Abstract
Diabetes is a dreaded, debilitating disease. It has got two types- Type 1 and type 2. The causes of T1D are hither to thought as of genetical and immunological nature, with no hope of treatment other than insulin administration. The causes of T2D are thought as of life style with the risk factor of obesity and genetical predisposition. The outbreak of this disease has assumed epidemic proportions. But the recent discovery of correlation between the vitamin D level in the blood and disease has given hope of containing the epidemic. It is shown by experimental studies that the level of 1, 25 di hydroxy vitamin D3, the active metabolite of vitamin, has got an inverse relation ship with the status of diabetes. It is proved that this vitamin plays an active role in synthesis, secretion, sensitivity and utilization of insulin. Deficiency in early stages of life leads to T1D in later life.
The fact that the patient’s condition got ameliorated on the administration of Vitamin D3 proves the premise. Periodic measurement of vitamin D level in the blood will prove to be a boon. The treatment is more effective with accompanying administration of Calcium. It is also proved that people living in the colder regions are more prone to onset of this disease, because of the lack of sunshine in these areas. It is difficult to manage the vitamin D level in the blood to the required level by dietary vitamin alone, as this vitamin is present only in foods of animal origin. Hence it is recommended to manage the vitamin D level with all the known sources- dietary, sunshine and supplementary.
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THE ROLE OF VITAMIN IN DIABETES
Diabetes is the current dreaded epidemic world vide. It is a killer disease with debilitating consequences. Even advanced countries like U.S and U.K are not exemption to it. Diabetes is widespread in the United States, with 24 million people diagnosed and 5.6 million undiagnosed, according to the U.S. Centers for Disease Control and Prevention, reports Gutierrez. The National Institute of Health estimates that a further 70 to 80 million people suffer from metabolic syndrome or other pre-diabetic conditions. There is a danger of epidemic going out of bounds, if the trend is not checked.
Diabetes is related to the synthesis, secretion, sensitivity and utilization of insulin. Insulin, released to the blood stream by pancreas at the instance of rise of blood glucose, binds to the insulin receptors on the cell membrane releasing the glucose transporter protein to the surface of the cell membrane; then the glucose transporter protein carries the glucose molecule to the interior of the cells, for further metabolism. Thus in the absence of insulin, glucose cannot be transported to the cells and the cells will starve of glucose. Hence, the failure of pancreas to produce insulin results in development of Type 1 Diabetes. This is probably due to the damage caused to the pancreatic beta cells. The causes for T1DM are hitherto believed to be of genetical and immunological factors.
In Type 2 Diabetic persons, though the pancreas produces insulin, there is resistance in the tissues to insulin and hence glucose is not metabolized properly, resulting in Diabetes 2. Here the body tissues do not respond to the action of insulin in transporting the glucose to the interior of the cells, resulting in elevated glucose in the blood- a phenomenon known as Hyper glycemia. The risk factors for T2DM are thought to be: genetic predisposal, obesity and life styles. In fact T2DM is branded popularly as a life style disease. The remedial measures for the above causes are difficult and time consuming and hence the spread of the epidemic.
The role of Vitamin D in combating Diabetes
Vitamin D
Vitamin D, popularly known as the sunshine vitamin, is a fat soluble prohormone with a steroid structure. The two important forms are: Vitamin D2-ergocalciferol and D3-cholecalciferol. The chemical formula of Vit.D3 is C27 H44 O. It is a Cholesterol derivative. Commercially it is produced by the action of UV light on 7- dehydro Cholesterol, which is obtained from Cholesterol, vide Vitamin basics .com The well known natural sources are: dairy, egg yolk and fatty fishes. Human skin, when exposed to sunlight, can produce vitamin D. The nutritive value of Vitamin D is well known by the fact, the deficiency of this causes diseases like rickets, and bone demineralizing. The functions of this vitamin, believed hitherto, are: it helps use the mineral calcium and phosphorus to build strong bones & teeth, aids in calcium absorption, prevents rickets, protects red blood cells, immunomodulatory functions, and anti-tumor activity.
