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9 - 2013 Neck circumference as a simple tool for identifying the metabolic sndrome and insulin resistance
9 - 2013 Neck circumference as a simple tool for identifying the metabolic sndrome and insulin resistance
9 - 2013 Neck circumference as a simple tool for identifying the metabolic sndrome and insulin resistance
ORIGINAL ARTICLE
*Laboratory of Research in Metabolism and Diabetes, Department of Medical Clinic, State University of Campinas UNICAMP,
†Laboratory of Research in Metabolism and Diabetes, Department of Surgery, State University of Campinas UNICAMP and
‡Department of Medical Clinic, State University of Campinas UNICAMP, Campinas, São Paulo, Brazil
Definition of metabolic syndrome method) and ultra-sensitive C-reactive protein (CRP) (chemilu-
minescence) were measured. Plasma insulin was measured using
Metabolic syndrome was defined using the International Diabe-
an ELISA kit for human insulin with negligible cross-reactivity
tes Federation criteria,18 which considers central obesity based
with proinsulin (Linco Research, St. Louis, MO, USA). The
on waist circumference plus any two of the following four fac-
intra-assay and interassay CVs were 29–94% and 55–85%,
tors: raised triglyceride levels (=1695 mM) or current treatment
respectively. Free fatty acids (FFA) and adiponectin concentra-
for this condition; reduced HDL cholesterol (<1036 mM in men
tions were measured using an ELISA kit (R&D Systems, Minne-
and <1295 mM in women) or current treatment for this lipid;
apolis, MN, USA).
raised blood pressure (systolic blood pressure = 130 or diastolic
blood pressure = 85 mmHg) or current treatment with an anti-
hypertensive drug (for a previously diagnosed hypertension); or Statistical analysis
raised fasting plasma glucose (=555 mM) or previously diag-
Statistical analysis was performed with the SPSS program for
nosed type 2 diabetes. The cut-off for waist circumference was
Windows (version 18.0). A P value <005 was considered statisti-
to set Europids (e.g. WC 94 cm to men; WC 80 cm for
cally significant. The Kolmogorov–Smirnov test was applied to
women).
assess the assumption of normality for the data. Data were
reported as mean ± standard deviation (SD) or median/inter-
Blood biochemical assays quartile range, according to the normal distribution status. Spear-
man correlations were performed to assess associations of
Blood samples were obtained after a 12-h overnight fast and
interest. Receiver operating characteristic (ROC) curves were
were stored at 20 °C for later evaluation. Plasma glucose (glu-
constructed to evaluate the performance of anthropometric
cose oxidase method), glycated haemoglobin (HPLC method),
parameters to identify the conditions IR and MetS. The areas
lipid profile (total cholesterol, high-density lipoprotein choles-
under the ROC curves were calculated, using a range of 95%. For
terol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and
the comparison of curves, Z-test was performed with multiple
triglycerides), uric acid, liver enzymes (enzymatic colorimetric
comparisons two by two – MedCalc program version 9.3. The
sensitivity and specificity of anthropometric indicators were cal-
culated for each cut-off point in the sample. The cut-off point
Table 1. Baseline study sample characteristics
Men Women
Table 2. Age-adjusted Spearman correlation between the neck circum-
Parameters n = 301 n = 752 P-value
ference and certain risk factors
*Mean ± SD (all such values). GGT, gamma glutamyltransferase; ALT, alanine transferase; AST, aspar-
NS, not significant. tate transferase; PTHemogl., proportion of total haemoglobin.
Fig. 1 Relationship between NC (cm) and MetS risk factors in men (●) and women (○). Correlation assessed by Spearman analysis. Systolic and
diastolic blood pressure were measured in mmHg; total cholesterol, uric acid, HDL-cholesterol, fasting glucose and fasting insulin were measured in
mg/dl.
Fig. 2 Relationship between NC (cm) and M value, LogHOMA-IR and adiponectin (μg/ml) in men (●) and women (○).Correlation assessed by
Spearman analysis.
Fig. 3 Receiver operating characteristics (ROC) curves comparing anthropometric variables as discriminators of insulin resistance and metabolic
syndrome in men and women. *Areas under the curve for each anthropometric measure (P < 0001. CI, confidence interval).
Table 3. Cut-off levels for determining the individuals with IR and MetS according to ROC analysis
Men Women
Cut-off Sensitivity (95% CI) Specificity (95% CI) Cut-off Sensitivity (95% CI) Specificity (95% CI)
IR >396 641 (524–747) 669 (588–743) >361 659 (584–729) 713 (666–757)
MS >396 715 (614–809) 626 (556–692) >361 635 (571–696) 697 (655–737)
ratio (WHR), CRP, FFA, adiponectin and HOMA-IR, were sig- The age-adjusted NC measurements were significantly asso-
nificantly different between the genders. ciated with WC, which is often used as a surrogate marker of
Correlations between the NC, obesity and MetS markers, abdominal (subcutaneous and intra-abdominal) fat mass4 as well
adjusted for age, are presented in Table 2. The NC was associ- as with markers of MetS and IR. Compared with WC, the NC
ated with the obesity markers, WC and BMI, in men and also showed association with VF and IS. NC and WC measure-
women, while the NC correlated with WHR only in men. ments shared significant and independent association with IR
Among the traditional markers of MetS, the NC showed a posi- risk, although the NC was a better marker for women than for
tive correlation with fasting triglycerides and fasting glucose and men. The WC shows the best correlation for determining MetS,
showed a negative association with HDL cholesterol in both followed by BMI and W-HR; however, the NC was also closely
men and women. However, only women showed an association associated with MetS.
