Magnesium Supplementation in Diabetic Nephropathy

The Impact of Magnesium Supplementation on the Clinical Outcome of Patients of Diabetic Nephropathy

Higher prevalence of hypomagnesaemia in diabetic patients with nephropathy was compared to those without nephropathy. Serum magnesium levels were significantly inversely correlated with serum creatinine and U-A/C ratio, and positively correlated with glomerular filtration rate (GFR).

Hence, Magnesium supplementation using magnesium salts could be a good approach to improve the cardiovascular complications, insulin resistance index, lipid profile and kidney function in diabetic nephropathy patients.

Study Overview

• Status: Completed
• Conditions: Diabetic Nephropathies
• Intervention / Treatment: Dietary supplement: Magnesium citrate; Drug: Antidiabetic

Detailed Description

Diabetic nephropathy is a serious kidney-related complication of type 1 diabetes and type 2 diabetes. It is also called diabetic kidney disease. Up to 40 percent of people with diabetes eventually develop kidney disease. Over time, elevated blood sugar associated with uncontrolled diabetes causes high blood pressure which in turn damages the kidneys by increasing kidney filtration pressure. Complications of diabetic nephropathy include heart and blood vessel disease (cardiovascular disease), fluid retention and hyperkalemia. Magnesium (Mg) is the fourth most abundant cation in the body and the second most important intracellular cation. It plays an essential role in biological systems as co-factor for more than 300 essential enzymatic reactions such as signal transduction, energy metabolism, vascular processes and bone metabolism. Normal serum Mg concentrations ranges from 0.7 to 1.1 mmol/L (1.4-2.0 mEq/L or 1.7-2.4 mg/dL). Outcome studies in the general population have indicated potential associations between low serum Mg levels and atherosclerosis, hypertension, diabetes, and left ventricular hypertrophy, as well as both CVD mortality and all-cause mortality. Low SMg levels (1.4-1.9 mg/dL; 0.58-0.78 mM) were independently associated with all-cause death in patients with prevalent CKD. Higher prevalence of hypomagnesaemia in diabetic patients with nephropathy compared to those without nephropathy. Serum magnesium levels were significantly inversely correlated with serum creatinine and U-A/C ratio, and positively correlated with glomerular filtration rate (GFR). Magnesium deficiency promotes hydroxyapatite formation and calcification of vascular smooth muscle cells . It is closely related to insulin resistance and metabolic syndrome. A lower Mg level is directly associated with a faster deterioration of renal function in T2DM patients. Moreover, hypomagnesemia is associated with the long-term micro- and macrovascular complications of T2DM. A dysregulation of mineral metabolism, reflected by altered levels of magnesium and FGF-23, correlates with an increased urinary albumin to creatinine ratio (UACR) in type 2 diabetic patients with CKD stages 2-4. Also, a link between hypomagnesemia and atherogenic dyslipidemia alterations exists; a significantly raised total cholesterol and LDL and non-HDL in patients with CKD are observed, suggesting a link to increased cardiovascular risk in CKD patients. Increasing magnesium levels could attenuate the cardiovascular risk derived from hyperphosphatemia, hence the CKD progression. Current literature suggests that Mg may have a protective effect on the CV system. Mg supplementation improves the insulin resistance index and beta-cell function, and decreases hemoglobin A1c levels in type 2 DM patients. In animal models of vascular calcification VC, dietary supplementation with magnesium results in marked reduction in VC and mortality, improved mineral metabolism, including lowering of PTH, as well as improvement in renal function. Hence, Magnesium supplementation using magnesium salts could be a good approach to improve the cardiovascular complications, insulin resistance index, lipid profile and kidney function in diabetic nephropathy patients.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• Egypt
  • Abbasseia
    • Cairo, Abbasseia, Egypt, 12345
      • Ain Shams University Hospitals

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age ≥ 18 years.
2. Type I or II diabetic patientCKD stage 3 ( eGFR = 30 - 59 ml/min) or stage 4 ( eGFR 15-29 ml/min)
3. Proteinuria 30-300 mg/dl (microalbuminuria)
4. Low SMg levels (1.4-1.9 mg/dL; 0.58-0.78 mM) to normal (1.7-2.4 mg/dL; 0.7 -1.1 mmol/L; 1.4-2.0 mEq/L).
5. Life expectancy >12 months.
6. Women of child-bearing age should be using contraceptives as Hormonal contraceptive or Intra-uterine device.

