sweet-thoughts-on-diabetes-mellitus

ON DIABETES MELLITUSINTRODUCTIONThis fascinating illness afflicts over 170 million people, a number that is expected to double by the year 2030. It consumes over 5% of the NHS healthcare budget and its various afflictions lead to a vastly increased use of hospital beds. It affects over 12% of Middle Eastern and Asian peoples and is therefore worthy of our greatest attention.I have heard it being said that having diabetes is worse than having cancer or HIV, and although this may be said in just pure frustration, there may be an element of truth in that. It is a disease of glucose utilisation, and since all body cells require glucose, all of them are afflicted by it. This contrasts with cancer, usually a disease of a single organ, or HIV, a disease of the CD4 cells of the immune system. Aretaeus, a Cappadocian physician of the second century vividly characterized it as “being a melting-down of the flesh and limbs into urine” and coined the term diabetes, meaning ‘to run through’.Diabetes occurs when we have a lack of (type 1), or deficient action (type 2) of the hormone insulin, which is involved in many different biochemical processes, including protein synthesis, lipid and carbohydrate metabolism. Some types of diabetes are secondary to increased antagonism of insulin, such as thyrotoxicosis, Cushing’s syndrome and phaeochromocytoma, but most are primary, due to insulin-related problems.EPIDEMIOLOGY OF DIABETESOne of the saddest things about diabetes is that it is more prevalent in the poor, and affects them in the worst manner with the most complications. A BBC report recently stated:“Britain's poorest communities are 2.5 times more likely to develop Type 2 diabetes than the general population, research suggests. They are also 3.5 times more likely to develop serious complications of diabetes, including heart disease.”Overall it is a common disorder, and is increasing in incidence. The table above shows the current prevalence of diabetes in many parts of the world, with over 10% of Hong Kong, Pakistanis and Czechs, and a ridiculously high prevalence among Egyptians and Cubans too. The following table illustrates how things will worsen within the next few decades:But by far, the highest prevalence of diabetes is in the Pima Indians, native American Indians who live in Arizona and Mexico – with a prevalence of 21%. The study of this population has taught us much about diabetes, most importantly, one of the biggest risk factors for type II diabetes – the sudden shift in diet from traditional agricultural goods towards processed foods. The more Westernised Arizona Pimans are those primarily affected, and the genetically similar Pimas in Mexico have virtually no type 2 diabetes. The rising incidence of diabetes around the world can be attributed to the rise of obesity, and the increasing inactivity (due to the comfortable lives we lead) and reliance on processed foods. The Arab world is increasingly afflicted by diabetes and its ills, which can be explained by the thrifty genotype hypothesis. As explained by Raz et al (2008):“This phenomenon of shifting disease patterns, termed epidemiological transition, initially occurred in developed countries and subsequently spread to developing nations. Arthur Koestler coined the term 'Coca- colonization' to describe the impact of the lifestyle of Western societies on developing countries. The devastating results of intrusion by Western society into the lives of traditional living indigenous communities can now be seen across the globe”.Having introduced syphilis and tuberculosis to the developing word in the 19th century, the West has introduced diabetes everywhere else. Does the answer for modern civilization still lie in the Western civilization, with so much mental and physical illness around? There is so much good in it no doubt, but anyone looking deeply into it, will find that all the basic ideas of any quality in the Western world are embodies, to an even greater extent.In addition, the great poverty that afflicts some leads to lack of education, and a further misunderstanding and poor treatment of the condition. Because it is a chronic condition, with poverty, appropriate drugs are not bought as they are too expensive, and traditional herbal remedies are used. For instance, in the Gaza Strip, where the annual income (for those lucky enough to work) is just under £350 a year, people are resorting to pomegranate seeds and chamomile for treatment, and the management of the condition is careless, with no monitoring facilities, a crucial aspect of its care. This sad truth illustrates the importance of justice, social equality and even distribution of wealth in medical care, things which can only be found in a fair society governed by wisdom and truth.There are many famous diabetics out there, what I would like to focus here on some of its more interesting victims, whose stories may teach us something about the condition.FAMOUS DIABETICSWith regards to aetiology, knowledge that former Egyptian president Jamal Abdel Nasser had diabetes, and possibly slipped into a diabetic coma before he died would help us recall two points – the high prevalence of the disease among Egyptians, and the existence of secondary cause of diabetes; his biographers insist that he had haemochromatosis, although his physician, Alsaway Habib recently published his memoirs and, “He denies that Nasser (1918-1970) had slipped into a diabetic coma before his death. Nor did Nasser suffer from bronzed diabetes as once published in the local press. "Nasser suffered from the ordinary type of adult diabetes," says Dr Habib.”One of the more recent victims is Halle Berry, the American award winning actress. Her story highlights one of the problems that celebrities can cause to the health awareness of people, and how misinformed they can be.Halle Berry is a type 1 diabetic – in other words dependent on insulin. She has made many fascinating comments on the condition, like "Diabetes turns out to be a gift. It gave me strength and toughness because I had to face reality, no matter how uncomfortable or painful it was", and interesting stories, like her diagnosis, when she “lay dangerously ill in a diabetic coma for a week before waking to a life that would never be the same again”. As a result of this, she became a spokesperson for Novo Nordisk, the pharmaceutical company specialising in diabetic products.But it is terrifying when such celebrities make comments on therapeutic aspects of a disease. On 6th of November 2007, the ABC News Channel reported Berry to have said, "I've managed to wean myself off insulin, so now I'd like to put myself in the Type 2 category". As everyone knows, this is nonsense, and what Berry is saying is suicidal. I very much doubt that Berry actually said that, because she remains with us to this day. But what her story highlights is that one should always take celebrities comments on the treatment of disease with a pinch of salt. Symptoms yes, management no. The damage that actors and actresses can cause by making statements such as these in our celebrity culture could be devastating. Another celebrity whose story I am tempted to discuss here is the Honorary Vice President of ‘Diabetes UK’, the great British oarsman and Olympic champion Sir Steve Redgrave, the only person ever to have won gold medals at five consecutive games. But I have opted to discuss his case in the section on ulcerative colitis, since that is a rarer disease, with fewer famous victims that I can think of. Talking of Diabetes UK, the creation of this excellent charity society which provides a lot of patient support and guidance as well as funding for scientific research and publications over the disease, was due to the efforts of two great men, both diabetic and both very influential.The story of Robert Daniel Lawrence, the ENT surgeon is so fascinating that his version is quoted in full in that excellent pharmacology book, ‘Clinical Pharmacology’, by Bennett and Brown (2005). I will do the same:“Many doctors, after they have developed a disease, take up the speciality in it... But that was not so with me. I was studying for surgery when diabetes took me up. The great book of Joslin said that by starving you might live four years with luck. [He went to Italy and, whilst his health was declining there, he received a letter from a biochemist friend which said] there was something called 'insulin' appearing with a good name in Canada, what about going there and getting it. I said 'No thank you; I've tried too many quackeries for diabetes; I'll wait and see'. Then I got peripheral neuritis ...So when [the friend] cabled me and said, 'I've got insulin — it works — come back quick', I responded, arrived at King's College Hospital,London, and went to the laboratory as soon as it opened ... It was all experimental for [neither of us] knew a thing about it... So we decided to have 20 units a nice round figure. I had a nice breakfast. I had bacon and eggs and toast made on the Bunsen. I hadn't eaten bread for months and months ... by 3 o'clock in the afternoon my urine was quite sugar free. That hadn't happened for many months. So we gave a cheer for Banting and Best.But at 4 pm I had a terrible shaky feeling and a terrible sweat and hunger pain. That was my first experience of hypoglycaemia. We remembered that Banting and Best had described an overdose of insulin in dogs. So I had some sugar and a biscuit and soon got quite well, thank you"The disease changed Lawrence’s life entirely, and he devoted all his time to research on the condition and the care of its patients. He set up a clinic which quickly became overcrowded, and this is where Herbert George Wells comes in. The great creator of science of fiction was also a diabetic and a patient of Lawrence. The details were summarised by Curnow (2002):“The number of people with diabetes attending the clinic doubled within four years, conditions were crowded and the equipment was inadequate. The hospital authorities supported Lawrence’s request to make a personal appeal to his more wealthy private patients to fund improvements to the facilities available to outpatients, and possibly build a small unit for in-patients. HG Wells, who had been referred to Lawrence in 1931, was one of the patients Lawrence approached. Wells donated half a crown, saying he was not a wealthy man and believed that the appeal should be of interest to all people with diabetes, and offered to write to The Times to involve a wider audience. The letter to ‘The Select Company of Diabetics – for the Benefit of Their Cult’ was published on 19th April 1933. He ended it saying, "I am a little surprised we have not already formed a Diabetic Association to watch over and extend this most benign branch of medicine to which we owe our lives" (Br J Diabetes Vasc Dis 2002;2:469–72).In 1934, the ‘Diabetic Association’ was founded, with RD Lawrence as the Chairman and HG Wells the President of the Association, with the nominated Vice Presidents including Professor FG Banting and Dr CH Best and two diabetic well-known novelists, GDH Cole and Hugh Walpole.I cannot help but digress and talk a little about H G Wells, who was one of the best writers of both fiction and non fiction of the 20th century. There are an abundant number of biographies of the great man, to which I would like to refer the kind reader, for he is a most interesting person. For the medical man, Wells is interesting for several reasons. Firstly, because of his diabetes, and his massive contribution to the creation of the ‘Diabetic Association’ (now Diabetes UK) together with Lawrence, as explained above. Indeed, the first time it was revealed to me that Wells was diabetic was while reading a very moving letter of his to the great Bertrand Russell, who incorporated it in his ‘Autobiography’, one of the most beautiful books I have ever read. An extract from the letter, written the year before his death in 1946, says a lot about the impact diabetes can have on one’s life:“I have been ill & I keep ill. I am President of the Diabetic Society and diabetes keeps one in and out, in and out of bed every two hours or so. This exhausts, and this vast return to chaos which is called the peace, the infinite meanness of great masses of my fellow creatures, the wickedness of organised religion give me a longing for a sleep that will have no awakening. There is a long history of heart failure on my paternal side but modern palliatives are very effective holding back that moment of release. Sodium bicarbonate keeps me in a grunting state of protesting endurance. But while I live I have to live and I owe a lot to the decaying civilisation which has anyhow kept alive enough of the spirit of scientific devotion to stimulate my curiosity and make me its debtor.” Secondly, because of his very interesting ideas regarding future health care. Wells was a great historian, and he illustrated this with his tour-de-force, ‘An Outline of History’, a 1324 page work that was the most popular book sold in America after its publication (after the Bible). Backed with this huge historical expertise, he gave some marvellous visions of how the future may turn out to be, and in one work, ‘An Englishman Looks At The World’, he envisages a system that seems to predate the GMC and NHS by many years:“In that extravagant world of which I dream, in which people will live in delightful cottages and ground rents will serve instead of rates, and everyone will have a chance of being happy--in that impossible world all doctors will be members of one great organisation for the public health, with all or most of their income guaranteed to them: I doubt if there will be any private doctors at all.Heaven forbid I should seem to write a word against doctors as they are. Daily I marvel at the wonders the general practitioner achieves, having regard to the difficulties of his position.But I cannot hide from myself, and I do not intend to hide from anyone else, my firm persuasion that the services the general practitioner is able to render us are not one-tenth so effectual as they might be if, instead of his being a private adventurer, he were a member of a sanely organised public machine. Consider what his training and equipment are, consider the peculiar difficulties of his work, and then consider for a moment what better conditions might be invented, and perhaps you will not think my estimate of one-tenth an excessive understatement in this matter.” How nice is it to see praise of the general practitioner, at a time when he or she is regarded, somewhat unfairly, as a second class physician!Moving on from Wells, who has taught us so much, we can move smoothly to another British genius, who shared much with Wells – his creativity and invention, disbelief in God, faith in eugenics (which is almost inextricably intertwined) and last but not least, his diabetes. It’s the great inventor of the telephone, Alexander Graham Bell.I will not deal here with the full biographical details of this great man, his numerous struggles and tragedies, his many success stories, and his great romanticism and his love and marriage to his deaf student Mabel Hubbard. But I will focus on what I regard as interesting from the medical point of view.Robert V. Bruce writes in his biography, ‘Bell: Alexander Graham Bell and the Conquest of Solitude’:“By 1915 Bell himself was in the grip of that incurable and (in pre-insulin days) perilous condition, diabetes. He had occasion for somber thought now in his sessions of nocturnal solitude. He could not have been deaf to the meaning of what was upon him. Diabetes had been the death of his uncle David 14 years before, but Bell's motto was 'keep on fighting'”.He was later diagnosed with pernicious anaemia, which is a recognized association with diabetes, although not with type 2 diabetes, which is what Bell likely had (no one with type 1 diabetes survives without insulin to the age of 75). And although it is stated in many places that Bell died of pernicious anaemia, including in the Wikipaedia article on him, I feel that is unlikely to be the case. Although it sounds paradoxical, diabetes, particularly when uncared for is a more pernicious than the pernicious disease! It is clear that Bell’s diabetes was uncared for, for obvious reasons. Firstly, he lived in the pre-insulin age – he was unlucky to have died in the same year Banting and Best discovered insulin, although it would be difficult to foresee if their treatment would have made any difference to him had he survived. For example, he developed neuropathy, as Charlotte