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Towards a link between magnesium, exercise, and risk of type 2 diabetes mellitus

Huang, Hsien-Haoa,b; Condello, Giancarloc; Chen, Chih-Yend,e,f,g,*

Journal of the Chinese Medical Association: July 2019 - Volume 82 - Issue 7 - p 527–528
doi: 10.1097/JCMA.0000000000000120
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aDepartment of Emergency Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC

bInstitute of Emergency and Critical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan, ROC

cGraduate Institute of Sports Training, Institute of Sports Sciences, University of Taipei, Taipei, Taiwan, ROC

dDivision of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC

eFaculty of Medicine and Institute of Emergency and Critical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan, ROC

fChinese Taipei Society for the Study of Obesity, Taipei, Taiwan, ROC

gKagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan

Received April 30, 2019; accepted April 30, 2019.

Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article.

Address correspondence: Dr. Chih-Yen Chen, Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, 201, Section 2, Shi-Pai Road, Taipei 112, Taiwan, ROC. E-mail address: chency@vghtpe.gov.tw (C.-Y. Chen).

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Exercise represents a potent stressor for both healthy and unhealthy individuals, causing the alteration of body homeostasis. In managing type 2 diabetes mellitus (T2DM), exercise is considered one of the three key counteracting strategies, along with a healthy diet and suitable medications. However, the full understanding of the mechanisms explaining the negative effects of magnesium deficiency remains unclear. Nevertheless, exercise can also manipulate blood magnesium levels, particularly in patients with T2DM,1 as demonstrated by the lower level of serum magnesium in patients with T2DM reporting higher amount of daily physical activity.1

Magnesium is an important intracellular cation that plays an important role in carbohydrate metabolism and insulin release.2 T2DM is often associated with magnesium deficits, especially in patients with poorly controlled glycemic profiles.3 Reduced intracellular Mg2+ is evidenced to decrease the insulin receptor activity and increase the insulin resistance.4 Chronic magnesium deficiency can cause postreceptorial insulin resistance, and consequently reduce glucose utilization in the cells, worsening the reduced insulin sensitivity occurring in patients with T2DM. Hypomagnesemia affects insulin resistance and is a risk factor for T2DM. Increased magnesium intake reduces the fasting glucose, insulin resistance, and progression from prediabetes to diabetes.5 Furthermore, it can be assumed that a relationship exists between magnesium, exercise, and the risk of T2DM, due to the impairment of glucose and insulin metabolism as a consequence of magnesium deficit.

Magnesium homeostasis is maintained by several molecules. Cyclin and CBS domain divalent metal cation transport mediator 2 (CNNM2), transient receptor potential melastatin 6 and 7 (TRPM6 and TRPM7), and solute carrier family 41 members 1 and 2 (SLC41A1 and SLC41A3) were studied in this article.6CNNM2 is as a gene involved in renal Mg2+ handling and regulates renal Mg2+ reabsorption.7 Mutated CNNM2 was observed in dominant hypomagnesemia.7 At present, there are no reported correlations between CNNM2 and diabetes. Both TRPM6 and TRPM7 are members of cation channels and regulate the magnesium homeostasis.8 The role of TRPM6 and TRPM7 in diabetes is still controversial. However, without insulin-induced activation, TRPM6 magnesium channels impaired the glucose tolerance during pregnancy. SLC41A1 and SLC41A2 are upregulated in hypomagnesemia,9 while SLC41A1 is downregulated during exercise.10 Insulin modulates intracellular Mg2+ concentration by regulating SLC41A1 activity.11 Therefore, TRPM6 and SLC41A1 might have the key roles in a three-way link between exercise, magnesium, and insulin metabolism.

Exercise prescription should take into account the two most important parameters (ie, volume and intensity) and the entire duration of the exercise program. Indeed, the acute changes in plasma magnesium strongly rely on exercise intensity and duration.12 Furthermore, different magnitudes of training adaptation could be reached when short, moderate, and long periods of exercise programs are prescribed. Additionally, exercise selection has an important role, as some exercises may involve specific muscle groups (eg, cycling) or the majority of muscle groups (eg, running and swimming). Further research is necessary to clarify this bidirectional link between magnesium manipulation and exercise, especially in patients with T2DM undergoing cycling exercise. Physical activity improves insulin sensitivity and diminishes the elevated blood glucose levels. However, there are still patients with poor response to aerobic exercise, such as patients with diabetics who have chronic hyperglycemia.13 In contrast, metabolic and bariatric surgery shows high efficacy in remitting T2DM even 2 years after intervention.14,15

