Trace Elements in Diabetes Mellitus
Praveeena S.1, Sujatha Pasula2, K. Sameera3
1 Assistant Professor, Department of Biochemistry, KAMRC Medical College and Hospital, L.B. Nagar, Hyderabad, A.P., India.
2 Assistant Professor, Department of Biochemistry, Era Lucknow Medical College and Hospital, Lucknow, U.P., India
3 Assistant Professor, Department of Biochemistry, Katuri Medical College and HospitalGuntur, A.P., India.
NAME, ADDRESS, E-MAIL ID OF THE CORRESPONDING AUTHOR: Dr. P. Sujatha, Assistant Professor, Department of Biochemistry, Era Lucknow Medical College and Hospital, Lucknow, U.P., India.
Phone: 9966355528;
E-mail: drsujathapasula@gmail.com
Introduction: Diabetes Mellitus is the commonest major metabolic disease and most prevalent diseases worldwide.Its related morbidity is due to its micro and macro angiopathic complications.
Aim: The aim of this study was to measure and compare the serum levels of zinc and magnesium in normal individuals and in diabetic patients.
Method: Analysis of minerals was done in plasma by using a Varian Spectra AA 220 model atomic absorption spectrophotometer.
Result: Our observations showed a definite lowering of serum magnesium (p<0.001) and serum zinc levels (p<0.001) were significant in diabetic group.
Conclusion: The cause of diabetic hypomagnesaemia is multifactorial. An altered metabolism, a poor glycaemic control and osmotic diuresis may be contributory factors. Decreased serum zinc levels in diabetes may be caused by an increase in urinary loss. These decreased levels of trace elements cause disturbances in glucose transport across cell membrane lead to insufficient formation and divretion of insulin by pancreas which compromise in the antioxidant defense mechanisms.
Introduction
The term, ‘diabetes mellitus’ describes a metabolic disorder of multiple aetiology, which is characterised by chronic hyperglycaemia, with disturbances of carbohydrate, fat and protein metabolism, which result from defects in insulin secretion, insulin action, or both. The effects of diabetes mellitus include long term damage, dysfunction and failure of various organs. Death may result from acute metabolic decompensation, while a long standing metabolic derangement is frequently associated with permanent and irreversible functional and structural changes in the cells of the body, with those of the vascular system being particularly susceptible.
A relationship was observed between diabetes mellitus and trace elements in many research studies [1]. In many cases, an alteration in the metabolism of these minerals was demonstrated [2–5]. Insulin action was reported to be potentiated by some trace elements like chromium, magnesium, vanadium, zinc, manganese, molybdenum and selenium [6]. Proposed mechanisms of enhancement of insulin action by trace elements include activation of insulin receptor sites [7], serving as cofactors or components for enzyme systems which are involved in glucose metabolism [8], increasing insulin sensitivity and acting as antioxidants for preventing tissue peroxidation [9].
The most dominant feature of the metabolism in diabetes is an abnormally high concentration of blood glucose [10]. The function of zinc in the body metabolism is based on its enzymatic affinity and way of a zn-enzyme complex or metallo-enzyme. In humans and animals, diabetes causes disturbances in this vital trace element [11]. Zinc is required for insulin synthesis and storage and insulin is secreted as zinc crystals. It maintains the structural integrity of insulin [3]. Zinc has an important role in modulating the immune system and its dysfunction in diabetes mellitus may be related in part to the status of zinc [12].
Magnesium has an important role in the phosphorylation reactions of glucose and its metabolism. Its deficiency has been implicated in insulin resistance, carbohydrate intolerance, dislipidaemia and complications of diabetes [13]. The association between diabetes mellitus and hypomagnesaemia is compelling, because of its wide ranging impact on diabetic control.
It is not known whether trace element status leads to disease or whether diseases sets in due to deficiency of trace elements [14]. Although it is generally believed that a strict metabolic control delays the development of late complications in diabetes mellitus [15]. Type 2 Diabetes mellitus and metabolic syndrome are important risk factors for atherosclerosis and further complications [16].
Hence, in this study, we evaluated the levels of zinc and magnesium in diabetic patients, in an effort to evaluate the status of these elements in such patients.
