International Journal of Diabetes Mellitus 2 (2010) 38–42

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

a r t i c l e i n f o a b s t r a c t

Article history: Objectives: The aim of this study was to assess the prevalence and effects of the presence of metabolic
Received 28 July 2009 syndrome in patients with type 1 diabetes.
Accepted 24 October 2009 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 albu-
Keywords: min: creatinine ratios were also measured. Patients were divided into those with and those without met-
Type 1 diabetes
abolic syndrome.
Metabolic syndrome
Hypertension
Results: Data from 365 type 1 diabetic patients was analysed. Hundred and twelve had metabolic syn-
Dyslipidaemia drome. There was no difference according to gender or smoking. Type 1 diabetic patients with metabolic
Obesity syndrome had longer duration of diabetes, were significantly older, heavier, had higher blood pressure,
Macro-vascular complications higher triglyceride and lower HDL cholesterol levels. There were significant increases in mean BMI, urea,
Micro-vascular complications serum creatinine, urinary albumin: creatinine ratio, cholesterol and triglyceride in the group with met-
Medication abolic syndrome even after controlling for both age and duration of diabetes. Neuropathy and macro-vas-
cular 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 significantly 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 diabetes-
related complications, a need for higher insulin doses and a more aggressive multifactorial intervention.
Ó 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 definitions,
consists of a clustering of cardiovascular risk factors. The most
recent definition 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 crite-
ria for the diagnosis of the metabolic syndrome [2–5].
The presence of metabolic syndrome is considered to be an
important risk factor for cardiovascular disease and mortality in pa-
tients with type 2 diabetes and non-diabetic subjects [6–9]. 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 [12–15].
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 mi-
cro-vascular complications, differences in metabolic parameters
and the types of medications that these patients received. Statisti-
cal analysis was carried out to determine whether the prevalence
of complications and the differences in the clinical and biochemical
parameters were significantly 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 (Top-
conTRC-NW6 Digital Retinal Camera (www.topcon.co.uk) fitted
with a Nikon D70 (www.nikon.co.uk)) and formally assessed by
trained graders.

1877-5934 Ó 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
 S. Ghosh et al. / International Journal of Diabetes Mellitus 2 (2010) 38–42 39

Assessment for peripheral neuropathy was performed by test-
ing using a 10 g nylon monofilament, and ankle reflexes 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 his-
tory of angina, myocardial infarction or coronary revascularisation
procedures. This was confirmed from history, clinical notes or
investigations (such as ECG/ETT/Angiography). Similarly, history
of stroke or Transient Ischaemic Attack was confirmed from his-
tory, clinical notes or investigations (such as neuroimaging).
Venous blood was taken for the measurement of HbA1c using
HPLC (Menarini–Arkray 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.Diabete-
sInScotland.org).We performed a retrospective analysis of our Dia-
betes 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 definition of the metabolic
syndrome. The WHO criterion uses either Body Mass index (BMI)
P30 kg/m2 to define obesity, or waist circumference for the diagno-
sis 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 classified as
having metabolic syndrome if two or more of the following criteria
were present:
 Obesity as defined 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 P2.5;
female P3.5 (mg/mmol).
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 inter-
val level variables was carried out using analysis of covariance
(ANCOVA) with group membership as the fixed 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 first block and metabolic syndrome is added in
the second block in order to determine the incremental improve-
ment in fit 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% pa-
tients were obese, 34.0% had dyslipidaemia, 27.4% had hyperten-
sion and 21.4% had microalbuminuria. Hundred and twelve
patients fulfilled the criteria for metabolic syndrome. There was
no difference according to gender or smoking status. Type 1 dia-
betic patients with metabolic syndrome were significantly older
and had a significantly 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 significant in-
creases 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 112 253
Mean age in years (SD) 55.43 (20.35) 38.62 (15.82) t(362) = 8.54, p < 0.01
Mean duration of diabetes in years (SD) 21.58 (13.38) 17.92 (12.58) t(356) = 2.48, p < 0.05
Males (%) 56.3 56.1 {2(1, N = 365) = 0.0005, p > 0.05
Smoking status (%) 42 (37.8%) 92 (36.7%) {2(1, N = 362) = 0.05, p > 0.05
Mean BMI (kg/m2) (SD)a 26.74 (3.96) 24.74 (3.23) F(1, 345) = 21.22, p < 0.01
Mean triglyceride (mmol/l) (SD)a 2.36 (1.29) 1.24 (0.67) F(1, 347) = 99.91, p < 0.01
Mean HDL (mmol/l) (SD)a 1.45 (0.43) 1.73 (0.46) F(1, 340) = 23.87, p < 0.01
Hypertension (%) 72.3% 7.5% {2(1) = 97.91, p < 0.01
a
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.

