Introduction

 Hyperglycemia is a frequent complication during cardiac surgery with cardiopulmonary bypass (CPB). The causes of hyperglycemia may be related to many factors; first: the reduced levels of blood insulin as a result of nonpulsatile flow during CPB and hypoperfusion of some vital organs such as the pancreas, thereby reducing the production and release of insulin by pancreas;^[1] second: the adsorption of insulin to the CPB circuit;^[2] and third: the insulin resistance.^[3] Magnesium is one of the cofactors that regulate blood glucose control by improving the insulin response and action as a result of the increased affinity of insulin to its receptors.^[4‑6] Hypomagnesemia is associated with insulin resistance and hyperglycemia.^[5‑8] Perioperative factors that lead to hypomagnesemia such as the renal loss of magnesium (diuretics and digitalis), preoperative proton‑pump inhibitors hemodilution, blood loss, blood transfusions, administration of large doses of calcium, the catecholamines that cause chelation of magnesium, intracellular shifts induced by the extracorporeal circulation, and the hypothermia during surgery.^{[9‑11]} The aim of the present study was done to evaluate the perioperative effect of magnesium infusion on blood sugar level in patients with diabetes mellitus undergoing cardiac surgery.

AIMS AND OBJECTIVES

AIM- The aim of study is to study the Effect of Perioperative Magnesium Sulfate on Blood Sugar in Patients with Diabetes Mellitus Undergoing Cardiac Surgery On Cardio Pulmonary Bypass

OBJECTIVE

The primary objective is to measure the efficacy of magnesium infusion in reducing the blood glucose levels.

 The secondary objective is to the requirement for insulin infusion in addition to the safety of the study medication, which is assessed by the occurrence of any adverse events.

MATERIAL AND METHODS

Study setting : 

This study will be conducted under the Department of Cardiac Anaesthesia , LPS institute of Cardiology, GSVM medical college, Kanpur

Study duration : One year  

Study design: Randomized control double blind study

After obtaining institutional ethical committee’s approval and  explaining the protocol to all patients, a written, valid and informed consent will be taken from all patients. This trial complies with the CONSORT 2010 statement guidelines for conducting a randomised controlled trial.

Sample size: a double‑blinded randomized study will include 100 diabetic patients undergoing cardiac surgery using CPB. The patients will be randomly allocated into two equal groups (n = 50 each). The concealment of allocation will be done using random numbers generated through Excel.

Inclusion Criteria :

·      Adult patients with diabetes mellitus

·      Ejection fraction >40%).

Exclusion criteria:

·      congestive heart failure

·      acute myocardial infarction

·      emergency cardiac surgery

·      redo cases

·      cardiomyopathies

·      heart rate < 50 bpm

·      pericardial disease

·      renal / hepatic impairment.

Preoperative evaluation

After admission in the ward, patient’s weight and height will be noted. Routine investigations like blood grouping, complete Haemogram, Fasting and Post Prandial Blood sugar, liver function tests, renal function tests, Serum Electrolytes (Na⁺, K⁺, Ca⁺⁺ ), Viral markers, Chest X-ray, Electrocardiograph, 2D transthoracic echocardiography, and coronary angiography will be done as indicated. A Coagulation Profile consisting of platelet count, bleeding time, clotting time, prothrombin time, activated partial thromboplastin time and international normalised ratio will be done in all patients.

DATA COLLECTION

The following will be noted preoperatively for each patient:

·      Age (years)

·      Weight(kgs)

·      Gender

·      Diabetics on -OHA/INSULIN/OHA PLUS INSULIN

·      Hypertension

·      Ischemic Heart Disease/ Valvular Heart Disease/ Ischemic Heart Disease plus Valvular Heart Disease

·      Atrial Fibrillation

·      Ejection Fraction (%)

·      On diuretics/ ACE inhibitors / Beta blockers / Calcium Channel Blockers / Aspirin / Statins

·      History of Stroke / Carotid Stenosis

·      History of Smoking- Current Smokers/ Ex smokers

·      NYHA Class II/III/IV

·      ASA Class III:IV

·      Euroscore II (%)

·      Hematocrit (%)

·      HbA1c(%)

·      Body Surface Area (m²)

Study procedure: 

Patients will be randomly allocated to one of the following two groups using computer generated random numbers. 

