August 31, 2009

Studies Shed Light on Falsification and Bias in Medical Studies

First off, I apologize for the drop off in post frequency. One "side effect" of getting a three book contract from a major publisher, as exciting as it is, is that I have to write the two sequels to the first book I sold. That gives me less time to read and report on the diabetes news. I'm still at it, but I'm blogging only about issues that stand out to me as important or those that readers write me email about.

I'm pleased to see that the most recent, extremely poorly designed study intended to prove that low carb diets will give people heart attacks has not raised a furor.

My readers, and most other people who know anything about science, realized that genetically engineering a mouse to be unable to process fat without developing heart disease and then feeding that mouse fat and giving it heart disease proved nothing except that some people will stop at nothing to defend a discredited theory.

Unengineered mice do not get heart disease eating fats. A large number of studies have found that humans do not get more heart disease eating a low carb/high fat diet. You can find links to these studies and to those proving that cutting out fat does not lower heart attack risk in humans HERE.

I also read in another blog that the "high fat" diet these particular mice were fed included a lot of fructose, which we know has a toxic effect on the liver and cardiovascular system.

The way in which these scientists tortured study design to come up with a study that would yield a finding satisfactory to those who share their religious beliefs (eating fat is bad!) along with something else that happened last week, made me think it was time to discuss a study I ran into last year that examined the question of how often scientists consciously misrepresent and skew data. The findings of that study, which got almost no play in the press, were horrifying.

The other thing that brought this to my attention was a visit to a specialist who wanted to prescribe me Celebrex for a foot problem. If you'll recall, Celebrex is a drug very similar to Vioxx--the pain killer that turned out to be a patient killer, thanks to its ability to promote heart attack.

Celebrex is still on the market, thanks to research that appeared to make it look slightly safer than Vioxx, though the official FDA prescribing information includes a warning that it may promote heart attack. What this doctor did not seem to know was that much of the data that had shown Celebrex to be effective turns out to have been faked, as you can read in this March 10, 2009 report published in the Boston Globe:

Springfield doctor accused of fabricating research results.

The specialist who wanted me to take this dangerous drug practices out of the same hospital as the fraudulent researcher. Current prescribing recommendations for Celebrex make it crystal clear it should never be prescribed to anyone with any possible heart disease, which means it should never be given to someone with diabetes. Deleting the fraudulent studies suggests that the very expensive Celebrex is no more effective than Tylenol, too. Nevertheless 2 billion dollars worth of Celebrex is still being prescribed each year. Probably by doctors unaware of the fraudulent research suppporting it's effectiveness.

Which brings me to the study that looked at how common such fraud and other research malfeasance might be. You can read the study in its entirety here:

How Many Scientists Fabricate and Falsify Research? A Systematic Review and Meta-Analysis of Survey Data. Daniele Fanelli. PLos One 4(5): e5738. doi:10.1371/journal.pone.0005738 (May 29, 2009).

This was a metastudy--a study that combined and analyzed data from other, smaller studies. It found,
A pooled weighted average of 1.97% (N = 7, 95%CI: 0.86–4.45) of scientists admitted to have fabricated, falsified or modified data or results at least once –a serious form of misconduct by any standard– and up to 33.7% admitted other questionable research practices. In surveys asking about the behaviour of colleagues, admission rates were 14.12% (N = 12, 95% CI: 9.91–19.72) for falsification, and up to 72% for other questionable research practices.
This is a horrific finding. Almost 2% of the scientists admitted (anonymously) to out right fraud. One third admitted "other questionable research practices" which included doing things like ignoring other previously published studies whose results would cast doubt on their own, nonpublication of results unfavorable to a sponsor like a drug company, and "altering and modifying data “to improve the outcome”".

That is bad enough, but the study also looked at what happened when you asked scientists not to report on their own behavior but about that of their colleagues.

Do that and the incidence of reported fraud (outright falsification and fabrication--making things up) goes up to 14.12--meaning one in seven scientists reports observing such behaviors in peers. The reports of other questionable research practices shoots up to 72%--meaning a whopping majority of these scientists believed they had observed these behaviors.

This should give you pause, because these statistics, as the authors point out, require people to admit to malfeasance, which we know many will not. The actual incidence of intentional research fraud is therefore likely to be much higher.

Another study on a similar topic analyzed impact that drug company sponsorship or the existence of financial ties between researchers and drug companies on the design and findings of studies of Actos and Avandia, the TZD drugs.

You can read this research, in full here:

Factors Associated with Results and Conclusions of Trials of Thiazolidinediones Gail Rattinger1, Lisa Bero. PLoS ONE 4(6): e5826. doi:10.1371/journal.pone.0005826. June 8, 2009.

The researchers here examined
61 published RCTs [random controlled trials] comparing a thiazolidinedione [Avandia or Actos] to another anti-diabetic drug or placebo for treatment of type 2 diabetes. Data on study design characteristics, funding source, author’s financial ties, results for primary outcomes, and author conclusions were extracted.
They found that trials that reported favorable glycemic control results for the glitazone were four times more likely to have a corresponding author with financial ties to the glitazone manufacturer (OR (95% CI) = 4.12 (1.05, 19.53); p = 0.04)."

In addition, "trials with conclusions favoring the glitazone were less likely to be funded by a comparator drug company than a glitazone company." Studies showing favorable results for Avandia and Actos also were "less likely to be published in journals with higher impact factors," i.e. the journals that apply more rigorous peer review to articles before accepting them for publication.

The authors note one factor that makes it likely that the real impact of drug company money on study results is much higher: Though 59% (36/61) of the trials studying Actos and Avandia were funded by industry, "39% (24/61) did not disclose any funding" This makes it very likely that many more of these studies were supported by and skewed by researcher financial ties with the drug companies.

Put the results of these two studies together and what emerges is not pretty. For every doctor whose fraudulent research, delivered in response to the marketing needs of his drug company paymasters, is exposed--as happened to Scott S. Reuben, MD of Baystate Medical Center in Springfield, MA, whose work impelled other doctors to prescribe the questionable drug Celebrex, dozens or perhaps even hundreds go undetected.

The fact that at least 59% of all studies of Actos and Avandia were sponsored by drug companies with a stake in proving them effective, or comparing them unfavorably with their own drugs, and that we don't know the sponsorship of another 39%, makes it crystal clear how little research about the effects of the drugs we take is untainted.

Scientists who are in the pay of drug companies face a lot of pressure to deliver the results their masters demand. The tools at their disposal include outright fraud, or the more subtle techniques described by Ms. Fanelli in the first study above: Neglecting to cite studies casting doubt on the desired result. "Tweaking" statistics, not publishing studies with results showing poor outcomes with the drug, designing studies with flawed methodologies intended to produce the desired result. Etc. etc.

All this should explain to you the reason I look with such skepticism on the drug and food studies that get such play in the press and why I analyze their methodology looking for signs that the study was designed to produce a certain result. In many cases the bias is obvious to anyone who hasn't drunken the drug company Kool-Aid, though apparently not to the peer reviewers.

By the same token, what these studies have not looked at, but what would also result in some useful information, is the extent to which drug company funding raises the likelihood that a study will be reported in the print and TV media outlets that are so dependent on drug company income for their revenue.

Very few of the studies I see that were done by scientists not affiliated with drug companies or other powerful interests make it into the health news headlines--especially not those studies that contradict the findings of the drug company supported research.