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The role of Vitamin D in the amelioration of Diabetes
Norman et al. (1980) has identified, as early as in 1980, a pancreatic receptor to the Vitamin D metabolite (1, 25-dihydroxyvitamin D) in their animal studies and contented that the vitamin deficiency decreased insulin secretion. But the studies performed during the ensuing period did not show convincing correlation or has shown only moderate relationship between Diabetes and vitamin D intake. The major limitations of these studies are: flaw in measurement, low vitamin dosage, small sample size, and short intervention period, asserts Scragg (2008).
But the studies in the later part of the present decade have shown convincing correlations. Forouhi et al. (2008) have established concrete evidence for the inverse relation between the Vitamin D metabolite (1, 25 di hydroxy vitamin D3) concentration in the serum and Blood glucose and insulin levels.
Chowdhury, T. (2010) enumerates the important effects of Vitamin on insulin action and suggests its deficiency “may impact on a number of pathways which may be of importance in the development of type 2 diabetes”. Pittas et al. (2007) has observed, in his studies, consistent association between low intake of Vitamin D and Calcium / dairy products and incidence of T2DM. He concludes, combined supplementation of both Vitamin D and Calcium will benefit in optimizing Glucose metabolism. A study by Loyola University shows, many of the American Diabetics have low Vitamin D levels, establishing a negative relation between Vitamin levels and Diabetes. The two plausible causes for the high incidence of Diabetes in these countries are: 1) scanty sunshine available in the colder regions and, 2) improper diet habit with low intake of dairy products which has both Vitamin D and calcium. The diabetic conditions of such persons got relieved on administering of Vitamin D supplement, proving the relationship. The study concludes that all sources of Vitamin – dietary, supplementary and sunshine will have to be administered for effective control of diabetes. Mathieu et al. (2006) states, the fact that the beta cells and immune cells have Vitamin D receptors (VDR) for the metabolite of the vitamin D, shows its role in synthesis and secretion of insulin, and its deficiency causes impairment of these functions causing both types of diabetes. Animal studies have proved this correlation: Therapeutical administration of 1, 25 di hydroxy vitamin D3 to non obese diabetic mice has alleviated the diabetic condition. He concludes “Vitamin D deficiency may, therefore, be involved in the pathogenesis of both forms of diabetes”. Palomer et al. (2008) affirms this premise saying, the pancreatic tissue has both VDR and DBP (vitamin D binding Protein) and there is some relationship between the VDR & DBP genes and Glucose tolerance & insulin secretion. He further states, it is already known that the vitamin D regulates the plasma calcium level which in turn regulates insulin synthesis and secretion. But the present findings points to direct action of vitamin D on pancreatic beta cell functions. Takiishi et al. (2010) gives the same opinion. He enumerates the clues obtained from various studies pointing out the relationship between Vitamin D and Diabetes: T1D and T2D patients have a higher incidence of hypovitaminosis D; Pancreatic beta-cells and immune system cells express the vitamin D receptor (VDR) and vitamin D-binding protein (DBP); Variations in genes involved in vitamin D metabolism and VDR are associated with glucose tolerance, insulin secretion, and sensitivity; Therapeutic administration of vitamin D (in active form), prevented insulitis and T1D in non obese diabetic (NOD) mice; The possible mechanisms are: immune modulation and direct effects on beta-cell function. Vitamin D administration improves Insulin sensitivity
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British researchers led by Dr. Christos Zipitis administered Vitamin D, – 25 to 400 IU depending on age, to 6455 participants from child hood to 30 years and found reduced risk of T1D by 29% and he states that it is the strongest evidence to show that Vitamin D administered early in life protects people against T1D in later life, reports Song (2008).
