PREVALENCE OF HYPOMAGNESAEMIA AND ITS CORRELATION WITH INSULIN RESISTANCE AND GLYCEMIC STATUS IN PATIENTS WITH TYPE 2 DM

Aim: To estimate the prevalence of hypomagnesaemia (Mg type 2 DM and its correlation with insulin resistance and glycemic status. Materials and Methods: 100 cases of type 2 diabetes mellitus fulfilling ADA criteria and 50 age and sex matched healthy controls presenting to a tertiary care hospital from Octobe 2014 to September 2016 were included in our Case-Control study. Serum Mg insulin, HbA1c along with other parameters were measured in all study subjects. Insulin resistance and sensitivity was calculated using the HOMA respectively. Results: 34% of cases and 18% of controls had hypomagnesaemia. Prevalence of Hypomagnesaemia increased with the duration of diabetes. retinopathy had a significantly higher prevalence of hypomagnesaemia compared to those without retinopathy (29% VS 5%). 23% of patients with HbA1c >7% had hypomagnesaemia as compared to 9% of patients with an HbA1c of <7%. A st significant inverse correlation was found between serum magnesium and HbA1c levels (r = -0.4395, P < 0.0001). 21% of patients with Insulin resistance (HOMA hypomagnesaemia whereas 12% of patients without Insulin resistance (HOMA The difference was significant. (P value = < 0.0001, RR = 0.1092, 95% CI = 0.6343 0.1879). A highly statistically significant inverse correlation was found between serum magnesium and HOMA-IR level (r = -0.6677, P < 0.0001). A statistically non correlation was found between serum magnesium and HOMA analysis showed fasting insulin levels, HbA1c levels and duration of diabetes to be independent predictors of hypomagnesaemia. Conclusion: Prevalence of hypomagnesaemia was significantly more in diabetics and it increased with the duration of disease. Hypomagnesaemia contributed toward development of insulin resistance and impaired glycemic status in patients with type 2 diabetes. Mg is a cofactor of almost all the rate limiting enzymes involved in glycolysis. It also plays an important role in regulation of insulin signaling, phosphorylation of tyrosine kinase, action of insulin at post receptor level and insu mediated cellular glucose uptake hypomagnesaemia hampers all the above mechanisms contributing towards development of insulin resistance. Lower the basal intracellular Mg, the greater the amount of insulin required to metabolize the indicating decreased insulin sensitivity concentrations of magnesium (and/ of calcium) may blunt insulin action and independently stimulates insulin secretion, leading to both hyperinsul and insulin resistance concurrently prevalence of hypomagnesaemia as well as Insulin resistance in type-2 diabetes mellitus in Indian population Hypomagnesaemia have been hypothesized both a cause and a consequence of various complications such as insulin 6505, Impact Factor: SJIF: 5.995


INTRODUCTION
Magnesium (Mg) is believed to play a pivotal role in glucose metabolism and insulin action. Diabetes mellitus have been suggested to be the most common metabolic disease associated with magnesium deficiency [1] . Hypomagnesaemia (Mg < 1.7 mg/dl) either latent or overt is commonly found in poorly controlled diabetes. Increased urinary loss and deficient dietary intake have been variably proposed as possible causes of hypomagnesaemia. Absorption deficits are rare [2] . Hyperglycemia and hyperinsulinemia increase urinary magnesium excretion by decreasing Mg tubular reabsorption [3] . Adequate glycemic control reduces urinary magnesium wasting [4] .
Magnesium (Mg) is believed to play a pivotal role in glucose metabolism and insulin action. Diabetes mellitus have been suggested to be the most common metabolic disease . Hypomagnesaemia (Mg < 1.7 mg/dl) either latent or overt is commonly found in poorly controlled diabetes. Increased urinary loss and deficient dietary intake have been variably proposed as possible causes of hypomagnesaemia. Absorption deficits are . Hyperglycemia and hyperinsulinemia increase urinary magnesium excretion by decreasing Mg tubular reabsorption . Adequate glycemic control reduces urinary magnesium Mg is a cofactor of almost all the rate limiting enzymes involved in glycolysis. It also plays an important role in regulation of insulin signaling, phosphorylation of tyrosine kinase, action of insulin at post receptor level and insu mediated cellular glucose uptake hypomagnesaemia hampers all the above mechanisms contributing towards development of insulin resistance. Lower the basal intracellular Mg, the greater the amount of insulin required to metabolize the indicating decreased insulin sensitivity concentrations of magnesium (and/ of calcium) may blunt insulin action and independently stimulates insulin secretion, leading to both hyperinsul and insulin resistance concurrently prevalence of hypomagnesaemia as well as Insulin resistance in type-2 diabetes mellitus in Indian population Hypomagnesaemia have been hypothesized both a cause and a consequence of various complications such as insulin

