Nutrition, Metabolism & Cardiovascular Diseases (2013) 23, 264e271

Available online at www.sciencedirect.com

journal homepage: www.elsevier.com/locate/nmcd

Anthropometric indices of fat distribution and

cardiometabolic risk in Parkinson’s disease
E. Cereda a,b,*, E. Cassani b, M. Barichella b, R. Caccialanza a, G. Pezzoli b

a
Nutrition and Dietetics Service, Fondazione IRCCS Policlinico San Matteo, Viale Golgi 19, 27100 Pavia, Italy
b
Parkinson Institute e Istituti Clinici di Perfezionamento, Milano, Italy

Received 4 December 2010; received in revised form 16 March 2011; accepted 7 April 2011
Available online 8 September 2011

KEYWORDS
Parkinson’s disease;
Cardiometabolic risk;
Waist circumference
(WC);
Waist-hip ratio (WHR);
Waist-to-height ratio
(WtHR)
Abstract Background & aims: To investigate the association between anthropometric indices
of body fat distribution and cardiometabolic risk factors in a population of Parkinson’s disease
(PD) patients.
Methods & results: One hundred and fifty-seven PD patients (57.3% males) were studied
measuring: waist circumference (WC), waist-hip ratio (WHR), waist-to-height ratio (WtHR),
body fat percentage (BF%) by impedance, fasting glucose, serum lipids. Information was
collected also on diabetes, hypertension and metabolic syndrome (MetS). Increased cardiome-
tabolic risk was defined by
2 MetS component traits other than abdominal adiposity. In the
whole population, prevalence of overweight and obesity were 35.0% and 19.2%, respectively.
However, prevalence of MetS and elevated cardiometabolic risk were 14.6% and 18.5%, respec-
tively. Prevalence was similar between genders, with one exception: adverse fat distribution
according to WC and WHR was more common in females (P < 0.001). Using a multivariable
model (adjustments: age, smoking status and disease duration), indices were highly correlated
with BF% in both genders. WC and WtHR were associated with the number of MetS criteria and
elevated risk. The only cardiometabolic parameters associated with anthropometric indices
were HDL in men and triglycerides in women. After adjusting also for BMI all the associations
found with anthropometric indices disappeared.
Conclusions: Despite their correlation with BF%, anthropometric indices of body fat distribu-
tion appear to poorly account for the reduced cardiometabolic risk of the PD patient. This
finding suggests a low metabolic activity within the adipose tissue. The implications of fat
distribution on the cardiometabolic risk of PD patients clearly deserves further investigation.
ª 2011 Elsevier B.V. All rights reserved.

* Corresponding author. Nutrition and Dietetics Service, Fondazione IRCCS Policlinico San Matteo, Viale Golgi 19, 27100 Pavia, Italy.
Tel.: þ39 0382 501615; fax: þ39 0382 502801.
E-mail address: e.cereda@smatteo.pv.it (E. Cereda).

