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Introduction
Magnesium is the second most common of the intracellular cations with 99%
in the intracellular fluid with the 1% around the outside of the cell1,2,3,4,5. It is found
in many unprocessed foods for example leafy green vegetables, or whole grains6,7,8.
Magnesium is essential for regulating cellular processes9 and is also an important
cofactor for many enzymatic reactions in the body, estimated to be around 300
1,2,8,10.
Increased evidence indicates that magnesium deficiency could be correlated
in the development of poor metabolic control7, and potentially chronic
complications in type 2 diabetes patients1. Some research has said that insulin
deficiency or resistance could promote magnesium-wasting resulting in the
reported low levels5,10. It has also been reported that magnesium could be a pivotal
factor for the maintaining of insulin signaling and insulin-mediated glucose
metabolism4. Magnesium is also said to be important for insulin sensitivity1,5,7, 11 ;
yet is one of the more common micronutrient deficiencies in type-2 diabetes
mellitus2,4,8.
The number of people with type 2 diabetes has gradually increased
worldwide and is expected to continue, approximately doubling between the years
of 2000 and 20302, 12. An estimated 245 million people around the world have
diabetes mellitus2. Ethnically, blacks are at a higher risk for developing diabetes
solely due to their lower intake of minerals compared to other ethnicities13,
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however in a study done by Chambers et al14 Hispanics were found at a higher risk
for diabetes than African-Americans. Much can be attributed to the western diet as
it consists largely of processed foods that have little to no Magnesium7. A probable
cause of the lower serum magnesium levels could be blamed in part to the higher fat
and lower fiber intake in obese type-2 diabetics5. Still, some studies suggest that
magnesium can play a protective role against type 2 diabetes12. Another proposal to
low magnesium levels could be low magnesium intake or increased renal loss as a
result of glomular hyperfiltration and reduced reabsorption4. Some research has
shown that low serum magnesium levels also cluster with that of metabolic
syndrome11,14.
Objective
The objective of this research paper is to explore the significance between
low serum magnesium levels and type-2 diabetes and discuss the contradictory
results many studies have gathered.
Methods
Many methods have been used to determine the cause of the deficiency of
magnesium many diabetics suffer. It is noteworthy to state that while many studies
use plasma and serum as means of collecting magnesium levels they are not good
indicators as magnesium is an intracellular ion9. Van Dam13 et al performed a
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prospective cohort study of nearly 59,000 women beginning in 1995. The
population was chosen through a questionnaire sent with a magazine popular
among African-American women. Follow-up questionnaires were sent biennially to
come to a total of only 41,186 after excluding anyone reporting a history of diabetes,
cancer, myocardial infarction, stroke, pregnancy, having not reached the age of 30
during follow-up questionnaires or not completing any of the follow-up
questionnaires. A 68-question Block food frequency questionnaire was used to
assess the diet from the previous year. The study found that a higher intake of
magnesium was associated with a lower risk in type-2 diabetes. It is important to
note that while it has been proved that diet does affect ones risk for developing
type-2 diabetes, research is lacking in the prevalence of African-Americans risk for
diabetes and magnesium intake.
Another study aimed to identify the frame to predict alterations in blood glucose
and how they correlate with magnesium intake9. Sales et al gathered 51 participants
from a hospital using inclusion criteria of type 2 diabetes diagnosis, aged 25-65, not
pregnant or lactating, absence of kidney failure, digestive, thyroid, congenital or
infectious disease, and no recent history of alcohol abuse or use of mineral, vitamin
or medication that could alter magnesium status. The participants were to visit the
hospital three times in a one month time period. At each visit a 24-hour dietary
recall was done by a trained nutritionist; utilizing an album with photographs of
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food and utensils to help participants in choosing the proper amount of food
consumed at their recalled meals. Also measured were the magnesium levels in
urine, plasma and erythrocytes. Cut off points for magnesium concentrations were
3.00-5.00 mmol/d in urine, 0.75-1.05 mmol/L in plasma, and 1.65-2.65 mmol/L in
erythrocytes. The study found that intake of the mineral was inadequate. In regards
to the biochemical tests 77% of the subjects exhibited values below reference levels
for one of more of the markers. The study found that an adequate intake of
magnesium is necessary in order to not exacerbate the effects diabetes has on
magnesium levels but it could also be correlated with other lasting effects diabetes
has on the body14.
