October 30, 2009

Does 5.5 A1c Predict Retinopathy?

A new, high quality study which I cited in my Updates to Blood Sugar 101 blog found a steep increase in the incidence of retinopathy in people not diagnosed with diabetes whose A1cs were 5.5% or more. The study found that the predictive value of the A1c was much stronger than the predictive value of fasting blood sugars in the same population.

At first glance this might be a very disturbing finding to those of us who find it difficult if not impossible to lower our A1cs below 5.5%. I have not been able to do this even when eating a very low carb diet. My A1cs are almost always between 5.7% and 5.8%.

I've discussed why some of us have higher than expected A1cs in another blog post.

But I want to raise another point here, one that is often lost when researchers use A1c:

The A1c reflects average blood sugar values over time, but there are many ways to attain an average.

In fact, what the A1c really measures the amount of glucose that has gotten bonded onto red blood cells over a period of time. The more exposure red blood cells have to high blood sugars, the more glucose they accumulate. Since these red blood cells live about 3 months, the A1c is supposed to reflect three month's worth of blood sugar exposure. In reality, though, the A1c reflects the several weeks right before the test, much more than it does the whole three month period.

Studies that compare CGMS readings with A1cs conclude that that A1c gives a close approximation to average blood sugars for a population as a whole, and much rougher approximations for the average blood sugar of the individuals in a population.

Note, however, that people with unusually high or low concentrations of red blood cells will get A1c readings that do not reflect the actual concentration of glucose in their blood. So will people whose red blood cells have longer than normal lives and those with certain genetic oddities that affect their red blood cells' ability to bond to glucose.

But even in people with absolutely typical red blood cells, two people with the identical A1c can achieve those A1cs while experiencing very different patterns of daily blood sugar fluctuation.

For example, a 7% A1c has been most recently equated with an average blood sugar of 155 mg/dl (8.6 mmol/L). A person can achieve this average by maintaining blood sugars that oscillate between 85 mg/dl (4.7 mmol/L) before meals and 225 mg/dl (12.5 mmol/L) after meals or they can get the same A1c by maintaining a blood sugar that oscillates between 130 mg/dl (7.2 mmol/L) and 180 mg/dl (10 mmol/L). Depending on which pattern they follow, the likelihood of developing diabetic complications is very different.

This was clearly demonstrated by the comparison of two studies--the UKPDS and the Kumamoto Study--where participants had the same 7% A1c but very different complication profiles because their post-meal blood sugars were very different. You can find the citations to the comparison of these studies HERE.

So before we panic about the finding that as A1cs go over 5.5% the incidence of retinopathy spikes upward, we need to give some thought to what the underlying blood sugar fluctuations might have been of the people with 5.5% and greater A1cs in this population.

An A1c of 5.5% corresponds (in large populations) with an average blood sugar of 112 mg/dl (6.2 mmol/L).

Since this group was made up of people not diagnosed with diabetes, we can make a pretty good guess at what kind of diet they were eating: One very high in carbohydrates. Remember, nutritionists consider 300 grams a day a normal carbohydrate intake.

It is likely some of these "normal people" who were prediabetic. In that case, they were likely to be experiencing very high post-meal numbers that dropped back to normal after two hours or even went low, as happens with reactive hypoglycemia. If that were true, they would be were seeing oscillations that veered between 75 and 150. The average of these two values just happens to turn out to be 112 mg/dl.

We already know that exposure to post meal blood sugar levels of 140 mg/dl (7.7 mmol/L) is associated with a rise in many different diabetic complications. So it no longer is mysterious why that 5.5% A1c might be the lower boundary after which retinopathy diagnoses start to rise steeply. Those "normal" people with the 5.5% and higher A1cs were probably eating high carbohydrate meals throughout the day and spending hours each day above that 140 mg/dl threshold that is already
documented as the level at which diabetic complications start to ramp up.

The graph showing normal people's blood sugars, which you will find HERE, shows that there is a significant proportion of "normal" people who are going up over 140 and staying there for almost 2 hours after eating their normal high carb breakfast. They are likely to do this every day and probably see similar patterns after lunch and dinner too. My guess is that it is these "normal" people who are most likely to developing diabetic complications in the prediabetic range that corresponds to A1cs at and above 5.5%.

But there is another blood sugar pattern that also leads to that 5.5% A1c--the pattern in which the blood sugar stays near 112 all day long, or perhaps where there is a relatively high fasting blood sugar--110 mg/dl, and very narrow fluctuations at meal time, perhaps up to 120 and then back down to 90.

This is the pattern characteristic of people who control their blood sugar by cutting way back on carbohydrates and using drugs like metformin and/or insulin to flatten out their blood sugar peaks. Many find that they cannot prevent higher than normal fasting blood sugars, but they can easily keep their blood sugar under 120 mg/dl after meals.

For people who achieved a 5.5% A1c--or even one slightly higher--by keeping their blood sugars under 140 mg/dl most of the time, the risk for retinopathy may well be much lower.

None of the published large scale studies links complications to post-meal blood sugars because post-meal numbers are too expensive to monitor in a large group, so it is impossible to prove this, but anecdotal reports from those of us in the online diabetes community who have kept our blood sugars under 140 mg/dl for years at a time suggest this is true.

So if you can keep your A1c under 5.5%, you can feel confident that you are doing what you need to do. If you can't, you are in the majority of people with diabetes and there is no need to panic if you keep track of your post-meal highs and keep them under 140 mg/dl as much as possible. (The technique described HERE will help you do just that.)

And if you do go high from time to time--and we ALL do--don't panic. It takes many hours spent at high blood sugar levels day after day, month after month, over a period of years that promote complications. If you spike high for an hour or two every now and then, it is not likely to cause massive damage.


October 28, 2009

Antioxidant Vitamins Raise Insulin Resistance and Render Exercise Useless











The first is this study, available in full text:





To read a description of this study in layman's terms view:
Reuters: Antioxidants may increase diabetes risk







October 26, 2009

Gestational Diabetes

I frequently receive emails asking me about Gestational Diabetes (GD), which is the term used for diabetes that is diagnosed only after a woman, previously considered normal, displays abnormal glucose tolerance test results during pregnancy.

Because obstetricians do a very good job of diagnosing and treating GD, I have not discussed it on my web site. If you are pregnant and have GD your doctors are almost certain to give you insulin to normalize your blood sugars. The blood sugar targets given pregnant women are much lower than those given the average person with Type 2 diabetes--low enough to ensure health. Follow them and you should avoid the problems associated with GD that were suffered by those of us whose GD was not well treated in the past.

Some women have found the chat boards at Diabetic Mommy helpful for finding support.

The real problems with GD only start after you give birth to your baby and bid goodbye to your obstetrician. Why? Because the average family doctor still appears to believe that GD is nothing more than one of the many complications of pregnancy and that if your blood sugar returned to "normal" after delivery, you need do nothing else.

The problem here is that the family doctor is all too likely to define "normal" as meaning "having an A1c under 7%" or, if he's a bit better educated 6.5%. Perhaps he won't even run an A1c test but will merely send you for a fasting glucose test. If the result comes back under 125 mg/dl, he may tell you you "aren't diabetic" and that will be that.

