Sunday 20th August 2017

Diabetes Treatment

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Insulin

Diabetes Mellitus is a chronic disorder of sugar metabolism, usually caused by insulin deficiency or insulin resistance leading to high blood sugar, also called blood glucose. Sugar is present in everyone's blood, including healthy people, but in a diabetic person the glucose in blood reaches too high, pathological levels.

Although not everything is yet fully undestood about diabetes and insulin's modes of action, we know that diabetes impairs the delivery to cells of the body's main fuel, glucose.

So that the single cells receive adequate nutrition, glucose is always present in the blood, and its concentration is regulated by the endocrine cells of the so-called insular apparatus. These cells are in the pancreas and produce insulin, whose deficiency causes diabetes.

Insulin permits glucose to enter all cells and be used as energy source. In diabetes, in the absence of adequate insulin, the glucose builds up in the bloodstream instead of entering the cells, leading to serious health issues.

Diabetes Mellitus is essentially due to absolute or relative deficiency of insulin, derived from insufficiency of beta-cells of the Islets of Langerhans in the pancreas. Their progressive exhaustion in the course of life, also due to congenital deficiency, plays an important role in the pathogenesis of diabetes; and so does their chronic overload for excessive sugar intake.

All this generates two problems: too high blood glucose levels and a deficiency of stored glucose, the body's major fuel source.

Not all cases and types of diabetes are the same. The most fundamental distiction is between type 1 and type 2 diabetes. This is an important distinction in terms of treatment as well.

Type 1 diabetes is also called insulin-dependent diabetes mellitus (IDDM) and juvenile diabetes. As the names imply, it is generally a more serious form of diabetes characterized by insufficient insulin production by the body and usually occurs in people under 40.

Type 2 diabetes is also known as noninsulin-dependent diabetes mellitus (NIDDM) and adult-onset diabetes, since the pancreas still produces insulin, albeit ineffectively used, and the condition usually develops in people over 40.

So, the first diabetes treatment is insulin. By definition, all diabetes type 1 patients and some diabetes type 2 patients are thought to need to take insulin to help keep their blood sugar levels in as normal a range as possible.

Insulin was originally derived from pork (porcine insulin) and beef (bovine insulin) from slaughterhouses and then purified. These animal insulins carried risks, for example contamination from transferring any potential animal diseases into the insulin given to patients. In 1978 so-called 'human' insulin was synthesized, introduced for treatment in the early 1980s and now this is what is generally used.

Insulin, which is the first protein whose complete sequence of amino acids has been determined and whose chemical synthesis has been performed, shows a composition which varies according to the animal species from which it is derived.

Synthetic human insulin's main advantage over insulin extracted from the pancreas of animals is that it causes fewer allergic or autoimmune reactions. Between the hormone insulin secreted by a human body and that of a pig there is only 1 different amino acid, and between the human and cattle insulins there are only 3 different amino acids, it's true, but small differences at the molecular level can have great effects on the whole organism's health. As an example, life-threatening diseases like sickle-cell anemia and cystic fibrosis are produced by just 1 deviant amino acid.

In some type 1 diabetic patients, in addition, the autoimmune reaction which killed the insulin-producing beta-cells in the pancreas acted against proinsulin, making them more vulnerable to this side effect.

Insulin has a protein nature, which means it is not active by mouth because it is destroyed by the digestive juices. It is therefore injected. Aids to insulin therapy are also an insulin pump or an insulin pen.

Insulin pump therapy, also called by the self-explanatory name "continuous subcutaneous insulin infusion (CSII)", continually infuses insulin into the tissue just underneath the skin. Insulin regimes usually consist in a slowly-released, long-acting insulin supplying the day's basal level of insulin and a smaller quantity of fast-acting insulin supplying the bolus level of insulin required after a meal, through two or more daily injections.

Insulin pumps, portable, small and attached to the patient, let diabetics at the same time regulate basal and bolus doses. The bolus dose given by an insulin pump continually throughout day and night varies, and is programmed to counteract the food being eaten. When you eat you can give yourself an additional dose. As the dose can be changed, the pump reproduces the mechanism and availability of insulin in non-diabetics. The basal rate can also be adjusted at any moment. Since the body gets a continuous, regular flow of insulin, the insulin's effect is more constant.

Insulin pens use an insulin cartridge, either replaceable or disposable, instead of a vial. They are easy to use, portable, less time-consuming than syringes. The exact dose required can be accurately pre-set on the insulin pen's dosage dial.

Lantus is an anti-diabetic drug, a long-acting insulin medication to control blood sugar levels. It works by providing a constant quantity of insulin throughout the day, which helps lower the sugar in the bloodstream. It is injectable and should be taken once a day. Lantus possible side effects are reactions at the site of injection and low blood sugar levels.