Exclusion Criteria:

1. Kidney donor recipient.
2. Current treatment with Mg supplements.
3. Any condition impairing intestinal absorption of Mg (e.g: chronic pancreatitis, short bowel syndrome)
4. Active malignancy.
5. Pregnancy or breastfeeding.
6. Cardiac Arrythmias.
7. Allergy towards the Mg supplement.
8. Participation in other interventional trials.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Magnesium arm; 30 patients will receive the standard therapy (anti-diabetic ) + magnesium supplement	Dietary supplement: Magnesium citrate; magnesium citrate equivalent 20-30 mmol elemental magnesium; Drug: Antidiabetic; insulin or oral hypoglycemics
Active Comparator: Control; 30 patients will receive the standard therapy (anti-diabetic)	Drug: Antidiabetic; insulin or oral hypoglycemics

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of Human Serum Osteocalcin level	Evaluation of the extent of cardiovadcular events	Change from baseline Human Serum Osteocalcin level at 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum Insulin	Evaluation of Glycemic Status	Samples will be measured at baseline and after 12 weeks
The homeostasis model assessment-estimated insulin resistance (HOMA-IR)	(HOMA-IR), developed by Matthews et al. will be used to assess insulin resistance. The following formula will be used in its calculation: HOMA IR = (fasting glucose mg/dl × fasting insulin μU/ml)/22.5 × 18. A normal value was considered to be <2.5	Assessed at baseline and after 12 weeks
Hemoglobin A1c level	Evaluation of Glycemic Status	Samples will be measured at baseline and after 12 weeks
Fasting and Post Prandial Blood Sugar level	Evaluation of Glycemic Status	Samples will be measured at baseline and after 12 weeks
Serum creatinine	Evaluation of kidney function	Samples will be measured at baseline and after 12 weeks
Blood Urea Nitrogen Concentration	Evaluation of kidney function	Samples will be measured at baseline and after 12 weeks
eGFR using the MDRD equation	Evaluation of kidney function. GFR (mL/min/1.73 m2) = 175 × (Scr)-1.154 × (Age)-0.203 × (0.742 if female) × (1.212 if African American)	Samples will be measured at baseline and after 12 weeks
Serum Magnesium	Evaluation of SMg level	Samples will be measured at baseline, 6 weeks and 12 weeks
Evaluation of Lipid profile	Serum Low-density Lipoprotein Cholesterol (LDL-C), High-density Lipoprotein Cholesterol (HDL-C), Total Cholesterol, Triglycerides	Samples will be measured at baseline and after 12 weeks
Fatigue Assessment	Fatigue Assessment using Fatigue Severity Scale (FSS). It is a 9-item scale which measures the severity of fatigue and its effect on a person's activities and lifestyle in a variety of disorders. > 4 points indicates no fatigue 4 points or more indicates increasing fatigue	Assessed at baseline and after 12 weeks
Quality of Life (QoL) Assessment: D-39 Questionnaire	Quality of Life (QoL) assessment using D-39 Questionnaire	Assessed at baseline and after 12 weeks

Collaborators and Investigators

• Sponsor: Ain Shams University
• Investigators: Principal Investigator: Nihal Halawa, Faculty of pharmacy - Ain Shams University

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2019
• Primary Completion (Actual): March 1, 2020
• Study Completion (Actual): March 1, 2020

Study Registration Dates

• First Submitted: January 26, 2019
• First Submitted That Met QC Criteria: January 29, 2019
• First Posted (Actual): January 31, 2019

Study Record Updates

• Last Update Posted (Actual): January 12, 2021
• Last Update Submitted That Met QC Criteria: January 11, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: magnesium; diabetic nephropathy; osteocalcin
• Additional Relevant MeSH Terms: Urologic Diseases; Endocrine System Diseases; Diabetes Complications; Diabetes Mellitus; Kidney Diseases; Diabetic Nephropathies; Physiological Effects of Drugs; Gastrointestinal Agents; Cathartics; Hypoglycemic Agents; Magnesium citrate
• Other Study ID Numbers: PHCL932

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No