0939-4753/$ - see front matter ª 2011 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.numecd.2011.04.004
Parkinson’s disease and cardiometabolic risk
Introduction
Obesity has proved to be a risk factor for both morbidity and
mortality [1,2], mainly on account of adipose tissue-related
metabolic complications, such as insulin resistance, hyper-
tension and dyslipidemia [3e6]. In this respect, the intra-
abdominal body fat compartment appears to play an
important role [5e8]. Accordingly, anthropometric surro-
gates of body fat distribution, such as waist circumference
(WC), waist-hip ratio (WHR) and waist-to-height ratio
(WtHR), have been introduced into clinical practice for
cardiovascular risk assessment in view of their association
with cardiometabolic parameters and outcome [8e12].
Along with this, increased abdominal adiposity is included
among the metabolic syndrome (MetS) criteria, being an
independent predictor of outcome [1,4,8,13].
In a previous population study the prevalence of obesity
in Parkinson’s disease (PD) patients was about 50% higher
than in the general population, with a highly prevalent
adverse fat distribution according to WHR [14]. During the
course of PD fluctuations of body weight may occur due to
typical motor symptoms (bradykinesia, resting tremor,
rigidity and postural instability) and the consequences of
anti-parkinson treatment, with changes being mainly
related to fat mass loss or accumulation [15e18]. Vascular
risk factors are reduced in PD patients [19,20], but results
related to cardiovascular (CV) mortality in PD patients are
inconsistent [21,22]. Moreover, intra-abdominal fat mass
has been associated also with chronic neurodegeneration
[23], and treatment of CV factors, such as dyslipidemia,
seems to result in slower PD progression [24].
As the relationship between indices of body fat distri-
bution and cardiometabolic risk profile has never been
investigated in PD, we designed the present study to
address this issue.
Methods
Patient population
PD patients admitted electively (routine hospital stay) to
the Parkinson Institute ward for periodic disease reassess-
ment were recruited consecutively from January 2008 to
October 2010. PD diagnosis was made according to UK Brain
Bank criteria [25]. All patients were potentially eligible for
study inclusion. Exclusion criteria were:
- refusal to participate;
- previous neurosurgical procedure for PD (deep brain
stimulation or similar procedures);
- thyroid disease;
- body weight changes (spontaneous or diet-induced) in
the previous 6 months.
All patients underwent a complete nutritional assess-
ment and medical examination, including blood pressure
measurement. Information on smoking history and phar-
macological treatment was also collected.
All the evaluations were performed early in the morning,
in fasting conditions and within 24 h of admission to the
Parkinson Institute, after taking PD medications in order to
265
avoid any potential evaluation bias, particularly in terms of
height and body composition, due to movement disorders
(e.g. rigidity or resting tremor).
Nutritional assessment
Nutritional assessment was based on the following
measurements
Anthropometry
Subjects were wearing only underwear. Height (to the
nearest 0.5 cm) and body weight (to the nearest 0.1 kg)
were measured using the same calibrated scale equipped
with a telescopic, vertical steel stadiometer (SECA 711;
Germany). The height of patients with evident spinal cord
deformities was calculated by the use of validated equa-
tions [26]. The body mass index (BMI) was derived accord-
ingly as the ratio between weight [kg] and height [m]
squared (kg/m2), and nutritional status was defined
according to WHO criteria [27]. Waist and hip circumfer-
ences (WC and HC, respectively) were assessed (to the
nearest 0.5 cm) using a plastic flexible tape. Placing the
tape perpendicular to the long axis of the body and parallel
to the floor, WC and HC were measured at the midpoint
between the lowest rib and the iliac crest and around the
largest portion of the buttocks, respectively [27]. Accord-
ingly, waist-hip ratio (WHR) and waist-to-height ratio
(WtHR) were calculated as the ratio between WC and HC
and height in centimeters, respectively [9,27].
Biochemistry
Venous blood samples were drawn after 8e12 h of fasting.
The following parameters were assessed using conventional
automated analyzers: glucose, total cholesterol, high and
low density lipoprotein cholesterol (HDL and LDL, respec-
tively) and triglycerides.
Body composition
Percentage of body fat mass (BF%) was measured using
a four-polar impedance meter (Tanita Segmental Multifre-
quency Body Composition Monitor, MC 180 MA, Sensor-
medics, Milano, Italy) according to the formula provided by
the manufacturer and in agreement with international
guidelines [28].
Fat distribution
Increased abdominal adiposity was defined by the following
criteria [9,13,27]:
- WC >102 cm in men and >88 cm in women;
- WHR >1.00 in men and >0.85 cm in women;
- WtHR
0.55 in men and
0.56 cm in women.
Cardiometabolic risk
The cardiometabolic risk was based on biochemical
parameters (total cholesterol, HDL, LDL, triglycerides and
glucose) and the presence of established comorbidities
(hypertension and diabetes). The presence of
2 metabolic
syndrome (MetS) component traits, with the exception of
266 E. Cereda et al.

abdominal adiposity, was considered to indicate high car-
diometabolic risk. Hypertension was diagnosed by repeated
blood pressure measurements
140/90 mmHg or the re-
ported use of antihypertensive medications. Diabetes was
defined as at least two blood glucose measurements

126 mg/dL or reported antidiabetic treatment. The
National Cholesterol Education Program’s Adult Treatment
Panel III criteria [13] were used to define MetS. Accordingly,
subjects had to have
3 of the following traits: (1) waist
circumference >102 cm in men and >88 cm in women; (2)
serum triglycerides
150 mg/dL and/or the use of lipid
lowering medications; (3) HDL-cholesterol <40 mg/dL in
men and <50 mg/dL in women and/or the use of lipid
lowering medications; (4) blood pressure
130/85 mmHg
and/or the use of antihypertensive agents; and (5) fasting
plasma glucose level
110 mg/dL. The total number of
criteria was also considered in the analyses.
Statistical analysis
Continuous variables are reported as mean and standard
deviation (SD) or median and interquartile range
(25the75th percentile), categorical variables as counts and
percentages.
Group comparisons were performed using Fisher’s exact
test (categorical variables) and Student’s t-test (continuous
variables). Patient grouping and categorization was per-
formed on the basis of:
 gender;
 increased abdominal adiposity according to WC, WHR
and WtHR [9,13,27];
 elevated cardiometabolic risk defined as the presence
of
2 MetS traits.
Afterward, stepwise multiple regression analysis was
performed to investigate the associations between meta-
bolic risk factors and fat distribution indices, including age,
gender, smoking status and disease duration as potential
confounders.
All statistical analyses were performed by MEDCALC for
Windows Version 11.3.0.0 (MedCalc Software, Mariakerke,
Belgium) setting the level of significance at a two-tailed P-
value <0.05.
Ethics disclosure
The study was performed in agreement with the principles
of the Declaration of Helsinki and the protocol was
approved by the local Ethic Committee. Written informed
consent was obtained from every patient recruited and
before any assessment was made.

