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High Glucose and Insulin Resistance
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03/17/05 01:48
Andrew 
03/17/05 01:48
Andrew 
Glucose or insulin?

Hi Kevin! - You have done us all a great service by pointing out in your website a connection between Dupuytren's and insulin, and indicating the direction we should go if we are looking for a regime to counter the disease.

However, I am not sure why you are so keen on the idea that Dupuytren's has something to do with low insulin. As far as I can see, nothing on your website indicates this. Almost all your 14 points show that there is a possible connection between Dupuytren's and insulin resistance. Now it is known that insulin resistance, by making it more difficult for glucose to get into the cells, causes glucose to back up in the bloodstream, creating an excess. It is not improbable that this excess of blood sugar, in susceptible individuals, causes Dupuytren's, just as it causes other damage in the body. (The quotation from Dr Rosedale's article, which I put in the first posting of this thread, describes a mechanism whereby excess glucose could cause collagen to accumulate.) So this evidence, combined with the evidence of studies that show that Dupuytren's is common in people with diabetes or with high fasting blood sugar, seems to indicate that excess glucose is the culprit. You yourself also pointed out to me that glucosamine is a form of glucose, which leads to the same conclusion. Even in individuals with hypoglycemia it is possible for them to have periods of excessive blood sugar, when their hypoglycemia develops to the 'dysinsulism' stage, when the blood sugar tends to rise dangerously high after a large meal, or when they drink alcohol on an empty stomach.

I don't think there's any need to be too pessimistic that the key to curing Dupuytren's will never be found, or for that matter that because there is an inherited element, nothing can be done to prevent it. (On the contrary, one study quoted by Dr Eaton showed that it is possible for one of a pair of identical twins to have Dupuytren's but not the other, so environmental factors play a part too.) The way forward seems to me to follow these clues, as you yourself have done, and to try out different diets that are thought to keep blood sugar from rising too high. If anyone has tried these (either the high protein low carbohydrate one, or the vegetarian low fat one) and has felt that their Dupuytren's disease has been alleviated, it would be interesting to hear.

03/17/05 01:37
Bigk200

not registered

03/17/05 01:37
Bigk200

not registered

glucose or insulin?

Andrew,

What I have said in my web site is that Dup's seems to be associated with either low levels of insulin in the blood, or low levels of insulin at the CELLULAR level. Could glucose play a part? Yes of course it could and probably does, because it is impossible to talk about insulin without also talking about glucose. They are "joined at the hip", so to speak.

Hypoglycemic persons could certainly experience brief periods when they have excess glucose, but I think you would agree that hypoglycemic's spend the majority of their time with low levels of glucose. And during their periods of low glucose, they will also gravitate toward low levels of insulin. (As a side note, hypoglycemic’s have actually been shown to be "insulin resistant", so perhaps the insulin levels in a hypoglycemic are actually high, much the same as for a type II diabetic?) So if glucose is the "smoking gun", are hypoglycemic persons developing Dup's during their occasional high glycemic periods, or during their longer low glycemic periods? This is a somewhat important point, because it is also commonly recognized that type II diabetics are prone to developing dup's while suffering from high levels of glucose and a diminished effectiveness of insulin at the CELLULAR level. Pulling this all together; is it possible for the hypoglycemic person to develop Dup's during BRIEF periods of high blood glucose, while a type II diabetic develops Dup's while having CONTINUOUSLY high levels of glucose?

The medical and research community is equally confused when it comes to fully understanding the action of insulin and glucose in the body, so I simply don't have definitive answers to these questions. Whether the cause ends up being glucose or insulin, what would it matter? As I said earlier, it’s really almost impossible to talk about one without the other. While we have a pretty good idea what can make a person become a type II diabetic, what is it that makes someone hypoglycemic? The research community hasn’t done much research on this question, and I think that hypoglycemia can be caused by a long list of problems, including dietary deficiencies, or an isolated failure in the endocrine system.

The reason that the cause of Dupuytren’s has not been solved is because it is found in such a wide variety of persons who exhibit seemingly unrelated or opposing medical histories, body types, etc. But looking at the wide range of persons who are commonly associated with Dupuytren’s, I think insulin is a more natural common thread, as compared to glucose. But would I “bet the ranch” on it… NO WAY!