The study medications will be prepared in 50 ml syringe and the infusion will be started by the staff nurse according to the study protocol .The anesthetist will be blinded to the contents of the syringe and the name of the medication infused by the syringe pump.

• Group M – (Magnesium sulfate group).

 The patients will receive a continuous infusion of magnesium sulfate (without a loading dose) at 15 mg/kg/h. The infusion will be started 20 min before induction maintained during surgery and the first postoperative 24 h. The medication will be prepared by adding 5 g magnesium sulfate in 50 ml syringe

ʉۢ Group CР(Control group). The patients will receive equal amount of normal saline.

Anesthetic technique

After taking the patient in operation theatre, monitors will be attached. The patient will be monitored for Heart rate, SpO2, ECG. After that Intravenous line will be taken (16G/18G) and intravenous fluid will be started . Patient put on O₂ Hudson Mask at flow rate 6L/min and given  pre medication with i.v. midazolam (0.1mg/kg) and fentanyl (1 µg/kg ) . For all patients under local anesthesia , a radial arterial cannula , central venous line and femoral arterial cannula will be inserted before operation to enable continuous hemodynamic monitoring. Induction will be done by intravenous fentanyl (3–5 µg/kg), etomidate (0.3 mg/kg), and rocuronium (0.8 mg/kg). The anesthesia will be maintained with oxygen/air (50%), sevoflurane (1%–3%)/propofol (50-150 µg/kg/min), and vecuronium (1–2 µg/kg/min). CPB will be established with cannulation of the ascending aorta and right atrium/Superior Vena Cava Inferior Vena Cava. At the end of surgical intervention, the patients will be prepared for weaning from CPB. If there will difficulty to wean from CPB, pharmacological support (dobutamine, epinephrine/ norepinephrine, nitroglycerine ,milronone ) or mechanical support intra‑aortic balloon pump (IABP) will be started.

During anesthesia, the elevated blood sugar (>10 mmol/L) will be controlled by insulin infusion (insulin infusion was started 2 units/h and the dose was modified every 30 min), and if the blood sugar levels decreases below 10 mmol/L, the insulin infusion will be discontinued. At the end of surgery, the patients will be transferred to cardiac surgery Intensive Care Unit (ICU) with full monitoring.

Monitoring of patients

Hemodynamic monitoring will include the heart rate, mean arterial blood pressure, a continuous electrocardiograph with automatic ST‑segment analysis (leads II and V), central venous pressure, urine output, temperature, arterial blood gas , activated clotting time , blood levels of magnesium, sugar, and potassium.

Requirement of insulin (total units and units/hr) will also be calculated.

Furthermore, the required pharmacological and mechanical support will be collected.

The values will be serially collected at the following timepoints:

T0: Baseline reading (before starting the administration of study medication);

T1: Reading before CPB;

T2: Reading after CPB;

T3: Reading 6th h after ICU admission;

T4: reading 12th h after ICU admission;

T5: Reading 24th h after ICU admission.

Intraoperative data

·      Cardiopulmonary Bypass Time (minute)

·      Cross Clamping Time (minute)

·      Dobutamine/Noradrenaline/Adrenaline(ug/kg/min) requirement

·      Nitroglycerine(ug/kg/min) requirement

·      Intra aortic ballon pump requirement

·      Pacing requirement

·      Transfusion of P-RBC( NO OF PATIENTS / NO OF UNITS)

·      Blood Loss

     Intraoperative(ml)/Postoperative(ml/24hrs)

·      Intraoperative Fluids / Post operative Fluids in 24hrs

            Crystalloids (ml)