Gray discloses in her biography of Bell, ‘Reluctant Genius’ (pages 418-419) – he was able to keep on wiggling “his toes, even though he had lost sensation in them. None of his family realized that the loss of sensation was an indication that he had pernicious anemia". (Although giving a clever possibility, it will never be known which one it is that led to his peripheral neuropathy). Neuropathy happens after years of damage, as we will soon see.There was an absence of the routine care we now have for diabetes (which has been formulated after many years of intensive research into its most appropriate management). Knowing the above, Bell would have surely benefited from seeing a chiropodist, something all diabetics of today are routinely familiar with. He would have also possibly benefited from a dietitian, but by sounds of things, he would have probably been, as are most diabetics, pretty non-compliant with their recipes. As Bruce illustrates in the aforementioned biography:“Always a hearty eater, Bell broke loose now and then from the coils of medical caution and, to the distress of his family, defied restrictions on starch and sugar. “Melville," he would say to his grandson as they walked by a redolent bakeshop on Wisconsin Avenue, "would you like some apple pie?" Bell himself would then join in the snack. "Don't you say a word to your grandmother," he would caution the boy. But when he toyed with his dinner, Mabel would notice. "Alec, you stopped in that bakeshop, I know." Ignoring the smoke screen of an exciting story, she would keep after him until he confessed like a small boy caught out. Charles Thompson kept an eye on the state of the refrigerator, but one night Bell made a raid, washed the china, and brushed up every crumb. Called to treat his acute indigestion, the doctor extracted the confession, "To go downstairs at three in the morning, load up on Smithfield ham, cold potatoes, macaroni cheese, and then go right to bed is the most ridiculous thing imaginable, " said the doctor severely; "that meal might have put an end to you, sir" "Well, as it is," said Bell, "the game was worth the candle. It was the best meal I've enjoyed in an age"!”In knowing that Alexander Graham Bell had type 2 diabetes we will immediately dispel the idea that type 2 diabetes is a twentieth century phenomenon. It is not, although it certainly has increased in prevalence since. Indeed, the two different types of diabetes were distinguished as early as 1875, by Apollinaire Bouchardat in his book on glycosuria (Kiple, 2003).In addition, the story of his doctor suspecting that “Bell’s diabetes had affected his liver” reveals a very clever insight into diabetes, which has only recently been recognized. Liver disease is now thought to be a not uncommon cause of problems in diabetics. Indeed, it is now felt that NASH, non-alcoholic steatohepatitis, the commonest liver pathology seen in diabetics is now a not uncommon cause of progressive chronic liver injury overall (Evans et al, 2002).Quite smoothly, history moves us on to discuss one of Bell’s close associates, Thomas Edison, the great American inventor. If Bell invented the telephone, it was Edison who made improved on it greatly and made it the technological masterpiece that it is today. He devised a mouthpiece for it that contained carbon powder, which when compressed, carried more current than when not compressed. As the sound waves compressed and decompressed it, the electric current fluctuated accordingly.Edison died of complications of diabetes aged 84, namely renal failure. In ‘Edison - Inventing the Century’, Neil Baldwin describes the experience of his physician:“Dr. Howe had a challenging patient in Thomas Edison - a totally deaf, eighty-four-year-old-man who did not bathe more than once a week, but did not believe in exercise, still (by his own account) "chewed tobacco continuously" and smoked several cigars a fay, and whose only foods were milk and the occasional glass of orange juice... In later years, Edison also suffered from diabetes and Bright's disease”. Bright’s disease is the old name for renal failure. He died uraemic on October 18th 1931. One can see how Edison would have benefited, like Bell, from attending a dietitian, and having smoking cessation advice. And unlike his Scottish counterpart, he would have been more likely to heed their advice. After all, wasn’t Edison the one who famously said:“The doctor of the future will give no medicine, but will interest her or his patients in the care of the human frame, in a proper diet, and in the cause and prevention of disease”?Now let us move on to diabetes itself. DIABETES – THOUGHTS ON PATHOPHYSIOLOGYOne of the biggest lessons of diabetes, is that it induces a feeling of appreciation of normal metabolism. The primitive human being, by virtue of instinct, knows that through lack of food and water, oxygen and warmth, he will die. We know this death is caused by cardiac arrest, and treating these three, if present, is part of the established cardiac arrest management algorithm (namely hypothermia, hypoxia, hypovolaemia). We always pierce the patient’s finger to check his blood glucose (in any comatose patient, including that due to a cardiac arrest). Both hypoglycaemia and hyperglycaemia are sinister and are treated aggressively, and what is important to realise is that they are both forms of ‘body starvation’ – not just hypoglycaemia. Whereas in hypoglycaemia, the body is starved of fuel, in diabetic hyperglycaemia, the body is starved of glucose utilisation, and in a desperate attempt, tries to consume other fuels, fats and proteins, which is only possible for a short while without severe consequences, which we shall discuss later. What is important to realise too is that hyperglycaemia not only leads to metabolic consequences, but also to hypovolaemia. This is because of the increased urine output and intracellular fluid loss due to osmotic shift. Indeed, in a patient with severe uncontrolled hyperglycaemia, such as diabetic ketoacidosis or HONK (hyperosmolar non-ketotic diabetic coma), it is dehydration that kills them, not the hyperglycaemia per se.Normal glucose regulation is maintained by several complex mechanisms. After any carbohydrate meal, the pancreas responds by releasing insulin from its beta cells (islets of Langerhans). This serves to stop gluconeogenesis and glycogenolysis, and stimulate glycogen synthesis (stimulating the enzyme glycogen synthase) by the liver (as well as glycerol for triglyceride synthesis), and shifts glucose intracellularly (via GLUT-4 receptors) into skeletal muscles and adipose tissue. Note that the liver does not need insulin to get glucose into its cells. It enters simply via a concentration gradient.Why should this be the case? Perhaps the body is being economical with its insulin, knowing that the insulin is required for the insulin-induced stimulation of glycogen synthase and triglyceride synthesis. I do not know, but am sure there is a clever reason behind it.One of the fascinating facts is that the brain, which consumes about 80% of the glucose utilised at rest in the fasting state, it too, like the liver, does not depend on insulin to get to it. The brain has exclusive GLUT-3 receptors. Now, imagine if the brain depended on insulin. This would be a disaster for all type 1 diabetics, who would quickly go into a coma and die once their pancreas is overwhelmed by the disease.Now we mentioned above a fact that everyone knows – after a high carbohydrate meal, the pancreas releases insulin. What we fail to realise and appreciate is that, these four words – ‘the pancreas releases insulin’ is one of the most majestic events of the cosmos. This is not an exaggeration, as I will explain below. Perhaps because we are see so many diabetic patients in hospital and in general practice that we regard it all as monotonous, and so we do not reflect on or appreciate this majesty. But let me break away and begin reflecting on this process like an intelligent child, and prove my point.To begin with – the pancreas needs to detect the glucose cells. Harun Yahya summarises this amazing process as follows, “First, the pancreas cells would find and distinguish the sugar molecules from among all the millions of other molecules in your blood. Moreover, they would count the sugar molecules to decide if the number were too high or too low. Amazingly, cells too small for the eye to see, without eyes, hands, or a brain know the correct proportion of sugar molecules in a fluid.” The glucose enters the beta cells by facilitated diffusion through the glucose transporter, GLUT-2. Although the majority of human cells require insulin to shift insulin into them, the pancreas, like the liver, doesn’t. It is a basic rule of the human body that an organ synthesising a chemical or hormone is never itself dependent on it. It is a form of altruism.Within the beta cells, glucose is metabolised to produce ATP. This ATP closes ATP-dependent potassium channels present in the beta cell membrane, which then depolarises the cell, causing calcium entry, which stimulates exocytosis of insulin. Sulphonylurea drugs, like gliclazide act like ATP here, inhibiting the ATP-dependent potassium channels.The insulin is synthesised as a large molecule – called pre-proinsulin. The reason for this is that it includes a signal peptide, called C-peptide, which is important for directing its proper folding and movement through the Golgi apparatus where it is synthesised (Kaufmann, p.240). Just before storage this is converted to insulin and C-peptide.Unfortunately, for reasons of space, we will not be able to talk about many of these magnificent processes which we are passing by here without much reflection. ATP manufature, depolarisation, insulin (protein) synthesis, exocytosis and cleavage. But the details may be found in any decent biochemistry textbook. I preferred Stryer back in the day.Once insulin is secreted into the bloodstream it exerts its action by binding to receptors primarily in the liver, muscle and adipose tissue; these are tyrosine kinase linked receptors which when bound to insulin result in a conformational change and autophosphorylation, and phosphorylation of IRS (insulin receptor substrate) proteins which activates intracellular signal cascades and enzymes.The actions of insulin are summarised in the table below:Following discussion of insulin’s roles, Harun Yahya concluded wondering, “How can it be that cells without a brain, nervous system, eyes or ears can manage to make such a complex calculation and carry out their function perfectly? How can these unconscious cells formed by the coming together of proteins and fat molecules do things too complicated for humans to achieve? What is the source of this remarkable awareness demonstrated by these unconscious molecules? Surely all of these delicate operations taking place in our bodies show us the existence and power of God Who rules over the universe and all living things.” I wish I were the first to say that!So insulin’s main role is in glucose homeostasis, and indeed, it is the only hormone in the human body that lowers blood glucose, whereas several other hormones can raise it. Why is this the case? As one researcher postulates, “Our body has no back-up system if insulin stops working. Why would that be, do you think? Does it not strike you as odd that in the fabulous system that is our body there is no back-up system for insulin, when our body tends to have all kinds of fall-back plans if something should fail? Perhaps it is worth looking at the question through the eyes of primitive humankind. Not having lived at that time I can't be certain, but I would imagine that there would have been times of limited food, and being able to increase blood sugar levels would have been critically important in order to fuel the body when there was very little or no food being consumed. Just like many other animals, in the spring and summer when fruit, plants and grains were available, it was advantageous to have insulin store some fat to aid chances of survival through the lean winter months. Fruit would be dried, and other foods fermented, but especially in the colder climates, people would rely on wild animals or fish for most of their food in the winter. Meat and fat do not induce a big insulin response. So, perhaps in the body's wisdom, it did not think it needed more than one method to lower blood sugar, as high carbohydrate (plant food) diets simply did not happen day in day out all year round except possibly in tropical climates.”So what happens if there is not enough insulin? Quite simply, there is unopposed action of glucagon and other anti-insulin hormones (catecholamines, cortisol), and the following results:DIABETES AETIOLOGY & PATHOGENESISBut how is diabetes caused? The general consensus is that type 1 is an autoimmune condition triggered by environmental and genetic factors.The autoimmune aspect is postulated because three reasons:The association of type 1 diabetes with other autoimmune diseases such as vitiligo, pernicious anaemia, Grave’s disease, and Addison’s disease.The presence of T-cell infiltrates within the islets of type 1 diabeticsDetection of antibodies to islet cell antibodies (ICA) and glutamic acid decarboxylase (GAD) in their serum.Autoimmune diseases are a minefield, and we will discuss them in more detail in the immunology section, but just to overview, they chiefly result from what is known as loss of tolerance. The normal human body has mechanisms that ensure B-cells are unresponsive to self-components, and that T-cells are not mobilized by self-peptides expressed on the MHC of healthy cells. This tolerance may be central, achieved by clonal inactivation or deletion of autoreactive T-cells in the thymus and B-cells in the bone marrow, as well as peripheral.Autoimmune diseases, although dreadful, highlight to the majority of mankind the presence of these mechanisms. Were they not present, would we have appreciated ‘tolerance’ and its very clever mechanisms? The answer is probably not. This is another argument for intelligent design – a normal human body cannot exist without a perfect immune system, which recognizes itself and only attacks others. Even with a normal heart, lung, joints, GI tract etc; if the immune system does not institute tolerance, disaster will follow, as all type 1 diabetics, and patients of other autoimmune disease know. Other examples of autoimmune disease are tabled below. The autoimmune event may be triggered or propagated by environmental factors. This is suggested by epidemiological studies, which show that clinical onset of type 1 diabetes peaks in the spring and autumn months, coinciding with higher incidence of viral infections at these times.Genetic factors are suggested by studies on its prevalence in twins – 50% in monozygotic twins, and 6% in dizygotic twins, and an increased risk of 6% of developing type 1 DM in first-degree relatives of patients with it. It is interesting to note that people at such increased risk may be monitored in the future by measuring the aforementioned ICA antibodies, which precede development of hyperglycaemia by many months, possibly years.An interesting observation is that the body has a huge reserve of islet cells, and that hyperglycaemia only develops once 75% of beta cells are lost. Such is the kindness of the Creator. He has given us more than we need.As for type 2 diabetes, there is no autoimmune component, but genetic, environmental and possibly also fetomaternal factors are important. Let us reflect on these aspects for a minute.Genetic factors are suggested by a higher concordance in monozygotic than dizygotic twins, as for type 1 diabetes, and also a higher prevalence in certain full-blooded populations compared to mixed races (e.g. Naurans in the South Pacific). Indeed, certain genetic defects have been illustrated in some cases (MODY – maturity onset diabetes of the young). These are listed in the tables below, with a table of the classification of MODY disorders. It is important to have an intact enzymatic pathway for insulin action and beta cell function. In addition, there are a number of ‘insulinopathies’, very rare genetic conditions inherited also in an AD fashion where abnormal insulin is secreted. The amino acid changes are so subtle, yet end in disaster, highlighting the magnificent accuracy of the human body in the majority of us with normal insulin. Had we not known about these insulinopathies, would we have appreciated this aspect, one wonders? Very unlikely, and the synthesis of insulin would have been taken for granted.

