Upload
others
View
1
Download
0
Embed Size (px)
Citation preview
Draft
Association of 25-hydroxyvitamin D and parathyroid
hormone with the metabolic syndrome in black South
African women
Journal: Applied Physiology, Nutrition, and Metabolism
Manuscript ID apnm-2016-0257.R1
Manuscript Type: Article
Date Submitted by the Author: 25-Nov-2016
Complete List of Authors: Sotunde, Olusola; North West University Faculty of Health Sciences, Centre
of Excellence for Nutrition; University of South Africa, Life and Consumer Science Kruger, Herculina; North West University Faculty of Health Sciences, Centre of Excellence for Nutrition; North West University Faculty of Health Sciences, Medical Research Council Hypertension and Cardiovascular Disease Research Unit Wright, Hattie; North West University Faculty of Health Sciences, Centre of Excellence for Nutrition; University of the Sunshine Coast, School of Health and Sports sciences Havemann-Nel , Lize; North West University Faculty of Health Sciences, Centre of Excellence for Nutrition Mels, Carina; North West University Faculty of Health Sciences,
Hypertension in Africa Research Team Ravyse, Chrisna; North West University Faculty of Health Sciences, Centre of Excellence for Nutrition; North West University, Physical activity, Sport and Recreation Research Focus Area Pieters, Marlien; North West University Faculty of Health Sciences, Centre of Excellence for Nutrition
Keyword: 25(OH)D, PTH, metabolic syndrome, adiposity, obesity
https://mc06.manuscriptcentral.com/apnm-pubs
Applied Physiology, Nutrition, and Metabolism
Draft
1
Association of 25-hydroxyvitamin D and parathyroid hormone with the metabolic syndrome
in black South African women
Authors: Olusola Funmilayo Sotunde, Herculina Salome Kruger, Hattie H Wright, Lize
Havemann-Nel, Carina MC Mels, Chrisna Ravyse, Marlien Pieters.
Corresponding Author: Olusola Funmilayo Sotunde, Department of Life and Consumer
Sciences, College of Agriculture and Environmental Sciences UNISA, c/o Christiaan de Wet
& Pioneer Ave, Florida, Private Bag X6, UNISA Florida, 1710, South Africa.
E mail: [email protected]
Affiliations and address of all authors:
Olusola Funmilayo Sotunde1 Centre of Excellence for Nutrition, North-West University,
Potchefstroom South Africa. [email protected]
Herculina Salome Kruger, Centre of Excellence for Nutrition, North-West University,
Potchefstroom and Medical Research Council Hypertension and Cardiovascular Disease
Research Unit, North-West University, Potchefstroom Campus, Potchefstroom, 2520, South
Africa. [email protected]
Hattie H Wright,2 Centre of Excellence for Nutrition, North-West University, Potchefstroom
South Africa. [email protected]
Lize Havemann-Nel, Centre of Excellence for Nutrition, North-West University,
Potchefstroom South Africa. [email protected]
Carina MC Mels, Hypertension in Africa Research Team, Faculty of Health Sciences, North-
West University, Potchefstroom, South Africa. [email protected]
1 Department of Life and Consumer Science, University of South Africa. [email protected] 2 School of Health and Sports sciences, University of the Sunshine Coast, Maroochydore,
Queensland, Australia. [email protected]
Page 1 of 29
https://mc06.manuscriptcentral.com/apnm-pubs
Applied Physiology, Nutrition, and Metabolism
Draft
2
Chrisna Ravyse, Centre of Excellence for Nutrition, North-West University, Potchefstroom
and Physical activity, Sport and Recreation Research Focus Area, North-West University,
Potchefstroom, 2520, South Africa. [email protected]
Marlien Pieters, Centre of Excellence for Nutrition, North-West University, Potchefstroom
South Africa. [email protected]
Page 2 of 29
https://mc06.manuscriptcentral.com/apnm-pubs
Applied Physiology, Nutrition, and Metabolism
Draft
3
ABSTRACT
The relationship between 25 hydroxyvitamin D (25(OH)D), parathyroid hormone (PTH) and
metabolic traits appear to differ among ethnicities and may be influenced by obesity. The aim
of the study was to examine the association of serum 25(OH)D and PTH, respectively, with
the metabolic syndrome (MetS) while controlling for adiposity in black women. Using a
cross-sectional study design, 209 urban black women aged ≥ 43 years from the North West
Province, South Africa, were included. Multiple regression models were used to explore the
relationship between 25(OH)D, PTH and body composition. To explore the association
between 25(OH)D, PTH and MetS, a separate variable was created including at least three of
the MetS criteria, but excluding elevated waist circumference as a diagnostic criterion in a
logistic regression model. The majority of the women (69.9%) were overweight or obese and
65.5% of the women had excessive adiposity using the age specific cut-off points for body fat
percentage. All body composition variables were positively associated with PTH, while BMI
and waist circumference, but not body fat % had negative associations with 25(OH)D, also
after adjusting for confounders. Before and after adjusting for age, body fat, habitual physical
activity, tobacco use, season of data collection and estimated glomerular filtration rate,
neither 25(OH)D nor PTH showed significant associations with the MetS. Although PTH was
positively and 25(OH)D was negatively associated with adiposity in black women, there was
no association between either 25(OH)D or PTH and the MetS in this study population, nor
did adiposity influence these relationships.
Key words: 25(OH)D, PTH, metabolic syndrome, adiposity, obesity.
Page 3 of 29
https://mc06.manuscriptcentral.com/apnm-pubs
Applied Physiology, Nutrition, and Metabolism
Draft
4
Introduction
The metabolic syndrome (MetS) is a global epidemic, which increases the risk for
development of type 2 diabetes mellitus and cardiovascular morbidity and mortality (Wang et
al. 2007). MetS is a cluster of metabolic disorders that includes at least three of the following
five criteria: elevated fasting blood glucose, hypertension, abdominal obesity, elevated
triglycerides and low high density lipoprotein cholesterol (HDL-C) (Alberti et al. 2009).
A number of studies indicated metabolic roles for 25 hydroxy-vitamin D (25(OH)D) and
parathyroid hormone (PTH) (Reis et al. 2008, Lee et al. 2009), demonstrating a
comparatively consistent inverse relationship between serum vitamin D and MetS and a
positive association of PTH and the MetS (Hypponen et al. 2008, Reis et al. 2008, Lee et al.
2009, Yin et al. 2012). However, the relationship between low serum vitamin D and
metabolic traits appear to differ among ethnicities. In the USA, NHANES III data showed an
inverse association between vitamin D status and insulin resistance in non-Hispanic whites
and Mexican Americans, with no relationship in black Americans (Scragg et al. 2004).
South Africa is in the nutrition-related non-communicable disease phase of the nutrition
transition (Vorster et al. 2011) associated with an obesity epidemic. The MetS prevalence is
high among blacks and Asian-Indian South Africans (Motala et al. 2011, George et al. 2013).
