Surraiya Shaikh  ( Department of Biochemistry, BMSI, JPMC, Karachi. )
Khemomal Asudo Karira  ( Sindh Medical Colleg0e, BMSI, JPMC, Karachi. )

Objective: To assess the serum magnesium level in heart failure patients with diabetes mellitus.
Methods: A case-control study was conducted at Basic Medical Sciences Institute (BMSI), Jinnah Postgraduate Medical Centre (JPMC), Karachi, in collaboration with National Institute of Cardiovascular Diseases (NICVD), Karachi, from April 2003 to December 2003. The study included 45 diagnosed cases of heart failure with diabetes mellitus, between the age group 35-65 years. Serum magnesium and glucose levels were estimated and compared by using the student "t" test and p value (<0.01, <0.05, <0.001) were used to analyze the statistical significance.
Results: Out of 45 cases of heart failure, 15 were diabetic. Of these, eleven (73.3%) had low serum magnesium (<1.8 mg/dl), one (6.7%) was within normal range (1.8-2.0 mg/dl) and three (20%) were in the high level range(>2.0 mg/dl).
Conclusion: The study showed low serum magnesium level in heart failure patients with diabetes mellitus.
Keywords: Serum Magnesium, Diabetes Mellitus, Heart failure (JPMA 61:901; 2011).

Diabetes mellitus is the most frequent chronic disease associated with secondary magnesium deficit. Hypomagnesaemia is the central feature of the deficit, which is often reported in experimental and clinical forms of the disease. Some studies indicate that increased urinary loss of magnesium caused by osmotic diuresis might contribute to diabetic hypomagnesaemia.¹
Magnesium deficiency could be important in diabetes for several reasons. Many of the enzymes involved in glycolysis are magnesium dependent. Increased insulin resistance has been found in patients with reduced free magnesium levels, and animal studies have shown increased glucagon stimulation decreased insulin secretion and reduced insulin uptake with magnesium deficiency.²
Abnormal dietary deficiency of magnesium as well as abnormalities in magnesium metabolism play important roles in different types of heart diseases such as ischaemic heart disease, congestive heart failure, sudden cardiac death, atherosclerosis, a number of cardiac arrhythmias and ventricular complications in diabetes mellitus.³
Individuals with diabetes mellitus are at 2 to 3 fold increased risk for cardiovascular disease (CVD) relative to those without diabetes.⁴
Inspite of the abundance of magnesium on the earth and in living tissue, it is very easy to develop a magnesium deficiency. This is caused by a relatively poor magnesium absorption and rapid turnover (the half-life is below 40 hours) of the magnesium pools relevant to the survival dependent biochemical pathways.⁵
This case control study was carried out to assess the serum magnesium level in heart failure patients with diabetes mellitus.

This case-controlled study was conducted at BMSI, JPMC, Karachi with collaboration of NICVD, Karachi from April 2003 to December 2003.
The study comprised of 45 diagnosed cases of heart failure with and without diabetes mellitus between the ages of 35-65 years. The inclusion factors were, subjects with major risk factors of heart failure; hypertension, diabetes, smokers and family history of heart diseases. Patients receiving drugs as diuretics and digoxin along with other cardiovascular medication were also included. Patients were excluded if they had renal failure, thyroid disorders, liver disease and history of alcohol consumption.
Diabetes mellitus was defined as a fasting glucose level > 126 mg/dl, a non-fasting glucose level > 200 mg/dl, use of hypoglycaemic agents or a history of physician diagnosed Diabetes mellitus.⁶ The normal serum magnesium level was considered as 1.8 to 3.0 mg/dl (=0.75 to 1.25 mmol/L = 1.5 to 2.5 mEq/L).⁷
Blood samples were collected under antiseptic measures. Serum glucose was determined by enzymatic colorimetric (GOD PAP) method, using kit, Lot No. B02868 B supplied by Pioneer Diagnostics.
Serum magnesium was determined by colorimetric method using kit Cat No.0137 supplied by STANBIO Laboratory.
Data feeding and analysis was carried out by using Computer package SPSS ver. 11.0. The results were calculated as number and percentages for qualitative data whereas mean and Standard deviation was used for quantitative data. For comparison between diabetic and non-diabetic, test of proportion was used for qualitative data and student t-test for quantitative data. In all statistical analysis, p <0.05, <0.01, and <0.001 were considered significant.

Table-1 shows the demographic distribution of diabetic and non-diabetic heart failure patients. Patients with diabetes were seen to be of a significantly older age.
It was also observed that female patients with diabetes were significantly (P<0.01) higher in percentage.


Table-2 shows biochemical comparison of variables of diabetic and non-diabetic patients. It was seen that patients with diabetes had a significantly higher serum glucose level. (187±84.2mg/dl). The serum magnesium in diabetics was lower than the non-diabetics..