With metabolic syndrome Without metabolic syndrome p Value

N 112 253
Mean urea (mmol/l) (SD)a 7.54 (4.19) 5.77 (2.01) F(1, 347) = 27.06, p < 0.01
Mean creatinine (lmol/l) (SD)a 122.39 (61.69) 96.55 (15.95) F(1, 345) = 31.19, p < 0.01
Mean cholesterol (mmol/l) (SD)a 5.21 (1.09) 4.71 (0.95) F(1, 347) = 15.65, p < 0.01
Mean LDL (mmol/l) (SD)a 2.64 (0.92) 2.43 (0.83) F(1, 327) = 3.49, p = 0.06
Mean albumin:creatinine (mg/mmol) (SD)a 8.99 (9.46) 2.01 (3.86) F(1, 305) = 72.94, p < 0.01
a
Estimated marginal means are evaluated at the mean values for covariates of length of diagnosis and age.
40 S. Ghosh et al. / International Journal of Diabetes Mellitus 2 (2010) 38–42

Table 3 ria, and less so with AHA/NCEP criteria [19]. The different defini-
Prevalence of complications in the two groups. tions used understandably give differing prevalence of metabolic
With metabolic Without metabolic p Value syndrome in type 1 diabetes [20].
syndrome syndrome The metabolic syndrome generally predicts an adverse outcome
N 112 253 and the risk of developing major micro- and macro-vascular com-
Neuropathy (%) 25 (22.3%) 10 (4.0%) {2(1) = 15.26, plications, but the prevalence obviously varies according to the
p < 0.01 definition used. Microalbuminuria, which is a criterion in some
Retinopathy (%) 12 (10.7%) 25 (9.9%) {2(1) = 0.15, p = 0.70
IHD/MI (%) 27 (24.1%) 10 (4.0%) {2(1) = 4.24, p < 0.05
definitions of the metabolic syndrome, seems to be the best marker
Stroke (%) 6 (5.4%) 5 (2.0%) {2(1) = 0.06, p = 0.81 of prediction for the development of micro- and macro-vascular
complications [21]. Microalbuminuria appears to reflect both insu-
lin resistance, which is central to both the concept of the metabolic
syndrome, and vascular damage, as originally postulated by the
4.2. Comparison of the biochemical parameters (Table 2)
Steno Group [22].
Cardiovascular disease is one of the leading causes of morbid-
Those with metabolic syndrome had significantly higher mean
ity and mortality in Scotland, in part due to the increasing prev-
levels of urea, serum creatinine, urinary albumin: creatinine ratio
alence of obesity [23]. Obesity is a major public health concern,
and total cholesterol levels after controlling for both age and dura-
with more than 40% of the adult population in the industrialised
tion of diabetes. Patients with metabolic syndrome had a higher
world being overweight or clinically obese [24]. The reasons for
mean LDL-cholesterol, but the difference was not significant.
the dramatic increase in obesity are complex, and include life-
style changes plus demographic and political factors [25]. It
4.3. Comparison of prevalence of complications (Table 3) seems likely that the prevalence of obesity in type 1 diabetes
parallels the prevalence of obesity in the general population.
Macro-vascular complications such as ischaemic heart disease/ With this increase, there is also an increased chance of clustering
myocardial infarction (IHD) was more common in patients with of cardiovascular risk factors including hypertension, dyslipida-
metabolic syndrome as was neuropathy. emia, central obesity and low physical activity, all of which are
Difference in the prevalence of retinopathy or stroke in patients associated with insulin resistance and contribute to the meta-
with metabolic syndrome failed to reach levels of statistical bolic syndrome. Hence, it comes as no surprise that a significant
significance. proportion of our patients with type 1 diabetes fulfilled the cri-
teria for the metabolic syndrome.
4.4. Comparison of the use of medication in the two groups (Table 4) In our study, patients with metabolic syndrome were older,
and had a longer duration of diabetes. As these type 1 patients
Patients with metabolic syndrome were more likely to be on would obviously have been younger and probably also leaner
statins, ACE inhibitors and angiotensin receptor blockers. Only at diagnosis, our study probably under-estimates the effect of
two patients were on fibrates, and while both were in the meta- the risk factors that make up metabolic syndrome. Despite this