Unfortunately, if you have experienced a diabetic pregnancy, "that" is far from that. Because no matter how "normal" your doctor may tell you you are, you would not have developed GD unless your ability to secrete insulin was so borderline, before you started your pregnancy, that the stress of adding your baby's metabolic demands to that of your own organs exhausted it.

Relieving this stress by giving birth to your baby may return you to your previous state--but even if it does, the fact that you had GD should make you realize that your blood sugar control is only marginal, and this means that any other stressor might well push you back into full fledged diabetes.

What are those stressors? There are many.

1. Environmental pollutants that increase insulin resistance or damage the beta cells. These can include exposure to pesticides and industrial chemicals. Atrazine--a commonly used herbicide has been linked to increased insulin resistance. Arsenic, which is given off by power plants, has also been linked to diabetes. So have PCBs.

2. The use of FDA approved medications known to raise blood sugar or increase insulin resistance. These include cortisone treatment--either injections or prednisone pills, most SSRI antidepressants and the atypical antipsychotic drugs.

If you wonder if a drug you are taking can stress your blood sugar control, download the official FDA "Prescribing Information" by googling the name of the drug and the words "Prescribing Information" and look in the "Side Effects" section of the Prescribing information for the word "hyperglycemia." Drugs known to cause weight gain also may cause the same kind of stress to your marginal insulin production capacity.

You can find links to the studies that discuss environmental and pharmaceutical causes of insulin resistance and diabetes HERE

3. Gaining more weight. Though weight gain is often the result, rather than the cause of insulin resistance, if your weight gain results from overconsumption of fructose and eating a high carbohydrate diet, even a low fat one, some of your new weight is likely to be intracellular liver fat, which has only recently been recognized as a significant cause of increased insulin resistance. Carbohydrates not dietary fat turn out to be what raises the triglycerides that get deposited in the liver.

4. Autoimmune attack on the beta cells of the pancreas. A small but significant proportion of those who develop GD suffer from LADA a slow developing form of autoimmune diabetes. These people may experience a slight improvement in their blood sugars after they give birth, but over time their ability to secrete insulin will decline because there is currently no way to halt this kind of autoimmune attack.

What Can You Do?

The best approach to take if you have experienced a diabetic pregnancy is this. Once every month or two, test your blood sugar at home after meals. If you can't afford the expensive prescription strips, use the cheaper strips and meter sold at Wal-Mart under the "Relion" brand.

If you see values over 140 mg/dl one hour after eating, test more frequently. Blood sugars routinely going over 140 mg/dl are capable of damaging your beta cells leading to full fledged diabetes. Even with out diabetes blood sugars in the "pre-diabetic" range have been shown to be capable of giving you the early diabetic complications.

If you see blood sugars over 140 mg/dl an hour or more after you eat, cut back on carbohydrates using the advice you will find here:

How To Get Your Blood Sugar Under Control

Cutting back on carbohydrates is usually all most people need to regain normal blood sugars, even those who have been given diagnoses of Type 2 diabetes.

When Diet Might Not Work

If you were thin when you became pregnant and still developed Gestational Diabetes--or if you developed GD very quickly after becoming pregnant no matter what your weight, your situation may be more complex. Pregnancy often gives the first sign that a person may have one of the rarer forms of diabetes often called "Type 1.5." If you think this might be the case, read these pages:

LADA - Slow Onset Type 1 Diabetes With Some Type 2 Features

MODY - It's Not Type 1 or Type 2 But Something Else

Before you attempt to diagnose yourself, please be aware that MODY is much, much rarer than LADA. But the incidence of LADA appears to be increasing swiftly as part of the whole society-wide explosion of autoimmune disease and if you have any other autoimmune disease in the family, or have relatives diagnosed with Type 1 diabetes the chance you might have a rare form of "Type 1.5" goes way up.

It is also worth noting that while most overweight people who get GD are most likely to move on to an ultimate diagnosis of "Type 2" diabetes, overweight people also can develop autoimmune diabetes. Unfortunately, doctors often assume any overweight person must have Type 2 diabetes and do not run the tests that could diagnose LADA. No matter what you weigh, if your "Type 2 diabetes" continues to deteriorate, does not respond to oral drugs or to cutting carbohydrates, it may not be Type 2 diabetes at all.

Since LADA requires a very different kind of treatment than regular Type 2, this is significant. Oral drugs will not correct LADA and over time a person with LADA who is not given insulin can end up in the emergency room in a dangerous state called "Diabetic ketoacidosis" that happens when the pancreas stops making insulin.

So if you have had a diabetic pregnancy, and afterwards your blood sugars continue to rise, even if you cut way back on carbohydrates--especially if you have a family or personal history of other autoimmune-related disorders, such as authoimmune Thyroid disease or rheumatoid arthritis--insist that your doctor test you for the antibodies associated with Type 1 diabetes to see if you actually have LADA.

If your family doctor isn't familiar with LADA--and many are not--insist on seeing an endocrinologist, ideally one associated with a large hospital that has a medical school.

Most women who were diagnosed with GD in mid pregnancy probably do have the genetic makeup that over time leads to the development of Type 2 Diabetes. If this is your situation, and you see abnormal blood sugars after eating, you will respond strongly to cutting back on your carbohydrate intake.

And because you got warning of borderline high blood sugars early, you can rejoice because you have been given a golden opportunity to prevent your diabetes from progressing because GD gave you the warning which let you catch oncoming Type 2 diabetes very early, before it has been given a chance to ravage your organs.

Aggressive control with diet and modest exercise, aided, perhaps by metformin, if your doctor will prescribe it to you, should keep your blood sugars in the normal range for decades.

You also will want to feed your children diets that are not high in carbohydrates because chances are if you don't handle them well, neither will they. Teaching them that each meal does not have to start with bread, continue on with potatoes, and end with dessert can go a long way to helping them stay metabolically normal no matter what genes they have inherited.


October 22, 2009

Only Christians Get Type 1 Diabetes?

The JDRF just sent me one of those mailings that makes me question whether to send them another dime.

You know the kind I mean--the ones that contain expensive "gifts" intended to guilt you into sending them a bigger contribution, but which, if you have already sent a contribution or two, make you wonder why your money went to buy greeting cards or stickers and expensive postage for oversize envelopes instead of funding research that might help people with Type 1 Diabetes.

I get a lot of these expensive mailings from the JDRF and they are turning me off to the organization.

This one was more annoying than usual, because it contained a big fat pack of Christmas cards. And I mean "Christmas" cards. Red and green with text and imagery that even on the cards that did not use the "C" word still made them unsuitable for sending to people who aren't Christian.

So I came away wondering why the JDRF's fundraising geniuses decided to send out a fundraiser that carries the subtext that people who do not celebrate Christmas need not feel guilty for not sending them money. Bad move folks!

But least they didn't send out candy cane stickers like the ADA does every year. Which reminds me it's time to remind you that before you respond to the American Diabetes Association you should check out what percentage of your dollar will go into "activities"--in California it may be less than 33% elsewhere not much better. The Charity Navigator gives them the very lowest ranking possible--one star out of four.

The ADA raised $213,464,233 last year. That's a lot of money. It does NOT fund its journals which are subscription only and very expensive--and which researchers must pay to get their studies published. Did it fund direct research? No. Because that isn't the ADA's mission.

