Hypomagnesemia in Patients with Type 2 Diabetes Mellitus.

BACKGROUND: Recent research has shown that low serum levels of magnesium are often linked to both microvascular and macrovascular complications in individuals with diabetes mellitus. Hence, monitoring of serum magnesium levels is needed in diabetic patients. Furthermore, the addition of magnesium through supplementation may present a novel therapeutic strategy for mitigating vascular complications in individuals with diabetes. OBJECTIVES: To assess the prevalence of hypomagnesemia in type 2 diabetes mellitus patients and to assess the association between hypomagnesemia and microvascular complications of diabetes mellitus in a tertiary care hospital in North Kerala. MATERIALS AND METHODS: An analytical cross-sectional study was conducted at a tertiary care hospital involving 230 diabetic patients receiving outpatient and inpatient care in the Department of Internal Medicine at Government Medical College, Kozhikode, Kerala. The study took place from January 2018 to December 2018, during which serum magnesium levels were assessed and analyzed in relation to the patients' microvascular complications and glycemic control. RESULTS: We observed that 19.13% of the participants had hypomagnesemia. This condition was found to be more common among older individuals with diabetes, as indicated by a p-value of 0.022. However, there were no significant differences in serum magnesium levels based on gender (p-value 0.18), body mass index (BMI) (p-value 0.223), or the duration of diabetes (p-value 0.36). The prevalence of diabetic retinopathy, diabetic neuropathy, and diabetic nephropathy was higher in diabetics with hypomagnesemia than their counterparts with normal magnesium, with a p-value of 0.001, 0.001, and 0.001, respectively. There was a significant negative correlation obtained between serum magnesium and glycated hemoglobin (HbA1C) values (Pearson coefficient = -0.240 and p-value = <0.01) and fasting blood sugar (FBS) values (Pearson coefficient = -0.265 and p-value = <0.01). CONCLUSION: Hypomagnesemia is negatively correlated with HbA1C and FBS but not related to duration of diabetes and gender. The prevalence of microvascular complications was higher among the diabetics with hypomagnesemia.

Horizontal Pendular Nystagmus and Ataxia Secondary to Severe Hypomagnesemia.

Background: Severe hypomagnesemia is an increasingly recognized cause of acute and reversible cerebellar ataxia, often accompanied by cerebellar oculomotor signs such as jerky horizontal or downbeat nystagmus and very rarely ocular flutter. Phenomenology Shown: This video illustrates horizontal pendular nystagmus in a patient with acute onset cerebellar ataxia associated with severe hypomagnesemia. Educational value: Acquired pendular nystagmus can be distinguished from macrosaccadic oscillations and ocular flutter in that the former is composed of two slow phases of equal velocity and the latter of two fast phases of saccadic type with or without intersaccadic interval, respectively. It is most commonly associated with demyelinating, toxic, metabolic, and genetic disorders, but has not been reported in association with severe hypomagnesemia.

The role of magnesium in the pathogenesis of osteoporosis.

Magnesium (Mg), a nutritional element which is essential for bone development and mineralization, has a role in the progression of osteoporosis. Osteoporosis is a multifactorial disease characterized by significant deterioration of bone microstructure and bone loss. Mg deficiency can affect bone structure in an indirect way through the two main regulators of calcium homeostasis (parathyroid hormone and vitamin D). In human osteoblasts (OBs), parathyroid hormone regulates the expression of receptor activator of nuclear factor-κ B ligand (RANKL) and osteoprotegerin (OPG) to affect osteoclast (OC) formation. In addition, Mg may also affect the vitamin D3 -mediated bone remodeling activity. vitamin D3 usually coordinates the activation of the OB and OC. The unbalanced activation OC leads to bone resorption. The RANK/RANKL/OPG axis is considered to be a key factor in the molecular mechanism of osteoporosis. Mg participates in the pathogenesis of osteoporosis by affecting the regulation of parathyroid hormone and vitamin D levels to affect the RANK/RANKL/OPG axis. Different factors affecting the axis and enhancing OC function led to bone loss and bone tissue microstructure damage, which leads to the occurrence of osteoporosis. Clinical research has shown that Mg supplementation can alleviate the symptoms of osteoporosis to some extent.