In a similar vein of thought, I thought I would paste below a couple of paragraphs from my website, which are somewhat related to this discussion:


"This web site has implied thus far that DC is only associated with the presence of insulin resistance and/or hypoglycemia. But looking beyond insulin resistance and hypoglycemia, the IDS theory is actually associated with the entire hypothalamus/pituitary/adrenal (HPA) axis, and there are many ways in which malfunctions of these glands can lead to hypoglycemia and/or insulin resistance.

The endocrine system can be thought of as a multi-dimensional model which can be viewed from many different angles. For example, instead of focusing on hypoglycemia and insulin resistance in persons with DC, another view of the multi-dimensional endocrine system might show that hypocalcemia is the common thread in persons with DC, and from yet another view, the common thread might appear to be hypomagesemia (low magnesium). Although this web site could have been written from several different perspectives, insulin resistance and/or hypoglycemia were chosen because a large amount of research is available which could be used to link many seemingly unrelated groups of persons who develop DC.

Regardless of whether the endocrine system is malfunctioning due to dietary deficiencies (vitamins & minerals) or a defective gland (thyroid, parathyroid, pituitary, hypothalamus, liver, kidney, adrenal glands, etc.), or a unique genetic defect, the most direct common thread between these seemingly disparate and unrelated problems is an impaired insulin metabolism. Thus, the name Insulin Deficiency Syndrome (IDS) was chosen.

The endocrine system is remarkable in that parts of the system can down-regulate or up-regulate in response to imbalances that have occurred elsewhere in the system. For example, an insufficient output of cortisol from the adrenal glands will cause the thyroid gland to produce less T4. But the opposite can also be true; an insufficient output of T4 from the thyroid gland can cause the adrenal glands to produce less cortisol. And this is just one example of the many ways in which the endocrine system can exhibit difficult to understand responses. Therefore, the task of discovering the root cause can sometimes be very difficult if not impossible. The difficulty is in knowing which is the chicken and which is the egg."

03/17/05 01:44
big

not registered

03/17/05 01:44
big

not registered

Glucoseamine & Hypoglycemia

I experienced hypoglycemia first hand when I stopped taking
a glucoseamine/MSM/condroitin supplement about 15 months
ago. Note the first part: glucose! Yes, glucoseamine is a form of glucose. I stopped taking it "cold turkey", and I had a really wild ride. I was suddenly hungry hungry hungry.... I ate everything in site and I didn't gain any weight at all. And if I didn't eat, I was always light headed and felt really shaky. It was the weirdest
thing I had ever experienced.

Slowly over time my body began to normalize, and things also got better when I adopted some basic eating guidelines in the "South Beach Diet". And then the final piece of the puzzle fell into place when I added vitamin D and Calcium to my diet (with supervision of a Doctor.) From then on, I've feel better now than I have in years.

If someone is reading this and presently taking glucoseamine, maybe you should try discontinuing it for a while? If it takes you an a wild ride like what I experienced, then perhaps you should consider not taking it anymore?

03/18/05 01:28
Andrew 
03/18/05 01:28
Andrew 
Final word

I started this thread and have made a number of contributions to it, so I'm going to back out now for a few days and give others a chance to have their say. But before I do, let me add one more thing. It seems to me that Dupuytren's should be thought of as not just a disease of the hand but of the whole body (just as glaucoma is not just a disease of the eye, but a symptom of an underlying condition, namely diabetes). We know this because (a) it is often preceded, accompanied, or followed by problems in other parts of the body (such as the other hand, the shoulder, the penis, or soles of the feet) (b) people with Dupuytren's are likely to die younger than those without (try Googling 'Dupuytren's mortality'). If Dupuytren's was just a disease of the hand, like a broken finger, this wouldn't happen. The appearance of Dupuytren's is therefore (as Susan, one of the contributors to this forum, put it) a 'wake-up call' to say that whatever you've been doing to your body over the last few years is not doing it any good. So it behoves us all to try to improve our health generally and cut out any harmful habits. Since there is evidence that in some cases at least there is a connection between Dupuytren's and blood sugar or insulin (whatever the exact connection), this seems a good place to start.

Concerning Kevin's point below about hypoglycemics (not that there is any firm evidence, as yet, that hypoglycemics are more prone to get Dupuytren's than anybody else, except in the fact that alcoholics tend to be hypoglycemic), I would not say that their periods of low blood sugar last longer than their periods of high blood sugar, since as soon as a hypoglycemic feels low they tend to eat something, have some coffee, take another drink, or whatever. So it is quite possible that the periods when their blood sugar is high (and they are pumping out insulin to try and counter it) are actually longer than the periods when it is low. The point about hypoglycemics is surely not that they produce less insulin than anyone else but that they produce more. Of course there are periods (e.g. during the night) when insulin production slows down, but that goes for non-hypoglycemics too, and surely cannot be harmful. No one has ever claimed that fasting (when insulin production ceases altogether) leads to Dupuytren's.