          Ringer

          Saline

       Colloids

·      Intraoperative urine output(ml)

Data of outcome of patients

·       Major Adverse Cardiac Event/Arrythmia

        -Atrial Fibrillation

        -Ventricular extrasystole

        -Any other

·      Organ Dysfunction

        -Neurological complications

        -Pulmonary complications

        -Multiple Organ Dysfunction Syndrome

·      ICU length of stay (days)

·      Hospital length of stay (days)

·      Mortality

Statistical analysis

 Data will be statistically described in terms of mean ± standard deviation, or frequencies (number of cases) and percentages when appropriate. Comparison of numerical variables between the study groups will be done using the Student t‑test for independent samples. Repeated measure ANOVA will be used to see the effect of magnesium on the blood sugar levels at different follow‑up intervals. For comparing categorical data, Chi‑square test will be performed. Exact test will be used instead when the expected frequency is < 0.05 is considered statistically significant. All statistical calculations will be done using computer program SPSS (Statistical Package for the Social Science; SPSS Inc., Chicago, IL, USA) version 15 for Microsoft Windows.

Review of Literature

Rosolová et al.(2000)^[12] reported that variations in the plasma Mg concentration have a relatively modest but significant effect on insulin-mediated glucose disposal in healthy subjects, with lower plasma Mg concentrations associated with increased insulin resistance.

Dong JY et al.(2011)^[8} examined the association between magnesium intake and risk of type 2 diabetes by conducting a meta-analysis of prospective cohort studies Meta-analysis of 13 prospective cohort studies involving 536,318 participants and 24,516 cases detected a significant inverse association between magnesium intake and risk of type 2 diabetes (relative risk [RR] 0.78 [95% CI 0.73-0.84]).

Veronese N et al.(2016)^[13] reported that Mg supplementation appears to have a beneficial role and improves glucose parameters in people with diabetes and also improves insulin-sensitivity parameters in those at high risk of diabetes.

Song Y et al (2006)^[14] reported that Oral magnesium supplementation for 4-16 weeks may be effective in reducing plasma fasting glucose levels and raising HDL cholesterol in patients with Type 2 diabetes. 

Simental‑Mendía LE et al (2016)^[15] reported that magnesium may be a beneficial supplement in glucose metabolic disorders. A systematic review and meta-analysis was conducted to evaluate the effect of oral magnesium supplementation on insulin sensitivity and glucose control in both diabetic and non-diabetic individuals. Magnesium supplementation for ≥4 months significantly improves the HOMA-IR index and fasting glucose, in both diabetic and non-diabetic subjects

Hruby A et al (2017)^[16] reported that higher magnesium intake is associated with lower risk of type 2 diabetes, especially in the context of lower carbohydrate-quality diets.

Hruby A et al (2014)^[17] concluded that Magnesium intake may be particularly beneficial in offsetting risk of developing diabetes among those at high risk

Jin-Woo Park et al (2022)^[18] reported that magnesium sulfate infusion was associated with an improved postoperative blood glucose profile in patients with diabetes. They retrospectively reviewed the medical records of patients with type 2 diabetes who had undergone total joint arthroplasty at a tertiary hospital, where intraoperative magnesium sulfate injections were frequently performed for postoperative analgesia.

Mohammad Vahid Touliat et al (2023)^[19] in rats reported that MgSO4 could reduce blood glucose levels and insulin resistance, and it could improve kidney function. .

 REFRENCES

1.   Herreros J, Berjano EJ, Sola J, Vlaanderen W, Sales‑Nebot L, Más P, et al. Injury in organs after cardiopulmonary bypass: A comparative experimental morphological study between a centrifugal and a new pulsatile pump. Artif Organs 2004;28:738‑42.

2.   Najmaii S, Redford D, Larson DF. Hyperglycemia as an effect of cardiopulmonary bypass: Intra‑operative glucose management. J Extra Corpor Technol 2006;38:168‑73.