Sameer Panda
To estimate the prevalence of hypomagnesaemia (Mg 2+ < 1.7 mg/dl) in patients with type 2 DM and its correlation with insulin resistance and glycemic status. 100 cases of type 2 diabetes mellitus fulfilling ADA criteria and 50 age and sex matched healthy controls presenting to a tertiary care hospital from October Control study. Serum Mg ++ , fasting insulin, HbA1c along with other parameters were measured in all study subjects. Insulin resistance and sensitivity was calculated using the HOMA-IR model and QUICKI 34% of cases and 18% of controls had hypomagnesaemia. Prevalence of Hypomagnesaemia increased with the duration of diabetes. Patients with diabetic retinopathy had a significantly higher prevalence of hypomagnesaemia compared to those 23% of patients with HbA1c >7% had hypomagnesaemia as compared to 9% of patients with an HbA1c of <7%. A statistically significant inverse correlation was found between serum magnesium and HbA1c levels (r = 21% of patients with Insulin resistance (HOMA-IR >2.6) had hypomagnesaemia whereas 12% of patients without Insulin resistance (HOMA-IR <2.6). The difference was significant. (P value = < 0.0001, RR = 0.1092, 95% CI = 0.6343lly significant inverse correlation was found between serum 0.6677, P < 0.0001). A statistically non-significant correlation was found between serum magnesium and HOMA-ß. Logistic regression levels, HbA1c levels and duration of diabetes to be Prevalence of hypomagnesaemia was significantly more in diabetics and it increased with the duration of disease. Hypomagnesaemia contributed towards development of insulin resistance and impaired glycemic status in patients with type 2 Mg is a cofactor of almost all the rate limiting enzymes involved in glycolysis. It also plays an important role in regulation of insulin signaling, phosphorylation of tyrosine kinase, action of insulin at post receptor level and insulin mediated cellular glucose uptake [5,6] . Consequently hypomagnesaemia hampers all the above mechanisms contributing towards development of insulin resistance. Lower the basal intracellular Mg, the greater the amount of insulin required to metabolize the same glucose load, indicating decreased insulin sensitivity [7] . Low intracellular concentrations of magnesium (and/ or elevated concentrations of calcium) may blunt insulin action and independently stimulates insulin secretion, leading to both hyperinsulinemia and insulin resistance concurrently [8] . There is high prevalence of hypomagnesaemia as well as Insulin resistance 2 diabetes mellitus in Indian population [9] . Hypomagnesaemia have been hypothesized both a cause and complications such as insulin

Research Article
This is an open access article distributed under the Creative Commons Attribution License, which permits Prevalence Of Hypomagnesaemia An Patients With Type 2 Dm resistance, dyslipidemia, atherosclerosis, hypertension and adverse pregnancy outcomes [10] . Some studies have also suggested that magnesium supplementation could be helpful in the treatment of diabetic patients by improving control and preventing the development of diabetes complications [11,12] .
Data in this field are scanty from our country such research work have been published from eastern India. The present study has been undertaken to prevalence of hypomagnesaemia in patients with type 2 DM and its association and correlation with insulin resistance and glycemic status.