What is Diabetes Mellitus?

Diabetes mellitus is a group of metabolic diseases characterized by high blood sugar (glucose) levels, which result from defects in insulin secretion, or action, or both. Diabetes mellitus, commonly referred to as diabetes (as it will be in this article) was first identified as a disease associated with 搒weet urine," and excessive muscle loss in the ancient world. Elevated levels of blood glucose (hyperglycemia) lead to spillage of glucose into the urine, hence the term sweet urine. Normally, blood glucose levels are tightly controlled by insulin, a hormone produced by the pancreas. Insulin lowers the blood glucose level. When the blood glucose elevates (for example, after eating food), insulin is released from the pancreas to normalize the glucose level. In patients with diabetes, the absence or insufficient production of insulin causes hyperglycemia. Diabetes is a chronic medical condition, meaning that although it can be controlled, it lasts a lifetime.
What is the impact of diabetes?
Over time, diabetes can lead to blindness, kidney failure, and nerve damage. These types of damage are the result of damage to small vessels, referred to as microvascular disease. Diabetes is also an important factor in accelerating the hardening and narrowing of the arteries
atherosclerosis), leading to strokes, coronary heart disease, and other large blood vessel diseases. This is referred to as macrovascular disease. Diabetes affects approximately 17 million people (about 8% of the population) in the United States. In addition, an estimated additional 12 million people in the United States have diabetes and don't even know it. From an economic perspective, the total annual cost of diabetes in 1997 was estimated to be 98 billion dollars in the United States. The per capita cost resulting from diabetes in 1997 amounted to $10,071.00; while healthcare costs for people without diabetes incurred a per capita cost of $2,699.00. During this same year, 13.9 million days of hospital stay were attributed to diabetes, while 30.3 million physician office visits were diabetes related. Remember, these numbers reflect only the population in the United States. Globally, the statistics are staggering.
Insufficient production of insulin (either absolutely or relative to the body's needs), production of defective insulin (which is uncommon), or the inability of cells to use insulin properly and efficiently leads to hyperglycemia and diabetes. This latter condition affects mostly the cells of muscle and fat tissues, and results in a condition known as "insulin resistance." This is the primary problem in type 2 diabetes. The absolute lack of insulin, usually secondary to a destructive process affecting the insulin producing beta cells in the pancreas, is the main disorder in type 1 diabetes. In type 2 diabetes, there also is a steady decline of beta cells that adds to the process of elevated blood sugars. For more, please read the Insulin Resistance article. Essentially, if someone is resistant to insulin, the body can, to some degree, increase production of insulin and overcome the level of resistance. After time, if production decreases and insulin cannot be released as vigorously, hyperglycemia develops.
Glucose is a simple sugar found in food. Glucose is an essential nutrient that provides energy for the proper functioning of the body cells. Carbohydrates are broken down in the small intestine and the glucose in digested food is then absorbed by the intestinal cells into the bloodstream, and is carried by the bloodstream to all the cells in the body where it is utilized. However, glucose cannot enter the cells alone and needs insulin to aid in its transport into the cells. Without insulin, the cells become starved of glucose energy despite the presence of abundant glucose in the bloodstream. In certain types of diabetes, the cells' inability to utilize glucose gives rise to the ironic situation of "starvation in the midst of plenty". The abundant, unutilized glucose is wastefully excreted in the urine.
Insulin is a hormone that is produced by specialized cells (beta cells) of the pancreas. (The pancreas is a deep-seated organ in the abdomen located behind the stomach.) In addition to helping glucose enter the cells, insulin is also important in tightly regulating the level of glucose in the blood. After a meal, the blood glucose level rises. In response to the increased glucose level, the pancreas normally releases more insulin into the bloodstream to help glucose enter the cells and lower blood glucose levels after a meal. When the blood glucose levels are lowered, the insulin release from the pancreas is turned down. It is important to note that even in the fasting state there is a low steady release of insulin than fluctuates a bit and helps to maintain a steady blood sugar level during fasting. In normal individuals, such a regulatory system helps to keep blood glucose levels in a tightly controlled range. As outlined above, in patients with diabetes, the insulin is either absent, relatively insufficient for the body's needs, or not used properly by the body. All of these factors cause elevated levels of blood glucose (hyperglycemia).
Diabetes mellitus is a metabolic disorder characterized by a congenital (similar to juvenile-onset or Type I diabetes mellitus in people) or acquired (similar to adult-onset or Type II diabetes mellitus in people) inability to transport sugar from the bloodstream into cells. Once inside cells, sugar (glucose) is used to generate the energy that is essential for normal cellular function. Diabetes in animals is most commonly the acquired form and typically occurs in middle-aged to older pets. The disease results when glucose transport channels on cell membranes are insensitive to the effects of insulin (or when there are too few channels) or when the quantity of insulin produced by the pancreas is inadequate to activate the number of glucose channels needed to maintain normal cellular metabolism. In other words, insulin is the “key” that allows special “gates” for sugar transport across cell membranes to be opened. A diabetic, therefore, has too much glucose in the bloodstream where most of it cannot be utilized, and not enough glucose within the cells themselves, where it is most needed for energy. As a result, cells attempt to derive energy from alternate metabolic pathways, such as fat breakdown. Excessive use of these alternate energy pathways culminates in production of harmful by-products called ketones. The accumulation of ketones causes the body’s pH to become acidic (ketoacidosis) which makes the cellular environment inhospitable for normal metabolic functions. This condition can ultimately become life-threatening and requires aggressive medical therapy.
Fortunately, most diabetics give some indication of their underlying condition, such as drinking and urinating excessively, before they develop ketoacidosis. Treating diabetics before they become ketotic is considerably more straightforward, safer, and of course less expensive than taking a "wait-and-see" approach to changes in drinking behavior. Equally important, diagnostic testing may reveal other serious conditions which can cause excessive urination and drinking, such as kidney or liver disease, adrenal hormone or electrolyte imbalances and uterus infections.