between the NC and blood pressure, uric acid, GGT and CRP This current study is the first to show a significant association
levels. between the NC and IR using the euglycemic-hyperinsulinemic
The NC was positively correlated with glycated haemoglobin, clamp, which is considered the gold standard method for mea-
fasting insulin, adiponectin and HOMA-IR levels in both groups. suring IS. Our findings are also in agreement with previous stu-
The main associations of the NC with MetS risk markers and VF dies, in which the NC and neck fat have been associated IR
are shown in Fig. 1. Figure 2 shows a negative association of the (measured by HOMA-IR), impaired glucose homeostasis, hyper-
NC with adiponectin and with the clamp-derived IS index as well lipidemia and hypertension.6,10,19–24 Moreover, a previous analy-
as a positive association of the NC with HOMA-IR. sis of the Framingham Heart Study demonstrated that the NC is
The ROC curves are presented in Fig. 3, along with their anal- associated with IR, elevated hypertension, and dyslipidemia,
yses. The AUC for different anthropometric measures were sta- independent of VF.25 Another previous study observed a signifi-
tistically significant (P < 0001). After performing Fisher’s Z-test, cant relationship between NC and carotid intima-media thick-
we observed that NC is not statistically different from WC, when ness, which is a direct measure of subclinical atherosclerosis, in
compared between both gender, for IR (P = 0992, for men; the general population.24
P = 0885 for women). In women, the NC presented the largest The NC is considered a surrogate marker of upper-body SF,
AUC for IR compared with men, which is similar to the WC. which is an important contributor to circulating FFA and is
For MetS, the WC showed the largest AUC in both genders more lipolytically active than lower body SF.26 Because FFA con-
(081 and 087 in men and women, respectively), followed by centrations are directly associated with IR,27 hepatic VLDL pro-
the BMI (078 and 084) and the WHR (079 and 078), duction,28 and endothelial dysfunction, upper body SF may have
although the NC also presented a large AUC (073 and 074). an important cardiovascular and metabolic impact.29
Table 3 shows the optimal cut-off values of the NC for IR and The regression procedure indicated that, for both gender, the
MetS. For men, the optimal NC cut-off values were >40 cm for enlargement of NC increases the chance to developing IR in 1·2
both IR and MetS. For women, the optimal cut-off NC values times. And only in women, was observed the relationship
were >361 cm for both IR and MetS (P < 0001). between the enlargement of NC and the chance to developing
After a binary logistic regression analysis, considering the MetS.
HOMA-IR and MetS as dependent variables and the NC and Another novelty of this study was determining the cut-off
WC as independent variables, the results were as follows: for value of the NC for the prediction of IR, regardless of the pre-
women, the enlargement of NC increased by 121 times the sence of MetS. Our study established that, for men, the NC cut-
chance of IR (β=020; P < 0001) and 113 times the chance of off value of >40 cm are suitable for assessing the likelihood of
MetS (β=012; P < 001), whereas the enlargement in WC both the same cutoff value for both IR and MS, either for men
increased by 104 times the chance of IR (β = 004; P < 0001) and women, considering the balance between specificity and sen-
and 108 times the chance of MetS (β = 008; P < 0001). For sitivity, respecting the assumption that there was less than 60%.
men, the enlargement of NC increased by 120 times the chance Thus we become the information with practical use. WC cutoffs
of having IR (β = 018; P < 0001) and was not related to the are clearly superior to NC regarding MetS but comparable with
increased chance of MetS, while the enlargement in WC respect to IR. It could be due to a weak association between
increased by 116 times the chance of having MetS (β = 015; WC and IR among diabetic individuals (data not show).
P < 0001) and 106 times the chance of having for IR One previous study10 determined cut-off values of the NC for
(β = 006; P < 0001). the prediction of MetS (but not for IR) that were very close to
those of our study: NC > 39 cm for men and NC > 35 cm for
women. Another study30 presented NC cut-off values of >39 cm
Discussion
for men and >35 cm for prediction of MetS in women with type
In this cross-sectional analysis of population-based data among 2 diabetes.
Brazilian adults, the NC was an indicator of central obesity, IR Our study has a few limitations, none of which affects the
(assessed by both euglycemic-hyperinsulinemic clamp and findings. First, the effects of life style and race were not assessed.
