Plasma Concentrations of Magnesium and Risk of Dementia: A General Population Study of 102 648 Individuals

Background Low and high concentrations of plasma magnesium are associated with increased risk of future all-cause dementia; however, the underlying reasons remain elusive. The magnesium ion is an important electrolyte serving as a cofactor in many enzymatic processes in the human organism. Magnesium affects both neuronal and vascular functions. We investigated the associations of plasma concentrations of magnesium associate with common subtypes of dementia as Alzheimer dementia and non-Alzheimer dementia, and potential pathways by which magnesium may affect risk of dementia. Methods Plasma concentrations of magnesium were measured in 102 648 individuals from the Copenhagen General Population Study. Cox regression and natural effects mediation analyses evaluated associations with either Alzheimer dementia or non-Alzheimer dementia. Results Multifactorially adjusted hazard ratios for non-Alzheimer dementia were 1.50(95% confidence interval (CI):1.21–1.87) for the lowest and 1.34(1.07–1.69) for the highest vs the fourth quintile (reference) of plasma magnesium concentrations. Diabetes, cumulated smoking, stroke, and systolic blood pressure mediated 10.4%(3.1–22.8%), 6.8%(1.2–14.0%), 1.3%(0.1–3.6%), and 1.0%(0.2–2.6%), respectively, in the lowest quintile, whereas stroke mediated 3.2%(0.4–11.9%) in the highest quintile. No associations were observed for Alzheimer dementia. Conclusions Low and high plasma magnesium concentrations were associated with high risk of vascular-related non-Alzheimer dementia, with the lowest risk observed at a concentration of 2.07 mg/dL (0.85 mmol/L). No association was observed for Alzheimer dementia. Mediation analysis suggested that diabetes may be in the causal pathway between low plasma magnesium concentrations and high risk of non-Alzheimer dementia, while cumulated smoking, stroke, and systolic blood pressure played minor mediating roles.

Low plasma magnesium concentration and future abdominal aortic calcifications in moderate chronic kidney disease

Background Higher plasma magnesium concentrations are associated with reduced cardiovascular disease risk in chronic kidney disease (CKD) patients. The importance of plasma magnesium concentration for vascular calcification in earlier stages of CKD remains underexplored. This study investigated whether plasma magnesium is a determinant for the presence and severity of vascular calcification in moderate CKD. Methods Retrospective analysis was performed using abdominal aortic calcification (AAC) scores in 280 patients with stage 3 and 4 CKD enrolled in the MASTERPLAN trial. Lateral abdominal X-ray was used to evaluate AAC. Plasma magnesium concentration were measured over time. A zero-inflated Poisson model determined the association between plasma magnesium concentration and AAC. Results 79 out of 280 patients did not have AAC, and in patients with AAC the median calcification score was 3.5 (interquartile range: 0.0–8.6). The mean plasma magnesium concentration was 0.76 ± 0.10 mmol/L at baseline. A 0.1 mmol/L higher plasma magnesium concentration was associated with lower AAC of 0.07 point (95% CI -0.28 – 0.14). A 0.1 mmol/L higher plasma magnesium lowered the odds of detecting any AAC by 30% (OR = 0.63; 95% CI 0.29–1.37). After 1 year and 4 years (at time of X-ray) of follow-up this association was attenuated (OR = 0.93; 95% CI 0.61–1.43 and 0.93; 95% CI 0.60–1.45, respectively). None of these associations reached statistical significance. Conclusions Plasma magnesium concentration at baseline is not associated with the risk for future AAC. Interventions increasing magnesium to avoid vascular calcification may have greatest potential in early CKD stages prior to onset of vascular calcification.

Relationships between vitamin D status and plasma levels of magnesium and parathormone in healthy young adults in Blida region (Algeria)

Introduction. Without magnesium, vitamin D cannot be converted to its biolo- gically active form, a relationship that is often overlooked. Objective. The aim of this study was to estimate the frequency of hypovitaminosis D and that of hypomagnese-mia on the one hand, and to analyze the relationship between vitamin D status, magnesium, and plasma parathormone on the other hand. Population and methods. A retrospective descriptive-analytical,and epidemiological study was conducted on a 112 apparently healthy young adult subjects. For this purpose, bioassays of 25-hydroxy-vitamin D, magnesium and plasma parathormone were performed. Results. The frequency of hypovitaminosis D (serum 25-hydroxyvitamin D  30ng/mL) represented 88.39%. Hypomagnesemia affeted 43.75% of the studied population. A highly significant positive correlation was noted between plasma magnesium levels and vitamin D status of the subjects (R= 0.849; P = 0.000), whereas, a very significant negative correlation was observed between magnesium and plasma parathormone levels (R=-0.92 ; P = 0.000). Conclusion. A high frequency of hypovitamin D, a significant frequency of hypomagne-semia, and a positive correlation between plasma magnesium and vitamin D status are observed. Magnesium level is a determining factor in the variation of serum calcidiol concentrations that should be considered in the assessment of vitamin D status.