So where did that money go? Good luck in finding out. Perhaps it went into printing and distributing flyers telling people to eat healthy whole grains, pasta and bananas or urging them to keep taking Avandia until more studies are done. That's the main "educational" message I've seen from the ADA over this past year. And of course it must be expensive gearing up to put "Diabetes friendly" labels on low fat boxed breakfast cereals--that's the ADA's next big "breakthrough".


October 20, 2009

Utterly Flawed Research Claims a Spurious Benefit for Mangosteen

Every now and then a piece of nutritional research crosses my desk that is so poorly conducted that I can't resist the temptation to post it here and use it as an example of how people who are supposed to be scientists degrade themselves in the pursuit of results that will please their corporate sponsors.

The study can be read in all its glorious full text awfulness here:

Evaluation of Mangosteen juice blend on biomarkers of inflammation in obese subjects: a pilot, dose finding study. Jay K. Udani. Nutrition Journal 2009, 8:48, doi:10.1186/1475-2891-8-48

The way this study is being reported in the media can be seen here:
Science Daily: Mangosteen Juice Could Protect Health In The Obese

So what's wrong with this study? Let's take a closer look.

The abstract of the study says "The purpose of this study was to evaluate the effect of multiple dosages of a proprietary Mangosteen Juice blend on indicators of inflammation and antioxidant levels in obese patients with elevated C-reactive protein (CRP) levels." Okay, that sounds reasonable.

So let's look at the methodology. Forty-four people were given tests of inflammatory markers like CRP. These were "screened" out of an original population of 122 people, though the researchers don't tell us what they were screened for.

These people were broken into four groups. Three of the groups were told to drink a branded mangosteen juice product twice a day, each group drinking it in different sized doses. The fourth group were given a placebo to drink, though we are not told what size dose they were given. So far this sounds reasonable.

But when you red the full text description of what the subjects were actually given to drink you see at once that the Science News report title is flawed. Because the researchers didn't really give any of their subjects mangosteen juice. Instead they gave them a branded "mangosteen juice blend" where only the "primary ingredient" was mangosteen juice.

And they had no idea what percentage of the juice blend was mangosteen, because the branded juice blend also contained:
apple fruit juice, pear fruit juice, grape fruit juice, pear fruit puree, blueberry fruit juice, raspberry fruit juice, strawberry fruit juice, cranberry fruit juice, and cherry fruit juice.
Now the way that the FDA defines a "primary ingredient" all something has to do to be listed first on the label is to make up a greater percentage of the total of the food in question than the ingredients that follow it.

So since this product contains 9 other juices or purees, the mangosteen might easily make up only 11% of the juice, while each of the other ingredients made up 9 or 10% of the product.

So whatever benefits the study found for the blend, it tells us little about the effects of mangosteen juice, because the substance being tested is probably 90% other juices, several of which--blueberry, raspberry, and cranberry juice have already been found to have very slight health effects (though probably the research that "prove" those benefits isn't much stronger than this research.)

Now let's look at the placebo: Here's how it is described.
The placebo consisted of water, sucrose (3 g/30 ml), citric acid, red grape juice concentrate, fiber complex, grape skin, natural flavors, red #40, cloud (ester gum), whey protein isolate, sodium benzoate, xanthan gum, blue #1, and caramel color.
Is a sugar water solution with a fruit juice NOT found in the other juice mixture, whey protein, artificial colors, and preservative a true placebo when compared with a mix of fruit juices?

It is very possible that any difference attributed to the mangosteen juice blend--which more honestly should have been called a blend of "standard fruit juices and puree with a touch of mangosteen"--might only be due to the fact it didn't contain sucrose, whey protein, or the chemical additives in this bioactive "placebo."

But let's move on. The conclusions section reports,
HS-CRP measurements dropped after 8 weeks treatment compared to baseline in all 3 dose groups and increased in the placebo group. The changes from baseline were not significant but the comparison of change from baseline was significant for the 18oz group when compared to placebo (p=0.02).[emphasis mine]

Other markers of inflammation (inflammatory cytokines) and a marker for lipid peroxidation (F2 Isoprostane) did not show any significant differences when compared with placebo. There was a trend towards a decrease in BMI in the juice groups.
Either I'm missing something here, or the conclusion of this study was that there were no real, or at least statistically significant differences found between the three groups drinking the juice and the placebo juice. Statistically, the results of the study could have been the result of chance.

But because the researchers needed to find proof that their sponsor's product worked--did I mention that the study was sponsored by the maker of the branded juice--they looked for some way to turn insignificance to significance, and they found it by computing the average change from baseline and glory be, this statistic derived from a meaningless statistic turned out to achieve statistical significance in the one groups of mangosteen blend drinkers that drank the largest dose.

But wait, let's look a little more closely at the make up of the three groups of juice drinkers. There were 9 people in the group whose change from baseline rose to statistical significance, which is a very small number. In contrast, there were 11 people in the group that drank the lowest dose of juice and 12 in the group that
drank the middling dose. Only 8 people were in the control group.

This is a lot of variance. It makes me think any statistically valid comparison between the groups highly suspect, especially when what is being compared is the statistic involving both mean and standard deviation which start to lose meaning as the size of the groups compared gets smaller.

Let's have a look at that standard deviation. That's the statistic that shows us the extent to which individual values clustered around the average. The smaller it is, the closer the clustering. As it turns out, the standard deviations seen in the "change from baseline" were very large: the average was 0.90 but the standard deviation was a whopping ± 9.5 [no units given] for the placebo group. The decrease in the one group that supposedly rose to significance was an average of -1.33 with a ± 3.0 standard deviation.


But, though by now you might think it couldn't, it gets worse. Because lets look closer at the groups involved. How well matched were they?

As it turns out, not very. The placebo group's average age was 45. The average ages of the groups drinking the juice were 52, 33, and 50. Given that the measures of inflammation being measured are very age sensitive, comparing groups of significantly different ages appears to invalidate the idea that what we had here was anything approaching a properly designed controlled trial. The measures of "obesity" were not very well matched either.

The description here claims that BMI and body fat percentage "trended downwards." This is backed up with Table 2 which to the eye that has any experience with the way weight fluctuates over the eight week period of this study, makes it clear that the "trend" was only in the mind of the hopeful sponsor. In fact, using the selective technique used by these researchers, we could say that the Placebo "trended" towards achieving weight loss benefits. But of course, it didn't any more than the juice because this study has by now completely lost any claim to being scientifically useful.

The study abstract concludes by stating
..a proprietary mangosteen juice blend (XanGo Juice) reduced CRP levels (increased change from baseline) compared to placebo for those taking the highest dose of 18 oz. per day. Further studies with a larger population are required to confirm and further define the benefits of this juice.
Only in the full text did the researchers tell the truth when they added,
... the use of multiple comparisons in the analysis of the study data increases the risk of statistical error resulting in a false positive.
In fact, these researchers failed to tease a convincing false positive out of anything but that pathetic "change from baseline" statistic used to amplify a statistically meaningless finding into one they could pawn off on a credulous public as a significant one. One wonders how they could have the nerve to suggest that "further studies are required to confirm and further define the benefits of this juice."