Diabetes mellitus Modern medical treatment

Modern medical treatment: 1. General treatment: To the patients or their families about the knowledge of this disease so that patients understand the long-term treatment of eating the meaning of purpose and importance of specific measures to meet the doctors consciously and strictly controlled diet, to establish the law of life, work and rest appropriate, to master oral Hypoglycemic drugs and insulin dosage and usage. 2. Physical therapy: Strong in normal physical activity or exercise, to reduce the secretion of insulin, adrenaline, cortisol, glucagon and growth hormone secretion increased, so that the peripheral organization of sugar to reduce the use of glycogen and increase output; However, due to increased muscle blood flow Faster increase in the number of insulin receptors, a significant increase in the use of sugar, so maintaining normal blood sugar. Regular exercise can enhance insulin receptor function, in light of diabetic patients, especially non-insulin-dependent diabetes mellitus (NIDDM) patients, appropriate physical activity can make high blood sugar dropped, from special treatment, and improve lipid metabolism And enhance heart function, reduce the incidence of complications. Lost in diabetes control, a significant lack of insulin, strong physical activity contrary to make high blood sugar, or even cause ketoacidosis. Insulin injections for patients, exercise will not reduce the level of insulin, and part of the campaign, subcutaneous injection of insulin absorption by fast, easily lead to low blood sugar reactions. Strong after exercise, liver glycogen and muscle glycogen storage needed to restore the 24-48h in order to achieve the level before the campaign. Therefore exercise and after exercise to increase the carbohydrate intake is very important, otherwise we will exercise or sports after a few hours or even 10-hour response出现低血糖(insulin injections patients). Obesity light of NIDDM patients with diabetes should be restricted calorie intake on the basis of strengthening exercise. Approach to the sport mainly exercise endurance, we must combine the characteristics of each patient, select the appropriate amount of physical load. Inappropriate or too much exercise or excitement of the sport can not only be the effect, and sometimes anti-blood sugar so high. Patients with diabetes than the general body is weak, started physical therapy should be preceded by a short period of time the light physical activity, with the enhancement of the physical, and then gradually increase the amount of exercise and sports, over-exertion without benefit not only the movement, but also so that the condition Deterioration. Physical exercise to be sustained, with the exception of acute disease has not stopped outside. 3. The treatment of eating: all diabetes patients are required to control diet. (1) of the total energy needs of diabetes patients is as follows. Children need calories, 1-year-old daily 4184kJ, by every 1-year-old Canadian 418kJ. Adolescent women need daily 10042-11300kJ, man 12552-15062kJ. Adult obesity should be limited to a day in 4184-6174kJ, pregnant women, breast-feeding, malnutrition and wasting disease are to be increased as appropriate. Protein per kilogram of body weight requirements are as follows: 15 children under the age of 1.5-2.5g. Adult 1g, pregnant women, 1.4g, breast-feeding women 1.7g. Carbohydrate accounted for 50% of the total calories -65%. Calories from fat to provide the rest. In the intake of total fat, saturated fatty acids should be reduced to only a total of 1 / 3, for the rest of the unsaturated fatty acids, cholesterol at the same time will be limited to 300mg a day of the following, obese patients should reduce the total calories and fat intake If no longer be effective to reduce the intake of carbohydrates. Staple food in the morning, afternoon and evening meals in the distribution of 1 / 5, 2 / 5, 2 / 5. Appropriate activities for a long time snacks. Insulin injections patients should occur before the peak insulin activity for a long time and snacks as necessary, the use of long-acting insulin are often required before going to bed at night snacks. The food should be calculated according to the local food supply in exchange of food ingredients designed to enable patients to better grasp the diet. High-fiber diet is the daily fiber intake of more than 40g, delay intestinal absorption of glucose in blood sugar and reduce the increase. (2) of the diet method: small sub-algorithms and an estimated two law: ① fine algorithm: patients with gender, age, body weight standards for calculating the daily calories needed a few cards and carbohydrates, protein and fat grams, the standard weight for height and weight people can refer to the standards table. Simple method can also be used (that is, the height -105 = weight (kg)). ② estimation: a fixed staple food, according to the physical needs) of patients a day to rest staple 200 ~ 250g, light manual 250 ~ 300g, moderate physical 300 ~ 400g, severe physical more than 400g. Huncai about 150g per day, vegetables 250 ~ 500g, cooking oil 3 to 4 key. Three meals a day by 1 / 5, 2 / 5, 2 / 5 allocation. According to everyone is different, can be early, middle and late to sort out three meals a day: 1 / 3 respectively in the 9 to 10:00 am, 3 to 4:00 pm and before going to bed around 10 o'clock. This will reduce the postprandial hyperglycemia, as well as a stronger role in the prevention of insulin at the time of low blood sugar reactions. 4. Oral hypoglycemic agents (1) sulfonylurea (su1fony1urea, SU): this class of drugs directly stimulate the islet cells to release insulin, so that the increase in endogenous insulin. Islet cells inhibited α reduce glucagon production, thus lowering blood sugar; inhibit decomposition of glycogen and gluconeogenesis, to reduce the output of glycogen; also by peripheral tissues of the role of insulin receptor. Mainly for middle-aged and older-onset non-insulin-dependent diabetes mellitus, and with the control diet plus exercise therapy are not satisfied with the control of blood sugar. Drugs commonly used are: ① tolbutamide (tolbutamide, D860): Each 0.5g. Daily 1.5 ~ 3.0g, taking fasting in three installments. ② C-methyl-urea (chlorpropamide, P607): Each 0.1g. Only once a day orally, in general 0.1 ~ 0.3g. A capacity of 0.5g. These two are the first generation of SU, D860 hypoglycemic effect is weak, less side effects. P607 hypoglycemic effect lasted for a long time, the emergence of hypoglycemic medication 4 hours, 10 hours a role in most, 24 hours after an effective, sustainable 40 to 60 hours. Yi Zhi low blood sugar reactions, and poor kidney function in elderly patients with the drug banned. ③ glibenclamide (glyburide, HB419): each 2.5mg, every day 7.5 ~ 15mg, three times to take fasting. Its role in hypoglycemic strong wind D860 is about 100 ~ 500 times. ④ Delta, Culture and Sport (topiramate-methyl urea, gliclazide): Each 80mg, every day 160 ~ 320mg, three times to take fasting. Its hypoglycemic glybenclamide role than the weak, the D860 for 10 to 20 times, characterized by anti-platelet aggregation, improve microcirculation. Can prevent and delay the complications. ⑤ Glurenorm (methyl quinoline cyclohexyl urea, g1iquidone): Each 30mg, daily 60 ~ 120mg, three times to take fasting. Its main metabolism in the liver, gastrointestinal tract after discharge. It is applicable to the merger Ⅱ diabetes and renal dysfunction, renal disease who were. ⑥ glipizide (topiramate methyl cyclohexyl urea, glipizide): each 5mg, a daily 15 ~ 30mg. Hypoglycemic effect was slightly lower than glibenclamide, the D860 to 100 times, characterized by hypoglycemia less safe. ⑦ grams of sugar Lee (MSA II urea ice, glutril, glibornuride) per tablet 25mg, daily 25 ~ 75mg. Hypoglycemic effect for 40 times the D860, with improvement in blood rheology, prevention of anti-thrombosis and atherosclerosis. ③ ~ ⑦ the above-mentioned five drugs for second-generation SU. Sulfonylurea indications: ① Ⅱ diabetes light and medium-sized patients, the diet plus exercise control over those who are not satisfied. ② Ⅱ type 2 diabetes patients with insulin every day just below 40U, 20U are less than effective. ③ 40 over the age of onset of diabetes Ⅱ fasting blood glucose> 11.1mmo1 / L, in the course of disease within 5 years, never using insulin treatment, normal weight or obese optional SU Shuanggua Lei and treatment. ④ has tried in recent years, and insulin treatment to strengthen the effect. Sulfonylurea drug side effects: About 5% of patients with anorexia, the deterioration of vomiting, abdominal pain, diarrhea, and other gastrointestinal reactions. About 2% to 3% of patients have skin itching, rash, and so on, sometimes exfoliative dermatitis, a small number of patients have bone marrow suppression. All sulfonylureas can cause low blood sugar, low blood sugar coma and even death. (2) Shuanggua Lei: This class of drugs hypoglycemic mechanism has not yet entirely clear. However, the known and sulfonylurea, does not stimulate the release of insulin β cells. According to animal experiments and clinical observation that the hypoglycemic effect may be three. First, inhibiting cell wall to absorb glucose: As the oral phenformin can improve glucose tolerance, intravenous injection when there is no role here. Hypoglycemic and at the same time, plasma insulin concentration does not increase, the non-stimulation caused by the release of insulin. In addition to inhibiting absorption of sugar, but also inhibit amino acids, fat, cholesterol, VitB12 absorption, and so on. Second, an increase of peripheral glucose utilization of the organization. Shuanggua Lei muscle can be increased permeability of cell membranes of glucose or insulin and to strengthen the receptor-binding cells into the role of muscle to promote the use of glucose. Third, there is to strengthen the role of insulin. Shuanggua