To the best of our knowledge, only one study in South Africa has examined the association
between 25(OH)D, PTH and the MetS in Africans (George et al. 2013). The study found a
positive association between PTH and the MetS, but no association between 25(OH)D and
the MetS (George et al. 2013). We postulate that the association between 25(OH)D, PTH and
the MetS may be mediated by adiposity due to several metabolic functions of adipose tissue
(Wortsman et al. 2000, Lips 2001, Bischof et al. 2006, Greenberg and Obin 2006, Reinehr et
al. 2007, Reis et al. 2007).
Page 4 of 29
https://mc06.manuscriptcentral.com/apnm-pubs
Applied Physiology, Nutrition, and Metabolism
Draft
5
As individuals become obese their adipocytes enlarge and adipose tissue undergoes
molecular and cellular changes affecting systemic metabolism (Greenberg and Obin 2006).
Adipocytes are active endocrine organs that play multiple roles in the body in addition to
their role as a storage reservoir of fat (Greenberg and Obin 2006). Vitamin D deficiency was
associated with excess body weight in some studies (Bischof et al. 2006, Greenberg and Obin
2006, Reinehr et al. 2007), which could be due to fat-soluble vitamin D getting trapped in
excess body fat, thereby reducing its bioavailability (Wortsman et al. 2000). Low serum
vitamin D is also associated with elevated PTH secretion (Lips 2001) which has been linked
to obesity (Reis et al. 2007) and the MetS (Reis et al. 2007, Ahlström et al. 2009).
Consequently, the aim of the study was to examine the association of serum 25(OH)D and
PTH, respectively, with the MetS while controlling for adiposity in black women of the North
West Province, South Africa.
Methods
Study design and subjects
The South African North West Province arm of the Prospective Urban and Rural
Epidemiology (PURE-SA-NWP) study commenced with baseline data collection in 2005 on
randomly selected apparently healthy adults older than 35 years (Teo et al. 2009, Kruger et al.
2011). Using a cross-sectional study design, urban black women measured at 7 years follow-
up of the PURE-SA-NWP study were included in this sub-study. The measurements for this
sub-study took place between September 2012 and June 2013. Only participants who had
undergone dual energy X-ray absorptiometry (DXA) measurements and provided blood
samples at follow-up and who were HIV negative were eligible for inclusion in this study
(n=209). The seasons of data collection were defined as September to early December 2012
Page 5 of 29
https://mc06.manuscriptcentral.com/apnm-pubs
Applied Physiology, Nutrition, and Metabolism
Draft
6
for spring (season 0, reference) and April to early June 2013 for autumn (season 1). The study
was approved by the Ethics committee of the North-West University (NWU), Potchefstroom
campus (NWU-00016-10-A1). All participants provided written informed consent and all
procedures followed were in accordance with the ethical standards of the Helsinki
Declaration.
Body composition measurements
Height (cm), weight (kg) and waist circumference (cm) were measured to the nearest decimal
according to the International Society for the Advancement of Kinanthropometry (ISAK)
criteria (Marfell-Jones et al. 2012). Body fat percentage was measured by a registered
radiographer using dual energy x-ray absorptiometry (Hologic Discovery W, APEX system
software version 12.7.3.1). Body mass index (BMI) was calculated (weight in kilograms
divided by height in meter squared). Abdominal obesity was defined as waist circumference
≥ 80 cm (Alberti et al. 2009). Age-specific cut-offs for high body fat percentage were defined
as ≥35.8% for women aged 43-49 years and ≥37.7% for women aged 50 years and above to
indicate adiposity (Heo et al. 2012).
Biochemical analyses and blood pressure measurement
Blood samples were collected from the ante-brachial vein following an overnight fast. Serum
samples were prepared and stored at -80ºC. All samples were analysed at the same time with
reagents from the same lot. Serum cholesterol, triglycerides (TG), HDL-C, high sensitivity C
reactive protein (CRP), creatinine and plasma glucose were analysed on the Cobas Integra
400 Plus (Roche, Basel, Switzerland). Insulin, 25(OH)D concentrations and PTH were
determined with an electrochemiluminescence immunoassay on the Elecsys 2010 (Roche,
Page 6 of 29
https://mc06.manuscriptcentral.com/apnm-pubs
Applied Physiology, Nutrition, and Metabolism
Draft
7
Basel, Switzerland). All inter- and intra assay coefficients of variation (CV) were less than
10%. We defined vitamin D deficiency as serum 25(OH)D concentrations < 20 ng/mL, and
vitamin D insufficiency as 25(OH)D between 21-29 ng/mL (Holick et al. 2011). Elevated
PTH was defined as PTH concentration > 65 pg/mL (Heil and Ehrhardt 2008). The
homeostasis model assessment (HOMA) technique was used to calculate insulin resistance
(HOMA-IR) (Matthews et al. 1985) and estimated glomerular filtration rate (eGFR) was
calculated with the modification of diet in renal disease (MDRD) formula (Levey et al. 2006).
After ten minutes’ rest, systolic and diastolic blood pressures were measured with an
OMRON HEM-757 instrument (Omron Healthcare, Kyoto, Japan), using appropriate sized
cuffs. The measurements were carried out in duplicate (5 minutes apart) on the right upper
arm, while the participants were seated with the right arm supported at heart level.
Questionnaires and physical activity
Structured questionnaires adapted for the PURE study were used by trained fieldworkers to
collect socio-demographic and lifestyle information, which included tobacco use (smoking
and/or snuff), in the participants’ language of choice (Teo et al. 2009). Habitual physical
activity was measured with a modified Baecke questionnaire (Kruger et al. 2000) and
physical activity scores were obtained (Kruger et al. 2011). A physical activity index value
from 1 to 3.3 was categorised as low, 3.34 to 6.67 was moderate and greater that 6.67 was
categorised as high physical activity (Kruger et al. 2011). Habitual activity energy
expenditure was also measured using an accelerometer with a combined heart rate monitor
(ActiHeart®, Camtech, UK) for 7 days (Brage et al. 2005). The time spent per individual in
each physical activity intensity category was recorded and activity energy expenditure (AEE)
was determined. Duration and intensity of activity were categorized as 1.1 – 2.9 METS as
Page 7 of 29
https://mc06.manuscriptcentral.com/apnm-pubs
Applied Physiology, Nutrition, and Metabolism
Draft
8
light-intensity activity, 3.0 – 5.9 METS as moderate-intensity activity and vigorous activity
as ≥ 6 METS (Donnelly et al. 2009). Total energy expenditure was also calculated (Kcal).
The reliability and validity of the ActiHeart® to evaluate physical activity in Sub-Saharan
Africans has been previously assessed (Assah et al. 2011).
