Similarly there are small studies with the use of rosiglitazone in
overweight subjects with type 1 diabetes which have demonstrated improved glycaemic control with lower insulin requirements [40].
Our study highlights the importance of the presence of the
metabolic syndrome in patients with type 1 diabetes and clearly
demonstrated that the metabolic syndrome is associated with a
higher incidence of diabetes-related complications, a greater need
for higher insulin doses and more aggressive treatment (multifactorial intervention). We would suggest that the presence of the
metabolic syndrome should be used as a clinical marker of insulin
resistance and that these patients should be encouraged to intensify lifestyle changes and should be considered for insulin sensitisers such as metformin. We would hope that this would lead
to a reduction in total daily insulin requirements, better glycaemic control, better clinical outcomes and fewer diabetes-related
complications.
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