Lei drugs currently used are: ① double-p Fox (hypoglycemic Ling, phenethylbiguanide, phenformin. DBI): Each 25mg, daily 25 ~ 100mg, ② metformin (metformin, metformin): each 0.25g, per day 0.25 ~ 1.0g. Shuanggua Lei drug indications: ① Ⅱ in patients with type 2 diabetes, especially with obesity and diet control are not satisfied. ② when used with sulfonylurea plus exercise therapy are ineffective. ③ Ⅰ of type 2 diabetes patients with large fluctuations in blood sugar, insulin trial Shuanggua Lei reduced the amount. ④ the use of low-dose insulin in patients with the hope that the switch to oral medication for the treatment of allergic sulfonylurea or failure. ⑤ patients resistant to insulin. ⑥ Ⅱ of obesity in patients with blood sugar control are not satisfied, can be combined with the use of SU. Shuanggua Lei drug side effects: toxic reactions are common metal mouth taste, loss of appetite, nausea, vomiting, abdominal pain and diarrhea, and so on. This class of drugs can lead to lactic acidosis, mostly for the soul to hypoglycemic. (3) glucosidase inhibitors: α glucosidase inhibitors (acarbose) is the biosynthesis of sugar to four, after oral administration in the small intestine in α glucosidase inhibition, so that the single-strand break down starch to glucose response to the significant Weakened, slow absorption of glucose, diabetics can effectively reduce high blood sugar after a meal. Its mechanism is different from the first two, and its role in the small intestine, just below 2% of the small intestine to absorb and emit very soon. Acarbose indications: ① diet treatment on the basis of the application of the drug alone, so that the peak postprandial blood glucose decreased, while plasma insulin levels. ② for the treatment of impaired glucose tolerance. ③ for NIDDM, with sulfonylurea, Shuanggua Lei and joint use of insulin. ④ for IDDM, with the joint use of insulin. Acarbose use of the method: every 50 ~ 200mg, three times a day with rice Jiaofu together. Acarbose side effects: flatulence, abdominal discomfort, nausea, vomiting, diarrhea and Chang Ming. 5. Insulin formulations of insulin from the pancreas of animals such as pigs and cattle to extract the insulin from the preparation process. The main pharmacological effect is to speed up the use of glucose; the promotion of glycolysis and glucose Oxide; to promote the synthesis of glycogen; inhibit gluconeogenesis; inhibit the activity of lipase, the fat so that the slower rate of decomposition; to promote protein synthesis; inhibiting protein Decomposition. Clinical prevention and treatment of acute complications, to correct metabolic disorders, to improve resistance to prevent all kinds of infections, improve nutrition, promote the growth of children, and so on, but microvascular and macrovascular complications of chronic diseases such as the ability to control, there are as yet no consensus. Apply to: Ⅰ diabetes; Ⅱ type 2 diabetes with diet and oral hypoglycemic agents in patients with ineffective treatment; diabetic patients with infection or wasting disease, or surgery, or pregnancy, diabetic ketoacidosis, or adult onset diabetes in elderly Acute weight loss are obvious; diabetic kidney disease and renal insufficiency who were. (1) the application of insulin: Insulin preparation and use of the principle of selection must be closely combined with the disease, the general principles of the urgent need for insulin treatment with short-acting categories, and I diabetic ketoacidosis and other acute complications and before and after surgery, his condition Those who can be a long-term stability of the preparation, the length of effect can also be used in combination. The estimated amount of insulin, the normal physiological insulin secretion each day is about 24U, the entire pancreas, after all, every day about 40 ~ 50U. Therefore, in severe cases such as the secretion of very few who can be a day to 40U, at 3 to 4 times injection. Case may be a light from small dose to start 24U, and then based on fasting glucose response to addition and subtraction, where a U-negative, the urine test was negative, or blue, not to increase the amount of insulin or minus 2U; blue-green or orange or ten ~ + + To increase 2 ~ 4U; orange or red brick +++~++++, increased 6 ~ 8U. U-positive patients should be increased according to dose. Also based on 2 hours postprandial and fasting blood glucose and a 24-hour urine volume adjustments sugars threshold for kidney patients with high blood sugar on the need to adjust the calculation method that is (now testing a few milligrams of glucose -80) × l0 × weight ( kg) × 0.6 = higher than the body's normal amount of sugar (mg), according to 2g sugar 1U need insulin. Dose required machinery can not act, we should practice law. In order to obtain precise requirements. (2) insulin treatment side effects and complications: The body can be divided into two groups and local. Systemic reaction ① low blood sugar reactions; ② allergic reactions; ③ insulin edema; ④ refractive disorders. Local reaction injection ① local red skin, swelling, heat, pain and skin nodules occurred. ② subcutaneous fat malnutrition, lack of sebum into depressed. ③ insulin resistance, insulin daily to be more than 200U, which lasted more than 48 hours, at the same time without ketoacidosis and other endocrine disease caused by diabetes are known as secondary insulin antibodies. Insulin pumps: they have the advantage of continuous injection of insulin, blood glucose levels close to the body so that the rationale for years under the conditions of the fluctuations in blood sugar regulation and better, but prevention and treatment of chronic complications can better than traditional insulin therapy is not known. Some of the transplanted pancreas and islet transplantation to carry out more foreign and domestic have been in the clinical trial, most of the post-transplant can only reduce the amount of insulin, long-term effect remains to be seen. Rejection, and other issues to be resolved. At present, the clinical use yet. 6. Acute complications of diabetes treatment (1) diabetic ketoacidosis and coma treatment of diabetic ketoacidosis as the main basis for the diagnosis ① strong positive urine sugar; high blood sugar in the majority of 16.65 ~ 27.76mmol / L (300 ~ 500mg/dl), sometimes Up to 55.5mmo1 / L (1000mg/d1); ② U strong positive; high-blood-general in the quantitative 5mmo1 / L (50mg/dl) above. Treatment should be based on severity of illness. If the early mild, not severe dehydration, acidosis lighter, non-circulatory collapse, patients with a clear mind, just enough for the regular insulin, every 4 to 6 hours, subcutaneous or intramuscular injection every 10 ~ 20U, and Encourage more drinking water, into liquid or semi-liquid, if necessary, intravenous rehydration and treatment of incentives in general are able to control, to return to pre-ketosis. For severe cases, C02 bonding in 0.898mmol / L (20% of the volume) below the blood (HC03) <10mmo1> 5mmol / L; even accompanied by circulatory failure, urinary oliguria Closed, the mind-shun die in a coma, should rescue, concrete measures are as follows: ① rehydration: fluid volume and speed depending on the degree of water loss and cardiovascular function and patients, patients generally by 10% of the estimated weight and speed rehydration, such as Heavier patients, admitted to 1 / 2 to 1 hour intravenous infusion of rapid 1L, every 1 to 2 hours re-1L, gradually slow down every 8 hours up 1L, the elderly and patients with heart disease can be based on central venous pressure monitoring. ② insulin: a clear diagnosis, and blood glucose> 16.65mmo1 / L (300mg/d1) to start accession to the intravenous infusion of normal saline ordinary insulin dose per hour by 2 ~ 8U (generally 4 ~ 6U) infusion, 2 hours after the check blood sugar If the drop in blood sugar <30%> 30% of the original volume will continue to drop until the blood sugar down to <13.88mmo1 2 =" required"> 30Vol% premium to stop when the base (Note: B, E, ECF for the remainder of extracellular base). ⑤ phosphorus up: When ketoacidosis led to the loss of phosphorus, phosphorus supplement in theory is good, but differences of opinion, that there are as renal failure can be induced hypocalcemia and calcium phosphate PAP, increasing the kidney Injury is not as a routine use, remains to be seen. ⑥ induced by the elimination of factors, the positive treatment of complications. (2) diabetic hyperosmolar coma treatment: diabetic hyperosmolar coma basic pathophysiological changes as a result of high blood sugar caused by the infiltration dehydration, electrolyte loss, resulting in insufficient blood volume and shock the brain and kidney damage and dehydration. ① basis for the diagnosis of blood glucose> 33.3mmol / L (600mg/dl); strong positive urine sugar. ② effective plasma osmolality> 320mOsm / L ③ U-negative or weak positive; ④ sodium> 145mmo1 / L. ① rehydration treatment of its principles: rehydration as soon as possible in order to restore blood volume, to correct dehydration and electrolyte imbalance. As the amount of fluid infusion and the degree of dehydration, such as severe loss of the original weight of more than 1 / 10 or more should be in batches in 2 to 3 days make up; in the first hour intravenous infusion of 1 ~ 1.5L, could be the beginning of 4 hours to 1 ~ 3L; rehydration of the dispute lies in the isotonic or hypotonic, when the use of low fluid. At present, most of that to start with, and other fluid, can be avoided, such as a large number of fluid caused by hemolysis, and is conducive to the resumption of blood volume and prevent excessive drop in blood pressure caused by cerebral edema. According to the clinical blood pressure and sodium can decide whether or not to use low-permeability, the blood pressure low sodium <150mmo1> 150mmo1 / L, could start with low fluid. ② the use of insulin: low-dose insulin treatment for diabetes and the principle