Diagnosis of the MetS
Using the harmonized definition, participants with at least three of the following criteria were
diagnosed to have the MetS (Alberti et al. 2009): elevated waist circumference (≥ 80cm);
hypertension (diagnosed hypertensive subjects on blood pressure medications or subjects
with systolic blood pressure ≥ 130 mmHg and/or diastolic blood pressure ≥ 85 mmHg);
elevated serum triglycerides (≥ 1.7 mmol/L); reduced serum HDL-C (<1.3 mmol/L) and
subjects on oral hypoglycemic medication or with elevated fasting blood glucose (≥ 5.6
mmol/L). None of the subjects used hypolipidemic drugs. A separate MetS variable was
created, excluding elevated waist circumference as a diagnostic criterion, due to the strong
collinear relationship between body fat percentage and waist circumference. Hence, this
variable was defined as the presence of 3 out of 4 MetS criteria (Alberti et al. 2009) and used
for the logistic regression analysis, with presence of the modified MetS as dependent variable
and body fat percentage as a covariate.
Statistical analysis
IBM SPSS version 22 (IBM Company, Armonk, NY, USA) was used for all analyses.
Normally distributed data are presented as means ± standard deviation. Non-normally
distributed data was logarithmically transformed for statistical purposes and presented as
medians and interquartile range. Categorical data were analysed using frequency tables and
Page 8 of 29
https://mc06.manuscriptcentral.com/apnm-pubs
Applied Physiology, Nutrition, and Metabolism
Draft
9
prevalence of specific conditions was expressed as percentages. Independent t-tests were used
to compare normally distributed variables and Mann-Whitney U-tests to compare non-
normally distributed variables between groups with MetS (modified MetS classification, 3
out of 4 criteria) and without MetS. Analysis of covariance (ANCOVA) was used to adjust
for body fat percentage while comparing means of 25(OH)D and PTH between groups with
and without MetS. To explore the relationship between 25(OH)D, PTH and MetS variables
the correlations between 25(OH)D, PTH and individual components of the metabolic
syndrome were assessed. Stepwise multiple regressions were then used to explore the
relationship between 25(OH)D, PTH and body composition variables while adjusting for age,
physical activity score, tobacco use, season of data collection, CRP and eGFR as possible
confounders, based on known relationships observed in the literature (Brossard et al. 2000,
Fröhlich et al. 2000, Reis et al. 2008, Young et al. 2008, Muntner et al. 2009, Jungert et al.
2012). CRP may be increased in individuals with acute infection, but chronic low-grade
inflammation with mildly elevated serum CRP is often reported in obese individuals (Yudkin
et al. 1999, Fröhlich et al. 2000). We performed a sensitivity analysis for possible
confounding effects of CRP in individuals with CRP<10mg/L (n=161), but CRP did not
contribute significantly to the models and we therefore excluded CRP from the final models.
Only the variables that entered the stepwise models are presented in the tables in order to
provide the best fit models. Multivariate ORs for the modified MetS with 25(OH)D or PTH
were calculated, adjusting for age, tobacco use, physical activity, body fat percentage, eGFR
and season of data collection in logistic regression. Statistical significance was set at p <
0.05.
Results
Page 9 of 29
https://mc06.manuscriptcentral.com/apnm-pubs
Applied Physiology, Nutrition, and Metabolism
Draft
10
Demographic, body composition and metabolic characteristics of the participants are
presented in Table 1. Using the World Health Organisation (WHO) BMI classification,
69.9% of the women were overweight or obese and 65.5% of the women had excessive
adiposity using the age specific cut-off points for body fat percentage (Heo et al. 2012).
Actiheart® data for 184 (88.04%) women were available for analysis. Habitual physical
activity measured by Actiheart® indicated that the women spent on average 13.4% of their
time (3.21 hours) engaging in light-intensity activity, 2% in moderate-intensity activity (0.49
hours) and only 0.005% of total time (0.07 hours) in activities representing ≥ 6 METS (i.e.
vigorous activity). Results of the Baecke physical activity questionnaire also showed a low
mean physical activity score, within the inactive range from 1 - 3.3 (Kruger et al. 2011).
Vitamin D status of women measured in autumn was significantly higher than those
measured in spring (p<0.001), with mean serum 25(OH)D concentrations of 36.5 (±7.30) and
27.5 (±9.23) ng/mL, respectively. Similarly more women were vitamin D insufficient in
spring compared to autumn (55.4% vs. 16.9% respectively, p<0.001).
Women who used tobacco had significantly lower measures of adiposity compared to women
who did not use tobacco (body fat percentage 38.6% vs 42.4%, p <0.001, BMI 28.0 vs 31.3
kg/m2, p <0.01 and waist circumference 87.4 cm vs 92.6 cm, p = 0.01). Univariate
correlations between 25(OH)D, PTH and individual components of the metabolic syndrome
showed no significant correlations, except for the expected significant correlations with
waist circumference and an unexpected positive correlation between 25(OH)D and diastolic
blood pressure (Table 2).
Using the harmonized definition, the MetS was diagnosed in 43.1% of the women, with
hypertension (85.6%) being the most common and elevated triglycerides (27.8%) being the
Page 10 of 29
https://mc06.manuscriptcentral.com/apnm-pubs
Applied Physiology, Nutrition, and Metabolism
Draft
11
least common component of MetS (Table 1). Women with the MetS had significantly higher
body fat percentage, BMI, waist circumference, HOMA-IR, plasma glucose, insulin,
triglycerides and CRP, while the eGFR and HDL-C of women with MetS were significantly
lower. There were no differences between the mean serum 25(OH)D, PTH and age of women
with and without the MetS, even after adjusting for body fat. There were no differences in the
prevalence of insufficient serum vitamin D or elevated PTH levels between women with and
without the MetS.
Unadjusted multiple regression models showed all adiposity variables to be inversely
associated with 25(OH)D and positively associated with PTH (Table 3, model 1). These
associations remained when adjusting for possible confounders, except for the association
between body fat % and 25(OH)D, which became non-significant. Apart from the adiposity
variables, age, season of data collection and eGFR remained as significant contributors to
PTH in the stepwise regression models, while eGFR did not contribute to 25(OH)D models
(Table 3, model 2)
In the logistic regression analysis using the modified MetS variable, neither 25(OH)D nor
PTH was significantly associated with the MetS (Table 4). In the adjusted models, only the
use of tobacco was significantly associated with the MetS (model 2) with women who use
tobacco being less likely to have the MetS.
Discussion
Studies showed inconsistent relationships between 25(OH)D and PTH, respectively and the
MetS and to our knowledge this study is the first study to investigate the influence of
adiposity on these relationships. The findings of this study indicate a general lack of
significant associations between 25(OH)D and PTH respectively, with the MetS, before and
Page 11 of 29
https://mc06.manuscriptcentral.com/apnm-pubs
Applied Physiology, Nutrition, and Metabolism
Draft
12
after adjusting for adiposity in black South African women. However, positive associations
between adiposity variables and PTH and negative associations with 25(OH)D were found.