Table-3 compares the mean values of serum magnesium, with the risk factors of heart failure. Patients were classified on the basis of their serum magnesium level, as low magnesium group (<1.8 mg/dl), high magnesium group (>2.0 mg/dl) and normal magnesium group (1.8 - 2.0 mg/dl). Out of 45 patients, 15 were diabetic. Eleven (73.3%) showed significant (P<0.05) low serum magnesium when compared with non-diabetic and other risk factors of heart failure.

Magnesium, the second most abundant intracellular cation plays a key role in cellular metabolism.⁸ The level of glycaemic control is found to be inversely proportional to magnesium deficiency. Both Type 1 and Type 2 diabetics have increased urinary losses and reduced serum and intracellular levels of magnesium.² In humans, sugar loading causes magnesiuresis, possibly converting a marginal intake to a deficient one. Previous studies showed that magnesium metabolism is altered in patients with diabetes mellitus. In type II diabetic patients, hypomagnesaemia can be a consequence or a cause of increased insulin resistance. It has been established that chronic magnesium supplements in diabetic patients improve both islets beta cell response and that hypomagnesaemia is closely related to insulin resistance in these patients.⁹
Domanski et al¹⁰ reported that diabetes mellitus is associated with increase in most adverse cardiovascular events including myocardial infarction (MI), chronic heart failure (CHF) and stroke. Diabetes is also associated with structural and metabolic abnormalities that can adversely affect myocardial function.
Established diabetes has been associated with reduced serum and tissue magnesium including myocardial magnesium concentration.³
Magnesium is an essential element as a cofactor in both glucose transporting mechanism of cell membranes and various enzymes important in carbohydrate oxidation. A study by Shafique et al¹¹ concluded, that magnesium supplementation improves the overall metabolic homeostasis and thus may be a useful adjuvant to the classic hypoglycaemic agents in the treatment of Type 2 Diabetic subjects.
The interrelationships between magnesium and carbohydrate metabolism have regained considerable interest over the last few years. Insulin secretion requires magnesium and magnesium deficiency results in impaired insulin secretion while magnesium replacement restores insulin secretion. Furthermore, experimental magnesium deficiency reduces the tissues sensitivity to insulin. Subclinical magnesium deficiency is common in diabetes. It results from both insufficient magnesium intakes and increase magnesium losses, particularly in the urine.¹²

The study showed that patients with diabetes mellitus have lower levels of magnesium and are therefore at increased risk of complications related to magnesium.
In light of these potential complications, periodic determination of magnesium levels and appropriate magnesium replacements should be considered.

We are thankful to Dr Altaf Ahmed and Dr Nudrat Zuberi for their support and guidance in finalizing this article.
Gratitude is extended to Prof Kundi for providing the patients for the study.
We also acknowledge the selected patients for providing the routine blood samples anonymously.

1.Ahmed M. Magnesium status in vascular complications of diabetes mellitus.Thesis. Library, JPMC, Karachi. 1994; pp 1-97.
2.Purvis JR, and Movahed A. Magnesium disorder and cardiovascular disease: Review. Clin Cardio 1992; 5: 556-68.
3.Chakaraborti S, Chakraborti T, Mandal M, Mandal, A, Das, S, Ghosh S. Protective role of magnesium in cardiovascular diseases: a review. Mol and Cell Miochem 2002; 238: 163-79.
4.Preis SR, Pencina MJ, Hwang SJ, D\\\'Agostino RB, Sarage PJ, Levy D, Fox CS. Trends in cardiovascular disease risk factors in individuals with and without diabetes mellitus in the Framingham Heart Study. Circulation 2009; 120: 212-20.
5.Zeiba A, Kata R, Dudek D, Zawadzka MS and Nowak G. Serum trace elements in animal models and human depression: Part III Magnesium. Relationship with copper. Hum Psychopharmacol Clin Exp 2000; 15: 631-5.
6.Lee CD, Folsom AR, Pankow JS, Brancati FL. For the Atherosclerosis Risk in Communities (ARIC) Study Investigators. Cardiovascular Events in Diabetic and Nondiabetic Adults with or without history of myocardial infarction. Circulation 2004; 109: 855-60.
7.Arsenian MA. Magnesium and cardiovascular disease. Progress in Cardiovascular Disease 1993; 35: 271-310.
8.Seyoum B, Siraj ES, Saenz C, Abdulkadir J. Hypomagnesium in Ethiopians with diabetes mellitus. Ethn Dis 2008; 18: 147-51.
9.Seeling M. Cardiovascular consequences of magnesium deficiency and loss: Pathogenesis, prevalence and manifestations - Magnesium and Chloride loss in refractory potassium repletion. Am J Cardiol 1989; 63: 4G-21G.
10.Domanski M, Krause-Steinrauf H, Deedwania P, Follmann D, Ghali JK, Gilbert E, et al. The effect of diabetes on outcomes of patients with advanced heart failure in the BEST Trial. J Am Coll Cardiol 2003; 42: 914-22.
11.Shafique M, Fayyaz KM, Nazir S. Diabetes mellitus; Role of magnesium. The Professional 2002; 9: 191-5.
12.Magnesium and carbohydrate metabolism. Therapie 1994; 49: 1-7.