ARTICLE
Auteur(s) : Diane Longstreet1,2, Robert
Vink2
1Queensland Aboriginal and Islander Health
Council, Queensland
2School of Medical Sciences, University
of Adelaide, Adelaide, South Australia, SA 5005, Australia
It is becoming increasingly accepted that optimal magnesium
homeostasis is associated with clinical well-being, and numerous
examples exist describing an association between altered magnesium
status and disease states [1-3]. For example, chronic low magnesium
levels have been associated with chronic diseases such as diabetes,
hypertension, cardiovascular disorders, neurological disorders and
osteoporosis whereas acute magnesium deficiency has been associated
with hypocalcaemia and hypokalaemia as well as asthma, stroke,
cardiac arrhythmias and neurological dysfunction [1, 2, 4-6].
While a variety of methods are now available to determine
magnesium status, the most commonly used methods in a clinical
setting are colorimetric methods and ion selective electrodes for
the determination of total or ionic serum concentration,
respectively [1, 7]. Since ionic magnesium is the biologically
active form of magnesium, a number of studies have accordingly
suggested that only the ionic magnesium pool accurately reflects
magnesium status and have recommended the routine use of ionic
magnesium analyzers for magnesium assessments in serum samples
[8-10]. Few studies, however, have examined the interrelationship
between total and ionic serum magnesium concentration in health and
chronic disease, especially across specific ethnic groups at high
risk for chronic disease [11, 12], rendering the choice of
appropriate assessment methodology difficult.
The current study therefore measured serum total and ionic
magnesium concentration, as well as ionic calcium/ionic magnesium
ratios, in a group of 286 participants made up of indigenous and
non-indigenous Australians, with and without type 2 diabetes.
Correlations between total and ionic magnesium were then described
in each of the subgroups divided on the basis of ethnicity and
diabetic status.
Methods
Subjects and setting
Townsville Aboriginal and Islander Health Services (TAIHS) is a
community-controlled Aboriginal Medical Service located in a
suburban area of Townsville, Queensland, Australia that serves a
community of over 16,000 indigenous residents [13]. About 20% of
the TAIHS patient population are non-indigenous, mostly pensioners
from the immediate neighbourhood. Diabetes is the number one reason
for TAIHS general practitioner (GP) consultations (11.3 times per
100 doctor consults) [14]. All Aboriginal and Torres Strait
Islander people recruited for this study were TAIHS patients who
presented for care and subsequently required fasting blood tests as
part of routine care between August 2004 and February 2006.
Additional non-indigenous people were recruited from five GP
practices in the Townsville area. Inclusion criteria included
persons over the age of 15 (Tanner Stage 5). Exclusion criteria
included chronic diarrhoea, alcoholism or binge drinking in the
past two weeks, use of diuretics, consumption of magnesium
supplements, reduced renal function (urinary albumin to creatinine
ratio exceeding > 2.5 mg/mmol in men and > 3.5 mg/mmol in
women), severe mental illness, pregnancy, or breastfeeding.
Ethics approval was obtained from the Townsville Health Service
District Ethics Committee and the TAIHS Board of Directors ethics
sub-committee. Additional community consultation was obtained at
community diabetes events and from small focus groups held at
TAIHS. As part of ethics approval under indigenous community
consultation, this cross-sectional study was restricted to a
convenience sample, integrated as part of on-going medical care,
and included non-indigenous subjects. All subjects gave informed
consent for participation in the study. A brief survey was
administered to all subjects to verify the exclusion criteria.
Medical records were reviewed for all TAIHS patients in the study,
and blood glucose and glycosylated hemoglobin (HbA1c) levels were
requested from the GP records. The diagnostic standard for diabetes
was a random (non-fasting) blood glucose > 11 mmol/L with
confirmed symptoms of diabetes, or fasting plasma glucose ≥ 7.0
mmol/L, or a 2-hour plasma glucose > 11 mmol/L during an oral
glucose tolerance test [15]. In total there were 286 participants,
made up of 152 indigenous and 134 non-indigenous participants. Of
these 139 were confirmed as having diabetes, leaving 147
non-diabetics.
Serum magnesium determinations
Venous blood samples were collected in sterile blood separation
tubes (Becton-Dickinson 5 mL vacutainer), refrigerated immediately,
and analysed for total serum magnesium (Mg-s) in less than 24 hours
using a colorimetric method with chlorphosphonazo III (COBAS
INTEGRA 400®). Serum was then stored at - 80°C
before being analyzed for ionic magnesium (Mg-i) and ionic calcium
(Ca-i) concentration using a NOVA-8 STAT analyzer equipped with ion
selective electrodes.