of ketosis is similar to when the general increase in blood sugar every 5.55mmol / L (100mg/dl) for regular insulin 10U, if there is severe dehydration, circulatory collapse may be intravenous drip , The dose per hour for 5 ~ 10U, No. 1 in total general 100U less than the smaller dose of diabetic ketoacidosis, ③ potassium supplement: with the treatment of diabetic ketoacidosis. ④ treatment of complications: a variety of complications in particular infection, the patient is often the latter part of the cause of death, so for complications from the start should be attached to the rational use of drugs. Syndrome differentiation treatment: (1) heat deficiency: Syndrome: polydipsia drink more, with the drink with thirst, Yanganshezao, good food and more hunger, red urinate constipation, less mamillata Jin Huang moss. Pulse chord slide or a few. Governing Law: Yin heat. Recipe: Diabetes flavored side. Fang pollen in order to reuse Shengjinzhike; heart with the Chinese to Reduce Pathogenic Fire; habitat, Ou Zhi, human milk, Lily Yin Runzao by liquid; stomach and ginger combined with anti-Shang Wei cold. Such as dry mouth Jiamai worse in winter, the puerarin 10g; KUI injuries were constipation plus cassia 30g; heat will increase the yellow junction 3 ~ 6g. (2) Yin Deficiency: Syndrome: fatigue, shortness of breath, spontaneous perspiration, then add to move, thirsty, drink more and more urine, five hot upset, constipation big knot, Yao Xi fatigued, short tongue or mamillata dark side of the tongue have Chihen, moss Jin low thin white, moss or less, thin and delicate veins. Governing Law: Yiqiyangyin. Recipe: Modified ShengmaiYin. Fang benefit ginseng vitality, Shengjinzhike; Ophiopogon Yin Chun-sheng; Schisandra Jin-sheng convergence solution. If the weak, spontaneous perspiration, shortness of breath are serious astragalus Health Canada 30g; more than good food to hungry odoratum plus 10 ~ 15g; thirst worse pollen plus 30g. (3) Yin and Yang deficiency: Syndrome: lack spontaneous perspiration, cold-Zhileng, Yao Xi limp, Jiaogan helix, more and more to drink urine, such as turbidity cream, or edema oliguria, Wu Geng or diarrhea, impotence premature ejaculation, tongue moss white light, pulse Shen Not fine. Governing Law: Yin Yu-yang. Recipe: Jingguishenqi pill. Aconite to Fang, cinnamon warming and recuperating the Kidney-Yang, the fire yuan; Liuweidihuang Shenyin nourishment, in order to Yin-Yang, the co-ordination of yin and yang. If the number of nocturnal or wealth of the people of urine, such as those Alpinia vera increases, the son of silk, the Health ginkgo 10 ~ 15g; oliguria or swelling of Health to increase Astragalus 30g, Atractylodes 10g, Menispermaceae 10 ~ 20g; psoralen plus those who spilled Wu Geng 10 ~ 15g, Wu Yu 10g, nutmeg 10g; of male erectile dysfunction, premature ejaculation Faerie spleen plus 10 ~ 15g, Curculigo 10 ~ 15g. (4) Blood and evidence: Syndrome: the above-card and could see blood stasis syndrome, such as noodles have petechiae, physical pain, numbness, headache, chest pain, Xie Tong, paraplegia, a tongue petechiae, or purple veins under the tongue or Nu Zhang, Blood disorders, such as the microcirculation. Governing Law: promoting blood circulation. Recipe: Taohongsiwu soup. Angelica Fang, Chuanxiong, peony, and Huang, nourishing and promoting blood circulation; peach kernel, safflower blood circulation. If the blood stasis can be used to light the top of the Senate Gadahn, the Leonurus 30g; stasis weight increase while leech 10g, Scorpio 3 ~ 5g. (5) stricken Yin and Yang (found in diabetic ketoacidosis or diabetic coma hyperosmolar coma patients): Syndrome: lack of consciousness, inactive, stupor, drowsiness, coma, dyspnea deep breathing have one taste, dry skin, urine, dry mamillata, vein or micro-stricken and several minor veins. Treatment: back to save Yin Yang Recipe: Modified Shengmaisan. Fang Dabu ginseng vitality, Yang back to save the inverse; japonicus, Schisandra convergence shade Tianjin, thirst heat. If the clock to increase micro-stricken Aconite 10 ~ 15g to reverse back to YANG save; if flaming hot invagination pericardium, which can be closed off outside the application, where appropriate, Angongniuhuang Pill or the crown of heat fails to grasp the situation with Dan. Recipe: (1) black bean soup: black beans (speculation) transfer trichosanthin is not equal to, for batter-Wan Ru Wu, each serving 30 to 50, twice a day, Diabetes Kidney rule. (2) Yu Hu pill: melon wilt root, ginseng equal to the end, such as Wu Shui Wan-large, serving 30 per pill, Ophiopogon soup, for the Diabetes-Yin Deficiency. (3) dry winter Guarang: 30g, Shuijian Fu, governance Diabetes upset. (4) Health root porridge, "Chinese Medicinal Diet": fresh root 30g, japonica rice 50g, to 1500ml water boiled root, Qu Zhi Zhu Yu 1000mL of food. (5) Trichosanthes root winter melon soup, "Chinese Medicinal Diet": de root wilt, claw winter, drinking stew. (6) of pig pancreas soup, "Chinese Medicinal Diet": Canadian pig Yizi yi meters 30g, astragalus 60g, Huai yam 120g, Shuijian Fu. Qigong: Meridian Qi Gong will enable the smooth, high blood, be able to adjust to achieve a balance of yin and yang. General Dynamic sub-Gong Gong and static two broad categories. Jing Gong, such as diabetes common ① cater to the needs of law: that is, conscious breathing training, including the thoracic and abdominal breathing. ② intended to abide by the law: that is, the idea of a centralized body to the site, reaching into the quiet, comfortable realm of law practice. ③ relaxation method: consciously to allow the body to gradually relax the practice of natural law. Practice, quiet environment, to clean air, light eyes closed, rule out the ideas and personal considerations, arrived on the E-tongue. Qigong more schools, there are many monographs introduced. The best time in practice experienced teachers under the guidance of qigong exercises in order to avoid bias. Chinese medicines: (1) Liuweidihuangwan: nourishing Shen Yin, Shui Wan, each serving 10 ~ 15g, day 3. Charge of Diabetes Shenyin inadequate. (2) Jinbian Shenqi Pill: warming recuperating the Kidney-Yang, Shui Wan, each serving 10 ~ 15g, day 3. Diabetes attending recuperating the Kidney-Yang deficiency. (3) Yuquan Pill: Yiqiyangyin, Shuiwan or capsules, by taking note, attending Yin Deficiency of Diabetes. Acupuncture and massage therapy: (1)-pin: Differentiation can eliminate the three main diagnosis and treatment. This disease complicated skin infections easily, the needle must be strictly disinfected. ① extinction on: Dazhui, Feishu, fish, He Gu, too yuan, Jin Jin, Yu Ye, and other points, divided into two groups to use the turn. Dazhui, fish, Hegu needle with diarrhea law, Feishu, too yuan, with pin-up Ping Xie, Jin Kim, Yuyejici not leave needles all the rest can be left pin hole 30 minutes a day of acupuncture: the next day or needle Spurs 1. ② extinction in: Ping-ping up the spilled Pi Yu, stomach and Yu Wan; with diarrhea three adequate needle method, in chambers, and He Gu Chi song, 30-minute stay needle, a needle a day or the next day acupuncture 1. ③ under extinction: reinforcing method Shenshu needle, liver Yu, Yuan Guan, Sanyinjiao point, and so on, point to stay within 30 minutes, 1 second acupuncture every other day. (2) ear: pancreas, endocrine, lung, thirst, hunger, stomach, kidney, bladder, and other off point. Every time the election 3 to 4 points, leaving 20 to 30 minutes needle, a needle or the next day, or buried Ear acupuncture. (3), massage with massage spleen kidney, blood circulation. Xie Qing heat of the role of the desirability of Pi Yu, Shenshu, in Wan, Zusanli, springs, such as pulp for points. In addition foot massage also point to a certain effect, massage the foot reflex zones, such as the head, pituitary, pancreas, kidney, adrenal gland, ureter, bladder, celiac plexus, and so on. Efficacy and prognosis: The Diabetes Control Standards Diabetes is the treatment of diabetes so that the patient's mental and physical strength returned to normal. Blood glucose, blood lipids and HbA1c decreased to normal or near normal levels, to ensure that sick children and young people with normal growth and development and have a strong ability to physical activity. Adult patients were asked to maintain normal work and social activities. Obese patients should lose weight. Since each patient's age. The type of disease and other circumstances vary, treatment and control of individual needs. The elderly are too stringent control of blood sugar, hypoglycemia risk, and even induced complications such as heart disease or coronary heart disease, and should be avoided. 1. Hematuria sugar control (1) the ideal control of fasting plasma <6.1mmol> 25g; Ⅱ diabetes> 10g. After a reasonable recuperate under medical treatment of diabetes, blood, urine sugar control in the normal range, and can prevent complications and delay the occurrence and development, but not eradicate, it should adhere to long-term treatment. Prevention: Diabetes prevention is more important than treatment. Should launch a wide range of medical, health workers, such as diabetes patients and their relatives to work together, learn prevention and treatment knowledge of this disease in order to carry out long-term control measures can achieve better results. The main disease of the treatment diet, medication and physical activity. Avoid over a five-chi, a long-term tension in the spirit of the thought. Appropriate attention to the work and rest, adhere to the physical training to maintain weight and prevent obesity, not to Feigan Anopheles, free hot drinks and tobacco, and sexual restraint. Pay attention to early detection and treatment of a variety of complications, hypoglycemic agents with the treatment of attention when changes in blood sugar, blood glucose decreased significantly, hypoglycemic agents should be adjusted in a timely manner to prevent the occurrence of low blood sugar.