In the current issue of J Chin Med Assoc, Chiang and his colleagues conducted a prospective study to investigate changes in blood glucose and magnesium levels and the expression of genes encoding magnesium transporters after a 3-month exercise period in 15 adult patients with diabetes (eight males and seven females).6 They found that fasting blood glucose, HbA1c, and waist circumference significantly decreased, and CNNM2, TRPM6, and TRPM7 were significantly downregulated. It is difficult to differentiate whether the changes of magnesium-responsive genes are related to the chronic exercise or to the improvement of hyperglycemia. Another weakness is the change of plasma magnesium in patients with T2DM after exercise. These patients frequently have magnesium deficits,3 and hypomagnesemia is known to increase insulin resistance.4 In this study, patients with T2DM exhibiting normal plasma magnesium levels have significantly decreased plasma magnesium levels after exercise. Therefore, the three-way link between hypomagnesemia, expression of genes encoding magnesium transporters, and status of T2DM still requires further advanced investigation.

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REFERENCES

1. Huang JH, Cheng FC, Tsai LC, Lee NY, Lu YF. Appropriate physical activity and dietary intake achieve optimal metabolic control in older type 2 diabetes patients. J Diabetes Investig 2014;5:418–27.
2. Saris NE, Mervaala E, Karppanen H, Khawaja JA, Lewenstam A. Magnesium. An update on physiological, clinical and analytical aspects. Clin Chim Acta 2000;294:1–26.
3. Ramadass S, Basu S, Srinivasan AR. SERUM magnesium levels as an indicator of status of diabetes mellitus type 2. Diabetes Metab Syndr 2015;9:42–5.
4. Barbagallo M, Dominguez LJ. Magnesium metabolism in type 2 diabetes mellitus, metabolic syndrome and insulin resistance. Arch Biochem Biophys 2007;458:40–7.
5. Hruby A, Meigs JB, O’Donnell CJ, Jacques PF, McKeown NM. Higher magnesium intake reduces risk of impaired glucose and insulin metabolism and progression from prediabetes to diabetes in middle-aged Americans. Diabetes Care 2014;37:419–27.
6. Chiang YF, Chen HY, Lee IT, Chien LS, Huang JH, Kolisek M, et al. Magnesium-responsive genes are downregulated in diabetic patients after a three-month exercise program on a bicycle ergometer. J Chin Med Assoc 2019;82:459–9.
7. Stuiver M, Lainez S, Will C, Terryn S, Günzel D, Debaix H, et al. CNNM2, encoding a basolateral protein required for renal Mg2+ handling, is mutated in dominant hypomagnesemia. Am J Hum Genet 2011;88:333–43.
8. Chubanov V, Waldegger S, Mederos y Schnitzler M, Vitzthum H, Sassen MC, Seyberth HW, et al. Disruption of TRPM6/TRPM7 complex formation by a mutation in the TRPM6 gene causes hypomagnesemia with secondary hypocalcemia. Proc Natl Acad Sci U S A 2004;101:2894–9.
9. Schmitz C, Deason F, Perraud AL. Molecular components of vertebrate Mg2+-homeostasis regulation. Magnes Res 2007;20:6–18.
10. Tseng AP, Wei H, Hsiung N, Chen SH, Chen HY, Cheng FC. SLC41A1, a Na+/Mg2+ exchanger, is downregulated during exercise. Biomed Rep 2014;2:599–601.
11. Mastrototaro L, Tietjen U, Sponder G, Vormann J, Aschenbach JR, Kolisek M. Insulin modulates the Na+/Mg2+ exchanger SLC41A1 and influences Mg2+ efflux from intracellular stores in transgenic HEK293 cells. J Nutr 2015;145:2440–7.
12. Bohl CH, Volpe SL. Magnesium and exercise. Crit Rev Food Sci Nutr 2002;42:533–63.
13. Solomon TP, Malin SK, Karstoft K, Haus JM, Kirwan JP. The influence of hyperglycemia on the therapeutic effect of exercise on glycemic control in patients with type 2 diabetes mellitus. JAMA Intern Med 2013;173:1834–6.
14. Yeh C, Huang HH, Chen SC, Chen TF, Ser KH, Chen CY. Comparison of consumption behavior and appetite sensations among patients with type 2 diabetes mellitus after bariatric surgery. PeerJ 2017;5:e3090.
15. Huang HH, Lee WJ, Chen SC, Chen TF, Lee SD, Chen CY. Bile acid and fibroblast growth factor 19 regulation in obese diabetes, and non-alcoholic fatty liver disease after sleeve gastrectomy. J Clin Med 2019;8:815.
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