As readers of my blog know, I reported years before these topics hit the headlines about the link between Avandia and Actos and heart failure, macular edema (a cause of blindness) and osteoporosis. These studies were ignored by the mainstream press. The mainstream press has yet to publish a word about the problems with the DPP-4 inhibitors, though a considerable body of research suggests they may be promoting cancers. When Avandia was finally revealed for the questionable drug it is, the media jumped on the bandwagon suggesting Actos was a safe alternative, though the data connecting Actos to heart failure and broken bones is identical to that involving Avandia.

In short, it's a jungle out there, and your doctor is much too busy to do the detective work it takes to protect you from the dangerous drugs, whose utility is supported by fraudulent research.

August 25, 2009

Another Cause of Diabetes? Weed Killer in Many Water Supplies Damages Mitochondria and Produces IR

An investigative journalist has learned that the EPA has failed to pass on to the public the information that drinking water in four states and more than 40 municipal water systems contains levels of atrazine, a commonly used herbicide, that violate federal safety standards.

Huffington Post: EPA Fails To Inform Public About Weed-Killer In Drinking Water

Why should you care? Because researchers have found "There is an apparent overlap between areas in the USA where the herbicide, atrazine (ATZ), is heavily used and obesity-prevalence maps of people with a BMI over 30."

Authors of a study that looked closely at this relationship explain,
Given that herbicides act on photosystem II of the thylakoid membrane of chloroplasts, which have a functional structure similar to mitochondria, we investigated whether chronic exposure to low concentrations of ATZ might cause obesity or insulin resistance by damaging mitochondrial function.
They conducted a rat experiment to see exactly what happened to mitochondria in mammals exposed to this herbicide. You can read the full study here:

Chronic Exposure to the Herbicide, Atrazine, Causes Mitochondrial Dysfunction and Insulin Resistance. Lim S, et al. PLoS ONE 4(4): e5186. doi:10.1371/journal.pone.0005186

This study found "Chronic administration of ATZ [atrazine] decreased basal metabolic rate, and increased body weight, intra-abdominal fat and insulin resistance without changing food intake or physical activity level".

The effect was worsened in rats fed a "high fat diet" (which we will look at more closely further on in this post.)

When the researchers looked at the mitochondria of the rats exposed to atrazine, they found
Mitochondria in skeletal muscle and liver of ATZ-treated rats were swollen with disrupted cristae. ATZ blocked the activities of oxidative phosphorylation complexes I and III, resulting in decreased oxygen consumption. It also suppressed the insulin-mediated phosphorylation of Akt [emphasis mine].

These results suggest that long-term exposure to the herbicide ATZ might contribute to the development of insulin resistance and obesity, particularly where a high-fat diet is prevalent.
The "high fat diet" fed the rats--which worsened the effect of this herbicide on obesity--is worth a look. This "high fat" diet was made up of
33.0% shortening, 7.0% corn oil, 10.0% sucrose, 13.2% dextrose, 5.0% cornstarch, 5.0% cellulose and 20.0% casein (by weight).
So it was in fact a high transfat and Omega 6 oil diet that was very rich in sugar. This is a very unhealthy diet quite apart from the fat percentage.

The HuffPost article reports that water customers in some Midwestern cities were sent reports of atrazine levels in their water that underreported actual levels by a factor of 10. According to the article:
based on the quarterly tests, residents of Mt. Olive, Ill., were told that the highest level of atrazine in their drinking water last year was 2 ppb. However, the EPA data shows a spike in June of 16.47 ppb. The same year, residents of McClure, Ohio, were told that the highest level of atrazine in their drinking water was 3.4 ppb. The EPA data shows a spike in June 2008 of more than ten times that amount -- 33.83 ppb.
The states where the highest levels have been reported are Illinois, Indiana, Ohio, and Kansas.

The EPA insists that atrazine poses no public health threat, though male frogs exposed to this herbicide have been known to produce eggs.

Perhaps, the levels of this herbicide might be safe, were they the only persistent organic pollutants (POPs) the public was exposed. But this chemical is only one of the POPs mixing in our blood streams. It joins detectable levels of bisphenol-a, the fertility-impairing organic fluorine compounds that leach from nonstick pans, the birth control pill hormones and pharmaceutical drugs that have leaked into public water supplies, and the pesticide residues that we get from the foods we import from all over the world.

These pollutants in our blood stream probably work synergistically. So the combined effect of all these chemicals may be far more destructive than that of each chemical in isolation.

Obviously, those who will show the strongest impacts from this exposure fall into two groups. The people with the greatest exposure: those who work with these chemicals or live in the most polluted neighborhoods, and those who have genes that already make them prone to insulin resistance and mitochondrial dysfunction. This latter group includes many people with family histories of Type 2 Diabetes.

We know that young, slim relatives of people with Type 2 diabetes often already have signs of mitochondrial dysfunction and higher than normal insulin resistance. (Details, HERE). When these people drink water that contains additional damaging factors like this herbicide they are likely to experience an escalation in insulin resistance,and as we know, as insulin resistance rises, so does post-meal blood sugar, hunger levels, and eventually, weight.

Read the HuffPost article, and if you live in one of the regions discuss, demand that your municipal authorities tell citizens the truth and let the EPA know that you do not want yourself or your children drinking water with detectable levels of a herbicide known to promote insulin resistance and obesity.

UPDATE: September 2, 2009: More insight on how the manufacturer of atrazine herbicide has used its influence to get the EPA to declare atrazine safe despite the evidence here:

HuffPost: Syngenta, Maker Of Weed-Killer Atrazine, Wants Lobbying Documents Excluded From Class-Action Lawsuit

 

August 24, 2009

Antidepressants NOT Depression Associated with Obesity

There is a major contributor to the so-called "obesity epidemic" which never gets cited in the press--the antidepressant drugs which are the most frequently prescribed class of drugs in the pharmacopoeia.

Now a study that analyzes data from the Canadian National Population Health Survey (NPHS), a longitudinal study of a representative cohort of household residents in Canada, finds a strong correlation between the use of SSRIs, Effexor, and the development obesity. Lest you think that this is because depression makes people fat, this same study found no correlation between a history of a major depressive episode and the development of obesity.

It's the drugs, folks.

Here's the study:

Major Depression, Antidepressant Medication and the Risk of Obesity
Scott B. Patten et al. Psychother Psychosom 2009;78:182-186 (DOI: 10.1159/000209349) Vol. 78, No. 3, 2009

How widespread use of these antidepressant drugs is, is very hard to pin down. Anecdotally, it sometimes seems like everyone who has good health insurance is on them.

A report published in 2005 that analyzed Canadian data reported that "...one in five women (19%) in the province over the age of thirty received at least one prescription for SSRIs in the period between August 1, 2002 and July 30, 2003."

Canada's public health system controls access to prescriptions in the way the US system does not. The data for the US is 7 years old and at that time the CDC reported that 1 in 10 American Women were taking antidepressants which were the single most highly prescribed class of drugs in the US. That 2002 report also reported that antidepressant use had tripled over the previous decade, which makes it likely that antidepressant use has risen significantly in the 7 years since those statistics were analyzed.

The Canadian report also points out that
Prior to the introduction of SSRIs, depression was considered to affect only 100 people per million. Since the introduction of SSRIs, prevalence rates for depression are now considered to be in the range of 50,000 to 100,000 cases per million (a 500 to 1,000 fold increase).
One reason for this huge spike in prescriptions is, of course, the heavy marketing by pharmaceutical companies of these drugs--especially to family doctors not trained in psychiatry who are the doctors most likely to prescribe them.

It has long been known to psychiatrists that fully 1/3 of all people who experience episodes of depression recover naturally without any treatment. This is close to the rate of recovery experienced with the antidepressant drugs, however, the drug companies suppressed publication of the studies that would have made it evident that their drugs were often not any more effective than placebo.