Does Magnesium Provide a Protective Effect in Crohn's Disease Remission? A Systematic Review of the Literature.

This systematic review evaluates the hypothesis that optimal serum magnesium levels may enhance remission rates in Crohn's disease (CD) and considers whether magnesium supplementation could be beneficial in CD management. This review aims to synthesize available evidence concerning the impact of serum magnesium on disease remission in CD, and to analyze the effectiveness and mechanistic roles of magnesium supplementation. Adhering to the PRISMA guidelines, we searched PubMed, Web of Science, and Scopus up to January 2024 using MeSH terms and free-text queries related to CD and magnesium. The inclusion criteria were studies that investigated serum magnesium levels, effects of supplementation, and the inflammatory mechanisms in CD remission. From the 525 records identified, eight studies met the inclusion criteria after the removal of duplicates and irrelevant records. These studies, conducted between 1998 and 2023, involved a cumulative sample of 453 patients and 292 controls. Key findings include significantly lower serum magnesium levels in CD patients (0.79 ± 0.09 mmol/L) compared to controls (0.82 ± 0.06 mmol/L), with up to 50% prevalence of hypomagnesemia in CD patients observed in one study. Notably, CD patients, particularly men, exhibited lower magnesium intake (men: 276.4 mg/day; women: 198.2 mg/day). Additionally, low magnesium levels correlated with increased sleep latency (95% CI -0.65 to -0.102; p = 0.011) and decreased sleep duration (95% CI -0.613 to -0.041; p = 0.028). Another key finding was the significant association between low serum magnesium levels and elevated CRP levels as an indicator of CD disease activity. The findings support the hypothesis that serum magnesium levels are significantly lower in CD patients compared to healthy controls and suggest that magnesium supplementation could improve CD management by enhancing remission rates and sleep quality. However, more rigorous, evidence-based research is necessary to define specific supplementation protocols and to fully elucidate the role of magnesium in CD pathophysiology.

Association between magnesium depletion score and chronic obstructive pulmonary disease risk: a secondary data analysis from NHANES.

BACKGROUND AND OBJECTIVE: The association between magnesium depletion score (MDS) and the risk of chronic obstructive pulmonary disease (COPD) has not been examined to date. Meanwhile, the potential impact of dietary magnesium intake on this association remains unclear. This study aimed to investigate the influence of dietary magnesium intake on the association between MDS and COPD incidence. METHODS: In this cross-sectional study using the National Health and Nutrition Examination Survey database, we analysed the relationship between MDS and COPD, while also exploring the role of dietary magnesium. RESULTS: A total of 39 852 participants, including 1762 patients with COPD and 38 090 patients with non-COPD, were included in the analysis. After adjusting for confounding factors, our results demonstrated a significant association between higher MDS and increased COPD incidence (OR=1.48, 95% CI: 1.10 to 1.99). Furthermore, it was observed that dietary magnesium intake did not significantly impact this association. CONCLUSION: This study highlights a significant positive correlation between MDS and the incidence of COPD. Nonetheless, no significant alteration in this association was observed with dietary magnesium intake.

The relationship between hypomagnesemia and albuminuria in patients with type 2 diabetes mellitus.