Could it be that the sponsor likelihood of sponsoring (i.e. paying for) further research had anything to do with it?

I'll leave you to determine that.

But really, the gall of the people who come up with this stuff. And the further gall of the journals that publish it, knowing that most people will only look at the abstract or the news report that will undoubtedly appear in the magazines and web sites supported by supplement sellers.

You can expect to see the hucksters using this "research" to prove that mangosteen has miraculous health giving effects. And the poor obese schnooks who fork out their hard earned cash for magical mangosteen juice? Too bad for them. Especially if they have diabetes, since the carb count on this juice whatever its putative "benefits" must be astronomical since it is mostly apple fruit juice concentrate and what little mangosteen juice it contains--very little I suspect, is very high in carbs.

BOTTOM LINE: The proprietary Mangosteen juice blend sold all over the internet will lighten only your wallet and improve the inflammation only of the egos of the dead enders who did this research.


October 14, 2009

Turning The Battleship Around: Low Carb Study at EASD

This week was the European Association for the Study of Diabetes (EASD) meeting. This is the European equivalent of the ADA Scientific Session and in my experience it usually features some worthwhile research.

Of interest to many of my readers was yet another study proving the efficacy of the low carb diet. This one was done by Richard Feinman, PhD, from the Downstate Medical Center in Brooklyn, New York. His study found to the surprise of no one who owns and uses a blood sugar meter, that a low carb diet is much better than a high carb diet in controlling blood sugar. The diet used in this study was one that was 20% carbohydrate, which would be one of 100 grams for a 2000 calorie intake, just north of the boundary where most people start spilling ketones.

This diet did not produce weight loss--it was designed not to, but still achieved dramatic improvements in blood sugar, overturning the touching, if false, belief of most doctors and nutritionists that it is weight loss that lowers blood sugar, rather than the lowering of carbohydrate intake that occurs with calorie restricted weight loss diets.

My point in mentioning this is not that the research is all that significant. We've had lots of research over the years that demonstrated this same effect. What's interesting is that, surrounded by Europeans, rather than the Drug Company and Food Industry goons who dominate the American Diabetes Association, Dr. Feinman mentioned the elephant in the room.

Here's what he said, as reported by Diabetes in Control: "...the science is not controversial but policy regarding dietary control in diabetes is."

He then added,
"The recommendations are for relatively high carbohydrates. When you press the ADA [American Diabetes Association] for their recommendations, they say they do not have a specific diet, but in fact they recommend a high-carbohydrate [diet] and give grudging support to a restricted-carbohydrate diet."

"I'd really like to see an impartial panel of scientists that doesn't necessarily have any commitment to nutrition, [such as] physicists or meteorologists. The goal would be a clearer analysis of the facts, laying out the options, especially for people with diabetes. Let the patient and the physician make the decision.
Predictably, he was met with a hail of fact-free objection from nutritionists who responded much like Jesuits confronted with Martin Luther.

You can read their science-free responses and the attempts of those who seek to smoothe the waters by claiming there is a middle way in the Diabetes in Control article which you will find here:

EASD: High-Protein/Low Carbohydrate Diet Effective for Weight Loss in Type 2 Diabetes NOTE: The title does not correctly reflect the finding which was that the Low carbohydrate diet is effective for blood sugar control in the absence of weight loss.

The fact is, there is no middle way. The low glycemic/high carbohydrate diet is very slightly better than a high glycemic/high carbohydrate diet, but it still produces blood sugars high enough to promote complications.

To avoid complications you need to get normal blood sugars, not slightly better diabetic blood sugars. To do that, you need to cut out a lot of carbs. Twenty percent works for many. I still need to use a bit of meal time insulin with a carb intake that high, but with insulin it works for me. Without fast acting meal time insulin, I need to drop to around 15% to get decent control.

The reason to highlight this presentation, though, is that for the very first time, a researcher has had the nerve to point to the fact that the ADA's promotion of the high carbohydrate diet is a political decision, not one based on science.

This, in the world of science, is a big deal. It isn't quite an accusation of corruption, but it is close.

In fact, I believe the American Diabetes Association is corrupt, and that its corruption is due to the fact that it is heavily funded by commercial interests who lose money when people with diabetes use an effective diet to control their blood sugar instead of drugs that cost almost $200 a month. Look at the cheap food conglomerates who sponsor the ADA and ask yourself how many of them sell high quality protein foods free of corn syrup, hydrogenated fats, and lots and lots of sugar and starch.


I'm off now to see my endo for my semi-annual checkup. My A1c will probably be higher than I'd like, because I had the flu three weeks ago. It's always higher than I expect, and because I was feverish for a few days and had high blood sugars much of the week I expect it to be even higher this time. In fact, save for when I was sick, I have kept my blood sugar under very good control throughout the last six months and even managed to knock off a few pounds, too.

Back later. . . .

My A1c turned out to be 5.8% which considering that I was seeing a bunch of 180s after meals the week after I had flu and the test was a week after that was extremely good news. Outside of the flu I thought I had been doing well. I'm also down 10 lbs since April, which is what I thought too. Partly that is due to going back on metformin, partly to getting food poisoning last summer which kept me from eating food for a week, and partly from the flu. I'll take it.

My blood pressure had shot up again--it's been fluctuating wildly of late since I got sick and can be anywhere from from 90/60 to 160/113 with no obvious explanation for why. It was fine yesterday--I measure at home--but it was awful at the office and on my home machine too. Back onto the Diovan!

I've been supplementing with 2000 IU of Vitamin D all year and she tested my Vitamin D level. It was 51, which is okay but I'm going to add another 1000 IU to the daily intake since it could be better. Finally all the kidney tests, microalbumin, creatinine etc. were completely normal.

The doc suggested that it would have been a good idea not to take the metformin while feverish with flu, given that during fever we produce higher levels of lactic acid and tend to get dehydrated. That's a bit of info to stash away for future use. I have been very exhausted since getting over this flu and she suggested going off the metformin for a week to see if that helped.


October 9, 2009

Chinese Herbal Medicines to Prevent Diabetes?

A new Cochrane review of studies of the impact of Chinese herbal medicines on preventing prediabetes. It concludes that,
Meta-analysis of eight trials showed that those receiving Chinese herbal medicines combined with lifestyle modification were more than twice as likely to have their fasting plasma glucose levels return to normal levels (i.e. fasting plasma glucose <7.8 mmol/L and 2hr blood glucose <11.1 mmol/L) compared to lifestyle modification alone (RR 2.07; 95% confidence intervall (CI) 1.52 to 2.82). Those receiving Chinese herbs were less likely to progress to diabetes over the duration of the trial (RR 0.33; 95% CI 0.19 to 0.58)
You can find the abstract, here:

Chinese herbal medicines for people with impaired glucose tolerance or impaired fasting blood glucose Suzanne J Grant et al., Cochrane Database of Systematic Reviews, 2009, Issue 4. Art. No.: CD006690 DOI: 10.1002/14651858.CD006690.pub2

You are going to be hearing a lot about this from practitioners of alternative medicine so it is important to add the REST of what the researchers concluded, which was, "all trials had a considerable risk of bias and none of the specific herbal medicines comparison data was available from more than one study."