3.   Nadler JL, Rude RK. Disorders of magnesium metabolism. Endocrinol Metab Clin North Am 1995;24:623‑41

4.   Paolisso G, Sgambato S, Gambardella A, Pizza G, Tesauro P, Varricchio M, et al. Daily magnesium supplements improve glucose handling in elderly subjects. Am J Clin Nutr 1992;55:1161‑7.

5.   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

6.   Larsson SC, Wolk A. Magnesium intake and risk of type 2 diabetes: A meta‑analysis. J Intern Med 2007;262:208‑14.

7.   Kim DJ, Xun P, Liu K, Loria C, Yokota K, Jacobs DR Jr., et al. Magnesium intake in relation to systemic inflammation, insulin resistance, and the incidence of diabetes. Diabetes Care 2010;33:2604‑10.

8.   Dong JY, Xun P, He K, Qin LQ. Magnesium intake and risk of type 2 diabetes: Meta‑analysis of prospective cohort studies. Diabetes Care 2011;34:2116‑22

9.   Classen HG, Gröber U, Kisters K. Drug‑induced magnesium deficiency. Med Monatsschr Pharm 2012;35:274‑80

10.                 Inoue S, Akazawa S, Nakaigawa Y, Shimizu R, Seo N. Changes in plasma total and ionized magnesium concentrations and factors affecting magnesium concentrations during cardiac surgery. J Anesth 2004;18:216‑9.

11.                 Manrique AM, Arroyo M, Lin Y, El Khoudary SR, Colvin E, Lichtenstein S, et al. Magnesium supplementation during cardiopulmonary bypass to prevent junctional ectopic tachycardia after pediatric cardiac surgery: A randomized controlled study. J Thorac Cardiovasc Surg 2010;139:162‑900

12.                 Rosolová H, Mayer O Jr., Reaven GM. Insulin‑mediated glucose disposal is decreased in normal subjects with relatively low plasma magnesium concentrations. Metabolism 2000;49:418‑20.

13.                 Veronese N, Watutantrige‑Fernando S, Luchini C, Solmi M, Sartore G, Sergi G, et al. Effect of magnesium supplementation on glucose metabolism in people with or at risk of diabetes: A systematic review and meta‑analysis of double‑blind randomized controlled trials. Eur J Clin Nutr 2016;70:1354‑9.

14.                 Song Y, He K, Levitan EB, Manson JE, Liu S. Effects of oral magnesium supplementation on glycaemic control in type 2 diabetes: A meta‑analysis of randomized double‑blind controlled trials. Diabet Med 2006;23:1050‑6.

15.                 Simental‑Mendía LE, Sahebkar A, Rodríguez‑Morán M, Guerrero‑Romero F. A systematic review and meta‑analysis of randomized controlled trials on the effects of magnesium supplementation on insulin sensitivity and glucose control. Pharmacol Res 2016;111:272‑82.

16.                 Hruby A, Guasch‑Ferré M, Bhupathiraju SN, Manson JE, Willett WC, McKeown NM, et al. Magnesium intake, quality of carbohydrates, and risk of type 2 diabetes: Results from three U.S. Cohorts. Diabetes Care 2017;40:1695‑702.

17.                 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

18.                  Park, J.-W.; Kim, E.-K.; Lee, J.; Chung, S.H.; Boo, G.; Do, S.-H. Effect of Intraoperative Magnesium Sulfate Administration on Blood Glucose Control following Total Joint Arthroplasty in Patients with Diabetes. J. Clin. Med. 2022, 11, 3040. https://doi.org/10.3390/ jcm11113040

19.                 Touliat MV, Rezazadeh H, Beyki M, Maghareh-Dehkordi S, Sharifi M, Talebi A, Soltani N. Impact of magnesium sulfate therapy in improvement of renal functions in high fat diet-induced diabetic rats and their offspring. Sci Rep. 2023 Feb 8;13(1):2273. doi: 10.1038/s41598-023-29540-w. PMID: 36755074; PMCID: PMC9908981.Introduction