OBJECTIVE: Diabetic nephropathy is a prevalent cause of chronic kidney disease worldwide. Magnesium plays a critical role in insulin resistance, and insulin, in turn, regulates magnesium levels. We aimed to investigate the association between hypomagnesemia and albuminuria in patients with type 2 diabetes mellitus (T2DM). DESIGN, PATIENTS AND MEASUREMENTS: This retrospective single-centre study encompassed 1178 patients aged 18 and above with T2DM, who attended our outpatient clinic between January 2019 and August 2020. Albuminuria levels were categorised according to Kidney Disease Outcomes Quality Initiative guidelines. In the literature, when examining cut-off values for hypomagnesemia, it is observed that studies typically use hospital normal level as a reference point. Hypomagnesemia, defined as magnesium levels below 1.6 mg/dL, was compared to normomagnesemia (magnesium between 1.6 and 2.4 mg/dL). The primary objective was to explore the impact of magnesium levels on albuminuria, while the secondary objective was to determine the prevalence of hypomagnesemia. The multivariate logistic regression analyses were performed according to age, gender (male), HbA1c, and presence of hypomagnesemia. RESULTS: The mean age of the participants was 58.7 ± 12.2 years, with 44% being male. Hypomagnesemia was identified in 5.3% of the patients. Advanced age and female gender were more common among patients with hypomagnesemia (p = .001). Magnesium levels exhibited a negative correlation with HbA1c and fasting blood glucose, and a positive correlation with creatinine levels (r = -.117, r = -.131, r = .117, p < .001 for all three variables). Hypomagnesemia was significantly more prevalent in patients with albuminuria (15.9% vs. 4.7%, p < .001). Moreover, participants with the presence of hypomagnesemia were independently associated with a higher risk of albuminuria (odds ratio 3,64 1.76-7.52, p = .001). CONCLUSION: Albuminuria is more frequently observed in patients with hypomagnesemia.

Association of serum magnesium levels with renal prognosis in patients with chronic kidney disease.

BACKGROUND: Magnesium deficiency is associated with various health conditions, but its impact on the progression of chronic kidney disease (CKD) remains unclear. This study aimed to investigate the association between serum magnesium levels and prognosis of renal function in CKD patients. METHODS: This is an analysis of the Japan Chronic Kidney Disease Database Ex　(J-CKD-DB-Ex), which is a multicenter prospective cohort including CKD patients enrolled from January 1, 2014 to December 31, 2020. We included adult outpatients with CKD stage G3 and G4 at the time of initial magnesium measurement. Patients were classified by magnesium levels as low (<1.7 mg/dl), normal (1.7-2.6 mg/dl), or high (>2.6 mg/dl). The primary outcomes were the composite of an eGFR < 15 ml/min/1.73 m2 or a ≥30% reduction in eGFR from the initial measurement, which was defined as CKD progression. We applied the Kaplan-Meier analysis and Cox regression hazard model to examine the association between magnesium levels and CKD progression. RESULTS: The analysis included 9868 outpatients during the follow-up period. The low magnesium group was significantly more likely to reach CKD progression. Cox regression, adjusting for covariates and using the normal magnesium group as the reference, showed that the hazard ratio for the low magnesium group was 1.20 (1.08-1.34). High magnesium was not significantly associated with poor renal outcomes compared with normal magnesium. CONCLUSION: Based on large real-world data, this study demonstrated that low magnesium levels are associated with poorer renal outcomes.

A Rare Case of Neonatal Hypomagnesemia with Secondary Hypocalcemia Caused by a Novel Homozygous TRPM6 Gene Variant.

BACKGROUND Familial hypomagnesemia with secondary hypocalcemia (HSH) is a rare autosomal recessive disorder (OMIM# 602014) caused by mutations in the gene encoding transient receptor potential melastatin 6 (TRPM6)) on chromosome 9q22, a channel involved in epithelial magnesium resorption. While a plethora of studies have delineated various clinical manifestations pertinent to this mutation, the literature is devoid of connections between TRPM6 mutations and bleeding diathesis, or sudden infant death syndrome (SIDS). This report presents a case of familial HSH associated with the novel homozygous TRPM6 gene variant c.5281C>G p. (Arg1761Gly) chr9: 77354845. CASE REPORT This report details a 26-day-old neonate, born full term with optimal Apgar scores, who experienced an abrupt emergence of apnea, cyanosis, bilateral nasal bleeding, and diminished alertness. Despite the neonate's initially unremarkable clinical birth indicators, a meticulous assessment unveiled a pronounced family history of SIDS, including a sibling previously diagnosed with hypomagnesemia. Laboratory examination of the infant demonstrated severe hypomagnesemia and hypocalcemia, conditions which were promptly ameliorated following intravenous administration of magnesium and calcium. Whole-exome sequencing identified a homozygous TRPM6 gene mutation c.5281C>G p. (Arg1761Gly) at chr9: 77354845. This gene is crucial for magnesium regulation. The mutation involves a cytosine-to-guanine shift, resulting in an arginine to glycine amino acid substitution at position 1761 of the TRPM6 protein. CONCLUSIONS This report has highlighted that infantile hypomagnesemia may be associated with symptoms and signs that can mimic infection, or it can present with seizures. Although familial HSH is a rare genetic disorder that can be identified by genetic testing, correction of hypomagnesemia is the most important and immediate clinical management strategy.