Statistical analysis
Linear regression analysis was performed using Graph Pad Prism v.
5.01 (www.graphpad.com), with statistical significance being set at
p < 0.05.
Results
The correlation between Mg-i and Mg-s in all participants was
highly significant (figure 1; r = 0.75; p <
0.001). This relationship was independent of ethnicity (figure 2), with a strong
correlation being observed between Mg-i and Mg-s in non-indigenous
participants (figure
2A; r = 0.81; p < 0.001) as well as in indigenous
participants (figure
2B; r = 0.71; p < 0.001). There was no effect of
diabetes on these correlations. The correlation between Mg-i and
Mg-s in non-diabetic participants was highly significant (figure 2C; r = 0.66; p
< 0.001), with a similar strong correlation being observed
between Mg-i and Mg-s in diabetic participants (figure 2D; r = 0.81; p <
0.001).
There was no correlation between Mg-s and Ca-i (r = 0.07), and
similarly none between Mg-i and Ca-i (r = 0.26). There was,
however, a significant negative correlation between Ca-I /Mg-i
ratio and Mg-s (figure
3; r = 0.80; p < 0.001) across all participants. This
significant relationship was independent of ethnicity (r = 0.83 for
non-indigenous and 0.77 for indigenous participants; p <0.001)
or diabetic status (r = 0.71 for non-diabetic and 0.83 for diabetic
participants; p < 0.001).
Discussion
In the current study, we have shown that serum ionic magnesium is
strongly correlated to serum total magnesium concentration, with
the relationship being apparent irrespective of either diabetic
status or ethnicity. Similarly, serum ionic calcium/ionic magnesium
ratio was also correlated to serum total magnesium irrespective of
diabetic status or ethnicity. Notably, there was no correlation
between serum total magnesium and serum ionic calcium suggesting
that the change in ionic calcium/ionic magnesium ratio was
dependent upon changes in total magnesium concentration, which were
reflected in the ionic magnesium pool.
Although a number of reports have suggested that the total serum
magnesium pool does not accurately reflect changes in the ionic Mg
pool [4, 8, 16-18], and vice versa, several studies have now
reported correlations between the two parameters in various disease
states. In particular, the group of Saha et al. [9, 19] have
published several reports showing strong correlations between total
and ionic Mg concentration in serum taken from hemodialysis
patients, patients with intestinal disease, alcoholic liver
disease, and chronic renal disease. In contrast, a poor correlation
was noted in critically ill patients in the study by Johansson and
Whiss (r = 0.59) and the study by Barrera et al. (r = 0.57) [17,
18]. Although the reasons for these differences are unclear, the
chronic or acute nature of the patients’ condition may be an
important factor. In most chronic conditions, a generalized
magnesium deficiency would manifest as both a decline in the total
and ionic magnesium pools, with the interrelationship between the
two maintained. Conditions affecting protein metabolism might
impact the total magnesium fraction independent of the ionic
unbound portion. In acute conditions that more commonly require
critical care, the rapid onset of a condition that alters the
binding status of serum ionic magnesium (e.g., hormonal changes,
stress) may result in a dissociation of total and ionic magnesium.
Thus, the chronic or acute nature of the condition should be
considered when deciding whether to assess total or ionic magnesium
in the assessment of magnesium status.
Diabetes is a chronic condition where a decline in serum total
magnesium has been well described. In the present study, we have
shown a strong correlation between serum total and ionic magnesium
in diabetic participants, as well as in non-diabetic controls. This
strong correlation was also apparent irrespective of the
participants’ ethnicity. Our findings are similar to a previous
report by Mikhail and Ehsanipoor [20] who also report a correlation
between the total and ionic Mg, although their study reported that
serum ionic but not serum total magnesium declined in diabetes.
This is in contrast with the widely reported phenomenon of
decreased serum total Mg in diabetes, which has been reported by a
number of different laboratories [21-23].
In conclusion, our results suggest that serum total magnesium
determination is sufficient for the assessment of magnesium status
in diabetic and non-diabetic patients, and that ethnicity does not
play a significant factor. While serum ionic magnesium
determination may be a better indicator of magnesium status in
acute disease states, the correlation between serum ionic magnesium
and total magnesium in more stable chronic states may not require
such assessment.
Acknowledgments
Supported, in part, by an equipment grant from the Neil Sachse
Foundation.
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