Some studies show inverse associations between 25(OH)D and the MetS (Hypponen et al.
2008, Yin et al. 2012) and positive associations between PTH and the MetS (Reis et al. 2007,
Ahlström et al. 2009). Other studies have reported no associations between 25(OH)D and/or
PTH and the MetS (Reis et al. 2007, Rueda et al. 2008). The lack of a negative relationship
between the MetS and 25(OH)D, despite the high prevalence (43%) of the MetS observed in
this present study could be explained in part by the low prevalence of vitamin D deficiency
(15.9%). In contradiction to this study, higher prevalence of vitamin D deficiency were found
in studies that showed inverse associations between 25(OH)D and the MetS (Hypponen et al.
2008, Yin et al. 2012). Another possible contributing factor may be that black individuals are
not sensitive to the metabolic effects of vitamin D (Scragg et al. 2004). A similar study
among black and Asian-Indian South Africans also found no association between 25(OH)D
and the MetS (George et al. 2013). The same study (George et al. 2013), however, found a
positive association between PTH and the MetS, which is in contrast to the findings of this
present study. Although results of this study showed a tendency for women with the MetS to
have a higher PTH compared to women without MetS (p = 0.09), this difference was
attenuated after adjustment for body fat % in the ANCOVA (Table 1). Univariate correlations
between 25(OH)D, PTH and individual components of the metabolic syndrome showed no
correlations, except for the expected significant correlations with waist circumference, as
well as an unexpected positive correlation between 25(OH)D and diastolic blood pressure
(Table 2). This positive correlation is difficult to explain, given that a systematic review and
meta-analysis concluded that there was weak evidence for an inverse, but not for a positive
association between vitamin D and blood pressure, although most included studies were
performed in hypertensive patients (Witham et al. 2009).
Page 12 of 29
https://mc06.manuscriptcentral.com/apnm-pubs
Applied Physiology, Nutrition, and Metabolism
Draft
13
It has previously been postulated that low 25(OH)D and resulting increases in PTH were both
consequences of obesity (Wortsman et al. 2000, Bischof et al. 2006, Reinehr et al. 2007).
Some studies on the other hand have suggested that elevated PTH promotes the accumulation
of adipose tissue, thereby suggesting the possibility that elevated PTH may play a role in the
development of obesity (McCarty and Thomas 2003, Valiña-Tóth et al. 2010). The results of
this study are consistent with previous reports on positive associations between PTH and
measures of adiposity (Wortsman et al. 2000, McCarty and Thomas 2003, Snijder et al. 2005,
Bischof et al. 2006, Reinehr et al. 2007, Valiña-Tóth et al. 2010). Adipose tissue also acts as
a reservoir for vitamin D in the body (Wortsman et al. 2000) and in addition to this,
abdominal adipose tissue releases inflammatory cytokines which further decrease the amount
of circulating 25(OH)D (Blum et al. 2008). In agreement with this evidence, adiposity
variables (except body fat percentage) retained their inverse associations with 25(OH)D after
adjusting for confounders in these African women. The relationship observed between
adiposity variables, 25(OH)D and PTH respectively in this study further corroborates the
results of earlier studies carried out in different study populations (Wortsman et al. 2000,
McCarty and Thomas 2003, Snijder et al. 2005, Bischof et al. 2006, Reinehr et al. 2007,
Valiña-Tóth et al. 2010, Jungert et al. 2012).
Age and season of data collection consistently contributed to 25(OH)D and PTH
concentrations respectively, while eGFR had consistent inverse associations with PTH
concentrations (Table 2, models 2). The observation that the vitamin D status of women
measured in autumn was significantly higher than those measured in spring and the inverse
relationship with PTH in this study sample, is consistent with results of other studies (Bischof
et al. 2006, Valiña-Tóth et al. 2010). Higher vitamin D status in autumn compared to spring is
assumed to be the result of greater sunlight exposure over the long South African summer
compared to less sunlight during winter. This could lead to individuals having a higher
Page 13 of 29
https://mc06.manuscriptcentral.com/apnm-pubs
Applied Physiology, Nutrition, and Metabolism
Draft
14
vitamin D store going into autumn compared to the vitamin D available in spring after winter.
This is an indication of the important effect of exposure to sunlight on vitamin D status
(Rucker et al. 2002). In addition we found a decline of 25(OH)D with advancing age which
corroborates results of previous studies (Rucker et al. 2002, Bischof et al. 2006). Although
aging itself does not necessarily cause a decrease in 25(OH)D, age-related impaired renal
function may interfere with vitamin D metabolism (Lips 2001). The increase in PTH with
advancing age observed in this present study is consistent with what has been previously
established and this too has been generally attributed to age-related decline in renal function
(Lips 2001, Lee et al. 2009). The consistent negative association between eGFR and PTH in
this study indicates a specific role for GFR on PTH concentration. This is in line with the
hypothesis that GFR influences the concentration of PTH which may be as a result of
decreased renal clearance of PTH as GFR decreases (Brossard et al. 2000, Muntner et al.
2009).
While 25(OH)D and PTH were not main contributors to the presence of the MetS in black
women in this study in neither the adjusted nor unadjusted model, tobacco use was found to
make a significant contribution. We found an unexpected negative association between
tobacco use on having the MetS. We propose that the relationship between tobacco use and
the MetS may, at least in part, be through the effect of smoking on adiposity (Klesges et al.
1989). This result contradicts the result of a previous study in which the relationship between
smoking and the MetS was found to be dose responsive with heavy smokers having a higher
risk of developing MetS in comparison to light or non-smokers (Slagter et al. 2014).
Despite significant differences in eGFR and body fat % between the MetS and non-MetS
groups, these variables did not enter the logistic regression model as significant contributors
to having the MetS. The non-significant contribution of eGFR to the MetS in this study could
Page 14 of 29
https://mc06.manuscriptcentral.com/apnm-pubs
Applied Physiology, Nutrition, and Metabolism
Draft
15
be due to the fact that the eGFR values of the majority of the study population including the
women with MetS, were within the normal range (Table 1). Only 9.5% of the women had
eGFR < 90 ml/min/1.73m2, indicating possible impaired kidney function (data not shown)
(Levey et al. 2006). We propose that the non-significant contribution of total body fat % to
the MetS in this present study could be explained by the phenomenon that most black South
African women have a larger percentage of their body fat distributed subcutaneously around
their hips than around their waists (Fox et al. 2007). This is supported by literature
demonstrating a stronger association between an adverse metabolic risk profile with visceral
compared to subcutaneous adipose tissue (Fox et al. 2007). A sub-analysis excluding
participants with acute inflammation (CRP > 10mg/L) was carried out to investigate the
contribution of CRP to the MetS and showed that CRP had no significant contribution to the
MetS and was not associated with serum 25(OH)D nor PTH in this study population.