You can read one study documenting the impact of drug company suppression of unfavorable research evidence HERE.

In addition, drug marketers deceptively promoted the factoid that that repeated episodes of depression are likely to lead to a form of permanent brain damage resulting in permanent depression. This is a twisted rendering of data that applies only to extremely severe depression of the kind that results in people being institutionalized because they cannot function at all. That kind of depression does not result from negative life experiences but appears to be a brain syndrome like schizophrenia. It is a very different kind of psychiatric condition from the bouts of sadness most people experience at some point of their lives when they suffer a serious loss or find themselves trapped in a situation, like a bad marriage or dead end career.

But this idea that one depressive episode, if not treated, will condemn a person to a life of worsening depression, has been used to scare family doctors into treating the normal periods of sadness characteristic of young people, who are facing the emotional challenges of growing up, as if they were medical emergencies.

People experiencing the normal struggles of adolescence and young adulthood are told that if they don't take the antidepressant drugs they'll end up permanently depressed. When they start feeling better after a month or two on the drugs--as they would without drugs--they are convinced that the drug saved them and are terrified to stop taking it.

Anyone who went through adolescence in the pre-antidepressant days knows it is not true that the periods of depression so common in early life invariably turn into severe psychiatric disease. Most of us grew out of the miseries of adolescence and have normal happy lives no matter how miserable we were when we broke up with our first serious boyfriend.

For many of us, depression was a signal that we needed to get help to learn why we made bad choices or to take the steps needed to get ourselves out of the dead end situations we had become trapped in. Sometimes therapists were helpful in giving us tools that made it possible to do this. Medicating the bad feelings away may prevented us taking those steps or making those changes which improved our lives and eliminated the causes of our depression.

But for the past decade any teen (or adult woman, for that matter) who experiences overwhelming sadness after breaking up with a boyfriend--or after failing to find an exciting career after earning a college degree in English--is very likely to be put on a powerful, mind altering SSRI drug that numbs their emotions--a drug, moreover, that can be extremely hard to stop since it causes withdrawal symptoms. Any teen with insurance, that is, since these drugs can be very costly.

And once people are, essentially, addicted to these mind-altering drugs, they do what all people who are dependent on mood-altering drugs do--defend their need to take the drugs very strongly and often with anger at any one who would take them away from them.

Because people who take these drugs have not learned that depression can be healed without drugs, and have not been taught the psychologically proven strategies that could help them cope with depressive episodes on their own, they are very frightened of what would happen if they stopped the drugs. Since the withdrawal symptoms when they do stop the drugs can be extremely unpleasant and long lasting, they may interpret this as proof that they need these drugs.

The common analogy--promoted heavily by the drug merchants, is that people with depression need SSRIs the way people with diabetes need insulin. This makes it sound like these drugs supply some essential, missing hormone.

In fact, this is completely untrue. The drugs don't supplement serotonin. It is not even clear if they actually raise serotonin levels long term. As the Canadian report point out, "there have been no studies that assess the effects of blocking serotonin over months or years. Most of the forty-two clinical trials for Prozac, Paxil, Zoloft, Celexa, Serzone and Effexor lasted only six weeks." Studies of other impacts of altering Serotonin levels in the gut suggest that long term use of SSRIs may actually lower Serotonin levels.

Some recent research suggests that these drugs actually work by remodeling the neurons in the hippocampus.You can read about what SSRIs really turn out to do, long term HERE.

Other drugs that affect Serotonin levels include Ritalin, Cocaine and Ecstasy. We know these drugs are addicting, but somehow the drug companies have been able to convince doctors that their mood-altering drugs are "habit forming" but not "addicting" though doctors also warn patients that it is dangerous to suddenly stop these drugs,just as it is with addicting drugs.

What all makes this relevant to diabetes is this: There has always been evidence that the SSRI drugs make people gain weight. Now this latest analysis of the Canadian health survey data makes it clear that the weight gain is almost certainly a side effect of the drugs, not of the depression that might have led to the prescription of the drug.

Obesity raises insulin resistance even in people with normal genes. For those of us who have the genes that lead to diabetes--genes that mean that even when we are thin our beta cells are barely keeping up with our insulin needs--the increase in insulin resistance obesity can push us into full fledged diabetes and by the time that diabetes is diagnosed, the high blood sugars we have lived with for years may have killed off so many of our beta cells we don't have a chance of regaining a normal blood sugar metabolism through weight loss.

Indeed, it is not irrational to wonder if the fact that these drugs are the single most frequently prescribed class of drugs in the US may have something to do with the development of the so-called "Obesity epidemic." SSRIs began to be prescribed in the late 80s. The "obesity epidemic" started catching the public's attention a decade later.

Yes, there are many other contributing factors to the obesity epidemic, including a huge growth in portion size. But when you mess with the brain chemistry involved in the pleasure response, one of the things you also do is mess with the in-built brain mechanisms that control satiety--the feeling that you've eaten enough.

A person with an intact brain satiety function is not likely to be able to eat a whole 10.5 ounce cinnamon roll at once. If they do, they will experience unpleasant emotional responses that are the body's way of teaching them that this is NOT something they should do again. Block those emotions, and they will do it again.

If you have become inadvertently addicted to mood altering drugs and believe that they are contributing to your weight problem and worsening your blood sugar control, you will probably need some help to get off them. A therapist who can help you deal with the emotions you will feel when you stop anesthetizing your feelings can be essential. A doctor who knows how to help you deal with the withdrawal symptoms in a way that does not involve putting you on another addictive drug is also essential.

Unfortunately, doctors have been prescribing antidepressants to pregnant women for the past decade too, which may have something to do with the concomitant epidemic of toddler obesity. How is it possible doctors have not considered the long term physiological consequences of exposing fetuses to a drug that remodels the neurons in their brain that control essential brain structures, while the brain is forming?

One reason is that few doctors have the time to read the research about the drugs they prescribe and so they don't understand what SSRIs really do, since they get all their information about these drugs from the drug company reps and the "education" the drug companies sponsor.

But thinking people cannot help but realize that thanks to aggressive drug company marketing a huge sector of the population--much of it young and female--and their babies--have been the subject of a decades long experiment to find out what it is that these drugs really do. The signal that is emerging out of the the very small amount of research NOT funded by the makers of these powerful, profitable drugs, is that they make people obese.

Note: In the comments that respond to this post, I'm asking you to limit your comments to discussion of the relationship between antidepressants, obesity and diabetes and the research connecting these topics. I am not going to make public the fervid and often hostile personal testimonials that are always provoked by any attempt to discuss the research that examines the true impact of these drugs. So don't waste your energy or mine posting them here.

August 19, 2009

Lots of Interesting New Diabetes News

There have been quite a few bits of recent diabetes news that don't, individually, rate a blog post, but are well worth your attention. You can find them on my other blog, the one that tracks updates to my main diabetes web site Blood Sugar 101.

This widget will give you the links:


Also, check out this exciting bit of news which Scott Strumello has just brought my attention to:

Exsulin Corporation Announces Publication Of Phase 2 Trial Results For Novel Islet Regeneration Treatment In Type 1 & Type 2 Diabetes

I've been hearing about INGAP almost as long as I have been following diabetes. This INGAP trial (the drug has been renamed) involves a peptide that appears to actually regenerate islet cells in both Type 1 and Type 2 diabetes. Most importantly, the increased C-peptide values remained "after washout" i.e. after the drug was discontinued.

The company behind INGAP has had a lot of trouble getting funding over the years, probably because a cure would rob big pharma of its chronic disease cash cows.