Table 1 Nutritional and cardiometabolic features of Parkinson’s disease patients by gender.

Overall (n Z 157) Males (n Z 90) Females (n Z 67) Pa
Age (years) 64.8  8.7 64.3  7.8 0.742
Body mass index (Kg/m2) 26.0  5.1 27.7  4.3 25.9  5.8 0.758
<18.5 (n, [%]) 7 [4.5] 3 [3.3] 4 [6.0] 0.574
[18.5e25[(n, [%]) 65 [41.4] 40 [44.4] 25 [37.3]
[25e30[(n, [%]) 55 [35.0] 29 [32.2] 26 [38.8]
[30e35[(n, [%]) 21 [13.4] 14 [15.6] 7 [10.4]

35 (n, [%]) 9 [5.7] 4 [4.4] 5 [7.5]
Waist circumference (cm) 96.0  14.3 98.1  13.5 93.0  15.0 0.036
Waist-hip ratio 0.94  0.08 0.97  0.07 0.91  0.08 <0.001
Waist-to-height ratio 0.58  0.08 0.58  0.08 0.59  0.09 0.237
Body fat mass (%) 23.8  10.2 20.4  7.1 28.6  11.8 <0.001
Glucose (mg/dL)b 85.2  10.1 86.3  11.3 83.3  7.4 0.086
T-CHOL (mg/dL)c 185.9  33.6 180.4  30.4 195.7  37.2 0.021
HDL (mg/dL)c 54.4  15.9 51.2  15.1 60.2  16.0 0.004
LDL (mg/dL)c 111.9  33.5 108.7  30.1 117.6  38.7 0.219
Triglycerides (mg/dL) 98.7  42.9 103.5  48.3 89.9  29.2 0.112
Diabetes (n, [%]) 7 [4.5] 5 [5.6] 2 [3.0] 0.699
Hypertension (n, [%]) 39 [24.8] 20 [22.2] 19 [28.3] 0.456
Lipid lowering drug (n, [%]) 9 [5.7] 3 [3.3] 6 [8.9] 0.172
MetS traits (n)d 0.7  0.8 0.8  0.8 0.7  0.8 0.512
MetS (n, [%]) 23 [14.6] 13 [14.4] 10 [14.9 1.000
MetS traits
2 (n, [%])d 29 [18.8] 17 [18.9] 12 [17.9] 1.000
Data are reported as mean  standard deviation or counts [%]. Percentages are calculated within single groups. Abbreviations: T-CHOL,
total cholesterol; HDL, high density lipoprotein cholesterol; LDL, low density lipoprotein cholesterol; MetS, metabolic syndrome.
a
P-values according to Student’s t-test or Fisher’s exact test.
b
Comparison of means performed after the exclusion of patients with diabetes (final sample size n Z 150 [85 Males, 65 females]).
c
Comparison of means performed after the exclusion of patients with diabetes and using lipid lowering drugs (final sample size
n Z 143 [83 Males, 60 females]).
d
Excluding abdominal adiposity by waist circumference.
Parkinson’s disease and cardiometabolic risk 267

Results

High Pa

Data are reported as mean  standard deviation or counts [%]. Abbreviations: WC, waist circumference; WHR, waist-hip ratio; WtHR, waist-to-height ratio; SE, standard error; T-CHOL,
<0.001
0.099

0.046
0.187

0.020
0.662

1.000
0.801
0.045
1.000

0.094
General features

A total of 157 PD patients (57.3% males) were recruited.

183.7  30.1

114.9  28.4
106.3  52.4
Normal
.55

87.0  10.9

48.2  13.8
Cardiometabolic variables according to high abdominal adiposity by anthropometric indexes of fat distribution in Parkinson’s disease male patients.

23.5  5.6
Mean age and median duration of disease were 64.6 years

0.9  0.9
13 [23.2]

14 [25.0]
(SD, 8.3) and 9 years [25the75th, 5e13 years], respectively.