SGLT2 inhibition versus sulfonylurea treatment effects on electrolyte and acid–base balance: secondary analysis of a clinical trial reaching glycemic equipoise: Tubular effects of SGLT2 inhibition in Type 2 diabetes

Sodium–glucose transporter (SGLT)2 inhibitors increase plasma magnesium and plasma phosphate and may cause ketoacidosis, but the contribution of improved glycemic control to these observations as well as effects on other electrolytes and acid–base parameters remain unknown. Therefore, our objective was to compare the effects of SGLT2 inhibitors dapagliflozin and sulfonylurea gliclazide on plasma electrolytes, urinary electrolyte excretion, and acid–base balance in people with Type 2 diabetes (T2D). We assessed the effects of dapagliflozin and gliclazide treatment on plasma electrolytes and bicarbonate, 24-hour urinary pH and excretions of electrolytes, ammonium, citrate, and sulfate in 44 metformin-treated people with T2D and preserved kidney function. Compared with gliclazide, dapagliflozin increased plasma chloride by 1.4 mmol/l (95% CI 0.4–2.4), plasma magnesium by 0.03 mmol/l (95% CI 0.01–0.06), and plasma sulfate by 0.02 mmol/l (95% CI 0.01–0.04). Compared with baseline, dapagliflozin also significantly increased plasma phosphate, but the same trend was observed with gliclazide. From baseline to week 12, dapagliflozin increased the urinary excretion of citrate by 0.93 ± 1.72 mmol/day, acetoacetate by 48 μmol/day (IQR 17–138), and β-hydroxybutyrate by 59 μmol/day (IQR 0–336), without disturbing acid–base balance. In conclusion, dapagliflozin increases plasma magnesium, chloride, and sulfate compared with gliclazide, while reaching similar glucose-lowering in people with T2D. Dapagliflozin also increases urinary ketone excretion without changing acid–base balance. Therefore, the increase in urinary citrate excretion by dapagliflozin may reflect an effect on cellular metabolism including the tricarboxylic acid cycle. This potentially contributes to kidney protection.

Association of low Serum Magnesium level with occurrence of Ventricular Arrhythmia in patients with Acute Myocardial Infarction

Background: Acute Myocardial Infarction is the leading cause of morbidity and mortality throughout the world. Its prevalence among developing countries has increased significantly over the past two decades. Acute myocardial infarction is associated with electrolyte imbalance most commonly hypomagnesemia and hypokalaemia. Both are associated with ventricular arrhythmia which can lead to increase hospital mortality and morbidity. Objectives: To find out association of hypomagnesemia with ventricular arrhythmia in patients with acute myocardial infarction. Methods: Patients with acute myocardial infarction admitted in the department of Cardiology, DMCH, within the study period and who fulfilled the inclusion and exclusion criteria were taken as study sample. Informed consent was taken from all patients and then the patients were evaluated by detailed history, clinical examination and relevant investigations. Serum magnesium level was measured after admission. The sample population was Grouped into Group A(Acute myocardial infarction with normal serum magnesium) and Group B(Acute myocardial infarction with hypomagnesemia). Patients were followed up regularly till discharge or death for evidence of ventricular arrhythmia. Then the obtained data was analysed with SPSS 22.0. Results: Among 110 patients of Acute MI, 44 patients were in Group A who had plasma magnesium level e”0.7 mmol/ l and 66 patients were in Group B who had plasma magnesium level <0.7 mmol/l. Incidence of hypoagnesemia was 60% and more common in male. Male vs female percentage of hypomagnesemia were 61% vs 39%. Mean age was 54.16±11.72 yrs vs 57.52±10.59 yrs in group A vs group B. On admission serum magnesium level was 0.9218 vs 0.523 mmol/L( group A vs group B). The study showed that group B patients were more haemodynamically unstable and mean SBP and DBP were found 89.39±19.93 and 60.67±11.56 mm-Hg respectively. Troponin I was markedly increased in group B than A (i.e 4.7±1.79 vs 14.6±4.3 vs ng/ml). Adverse cardiac events such as cardiogenic shock (group A vs group B = 11.36% vs 28.27%) and ventricular arrhythmias(group A vs group B = 34% vs 72.73%) were also higher in group B than group A. Mean hospital stay for group B patient was higher than group A(6.78±0.85 vs 5.31±0.35 days). The study result showed that ventricular arrhythmia is negatively correlated with serum magnesium and the correlation coefficient was - 0.541. It also showed that serum Magnesium is positively correlated with Potassium(r= 0.831, p<0.01) and Calcium(r= 0.902, p<0.001). Multiple logistic regression analysis showed that hypomagnesemia is an independent risk factor for ventricular arrhythmia. Conclusions: This study showed that in patients with acute myocardial infarction, hypomagnesemia is common and it is significantly associated with ventricular arrhythmia. So the presence of hypomagnesemia should alert the physicians to adopt corrective measures as it increases both mortality and morbidity. Bangladesh Heart Journal 2020; 35(1) : 39-46