Let's pray that the next stage of testing of this drug finds it to be safe and that some company that cares more about your health than its profits will get behind it.

 

August 18, 2009

Can Type 2 Diabetes Be "Reversed?"

This is a question a lot of my readers ask me. Their doctors may tell them that if they lost weight they'd reverse their diabetes and there are books on the market that claim the same thing.

Unfortunately, the concept of "reversing" diabetes doesn't hold up well to scrutiny.

The media version is that Type 2 Diabetes is caused by gluttony and sloth and can be prevented or cured by diet and exercise, but the truth is quite different. The research makes it it very clear that overeating doesn't cause diabetes. You can read the documentation for this HERE.

This should help you stop blaming yourself for your condition if you have Type 2 diabetes, but it also implies that if you have the underlying condition, which manifests clear clinical indicators when people with diabetic heritages are young and thin, you aren't going to cure the underlying condition with simple interventions.

But what about the studies where interventions "prevent" diabetes? Well, a lot of them turn out to be studies where a group of people with marginal blood sugars--for example an average fasting blood sugar of 123 mg/dl (6.8 mmol/L)-- do something that keeps their blood sugar at 123 mg/dl compared to another group who start out the same but end up with a blood sugar of 126 mg/dl (7 mmol/L). Because diabetes is diagnosed with strict cutoffs, and the fasting cutoff for diagnosing diabetes is 125 mg/dl (7 mmol/L), the first group "prevents diabetes" and the second develop it. The actual difference between the two groups is minuscule and they both have the same likelihood of developing diabetic complications.

This is what happened in the DPP trial that supposedly found metformin "prevented" people with pre-diabetes from developing diabetes. As soon as the study was over, when the people taking metformin stopped taking it their blood sugar rose the couple of points that put them into the diabetic range. Had they prevented diabetes? Of course not. They had controlled their marginal blood sugars a bit, which is something else entirely.

Weight loss can make blood sugar control easier, and there are studies of people who have pre-diabetic blood sugars that make it look like losing weight can "prevent diabetes." But it is worth remembering that the vast majority of the obese who have pre-diabetic blood sugars will never develop diabetes. So interventions where people with pre-diabetes lose weight and with it the insulin resistance caused by overweight may make it look like they "prevented diabetes" but the intervention may have only been effective in those people whose marginal blood sugars were caused by factors other than the genetic damage that leads to diabetes--people, in short, who would never have developed diabetes.

It is also possible that the diet "prevented" diabetes by cutting hundreds of grams of carbs out of the diet--this happens when you cut way down on food. So blood sugar did drop--while the diet was in force, but will come right back up once the diet is abandoned, as most diets are.

This appears to be the main reason that gastric bypass appears to "reverse diabetes." As I blogged earlier, the long term data do not support this claim and over time people whose blood sugars improved with WLS see them deteriorate again.

Indeed, over my eleven years of interacting with the diabetes community online I have met a lot of people with diabetes who have lost enough weight to make it into the normal BMI range who have maintained their weight loss. I did that myself. I have never met anyone with diabetes whose blood sugars became truly normal after losing weight.

Now before I get a load of email from those of you who have cut the carbs, lost a lot of weight, and now have A1cs of 5.0 and fasting blood sugars of 83 mg/dl I want to take a moment to discuss what I mean by "truly normal".

True normal to me means you can eat anything and end up with a blood sugar under 100 at 90 minutes past mealtime. My son can do that. My 93 year old mother can do that. They don't have diabetes genes and they can metabolize any amount of carbohydrate. That's what I consider true normal. Roughly one third of the population appears to have that kind of blood sugar control.

Normal people are the ones who can go on a low fat diet and drop weight without feeling hungry--and who insist we people with diabetes should be able to do the same thing. Because they really can eat bananas on their oatmeal and see completely normal blood sugars, normal people have no clue what we people with diabetes are up against. And sadly, many doctors and nutritionists appear to have normal blood sugars which is one reason they give such flawed advice to the rest of us.

But those of us who have damaged glucose regulation systems are never going to be normal by that definition. If we think we will, because that's what the doctors tell us, and deny our selves food, overwork ourselves at the gym, because of that belief, only to learn we still can't eat a single bagel at coffee break without seeing our blood sugars soar, we may end up very disappointed indeed.

I believe one reason so many people with diabetes give up after a few years of pursuing diet and exercise is because they don't see the promised "reverse" no matter how hard they work--especially if they use the low fat strategies that too many dietitians and doctors still promote.

But this is a shame, becuase while we can't reverse our diabetes we can control that diabetes.

"Control" means doing whatever it takes to give ourselves normal blood sugars. The people in the metformin study were controlling their blood sugars, not reversing their pre-diabetes. People who cut way back on their carbohydrate intake are controlling their diabetes. People who take a brisk walk after dinner to lower their blood sugar are controlling their blood sugar.

Control is different from reversal in that as soon as you stop using the tools and techniques of control your blood sugars will start climbing right back up.

It may take a couple weeks for the deterioration to set in. I often hear from people who report that have been eating low carb diets for months and have lost weight who say that when they eat carbs now they get much better blood sugars. They probably do, but if they keep eating carbs they will see those blood sugars start rise again and they'll also start gaining weight because the rising blood sugars will trigger the secondary insulin resistance which causes weight gain.

Once you have established good control, you can take the occasional day off without harm. But when the occasional turns into the daily, you will quickly learn the difference between control and cure.

You may have been told some drugs can "rejuvenate beta cells" and that they can reverse your diabetes. This claim has been made (and debunked) for Avandia, and is now being made, very loudly for Byetta and Januvia, though without compelling proof.

In fact, I have never yet seen a single study where the blood sugar improvements produced by a drug lasted for any significant time after the drug was discontinued. With one sole exception: people with Type 2 diabetes who are given insulin for a few weeks at diagnosis appear to have much better blood sugars years later. Details HERE. Unfortunately, very few people are given insulin at diagnosis. Instead they are given oral drugs, and none of them produce lasting effects when discontinued.

Someday science may find ways to truly reverse diabetes. But for now we have to be grateful we have learned how to achieve effective control. Because control works. If you keep your blood sugars normal you can avoid diabetic complications. The best way to do this is to follow the advice you'll find on HERE.

But when you find a method of control that works, don't expect your diabetes to go away. Because your diabetes wasn't caused by overeating or lack of exercise, it can't be cured by those tools either. Your diabetes can be managed, superbly, and we have to be grateful for that. But I'd like to see a cure and for me a cure would mean that I could stop counting carbs, stop testing blood sugar and have the same rock solid normal blood sugars a normal person would have.

The drug companies are not working on cures, because if you were cured you wouldn't need to buy $400 dollars worth of their drugs every month. Their drugs provide only control, and not very good control at that. Until we start funding research that is not undertaking to fatten someone's bottom line things are going to stay that way. Why kill the golden goose?

Drug companies sell doctors (and the public) the idea that their drugs do reverse diabetes. The media tell the public people with diabetes could prevent their condition and save the public a ton of money with a few "simple lifestyle changes."
Don't be taken in. We need cures and true reversal of diabetes and the first step to get there is for society to get out of denial.

The only way we will prevent diabetes is to eliminate the toxic pesticides and other pollutants that flow through our blood streams and modify the brains and pancreases of our fetuses. We need to stop prescribing SSRI drugs that modify blood sugar metabolism to every teenager who breaks up with their boyfriend. We need to realize that plastics are bioactive and get them out of our food supply--and our blood streams. We need to demand that fast food outlets take the MSG, transfat and high fructose corn syrup out of their offerings.