HOMA-IR), MetS and related biochemical parameters. Further- Racial classification might be inaccurate due to the admixture of
more, gender-specific cut-off values of the NC for IR and MetS races in the Brazilian population. Second, we did not assess sleep
were established. apnea, which might link the NC to some metabolic markers. A
third question is that our study includes a high prevalence of 4 Pouliot, M.C., Després, J.P., Lemieux, S. et al. (1994) Waist cir-
T2DM and there is a lack of adjustment for MetS components. cumference and abdominal sagittal diameter: best simple anthro-
Anthropometry is a simple evaluation tool with a well- pometric indexes of abdominal visceral adipose tissue
established relationship with body fat distribution and metabolic accumulation and related cardiovascular risk in men and
women. American Journal of Cardiology, 73, 460–468.
complications that overcomes the cost and availability limita-
5 Klein, S., Allison, D.B., Heymsfield, S.B. et al. (2007) Waist cir-
tions of the gold-standard methods (computed tomography,
cumference and cardiometabolic risk: a consensus statement
magnetic resonance).31–33 The NC requires a single measurement
from Shaping America’s Health: Association for Weight Manage-
site with low bias of anatomical and observer variations, ment and Obesity Prevention; NAASO, the Obesity Society; the
although there is no established guideline for measurement of American Society for Nutrition; and the American Diabetes
NC. Several studies show different positions for measurement of Association. Obesity (Silver Spring), 15, 1061–1067.
NC. [above the cricothyroid cartilage;2 at the level of the upper 6 Preis, S.R., Massaro, J.M., Hoffmann, U. et al. (2010) Neck cir-
margin of the thyroid cartilage;3 just below the laryngeal promi- cumference as a novel measure of cardiometabolic risk: the Fra-
nence;4–7 at the upper margin of the laryngeal prominence mingham Heart study. Journal of Clinical Endocrinology and
(Adam’s apple)8]. We choose to measure the NC below the cri- Metabolism, 95, 3701–3710.
cothyroid cartilage in order to standardize both for men and 7 Wang, Y., Rimm, E.B., Stampfer, M.J. et al. (2005) Comparison
of abdominal adiposity and overall obesity in predicting risk of
women, independent of the laryngeal prominence. It offers an
type 2 diabetes among men. American Journal of Clinical Nutri-
alternative to WC, especially in health conditions that affect the
tion, 81, 555–563.
abdominal wall, organs and cavity (lipoabdominoplasty, volumi-
8 Wang, J., Thornton, J.C., Bari, S. et al. (2003) Comparisons of
nous skin folds and pendulous abdomen in obese subjects or waist circumferences measured at 4 sites. American Journal of
after great weight loss, hernia and ascitis).3 In addition, different Clinical Nutrition, 77, 379–384.
anatomic landmarks also have been used to determine the exact 9 Poirier, P., Giles, T.D., Bray, G.A. et al. (2006) Obesity and car-
location for measuring the WC in different clinical studies, diovascular disease: pathophysiology, evaluation, and effect of
which influences the absolute WC value that is obtained.7,8 The weight loss: an update of the 1997 American Heart Association
specific site used to measure the WC influences the absolute Scientific Statement on Obesity and Heart Disease from the
WC value that is obtained and can limit the evaluation of fat Obesity Committee of the Council on Nutrition, Physical Activ-
body distribution. ity, and Metabolism. Circulation, 113, 898–918.
10 Onat, A., Hergenç, G., Yüksel, H. et al. (2009) Neck circumfer-
The NC is an alternative and innovative approach for the
ence as a measure of central obesity: associations with metabolic
determination of body fat distribution, which is associated with
syndrome and obstructive sleep apnea syndrome beyond waist
visceral fat, Metabolic Syndrome components and insulin resis-
circumference. Clinical Nutrition, 28, 46–51.
tance, specially in women. It is easily measured and has popula- 11 WHO (2000) Obesity: preventing and managing the global epi-
tion-based cut-off values for metabolic risk evaluation. demic. Report of a WHO Consultation. World Health Organ
Therefore, NC is a useful screening tool in clinical and research Tech Rep Ser. 894:i-xii, 1–253.
settings. 12 Sampaio, L.R., Simões, E.J., Assis, A.M.O. et al. (2007) Validity
and reliability of the sagittal abdominal diameter as a predictor
of visceral abdominal fat. Arquivos Brasileiros de Endocrinologia e
Acknowledgement Metabologia, 51, 980–986.
This research was supported by Foundations that support 13 Laakso, M., Matilainen, V. & Keinänen-Kiukaanniemi, S. (2002)
research in the State of Sao Paulo (FAPESP – Fundação de Association of neck circumference with insulin resistance-related
factors. International Journal of Obesity and Related Metabolic
Amparo a Pesquisa do Estado de São Paulo – 2007/58638-0).
Disorders, 26, 873–875.
14 Ribeiro-Filho, F.F., Faria, A.N., Azjen, S. et al. (2003) Methods
Conflict of interests of estimation of visceral fat: advantages of ultrasonography.
Obesity Research, 11, 1488–1494.
Nothing to declare. 15 Muscelli, E., Mingrone, G., Camastra, S. et al. (2005) Differential
effect of weight loss on insulin resistance in surgically treated
obese patients. American Journal of Medicine, 118, 51–57.
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