2 [3.6]
3 [5.3]
Most of them were taking levodopa (88.5%; mean dose SD,

Waist-to-height ratio
8.4  4.7 mg/kg/day), either alone (30.6%) or in combina-
tion with other therapies. Other pharmacological treat-
ments were: dopamine agonists (47.8%; pramipexole,

173.9  27.2

100.8  46.2
98.2  25.8
ropinirole or apomorphine), MAO inhibitors (12.7%; rasagi-

13.5  4.9
82.8  8.6

5.5  15.4

0.5  0.7
line or selegiline), COMT inhibitors (11.5%; entacapone or

7 [20.6]
1 [2.9]
2 [5.9]

3 [8.8]
tolcapone), amantadine (3.8%), anti-cholinergic drugs

<.55
(1.3%; biperidene).
The nutritional and cardiometabolic features of the

Comparison of means performed after the exclusion of patients with diabetes and using lipid lowering drugs (final sample size, n Z 83).
study population are presented in Table 1. The distribution

(n Z 56)
of patients among nutritional status categories was as

0.447
0.809

<0.001
0.969

0.382
0.116

1.000
0.171
0.123
0.129

0.549
follows: underweight, 4.5%; normal weight, 41.4%; over-

a
weight, 35.0%; mild obesity, 13.4%; moderate/severe

P
obesity, 5.7%. The prevalence of MetS and elevated risk
(MetS traits
2) was 14.6% (95% CI, 8.8e20.5) and 18.5%

180.3  33.7

115.1  30.3
129.6  64.5
High >1.00
(95% CI, 12.1e28.9). In this respect, proportions were

21.7  6.5
84.9  8.6

39.2  7.0

1.0  1.1
(n Z 34)
similar in both genders. However, PD women were char-

3 [12.0]

3 [12.0]

6 [24.0]
1 [4.0]
acterized by lower WC and higher WHR, BF%, and total and

Comparison of means performed after the exclusion of patients with diabetes (final sample size, n Z 85).
HDL cholesterol.

total cholesterol; HDL, high density lipoprotein; LDL, low density lipoprotein; MetS, metabolic syndrome.
Waist-hip ratio

Central body fat distribution and cardiometabolic

Normal 1.00

180.6  28.8

107.3  28.9
85.6  11.0

53.7  14.6

99.2  44.5
profile

19.9  7.3
0.7  0.7
17 [26.1]

11 [16.9]
(n Z 25)

2 [3.1]
2 [3.1]
The prevalence of increased abdominal adiposity according
to WC, WHR and WtHR in the whole study sample was
49.0%, 49.7% and 64.3%, respectively. Adverse fat distri-
bution was less common in male patients: according to WC,
(n Z 65)

36.7% (P < 0.001 vs females, 65%); WHR, 27.8% (P < 0.001 vs

0.195

0.795

<0.001
0.519
<0.001
0.099
0.028
1.000
0.552

<0.001
<0.001
females, 79.1%); WtHR, 62.2% (P Z 0.614 vs females,
a

67.2%).
P

According to simple parametric statistics, increased

abdominal adiposity based on all the indices considered was
183.1  31.4

116.5  29.7
125.1  59.4
87.9  12.7

43.2  10.8

associated with lower HDL and higher triglyceride levels in

P-values according to Student’s t-test or Fisher’s exact test.
26.8  4.7
High >102

1.3  1.0
13 [39.4]
(n Z 33)

male and female patients, respectively. In PD men we also

Waist circumference (cm)

8 [24.2]
2 [6.1]
2 [6.1]

Excluding abdominal adiposity by waist circumference.

observed higher triglyceride values in the presence of
a high WC and higher LDL in the presence of a increased
WtHR. In both genders, patients with increased WC and
WtHR were characterized by higher BF% and mean number
Normal 102

178.3  28.1

104.3  27.2
55.1  15.0

93.4  40.8

of MetS component traits. However, the association with

84.2  8.6

16.9  5.6
0.5  0.6
12 [21.1]

the number of MetS criteria in women was marginally

(n Z 57)

3 [5.3]
1 [1.7]

4 [7.0]

significant. No difference in these parameters was detected

according to WHR. Along with this, high WC in male patients
was associated more frequently with high cardiometabolic
risk (Table 2 and Table 3). These associations were
Lipid lowering drug (n [%])

substantially confirmed by stepwise regression models. In

the whole population, after adjusting for potential
MetS traits
2 (n [%])d
Triglycerides (mg/dL)c

Hypertension (n [%])

confounders (age, sex, smoking status and disease dura-

Body fat mass (%)
Glucose (mg/dL)b

tion), fat distribution according to all anthropometric

T-CHOL (mg/dL)c

Diabetes (n [%])