MATERIALS AND METHODS
A case control study was conducted at Department of Medicine after obtaining approval from Institutional Ethics Committee. 100 cases and age and sex matched 50 healthy controls were included in the study. Patients aged between 18 to 70 years fulfilling ADA criteria [15] were included as cases.
Patients with chronic kidney disease , hepatic dysfunction , acute myocardial infarction, other endocrine and rheumatologic diseases, chronic alcoholism, malabsorption, prolonged diarrhea, current malignancy, pregnant and lactating women, post-surgery , severe burns, patients on medications like lithium carbonate, magnesium and magnesium-containing antacids or laxatives, long term diuretic use (>6 months) were excluded from our study.
Along with a detailed history and clinical examination, laboratory parameters were measured at the first contact including fasting and post prandial glucose, HbA1c, renal and liver function tests, fasting insulin levels, serum magnesium in all patients and controls. 12 lead ECG and fundoscopic examination was done in all subjects. Insulin resistance was calculated by using Homeostatic model assessment ( IR) and insulin sensitivity by using quantitative insulin sensitivity check index (QUICKI) [16,17] .

Statistical Analysis
The data were analyzed by using SPSS software (version 20.0 for Windows). The results were expressed as a mean 95% confidence limits or SD. A p-value of <0.05 was considered significant. Chi-square test was used to analyze the association between categorical variables. Pearson's correlation coefficient was used to describe continuous risk factors. An independent sample t-test was used for comparing two means variables that were normally distributed. Logistic regression analysis was used to determine the independent variables in the model.

RESULTS
Baseline characteristics of 100 cases and 50 controls was compared [

Prevalence Of Hypomagnesaemia And Its Correlation With Insulin Resistance And Glycemic Status In
3440 resistance, dyslipidemia, atherosclerosis, hypertension and . Some studies have also suggested that magnesium supplementation could be helpful in the treatment of diabetic patients by improving glycemic control and preventing the development of diabetes-related Data in this field are scanty from our country [13,14] and no such research work have been published from eastern India. The present study has been undertaken to estimate the prevalence of hypomagnesaemia in patients with type 2 DM and its association and correlation with insulin resistance and A case control study was conducted at Department of roval from Institutional Ethics Committee. 100 cases and age and sex matched 50 healthy controls were included in the study. Patients aged between 18 were included as cases. patic dysfunction , acute myocardial infarction, other endocrine and hronic alcoholism, malabsorption, prolonged diarrhea, current malignancy, pregnant and surgery , severe burns, patients on lithium carbonate, magnesium and containing antacids or laxatives, long term diuretic use (>6 months) were excluded from our study.
Along with a detailed history and clinical examination, laboratory parameters were measured at the first contact including fasting and post prandial glucose, HbA1c, renal and liver function tests, fasting insulin levels, serum magnesium in all patients and controls. 12 lead ECG and fundoscopic examination was done in all subjects. Insulin resistance was using Homeostatic model assessment (HOMAand insulin sensitivity by using quantitative insulin IR= fasting insulin (μIU/ml) x fasting glucose (mg/dl) QUICKI=1 / (log (fasting insulin μU/mL) + log (fasting Patients were considered as insulin resistant when, HOMA The data were analyzed by using SPSS software (version 20.0 for Windows). The results were expressed as a mean with value of <0.05 was square test was used to analyze the association between categorical variables. Pearson's correlation coefficient was used to describe continuous risk test was used for comparing two means variables that were normally distributed. Logistic regression analysis was used to determine the independent Baseline characteristics of 100 cases and 50 controls was 1]. Cases exhibited Insulin resistance as determined by a higher fasting insulin and HOMA-IR levels (P<0.0001) and a lower QUICKI (P<0.0001). Serum magnesium was significantly lower in cases as compared to controls (P=0.0308). Lipid profile an was significantly higher in cases as compared to controls.
The mean age was 51.13±10.03 years in cases and 51.42±10.09 years in controls. The male to female ratio in the study group was 1:1 in cases and 1:1.17 in controls. The average duration of diabetes among th years. 56% of the cases were having diabetes for 5 years duration, 30% for 6-10 years and only 14% for more than 10 years. Hypertension was associated with 58% of the cases whereas Ischemic Heart Disease (IHD) was associated with 11% of cases. No associated comorbidities were found in 39% of cases included in the study population. The healthy controls were not associated with any comorbidities nor had diabetes at any point of time. In our study 68% of cases were taking some form of Oral hypoglycemic agents, 18% were only on insulin therapy whereas 14% of cases were taking both OHA and Insulin. 35% had retinopathy at the time of initial fundoscopy. 34% of cases and only 18% of controls had hypomagnesaemia.  Table 1 shows characteristics and metabolic parameters of the study subjects. Mean ± standard deviation for all parameters. Figure 1 shows prevalence of hypomagnesaemia in study population: cases and controls. 34% of cases had hypomagnesaemia whereas only 18% of controls had hypomagnesaemia. The mean magnesium levels in cases was 1.76 ± 0.495 and in controls was found to be 1.972 ± 0.274, with a 2-tailed p-value of 0.0308 which is considered significant.