Diabetes mellitus

Key words :
low blood sugar in type 2 diabetes glucose monitoring of blood glucose CGMS drift Abstract Objective glucose monitoring system (CGMS) study of type 2 diabetes (T2DM) treatment to strengthen the process of the characteristics of low blood sugar occur. (1) the subjects were divided into insulin in the treatment group, sulfonylurea in the treatment group and Novo-long treatment group; (2) of the CGMS with 66 cases of patients with T2DM in a stable blood sugar after 72 h blood glucose monitoring, during which the fingertip blood glucose monitoring Spectrum and enter the correction to CGMS, according to the pattern of blood glucose measured in each group to observe the characteristics of low blood sugar occur. And each of the patients with blood sugar testing or related hormones, lower blood sugar occurs when blood sugar and low-sugar or hormone-related differences and similarities. Results (1) the group of low blood sugar more than 12:00,21:00 ~ 11:00 to 5:00 the next day took place, found in up to 2:00. (2) 3 h after meal after meal blood sugar than 2 h can better predict the occurrence of low blood sugar. (3), hypoglycemia, or sugar-related hormone did not change significantly. (4) of insulin Sulfonylurea the treatment group than in the treatment group, the Snow Dragon and hypoglycemia in the treatment group were significantly higher. Concluding CGMS be able to find timely and accurate low-sugar, low blood sugar understanding of the factors and the impact of low blood sugar after the reaction to guide clinical treatment, the development of targeted therapies. Drift of glucose in patients with type 2 diabetes mellitus observed with continuous glucose monitoring system LI Xiang-dong, LI Su-zhen.Kuerle Second People's Hospital, Kuerle 841001, China [Abstract] Objective To study drift of glucose in patients with type 2 diabetes mellitus (T2DM) with continuous glucose monitoring system (CGMS). Methods 66 patients were analyzed to assess incidence of hypoglycemia in patients treated with insulin, sulfonylureas and non-sulfonylureas, respectively, and to obtain characteristic of the hypoglycemia and the level of anti-insulin hormone when hypoglycemia occurred.Results (1) The majority of hypoglycemia occurved during 11:00 ~ 12:00,21:00 ~ 5:00, especially at 2 : 00; (2) Compared with the 2 h postprandial glucose, the 3 h postprandial glucose significantly predicted the incidence of hypoglycemia before next meal; (3) The levels of anti-insulin hormone didn't change significantly when hypoglycemia appeared; (4 ) The frequency of hypoglycemia increased remarkably in group treated with sul-fonylureas compared with that of insulin and non-sulfonylureas.Conclusion CGMS can reflect the characteristic of hypoglycemia accurately and offer valuable inform-ation for us about clinical therapy. [Key words] type 2 diabetes mellitus; blood glucose monitoring, tendencies; glucose drift Blood glucose monitoring is reflected in diabetes patients, an important indicator to guide treatment. In recent years, as a result of type 2 diabetes (T2DM) patients with strict control of blood sugar and to promote the application of early intensive insulin treatment of T2DM, so that the possibility of occurrence of low blood sugar significantly increased. Some of the patients in the treatment of blood sugar during the volatile, with treatment more difficult. Although the fingertip for testing blood sugar spectrum in a timely manner and objectively reflect the changes in blood sugar in diabetic patients, we have been recognized as the most common and most convenient way of a check, but only glucose determination of the moment, the lack of continuity, and due to take The number of frequent blood have been difficult for patients to accept. Applications Division I glucose monitoring system (CGMS) in patients with T2DM on the blood glucose monitoring and analysis of the report are as follows. 1 target and method 1.1 target in March 2006 to June 2007 in the second Korla City People's Hospital of Internal Medicine T2DM patients treated 66 patients, are in line with the 1999 WHO diagnostic criteria. 35 cases in which men and women 3l cases, the average age (58 ± 6) years old, the course l ~ 20 years. 1.2 (1) the subjects were divided into insulin in the treatment group (including pre-mixed insulin aspart and 30), sulfonylurea in the treatment group and the Novo-long treatment group, more than 3, if necessary, a joint group to promote non-insulin secretion agent. (2) of the patients were hospitalized for diabetes health education in diabetes doctors carried out under the guidance of diabetes diet, by the medical staff to guide the activities and accept the oral hypoglycemic agents or insulin treatment, or both combined, the next day to monitor blood sugar finger spectrum, According to the results of blood sugar dose adjustments, so that the fasting blood glucose control in the 6 ~ 7 mmol / L, postprandial 2h blood glucose control in 8 ~ 9 mmol / L. (3) the stability of blood glucose after 72 h application CGMS monitor blood sugar, during which the tip of finger to monitor blood sugar and enter the spectrum to be calibrated. Health care by guiding patients with hypoglycemic drug application records, diet, exercise and so on, and record the specific amount of food and diet, exercise intensity and time, with or without hunger, cold sweat, nervous, dizziness, as the material does not change, and so on. (4) If the patients have a typical response to low blood sugar or glucose test finger <4 2 =" 10.633," p =" 0.005)." 2 =" 1.614," p =" 0.204)," 2 =" 9.139," p =" 0.003),"> 0.05) . Table 3 group of low blood sugar and blood sugar normal blood sugar all day in a row compared with Table 3 shows that postprandial hyperglycemia 3h well in the forecast before going to bed before dinner and low blood sugar, in their 6 mmol / L below, before and during dinner Low blood sugar before going to bed have taken place in 6 mmol / L over, most of the blood sugar in normal range. And 2 h after meal at the average of 6.3 ~ 8.5 mmol / L, although in the control of blood sugar goals, but before going to bed and have dinner before the occurrence of hypoglycemia. 3 discussion CGMS is a new means of monitoring blood sugar, which overcame the fingertip test blood glucose spectrum repeated needle can not be continuous monitoring of blood glucose, and other defects, with continuous and accurate Video, without pain and without prejudice to the merits of daily life, and so on. And download configuration, system analysis, a comprehensive understanding of blood sugar in diabetic patients, found that blood sugar level is too high or too low, and system analysis. At present, insulin for treatment of patients with T1DM and gestational diabetes patients to monitor blood glucose [1 ~ 3], and have achieved good results. To sum up, CGMS is an ideal means of monitoring blood sugar, especially at night with low blood sugar monitoring is all the more important [4]. However, their fingers and capillary blood glucose monitoring and blood glucose value the existence of consistency yet to be further study [6]. Low blood sugar is the sugar concentration below 2.8 mmol / L (50 mg / dl), central nervous system due to the lack of energy sources, the emergence of dysfunction. For the body, this is a strong stress, to the early symptoms of autonomic nervous system in particular, excited sympathetic mainly for the performance of the heart palpitations, weakness, sweating, hunger, pale, tremor, nausea, vomiting, and other long-term Low blood sugar, can lead to central nervous system damage, severe low blood sugar than would appear vague sense of mental disorders, paralysis of limbs, incontinence, drowsiness, coma and so on. As the body's blood sugar in diabetic patients with poor conditioning, especially in the use of hypoglycemic drugs to stimulate insulin secretion or injection of insulin, leading to insulin and glucagon loss of balance, low blood sugar significantly increase the probability of occurrence. This study on the treatment of different groups hypoglycemia χ2 analysis of the situation and found that with insulin in the treatment group and the Snow Dragon and the treatment group compared to sulfonylurea group the incidence of hypoglycemia highest, with a statistically significant difference (χ2 = 9.139, P = 0.003), which may sulfonylurea oral hypoglycemic agents and the role of a strong metabolism for a long time and easy-related accumulation in the body. The study also found that 3 h postprandial blood glucose in the forecast before going to bed before dinner and the incidence of low blood sugar than 2 h postprandial blood glucose is more sensitive. As shown in Table 3, 2 h postprandial blood glucose in the average 6.3 ~ 8.5 mmol / L, according to the ADA standards to achieve the target blood sugar control, and 3 h postprandial blood glucose in the 4.8 ~ 6.7 mmol / L. When the 3 h postprandial blood glucose> 6 mmol / L, in the pre-dinner and bedtime blood sugar in normal range, and when 3 h postprandial blood glucose <6> 0.05), may be long-term blood sugar caused by nerve disorder - caused by endocrine dysfunction. This study found that three groups of patients with low blood sugar more than 11:00 to 12:00, 21:00 to 5:00 occurred, the most seen at 2:00. Night of a longer duration of hypoglycemia. For older patients with diabetes, low blood sugar more than the harm of high blood sugar, serious long-term recurrent low blood sugar can lead to irreversible central nervous system damage caused by variations in patients with personality, mental disorders, dementia and so on. At the same time, low blood sugar can stimulate the heart and brain vascular system, lead to cardiac arrhythmia, myocardial infarction, stroke, and so on. Low blood sugar had been misdiagnosed as heart and cerebrovascular diseases are often reported. Low blood sugar found in a coma for too long can lead to the death of the incident. Elderly patients with T2DM than hypoglycemia at night, can not easily be detected, the great danger that can be taken to a small number of meals before going to bed at night so as to effectively prevent low blood sugar.