MetS traits (n)d

indices was inversely associated with HDL levels and

HDL (mg/dL)c
LDL (mg/dL)c

directly associated with BF%, the number of MetS compo-

nent traits and high cardiometabolic risk (MetS traits
2).
Table 2

TG were also associated with WC and WHR (Table 4). In

gender specific analyses, adjusted for age, smoking status
b

d
a

and disease duration, only the relationship between indices

 268
Table 3 Cardiometabolic variables according to high abdominal adiposity by anthropometric indexes of fat distribution in Parkinson’s disease female patients.
Waist circumference (cm) Waist-hip ratio Waist-to-height ratio
Normal 88 High >88 Pa
Normal 0.85 High >0.85 Pa
Normal <0.56 High
0.56 Pa
(n Z 23) (n Z 44) (n Z 14) (n Z 53) (n Z 22) (n Z 45)
Glucose (mg/dL)b 85.2  14.8 82.3  13.7 0.271 86.1  9.1 82.6  7.3 0.248 84.6  7.9 82.5  7.7 0.418
T-CHOL (mg/dL)c 203.5  29.9 195.7  40.3 0.534 200.0  34.1 198.3  37.7 0.911 205.2  29.6 194.3  40.6 0.375
HDL (mg/dL)c 67.1  13.2 59.3  18.3 0.171 67.0  13.4 61.3  17.5 0.415 66.3  13.1 59.5  18.7 0.229
LDL (mg/dL)c 121.5  28.6 116.7  44.4 0.721 119  29.9 118.4  41.0 0.963 123.6  28.7 115.3  44.7 0.481
Triglycerides 74.3  17.0 100.2  31.2 0.003 69.3  20.0 95.3  29.2 0.033 76.1  17.9 100.1  31.9 0.007
(mg/dL)c
Diabetes (n [%]) 1 [4.3] 1 [2.3] 1.000 0 [0] 2 [3.8] 1.000 1 [4.5] 1 [2.2] 1.000
Lipid lowering 0 [0] 6 [13.7] 0.087 2 [14.3] 4 [7.5] 0.597 0 [0] 6 [13.3] 0.167
drug (n [%])
Hypertension (n [%]) 4 [17.4] 15 [34.1] 0.169 4 [28.6] 15 [28.3] 1.000 4 [18.2] 15 [33.3] 0.255
MetS traits (n)d 0.4  0.7 0.8  0.9 0.050 0.5  0.78 0.7  0.8 0.605 0.4  0.7 0.8  0.9 0.050
MetS traits
2 (n [%])d 2 [8.7] 10 [22.7] 0.195 2 [14.3] 10 [18.9] 0.731 2 [9.1] 10 [22.2] 0.310
Body fat mass (%) 18.2  9.8 33.9  9.2 <0.001 17.4  11.4 29.7  11.4 0.115 18.7  9.8 34.3  9.1 <0.001
Data are reported as mean  standard deviation or counts [%]. Abbreviations: WC, waist circumference; WHR, waist-hip ratio; WtHR, waist-to-height ratio; SE, standard error; T-CHOL,
total cholesterol; HDL, high density lipoprotein; LDL, low density lipoprotein; MetS, metabolic syndrome.
a
P-values according to Student’s t-test or Fisher’s exact test.
b
Comparison of means performed after the exclusion of patients with diabetes (final sample size, n Z 65).
c
Comparison of means performed after the exclusion of patients with diabetes and using lipid lowering drugs (final sample size, n Z 60).
d
Excluding abdominal adiposity by waist circumference.