Hypomagnesemia in Obese Subjects: Evidence of Systematic Review and Meta-analysis

Background:: Magnesium deficiency is a global nutritional problem which seems to influence obesity-associated metabolic disorders because magnesium plays an important role in the prevention and treatment of many diseases. Objective:: We conducted a systematic review and meta-analysis to evaluate the relationship between plasma magnesium concentrations and obesity. Methods:: A systematic review and meta-analysis of case-control studies was conducted. Relevant studies were identified from a literature search using electronic databases. Results:: Ten case-control studies were evaluated in this meta-analysis. Results demonstrated that obese individuals presented lower plasma magnesium concentration than healthy individuals (standardized mean difference [SMD] = -0.44, 95% confidence interval = -0.88 to -0.01). In subgroup analyses, there were differences in plasma magnesium concentration between obese and healthy individuals according to study location, gender, case age, control age, method for assessment of magnesium concentration and study quality. Furthermore, meta-regression analyses showed that the source of heterogeneity of magnesium levels among studies was control age. Conclusion:: Evidence of this systematic review and meta-analysis show hypomagnesemia in obese individuals of both genders.

The Role and the Effect of Magnesium in Mental Disorders: A Systematic Review

Introduction: Magnesium is an essential cation involved in many functions within the central nervous system, including transmission and intracellular signal transduction. Several studies have shown its usefulness in neurological and psychiatric diseases. Furthermore, it seems that magnesium levels are lowered in the course of several mental disorders, especially depression. Objectives: In this study, we wish to evaluate the presence of a relationship between the levels of magnesium and the presence of psychiatric pathology as well as the effectiveness of magnesium as a therapeutic supplementation. Methods: A systematic search of scientific records concerning magnesium in psychiatric disorders published from 2010 up to March 2020 was performed. We collected a total of 32 articles: 18 on Depressive Disorders (DD), four on Anxiety Disorders (AD), four on Attention Deficit Hyperactivity Disorder (ADHD), three on Autism Spectrum Disorder (ASD), one on Obsessive–Compulsive Disorder (OCD), one on Schizophrenia (SCZ) and one on Eating Disorders (ED). Results: Twelve studies highlighted mainly positive results in depressive symptoms. Seven showed a significant correlation between reduced plasma magnesium values and depression measured with psychometric scales. Two papers reported improved depressive symptoms after magnesium intake, two in association with antidepressants, compared to controls. No significant association between magnesium serum levels and panic or Generalized Anxiety Disorder (GAD) patients, in two distinct papers, was found. In two other papers, a reduced Hamilton Anxiety Rating Scale (HAM-A) score in depressed patients correlated with higher levels of magnesium and beneficial levels of magnesium in stressed patients was found. Two papers reported low levels of magnesium in association with ADHD. Only one of three papers showed lower levels of magnesium in ASD. ED and SCZ reported a variation in magnesium levels in some aspects of the disease. Conclusion: The results are not univocal, both in terms of the plasma levels and of therapeutic effects. However, from the available evidence, it emerged that supplementation with magnesium could be beneficial. Therefore, it is necessary to design ad hoc clinical trials to evaluate the efficacy of magnesium alone or together with other drugs (antidepressants) in order to establish the correct use of this cation with potential therapeutic effects.

