Pill Developed to Prevent Type II Diabetes

Pill Developed to Prevent Type II Diabetes

Postby Captain Picard's Hair » Fri Mar 25, 2011 2:39 pm

Too late for me, and not relevant to Mikey (as a Type I) but it's a step nonetheless.

http://www.sciencedaily.com/releases/2011/03/110323183808.htm

ScienceDaily (Mar. 23, 2011) — A pill taken once a day in the morning prevented type 2 diabetes in more than 70 percent of individuals whose obesity, ethnicity and other markers put them at highest risk for the disease, U.S. scientists report.

The team also noted a 31 percent decrease in the rate of thickening of the carotid artery, the major vessel that supplies blood to the brain. The study, which enrolled 602 participants through The University of Texas Health Science Center San Antonio and seven collaborating centers, is described in the New England Journal of Medicine and has direct implications for the care of 40 million Americans who are pre-diabetic.

"It's a blockbuster study," said senior author Ralph DeFronzo, M.D., professor in the School of Medicine and chief of the diabetes division at the UT Health Science Center San Antonio. "The 72 percent reduction is the largest decrease in the conversion rate of pre-diabetes to diabetes that has ever been demonstrated by any intervention, be it diet, exercise or medication."
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Re: Pill Developed to Prevent Type II Diabetes

Postby Mikey » Fri Mar 25, 2011 2:56 pm

Wow. I never thought I'd see an actual therapy for type-II diabetes - rather than a palliative - that actually attacks the root cause, which is insulin insensitivity. While there are cases (like CPH) in which type-II diabetes is unrelated to lifestyle, the majority of cases are linked to changeable lifestyle choices. I wonder, then, if this will be a grand chemical excuse for people to not change dangerous ways.

I think it's a bit misleading to state that this drug induces a lessening of the thickening of the carotid. Thickening of the arteries is a direct response to locally-perceived blood pressure; pressure is locally perceived as higher when the blood is thickened due to a high amount of glucose-bonded A1c hemoglobin, which is the primary effect of diabetes. Therefore, the lessening of the thickening of an artery is more an effect of the lack of diabetes rather than a direct effect of the drug itself.

Meanwhile, this is nonetheless an incredible breakthrough. Now if we can just get them started on those Shadowrun-style vat-grown pancreases...
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Re: Pill Developed to Prevent Type II Diabetes

Postby IanKennedy » Fri Mar 25, 2011 3:59 pm

Mikey wrote:Wow. I never thought I'd see an actual therapy for type-II diabetes - rather than a palliative - that actually attacks the root cause, which is insulin insensitivity. While there are cases (like CPH) in which type-II diabetes is unrelated to lifestyle, the majority of cases are linked to changeable lifestyle choices. I wonder, then, if this will be a grand chemical excuse for people to not change dangerous ways.

I know a large number of people who would argue about the root cause of diabetes being insulin insensitivity. Our professor for example, who's the only medical expert ever asked to speak to congress on his topic and who isn't from the USA. As the guy who ran the trial said:
Dr. DeFronzo said. "This particular medication does two things -- improves insulin resistance and improves beta cell function, which are the two core defects of diabetes."

We say that the reduced beta cell function is the root cause, not the insulin resistance. If this drug does not address the cause of the death of the beta cell then all it is doing is delaying the onset of diabetes not preventing it.

That's not to say that this isn't important and delaying the onset is very worth while, it just may not be the 'cure' it's being described as. Longer term studies are going to be required to find out.
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Re: Pill Developed to Prevent Type II Diabetes

Postby Mikey » Fri Mar 25, 2011 4:07 pm

IDK... the way it's always been described to me - and I've had a bit of education from doctors and other practitioners on the subject, as you can imagine - is that the differential criterion between type-I and type-II diabetes is that type-I is lack of insulin production (i.e., death of beta cells) and type-II is insulin resistance (i.e., insensitivity.) This drug does not address the death of beta cells, nor did the article ever imply it - it said specifically "type-II diabetes." Now, of course as type-II diabetes progresses, that resistance will lead to poorer function of beta cells, though they will still certainly continue some production; that effect is the only explanation for DeFronzo's statement.
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Re: Pill Developed to Prevent Type II Diabetes

Postby Captain Picard's Hair » Fri Mar 25, 2011 4:11 pm

IanKennedy wrote:That's not to say that this isn't important and delaying the onset is very worth while, it just may not be the 'cure' it's being described as. Longer term studies are going to be required to find out.


Honestly that thought had occurred to me: the word "prevent" is a strong one. The study mentioned that patients had been followed up to four years and 2.4 on average, but will some still develop diabetes later on anyway?
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Re: Pill Developed to Prevent Type II Diabetes

Postby Mikey » Fri Mar 25, 2011 4:16 pm

Indeed, and I was careful to call it a "therapy" rather than a cure - much the same way that pancreatic transplants "cure" type-I diabetes... for up to about three years or so.
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Re: Pill Developed to Prevent Type II Diabetes

Postby IanKennedy » Fri Mar 25, 2011 4:21 pm

Mikey wrote:IDK... the way it's always been described to me - and I've had a bit of education from doctors and other practitioners on the subject, as you can imagine - is that the differential criterion between type-I and type-II diabetes is that type-I is lack of insulin production (i.e., death of beta cells) and type-II is insulin resistance (i.e., insensitivity.) This drug does not address the death of beta cells, nor did the article ever imply it - it said specifically "type-II diabetes." Now, of course as type-II diabetes progresses, that resistance will lead to poorer function of beta cells, though they will still certainly continue some production; that effect is the only explanation for DeFronzo's statement.