E. Cereda et al.
Parkinson’s disease and cardiometabolic risk
Table 4 Partial correlation coefficients between anthropometric indices of fat distribution and metabolic risk factors for
Parkinson’s disease patients (adjusting variables: age, sex, smoking status and disease duration).
Waist circumference
Glucosea 0.14
T-CHOLb 0.04
HDLb 0.21d
LDLb 0.09
Triglyceridesb 0.19d
Hypertension 0.16
MetS traitsc 0.33f
MetS traits
2c 0.27f
Body fat massc 0.77f
Data are reported as mean  standard deviation or counts [%]. Percentages are calculated within single groups. Abbreviations: T-CHOL,
total cholesterol; HDL, high density lipoprotein cholesterol; LDL, low density lipoprotein cholesterol; MetS, metabolic syndrome.
a
Excluding patients with diabetes (final sample size, n Z 150 [85 Males, 65 females]).
b
Excluding patients with diabetes and using lipid lowering drugs (final sample size, n Z 143 [83 Males, 60 females]).
c
Excluding abdominal adiposity by waist circumference.
d
P < 0.05.
e
P < 0.01.
f
P < 0.001.
and BF% and the number of MetS criteria and high car-
diometabolic risk remained significant while the associa-
tions with triglycerides in men and those with HDL in
females disappeared.
After adjusting also for BMI all the associations found
with anthropometric indices disappeared.
Discussion
The present study shows that the prevalence of overweight
and obesity in PD patients is higher than in the general
Italian population [3,29] and that the prevalence of adverse
fat distribution in PD is high, as already reported by Bar-
ichella et al. [14]. Despite this, we report for the first time
that the prevalence of MetS in PD patients is 50% lower than
in the sex- and age-matched general population [30].
Indices of body fat distribution were unrelated to most
cardiometabolic factors in spite of being highly correlated
with body fat mass. Only WC and WtHR showed an associ-
ation with the number of MetS criteria and high car-
diometabolic risk, and the same indices appeared to
perform slightly better in male PD patients.
The present findings could be primarily explained by the
particular metabolic features of PD patients.
Previous studies have shown that visceral adipose tissue
is associated with several disorders, such as insulin resis-
tance, dyslipidemia, high blood pressure, chronic low-grade
inflammation and, ultimately, CV disease [6,7]. It has been
postulated that macrophage infiltration of visceral adipose
tissue and the related over-production of cytokines, as well
as the sympathetic over-activity within the same fat
compartment, are major promoters of metabolic distur-
bances due to enhanced lipolysis, free fatty acid outflow to
the liver and peripheral vessel hypertonia [6,31].
Previous research has demonstrated that PD is associated
with a reduction in the production of catecholamines by the
adrenal medulla and in their release by the peripheral
nervous system. The outcome is generalized sympathetic
269
Waist-hip ratio Waist-to-height ratio
0.02 0.10
0.10 0.04
0.21e 0.20d
0.16 0.10
0.18d 0.17
0.05 0.12
0.20d 0.29f
0.14 0.25f
0.40f 0.78f
denervation [32e34]. In regard with this, an improvement in
cardiometabolic parameters has been reported after the
inception of levodopa treatment, which may also modulate
sympathetic activity [20], and seems to translate into (or
induce) atherosclerosis regression [35].
Reduced sympathetic activity results in normal insulin
and glucagon secretions, free fatty acid mobilization from
the visceral adipocytes and glucose uptake by skeletal
muscle [6,36,37]. Levodopa may also restore the activity of
the growth hormone (GH) - IGF-1 axis, which is depressed in
visceral obesity, by inducing the secretion of GH [38,39].
It is reasonable to argue that visceral adipose tissue is
less metabolically active in PD, with the pathophysiologic
pathways relating abdominal body fat to metabolic
complications being probably less impaired. Particularly,
according to the aforementioned pathophysiologic consid-
erations, it is likely that PD patients are characterized by
a higher degree of insulin sensitivity that could be also
secondary to intrinsic motor complications (e.g. rigidity or
resting tremor). However, given the lack of data on insulin
levels and insulin resistance (e.g. by the HOMA [HOmeo-
stasis Model Assessment] index) we were not able to fully
explore this hypothesis.
In interpreting the results of this study other limitations
should be taken into account. Although anthropometric
surrogates of abdominal adiposity have shown a strong
correlation with visceral adiposity as assessed by advanced
imaging techniques [40], these indices do not enable the
distinction between intra-abdominal and subcutaneous fat
compartments. This consideration may contribute to
explain the even lower association with cardiometabolic
risk found in female patients, as body fat is characteristi-
cally higher in women than in men [6]. Along with this, it
should be taken into account that fluctuations of body
weight during the course of PD have been mainly related to
changes in subcutaneous fat mass [15e18].
A potential for bias could be also related to the dietary
pattern. PD patients are usually advised to redistribute,