Material and Methods
In the present study, fasting blood sugar, zinc and magnesium levels were estimated in the blood samples of 80 patients, among which 40 patients without diabetes were taken as controls and 40 patients with diabetes mellitus were considered as cases.
Criteria for selection of patients: Individuals who were 35 years to 60 years old and who were of both sexes were selected for this study and they were divided into two groups. The controls formed Group-1 and patients who had diabetes for more than 5 years were considered as Group 2, who are not taking any kind of trace element supplements. Samples with haemolysis and jaundice were excluded.
Glucose was estimated by GOD-POD method. This method was used, because of its specificity, reliability and simplicity. Analysis of minerals was done in plasma by using a Varian Spectra AA 220 model atomic absorption spectrophotometer.
Results
The studies were carried out on 40 normal controls and 40 diabetic patients.
Serum magnesium level in diabetic patients was12.30 ± 2.10 μ gm/ml, which was were significantly lower (p< 0.001) than that of the controls, the value being 18.49 ± 4.76 μ gm/ml.
Serum zinc level of Group II was significantly lower (0.425 ± 0.24 μ gm/ml) than that of the control group (1.20 ± 0.202 μ gm/ml),(p< 0.001).
The Mean ± SD of fasting Blood glucose level (mg%)
| Group | Mean + SD | S.E |
|---|
| Group-I Normal controls | 82.36+14.3 | 2.868 |
| Group-II Diabetic patient | 145.76+54.44 | 10.88 |
The Mean ± S.D of Serum Magnesium levels (μgms/ml) in various study Groups
| Group | Mean + SD | S.E |
|---|
| Group-I Normal controls | 18.49±4.76 | 0.952 |
| Group-II Diabetic patient | 12.3±2.1 | 0.421 |
Comparison of Mean values of Serum Magnesium levels (μgms/ml) in the groups
The Mean ± S.D of Serum Zinc levels (μgms/ml) in study Groups
| Group | Mean + SD | S.E |
|---|
| Group-I Normal controls | 1.2±0.202 | 0.0404 |
| Group-II Diabetic patient | 0.425±0.246 | 0.0492 |
Comparison of Mean values of Serum Zinc (μgms/ml) in the study Groups
Discussion
In order to understand the role and status of trace elements in diabetic patients, this study was undertaken to compare the serum zinc and magnesium levels in normals and diabetic patients . Serum magnesium and zinc levels were found to be decreased in patients with diabetes as compared to those in normal controls.
Magnesium is an essential ion which is involved in glucose homeostasis at multiple levels. A complex interplay exists between magnesium and glucose metabolisms. It plays an important role in the activities of various enzymes which are involved in glucose oxidation, and it may play a role in the release of insulin [17–19]. It is mainly intracellular and its uptake is stimulated by insulin [19,20]. A cellular magnesium deficiency causes reduction of inositol transport and depletion. This can alter the activity of membrane bound sodium, potassium ATPase [21,22], which is involved in the maintenance of gradients of sodium and potassium and in glucose transport. Low levels of magnesium can reduce secretion of insulin by the pancreas [23].
Our observations showed a definite lowering of serum magnesium in diabetic patients (p<0.001), which was in correlation with findings of Berhane Seyoum et al., [24] Chetan P.Hans et al.,[25] Monika K et al., [8].
The cause of diabetic hypomagnesaemia is multifactorial [26].Osmotic actions of glycosuria and hyperglycaemia may work together in causing hypomagnesaemia and hyperglycaemia per se alone, which are known to depress the net tubular reabsorption of magnesium in normal humans [22,24,25,27].
Zinc is an essential trace element and it is important in glucose metabolism. It is a component of many enzymes and it plays an important role in the maintenance of several tissue functions [19].The relationship between diabetes, insulin and zinc is complex, with no clear cause and effect relationships. Zinc plays a clear role in the synthesis, storage and secretion of insulin, as well as conformational integrity of insulin in the hexameric form. It has the ability to regulate insulin receptor intracellular events that determine glucose tolerance and the ability to support a normal pancreatic reaction to a glucose load [28]. It has a protective effect against β cell destruction and it has well known antiviral effects. The complications of diabetes may be mediated, at least in part, through oxidative stress, and zinc plays a key role in the cellular anti oxidative defense [29]. Hence, it has been suggested that an abnormal zinc metabolism may play a role in the pathogenesis of diabetes and some of its complications [10].