prevalence of hypomagnesaemia in cases and controls
Hypomagnesaemia Resistance And Glycemic Status In magnesium was significantly lower in cases as compared to controls (P=0.0308). Lipid profile and WHR and not BMI was significantly higher in cases as compared to controls.
The mean age was 51.13±10.03 years in cases and 51.42±10.09 years in controls. The male to female ratio in the study group was 1:1 in cases and 1:1.17 in controls. The average duration of diabetes among the cases was 5.89±4.67 years. 56% of the cases were having diabetes for 5 years 10 years and only 14% for more than 10 years. Hypertension was associated with 58% of the cases whereas Ischemic Heart Disease (IHD) was associated with of cases. No associated comorbidities were found in 39% of cases included in the study population. The healthy controls were not associated with any comorbidities nor had diabetes at any point of time. In our study 68% of cases were l hypoglycemic agents, 18% were only on insulin therapy whereas 14% of cases were taking 35% had retinopathy at the time of 34% of cases and only 18% of controls  International Journal of Current Advanced Research Vol 6, Issue 04, pp 3439-3443 3441 magnesium levels in cases was 1.84 ± 0.465 and in controls was found to be 1.972 ± 0.274, with a 2-tailed pvalue of 0.0308 which is considered significant [ Figure-1]. No significant differences were found in the rate of cases (36% and 32% square value = 0.044, P = 0.833, DF = 1). Similarly the difference in rates of hypomagnesaemia in controls had no statistical significance (20% and 16% square value = 0.1355, P = 1.0, DF = 1). A her prevalence of hypomagnesaemia was observed in patients treated with insulin as compared to oral hypoglycemic agents (OHA). (16% for Insulin vs 8% for OHA). The difference was statistically significant. As duration of diabetes increased from <5 years to 5-10 years, the prevalence of hypomagnesaemia increased from 7% to 56.6% which further increased to 92.85% in >10 years duration of diabetes. Prevalence of Hypomagnesaemia significantly higher prevalence of hypomagnesaemia compared to those without retinopathy (29% VS 5%). The difference was statistically 52.97, P value <0.0001, at degree of freedom=1). 76.9% cases of NPDR were having saemia, whereas all cases of PDR had hypomagnesaemia at the time of presentation. 92.3% cases without any evidence of retinopathy during fundoscopy were 23% of patients with HbA1c >7% had hypomagnesaemia as h an HbA1c of <7%. The difference was just significant. (P value = 0.0153, RR = 0.9058). A highly statistically significant inverse correlation was found between serum 0.4395, P < 0.0001) 21% of patients with Insulin resistance (HOMA-IR >2.6) had hypomagnesaemia as compared to 12% of patients without IR <2.6). The difference was extremely significant. (P value = < 0.0001, RR = 0.1092, 95% 0.1879). A highly statistically significant inverse between serum magnesium and 0.6677, P < 0.0001) [ Figure- A highly statistically significant inverse correlation was found 0.4395, P < 0.0001).

Figure 3
A highly statistically significant inverse correlation was found between serum magnesium and HOMA 0.0001).

Figure 4
A highly statistically significant positive correlation was found between serum magnesium and QUICK cell function was significantly lower in cases as compared with controls. (42.115 ± 21.612 vs value < 0.0005). However, a statistically significant correlation was found between serum ß (r = 0.03218, P < 0.6959) [ Figure-Also a highly statistically significant negative correlation was found between serum magnesium and fasting insulin level 0.6911, P < 0.0001) [ Figure-6]. From logistic regression analysis, fasting insulin levels was found to be an independent predictor of hypomagnesaemia. (odds ratio 0.651, 95% CI = 0.492 to 0.861, and P value of 0.003) along with HbA1c A highly statistically significant inverse correlation was found between serum magnesium and HOMA-IR level (r = -0.6677, P < 0.0001).
A highly statistically significant positive correlation was found between serum magnesium and QUICKI level (r = 0.6036, P < 0.0001). significant correlation was found between serum magnesium and HOMA-ß (r = 0.03218, P < 0.6959).