Mechanism of action of Vitamin D
Zella (2003) indicates the mechanism of action of Vitamin D in control of diabetes, “The biologically active form of vitamin D, 1, 25(OH) 2D3, is a potent modulator of immune system. This may modulate T1D pathogenesis by repression of type 1 cytokines, inhibit dendritic cell maturation and up regulation of the regulatory T cells” (216).
Strugnell and DeLuca, says, 1, 25 (OH)2 D3 is the hormonally active form of Vitamin D and acts on target tissues by binding to Vitamin D receptor (VDR), cites Zella (216).
Jones et al., postulates , “Upon ligand binding, this nuclear hormone receptor, in conjunction with its heterodimeric partner, the retinoid X receptor (RXR), regulates gene transcription through vitamin D responsive elements (VDRE) in the promoter regions of vitamin D target genes,” cites Zella (216).
Geographic influence
The study conducted in 1978 – 80 by Diabetes Epidemiology Research International Group, found out a correlation between geographic location and incidence of Diabetes. 50 million children of age less than 15, from 22 countries of four continents were screened for their serum levels of 1, 25- di hydroxy vitamin D3, their T1D risk, the prevailing temperature in their location, and the relative distance from the equator. Stryd et al 1979 reports significant correlation between increased T1D risk and the lower temperature of the location. This in turn is influenced by the latitude of the location (Zella 216, 217).
Effective dosage
The present RDA for persons aged 50 is 400 IU/day. Holick (2004) suggests a minimum of 1000 IU/D for maintaining a healthy concentration of the active vitamin metabolite in the blood stream. He recommends getting the 1,25-di hydroxy vitamin D3 analyzed periodically. Scragg et.al suggests raising the 1,25 (OH)2 D3 levels in the blood to 80 n mol/l as the diabetic risk is lowest at this level. A dosage of 2000 IU /D needs to be given to realize this level. Barengolts (2010) says levels of 25(OH) D less than 30 n mol/l indicate insufficiency. Loyola University Health system recommends a 25(OH) 2 D3 level of 30-60ng /ml, i.e. (72 – 144 n mol/l).Researchers from Massey University have found in their experimental study, that on administering a dose of 4000IU /D for six months on South Asia women suffering from insulin insensitivity, their vitamin content in blood got raised from 50 to 119 n mol/ l, and their
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condition improved with better insulin sensitivity and reduced insulin resistance; reports Gutierrez. Sitaram Bhartia Institute of Science and Research in New Delhi reports similar study results in the journal Diabetic Medicine .The Vitamin D council recommends a vitamin D level of 125 n mol/l.
Prospects for future study
One has to ponder over the cause of the spurt of the epidemic of Diabetes in the past few decades in the advanced countries. It is tempting to see a correlation with the epidemic and the influence of the lipid hypothesis advanced by Ancel Keys during 1950.
We may consider the following facts.
Vitamin D is a fat soluble vitamin, present only in fatty foods of animal origin- meat, dairy and poultry products (egg). Vitamin D is associated with cholesterol- both are present concurrently in animal origin foods and Vitamin D is produced from Cholesterol naturally as well as synthetically. Fat is needed for the absorption of this vitamin. Vegetable origin fats do not contain this vitamin.
Shunning of the animal origin foods and fats from the common diet, based on the Cholesterol theory, has become the order of the day from the proposition of the Lipid Hypothesis. The incidence of T2D in vegan communities is significant. The present dietary habit of low fat, low cholesterol diet would have reduced Vitamin D consumption and absorption. Prior to the advent of this theory, the western countries did not have this obese- T2D epidemics.
A study on this aspect is worthwhile.
Conclusion
Maintaining optimum levels of Vitamin D promises to be an effective means of controlling both types of diabetes. But managing the required vitamin D level with diet alone may not be possible as the natural foods having Vitamin D are limited to fish, dairy and egg. Adequate sunshine will ensure a major portion of the requirement. The balance requirement will have to be met with supplements.
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