What this means is that the studies were done by people with a stake in the outcome--i.e. people selling the product. That's the "risk of bias"--and, in addition, that each study evaluated a different herb.

So what the review really found was this. Studies conducted by people selling particular herbs find them dramatically effective. With this in mind, the Cochrane researchers conclude more study is needed.

Let's assume for a moment that Chinese herbs do slow the progression from pre-diabetes to diabetes. What does this really mean?

It means that the researchers started with two groups of people whose fasting blood sugar at the beginning of the study was above 100 mg/dl or whose 2-hour Glucose Tolerance Test (GTT) result was over 140 mg/dl (7.7 mmol/L). At the end of the study one group had fewer people whose fasting blood sugar was now over 125 mg/dl or whose 2 hour GTT result was over 200 mg/dl (11 mmol/L).

However, these kinds of studies are always binary--a subject is judged to have diabetes or not. So if one group of pre-diabetics ends up with an average 2 hour GTT blood sugar of 198 mg/dl they are "not diabetic. If the other group ends up with an average GTT blood sugar of 201 mg/dl, they are diabetic.

In practice of course, the likelihood of complications is identical for both groups. The 3 mg/dl average difference may be statistically significant (i.e. not due to chance) but it is clinically meaningless.

This is the methodology used in every "diabetes prevention trial" I have ever read. What isn't measured is the extent to which blood sugar control deteriorates in each individual over the course of the trial. A person whose GTT result rises from 142 to 195 mg/dl is still considered "not diabetic" while one whose GTT blood sugar progresses from 190 to 201 is.

By manipulating the characteristics of the two groups it is possible to get better results in one group simply because that group started out with more people whose blood sugars were at the low end than was true in the other. The averages in both groups will be the same if the other group starts out with most people having individual sugars near the center. Since that group has more individuals with higher values, they will be more likely to progress no matter what treatment is used.

But that's not the only issue here. Let's say that the difference in the two groups is greater and they start out with the same average AND standard deviation (that's a measure of the distribution of values through the group.). One group has a mean GTT two hour test result of 201 mg/dl and the other has the average of 180 mg/dl.

The next question must be, what explains this difference?

In many cases the answer is that herb contains a natural form of a substance, like the active component in the sulfonylurea drugs, that stimulates insulin production. Is this good? Not necessarily. Drugs that stimulate insulin production also turn out to do several other things.

They produce significant weight gain, often because they stimulate insulin secretion in the absence of food, which causes swiftly dropping blood sugars which result in intense hunger.

They stimulate receptors on other organs besides the pancreas--most notably the heart. The first generation sulfonylurea drugs caused excess heart attacks for this reason and there is some evidence that Prandin and Starlix may do this, too. The evidence for the newer sulfonylurea drugs is missing--but there is a black box warning on those drugs citing heart attack risk as a possibility.

However, there's a further problem with the blood sugar-lowering herbs. When you are getting your "drug" from an herb you have the additional problem that you have no idea what else is in the herb or how toxic the substance lowering your blood sugar might be to you. There are plenty of drugs that lower blood sugar that fail in clinical trials because they also cause kidney damage, or liver damage, or cancer or other serious problems.

Since herbs are not subject to any oversight the way prescription drugs are, you have no idea what the active component of your herb is doing to the rest of your body.

And that's just looking at the active component! Other substances may be contaminating your herb and they too may be dangerous. If the herb was grown using dangerous neurotoxic pesticides (illegal in the US but used elsewhere) it may be harming your nerves while it lowers your blood sugar. If it was grown using polluted water, you might be getting arsenic or any number of other dangerous chemicals with your "natural" herb.

Since herbs are completely unregulated, you have no way of knowing what you are actually getting. Unscrupulous sellers have been known to doctor "natural" supplements with cheap first generation sulfonylureas to make them "effective." Those are, you remember, the drugs that lower blood sugar while increasing the risk of heart attack.

There's one last problem with any strategy to "prevent diabetes." In every well conducted, double blinded clinical trial, as soon as people are taken off of the drug or treatment that "prevents" progression, many people's blood sugar goes right back up, and the same proportion turn out to be diabetic (i.e. they test with blood sugars over the cut off number on the glucose lab test) as were found in the other group.

That's probably because none of the drugs or treatments tested lower blood sugar low enough to avoid glucose toxicity. "Glucose toxicity" is the term for what happens when blood sugar gets so high, it starts poisoning beta cells.

If your blood sugar is over 160 mg/dl for hours at a time, you may be officially "pre-diabetic" but your blood sugars are high enough to kill beta cells. (Details on this phenomenon are discussed HERE.) People who develop diabetes have underlying genetic conditions where a) they start out with less effective beta cells than normal people and b) they are unable to grow new beta cells to take up the slack when their existing ones are stressed. If they lose a beta cell from glucose toxicity, it's gone, and because they started out with already marginal glucose control, it doesn't take much to kill off enough beta cells to render them fully diabetic.

One last issue here is that there is ANOTHER reason some people don't progress from pre- to full fledged diabetes. That is that many people who do NOT have family histories of diabetes and lack the genes associated with diabetes will become "pre-diabetic" entirely due to insulin resistance but, because they have the ability to grew new, healthy beta cells, they respond to rising blood sugars by growing new beta cells and never become diabetic. There are a lot more of these people than those who become diabetic, because it almost always takes the existance of the underlying genetic flaw to produce diabetes.

So a well-conducted study should only look at people who have family histories of diabetes, not at a population with "pre-diabetes" many of whom are not capable of developing diabetes because their genes are normal.

With this in mind, it's worth noting that there is NO data available to answer the question, "Does lowering blood sugar to normal levels that avoid beta cell death from glucose toxicity really prevent progression?"

It's worth attempting the experiment with a study group of one--i.e. yourself. If you have been diagnosed with pre-diabetes, cut back on your carbohydrates until your blood sugar is always under 140 mg/dl at 1 hour after eating and 100 at 2 hours (if possible) and see what happens over the next decade.

Many of us who have tried this experiment find that our blood sugars do not deteriorate significantly after we get blood sugars down to normal.

This approach is not going to bring back dead or dying beta cells, but it can keep you from damaging more of those that are left.

Don't expect anyone to fund that research, though. It doesn't sell product.

And do expect those who are selling product to keep showing you poorly conducted studies run by people who profit from the herb involved that "prove" that this or that ancient remedy from [insert distant land or exotic culture here] "reverses" or prevents diabetes.

NOTE: If your beta cells are dying from an autoimmune attack as happens in about 8% of those diagnosed with Type 2 who really have a slow form of Type 1, you will probably not be able to stop the attack. Nothing yet has been shown to stop autoimmune diabetes from progressing though interesting research is going on in this area.


October 7, 2009

Recent Research: Same Old Same Old

I have not been blogging much about recently published diabetes-related research papers because there has been nothing in any of the major journals worth noting.

As usual, the published research breaks down into the usual categories:

1) Lots of research in rodents fed "high fat diets" that confirm the religious beliefs of the researchers, i.e. fat is bad. The "low fat diets" are always high carb/high fat diets. Even when they aren't the fact that rodents are adapted to completely different diets than humans and that they have differences in their pancreases and digestive systems from humans render 99% of the rodent research meaningless.