03/21/05 01:11
Michael

not registered

03/21/05 01:11
Michael

not registered

Don~sq~t worry, be happy


Andrew,

Though I've played devil's advocate to some of your points, let me say that I admire your efforts to understand and combat the disease.

In regards to your point about Dup's and mortality, I too went through a phase (see my posts in the topics 'Thoughts about the forum' and 'Dupuytren's and Mortality') where I worried about this. But I eventually realized that there just isn't enough data to know if the increased mortality is due to Dup's per se, or to the conditions like diabetes that are statistically associated with it. The two studies that deal with this (Wilbrand's Uppsala study and Godmundson's Reykjavik study) come to differing conclusions on this point, and there's no way to resolve the issue without further studies. And unfortunately, there don't seem to be any in the works, according to Wilbrand.

So (as many people advised me) there's no point in worrying until it becomes clear what exactly there is to worry about.

Regards, MML

03/21/05 01:10
Anon

not registered

03/21/05 01:10
Anon

not registered

Adding to the mix

Dr Gan's study can be found under Pubmed type in
'Gan BS'.

Anon

03/26/05 01:35
Andrew 
03/26/05 01:35
Andrew 
More on Glucosamine

We discussed earlier in this thread how glucosamine (which is derived from sugar) might have the same effect on cells as glucose itself. The following article confirms this. In view of what it says, especially in the last two paragraphs, it seems all the more likely that if excessive levels of glucose cause Dupuytren's in some people (e.g. diabetics), then the same is true about excessive levels of glucosamine. This may be of interest to Dupuytren's sufferers who have been taking this supplement. (I have omitted a few paragraphs from the middle of the article, where you see [...], but you can easily find them through Google.)

Here is the article:

Scientists Close in on Trigger of Insulin Resistance
Source: Johns Hopkins Medical Institutions
04/15/2002

Extra sugar can cause insulin resistance in cells

In experiments with fat cells, Johns Hopkins scientists have discovered direct evidence that a build-up of sugar on proteins triggers insulin resistance, a key feature of most cases of diabetes.

The results underscore the importance of glycosylation - attachment of a sugar to a protein - as a way cells control proteins' activities, the scientists report in the April 16 issue of the Proceedings of the National Academy of Sciences. The scientists found that at least two proteins involved in passing along insulin's message were unlikely to work properly when coated in extra sugar.

Type 2 diabetes, the most common form in adults, occurs when muscle, fat and other tissues stop responding to insulin's signals to mop up sugar from the blood. The resulting high blood sugar, if uncontrolled, can lead to blindness, amputation and death. Understanding sugar's precise influence on insulin's activity may help improve treatment and prevention, scientists hope.

"Cells don't respond to insulin itself. Instead, a whole cascade of events, set in motion by insulin, eventually causes cells to take in sugar," explains Gerald Hart, Ph.D., professor and director of biological chemistry in the school's Institute for Basic Biomedical Sciences. "We now have an explanation of how sugar can affect these signals, and even a hypothesis for how high blood sugar could cause tissue damage in diabetes - by improperly modifying proteins."

Hart's lab discovered 18 years ago that sugar is used routinely inside cells to modify proteins, turning them on and off. The more commonly known protein-controller, phosphate, actually binds to some of the same building blocks of proteins as sugar does. If proteins have too many sugars on them, they can't be controlled properly by the cell and are unlikely to work correctly, suggests Hart.

"We think we've come across a major mechanistic reason for insulin resistance," says Hart. "These cells developed insulin resistance simply because their proteins, and specific proteins in fact, had more than the normal number of sugar tags."

If key proteins laden with sugar are present in patients with diabetes, the findings may provide a target for developing new strategies to deal with this growing public health threat, says Hart. While diabetes can be fairly well controlled by diet and carefully monitoring one's blood sugar levels, finding a way to remove extra sugar tags may help treat or prevent diabetes someday, the researchers suggest.

"Textbooks frequently and incorrectly show glycosylation only happening to proteins on the cell surface," says Hart. "Complex sugars are added only to proteins outside the cell, but simple sugars are used all the time in the nucleus and cytoplasm to modify proteins. It's this glycosylation that happens inside the cell, involving simple sugars, that is the key in insulin resistance."