Rare cause of recurrent hypocalcaemia and functional hypoparathyroidism due to hypomagnesaemia caused by TRPM6 gene mutation.

Magnesium is essential for the functioning and release of parathyroid hormone. Therefore, its deficiency can present as functional hypoparathyroidism. This case report describes a rare inherited disorder called congenital hypomagnesaemia with secondary hypocalcaemia due to TRPM6 gene mutation. This disease clinically and biochemically mimics hypoparathyroidism. However, unlike hypoparathyroidism, it can be treated only by long-term oral magnesium supplements. The patient presented to us with recurrent hypocalcaemic convulsions. The laboratory picture in each admission was similar to that of hypoparathyroidism. However, the hypocalcaemia persisted, and it was noticed to be associated with persistent hypomagnesaemia. A defect in the tubular magnesium reabsorption was postulated and a genetic analysis of the patient was done, which revealed a TRPM6 mutation causing hypomagnesaemia by excessive renal excretion of magnesium. The child responded well to oral magnesium supplements and is currently developmentally appropriate for her age and thriving well.

Association of Magnesium Depletion Score with Congestive Heart Failure: Results from the NHANES 2007-2016.

The magnesium depletion score (MDS) is considered a new valuable and reliable predictor of body magnesium status. This study aimed to explore the association between MDS and congestive heart failure (CHF) among US adults. A total of 19,227 eligible participants from the 2007-2016 National Health and Nutrition Examination Survey were enrolled in this study and then divided into three groups according to the level of MDS (none to low: MDS=0-1, middle: MDS=2, high: MDS=3-5). Sample-weighted logistic regression models were applied to calculate odds ratios (ORs) and 95% confidence intervals (CIs) exploring the independent relationship between MDS and CHF. The estimated prevalence of CHF increased with the increasing level of MDS (none to low: 0.86%, middle: 4.06%, high: 13.52%; P < 0.001). Compared to those in the none-to-low group, participants in the middle and high groups were at significantly higher risk of CHF after adjusting for various covariates (model 3: OR=1.55, 95%CI: 1.05-2.30, P < 0.001; OR=3.20, 95%CI: 2.07-4.96, P < 0.001; respectively). Subgroup analyses indicated that adequate dietary magnesium intake could reduce the risk of CHF in participants who did not meet the recommended dietary allowance (RDA) for magnesium. Besides, there was an interaction between coronary artery disease and MDS on CHF (P for interaction < 0.001). These findings indicated that MDS, a novel indicator estimating magnesium deficiency, is associated with the risk of CHF in non-institutionalized US civilians. Participants whose dietary magnesium intake reaches the RDA might be at lower risk.

Global prevalence of hypomagnesemia in type 2 diabetes mellitus - a comprehensive systematic review and meta-analysis of observational studies.