References 【】 1 Kemsen A, deValk HW, Visser GH.The continuous glucose monitoring system during pregnancy of women with type 1 diabetes mellitus: accuracy assessment.Diabetes Technol Ther, 2004,6 (5) :645-665. 2 Deiss D, Ha rmann R, Hoeffe J, et al.Assessment of glycemic control by continuous ucose monitoring system in 50 children with type 1 diabetes starting on insulin pump therapy.Pediatr Diabetes, 2004,5 (3) :117-121. 3 Weintrob N, Schechter A, Benzaquen FT, et al.Glycemic patterns detected by continuous subctltaueous ucose sensing in children and adoles cents with type 1 diabetes mellitus treated by multiple daily injections vs continuous subcutaneous insulin inlusion.Arch Pediatr Adolese Med, 2004,158 (7) :677-684. 4 Kubiak T, Hernmnns N, Schrecklinglq J, et al.Assessment of hypoglyeaemia awareness using eontimlous glucose mulfitoring.Diabet Med, 2004,21 (5) :487-490. 5 Chieo A, Vidal-Rios P, Subira M. Tlle continuous glucose monitoring system is useful for detecting unrecognized hypoglycemias in patients with type 1 and type 2 diabetes but is not better thau frequent capillary glucose measurements for improving metabolic contro1.Diabetes Care, 2003 , 26 (4) :1153-1157. 6 shillings Wang, Lu Ming, Chang Yu Pan. Dynamics of blood glucose monitoring system for clinical application. Learning Institute of Military Medical Journal, 2005,26 (1) :63-65. SHI Yi-fan 7. Endocrine and metabolic Concord school (modern clinical medicine books). Beijing: Science Press ,1999,217-223.

college consolidation loans（4）

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college consolidation loans（3）

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college consolidation loans（2）

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Student Loan Consolidation Program

School and College education both are fundamental, as by getting the same one can become a successful person. But education is a costly affair and not every one can afford the same. But today there are many banks and financial organizations that are offering Student Loan Consolidation Program. Under this type of program the students taking the loan for their education purpose need to pay the full amount along with a new loan taken from another lender.
One can get such financial program from Govt. as well as private banks! Whatever be the source one must make sure that it is safe and reputable. Before applying for Student Loan Consolidation Program one should do research about the Interest rates, payment procedure etc. For doing the research work one needs to visit various banks, have a talk with the lenders and compare the interest rates being offered by the banks. By doing so one can come across the best program.
This program is a great way to lower down the loan payments. Under the Student Loan Consolidation Program if the payments are extended then the amount of Interest rate would increase over the period of time. The benefit of such kind of financial program is that the borrower, can payback the loan amount with an extended repayment period. However payment needs to be done on time or else the bank can take legal actions.
One can avail the advantage of the Student Loan Consolidation Program only if he does not have a bad credit history! When applying for this program one can suffer from loosing in of Grace periods, cancellation provisions etc. Therefore one should be careful when dealing with such program

House adopts crackdown on student loan business

WASHINGTON (Reuters) -- The U.S. House Wednesday overwhelmingly passed a bill cracking down on conflicts of interest in the $85 billion student loan market amid a widening scandal.
Adopted by a 414-3 vote, the bill would require colleges and lenders to abide by new codes of conduct; ban gifts from lenders to college aid officers; require disclosure of college-lender relationships; and protect students from aggressive marketing practices.
Investigations by Congress and New York Attorney General Andrew Cuomo have accused lending institutions of providing pay and perks to college financial aid officers in return for being put on "preferred lender" lists shown to students looking to borrow money for their education.
Allegations have also emerged of questionable stock dealings involving lenders, financial aid officers and an employee of the U.S. Department of Education, which oversees the nation's complex student financial aid system.
"Corrupt practices among lenders, schools, and public officials have undermined our student loan programs," said House Speaker Nancy Pelosi in a statement, calling the bill a needed action to clean up the student loan industry.
America's Student Loan Providers, a group that represents student lenders, backed passage of the bill. It said in a statement that revelations of misconduct "are inexcusable and have deeply embarrassed the student loan community."
Facing the world's highest tuition fees, U.S. university students increasingly borrow money for their education. Typical undergraduates leave school today owing around $20,000.
For many U.S. students and their families, college costs are a worry at this time of year with college admission letters arriving in the mail and aid application deadlines nearing.
Under the bill, "preferred lender" lists would not be banned but would be more tightly regulated, while ensuring students have access to lenders not on the lists, as well.
House Education Committee Chairman George Miller told reporters after the vote that the bill -- known as the Student Loan Sunshine Act -- will help restore student loan ethics.
The California Democrat said he hoped the Senate will move swiftly to adopt a similar bill so a measure can be sent to the White House. If the Senate moves slowly, Miller said, "I would be concerned."
California Rep. Buck McKeon, senior Republican on the House Education Committee, said: "We do need to reaffirm our trust in the system. I believe this bill does just that ... I'm hopeful the other body will pick up this legislation."
Edward Kennedy, chairman of the Senate Education Committee, said there is bipartisan agreement on a Senate package of student loan industry reforms that he expects to include in an upcoming Higher Education Act reauthorization bill.
"These reforms will include many of the measures included in the version of the Sunshine Act I introduced in February, including a ban on lender gifts, reform of 'preferred lender lists,' and disclosures to make ... education loans more transparent," the Massachusetts Democrat said in a statement.
In the House, Texas Democratic Rep. Ruben Hinojosa said, "The daily drumbeat of scandal in the student loan industry cries out for action. With the Sunshine Act, we are taking a critical first step towards restoring public confidence."
Some congressional Democrats want further reforms, including a measure to channel more students into direct government loans and away from federally guaranteed loans.
But this effort faces stiff opposition and threatens the business models of major student lenders such as Sallie Mae , Citigroup, Wells Fargo, Wachovia, Bank of America and JPMorgan Chase.