2) Lots of associational studies where epidemiologists "prove" that diabetes can be prevented with exercise and low fat or low meat diets by analyzing epidemiological studies that really just show that thin people are less likely to develop diabetes. These studies never eliminate the possibility that thin people are thin because they don't have the underlying genetic flaws that lead to abnormal glucose tolerance--primarily defective beta cells and mitochondria--and hence can eat high carb diets without gaining the weight people with genetic problems gain on that diet.

3) Lots of drug studies where people with A1c of 8-11% are given a drug that drops their A1c around .5% which the researchers conclude shows the drug (always extremely expensive) is extremely effective even though the resulting A1c is high enough to guarantee complications.

4) A few studies run in an attempt to come up with a way of justifying the widespread prescribing of yet another expensive, side effect prone non-diabetes drug to everyone with diabetes. Drugs for depression and psychiatric drugs prescribed for neuropathy feature heavily here.

5) A few very troubling studies that are misinterpreted to conclude that lowering blood sugar is dangerous. Invariably the blood sugar has been lowered with oral drugs that have nasty cardiac side effects. Even in these studies, though, lowering blood sugar significantly decreases kidney failure and neuropathy.

6.) A few studies paid for by food industry organizations which prove based on test tube findings that this, that or another food has miracle healing properties and can reverse diabetes. These studies have in common that blood sugar in people with diabetes is never tested after a sustained period of eating the miracle food.

So for now, nothing has changed.

The best way for someone with Type 2 diabetes to lower blood sugar is still to cut back on carbs, add metformin if they can tolerate it, and start insulin as soon as possible if the first two steps didn't achieve normal blood sugars.

The best way to combat the pain of diabetic neuropathy is to keep your blood sugar under 140 mg/dl at all times. The technique described HERE will do that for most people.

Despite what you read and what doctors tell people, losing weight will NOT reverse diabetes or eliminate insulin resistance. That some studies show this is only because the low calorie diets used to achieve weight loss require the study subjects to cut way down on food which caused them to cut back significantly on carbohydrates no matter what kind of diet they are eating. The good news is you don't have to lose weight to improve your blood sugar. All you have to do is cut back on carbs.

And on that subject, doctors (and most researchers) still have no clue that cutting way down on carbs can normalize blood sugars for most people newly diagnosed with Type 2 and many who have had it for a long time.

Environmental factors are clearly causing a surge in obesity and diabetes. High on the list of these are the domination of our food supply by artificially created food ingredients: High fructose corn syrup turns into insulin-resistance-producing liver fat. Trans fat clogs arteries because your body has no way of removing it. MSG bypasses the normal hunger control mechanisms in the brain and is hidden in most processed and fast foods under deceptive ingredient names. It makes people overeat. The phosphates in sodas and processed foods are also hard on your kidneys. The best thing a person with diabetes can do is to learn to cook from scratch and make as much food at home themselves from basic ingredients.

The side effects of the most heavily marketed drugs continue to be very troubling and the medical press continues to ignore them.

Avandia and Actos are too dangerous for anyone to use. Long term they cause serious osteoporosis. Short term they cause weight gain and the possibility of crippling edema which can lead to heart failure or macular edema leading to blindness.

Sulfonylureas have long been linked to possible heart problems and most recently to a higher risk of cancer.

Januvia and Onglyza cause disturbing changes in the immune system, including rashes, permanent sinusitis, and of most concern they turn off a cancer surpressor gene.

Byetta appears to be helpful as a weight loss drug to one third of those who try it. The possible connection with pancreatitis does not appear to be significant.

Metformin is by far the safest drug available to people with diabetes (unless they have liver or kidney disease) and appears to fight cancer.

Insulin taken early after diagnosis greatly improves the long term outcome for people with Type 2 diabetes but high doses of insulin may promote cancers, so you want to take the very lowest doses of insulin possible, which means you need to keep your carbs low and take metformin with your insulin if possible.

If you are new to diabetes, that's what you need to know in a nutshell.

Too bad the people paid to do diabetes research don't know most of this!


October 4, 2009

What Is Really Known about Fatty Liver?

The latest fad diets promise to reduce the fat in your liver. This is a noble aim--the amount of fat in your liver correlates closely to cardiovascular risk. Liver fat also appears to increase insulin resistance, though it is interesting to note that very recent research has found that pancreatic fat has a strong relationship to the development of Type 2 diabetes and may in fact be more important than liver fat.

The problem with the premise behind the fad diets, though, is that there is no significant research showing any treatment, be it a drug, diet or exercise, to be uniformly effective in reducing pre-existing liver fat.

The studies usually cited to advance one or the other dietary approach as a cure for fatty liver are either correlational studies, rodent studies, or studies that examine only surrogate markers--lab tests--rather than studies that biopsy the liver to see how much fat is in it.

The correlational studies are those where the researchers link a population's reported food intake with their risk of developing fatty liver. This kind of research may point to factors that cause fatty liver--though it also may not, given the poor track record of these kinds of studies, since they are based on questionnaires that do not accurately reflect what people really eat.

The correlation studies suggest that eating a high carbohydrate diet raises the risk of developing fatty liver. Fructose in particular seems to pile on the liver fat but any diet that results in high triglyceride levels looks like one that can damage the liver.

But the problem in applying this data to reversing liver disease is this: Once you develop a condition that correlates to a food intake pattern, it is not at all clear that eliminating the causative foods will eliminate the condition.

In the case of fat-related problems, you have only to remember that once new fat cells form, they never go away. You can reduce the amount of fat in each cell, but the cells themselves remain. (This is one reason why Avandia and Actos are such worrisome drugs, because they work by creating new fat cells in the arms and legs, cells that you are stuck with for life after taking these drugs.)

So once you have created a new population of fat cells in your liver, while it is possible dietary interventions may reduce the fat they contain, you are not going to get rid of the cells.

Beyond that, there is the problem that if the fat becomes inflamed--which it often is in NAFLD--you are likely to develop fibrosis--scarring--in the liver. This scarring is a large part of what destroys liver function. "Reversing" scarring is a whole different proposition than preventing that scarring from occurring.

With this in mind, I have spent quite a lot of time looking for studies that demonstrate that specific treatments cause significant real improvement in existing fatty liver disease. If we define "significant" not in the statistical manner but in terms of whether it makes any difference in your health. They are rare.

To understand this you need to understand that statistical significance refers to any difference between two numbers that is large enough not to be attributable to chance fluctuations. So one job pays $50,000 and another $50,500 the difference in salary here may well be statistically "significant." But you wouldn't leave your current job just because you could earn that extra $500. For the difference to be significant in terms of value, you'd probably want the second job to pay at least $55,000. Maybe more.

So when you see that a drug made a "significant" difference in fatty liver, but the research (often paid for by a drug manufacturer) avoids quantifying the actual difference in the abstract--the only part of the study most people ever see--you can safely bet that the actual amount of change wasn't anything you'd pay the inflated price of the drug to achieve.

Almost all studies claiming that this or that treatment reduces liver fat report surrogate markers--lab test results, rather than biopsy findings. This is not surprising. It's easy to take blood, not so easy to remove slices of a human liver. So almost all of the studies about fatty liver treatment evaluate the effect of the treatment on liver enzymes, specifically ALT.