Once people have diabetes, we need to stop blaming them for it, and put some public money into looking for interventions that will really cure them, not just control them.

Will any of this happen? Not likely. Too many people make money from poisoning our environment and selling us bio-destructive products. But that is what we need.

UPDATE August 19, 2009: A day after I published this post, Scott Strumello drew my attention to this incredibly exciting piece of news:

Exsulin Corporation Announces Publication Of Phase 2 Trial Results For Novel Islet Regeneration Treatment In Type 1 & Type 2 Diabetes

I've been hearing about INGAP almost as long as I have been following diabetes. This INGAP trial (the drug has been renamed) involves a peptide that appears to actually regenerate islet cells in both Type 1 and Type 2 diabetes. Most importantly, the increased C-peptide values remained "after washout" i.e. after the drug was discontinued.

The company behind INGAP has had a lot of trouble getting funding over the years, probably because a cure would rob big pharma of its chronic disease cash cows.

Let's pray that the next stage of testing of this drug finds it is safe and that some company that cares more about your health than its profits will get behind it.

 

August 12, 2009

A New MODY Gene Identified

A team at Joslin has been looking for more MODY genes and has found one they say should be added to the six currently tested for. This gene is named BLK. One of its many functions is to trigger insulin production.

The discovery is reported here:

Mutations at the BLK locus linked to maturity onset diabetes of the young and β-cell dysfunction. Maciej Borowie et al. PNAS, Published online before print August 10, 2009, doi: 10.1073/pnas.0906474106

You can read a slightly more informative report on this study here:

Joslin Study Identifies Gene Linked To Rare Form Of Diabetes

MODY is believed to cause 2% to 3% of all cases of diabetes. As reported there are currently eight genes known to cause MODY, but these account for only 85% of those whose family histories are suggestive. Joslin's researchers are looking for the genes that cause the other 15%.

I had volunteered for this study but was unable to participate because one requirement is that participants have a fairly large number of relatives with diabetes. My extended family was too small to qualify.

Unfortunately, when I contacted them two years ago, the Joslin researchers were not willing to share findings with the study subjects. So whatever the benefits of this study for science, it won't help those of you with clear-cut MODY family histories who don't test for the known genes.

For those of you who aren't familiar with MODY, you can find a detailed description of what it is here: MODY: It's Not Type 1 or Type 2 but Something Else.

Because I maintain this MODY page I get a lot of mail from people diagnosed with Type 2 Diabetes who are not fat who are wondering if they have MODY. Most of them do not. Slow onset autoimmune diabetes (LADA) is much more common than MODY and is a much more likely cause for high blood sugars in normal weight people in their 30s and older.

One key thing to understand about MODY is that if you have it, you will have had abnormal blood sugars all your life in some form or other. Blood sugar problems that emerge suddenly and deteriorate over a year or two are much more likely to be autoimmune in nature. The blood sugars associated with MODY tend to stay relatively stable.

So if you are a thin or normal weight person diagnosed with Type 2 diabetes, don't even consider MODY as a possible cause for your diabetes unless you have had a full set of Type 1 antibody tests that are negative, a normal fasting C-peptide test (several forms of MODY only affect insulin secretion in response to meals), have no history of any other autoimmune disease, and have a life long history suggestive of abnormal glucose tolerance.

Unfortunately, as you can see from the reporting of this story in Medical News Today, the only reason scientists are working on MODY is because they hope to find genes implicated in Type 2 diabetes. Once they find a new gene that affects insulin secretion they are done. This means that once you are diagnosed with MODY by a gene test you rarely will be able to find out anything further about the probable course of the kind of MODY you have or even about the best treatments.

This is because all the money in diabetes is in treating the millions with Type 2 and the funding goes into studies that could turn into blockbuster drugs for Type 2.

Meanwhile we people with MODY have to muddle along on our own, often without the help of doctors who have any knowledge of what MODY is.

One thing I would like to make clear before I leave this discussion is this: It is not true that "MODY is simpler to diagnose and treat than the other forms of diabetes," as stated in the Medical News Today article. In fact, most of us with MODY go through years of misdiagnosis and inappropriate treatment.

Each genetic form of MODY is different, and they each require different treatment approaches. Finding the one that works for your own specific case can take a lot of work and because prescription drugs are involved you will need the support of an endocrinologist willing to work with you.

Since many endos have zero knowledge about MODY, many people with MODY get the same miserably poor treatment as the rest of the Type 2 community, and end up with the 8%+ A1cs that guarantee they will develop complications.

Because contrary to what you may read online, every form of MODY causes complications, it is only a matter of which one. MODY-2 (GCK) doesn't cause neuropathy or retinopathy, just fatal heart attacks, often striking the young. The HNF MODYs cause blood sugars high enough to produce all the classic -pathies and the sulfonylurea drugs often prescribed for them do not give the normal blood sugars that will prevent these complications. Only meal-time insulin can do this though some people with MODY-3 respond very well to Byetta. The gene responsible for MODY-3 can also cause congenital kidney malformations that lead to an early death if not diagnosed correctly.

So if you are diagnosed with MODY in any form, you will have to fight very hard to get appropriate treatment. If you just rely on your doctor and believe that MODY is "easy to treat" and that A1cs near 7% are all you need to attain, you are deluding yourself.

I have written to the researchers who identified this latest MODY gene to see if I can find out anything more about BLK MODY, but my guess is that having found the gene they will move on and those who have the gene will be left in the dark as to what it means and how to best treat it.

August 11, 2009

More Insight into What Blood Pressure Level is Safe

People with diabetes have been told for the past five years that they should shoot for a lower blood pressure target than the normal population, ideally one under 120/80. However, recent research is refining the usefulness of this recommendation.

Blood pressure control is the second most import step a person with diabetes can take. That is because high blood pressure promotes both heart attack and kidney failure. These are among the most dreaded complications of diabetes.

But, as I have learned the through my own experience, for some of us striving for the 120/80 blood sugar target can be a problem, because blood pressure tends to drop during the night. When my blood pressure is under the 120/80 target in the daytime I am prone to wake up at 4 AM with the pounding pulse and throbbing heart that occur when my blood pressure has dropped so low that a counterregulatory response kicks in to raise it. I also tend to develop postural hypotension when I am taking blood pressure drugs and may keel over and nearly black out when working in my garden if I kneel down and stand up too often.

So the latest news about how low blood pressure needs to be to maintain health is very reassuring.

The first piece of it is a Cochran Review look at blood pressure studies. The chief researcher here concluded, "'At present there is no evidence from randomized trials to support aiming for a blood pressure target lower than 140/90, in the general population of patients with elevated blood pressure.'"

You can read more about this in the Science Daily report: Blood Pressure Targets: Aiming Lower Produces No Benefit Review Finds.

As reported in Science Daily,
The review is based on the results of seven trials, which together involved 22,089 people. Whilst patients aiming for targets below 135/85 mmHg did succeed in achieving greater reductions in blood pressure than those in the standard target group, there was no difference between the two groups in terms of the number of patients dying or suffering heart attacks, strokes, heart failure or kidney failure.
The researchers noted that they did not break out the data for people with diabetes separately. The study also did not draw conclusions about whether it is safe to lower blood pressure aggressively.

Another study published in the American Journal of Kidney Diseases may provide a bit more insight into when borderline blood pressure becomes dangerous.

Prehypertension, Obesity, and Risk of Kidney Disease: 20-Year Follow-up of the HUNT I Study in Norway. John Munkhauge et al. American Journal of Kidney Diseases doi:10.1053/j.ajkd.2009.03.023 Article in press 8/11/2009.