270
and partly reduce, protein intake to avoid motor compli-
cations resulting from the interaction with levodopa
absorption [15,41,42]. However, it has been demonstrated
that dietary habits of PD patients are substantially similar
to those of the general population [43].
Finally, it should be recognized that PD patients are
frequently characterized by multi-drug treatments. Unfor-
tunately, the effects of other drugs improving the dopa-
minergic activity (e.g. levodopa degradation inhibitors
and/or dopamine agonists) have been not extensively
studied as much as those of levodopa and a possible
contribution to the cardiometabolic profile still needs to be
assessed and could not be excluded.
Conclusions
In PD patients, despite the significant association with BF%,
anthropometric indices of body fat distribution are poorly
correlated with cardiometabolic risk parameters. The
present data suggest low metabolic activity within adipose
tissue. However, PD patients are still susceptible to CVD
and improvement in vascular factors has been associated
with favorable effects on vascular disease and PD progres-
sion [20,24]. Given the evidence that visceral adipose tissue
may have a role also in neurodegenerative processes
[23,23], the role of abdominal adiposity in affecting the
health status of PD patients deserves further investigation.
In this respect, the usefulness of anthropometric indices of
body fat distribution in risk assessment should be investi-
gated by prospective studies, which should also evaluate
the association between adipose tissue-related factors and
health outcomes.
Funding sources
This work was supported by the “Fondazione Grigioni per il
Morbo di Parkinson.”
Statement of authorship
All authors significantly contributed to the work, read and
approved the final version of the manuscript. All authors,
external and internal, had full access to all of the data
(including statistical reports and tables) in the study and
can take responsibility for the integrity of the data and the
accuracy of the data analysis. In particular, contributions
were as follows: Study design: E.Cereda, M.B., G.P., Data
collection: E.Cassani, M.B., Data analyses: E.Cereda, Data
interpretation: E.Cereda, M.B., R.C., G.P., Manuscript
drafting: E.Cereda, Critical revision of the manuscript:
E.Cereda, E.Cassani, M.B., R.C., G.P.
Competing interest statement
All the Authors certify that there are no affiliations with or
involvement in any organization or entity with a direct
financial interest in the subject matter or materials dis-
cussed in the manuscript.
E. Cereda et al.
Acknowledgments
The authors wish to thank Jennifer Hartwig MD for assis-
tance in drafting the manuscript.
References
[1] Pischon T, Boeing H, Hoffmann K, Bergmann M, Schulze MB,
Overvad K, et al. General and abdominal adiposity and risk of
death in Europe. N Engl J Med 2008;359:2105e20.
[2] Whitlock G, Lewington S, Sherliker P, Clarke R, Emberson J,
Halsey J, et alProspective Studies Collaboration. Body-mass
index and cause-specific mortality in 900 000 adults: collab-
orative analyses of 57 prospective studies. Lancet 2009;373:
1083e96.
[3] Calza S, Decarli A, Ferraroni M. Obesity and prevalence of
chronic diseases in the 1999e2000 Italian national health
survey. BMC Public Health 2008;8:140.
[4] The Obesity Epidemic. Strategies in reducing cardiometabolic
risk. Am J Med 2009;122(4 Suppl. 1):S1e52.
[5] Montague CT, O’Rahilly S. The perils of portliness: causes and
consequences of visceral adiposity. Diabetes 2000;49:883e8.
[6] Wajchenberg BL. Subcutaneous and visceral adipose tissue:
their Relation to the metabolic syndrome. Endocr Rev 2000;
21:697e738.
[7] Ritchie SA, Connell JMC. The link between abdominal obesity,
metabolic syndrome and cardiovascular disease. Nutr Metab
Cardiovasc Dis 2007;17:319e26.
[8] Janssen I, Katzmarzyk PT, Ross R. Waist circumference and
not body mass index explains obesity-related health risk. Am
J Clin Nutr 2004;79:379e84.
[9] Schneider HJ, Glaesmer H, Klotsche J, Böhler S, Lehnert H,
Zeiher AM, et al. DETECT Study Group. Accuracy of anthro-
pometric indicators of obesity to predict cardiovascular risk.
J Clin Endocrinol Metab 2007;92:589e94.
[10] de Koning L, Merchant AT, Pogue J, Anand SS. Waist circum-
ference and waist-to-hip ratio as predictors of cardiovascular
events: meta-regression analysis of prospective studies. Eur
Heart J 2007;28:850e6.
[11] Huxley R, Mendis S, Zheleznyakov E, Reddy S, Chan J. Body
mass index, waist circumference and waist:hip ratio as
predictors of cardiovascular riskea review of the literature.
Eur J Clin Nutr 2010;64:16e22.
[12] Schneider HJ, Friedrich N, Klotsche J, Pieper L, Nauck M,
John U, et al. The predictive value of different measures of
obesity for incident cardiovascular events and mortality.
J Clin Endocrinol Metab 2010;95:1777e85.
[13] Expert panel on detection. Evaluation, and treatment of high
blood cholesterol in adults. Executive summary of the third
report of the National Cholesterol Education Program (NCPE)
expert panel on detection, evaluation and treatment of high
blood cholesterol in adults (Adult treatment panel III). JAMA
2001; 2001: 2486e97.