 Hyperglycemia is a frequent complication during cardiac surgery with cardiopulmonary bypass (CPB). The causes of hyperglycemia may be related to many factors; first: the reduced levels of blood insulin as a result of nonpulsatile flow during CPB and hypoperfusion of some vital organs such as the pancreas, thereby reducing the production and release of insulin by pancreas;^[1] second: the adsorption of insulin to the CPB circuit;^[2] and third: the insulin resistance.^[3] Magnesium is one of the cofactors that regulate blood glucose control by improving the insulin response and action as a result of the increased affinity of insulin to its receptors.^[4‑6] Hypomagnesemia is associated with insulin resistance and hyperglycemia.^[5‑8] Perioperative factors that lead to hypomagnesemia such as the renal loss of magnesium (diuretics and digitalis), preoperative proton‑pump inhibitors hemodilution, blood loss, blood transfusions, administration of large doses of calcium, the catecholamines that cause chelation of magnesium, intracellular shifts induced by the extracorporeal circulation, and the hypothermia during surgery.^{[9‑11]} The aim of the present study was done to evaluate the perioperative effect of magnesium infusion on blood sugar level in patients with diabetes mellitus undergoing cardiac surgery.

AIMS AND OBJECTIVES

AIM- The aim of study is to study the Effect of Perioperative Magnesium Sulfate on Blood Sugar in Patients with Diabetes Mellitus Undergoing Cardiac Surgery On Cardio Pulmonary Bypass

OBJECTIVE

The primary objective is to measure the efficacy of magnesium infusion in reducing the blood glucose levels.

 The secondary objective is to the requirement for insulin infusion in addition to the safety of the study medication, which is assessed by the occurrence of any adverse events.

MATERIAL AND METHODS

Study setting : 

This study will be conducted under the Department of Cardiac Anaesthesia , LPS institute of Cardiology, GSVM medical college, Kanpur

Study duration : One year  

Study design: Randomized control double blind study

After obtaining institutional ethical committee’s approval and  explaining the protocol to all patients, a written, valid and informed consent will be taken from all patients. This trial complies with the CONSORT 2010 statement guidelines for conducting a randomised controlled trial.

Sample size: a double‑blinded randomized study will include 100 diabetic patients undergoing cardiac surgery using CPB. The patients will be randomly allocated into two equal groups (n = 50 each). The concealment of allocation will be done using random numbers generated through Excel.

Inclusion Criteria :

·      Adult patients with diabetes mellitus

·      Ejection fraction >40%).

Exclusion criteria:

·      congestive heart failure

·      acute myocardial infarction

·      emergency cardiac surgery

·      redo cases

·      cardiomyopathies

·      heart rate < 50 bpm

·      pericardial disease

·      renal / hepatic impairment.

Preoperative evaluation

After admission in the ward, patient’s weight and height will be noted. Routine investigations like blood grouping, complete Haemogram, Fasting and Post Prandial Blood sugar, liver function tests, renal function tests, Serum Electrolytes (Na⁺, K⁺, Ca⁺⁺ ), Viral markers, Chest X-ray, Electrocardiograph, 2D transthoracic echocardiography, and coronary angiography will be done as indicated. A Coagulation Profile consisting of platelet count, bleeding time, clotting time, prothrombin time, activated partial thromboplastin time and international normalised ratio will be done in all patients.

DATA COLLECTION

The following will be noted preoperatively for each patient:

·      Age (years)

·      Weight(kgs)

·      Gender

·      Diabetics on -OHA/INSULIN/OHA PLUS INSULIN

·      Hypertension

·      Ischemic Heart Disease/ Valvular Heart Disease/ Ischemic Heart Disease plus Valvular Heart Disease

·      Atrial Fibrillation

·      Ejection Fraction (%)

·      On diuretics/ ACE inhibitors / Beta blockers / Calcium Channel Blockers / Aspirin / Statins

·      History of Stroke / Carotid Stenosis

·      History of Smoking- Current Smokers/ Ex smokers

·      NYHA Class II/III/IV

·      ASA Class III:IV

·      Euroscore II (%)

·      Hematocrit (%)

·      HbA1c(%)

·      Body Surface Area (m²)

Study procedure: 

Patients will be randomly allocated to one of the following two groups using computer generated random numbers. 