This study is particularly compelling because it is a huge epidemiological study that studied the relationship of borderline blood pressure and kidney failure over a period of 20 years.

The subjects were 88.2 percent of all inhabitants 20 years or older in Nord-Trøndelag county, in mid-Norway. This kind of broad reach means that the study was more likely to include all kinds of people of all social and economic classes. The one major limitation is that being they were in Norway, the racial mix of the population would have been very limited compared to the population you'd find in a county in middle America.

This study's findings are informative for people with diabetes because, though they did not examine risk specifically relative to diabetes (the medical definition of which has changed greatly over the 20 year period of the study), they did look at risk relative to obesity.

What the Norway study found was this: Borderline blood pressure, defined as blood pressures between 120/80 and 139/89 were not associated with a higher risk of kidney failure or cardiovascular related death until BMI rose over 30.*

This BMI correlates to a weight of 175 lbs in a woman 5' 4" tall or of 203 lbs in a man 5' 9" tall. You can compute your own BMI HERE.

However, while risk rose in the borderline blood pressure category the study also found "In participants with BP less than 120/80 mm Hg, risk did not increase with increasing BMI." [emphasis mine]

BMI can be very deceptive because it doesn't distinguish between body fat and muscle mass, so an athlete may be classified as obese while having a normal or even low body weight percentage.

For example, when my son was playing college football he had a BMI of 32 which is well into the "obese" category, but his body fat was measured at 17%, which is far from obese. But if you aren't a teenaged boy who leg presses 700 lbs, the BMI is usually a pretty good guide to how fat you are.

This study points to two important conclusions.

If you are not obese as defined by BMI, you are probably fine maintaining a blood pressure lower than 139/89.

If you are obese, you should shoot for a blood pressure of 120/80.

This robust long term epidemiological data also appears to back up the NHANES finding that I've blogged about before that overweight is a healthy weight, especially for people in the latter half of life. Overweight is officially defined as having a BMI of 25-29.

If you are trying to lose weight this data might convince you that it is worth shooting for a weight that gives you a BMI under 30. For any of us is an attainable goal--and one we are far more likely to reach than the dream weights suitable for people in their early 20s most obese dieters shoot for.

Choosing an attainable realistic goal is one of the keys to successful dieting. This is because unrealistically low weight goals often derail people's diets. A goal set too low is a goal the dieter can't reach. That failure often frustrates otherwise successful dieters to the point where they often blow off their diet because they still think they are fat--even if they have lost 20, 30 or even 100 lbs.

If you can get to a BMI of 29 you have succeeded, as far as your health goes. For that matter, if you have lost any significant amount of weight you've done something positive for your health. Risk for many conditions rises along with weight as it continues to rise over that 30 BMI.

Set that 30 BMI weight as your first and most important goal. If you can do better. Great! If not, you can rest assured that you have done what you need to do to maintain your health.

One nice thing about blood pressure is that, unlike the case with blood sugar, you can buy a blood pressure meter for a one time charge and test your blood pressrue as often as you want without ever having to pay for a single consumable.

It is a good idea for any person with diabetes to invest in a blood pressure meter and get into the habit of checking your blood pressure now and then to make sure it isn't rising dangerously high without your realizing it. If you see blood pressures over 139/89 make an appointment to talk to your doctor about it. Doctors are much better at treating blood pressure than blood sugar.

I recommend a blood pressure meter that plugs into the wall not the slightly cheaper meters that run on batteries. Long term they are cheaper and you don't end up with unpredictable results from failing batteries. Use a meter that measures arm pressure, not wrist pressure. The arm meters are more accurate. I like the Omrons, personally. They are a lot cheaper on Amazon than at the drug store.

----
* The mention of cardiovascular related deaths comes from the report of this study in Science Daily: Prehypertension, Obesity And Kidney Disease Risks

August 9, 2009

Who Is Really Getting Euthanized

UPDATE: Health Care Protesters Largely From Out of District

The forces trying to keep us from getting a new health care system are bussing operatives in to disrupt congresspeople's meetings. These protesters are not people who live in the district. The pattern of using violence to shut down discourse is very disturbing. Contact your congresspeople and let them know you don't want policy set in response to gun toting people brought in from outside to threaten violence.


The right wing fringe is trying to frighten the public with the claim that health reform will mean those close to death will be forced to die because medical care will be withheld.

They prefer the old system, where only those who are poor, unemployed, or have a chronic condition are forced to die because care is withheld.

Shame on them.

Next time some fear monger tries to tell you that health reform means rationing care, remind them we already ration care.

Those with high status jobs get it. Those who work for small business, are laid off for more than 18 months, or are self-employed in businesses that don't earn enough to pay $12,000 a year for an insurance plan do not. Those with a preexisting diagnosis can't get insurance in many states no matter what they are willing to pay.

I get mail every week from people in their 30s and 40s who have LADA (a slow form of Type 1) and severe Type 2 diabetes who have lost their jobs or have jobs without health insurance who cannot afford to see a doctor or pay for the drugs they need.

The media tells you that there are programs for these people. Try finding one when you are faced with a person whose average blood sugar is running around 400 mg/dl but who the emergency room doctor diagnosed as "Type 2." Until they are in DKA or a hyperosmolar state, or have gangrene or kidney failure, they aren't considered in danger. So if cutting carbs doesn't bring down their sugars, they are SOL.

That looks a lot more like euthanasia to me than denying open heart surgery to a demented 90 year old who can no longer recognize her own family.

Who benefits from the current system? Someone, obviously, because a lot of money is going into funding the noisy rent-a-mob protests against health reform.

A country that can pay billions to bail out banks can afford to provide adequate health coverage for every single citizen. My stomach is turned by the arguments that health care reform must save money, while bank bailouts and car bailouts can lose as much as it takes to "keep our economy stable."

Where is it written that some people have a god given right to get wealthy off the sickness and suffering of others? What sick religious belief tells us that we should only help the suffering if we can do it without it costing us money?

The right wing uses fear, lies, violence and name calling when they have no real arguments left. Anyone familiar with the history of fascism should recognize the patterns. Perhaps the right wing is flinging the word "Nazi" around because they have been dipping so freely into the very techniques the Nazis used to rise to power. Scream your lie loud enough, gather a violent mob to attack those who attempt to argue with you, and you can take over a country. For a while.

I think the American people are better than that. If you agree, contact your representatives in congress and let them know what you want to see in health care reform. Let them know that you don't make death threats to those who disagree with you but that you vote and that your friends with diabetes vote and you will be voting for those who do not let the huge corporate interests define "health care" as "The right to profit from the wealthy, employed, privileged sick."

August 8, 2009

GSK Marketed Paxil Heavily to Pregnant Women Though It Causes Birth Defects

This isn't a diabetes story, but I am writing about it because the manufacturer involved in this case, GlaxoSmithKline (GSK), is the same company that sells and promotes Avandia and Avandamet to people with diabetes. The behavior of GSK in the way it is promoting blockbuster profit maker Paxil is very similar to what we saw with Avandia: complete disregard for the damage the company's drug caused patients.

You can read an excellent discussion of the problems with Paxil in this story published in today's Guardian. It's important to note that these stories appear in a British publication, not a US publication. The reason may have something to do with the fact that US print publications rely heavily on drug company advertising which is illegal in the UK.

Antidepressants once seen as miracle drugs: now risks are becoming evident US courts to hear claims that insufficient attention was paid to dangers to foetus.

What is most disturbing here is that the company specifically marketed Paxil, an SSRI which is notoriously difficult to quit, to pregnant women and women of childbearing age, even when there was growing evidence that the drug caused severe withdrawal symptoms in newborns and possibly was causing heart defects.