Lecube et al5 took on a heavy load examining the difference between type 2
diabetes presence and metabolic control in magnesium levels. Two studies were
performed, the first being a case control study including 200 obese subjects, 50 with
type 2 diabetes and 150 without, and the second study being an interventional study
examining the effect of bariatric surgery on serum magnesium levels 40 of the 120
subjects have type 2 diabetes. For the control case study participants the correlation
between type 2 diabetes and serum magnesium levels was observed. The study
proved, like most, that magnesium levels were far lower in diabetic participants
than those without. In the population as a whole, fasting plasma glucose and HbA1c
were both independently related to serum magnesium levels. The interventional
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study participants underwent RYGBP (Roux-en-Y gastric bypass). The effect of the
surgery on magnesium levels was examined by blood sample at 3 and 6 months post
surgery. The results nothing short of expected, for those who resolved diabetes at 3
months magnesium levels were tremendously increased; and remained unchanged
in those whose diabetes complications were still present. The findings are in no
relation to the weight loss as both groups had significant amounts of weight lost.
The 6-month follow up alike with the previous findings. The study provides
evidence that while magnesium levels are affected by type-2 diabetes the
mechanism by this leaves more research to be done 5.
Another study, Simmons et al 15, took a different approach to examine whether
magnesium levels were low before diabetes was diagnosed or if the deficiency
presented itself after progression in the disease. Participants in the group were
recruited by home visits, where an interviewer filled out a personal questionnaire
about the participant. Proceeding the interview, participants were invited to attend
the study by visiting a clinic, fasting, to have biochemical tests run. Of the 2376
participants invited, 1,453 chose to participate. The biochemical tests proved that
those with a lower magnesium level tended to be older, women, have a higher blood
glucose after fasting, and HbA1c rate. The participants with known diabetes for a
longer period of time in comparison to the new diabetics were more likely to have
hypomagnesmia. Researchers also found that a majority of those diagnosed with
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diabetes were also diagnosed with hypertension. This could play a role in the
findings of low magnesium as patients with hypertension are often prescribed
diuretics. However the study went on to say, like many others, hypomagnesmia is
likely associated with diabetes itself, rather than the development of diabetes 15.
Results
As demonstrated above, it is clear that magnesium levels tend to be lower in
type-2 diabetics 1,2,3,4,5,7,9,10,11,12,13,15. In 1976 Sales et al9 set out to find medical
information on nurses sending 2 year follow-up letters until the year 1986. They
found that those who had an intake high in magnesium tended to be leaner and
more physically active. They also found that magnesium intake positively correlated
with risk for developing type-2 diabetes. There are few studies that demonstrate the
differences between ethnicities as Van Dam et al7 proved that while African
Americans are at a higher risk for developing diabetes, they are at no higher a risk
than any other ethnicity for developing hypomagnesmia. Lecube et al5 suggests that
low magnesium levels could be the result of enhanced renal magnesium excretion.
Yet many studies will suggest that the low intake of magnesium could be to blame
for the low serum levels7,9 . Still some researchers have found that lower magnesium
intake is a probable risk factor for diabetes 1,8. However, as stated in Van Dam et al13
many studies will agree there is great difficulty in attaining accurate results for
magnesium as it is an intracellular ion and only serum magnesium levels are
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measured3,8,9,14. Many studies found that once diabetes was resolved magnesium
status improved5.