In the present study, serum zinc levels were found to be significantly lowered in diabetic group (p<0.001), which was in correlation with findings of Chausmer AB et al., [3] A C Nsonwu et al., [14] and Alena Viktorinovaa et al., [30].
The cause of decreased serum zinc levels in diabetes may be an increase in urinary loss. Hyperglycaemia has been postulated to interfere with the active transport of zinc back in to the tubular cells [14, 3]. Other possible causes may be disturbed metabolisms of zinc metalloenzymes and an abnormal binding of zinc to tissue proteins, which cause hyperzincuria. Zinc has been found to enhance the effectiveness of insulin in–vitro and hence, a zinc deficiency may aggravate the insulin resistance in type II diabetes. This may cause complications [19,31]. Antioxidant enzymes such as oxide desmutase, catalase and peroxidase require zinc [32].
Hence, these trace element deficiencies appear to be an additional risk factor in the development and progress of disease and they contribute to the pathogenesis of diabetes mellitus and its complications. Their repletion may be an effective therapeutic intervention in prevention of the progression of the diabetes and its complications, along with a glycaemic control and control of other risk factors [33].
[1]. Murray RK, Granner D, Mayes P, Rodwell V, Harper’s Biochemistry (25 th International Edition) 2000 USAAppleton and Lange [Google Scholar]
[2]. Powers MA, Handbook of Diabetes Nutritional Management 1987 MarylandAspen Publishers Inc:195 [Google Scholar]
[3]. Chausmer AB, Zinc, insulin and diabetes J Am College Nutr 1998 17:109-14. [Google Scholar]
[4]. Nielsen Forrest H, New essential trace elements for the life sciences Biological Trace Element Research 1990 26-27(1):599-611. [Google Scholar]
[5]. Nerlich AG, Sauer U, Kolm-Litty V, Wagner E, Koch M, Schleicher ED, Expression of glutamine:fructose-6-phosphate amidotransferase in human tissues: evidence for high variability and distinct regulation in diabetes Diabetes 1998 47:170-178. [Google Scholar]
[6]. Candilish DJ, Minerals J. Am. Coll. Nutr 2000 17:286-310. [Google Scholar]
[7]. Vincent JB, Quest for the molecular mechanisms of chromium action and its relationship to diabetes Nutr. Rev 2000 58:67-72. [Google Scholar]
[8]. Waltr Monika K, Zimmermann Michael B, Spinas Giatgen A, Hurrell Richard F, Low plasma magnesium in type 2 diabetes Swiss Med Wkly 2003 133:289-92. [Google Scholar]
[9]. Kruse-Jarres J.D, Rukguaer M, Trace Elements in Diabetes Mellitus.Peculiarities and Clinical Validy of determinations of red blood cells J Trace Elem. Med. Biol 2000 14:21-27. [Google Scholar]
[10]. Rai V, Iyer U, Mani I, Mani U V, Serum Biochemical Changes in Insulin Dependent and Non-Insulin Dependent Diabetes Mellitus and their Role in the Development of Secondary Complications Int. J. Diab. Dev. Countries 1997 :17 [Google Scholar]
[11]. Kowluru R. A, Kennedy A, Expert. Opin. Invest. Drugs 2000 10:1665-76. [Google Scholar]
[12]. Mocchegianai E, Boemi M, Fumelli P, Fabris N, Zinc-dependent low thymic hormone level in type I diabetes Diabetes 1989 38:932-7. [Google Scholar]
[13]. Resnick LM, Gupta RK, Bhargava KK, Hgruenspan H, Alderman MH, Laragh J, Magnesium deficiency in diabetes Hypertension 1991 17:951-57. [Google Scholar]
[14]. Nsonwu AC, Usoro CAO, Etukudo MH, Usoro IN, Glycemic contro Serum and Urine Levels of Zinc and Magnesium in Diabetics in Calabar, Nigeria Pakistan Journal of Nutrition 2006 5(1):75-78. [Google Scholar]