The study medications will be prepared in 50 ml syringe and the infusion will be started by the staff nurse according to the study protocol .The anesthetist will be blinded to the contents of the syringe and the name of the medication infused by the syringe pump.

• Group M – (Magnesium sulfate group).

 The patients will receive a continuous infusion of magnesium sulfate (without a loading dose) at 15 mg/kg/h. The infusion will be started 20 min before induction maintained during surgery and the first postoperative 24 h. The medication will be prepared by adding 5 g magnesium sulfate in 50 ml syringe

ʉۢ Group CР(Control group). The patients will receive equal amount of normal saline.

Anesthetic technique

After taking the patient in operation theatre, monitors will be attached. The patient will be monitored for Heart rate, SpO2, ECG. After that Intravenous line will be taken (16G/18G) and intravenous fluid will be started . Patient put on O₂ Hudson Mask at flow rate 6L/min and given  pre medication with i.v. midazolam (0.1mg/kg) and fentanyl (1 µg/kg ) . For all patients under local anesthesia , a radial arterial cannula , central venous line and femoral arterial cannula will be inserted before operation to enable continuous hemodynamic monitoring. Induction will be done by intravenous fentanyl (3–5 µg/kg), etomidate (0.3 mg/kg), and rocuronium (0.8 mg/kg). The anesthesia will be maintained with oxygen/air (50%), sevoflurane (1%–3%)/propofol (50-150 µg/kg/min), and vecuronium (1–2 µg/kg/min). CPB will be established with cannulation of the ascending aorta and right atrium/Superior Vena Cava Inferior Vena Cava. At the end of surgical intervention, the patients will be prepared for weaning from CPB. If there will difficulty to wean from CPB, pharmacological support (dobutamine, epinephrine/ norepinephrine, nitroglycerine ,milronone ) or mechanical support intra‑aortic balloon pump (IABP) will be started.

During anesthesia, the elevated blood sugar (>10 mmol/L) will be controlled by insulin infusion (insulin infusion was started 2 units/h and the dose was modified every 30 min), and if the blood sugar levels decreases below 10 mmol/L, the insulin infusion will be discontinued. At the end of surgery, the patients will be transferred to cardiac surgery Intensive Care Unit (ICU) with full monitoring.

Monitoring of patients

Hemodynamic monitoring will include the heart rate, mean arterial blood pressure, a continuous electrocardiograph with automatic ST‑segment analysis (leads II and V), central venous pressure, urine output, temperature, arterial blood gas , activated clotting time , blood levels of magnesium, sugar, and potassium.

Requirement of insulin (total units and units/hr) will also be calculated.

Furthermore, the required pharmacological and mechanical support will be collected.

The values will be serially collected at the following timepoints:

T0: Baseline reading (before starting the administration of study medication);

T1: Reading before CPB;

T2: Reading after CPB;

T3: Reading 6th h after ICU admission;

T4: reading 12th h after ICU admission;

T5: Reading 24th h after ICU admission.

Intraoperative data

·      Cardiopulmonary Bypass Time (minute)

·      Cross Clamping Time (minute)

·      Dobutamine/Noradrenaline/Adrenaline(ug/kg/min) requirement

·      Nitroglycerine(ug/kg/min) requirement

·      Intra aortic ballon pump requirement

·      Pacing requirement

·      Transfusion of P-RBC( NO OF PATIENTS / NO OF UNITS)

·      Blood Loss

     Intraoperative(ml)/Postoperative(ml/24hrs)

·      Intraoperative Fluids / Post operative Fluids in 24hrs

            Crystalloids (ml)