 

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Diet

There is some controversy over the role and importance of diet in diabetes treatment. Although diet has certainly a major role in diabetes prevention, particularly but not only in genetically susceptible individuals, it's not been established that dietary restrictions are sufficient to treat diabetes without insulin in all cases. Medicine writer Hans Ruesch says, in his book Slaughter of the Innocent:

"In fact today, as in Hippocrates' day, diabetes is preventable through appropriate diet. Although a ruined pancreas cannot always be restored to full efficiency, the only effective treatment, if the damage is not too far gone, consists in a simple diet - which is of no advantage to anyone, except to the patient."

Ruesch was a great author, a pioneer in the line of arguments put forward on this site analyzing and criticizing the medical foundations of animal experiments. That obviously does not mean that he always got it right. I think that there is a confusion here between prevention and treatment: in the prevention of diabetes, as of many other major disesases of countries with advanced economies, diet plays a key role. Even in the presence of a genetic predisposition to diabetes, a correct nutrition may be enough to prevent the development of the illness, as exemplified by the fact that, although 20 to 30 percent of children are born with a genetic predisposition to diabetes, most do not develop the disease. But in the treatment, there are distinctions to be made, like the one between type 1 and type 2 and the severity of the illness.

The World Health Organization recommendations are consistent with this:

"Healthy diet, regular physical activity, maintaining a normal body weight and avoiding tobacco use can prevent or delay the onset of type 2 diabetes. ...eat a healthy diet of between three and five servings of fruit and vegetables a day and reduce sugar and saturated fats [mostly found in meat and other animal products] intake. "

A large, recent study published in the American Journal of Clinical Nutrition and reported in Scientific American is only the last in a long series of research that have found a link between red meat and diabetes risk:

"Daily Red Meat Raises Risk for Diabetes, Large Study Says. People who eat as little as one serving of red meat a day, whether it is processed or unprocessed, have an increased chance of getting type 2 diabetes."

A review of meta-analyses, considering many different studies and therefore carrying more weight than a single study, came to the same conclusions on the right diet and weight loss as crucial in diabetes prevention:

"Diets rich in whole-grain, cereal high fiber products, and non-oil-seed pulses are beneficial. Whereas, frequent meat consumption has been shown to increase risk... Obesity is the most important factor accounting for more than half of new diabetes' cases; even modest weight loss has a favorable effect in preventing the appearance of diabetes. Also, physical exercise with or without diet contributes to a healthier lifestyle, and is important for lowering risk."

Being overweight favours and anticipates the onset of diabetes. The obese suffer from gallstones and kidney stones with a frequency 4 times greater than slim people: as for diabetes the frequency is tripled and for apoplexies it is doubled compared to slim subjects.

However, whereas a good diet may very well be enough to prevent diabetes, it may not be sufficient in the treatment of all diabetic patients. It is part of the treatment for all patients, and can be the only treatment for some patients. But in the treatment, there are distinctions to be made, like the one between type 1 and type 2 and the mildness or severity of the illness. This does not mean, however, that diet and exercise are not a major part of diabetes treatment. Both type 1 diabetics and type 2 diabetics should follow a healthy diet, anyway, also considering that this is good advice for anyone.

Jan Derbyshire, who developed diabetes when she was 27, says in an interview in the British paper The Sunday Times of 4th June 2000:

"The medical profession's attitude towards managing diabetes has changed over the past 10 years. At first, I was given a very strict diet to follow, with no cakes, chocolate or alcohol. Now you're simply told to eat a healthy, balanced diet and consume sweet stuff and alcohol in moderation. So, as long as I remember to inject insulin 20 minutes before I eat, I can pretty much forget I'm diabetic."

Generally, it is believed that it is possible for all diabetic patients to lead a normal life if they follow dietary recommendations and restrictions and take insulin injections.

Anyway, healthy eating and weight control are not just a strong factor for diabetes prevention but also for diabetes treatment, and may even help to stop taking insulin, as this post titled "I have come off insulin!" on a forum for diabetics shows:

"I have been dieting since May, and have lost almost 5 stone now. Ever since starting the diet my sugar levels have been so low I have been in danger of hypos (I used to inject Insulatard twice a day and Novarapid before meals) - After about a week of dieting stopped injecting regularly, just checking myself after meals to make sure I was still under control.
I went to see my HCP and to my surprise he took insulin off my repeat prescription immediately! This gave me a slight panic - What if I needed some! How would I cope knowing it wasn't available? Well everything has been fine. I have had a small supply still in the fridge in case of emergencies but have not needed to use it at all.
I have lost almost 5 stone now - I am delighted to report that my levels seem really really good, fasting levels around 4.5mmol and 2 hours after eating is between 5 and 6mmol. This weekend I went to an italian restaurant for lunch, had starter, main and very sweet pudding - Tested myself at home and it was a very reasonable 6.5, so whilst I don't want to say something crazy like 'I'm cured', it's looking good.
I'm due a Hb1Ac in a couple of weeks so it will be interesting to see what that says...
I'm not normally one to blow my own trumpet, but the benefits have been so great it is worth sharing my success with others and hopefully inspire someone else to do something about their weight (if that is a contributing factor to their diabetes). When I was diagnosed a few years ago, the various healthcare practitioners I met said it would help if I lost weight, but if someone suggested I would have to inject insulin any more, I would have given this a try long ago!
Cheers all!
Adam."