[14] Barichella M, Marczewska A, Vairo A, Canesi M, Pezzoli G. Is
underweightness still a major problem in Parkinson’s disease
patients? Eur J Clin Nutr 2003;57:543e7.
[15] Barichella M, Cereda E, Pezzoli G. Major nutritional issues in
the management of Parkinson’s disease. Mov Disord 2009;24:
1881e92.
[16] Markus HS, Tomkins AM, Stern GM. Increased prevalence of
undernutrition in Parkinson’s disease and its relationship to
clinical disease parameters. J Neural Transm Park Dis Dement
Sect 1993;5:117e25.
[17] Beyer PL, Palarino MY, Michalek D, Busenbark K, Koller WC.
Weight change and body composition in patients with Par-
kinson’s disease. J Am Diet Assoc 1995;95:979e83.
Parkinson’s disease and cardiometabolic risk
[18] Montaurier C, Morio B, Bannier S, Derost P, Arnaud P, Bran-
dolini-Bunlon M, et al. Mechanisms of body weight gain in
patients with Parkinson’s disease after subthalamic stimula-
tion. Brain 2007;130:1808e18.
[19] Scigliano G, Musicco M, Soliveri P, Piccolo I, Ronchetti G,
Girotti F. Reduced risk factors for vascular disorders in Par-
kinson disease patients: a case-control study. Stroke 2006;37:
1184e8.
[20] Scigliano G, Ronchetti G, Girotti F, Musicco M. Sympathetic
modulation by levodopa reduces vascular risk factors in Par-
kinson disease. Parkinsonism Relat Disord 2009;15:138e43.
[21] Fall PA, Saleh A, Fredrickson M, Olsson JE, Granérus AK.
Survival time, mortality, and cause of death in elderly
patients with Parkinson’s disease: a 9-year follow-up. Mov
Disord 2003;18:1312e6.
[22] Beyer MK, Herlofson K, Arsland D, Larsen JP. Causes of death
in a community-based study of Parkinson’s disease. Acta
Neurol Scand 2001;103:7e11.
[23] Cereda E, Sansone V, Meola G, Malavazos AE. Increased
visceral adipose tissue rather than BMI as a risk factor for
dementia. Age Ageing 2007;36:488e91.
[24] Mutez E, Duhamel A, Defebvre L, Bordet R, Destée A,
Kreisler A. Lipid-lowering drugs are associated with delayed
onset and slower course of Parkinson’s disease. Pharm Res
2009;60:41e5.
[25] Hughes AJ, Ben-Shlomo Y, Daniel SE, Lees AJ. What features
improves the accuracy of clinical diagnosis in Parkinson’s
disease: a clinicopathologic study. Neurology 2001;57
(Suppl 3):S34e8.
[26] Cereda E, Bertoli S, Battezzati A. Height prediction formula
for middle-aged (30e55y) Caucasians. Nutrition 2010;26:
1075e81.
[27] World Health Organization. Physical status: the use and
interpretation of anthropometry. Report of a WHO expert
committee. World Health Organ Tech Rep Ser 1995;854:
1e452.
[28] Kyle UG, Bosaeus I, De Lorenzo AD, Deurenberg P, Elia M,
Gómez JM, et al. Composition of the ESPEN working group.
Bioelectrical impedance analysisepart I: review of principles
and methods. Clin Nutr 2004;23:1226e43.
[29] Mappe, Popolazione, Statistiche Demografiche dell’Istituto
Nazionale di Statistica [accessed September 01.09.10], at
http://demo.istat.it/.
[30] Miccoli R, Bianchi C, Odoguardi L, Penno G, Caricato F,
Giovannitti MG, et al. Prevalence of the metabolic syndrome
271
among Italian adults according to ATP III definition. Nutr
Metab Cardiovasc Dis 2005;15:250e4.
[31] Xu H, Barnes GT, Yang Q, Tan G, Yang D, Chou CJ, et al.
Chronic inflammation in fat plays a crucial role in the devel-
opment of obesity-related insulin resistance. J Clin Invest
2003;112:1821e30.
[32] Wakabayashi K, Takahashi H. Neuropathology of autonomic
nervous system in Parkinson’s disease. Eur Neurol 1997;
38(Suppl 2):2e7.
[33] Carmichael SW, Wilson RJ, Brimijoin WS, Melton LJ,
Okazaki H, Yaksh TL, et al. Decreased catecholamines in the
adrenal medulla of patients with Parkinsonism. N Engl J Med
1988;28:254.
[34] Whitsett TL, Halushka PV, Goldberg LI. Attenuation of post-
ganglionic sympathetic nerve activity by L-dopa. Circ Res
1970;27(561):e70.
[35] Lee JM, Park KW, Seo WK, Park MH, Han C, Jo I, et al. Carotid
intima-media thickness in Parkinson’s disease. Mov Disord
2007;22:2446e9.
[36] Nonogaki K. New insights into sympathetic regulation of
glucose and fat metabolism. Diabetologia 2000;43:533e49.
[37] Leblanc H, Lachelin GC, Abu-Fadil S, Yen SS. The effect of
dopamine infusion on insulin and glucagon secretion in man.
J Clin Endocrinol Metab 1977;44(196):e8.
[38] Sirtori CR, Bolme P, Azarnoff DL. Metabolic responses to acute
and chronic L-dopa administration in patients with Parkin-
sonism. N Engl J Med 1972;287:729e33.
[39] Møller N, Jørgensen JO. Effects of growth hormone on
glucose, lipid, and protein metabolism in human subjects.
Endocr Rev 2009;30:152e77.
[40] Rankinen T, Kim SY, Pérusse L, Després JP, Bouchard C. The
prediction of abdominal visceral fat level from body compo-
sition and anthropometry: ROC analysis. Int J Obes Relat
Metab Disord 1999;23:801e9.
[41] Cereda E, Barichella M, Pezzoli G. Controlled-protein dietary
regimens for Parkinson’s disease. Nutr Neurosci 2010;13:
29e32.
[42] Cereda E, Barichella M, Pedrolli C, Pezzoli G. Low-protein and
protein-redistribution diets for Parkinson’s disease patients
with motor fluctuations: a systematic review. Mov Disord
2010;25:2021e34.
[43] Marczewska A, De Notaris R, Sieri S, Barichella M, Fusconi E,
Pezzoli G. Protein intake in Parkinsonian patients using the
EPIC food frequency questionnaire. Mov Disord 2006;21:
1229e31.