          Ringer

          Saline

       Colloids

·      Intraoperative urine output(ml)

Data of outcome of patients

·       Major Adverse Cardiac Event/Arrythmia

        -Atrial Fibrillation

        -Ventricular extrasystole

        -Any other

·      Organ Dysfunction

        -Neurological complications

        -Pulmonary complications

        -Multiple Organ Dysfunction Syndrome

·      ICU length of stay (days)

·      Hospital length of stay (days)

·      Mortality

Statistical analysis

 Data will be statistically described in terms of mean ± standard deviation, or frequencies (number of cases) and percentages when appropriate. Comparison of numerical variables between the study groups will be done using the Student t‑test for independent samples. Repeated measure ANOVA will be used to see the effect of magnesium on the blood sugar levels at different follow‑up intervals. For comparing categorical data, Chi‑square test will be performed. Exact test will be used instead when the expected frequency is < 0.05 is considered statistically significant. All statistical calculations will be done using computer program SPSS (Statistical Package for the Social Science; SPSS Inc., Chicago, IL, USA) version 15 for Microsoft Windows.

Review of Literature

Rosolová et al.(2000)^[12] reported that variations in the plasma Mg concentration have a relatively modest but significant effect on insulin-mediated glucose disposal in healthy subjects, with lower plasma Mg concentrations associated with increased insulin resistance.

Dong JY et al.(2011)^[8} examined the association between magnesium intake and risk of type 2 diabetes by conducting a meta-analysis of prospective cohort studies Meta-analysis of 13 prospective cohort studies involving 536,318 participants and 24,516 cases detected a significant inverse association between magnesium intake and risk of type 2 diabetes (relative risk [RR] 0.78 [95% CI 0.73-0.84]).

Veronese N et al.(2016)^[13] reported that Mg supplementation appears to have a beneficial role and improves glucose parameters in people with diabetes and also improves insulin-sensitivity parameters in those at high risk of diabetes.

Song Y et al (2006)^[14] reported that Oral magnesium supplementation for 4-16 weeks may be effective in reducing plasma fasting glucose levels and raising HDL cholesterol in patients with Type 2 diabetes. 

Simental‑Mendía LE et al (2016)^[15] reported that magnesium may be a beneficial supplement in glucose metabolic disorders. A systematic review and meta-analysis was conducted to evaluate the effect of oral magnesium supplementation on insulin sensitivity and glucose control in both diabetic and non-diabetic individuals. Magnesium supplementation for ≥4 months significantly improves the HOMA-IR index and fasting glucose, in both diabetic and non-diabetic subjects

Hruby A et al (2017)^[16] reported that higher magnesium intake is associated with lower risk of type 2 diabetes, especially in the context of lower carbohydrate-quality diets.

Hruby A et al (2014)^[17] concluded that Magnesium intake may be particularly beneficial in offsetting risk of developing diabetes among those at high risk

Jin-Woo Park et al (2022)^[18] reported that magnesium sulfate infusion was associated with an improved postoperative blood glucose profile in patients with diabetes. They retrospectively reviewed the medical records of patients with type 2 diabetes who had undergone total joint arthroplasty at a tertiary hospital, where intraoperative magnesium sulfate injections were frequently performed for postoperative analgesia.

Mohammad Vahid Touliat et al (2023)^[19] in rats reported that MgSO4 could reduce blood glucose levels and insulin resistance, and it could improve kidney function. .

 REFRENCES

1.   Herreros J, Berjano EJ, Sola J, Vlaanderen W, Sales‑Nebot L, Más P, et al. Injury in organs after cardiopulmonary bypass: A comparative experimental morphological study between a centrifugal and a new pulsatile pump. Artif Organs 2004;28:738‑42.

2.   Najmaii S, Redford D, Larson DF. Hyperglycemia as an effect of cardiopulmonary bypass: Intra‑operative glucose management. J Extra Corpor Technol 2006;38:168‑73.