Limitations of this study include its cross-sectional design, thus we cannot draw conclusions
regarding causality. This study was performed in black urban women and the results may not
be generalizable to the greater black South African population. Furthermore we could not get
accurate records from the self-report of the quantity of tobacco used, in order to separate light
and heavy tobacco users. Despite the limitations, this study has further highlighted the
differences between the risk factors for the MetS in Africans compared to other ethnic
groups.
Conclusions
In conclusion, PTH was positively and 25(OH)D negatively associated with measures of
adiposity in black South African women. There were, however, no association between PTH
nor 25(OH)D and the MetS in black South African women, nor were these associations
Page 15 of 29
https://mc06.manuscriptcentral.com/apnm-pubs
Applied Physiology, Nutrition, and Metabolism
Draft
16
influenced by obesity. In view of the high prevalence of overweight and obesity with the
associations observed between PTH, 25 (OH)D and measures of adiposity respectively,
intervention programs aimed at healthier lifestyles should be promoted to prevent and combat
obesity and its associated negative health effects.
Conflict of interests
The authors declare that they have no conflict of interests.
Acknowledgments
1. The authors would like to thank all supporting staff and the participants of the PURE
study and in particular: PURE-South Africa: The PURE-NWP-SA research team, field
workers and office staff in the Africa Unit for Transdisciplinary Health Research
(AUTHeR), Faculty of Health Sciences, North-West University, Potchefstroom, South
Africa. PURE International: Dr S Yusuf and the PURE project office staff at the
Population Health Research Institute (PHRI), Hamilton Health Sciences and McMaster
University. ON, Canada. Funders: South African Medical Research Council, SANPAD
(South Africa - Netherlands Research Programme on Alternatives in Development),
South African National Research Foundation (NRF GUN numbers 2069139 and
FA2006040700010), North-West University and PHRI. Any opinion, findings, and
conclusions or recommendations expressed in this material are those of the authors and
therefore the National Research Foundation does not accept any liability in regard thereto.
Sincere appreciation to Prof Edith Feskens of Wageningen University for critically
reviewing the first draft of this manuscript.
Statistical support: Dr Suria Ellis
Page 16 of 29
https://mc06.manuscriptcentral.com/apnm-pubs
Applied Physiology, Nutrition, and Metabolism
Draft
17
References
Ahlström, T., Hagström, E., Larsson, A., Rudberg, C., Lind, L., and Hellman, P. 2009.
Correlation between plasma calcium, parathyroid hormone (PTH) and the metabolic
syndrome (MetS) in a community-based cohort of men and women. Clin. Endocrinol.
(Oxf). 71(5): 673–678.
Alberti, K.G.M.M., Eckel, R.H., Grundy, S.M., Zimmet, P.Z., Cleeman, J.I., Donato, K. a,
Fruchart, J.-C., James, W.P.T., Loria, C.M., and Smith, S.C. 2009. Harmonizing the
metabolic syndrome: a joint interim statement of the International Diabetes Federation
Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute;
American Heart Association; World Heart Federation; International Atherosclerosis
Society; and International Association for the Study of Obesity. Circulation 2009;
120(16):1640–1645.
Assah, F.K., Ekelund, U., Brage, S., Wright, A., Mbanya, J.C., and Wareham, N.J. 2011.
Accuracy and validity of a combined heart rate and motion sensor for the measurement
of free-living physical activity energy expenditure in adults in Cameroon. Int. J.
Epidemiol. 40(1): 112–20. doi:10.1093/ije/dyq098.
Bischof, M.G., Heinze, G., and Vierhapper, H. 2006. Vitamin D status and its relation to age
and body mass index. Horm. Res. 66(5): 211–215.
Blum, M., Dolnikowski, G., Seyoum, E., Harris, S., Booth, S., Peterson, J., Saltzman, E.,
Dawson-Huges, B., and Dawson-Hughes, B. 2008. Vitamin D3 in fat tissue. Endocrine
33(1): 90–94. Humana Press Inc. doi:10.1007/s12020-008-9051-4.
Brage, S., Brage, N., Franks, P.W., Ekelund, U., and Wareham, N.J. 2005. Reliability and
validity of the combined heart rate and movement sensor Actiheart. Eur. J. Clin. Nutr.
59(4): 561–570.
Page 17 of 29
https://mc06.manuscriptcentral.com/apnm-pubs
Applied Physiology, Nutrition, and Metabolism
Draft
18
Brossard, J.H., Lepage, R., Cardinal, H., Roy, L., Rousseau, L., Dorais, C., and D’Amour, P.
2000. Influence of glomerular filtration rate on non-(1-84) parathyroid hormone (PTH)
detected by intact PTH assays. Clin. Chem. 46(5): 697–703.
Donnelly, J.E., Blair, S.N., Jakicic, J.M., Manore, M.M., Rankin, J.W., and Smith, B.K.
2009. Appropriate physical activity intervention strategies for weight loss and
prevention of weight regain for adults. Med Sci Sports Exerc.41(2):459–471.
Fox, C.S., Massaro, J.M., Hoffmann, U., Pou, K.M., Maurovich-Horvat, P., Liu, C.Y., Vasan,
R.S., Murabito, J.M., Meigs, J.B., Cupples, L.A., D’Agostino, R.B., and O’Donnell, C.J.
2007. Abdominal visceral and subcutaneous adipose tissue compartments: Association
with metabolic risk factors in the framingham heart study. Circulation 116(1): 39–48.
Fröhlich, M., Imhof, A., Berg, G., Hutchinson, W.L., Pepys, M.B., Boeing, H., Muche, R.,
Brenner, H., and Koenig, W. 2000. Association between C-reactive protein and features
of the metabolic syndrome. Diabetes Care 23(12): 1835–1839.
George, J.A., Norris, S.A., van Deventer, H.E., Crowther, N.J. 2013. The Association of 25
Hydroxyvitamin D and Parathyroid Hormone with Metabolic Syndrome in Two Ethnic
Groups in South Africa. PLoS One 8(4): e61282. Public Library of Science.
doi:10.1371/journal.pone.0061282.
Greenberg, A.S., and Obin, M.S. 2006. Obesity and the role of adipose tissue in inflammation
and metabolism. Am J Clin Nutr. 83:461S–465S.
Heil, W., and Ehrhardt, V. 2008. Reference ranges for adults and children: Pre-analytical
considerations. Mannheim, Germany, Roche diagnostics.