PURPOSE: Hypomagnesemia, characterized by low magnesium levels, has been implicated in the pathophysiology of Type 2 Diabetes Mellitus (T2DM). This meta-analysis aims to provide a comprehensive assessment of hypomagnesemia prevalence in individuals with T2DM as well as its potential implications for diabetes management and complications. METHODS: We conducted a comprehensive systematic review and meta-analysis using databases like PubMed, Google Scholar, Science Direct, and Research Gate to identify relevant studies between January 2008 and August 2023. We focused on observational studies related to serum magnesium levels and Type 2 Diabetes in individuals aged 19 and older. Newcastle Ottawa tool was used for quality assessment. A random effect meta-analysis was performed to calculate the prevalence of hypomagnesemia in T2DM. RESULTS: We identified a total of 671 studies, and after screening 383 abstracts and full texts by two independent reviewers, we identified 19 eligible studies encompassing 4192 patients diagnosed with T2DM. The mean age was 55.4 (SD, 4.39) years with a mean HbA1C level of 8.01. The pooled prevalence of hypomagnesemia in T2DM was 32% (95% CI: 22-36%) out of 4192 cases. On subgroup analysis, the prevalence of hypomagnesemia in male and female were 19.8% and 20.1%, respectively. Geographically, Asia had the highest prevalence of hypomagnesemia with 31.9% (95% CI: 24-41.1%). CONCLUSION: This meta-analysis highlights a significant prevalence of hypomagnesemia in individuals with T2DM, emphasizing the need for further investigation due to the intricate nature of the association between serum magnesium levels and T2DM.

[Severe hypomagnesemia in a man with alcohol dependence: a forgotten electrolyte in a neglected population]. / Ernstig magnesiumtekort bij alcoholverslaving.

BACKGROUND: Symptoms of acute alcohol withdrawal like tremors, seizures and delirium are commonly treated with benzodiazepines and vitamins. When complaints are not reacting to this treatment, an alternative diagnosis must be considered. Although hypomagnesemia is present in at least 30 percent of the patients with alcohol dependence, it can provoke and maintain these complaints. CASE DESCRIPTION: We present a 43-year-old man with alcohol dependence, who shows neurological, muscular, and cardiac consequences of an undiagnosed hypomagnesemia. CONCLUSION: In daily clinical practice there is not enough attention for magnesium deficits, especially in patients with alcohol dependence. Serious complications can be prevented by recognizing and treating magnesium deficiency more adequately.

Role of magnesium-L-Threonate in alleviating skin/muscle incision and retraction induced mechanical allodynia and anxiodepressive-like behaviors in male rats.

Chronic postsurgical pain (CPSP) and its emotional comorbidities poses health burden to patients who have received the surgical treatment. However, its underlying mechanism remains unclear. Emerging studies indicate that magnesium deficiency is associated with neurological diseases, and magnesium supplement confers protection under these disease conditions. In this study, we examined the role and mechanism of magnesium deficiency in the pathology of surgery-induced allodynia and negative emotion using a rat model of skin/muscle incision and retraction (SMIR) and investigated the therapeutic effects of magnesium supplementation by oral magnesium-L-Threonate (L-TAMS) in SMIR-injured rats. In the SMIR model, rats developed mechanical allodynia and anxiodepressive-like behaviors. Further, SMIR caused microglia and astrocyte activation and enhanced expression of pro-inflammatory cytokine (TNF-α, IL-1ß and IL-6) in the anterior cingulate cortex (ACC). Importantly, magnesium ion (Mg2+) levels decreased in the serum and cerebrospinal fluid (CSF) of SMIR-injured rats, which exhibited high correlation with pain and emotion behavioral phenotypes in these rats. Repeated oral administration of L-TAMS increased serum and CSF levels of Mg2+ in SMIR-injured rats. Notably, L-TAMS administration reversed SMIR-induced mechanical allodynia and anxiodepressive-like behaviors but did not affect pain and emotional behaviors in sham rats. Moreover, L-TAMS administration suppressed SMIR-caused glial activation and proinflammatory cytokine expression in the ACC but had no such effect in sham rats. Together, our study demonstrates the contributing role of magnesium deficiency in the pathology of surgery-induced chronic pain and negative emotion. Moreover, we suggest that L-TAMS might be a novel approach to treat CPSP and its emotional comorbidities.

Magnesium Deficiency and Cardiometabolic Disease.