3.   Nadler JL, Rude RK. Disorders of magnesium metabolism. Endocrinol Metab Clin North Am 1995;24:623‑41

4.   Paolisso G, Sgambato S, Gambardella A, Pizza G, Tesauro P, Varricchio M, et al. Daily magnesium supplements improve glucose handling in elderly subjects. Am J Clin Nutr 1992;55:1161‑7.

5.   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

6.   Larsson SC, Wolk A. Magnesium intake and risk of type 2 diabetes: A meta‑analysis. J Intern Med 2007;262:208‑14.

7.   Kim DJ, Xun P, Liu K, Loria C, Yokota K, Jacobs DR Jr., et al. Magnesium intake in relation to systemic inflammation, insulin resistance, and the incidence of diabetes. Diabetes Care 2010;33:2604‑10.

8.   Dong JY, Xun P, He K, Qin LQ. Magnesium intake and risk of type 2 diabetes: Meta‑analysis of prospective cohort studies. Diabetes Care 2011;34:2116‑22

9.   Classen HG, Gröber U, Kisters K. Drug‑induced magnesium deficiency. Med Monatsschr Pharm 2012;35:274‑80

10.                 Inoue S, Akazawa S, Nakaigawa Y, Shimizu R, Seo N. Changes in plasma total and ionized magnesium concentrations and factors affecting magnesium concentrations during cardiac surgery. J Anesth 2004;18:216‑9.

11.                 Manrique AM, Arroyo M, Lin Y, El Khoudary SR, Colvin E, Lichtenstein S, et al. Magnesium supplementation during cardiopulmonary bypass to prevent junctional ectopic tachycardia after pediatric cardiac surgery: A randomized controlled study. J Thorac Cardiovasc Surg 2010;139:162‑900

12.                 Rosolová H, Mayer O Jr., Reaven GM. Insulin‑mediated glucose disposal is decreased in normal subjects with relatively low plasma magnesium concentrations. Metabolism 2000;49:418‑20.

13.                 Veronese N, Watutantrige‑Fernando S, Luchini C, Solmi M, Sartore G, Sergi G, et al. Effect of magnesium supplementation on glucose metabolism in people with or at risk of diabetes: A systematic review and meta‑analysis of double‑blind randomized controlled trials. Eur J Clin Nutr 2016;70:1354‑9.

14.                 Song Y, He K, Levitan EB, Manson JE, Liu S. Effects of oral magnesium supplementation on glycaemic control in type 2 diabetes: A meta‑analysis of randomized double‑blind controlled trials. Diabet Med 2006;23:1050‑6.

15.                 Simental‑Mendía LE, Sahebkar A, Rodríguez‑Morán M, Guerrero‑Romero F. A systematic review and meta‑analysis of randomized controlled trials on the effects of magnesium supplementation on insulin sensitivity and glucose control. Pharmacol Res 2016;111:272‑82.

16.                 Hruby A, Guasch‑Ferré M, Bhupathiraju SN, Manson JE, Willett WC, McKeown NM, et al. Magnesium intake, quality of carbohydrates, and risk of type 2 diabetes: Results from three U.S. Cohorts. Diabetes Care 2017;40:1695‑702.

17.                 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

18.                  Park, J.-W.; Kim, E.-K.; Lee, J.; Chung, S.H.; Boo, G.; Do, S.-H. Effect of Intraoperative Magnesium Sulfate Administration on Blood Glucose Control following Total Joint Arthroplasty in Patients with Diabetes. J. Clin. Med. 2022, 11, 3040. https://doi.org/10.3390/ jcm11113040

19.                 Touliat MV, Rezazadeh H, Beyki M, Maghareh-Dehkordi S, Sharifi M, Talebi A, Soltani N. Impact of magnesium sulfate therapy in improvement of renal functions in high fat diet-induced diabetic rats and their offspring. Sci Rep. 2023 Feb 8;13(1):2273. doi: 10.1038/s41598-023-29540-w. PMID: 36755074; PMCID: PMC9908981.