Rury Holman (our prof) is a world expert in diabetes, especially type II, and he believes that beta cell function is the root cause. I'm just reading the original article and I have concerns over their method of calculating insulin resistance. We have developed a computer model of the human body that provides that information and they haven't used it. Which is odd as it's been the international standard method for the last 20 years. The problem is that insulin sensitivity cannot be measured, all you can do is look at the glucose and insulin values and try and work out why they are what they are. Our model Homeostasis Model Assessment (HOMA for short) models the various parts of the body and how the interact with each other to calculate values for beta cell function and insulin sensitivity. They seem to have simply calculated ΔI0–120/ΔG0–120×Matsuda index which isn't anything I recognise.
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Re: Pill Developed to Prevent Type II Diabetes

Postby Graham Kennedy » Fri Mar 25, 2011 4:35 pm

He's not joking about his boss. The guy is not just "an" expert, he's one of the foremost experts in the world on the subject. :)
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Re: Pill Developed to Prevent Type II Diabetes

Postby IanKennedy » Fri Mar 25, 2011 4:37 pm

Interesting quote from the original paper:
Insulin sensitivity as measured with the Matsuda index increased more with pioglitazone than with placebo (4.31±0.24 to 7.65±0.34 vs. 4.31±0.30 to 5.23±0.31, P<0.001). Insulin sensitivity as determined with the use of an intravenous glucose-tolerance test with frequent sampling in a subgroup of 191 patients was not altered in either group.

So by one of their chosen methods of calculating IR there was no change in either group. I'm now extremely interested to find out what happens if they use the HOMA model (the standard method) of calculating IR. This does not mean the drug didn't prevent diabetes, just that they may be wrong about the method by which it worked.

Interestingly for type II diabetics beta cell function in type II patients declines throughout their entire life. If this drug is working on preventing or slowing that loss it will also be a potential drug for retarding the progression of the disease it's self. The weight gain (mean 3.6 kg/7.92lb) shown in the trial is a little worrying, particularly as:
Metformin reduces the risk of conversion to type 2 diabetes mellitus by 31%, without weight gain
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Re: Pill Developed to Prevent Type II Diabetes

Postby IanKennedy » Fri Mar 25, 2011 5:00 pm

Interestingly the difference in FPG (fasting plasma glucose, ie glucose levels in the blood when you haven't eaten for about 10 hours) start out about 7% lower in the active group vs the placebo group after one year. However, by 3 years, the difference is down to about 2%. Equally the two hour values also show the same pattern. This suggests that the effect of the drug is falling off over time, again, indicating a delay of progression rather than a cure. It would seem that it may buy you about 5 years.
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Re: Pill Developed to Prevent Type II Diabetes

Postby Mikey » Fri Mar 25, 2011 5:05 pm

That's all well and good. My point was (and remains) that type-II diabetes, unless progressed to a hypothetically advanced state which probably doesn't occur in reality, doesn't involve a total lack of beta cell function. It may involve - most likely, as an effect rather than a cause - impaired beta cell function, with which pioglitazone helps, but that's not the same as complete lack of function. In fact, even type-I diabetics show chemical reaction to sugar intake; I, for example, show almost-normal c-peptide response. Unfortunately, the problem is that it doesn't precipitate any insulin production.

IanKennedy wrote:So by one of their chosen methods of calculating IR there was no change in either group. I'm now extremely interested to find out what happens if they use the HOMA model (the standard method) of calculating IR. This does not mean the drug didn't prevent diabetes, just that they may be wrong about the method by which it worked.


The glucose-tolerance may show that lack of effect because there was no testing done on diabetics; further, I'd call a 602-person experimental group statistically unsound. I also don't recall (though I've been chasing a two-year-old around while perusing this) reading about the size of a control group that was taken at the same pre-diabetic state and treated with lifestyle changes before the onset of diabetes.

IanKennedy wrote:Interestingly the difference in FPG (fasting plasma glucose, ie glucose levels in the blood when you haven't eaten for about 10 hours) start out about 7% lower in the active group vs the placebo group after one year. However, by 3 years, the difference is down to about 2%. Equally the two hour values also show the same pattern. This suggests that the effect of the drug is falling off over time, again, indicating a delay of progression rather than a cure. It would seem that it may buy you about 5 years.


Probably. It is possible, though, that the body can adapt over time to allow for more normal essential glucose production in the liver, "through" the effects of the drug as it were. Lord knows that my pre-prandial morning serum glucose is creeping up and up on average; while the long-acting insulin I take is in general effective, and right at the limit of where my dosage can be without causing rampant hypoglycemic reactions, essential glucose production has began to adapt to it and creep up to non-treated levels.
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