Even now the company spokesmen continue to downplay the dangers.

This is the same company that used threats of lawsuits to silence those who attempted to inform the public of the heart-attack potential of Avandia. While intelligent people can debate the facts about Avandia's link to heart attack, the heavy handed Mafia-like tactics the company employed to prevent that discourse from taking place speaks far louder than any research study about what the company really knew about Avandia's side effect profile.

If you are taking any SSRI and are thinking about becoming pregnant or have friends or relatives in that situation, you need to read this article and get the word out about what SSRIs may do to a baby. These drugs can be extremely difficult to stop (which in my youth was the definition of "addictive drug"--a definition which the SSRI manufacturers have managed to change). So women on these drugs should get their doctor's help to detox months before becoming pregnant.

And the rest of us have one more reason to distrust drug companies who prove month in and month out that they are willing to boost profits even if it means ruining the lives of innocent men, women, and now it appears, children.

August 5, 2009

Why Type 2s Get Complications: Delayed Treatement until A1c Reaches 9%

The great tragedy of Type 2 diabetes it's terrible complications are all avoidable, but they occur because family doctors ignore their patients' Type 2 Diabetes until their blood sugars have been damagingly high for many years.

This was documented in a recent study published in Diabetes Care.

Sustained Hyperglycemia Among Patients With Diabetes: What matters when action is needed? Jennifer E. Lafata et al. Diabetes Care, Diabetes Care August 2009 vol. 32 no. 8 1447-1452 doi: 10.2337/dc08-2028.

The abstract is difficult to understand, but you can read a clearer discussion of the results in Diabetes in Control here:

DiC: Income Level Affects Treatment of Hyperglycemia.

As explained in Diabetes in Control, the study found that "41% of people with sustained hyperglycemia failed to get appropriate care within six months; 25% failed to get care within a year; and 11% failed to get appropriate care for as much as two years." "Sustained hyperglycemia" was defined as "two A1cs >8% and no recent medication intensification."

To put this in perspective, it helps to know that an A1c over 8% represents an average blood glucose of 183 mg/dl (10 mmol/L) . But the study found that many doctors did not begin to address these dangerously elevated blood sugars until the A1c was over 9% which represents an average blood glucose of 212 mg/dl (11.8 mmol/L).

Another study also published in the same issue of Diabetes Care puts this information into stark perspective. It tracked
...adults aged ≥20 years who participated in Third National Health and Nutrition Examination Survey (1988–1994) and had complete information, including baseline diabetes status by self-report and measured GHb (n = 19,025) and follow-up through the end of 2000 for mortality.
and found:
Among adults with diagnosed diabetes, having GHb ≥8% compared with GHb <6% was associated with higher all-cause mortality (RH 1.68, 95% CI 1.03–2.74) and heart disease mortality (2.48, 1.09–5.64)
That means that you are two and a half times more likely to die with an 8% A1c than with one below 6%. And these statistics don't even begin to get into what happens to your eye, toes, and kidneys while you're waiting for that heart attack.

All the traditional diabetic complications begin when post-meal blood sugar stays over 140 mg/dl for a few hours. All: Neuropathy, Retinopathy, and kidney failure. So a study that documents that some patients have to wait as long as five years for doctors do get more aggressive about lowering their blood sugars should answer the question, "Do all people with diabetes have to deteriorate?" with this answer: "No. Only those with doctors who ignore their plight."

Sadly even when doctors do "treat" those people with 8% A1cs, they usually do it by prescribing oral drugs which, as you've seen in the many posts I've written about new drugs can usually lower A1c about .5% and almost never can bring A1c down to the 5% range that we know eliminates complications.

That's because the only way most of us can lower our blood sugars to safe levels is to cut back dramatically on our carbohydrate intake. For many of us, just cutting way down on carbs is all it will take. Some of us will need to add carefully chosen oral drugs to a regimen of carb restriction. Some of us, self included, will need to use insulin or insulin and oral drugs along with carb restriction. But with some combination of these tools ALL of us can achieve safe blood sugars and avoid complications.

But sadly most doctors have no understanding of the power of carb restriction. They are deluged with drug company promotional materials which suggest that oral drugs alone are enough for most people with Type 2 Diabetes.

This is simply not true. There is no drug that will allow a person with diabetes to eat 300 grams of carbohydrate a day no matter how "low glycemic" and see an A1c low enough to protect health. Most of us can't eat even 150 grams. I can get away with eating up to 100 grams a day using insulin at meal times but not every day. An intake of 80 grams a day is a much better level for me.

I hope the information in this study should help you understand why so many people with Type 2 diabetes do develop complications and see their health deteriorate: because they spend years with extremely high blood sugars that are continually at levels we know destroy organs.

Knowing this should help put to rest your fears that you are doomed to deteriorate because you have been given a Type 2 Diabetes diagnosis. People whose doctors let them continue with A1cs just under 9% will deteriorate, guaranteed. For that matter, so will many people whose A1cs are at the 7% level the ADA recommends. This is the lowest A1c most people can achieve when taking a full complement of oral drugs or even insulin when they continued to eat diet high in carbohydrate. The 7.0% A1c corresponds to an average blood glucose of 155 mg/dl (8.6 mmol/L) which is still well over the 140 mg/dl (7.7 mmol/L) ceiling of the safe zone.

But if you keep your average glucose at least under 125 mg/dl (7 mmol/L)and ideally closer to 100 mg/dl (5.6 mmol/L) you should end up with the 5% A1c that normal people have and the normal health that they experience.

If you are having trouble getting your A1c down and you aren't getting help from your doctor, try the technique described here:

How to Get Your Blood Sugar Under Control

It's simple and it works.

But what it will take to get doctors to realize that their neglect is causing an epidemic of completely unnecessary death, amputation, blindness and kidney failure is harder to understand.

Type 1s are getting a lot fewer complications these past couple years, thanks to their access to pumps and continuous glucose monitoring. Most Type 1s are shooting for truly healthy blood sugar goals now, and it shows.

But, if anything, many Type 2s are getting poorer treatment now than they were in the 1990s. This is because there are many more oral drugs on the market than there were then. Some NHANES data suggests doctors are less likely to prescribe insulin now to people with extremely high blood sugars, preferring to add oral drug after oral drug, even though the oral drugs are far less effective than insulin in lowering very high blood sugars. As a result the number of people with Type 2 whose A1cs are in the 7-8% range that are the best the oral drugs can achieve climbs--along with the profits of the drug companies whose marketing is so effective in convincing doctors to put off insulin therapy.

Tragic, isn't it?

 

August 3, 2009

Onglyza: Just Like Januvia but with More Serious Side Effects?

NOTE (April 2, 2013): Before you take Onglyza or Januvia please read about the new research that shows that they, and probably all incretin drugs, cause severely abnormal cell growth in the pancreas and precancerous tumors. You'll find that information HERE.

When the FDA approves a new drug it requires no proof that the drug is more effective than similar, existing drugs, only that it is better than placebo. Which is something to keep in mind as Bristol-Myers Squibb unveils what is sure to be a saturation advertising campaign for its new DPP-4 inhibitor, Onlgyza.

This mellifluous moniker is the brand name for Saxagliptin, which alert followers of drug news remember as the Januvia clone developed at the same times as Januvia whose release has been blocked due to its ability to cause "skin lesions" some of which necrotized (i.e. died and fell off) in monkeys.

I have read through the Prescribing Information for Onglyza and cannot see any benefit it offers in comparison to Januvia, the other DPP-4 inhibitor currently on the market.