Conclusion
While there is still controversy over whether low magnesium is a result of
diabetes or if itself is one cause of diabetes, the majority of research in this paper
points in the direction that magnesium will help with insulin sensitivity and blood
glucose control. It is clear that more research should be done on magnesium intake
as a risk factor for diabetes, and the mechanism by which it is believed for the low
level of magnesium in type two diabetics.
References
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1. Olatunji LA, Soladoye LA. Increased magnesium intake prevents
hyperlipidemia and insulin resistance and reduces peroxidation in fructosefed rats. Pathophysiology. 2007; 14: 11-15
2. Agrawal P, Arora S, Singh B, Manamalli A, Dolia P. Association of
macrovascular complications of type 2 diabetes mellitus with serum
magnesium levels. Diabetes and Metabolic Syndrome: Clinical Research and
Reviews. 2011; 5: 41-44
3. Babagallo M, Dominguez L. Magnesium metabolism in type 2 diabetes
mellitus, metabolic syndrome, and insulin resistance. Archives of
Biochemistry and Biophysics. 2007; 458: 40-47
4. Sharma A, Dabla S, Agrawal RP, Barjatya H, Kochar DK, Kothari RP. Serum
magnesium: an early predictor of course and complications of diabetes
mellitus. Journal of Indian Medical Association. 2007; 105: 16-18
5. Lecube A, Baena-Fustegueras J, Fort J, Pelegri D, Hernadez C, Simo R. Diabetes
is the main factor accounting for Hypomagnesemia in obese subjects. pLoS
ONE. 2012; 7: 1-7
6. Schulze M, Schulz M, Heidemann C, Schienkiewitz A, Hoffman K, Boeing H.
Fiber and magnesium intake and incidence of type 2 diabetes. Archives of
Internal Medicine. 2007; 167: 956-965
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7. Lopez-Ridaura R, Willet W, Rimm E, Liu S, Stampfer M, Manson J, Hu F.
Magnesium intake and risk of type 2 diabetes in men and women. Diabetes
Care. 2004; 27: 134-140
8. Kim D, Xun P, Liu K, Loria C, Yokota K, Jacobs D, He K. Magnesium intake in
relation to systemic inflammation, insulin resistance, and the incidence of
diabetes. Diabetes Care. 2010; 33: 2604
9. Sales C, Pedrosa L, Lima J, LemosT, Colli C. Influence of magnesium status and
magnesium intake on the blood glucose control with type 2 diabetes. Clinical
Nutrition. 2011; 30: 359-364
10. Sharifi F, Mazloomi S, Hajihosseini R, Mazloomzadeh S. Serum magnesium
concentrations in polycystic ovary syndrome and its association with insulin
resistance. Gynecological Endocrinology. 2012; 28: 7-11
11. Kirii K, Hiroyasu I, Date C, Fukui M, Tamakoshi A. Magnesium intake and risk
of self-reported type 2 diabetes among Japanese. Journal of the American
College of Nutrition. 2010; 29: 99-106
12. Longstreet DA, Heath DL, Panaretto KS, Vink R. Correlations suggest low
magnesium may lead to higher rates of type 2 diabetes in Indigenous
Australians. Rural and Remote Health. 2007; 843: 1-13
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13. Van Dam R, Hu F, Rosenburg L, Krishnan S, Palmer J. Dietary calcium and
magnesium, major food sources, and risk of type 2 diabetes in US black
women. Diabetes Care. 2006; 29: 2238
14. Chambers E, Heshka S, Gallagher D, Wang J, Xavier PS, Pierson R. Serum
magnesium and type-2 diabetes in African-Americans and Hispanics: a new
york cohort. Journal of American College of Nutrition. 2006; 25: 509-513
15. Simmons D, Joshi S, Shaw J. Hypomagnesaemia is associated with diabetes;
not pre-diabetes, obesity, or the metabolic syndrome. Diabetes Research and
Clinical Practice. 2010; 87: 261-266