It is not just anectdotal evidence that supports better diet as a diabetes treatment. Many studies, especially in recent years, have also tested various diets on diabetic patients and found in particular Mediterranean diets with reduced carbohydrates beneficial.

A systematic review of several 4-week or longer randomised controlled trials that compared a low glycaemic index diet with a higher glycaemic index or other diet for type 1 or 2 diabetes mellitus patients, premising that "Improved glycaemic control through diet could minimise medications, lessen risk of diabetic complications, improve quality of life and increase life expectancy", concluded that "A low-GI diet can improve glycaemic control in diabetes without compromising hypoglycaemic events".

A study published in Diabetes Care, the journal of the American Diabetes Association, found that "a low-fat vegan diet improves glycemic control and cardiovascular risk factors in a randomized clinical trial in individuals with type 2 diabetes".

Similarly, exercise is an excellent therapy since it helps diabetics by reducing their need for insulin. Alcohol excess and smoking should also be avoided.

 

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Oral Antidiabetic Medications

Since, as explained, insulin cannot be taken orally, but on the other hand patients have difficulty in tolerating the treatment of insulin injections throughout their lives, alternative specific remedies which are also active by mouth have been studied. Research led to compounds of the very wide group of the Sulphonamides, which, administered orally, cause a reduction in the level of blood sugar.

Sulfonylureas stimulate the body to produce more insulin and these oral medications have kept many type 2 diabetics off injected insulin. With sulfonylureas we can obtain an increase in the production of insulin by the damaged or inhibited beta-cells; treating diabetes with remedies of this type is only possible, however, if there is still some potential activity of beta-cells. Sulfonylureas are not effective for type 1 diabetics (except for a specific kind) or in type 2 patients whose body's beta cells no longer produce insulin.

Possible side effects of sulfonylureas are hypoglycemia and weight gain. Other oral antidiabetic medications are also available.

 

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Stem Cell Therapy & Islet Cell Transplantation Therapy

A cure for diabetes, as opposed to a treatment, can only be achieved by providing the patient with functional insulin-producing beta cells, with either pancreas or beta-cell transplants. Beta cells are not easily obtainable, and must be recovered from cadavers within eight hours from death. Because of lack of donor organs this is not easy to achieve, and hence the recent research into alternative ways of generating beta cells from encapsulated islet xenografts, islet expansion, human islet cell-lines, and in particular stem cells.

A relatively new possible treatment is stem cell therapy, believed by many scientists to have great potential for many diseases, including diabetes. Stem cells are "non-specialized" cells, found in both embryos and adults, which can develop into diverse specialized types of cell like red blood cells or muscle cells. In diabetes, they may replace missing or damaged insulin-producing beta cells found in the Islands of Langerhans area of the pancreas. They could, furthermore, replace cells of organs or tissues damaged by diabetes, as in the case of retinopathy.

Finally, they may serve to 'reset' the faulty immune system in people at risk of developing diabetes type 1 before the autoimmune response destroys the insulin-producing islet cells, therefore preventing the disease.

For the last use it's early days yet, as there is still not enough evidence. Researchers involved say that this method can be used only if the condition is caught early. Diabetes type 1 may prove to be particularly difficult to cure, because the cells are destroyed by the body's own immune system. This autoimmunity must be overcome in order to transplant cells replacing the diseased ones.

A study carried out in Edmonton, Canada, has produced the method of immunosuppressive therapy known as the 'Edmonton Protocol,' reputedly more effective and beneficial in the initial stages but difficult to replicate. Besides, immuno-suppressant drugs can make patients vulnerable to serious infections and diseases.

Islet cell transplantation therapy has made advances in the last decade or so. Canadian researcher James Shapiro and others developed the Edmonton Protocol, treating a patient with it for the first time in 1999, and publishing a report on it in 2000. This team successfully transferred human beta-cells into 8 diabetic patients who have been living without insulin for almost a year.

Of 36 patients transplanted, 16, that is 44 percent, were insulin-independent after one year; 10, or 28 percent, had partial graft function after one year; and another 10 had complete graft loss after one year. Although insulin independence is generally unsustainable in the long term, the transplanted islet cells work well enough to protect from unconsciousness and severe hypoglycemic episodes. Possibly the main problem facing islet transplantation for type 1 diabetics is the shortage of organ donors.

 

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