Magnesium (Mg2+) has many physiological functions within the body. These include important roles in maintaining cardiovascular functioning, where it contributes to the regulation of cardiac excitation-contraction coupling, endothelial functioning and haemostasis. The haemostatic roles of Mg2+ impact upon both the protein and cellular arms of coagulation. In this review, we examine how Mg2+ homeostasis is maintained within the body and highlight the various molecular roles attributed to Mg2+ in the cardiovascular system. In addition, we describe how nutritional and/or disease-associated magnesium deficiency, seen in some metabolic conditions, has the potential to influence cardiac and vascular outcomes. Finally, we also examine the potential for magnesium supplements to be employed in the prevention and treatment of cardiovascular disorders and in the management of cardiometabolic health.

The kidney reabsorption-related magnesium depletion score is associated with increased likelihood of abdominal aortic calcification among US adults.

BACKGROUND: Kidney reabsorption plays a vital role in magnesium homeostasis. This study aimed to determine the relationship between the kidney reabsorption-related magnesium depletion score (MDS) and abdominal aortic calcification (AAC). METHODS: We obtained data for 2640 individuals from the National Health and Nutrition Examination Survey database and analysed the relationship between the MDS and AAC score. The MDS is a scoring system developed to predict the status of magnesium deficiency that fully considers the pathophysiological factors influencing the kidneys' reabsorption capability. AAC was quantified by the Kauppila score system based on dual-energy X-ray absorptiometry. We performed stratified analysis and multiple equation regression analysis. R and EmpowerStats were used for data analysis. RESULTS: A total of 2640 participants were included with the mean AAC score of 1.47 ± 0.07. Participants with higher MDSs tended to have higher AAC scores [MDS 0: 0.75 (0.56-0.93), MDS 1: 1.02 (0.84-1.21), MDS 2: 2.34 (1.80-2.87), MDS 3: 3.19 (2.46-3.92), MDS ≥4: 4.99 (3.49-6.49)]. Compared with those with an MDS of 0, the highest subgroup (MDS ≥4) was associated with a higher AAC score {ß = 4.24 [95% confidence interval (CI) 2.78-5.70], P < .001} and the association was not altered [ß = 1.81 (95% CI 0.54-3.09), P = .002] after adjusting for numerous covariates. Subgroup analyses showed that stronger associations between the MDS and AAC score were detected in adults with lower levels of magnesium intake and older age (all P for interaction <.05). CONCLUSIONS: The MDS is a promising tool for identifying individuals with magnesium deficiency status who may benefit from dietary magnesium supplementation to reduce the risks of AAC.

Higher magnesium levels are associated with better glycaemic control and diabetes remission post-bariatric surgery.

BACKGROUND: Low Magnesium (Mg) dietary intake has been associated with increased risk of type 2 diabetes mellitus (T2DM). Furthermore, in patients with T2DM, hypomagnesemia is associated with worst glycaemic control. Bariatric surgery (BS) remains the most effective treatment in severe obesity and also provides resolution/improvement of T2DM. Our aim is to evaluate the association between Mg supplementation post-BS and Mg serum levels with diabetes status after BS. METHODS: We performed an observational study on patients with obesity and T2DM who underwent BS. Data was assessed pre-BS and one-year post-BS. RESULTS: We included a total of 403 patients with T2DM. At baseline, 43.4% of the patients had Mg deficiency. Pre-BS, patients with Mg deficiency had poorer glycaemic control - HbA1c 7.2 ± 1.6% vs 6.4 ± 1.0% (p < 0.001), fasting plasma glucose 146.2 ± 58.8 mg/dL vs 117.5 ± 36.6 mg/dL (p < 0.001) and were under a greater number of anti-diabetic drugs 1.0 (IQR 0-2.0) vs 1.0 (IQR 0-1.0) (p = 0.002). These findings persisted at one-year post-BS. At the first-year post-BS, 58.4% of the patients had total remission of T2DM and 4.1% had partial remission. Patients without Mg deficiency at one-year post-BS had higher rates of total and partial remission. Higher serum Mg levels at baseline is an independent predictor of total T2DM remission (p < 0.0001). The optimal cut-off of baseline Mg to predict total T2DM remission was 1.50 mg/dL with a sensitivity of 73% and a specificity of 58% (area under ROC = 0.65). Patients that were under Mg supplementation post-BS had serum Mg values, glycaemic control and total remission of T2DM similar to patients non-supplemented. CONCLUSION: In patients with T2DM submitted to BS, higher Mg serum levels at baseline and 1-year after BS were associated with better glycaemic control and higher rates of total T2DM remission at the first year post-BS.