Heo, M., Faith, M.S., Pietrobelli, A., and Heymsfield, S.B. 2012. Percentage of body fat
cutoffs by sex, age, and race-ethnicity in the US adult population from NHANES 1999-
2004. Am. J. Clin. Nutr. 95(3): 594–602.
Page 18 of 29
https://mc06.manuscriptcentral.com/apnm-pubs
Applied Physiology, Nutrition, and Metabolism
Draft
19
Holick, M.F., Binkley, N.C., Bischoff-Ferrari, H. a, Gordon, C.M., Hanley, D. a, Heaney,
R.P., Murad, M.H., and Weaver, C.M. 2011. Evaluation, treatment, and prevention of
vitamin D deficiency: an Endocrine Society clinical practice guideline. J. Clin.
Endocrinol. Metab. 96(7): 1911–30. doi:10.1210/jc.2011-0385.
Hypponen, E., Boucher, B., Berry, D., and Power, C. 2008. 25-hydroxyvitamin D, IGF-1 and
metabolic syndrome at age 45y: a cross-sectional study in the 1958 British birth cohort.
Diabetes 57(2): 298–305. Available from http://dx.doi.org/10.2337/db07-1122.
Jungert, A., Roth, H.J., and Neuhäuser-Berthold, M. 2012. Serum 25-hydroxyvitamin D3 and
body composition in an elderly cohort from Germany: a cross-sectional study. Nutr.
Metab. (Lond). 9(1): 42. BioMed Central. doi:10.1186/1743-7075-9-42.
Klesges, R.C., Meyers, a W., Klesges, L.M., and La Vasque, M.E. 1989. Smoking, body
weight, and their effects on smoking behavior: a comprehensive review of the literature.
Psychol. Bull. 106(2): 204–230. doi:10.1037//0033-2909.106.2.204.
Kruger, H.S., Venter, C.S., and Steyn, H.S. 2000. A standardised physical activity
questionnaire for a population in transition: the THUSA study. Afr J. Phys. Health.
Educ. Recreat. Danc. 6(1): 54 – 64.
Kruger, M.C., Kruger, I.M., Wentzel-Viljoen, E., and Kruger, A. 2011. Urbanization of black
South African women may increase risk of low bone mass due to low vitamin D status,
low calcium intake, and high bone turnover. doi:10.1016/j.nutres.2011.09.012.
Lee, D.M., Rutter, M.K., O’Neill, T.W., Boonen, S., Vanderschueren, D., Bouillon, R.,
Bartfai, G., Casanueva, F.F., Finn, J.D., Forti, G., Giwercman, A., Han, T.S.,
Huhtaniemi, I.T., Kula, K., Lean, M.E.J., Pendleton, N., Punab, M., Silman, A.J., and
Wu, F.C.W. 2009. Vitamin D, parathyroid hormone and the metabolic syndrome in
middle-aged and older European men. Eur. J. Endocrinol. 161(6): 947–954.
Page 19 of 29
https://mc06.manuscriptcentral.com/apnm-pubs
Applied Physiology, Nutrition, and Metabolism
Draft
20
Levey, A.S., Coresh, J., Greene, T., Stevens, L.A., Zhang, Y., Hendriksen, S., Kusek, J.W.,
and Van Lente, F. 2006. Using standardized serum creatinine values in the modification
of diet in renal disease study equation for estimating glomerular filtration rate. Ann.
Intern. Med. 145(4): 247–254.
Lips, P. 2001. Vitamin D deficiency and secondary hyperparathyroidism in the elderly:
Consequences for bone loss and fractures and therapeutic implications. Endocr. Rev.
2001;22(4):477–501.
Marfell-Jones, M.J., Stewart, A.D., and de Ridder, J.H. 2012. International standards for
anthropometric assessment. Australia: The international society for the advancement of
Kinanthropometry.
Matthews, D.R., Hosker, J.P., Rudenski, a. S., Naylor, B. a., Treacher, D.F., and Turner,
R.C. 1985. Homeostasis model assessment: insulin resistance and B-cell function from
fasting plasma glucose and insulin concentrations in man. Diabetologia 28(7): 412–419.
doi:10.1007/BF00280883.
McCarty, M.F., and Thomas, C.A. 2003. PTH excess may promote weight gain by impeding
catecholamine-induced lipolysis-implications for the impact of calcium, vitamin D, and
alcohol on body weight. Med. Hypotheses 61(5-6): 535–542.
Motala, A.A., Esterhuizen, T., Pirie, F.J., and Omar, M.A.K. 2011. The prevalence of
metabolic syndrome and determination of the optimal waist circumference cutoff points
in a rural South African community. Diabetes Care 34(4): 1032–1037.
Muntner, P., Jones, T.M., Hyre, A.D., Melamed, M.L., Alper, A., Raggi, P., and Leonard,
M.B. 2009. Association of serum intact parathyroid hormone with lower estimated
glomerular filtration rate. Clin. J. Am. Soc. Nephrol. 4(1): 186–94.
doi:10.2215/CJN.03050608.
Page 20 of 29
https://mc06.manuscriptcentral.com/apnm-pubs
Applied Physiology, Nutrition, and Metabolism
Draft
21
Reinehr, T., de Sousa, G., Alexy, U., Kersting, M., and Andler, W. 2007. Vitamin D status
and parathyroid hormone in obese children before and after weight loss. Eur. J.
Endocrinol. 157(2): 225–32. doi:10.1530/EJE-07-0188.
Reis, J.P., von Muhlen, D., Kritz-Silverstein, D., Wingard, D.L., Barrett-Connor, E., and Eis,
J.A.P.R. 2007. Vitamin D , Parathyroid hormone levels , and the prevalence of
metabolic syndrome in community-dwelling older adults. Cardiovasc. Metab. Risk
30(6): 1549–1555. doi:10.2337/dc06-2438.
Reis, J.P., von Mühlen, D., and Miller, E.R. 2008. Relation of 25-hydroxyvitamin D and
parathyroid hormone levels with metabolic syndrome among US adults. Eur. J.
Endocrinol. 159(1): 41–8. doi:10.1530/EJE-08-0072.
Rucker, D., Allan, J.A., Fick, G.H., and Hanley, D.A. 2002. Vitamin D insufficiency in a
population of healthy western Canadians. CMAJ 166(12): 1517–1524.
Rueda, S., Fernández-Fernández, C., Romero, F., Martínez de Osaba, J., and Vidal, J. 2008.
Vitamin D, PTH, and the metabolic syndrome in severely obese subjects. Obes. Surg.
18(2): 151–4. doi:10.1007/s11695-007-9352-3.
Scragg, R., Sowers, M., and Bell, C. 2004. Serum 25-hydroxyvitamin D, diabetes, and
ethnicity in the Third National Health and Nutrition Examination Survey. Diabetes Care
2004; 27(12):2813-8.
Slagter, S.N., Van Vliet-Ostaptchouk, J. V., Vonk, J.M., Boezen, H.M., Dullaart, R.P.F.,
Muller Kobold, A.C., Feskens, E.J.M., Van Beek, A.P., Van Der Klauw, M.M., and
Wolffenbuttel, B.H.R. 2014. Combined effects of smoking and alcohol on metabolic
syndrome: The lifelines cohort study. PLoS One 9(4):e96406.