bolic syndrome group the numbers were too small. under-estimation, our study clearly demonstrates a much higher
Finally, an analysis of covariance showed that patients with prevalence of complications in this group of patients. Even after
metabolic syndrome had a significantly higher mean insulin dose adjustment for age and duration of diabetes, these patients were
requirement per kg after controlling for age and duration. more likely to have hypertension, dyslipidaemia and worse gly-
caemic control. In addition, the risk of developing macro-vascu-
lar complications such as ischaemic heart disease, myocardial
5. Conclusions
infarction and peripheral vascular disease, along with micro-vas-
In our cross-sectional study, metabolic syndrome was evident cular complications such as nephropathy and neuropathy, were
in 30% of type 1 diabetic patients, which is similar to that of higher in the group with metabolic syndrome, despite receiving
the FinnDiane Study. The FinnDiane study, which used NCEP crite- much greater therapeutic interventions.
ria, demonstrated that 38% of men and 40% of women with type 1 Longitudinal studies, such as the Pittsburgh study and the DCCT
diabetes had metabolic syndrome [17,18]. The DCCT Follow-up Follow-up, clearly showed that patients with type 1 diabetes gain
group and the Pittsburgh Epidemiology of Diabetes Complications weight with time. It would seem likely that this weight gain would
study groups had a lower prevalence (between 8% and 22%). In the be associated with an increase in the prevalence of the metabolic
Pittsburgh Epidemiology of Diabetes Complications study groups, syndrome [26–29]. However, the DCCT Follow-up study showed
metabolic syndrome was most commonly found with the IDF crite- that the intensively treated group fared better with diabetes-re-
lated outcomes despite the weight gain. It would appear from this
study that the long-term benefits of good glycaemic control out-
Table 4 weigh the deleterious effects of weight gain associated with the
The comparative use of medication between the two groups. treatment of diabetes [30].
With Without p Value Even with relatively small numbers, our study demonstrates
metabolic metabolic an increase in the prevalence of neuropathy and nephropathy
syndrome syndrome in patients with metabolic syndrome confirming the findings of
N 112 253 previous studies, including the Metascreen study [31]. Previous
On statins (%) 27 (24.1%) 20 (7.9%) {2(1) = 6.03, p < 0.05 studies have demonstrated that the risk of stroke is higher in
On fibrates (%) 2 (1.8%) 0 (0.0%) NS
patients with type 1 diabetes with metabolic syndrome.[32]
On ACE I (%) 45 40.2%) 9 (3.6%) {2(1) = 38.64,
p < 0.01 Our study demonstrated that in patients with the metabolic syn-
On ARB (%) 7 (6.3%) 4 (1.6%) {2(1) = 3.89, p < 0.05 drome patients there was a threefold increase in the prevalence
Mean insulin dose 0.86 (0.36) 0.73 (0.35) F(1, 324) = 9.01, of stroke; however this did not reach levels of statistical
per kg (SD)a p < 0.01 significance.
a
Estimated marginal means are evaluated at the mean values for covariates of The prevalence of retinopathy in our study was not increased
length of diagnosis and age. in those with metabolic syndrome. Our results are similar to the
 S. Ghosh et al. / International Journal of Diabetes Mellitus 2 (2010) 38–42
findings 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 meta-
bolic 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 significant ef-
fects 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 metfor-
min 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 demon-
strated improved glycaemic control with lower insulin require-
ments [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 (multifac-
torial 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 inten-
sify lifestyle changes and should be considered for insulin sensi-
tisers such as metformin. We would hope that this would lead
to a reduction in total daily insulin requirements, better glycae-
mic control, better clinical outcomes and fewer diabetes-related
complications.
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