Setting aside for the time being the advisability of controlling your blood sugar by turning off a tumor suppressor gene Onglyza offers nothing not offered by Januvia.

Both inhibit the expression of the DPP-4 gene for a full 24 hours--which means that if your body was fighting a new, very small DPP-4 sensitive tumor, like ovarian cancer, melanoma, prostate cancer or lung cancer, the drug would keep DPP-4 from killing off the tumor cells.

1. Feeble impact on blood sugar: Onglyza lowered A1cs that averaged 8% by .5%, which does not bring them anywhere near a safe level even by the anemic standards of the ADA. When the highest dose of Onglyza was compared to a placebo, it allowed only 14% more of those taking it to achieve 7% A1cs.

To better understand how "Effective" it is, consider what that A1c really meant: Onglyza lowered the average fasting glucose in those who took it from 171 mg/dl to 162 mg/dl (9.5 mmol/L) to 162 mg/dl (9 mmol/L). It lowered the average two hour post-meal blood sugar reading from a damaging 278 mg/dl (15.4 mmol/L) to an equally complication-guaranteeing 235 mg/dl (13 mmol/L).

So my immediate question would be: Why take this drug which is likely to cost 3 or 4 dollars a day to "achieve" blood sugars that are still high enough to lead to amputation, blindness and kidney failure when for the same money or less you could use insulin to get normal blood sugars?

2. Negative impact on the immune system. Inhibiting the DPP-4 gene, which produces an enzyme that rids the body of GLP-1 by chopping it up, lowers blood sugar because GLP-1 lowers blood sugar. However DPP-4 is used by the immune system for other functions most doctors know nothing about. Januvia's initial testing showed that it caused changes in white blood cell counts which the drug company dismissed as being of unknown significance.

Onglyza has a stronger impact on your immune system's white blood cells. In the prescribing information we read:
There was a dose-related mean decrease in absolute lymphocyte count observed with ONGLYZA. From a baseline mean absolute lymphocyte count of approximately 2200 cells/microL, mean decreases of approximately 100 and 120 cells/microL with ONGLYZA 5 mg and 10 mg, respectively, relative to placebo were observed at 24 weeks in a pooled analysis of five placebo-controlled clinical studies. Similar effects were observed when ONGLYZA 5 mg was given in initial combination with metformin compared to metformin alone. There was no difference observed for ONGLYZA 2.5 mg relative to placebo. The proportion of patients who were reported to have a lymphocyte count ≤750 cells/microL was 0.5%, 1.5%, 1.4%, and 0.4% in the saxagliptin 2.5 mg, 5 mg, 10 mg, and placebo groups, respectively. In most patients, recurrence was not observed with repeated exposure to ONGLYZA although some patients had recurrent decreases upon rechallenge that led to discontinuation of ONGLYZA.


Translated into English, this means than in 1 person in 100 who take it, Onglyza lowers the white blood count to a dangerously low level.

If your doctor prescribes Onglyza without requiring that you have a blood count periodically, you can be sure the doctor has not read the prescribing information. Few doctors do.

3. Onglyza conflicts with common drugs and grapefruit juice Because of the way it is removed from the body Onglyza may build up in the blood stream when taken with common yeast medication, ketoconazole, as well as with erythromycin, calcium channel blocker verapamil, and grapefruit juice. Onglyza levels also rise in people with poorly functioning kidneys. The manufacturer says that dose must be cut back in people using these drugs. Whether busy doctors will know this and warn patients about lowering the dose when needed is another story.

4. Onglyza raises the peak Concentration of Sulfonylureas and TZDs. This makes it more likely people whose doctors prescribe this new drug with a sulfonylurea drug will experience hypos. Onglyza also reduces the peak concentration of metformin.

5.Side effects The main side effects reported with Onglyza are the headache and runny nose that are also found with Januvia and which result from the inhibition of the immune system these drugs cause. Over time, my experience with taking Januvia for several months was that the headaches increased in intensity in a way that made me glad to stop taking the drug.

However, Onglyza also causes other immune reactions: As reported, "Hypersensitivity-related events, such as urticaria [rash] and facial edema [swelling] in the 5-study pooled analysis up to Week 24 were reported in 1.5%, 1.5%, and 0.4% of patients."

Januvia also turns out to cause rashes, including, very rarely, the life threatening Stevens-Johnson syndrome where people's skin peels off the body. It is significant, though that rash did not appear as a side effect of Januvia until after the approval testing was complete. That Onglyza produced such a high rate of rash during testing seems to suggest that it has a higher potential to disrupt the immune system.

6. No evidence that this or any other DPP-4 inhibitor preserves beta cells I mention this because the drug reps are selling these drugs to doctors claiming, based on weak animal evidence that these drugs preserve beta cells. No drug can preserve or regenerate beta cells when blood sugars are rising over 140 mg/dl for long periods of time, because sustained high blood sugars cause glucotoxicity--poisoning of beta cells. With the many years that BMS has been testing Onglyza you can be sure they have run every test they could find to demonstrate beta cell preservation and the complete lack of any cite to this in the prescribing information suggests they could not find it.

Why Take Onglyza?

Nothing in the prescribing information suggests any advantage in taking Onglyza compared to Januvia, while at the same time suggesting strongly that Onzglya's impact on the immune system is stronger than Januvia's. No research was done into whether Onglyza increases the incidence of tumors in those who take it, and because of the very small numbers involved in the clinical trials and the way the drug companies bury tumor incidence (combining benign and cancerous tumors in one category, as in the Januvia trials), that data is not likely to emerge.

Nevertheless, I'm sure a BMS drug rep is hard at work motivating doctors to switch patients to their new drug. Don't be surprised if your doctor suggests you enroll in a "study" using Onglyza, as this is a common way to divert patients from an existing drug. The "study" will provide you with one or two month's free supply of the drug because the companies know that once you are used to taking it you are likely to continue taking it. You'll be seeing free samples and eventually saturation advertising on diabetes web sites and TV.

The really sad part is that the net effect of all this will be only that patients with A1cs of 8% whose fasting blood sugar is well over 150 mg/dl and whose post meal blood sugars are in the range the ADA long ago defined as causing blindness (over 200 mg/dl two hours after eating) will take another expensive drug that ensures they won't get the kind of control that prevents the classic complications.

If you have blood sugars that high before you pay a couple hundred bucks a month for a potentially harmful new drug try the following:

1. Try the technique described here: How to Get Your Blood Sugar Under Control. It really works. Even for people who have had diabetes for as long as a decade.

2. Add extended release metformin if you can tolerate it and have no kidney or liver problems. Metformin is much more effective and less prone to cause digestive distress when used along with a diet lower in carbohydrate.

3. If cutting back on the carbs in your meals and adding metformin doesn't lower your blood sugar to safe levels (Under 140 mg/dl after eating) demand that your doctor send you to an endocrinologist so that you can get a tailored insulin regimen that gives you normal blood sugars.

Do not settle for the kind of insulin regimen family doctors usually prescribe which almost always leave you with blood sugars that are damagingly high. These inadequate insulin regimens are designed to keep your blood sugar high so as to avoid hypos--and to avoid the need to give you the kind of diabetes education routinely offered people with Type 1. With proper diabetes education you can avoid hypos and get great control. But for most Type 2s, to get the right kind of insulin regimen prescribed you will have to find a young, knowledgeable endocrinologist who will take the time to work with you on tuning your insulin regimen.

If your doctor won't help you get normal blood sugars, and insists that all you need are oral drugs fire him or her and find one who will give you the help you need.

Every person with diabetes can achieve normal blood sugars and normal blood sugars produce normal health.