Snijder, M.B., van Dam, R.M., Visser, M., Deeg, D.J.H., Dekker, J.M., Bouter, L.M., Seidell,
J.C., and Lips, P. 2005. Adiposity in relation to vitamin D status and parathyroid
Page 21 of 29
https://mc06.manuscriptcentral.com/apnm-pubs
Applied Physiology, Nutrition, and Metabolism
Draft
22
hormone levels: a population-based study in older men and women. J. Clin. Endocrinol.
Metab. 90(7): 4119–23. doi:10.1210/jc.2005-0216.
Teo, K., Chow, C.K., Vaz, M., Rangarajan, S., and Yusuf, S. 2009. The Prospective Urban
Rural Epidemiology (PURE) study: Examining the impact of societal influences on
chronic noncommunicable diseases in low-, middle-, and high-income countries. Am
Heart J. 158(1):1–7 doi:10.1016/j.ahj.2009.04.019.
Valiña-Tóth, A.L.B., Lai, Z., Yoo, W., Abou-Samra, A., Gadegbeku, C.A., and Flack, J.M.
2010. Relationship of vitamin D and parathyroid hormone with obesity and body
composition in African Americans. Clin. Endocrinol. (Oxf). 72(5): 595–603.
Vorster, H.H., Kruger, A., and Margetts, B.M. 2011. The nutrition transition in Africa: can it
be steered into a more positive direction? Nutrients. 3(4):429–441.
Wang, J., Ruotsalainen, S., Moilanen, L., Lepistö, P., Laakso, M., and Kuusisto, J. 2007. The
metabolic syndrome predicts cardiovascular mortality: A 13-year follow-up study in
elderly non-diabetic Finns. Eur. Heart J. 28(7): 857–864.
Witham, M.D., Nadir, M.A., and Struthers, A.D. 2009. Effect of vitamin D on blood
pressure: a systematic review and meta-analysis. J. Hypertens. 27(10):1948-1954.
Wortsman, J., Matsuoka, L.Y., Chen, T.C., Lu, Z., and Holick, M.F. 2000. Decreased
bioavailability of vitamin D in obesity. Am. J. Clin. Nutr. 72(3): 690–693.
Yin, X., Sun, Q., Zhang, X., Lu, Y., Sun, C., Cui, Y., and Wang, S. 2012. Serum 25(OH)D is
inversely associated with metabolic syndrome risk profile among urban middle-aged
Chinese population. Nutr. J. 11: 68.
Young, J.A., Hwang, S.J., Sarnak, M.J., Hoffmann, U., Massaro, J.M., Levy, D., Benjamin,
E.J., Larson, M.G., Vasan, R.S., O’Donnell, C.J., and Fox, C.S. 2008. Association of
visceral and subcutaneous adiposity with kidney function. Clin. J. Am. Soc. Nephrol.
Page 22 of 29
https://mc06.manuscriptcentral.com/apnm-pubs
Applied Physiology, Nutrition, and Metabolism
Draft
23
3(6): 1786–1791.
Yudkin, J.S., Stehouwer, C.D.A., Emeis, J.J., and Coppack, S.W. 1999. C-Reactive Protein in
healthy subjects: Associations with obesity, insulin resistance, and endothelial
dysfunction:a potential role for cytokines originating from adipose tissue? Arterioscler.
Thromb. Vasc. Biol. 19: 972–978. doi:10.1161/01.ATV.19.4.972.
Page 23 of 29
https://mc06.manuscriptcentral.com/apnm-pubs
Applied Physiology, Nutrition, and Metabolism
Draft
24
Table 1: Demographic, body composition, health and lifestyle measures
Variable Total group
(n=209)a
Women without
Metabolic
Syndrome
(n=119)a
Women with
Metabolic
Syndrome
(n=90)a
pb
Age(years) 59.6 ± 10.6 59.8 ±10.5 59.4 ± 10.9 0.78
Body fat % 40.4 ± 7.41 38.5 ± 8.11 42.9 ± 5.51 <0.0001
Body mass index (kg/m2) 29.5 ± 7.58 27.0 ± 7.64 32.8 ± 6.14 <0.0001
Waist circumference (cm) 89.8 ± 14.4 84.0 ± 14.8 97.3 ± 9.64 <0.0001
Serum 25(OH)D (ng/mL) 30.6 ± 9.52 31.3 ± 9.44 29.7 ± 9.61 0.24 (0.57c)
Serum PTH (pg/mL) 44.3 (34.2, 58.8) 41.9 (32.7, 54.3) 47.9 (35.1, 63.5) 0.09 (0.58c)
HOMA-IR 2.67 (1.43, 4.99) 2.14 (1.00, 4.29) 3.33 (1.91, 7.53) <0.0001
Plasma glucose (mmol/L) 4.74 (4.27, 5.37) 4.48 (4.10, 4.88) 5.35 (4.61, 6.37) <0.0001
Insulin (µU/ml) 12.58 (6.51, 21.58) 11.47 (5.67, 19.78) 14.43 (8.40, 24.18) 0.004
Triglycerides (mmol/L) 0.99 (0.74, 1.41) 0.91(0.70,1.22) 1.18 (0.81, 1.79) <0.0001
HDL-cholesterol (mmol/L) 1.19 (0.98, 1.56) 1.46 (1.14, 1.82) 1.05 (0.86, 1.17) <0.0001
Systolic BP(mmHg) 128.1 ± 22.8 125.0 ± 23.7 132.1 ± 21.1 0.03
Diastolic BP (mmHg) 81.2 ± 12.6 79.0± 13.5 84.0 ± 10.8 0.005
CRP (mg/L) 4.47 (1.99, 8.75) 3.89 (1.17, 8.18) 5.18 (3.24, 9.81) 0.01
eGFR (ml/min/1.73m2) 136.58 ± 38.78 142.1 ± 39.4 129.7 ± 37.2 0.03
AEE (Kcal/day) 884.0 (521.25, 1622.0) 737.0 (522.0,
1314.0)
1073.0 (494.5,
1912.0)
0.09
Light-intensity activity/
day(1.1-2.9 METs) (min)
192.36 ± 39.1 195.6 ± 38.3 187.84 ± 40.2 0.19
Moderate-intensity activity/ day
(3-5.9 METs) (min)
29.14 ± 37.3 26.1 ± 37.9 33.3 ± 36.3 0.20
Vigorous activity /day (>6
METs) (min)
0.65 ± 1.92 0.65 ± 2.2 0.65 ± 1.39 0.99
Physical activity score 2.08 (1.43, 2.64) 2.18 (1.61, 2.73) 1.90 (1.29, 2.60) 0.06
Tobacco users n (%) 100 (47.8) 66 (58.4) 34 (39.5) 0.01
Elevated fasting glucose n (%) 41 (19.6) 5 (4.7) 36 (44.4) <0.0001
Elevated triglycerides n (%) 34 (16.3) 9 (8.0) 25 (27.8) <0.0001
Page 24 of 29
https://mc06.manuscriptcentral.com/apnm-pubs
Applied Physiology, Nutrition, and Metabolism
Draft
25
Reduced HDL-C n (%) 118 (56.5) 37 (32.7) 81 (90.0) <0.0001
Hypertensive n (%) 151 (72.2) 74 (62.2) 77 (85.6) <0.0001
Abdominal obesity: WC ≥ 80cm
n (%)
150 (71.8) 62 (53.0) 88 (97.8) <0.0001
Abdominal obesity: WC ≥ 92cm
n (%)
104 (49.8) 40 (34.2) 64(71.1) <0.0001
Excess adiposity d n (%) 137 (65.6) 66 (55.5) 71 (78.9) <0.0001
Overweight/ obese n (%) 146 (69.9) 65 (55.1) 81 (90.0) <0.0001
Vitamin D deficiency (<20
ng/mL)
32 (15.9) 16 (13.4) 16 (17.8) 0.44
Vitamin D insufficiency (21-29
ng/mL)
49 (24.4) 32 (28.3) 17 (19.3) 0.23
Elevated PTH (>65 pg/mL) 37 (17.7) 17(15.2) 20(22.2) 0.20
Note: 25(OH)D = serum 25 hydroxy vitamin D, PTH= parathyroid hormone, HOMA-IR= Homeostasis model assessment
Insulin resistance, HDL= high density lipoprotein, BP= Blood pressure, CRP = C- reactive protein, eGFR = estimated
glomerular filtration rate, AEE = activity energy expenditure, METs = metabolic equivalents, min = minutes.