The "simple sugar" to which he refers is O-linked beta-N-acetylglucosamine, a complex name that condenses to a difficult acronym - O-GlcNAc - with an ugly pronunciation -- "oh-gluck-nack."
"Our experiments show that increasing O-GlcNAc on proteins is, by itself, a cause of insulin resistance, rather than an effect or a coincidence," says Vosseller. [...]

In the body, sugar (glucose) is changed into glucosamine, which is changed into O-GlcNAc. Other scientists have shown that giving cells or animals excessive amounts of sugar or glucosamine, along with extra insulin, leads to insulin resistance. The new findings provide an explanation for others' experience with animal and laboratory models of insulin resistance.

There has been little study of glucosamine, a commonly used dietary supplement, in people. It is suggested that people taking glucosamine consult their doctors if they are concerned about the possibility of increasing their risk of developing diabetes.

03/27/05 01:52
Andrew 
03/27/05 01:52
Andrew 
Which is the best diet?

Michael - thank you for your kind words. By the way, for a good article about the effects of drinking lots of coffee, try putting 'caffeine insulin resistance' into Google.

Earlier on in this thread you argued that since westerners are tending to get fatter on the whole, then - if I am right that fat cells protect against Dupuytren's - one should expect the number of Dupuytren's cases to be going down; but this argument is not very logical. One might equally well argue that as increasing fatness is a sign of unhealthier diet, one would expect the rate of Dupuytren's to be going up! Alternatively, the two factors (the damaging effect of an unhealthy diet versus the protective effect of extra fat cells) might balance each other out and the number of Dupuytren's cases remain unchanged. So I don't think the number of Dupuytren's cases can be used as an argument for or against my hypothesis that fat cells, up to a certain point, protect against Dupuytren's by mopping up excess glucose in the bloodstream.

Just about the only thing we know for sure about Dupuytren's (apart from the fact that it affects men more than women) is that (according to studies cited on Dr Eaton's website) diabetics are five to ten times more likely to get it than non-diabetics. This tends to suggest that - in these cases at least - it is caused by excessive blood sugar. (An alternative explanation could be that it is caused by the high levels of insulin that are usually provoked by high levels of blood sugar; however, this seems less likely, in view of the fact that type 1 diabetics, who don't make enough enough insulin, are just as likely to get Dupuytren's as type 2 diabetics, who make enough insulin, but whose cells have become resistant to it.) In view of this, I speculated that, in cases where Dupuytren's strikes non-diabetics like myself, it affects those whose blood sugar is not stable but swings up and down in a typical hypoglycemic fashion. (Hypoglycemia is apparently quite common even in otherwise healthy people: a study by United Airlines in the 1970s found that 44 out of 177 pilots tested were hypoglycemic.)

If you accept this much, the next step is to ask which diet is best to try to stabilise the blood sugar level and to increase general health. What I did not realise, before I started to research the matter, is that there is a big difference of opinion in diets. All the diets (whether for diabetes or hypoglycemia or general health) agree in certain things: avoid high-glycemic sugary or starchy foods (like soft drinks or cake) and highly processed foods; avoid coffee, smoking, and alcohol; eat plenty of green vegetables; exercise regularly; sleep adequate hours.

But beyond that, there is a large disagreement. Diabetics are usually recommended to eat a high-carbohydrate, low-protein, low-fat near vegetarian diet; hypoglycemics have traditionally been recommended to eat a low-carbohydrate, high-protein, high-fat diet. However, some people recommend the exact opposite for each condition. Others follow the 'zone' diet, which recommends proportions of 40-30-30 for carbohydrate, protein, and fat (that's by calories; by weight the proportion is 9-7-3, since fat has more calories than the other two).

The answer may be found in a book called 'The Metabolic Typing Diet' by W. Wolcott and T. Fahey (a rather unfortunate title, since it suggests one can get thin by frenetic work at the keyboard). This book explains why a diet which benefits one group of people is exactly the wrong diet for another, and vice versa, according to their metabolic type and ancestry. It may well be that people of southern origin (who have a greater tendency towards diabetes, and whose ancestors lived in climates where fruits and vegetables were abundant) do better on a vegetarian diet, while people of northern origin (who have a greater tendency towards hypoglycemia and Dupuytren's, and whose ancestors lived in a climate where meat and fish were the main sources of food) do better on a meat diet.

By the same token, Wolcott and Fahey explain that vitamin D, which Kevin in his website praises as helpful for Dupuytren's sufferers, might not benefit everybody, since for some metabolic types is it actually harmful. In general, though, Kevin's recommendations seem very good.