Because liver biopsy is a massively expensive undertaking, the few human studies that do it are often done in people with other conditions that require abdominal surgery--conditions that might skew the results. Or they involve a very small sample--small enough that the results are not compelling.

The majority of studies that present liver biopsy results are rodent studies, and as we know, rodents are not furry little humans. Invariably they are done with rodents fed a very high fat diet--one that is very different from the diet rodents have evolved to eat and which cause changes in the rodent body often quite different from the effect they have on human bodies.

So the bottom line is this: there is a very small amount of evidence showing that low carb diets and exercise might prevent fatty liver, though even here it is hard to know how seriously to take them because they are so often based on surrogate markers.

There is virtually no evidence that conclusively proves that any treatment reverses fatty liver in everyone or even the majority of those who pursue it.

There is an excellent balanced review of Fatty Liver diagnosis and treatment on Medscape which I urge you to read if you are interested in this issue. It includes an extensive list of research references. I will cite some points made in it, but the whole thing is worth your attention.

Medscape: How Should We Manage Patients With Non-alcoholic Fatty Liver Disease in 2007? Henry L-Y Chan; H. Janaka de Silva; Nancy W-Y Leung; Seng-Gee Lim; Geoffrey C. Farrell; the Asia-Pacific Working Party on NAFLD (2007)

Do You Have Fatty Liver?

An important point this review brings out is that though they are usually used to diagnose fatty liver, it turns out that ALT levels (ALT is a liver enzyme released when the liver is damaged) do not correlate well with how much fat or scarring you have in your liver.

The review explains,
Serum ALT level cannot accurately reflect the severity of NAFLD [non-alcoholic fatty liver disease]; a significant proportion of patients with normal ALT have bridging fibrosis and even cirrhosis on histology. An AST to ALT ratio more than 1.0,[19] increased serum hyaluronic acid[20] and high homeostasis model assessment–insulin resistance (HOMA-IR) score, which is calculated by serum glucose × serum insulin (both in mmol/L) divided by 22.5,[21] are the common biomarkers associated with liver fibrosis.
However the review goes on to state that the predictive value of all biomarkers, including some fancy ones tested only in studies, is only 75-80%, and the only truly reliable diagnostic method is liver biopsy.

If your doctor has told you that you have fatty liver disease, ask on what basis he or she makes this diagnosis. Chances are it is your ALT level or the ratio of ALT to AST.

If You Did, Why Your "Cure" Probably Wasn't A Cure

The problem with ALT is that you can make it go down with many different treatments, without having any actual impact on the composition of your liver.

The review reports later,
Although elevated ALT is a well-recognized feature of NAFLD, ALT elevation can be present or absent in both simple steatosis and NASH [nonalcoholic Steatohepatitis--liver inflammation]. In most studies on lifestyle modification and pharmacological treatment in NAFLD, improvement in ALT is usually accompanied by improvement in histologic steatosis grading. The relationships between changes in ALT and changes in necroinflammation or fibrosis are less consistent. In a study in Hong Kong comparing patients with simple steatosis and NASH, patients with more advanced disease tended to have lower ALT levels.[7] Lowering of ALT should not therefore be considered a valid marker for improvement of liver disease in the follow up of patients with NAFLD.[Emphasis mine]
Once you realize that lowering ALT levels may not mean you have improved the state of the liver, several "cures" lose their efficacy.

For example, Metformin. Metformin can dramatically lower the ALT liver enzyme, but a recent study that did the liver biopsies showed no actual improvement in the subjects' livers.

Metformin in patients with non-alcoholic fatty liver disease: A randomized, controlled trial.
HAUKELAND John Willy, et al. Scandinavian journal of gastroenterology 2009, vol. 44, no7, pp. 853-860

There are a few small studies that claim that Avandia or Actos made "significant" improvements in NAFLD on biopsy, but because the abstracts do not present the numbers, the "significance" might well be a tiny amount of change that doesn't mean much clinically. There are conterbalancing studies that show no effect from Avandia or Actos, too. My guess is that examination of who paid for these studies--drug company or others, may explain the difference in their findings.

The Medscape review suggests, rightfully, that the weight gain side effect of Actos and Avandia may counterbalance any small change they make in liver status.

Weight Loss Surgery is being promoted very heavily as a cure for NAFLD (and just about everything else.) The studies demonstrating improvement involve very few subjects and because of the huge profits to surgeons and hospitals involved in this surgery one should approach these studies with the same skepticism with which you approach drug company sponsored studies. The other side effects of WLS can be life-ruining and/or even fatal, so it is not a "cure" to be adopted without much prior study and investigation.

Fatty Liver and Insulin Resistance

Most researchers seem to believe that fatty liver is linked to insulin resistance though whether it is caused by the IR or causes it is not at all clear to me. Nor is it clear that the idea common in research that lowering insulin resistance will improve fatty live is realistic.

Why? Because truly reducing insulin resistance, rather than blood sugar, appears to be almost impossible. This truth is obscured by faulty methods of measuring IR that do not account for the impact of lowering carbohydrate intake on blood sugar levels.

Most people who have Type 2 diabetes remain seriously insulin resistant no matter what drug they take or what diet they eat. Diet, especially the low carb diet, can normalize their blood sugar, eliminating most diabetic complications, but the amount of insulin the person with Type 2 Diabetes needs to inject to lower their blood sugar 10 mg/dl is always much higher than that a normal person would need. Anywhere from five times higher to twenty times higher.

Losing weight doesn't normalize insulin sensitivity in most people with Type 2 Diabetes either. We know thin, active young relatives of people with Type 2 already show higher than normal insulin resistance. So it is possible the IR associated with fatty liver precedes the depositing of liver fat rather than, as is commonly assumed, the fat is causing the IR. In any case, because we have no reliable method of reducing insulin resistance that doesn't have side effects worse than the conditions (viz Avandia and Actos) fad diets that claim to reduce insulin resistance, which actually only reduce blood sugar, are not going to reverse your fatty liver.

What we can conclude, tentatively is that diets that lower blood sugar and triglycerides are better than those that raise them. There is some possibility that they may prevent further deterioration of fatty liver disease though until we understand the real causes of insulin resistance, this is only a guess.

Such diets, and metformin, often will normalize liver enzymes, the significance of which is unknown. What we do not know is whether any diet will lower the amount of fat stored in the liver.

But there is another huge issue to consider when reviewing a fad diet: Diets that cause very fast weight loss have been linked to raising the risk of developing fatty liver. So the last thing you want to do if you are fighting fatty liver is adopt a diet that promises to take off a lot of weight in a very short time. If you are losing more than a pound a week (two if you are seriously obese) you may be stressing your liver.

If your fad diet is high in carbs, you are most certainly stressing your liver and making your fatty liver worse.

Did You Really Reverse Your Fatty Liver? Normal ALT is Not What The Lab Range Tells You

Keeping in mind that ALT levels don't tell you if you have reversed your fatty liver, I discovered something rather disturbing. It turns out that the lab ranges currently used for "normal" on ALT tests are (like glucose reference ranges) much too high, probably because the populations used to establish them included large numbers of people with undiagnosed fatty liver disease. It also turns out that males and females have very different truly normal ranges. The true female normal range is much, much lover.