a Sample size varies due to missing values.
b Difference between groups with and without the metabolic syndrome . t-test/Mann-Whitney test/chi-square test
c Difference between groups with and without the metabolic syndrome, adjusted for body fat percentage (ANCOVA)
d age specific cut off values for adiposity based on body fat percentage (≤ 35.8 - > 37.7 %).
Data presented as mean ± SD for normally distributed data and median (IQR) for non-normally distributed data
Page 25 of 29
https://mc06.manuscriptcentral.com/apnm-pubs
Applied Physiology, Nutrition, and Metabolism
Draft
26
Table 2: Correlation between 25(OH)D and PTH, respectively and individual MetS
components
25(OH)D PTH
MetS component r p R p
Waist circumference -0.19 0.008 0.18 0.01
Plasma glucose (mmol/L) -0.06 0.37 -0.05 0.49
Triglycerides (mmol/L) -0.009 0.90 0.08 0.26
HDL-cholesterol (mmol/L) 0.06 0.38 -0.02 0.75
Systolic BP(mmHg) 0.11 0.11 0.08 0.23
Diastolic BP (mmHg) 0.20 0.004 -0.03 0.71
Page 26 of 29
https://mc06.manuscriptcentral.com/apnm-pubs
Applied Physiology, Nutrition, and Metabolism
Draft
27
Table 3: Multiple regression analysis for 25(OH)D or PTH on body composition variables
25(OH)D PTH
β p Β p
Waist circumference
Model 1 Unadjusted model
Waist circumference -0.19 0.01 0.19 0.01
Model 2 Model with best fit
Waist circumference -0.18 0.01 0.18 0.01
Age -0.18 0.01 0.24 0.002
Season (0=Spring; 1=Autumn) 0.40 <0.001 -0.11 0.13
eGFR (ml/min/1.73m2) -- -- -0.17 0.03
Body mass index
Model 1 Unadjusted model
Body mass index -0.20 0.004 0.22 0.002
Model 2 Model with best fit
Body mass index -0.18 0.01 0.19 0.01
Age -0.19 0.01 0.24 0.002
Season (0=Spring; 1=Autumn) 0.41 <0.001 0.11 0.12
eGFR (ml/min/1.73m2) -- -- -0.19 0.02
Body fat %
Model 1 Unadjusted model
Body fat % -0.15 0.04 0.27 <0.001
Page 27 of 29
https://mc06.manuscriptcentral.com/apnm-pubs
Applied Physiology, Nutrition, and Metabolism
Draft
28
Model 2 Model with the best fit
Body fat % -0.12 0.09 0.18 0.01
Age -0.16 0.02 0.21 0.01
Season (0=Spring; 1=Autumn) 0.42 <0.001 -0.12 0.09
eGFR (ml/min/1.73m2) -- -- -0.19 0.01
Note: 25(OH)D = serum 25 hydroxy vitamin D, PTH= parathyroid hormone, eGFR = estimated glomerular filtration rate.
Model 1 is unadjusted . Models 2 are adjusted for age, physical activity, tobacco use, season and eGFR
Page 28 of 29
https://mc06.manuscriptcentral.com/apnm-pubs
Applied Physiology, Nutrition, and Metabolism
Draft
29
Table 4: Multiple logistic regression analysis for the association between 25(OH)D or PTH
and other covariates and the metabolic syndrome (modified definition)
Dependent variable MetS (modified definition, excluding
waist circumference)
MetS (modified definition excluding waist circumference)
Odds
ratios
95% CIs p Odds
ratios
95% CIs p
Model 1: Unadjusted model
25(OH)D 1.03 0.98, 1.07 0.24 Log PTH 1.22 0.17, 8.83 0.84
Model 2 25(OH)D (Model with best fit) Log PTH (Model with best fit)
25(OH)D 1.04 0.99, 1.10 0.14 Log PTH 0.45 0.03, 6.12 0.55
Age (years) 1.00 0.95, 1.04 0.88 Age (years) -- -- --
Body fat % 1.04 0.97, 1.12 0.26 Body fat % 1.04 0.97, 1.12 0.23
Physical activity
score
0.51 0.24, 1.11 0.09
Physical activity score
0.56 0.27, 1.14 0.11
Tobacco use (0=no;
1=yes)
0.35 0.13, 0.92 0.03
Tobacco use (0=no;
1=yes)
0.45 0.18, 1.14 0.09
Season (0=Spring;
1=Autumn)
1.36 0.47, 3.92 0.57 Season (0=Spring;
1=Autumn)
1.87 0.73, 4.81 0.19
eGFR
(ml/min/1.73m2)
1.00 0.99, 1.02 0.47
eGFR
(ml/min/1.73m2)
1.00 0.99, 1.02 0.54
Note: 25(OH)D = serum 25 hydroxy vitamin D, PTH= parathyroid hormone, eGFR = estimated glomerular filtration rate.
*MetS =Metabolic syndrome excluding the elevated waist circumference component.
Page 29 of 29
https://mc06.manuscriptcentral.com/apnm-pubs
Applied Physiology, Nutrition, and Metabolism