Increased Wnt/ß-catenin signaling contributes to autophagy inhibition resulting from a dietary magnesium deficiency in injury-induced osteoarthritis.

BACKGROUND: Dietary magnesium deficiency, which is common in modern diet, has been associated with osteoarthritis (OA) susceptibility. Despite this clinical association, no study has addressed if dietary magnesium deficiency accelerates OA development, especially at molecular level. This study aimed to explore aggravating effects of dietary magnesium deficiency on cartilage damage in an injury-induced murine OA model and to determine the underlying mechanism. METHODS: Twelve-week-old C57BL/6J mice subject to injury-induced OA modeling were randomized into different diet groups in which the mice were fed a diet with daily recommended magnesium content (500 mg/kg) or diets with low magnesium content (100 or 300 mg/kg). Articular cartilage damage was evaluated using the OARSI score. To determine molecular mechanisms in vitro, mouse chondrocytes were treated with media of low magnesium conditions at 0.1 and 0.4 mM, compared with normal magnesium condition at 0.7 mM as control. Anabolic and catabolic factors, autophagy markers, ß-catenin, Wnt ligands, and a magnesium channel transient receptor potential cation channel subfamily member 7 (TRPM7) were analyzed by quantitative real-time PCR and immunoblotting. Autolysosomes were detected by DALGreen staining via fluorescence microscopy and autophagosomes were evaluated by transmission electron microscopy. Autophagy markers, ß-catenin, and TRPM7 were assessed in vivo in the mouse cartilage, comparing between dietary magnesium deficiency and normal diet, by immunohistochemistry. RESULTS: Dietary magnesium deficiency aggravated injury-induced cartilage damage, indicated by significant higher OARSI scores. Autophagy markers LC3-II and Beclin-1 were decreased both in low magnesium diet-fed mice and low magnesium-treated chondrocytes. The number of autolysosomes and autophagosomes was also reduced under low magnesium conditions. Moreover, magnesium deficiency induced decreased anabolic and increased catabolic effect of chondrocytes which could be restored by autophagy activator rapamycin. In addition, reduced autophagy under low magnesium conditions is mediated by activated Wnt/ß-catenin signaling. The expression of TRPM7 also decreased in low magnesium diet-fed mice, indicating that downstream changes could be regulated through this channel. CONCLUSIONS: Dietary magnesium deficiency contributes to OA development, which is mediated by reduced autophagy through Wnt/ß-catenin signaling activation. These findings indicated potential benefits of adequate dietary magnesium for OA patients or those individuals at high risk of OA.

The Role of Magnesium in the Pathogenesis of Metabolic Disorders.

Magnesium (Mg) is an essential nutrient for maintaining vital physiological functions. It is involved in many fundamental processes, and Mg deficiency is often correlated with negative health outcomes. On the one hand, most western civilizations consume less than the recommended daily allowance of Mg. On the other hand, a growing body of evidence has indicated that chronic hypomagnesemia may be implicated in the pathogenesis of various metabolic disorders such as overweight and obesity, insulin resistance (IR) and type 2 diabetes mellitus (T2DM), hypertension (HTN), changes in lipid metabolism, and low-grade inflammation. High Mg intake with diet and/or supplementation seems to prevent chronic metabolic complications. The protective action of Mg may include limiting the adipose tissue accumulation, improving glucose and insulin metabolism, enhancing endothelium-dependent vasodilation, normalizing lipid profile, and attenuating inflammatory processes. Thus, it currently seems that Mg plays an important role in developing metabolic disorders associated with obesity, although more randomized controlled trials (RCTs) evaluating Mg supplementation strategies are needed. This work represents a review and synthesis of recent data on the role of Mg in the pathogenesis of metabolic disorders.