A study that established true normal for ALT values is found here:

Re-evaluation of Serum Alanine Aminotransferase Upper Normal Limit and Its Modulating Factors in a Large-Scale Population Study Moshe Leshno et al. Liver International Full Text on Medscape.

When I looked at my own liver function tests over the years, keeping in mind the data presented here, and also using a biomarker the review suggested, the ratio of ALT to AST, I discovered that in liver function tests performed at several different times back when I had been eating a ketogenic low carb diet of no more than 65 grams of carbohydrate a day for more than 2.5 years, my AST was well over the normal range for females and my AST/ALT ratio was high enough to suggest NAFLD.

These biomarkers normalized completely when I started Metformin--at which point my high end of normal triglycerides also plummeted, but as the biopsy results suggest, this doesn't mean that my liver is in any better shape.

I also learned that another sign of fatty liver disease may be very high iron levels in the absence of the gene for hemochromatosis. Another member of my family who has a different kind of diabetes--one that has the pattern of very high fasting blood sugar but normal post-prandial blood sugar, was diagnosed with this very high iron level. He is at a normal weight but carries a gene that is associated with lipid abnormalities. This makes me wonder about whether the minority pattern of diabetes characterized by high fasting glucose but normal post-meal numbers points to fatty liver disease even in normal weight people.

So What to Do?

There really is no easy answer here. Slow steady weight loss might help, except that the weight of the evidence relating to weight loss is that it is almost impossible to maintain a weight loss of more than 20% no matter what diet you eat. I had made that kind of weight loss several years before my ALT/AST values tested ugly.

Exercise may help if it truly reduces insulin resistance rather than just blood sugar. Whether this happens has a lot to do with your own unique physiology and what causes your individual insulin resistance.

Avoiding the high carb foods and especially fructose that appear to worsen liver fat is a good idea.

There is also some question about the impact of the statin drugs given that they often worsen liver enzymes. Very little of the research addressing this examined the livers of those taking statins.

A small study that did came up with conflicting data:

Statins in non-alcoholic fatty liver disease and chronically elevated liver enzymes: A histopathological follow-up study Mattias Ekstedt et al. Journal of Hepatology Volume 47, Issue 1, Pages 135-141 (July 2007).

Here are the findings of this study:
At baseline, patients that later were prescribed statins had significantly higher BMI and more pronounced hepatic steatosis. At follow-up patients on medication with statins continued to have significantly higher BMI. Diabetes was significantly more common among patients on medication with statins and they had significantly more pronounced insulin resistance. However, they exhibited a significant reduction of liver steatosis at follow-up as opposed to patients not taking statins. Despite exhibiting a high risk profile for progression of liver fibrosis, only four patients on statin treatment progressed in fibrosis stage.

Final verdict

Sometimes it helps to know what it is you don't know. What we don't know is how to reverse fatty liver in a way that is safe and improves health. So be very wary of any mass market diet book that claims that its diet will reverse your fatty liver. There is not enough good quality data to make any prescription here.


October 2, 2009

Sleazy Kinde Pirate Hijacks Blood Sugar 101 on Amazon

UPDATE OCT 3, 2009: Today Amazon has finally cleaned up the mess left by the attempt by the pirate to sell a sleazy Kindle book as if it were Blood Sugar 101 . Amazon also stopped the sale of the pirate's diabetes book. However, there are still a bunch of other titles that have been hijacked by the same sleazy company the same way mine was on Amazon, and though Amazon unlinked a few other Kindle downloads that were linked fraudulently to print books that had different titles, after I notified them about them, the sleazy versions of those Kindle titles are still for sale. Other hijacked books remain in Amazon's catalog and I have notified the rights holder where I could find contact information.

So before you buy a Kindle book, check that the author and title of the Kindle edition you are buying is identical to the printed book. It beggars belief that Amazon allows people to link their Kindle books to print titles that have different titles and author names, but they do.


Monday I logged into Amazon to see if there were any new reviews of my book, Blood Sugar 101. Imagine my surprise when I saw that Amazon was selling a Kindle edition of the book.

Technion Books, publisher of Blood Sugar 101, has not released a Kindle edition.

It turns out a sleazy publisher of generic mobipocket downloads, a company that publishes downloads on any topic that might sell, had linked the Kindle edition of "Diabetes Care Study Guide" to the paperback version of Blood Sugar 101.

People who clicked through from Blood Sugar 101's paperback page to the Kindle page saw a picture of the cover of Blood Sugar 101, but were sold the Kindle version of something called "Diabetes Care Study Guide" which was some junk offering of generic publisher MobileReference

I contacted Amazon's copyright department immediately and was assured the problem would be taken care of. Five days later, they have removed the link to the bogus Kindle edition and removed the picture of my cover from the page of the bogus Kindle book. But that page is still there, and Amazon left all the reviews of Blood Sugar 101 on the pirate Kindle book's page!

Visitors to the Kindle page read a bunch of reviews saying that the book (rarely identified by title) is essential reading for anyone with diabetes. The appearance today on the Kindle page of four "people who bought this book also bought" items suggests at least four people were suckered into buying the Kindle pirate's book thinking it was Blood Sugar 101.

It gets worse. Amazon now displays a long rambling screed from MobileReference on the page selling the REAL, printed version of Blood Sugar 101. This makes it look like my book is published by this sleazy company.

I am outraged. I have contacted Amazon's copyright department three times about this problem and they keep assuring me it will be fixed. So far, it isn't.

I found six other titles where the MobileReference company had linked their download to a similar, but completely different, print book. When I contacted Amazon about this, I was told that only the copyright holder could complain. In each case, the cover of a different book is displayed along with the MobileReference Kindle download of a book with a slightly different title.

If you are a Kindle owner, I would urge you to complain loudly to Amazon about the deceptive practices being used by MobileReference to sell inferior downloads to Kindle owners and the fact that reviews from a bestselling print book are being displayed on an unrelated Kindle download in a way that could really hurt people
with diabetes.

IMPORTANT NOTE: DO NOT post comments on the sleazy company's Kindle page because the way they have linked to my book, any comment posted on "Diabetes Care Study Guide" becomes a review and a RATING of Blood Sugar 101. Infuriating.

Since the company continues to benefit from their fraud, my guess is they will perpetrate many more, as will other sleazy Kindle vendors. Amazon's policy appears to be that they are willing to profit from piracy. Not all copyright holders check their book's page every week to see what is going on, and a Kindle vendor who links to a successful book with an owner who isn't paying attention may sell a lot of books before the fraud is discovered.

And since Amazon does not remove the Kindle version that profits from this piracy, it's pretty clear how seriously they take such shenanigans.

I have no way of knowing how many people fell into the trap set by MobileReference. I know only that Amazon does not consider it a priority to keep Kindle owners from buying fraudulent goods and they are not in any hurry to remove the glowing reviews from the pirate Kindle page.

You can easily tell if you downloaded the pirate's Kindle version when you ordered Blood Sugar 101 for your Kindle. There is NO Kindle edition of Blood Sugar 101, so anything you downloaded thinking it was my book was the pirate's!

Meanwhile, if you order the print book from THIS PAGE
you will get the printed book.

Or you can make life even simpler for yourself by ordering the book from any of the other online vendors listed on THIS PAGE.