[15]. Cahill GF, Etzwiler DD, Freinkel N, Control and Diabetes N. Engl. J. Med 1976 294:1004-1005. [Google Scholar]
[16]. Sujatha Pasula, Serum sialic acid, lipid profile and fibrinogen as markers of ST- elevated ECG in myocardial infarction Jour of Med Sc and Tech 2012 1(3):29-35. [Google Scholar]
[17]. Yajnick CS, Smith RF, Hockaday TDR, Ward NL, Fasting plasma magnesium concentrations and glucose disposal in diabetes BMY 1984 288:1032-4. [Google Scholar]
[18]. Goldman J, Fisher V, Magnesium is required in addition to calcium for insulin stimulation of glucose transport (abstract) Endocrinology 1983 112:271 [Google Scholar]
[19]. Zargar Abdul Hameed, Shah NA, Masoodi SR, Laway BA, Dar FA, Khan AR, Sofi F A, Wani AI, Copper, zinc, and magnesium levels in non-insulin dependent diabetes mellitus Postgrad Med J 1998 74(877):665-68. [Google Scholar]
[20]. Viktorinova Alena, Toserova Eva, Krisko Marian, Durackova Zdenka, Altered Metabolism of Copper, Zinc, and Magnesium is Associated with Increased levels of Glycated Hemoglobin in patients with Diabetes Mellitus 2009 58:1477-82. [Google Scholar]
[21]. Grafton G, Baxter MA, J Diab. Complications 1992 6:143-49. [Google Scholar]
[22]. Kareem Ishrat, Jaweed SA, Bardapurkar JS, Patil VP, Study of Magnesium, Glycosylated Hemoglobin and Lipid Profile in Diabetic Retinopathy Indian Journal of Clinical Biochemistry 2004 19(2):124-27. [Google Scholar]
[23]. Durlach J, Altura B, Altura BM, Highlights and summary of the 10th Annual French Colloquium on Magnesium Magnesium 1983 2:330-36. [Google Scholar]
[24]. Seyoum Berhane, Siraj Elias S, Christopher Saenz, Jemal Abdulkadir. Hypomagnesemia in Ethiopians with Diabetes Mellitus Ethnicity and Disease 2008 18 [Google Scholar]
[25]. Hans Chetan P, Sialy R, Devi D, Bansal ,Magnesium deficiency and diabetes mellitus Current Science 2000 83:12 [Google Scholar]
[26]. Hussain F, Maan M Arif, Sheikh MA, Nawaz H, Jamil A, Trace elements status in type 2 diabetes Bangladesh Journal of Medical Sciences 2009 8(3):52-56. [Google Scholar]
[27]. Worcester Elaine M, Coe Fredric L, New Insights Into the Pathogenesis of Idiopathic Hypercalciuria 2008 28(2):120-32. [Google Scholar]
[28]. Andrews Chris, Zinc, Diabetes Mellitus and Oxidative Disease A Nutritional 2005 :22 [Google Scholar]
[29]. Chausmer Arthur B, Zinc, Insulin and Diabetes Journal of the American College of Nutrition 1998 17(2):109-15. [Google Scholar]
[30]. Viktorinova Alena, Toserova Eva, Krisko Marian, Durackova Zdenka, Altered Metabolism of Copper, Zinc, and Magnesium is Associated with Increased levels of Glycated Hemoglobin in patients with Diabetes Mellitus 2009 58(10):1477-82. [Google Scholar]
[31]. Hashemipour M, Kelishadi R, Shapouri J, Sarrafzadegan N, Amini M, Effect of zinc supplementation on insulin resistance and components of the metabolic syndrome in prepubertal obese children Hormones 2009 Oct-Dec 8(4):279-85. [Google Scholar]
[32]. Santoro D, Natali A, Palombo C, Brandi L S, Piatti M, Effects of chronic angiotensin converting enzyme inhibition on glucose tolerance and insulin sensitivity in essential hypertension Hypertension 1992 20:181-91. [Google Scholar]
[33]. Linderman RD, Adler S, Yeingst MJ, Beard ES, Influence of various nutrients on urinary divalent cation excretion J. Lab. Clin. Med 1967 70:236-45. [Google Scholar]