Dr Paavo Airola, who in 1977 published a book called 'Hypoglycemia: a better approach', arguing that a high-protein diet is unhealthy in the long term, quoted a letter he received from two doctors who had been treating patients for hypoglycemia. They wrote: 'Initially, the diet we recommended was the traditionally accepted high-protein, low-carbohydrate diet. As we became increasingly aware, through the writings of Airola and others, of the disadvantages and dangers inherent in the long-term use of high-protein diets, we began recommending the Airola Diet. We have been doing so regularly for the past 2½-3 years. We have found that for most patients, either diet (and indeed other specific diets such as the low-fat diet described by Pritikin) will help to control the low blood sugar condition equally well. There is a small group of patients who will do much better on one of these diets than they will on the other (of these, the majority will fare better on the Airola diet)...'

Another doctor treating hypoglycemics wrote to Dr Airola: 'Your approach to nutrition has almost infallibly cured hypoglycemia in my experience. For the first two years of practice, I treated hypoglycemia patients with the high-protein diet. I found their hypoglycemic symptoms moderately well controlled, but the patients felt much worse. They developed low energy levels, headaches, skin problems, arthritis, and various digestive disturbances. An interesting observation that I have not yet been able to explain: People on high-protein diets have their hypoglycemic symptoms controlled, but they have worse reactions to smaller amounts of sugar...'

It is therefore up to us not just to accept blindfold the recommendations of one or another of the various diets which are touted in various books or on the Internet, but to experiment, adjusting the proportions of food according to what seems to agree with us best. In this regard I would recommend a very good book called 'The Wright Diet' by Celia Wright (it may be out of print now, but is well worth obtaining), in which the author not only gives some very sound advice on healthy eating and cooking in general, but also teaches how to eliminate and reintroduce different groups of foods to find out which are most suitable for you. For example, one week you may eliminate all red meat and dairy products for four days (enough time to clear the system), and then try introducing them one by one to check for the reaction (headache, cloudy thinking, loss of muscle power, etc.). Another week you might try eliminating all grains and grain products; a third week eggs, white meat, and fish; another week fruits, nuts and sweeteners; three weeks where vegetables of various sorts are eliminated; the eighth week caffeine; and the final week various foods like grapes, apples, and strawberries which she claims contain a natural form of aspirin.

Speaking for myself, I don't think I've got the balance quite right yet, but I have made a big improvement. The lump on my palm is still there, but it is less bothersome than before (for example, when I clean a whiteboard with my hand flat I no longer feel it pulling); a couple of friends have told me that the lump seems less prominent than it was a few weeks ago. My shoulders and knees have become freer. Food also tastes more delicious than it did before. Kevin showed the way, and I jumped in after him. So if, like me, you think that diet has something to do with Dupuytren's and that, even if you have surgery, the disease will continue growing unless you change your diet, come along, jump in, the water is fine!

Andrew Goodson
agdg@supanet.com

03/27/05 01:03
jim h

not registered

03/27/05 01:03
jim h

not registered

Me illogical?

An interesting thread with some well-reasoned posts. It's definitely gotten me thinking - I'm on the thin side with maybe a bit of a blood-sugar roller-coaster. The main problem I have with this sort of theorizing is that it doesn't lead to any testable predictions.

For one thing the progression of Dupuytren's is slow and unpredictable - I can't justify a years-long commitment to a nutritional plan given the slim chance of success, and the fact that no consensus has even developed on wwhat plan to try.

Also, as I've read this forum over the years I've seen countless reports of things that apparently 'made the nodules a little smaller', 'slowed the progression', 'reduced the discomfort' etc. What I've never heard is a credible claim of actual functional improvement - i.e. reversal of contracture.

03/28/05 02:34
Michael

not registered

03/28/05 02:34
Michael

not registered

Me illogical?


Andrew,

It is not logically consistent to claim that fatter individuals are less prone than thin individuals to Dupuytren's (both individuals having similar genetic makeup), and yet also claim that fatter populations may not be less prone than thinner populations with the same gene pool. You cannot square those two claims.

Here's a way to test your hypothesis - and one test is better than a hundred blue-sky theories. Get the per capita number of Dupuytren's surgeries performed in Sweden, say from 1965 to 2004. The numbers would have to be interpreted with care, of course, but if you're right, the trend should be down. You probably could correlate the trend with increasing weight.

Glad to hear your diet & exercise regimen is going so well - MML

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