P1679HYPOMAGNESAEMIA AND HYPERGLYCAEMIA AFTER KIDNEY TRANSPLANTATION

Background and Aims Hypomagnesaemia has been associated with increased insulin resistance and decreased insulin secretion. Recent data suggest that early post-engraftment hypomagnesaemia may play a role in development of post-transplant diabetes mellitus (PTDM). This single-centre study investigated the association between hypomagnesaemia 8 weeks post-engraftment and glucose metabolism changes 1 year after kidney transplantation. Method The study included 425 renal transplantation recipients, transplanted at Oslo University Hospital between March 2015 and May 2018. All included patients had functioning grafts with valid blood sampling and oral glucose tolerance tests 8 weeks and 1 year after transplantation. Patients with known pretransplant diabetes and those developing PTDM the first 8 weeks after transplantation were excluded. The association between plasma magnesium 8 weeks after transplantation and HbA1c, fasting plasma glucose and 2-hr glucose after 1 year was tested using both unadjusted and multiple linear regression, adjusted for: gender, age, body mass index (BMI), systolic blood pressure (SBP), tacrolimus (trough), measured glomerular filtration rate (mGFR; iohexol clearance) and plasma triglycerides. Results Patients had a median age of 54 (range 18-83) years, 65% were men and mean mGFR 1 year after transplantation was 56 (SD±14) ml/min/1.73m2. Median plasma magnesium was 0.72 (0.46-0.94) mmol/L 8 weeks after Tx and patients with hypomagnesaemia (Mg&lt; 0.7 mmol/L) (n=169) were not different compared to patients with normal plasma magnesium (n=256) regarding age, gender, BMI, tacrolimus, mGFR, SBP or plasma triglycerides after 1 year. In unadjusted linear regression 1 mmol/L higher plasma magnesium at 8 weeks was associated with the following glycaemic endpoints 1 year after transplantation (β-coefficient, CI 95%, p-value); fasting glucose: HbA1c: +9 mmol/mol (1;16, P=0.02); +0.5 mmol/L (-0.7;1.7, P=0.39); 2-hour glucose: +0.74 mmol/L (-2.5;3.9, P=0.65). In multiple linear regression the following numbers were: Fasting glucose: HbA1c: +8 mmol/mol (0.3;16, P=0.042); +0.7 mmol/L (-0.5;2.0, P=0.26); 2-hour glucose: +2.8 mmol/L (-0.6;6.2, P=0.11). Conclusion In both unadjusted and multiple linear regression there was a positive correlation between 8-week plasma magnesium and HbA1c 1 year after transplantation. A similar trend was found for fasting and 2-hour glucose, although this was not statistically significant.

Plasma magnesium and the risk of new-onset hyperuricaemia in hypertensive patients

We aimed to evaluate the relationship of plasma Mg with the risk of new-onset hyperuricaemia and examine any possible effect modifiers in hypertensive patients. This is a post hoc analysis of the Uric acid (UA) Sub-study of the China Stroke Primary Prevention Trial (CSPPT). A total of 1685 participants were included in the present study. The main outcome was new-onset hyperuricaemia defined as a UA concentration ≥417 μmol/l in men or ≥357 μmol/l in women. The secondary outcome was a change in UA concentration defined as UA at the exit visit minus that at baseline. During a median follow-up duration of 4·3 years, new-onset hyperuricaemia occurred in 290 (17·2 %) participants. There was a significantly inverse relation of plasma Mg with the risk of new-onset hyperuricaemia (per sd increment; OR 0·85; 95 % CI 0·74, 0·99) and change in UA levels (per sd increment; β −3·96 μmol/l; 95 % CI −7·14, −0·79). Consistently, when plasma Mg was analysed as tertiles, a significantly lower risk of new-onset hyperuricaemia (OR 0·67; 95 % CI 0·48, 0·95) and less increase in UA levels (β −8·35 μmol/l; 95 % CI −16·12, −0·58) were found among participants in tertile 3 (≥885·5 μmol/l) compared with those in tertile 1 (<818·9 μmol/l). Similar trends were found in males and females. Higher plasma Mg levels were associated with a decreased risk of new-onset hyperuricaemia in hypertensive adults.