Prevalence Of Hypomagnesaemia An
Patients With Type 2 Dm levels (odds ratio 6.087, 95% CI = 1.025 to 36.140, and P value of 0.047) and duration of diabetes (odds ratio 0.502, 95% CI = 0.261 to 0.969, and P value of 0.040).

DISCUSSION
Prevalence of hypomagnesaemia was significantly more in diabetics (34%) in our study and the prevalence increased with the duration of disease. Kulkarni et al prevalence of hypomagnesaemia in diabetics at around 37% in his study.
Past history of hypertension and presence of diabetic retinopathy, had a significant positive correlation with hypomagnesaemia. Ischemic heart disease did not have a correlation with hypomagnesaemia. Studies by Antin was consistent with our observations but they did not find any significant correlation between hypomagnesaemia and hypertension. A highly statistically significant inverse correlation was found between HbA1c levels with serum magnesium levels in our study. Antin et al higher prevalence of hypomagnesaemia with poor glycemic control but the correlation was statistically not significant.
A highly statistically significant inverse correlation was found between fasting insulin levels, HOMA-IR (marker of insulin resistance) with serum magnesium levels in our study. Asignificantly positive correlation was found between serum magnesium and QUICKI level (marker of insulin sensitivity). Observations made by Chutia et al [13] corroborated with our findings. In our study, we found a statistically non correlation was found between serum magnesium and HOMA-ß, indicator of ß-cell function.
Our study revealed fasting insulin levels, duration of diabetes and HbA1c levels to be independent predictors for the development of hypomagnesaemia in cases with diabetes mellitus. Such an observation have not been reported by any other studies carried out in the past.

Limitation
The sample size of the study was small. A larger sample size would have created a better outlook towards the study end points. Intracellular magnesium has been found to be a better correlate with the development of insulin resistance than serum magnesium levels. Lack of facilities to determine intracellular magnesium in our hospital have prompted us to use serum magnesium for the study.

Prevalence Of Hypomagnesaemia And Its Correlation With Insulin Resistance And Glycemic Status In
3442 levels (odds ratio 6.087, 95% CI = 1.025 to 36.140, and P value of 0.047) and duration of diabetes (odds ratio 0.502, 95% CI = 0.261 to 0.969, and P value of 0.040).
Prevalence of hypomagnesaemia was significantly more in diabetics (34%) in our study and the prevalence increased et al [20] reported the prevalence of hypomagnesaemia in diabetics at around 37% Past history of hypertension and presence of diabetic retinopathy, had a significant positive correlation with hypomagnesaemia. Ischemic heart disease did not have any correlation with hypomagnesaemia. Studies by Antin et al [21] was consistent with our observations but they did not find any significant correlation between hypomagnesaemia and A highly statistically significant inverse nd between HbA1c levels with serum et al [21] reported a higher prevalence of hypomagnesaemia with poor glycemic control but the correlation was statistically not significant. correlation was found IR (marker of insulin resistance) with serum magnesium levels in our study. Asignificantly positive correlation was found between serum magnesium and QUICKI level (marker of insulin sensitivity). corroborated with our findings. In our study, we found a statistically non-significant correlation was found between serum magnesium and s, duration of diabetes and HbA1c levels to be independent predictors for the development of hypomagnesaemia in cases with diabetes mellitus. Such an observation have not been reported by any ize of the study was small. A larger sample size would have created a better outlook towards the study end points. Intracellular magnesium has been found to be a better correlate with the development of insulin resistance than of facilities to determine intracellular magnesium in our hospital have prompted us to CONCLUSION Our study highlights the importance of serum hypomagnesaemia in the development of insulin resistance and impaired glycemic status in patients with type 2 diabetes mellitus as compared to healthy controls. Replacement of magnesium to maintain normal serum levels might aid in better glycemic control and associated decrease in insulin resistance in diabetic patients. Fur to establish this hypothesis.