March 31, 2009

Know Your CRP!

It's been known for a while that a substance called C-Reactive Protein (CRP) rises in our blood stream in the presence of inflammation. It's also becoming clear that high levels of CRP may point to the presence of inflammation in our blood vessels and be an early marker for heart disease.

CRP Levels Rise Before Diabetes Diagnoses Especially in Women

Now new research is finding that higher than normal CRP levels correlate with the likelihood of developing of Type 2 diabetes, especially in women. This is a very interesting finding.

Here's the study that established this:

Association of Serum C-Reactive Protein Level with Sex-Specific Type 2 Diabetes Risk: A Prospective Finnish Study
Gang Hu, et al., Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2008-2260

What the researchers did here was this. The started out with 12,861 Finnish men and women who were 35 to 74 years of age and free of diabetes, coronary heart disease, stroke and cancer. They measured their CRP. Then they followed them them for some years--unfortunately, they don't tell us how many years in the abstract.

During the follow-up period 208 men and 113 women developed diabetes. This works out to 2.5% of the group as a whole, a very small number. After adjusting for a huge number of other factors known to increase diabetes risk, the researchers concluded that the CRP level was still predictive for both men and women, but much more predictive for women.

The CRP levels they looked at were these.

LOW: .05-.99 mg/L
MEDIUM: 1.0- 2.99 mg/L
HIGH greater than 3.0 mg/L

Men in the medium CRP group were 50% more likely to become diabetic as those in the low CRP group.

Men in the high CRP group were almost twice as likely to become diabetic.

Women in the medium CRP group were almost 4 times as likely to become diabetic.

Women in the high CRP group were 8 times as likely to become diabetic.

I'm not entirely happy about how many other variables were "adjusted for" in this study, as the researchers "adjusted" their data to screen out, supposedly, the effect of 14 other factors known to correlate with diabetes. This may render the CRP statistics meaningless. Medical researchers are notorious for using statistical techniques incorrectly, so this is a concern.

It's also important to realize that this finding is a correlation. It does not imply that high CRP causes diabetes.

CRP Rises with Impaired Fasting Glucose and Impaired Glucose Tolerance

The blood sugar/CRP association is found in another, different study published last month too.

Association between C-reactive protein and pre-diabetic status in a Chinese Han clinical populationJie Lin et al., Diabetes/Metabolism Research and Reviews. Volume 25 Issue 3, Pages 219 - 223

This study looked at the correlation between CRP in a population of 1730 Han Chinese with blood sugars ranging from normal (1258 subjects) to Impaired Fasting Glucose (126 subjects) or Impaired Glucose Tolerance (346 subjects). It found that in this population, which was characterized as "a thinner healthy population," CRP rose as blood sugar dysfunction increased. The correlation was strongest in those with impaired glucose tolerance (i.e. those with blood sugars between 140 and 200 mg/dl at 2 hours on glucose tolerance testing.)

Is Gycosylation to Blame?

It's noteworthy that the Wikipedia entry on CRP cites an study that found CRP is subject to glycosylation, though it isn't clear what the impact of glycosylation is on the function of CRP. This suggests, tome that the association between rising blood sugar and rising CRP may be caused by glycosylation from high blood sugar rendering CRP less effective leading the body to produce more of it, rather than pointing to the idea that inflammation is what is causing the elevated blood sugars.

If this were the case, lowering blood sugars should, over time, lower CRP to some extent, though it might NOT necessarily lower the underlying inflammation that raises the CRP in the first place.

Other Studies Flag Inflammation as a Concern

And this inflammation is looking like it is a VERY important issue to anyone with abnormal blood sugar.

We learned recently from the JUPITER study, that the effectiveness of statins in preventing heart attack appears to correlate with the subject's CRP level rather than the level of LDL cholesterol.

We also have seen, as I have blogged in the past that systemic inflammation associated with gum disease raises blood sugars significantly.

So it's becoming clear that testing CRP maybe as important, or quite possibly much MORE important than testing cholesterol for anyone whose blood sugar is not rock solid normal.

I am going in for my annual battery of lab tests tomorrow and I just called my endo and asked to have my CRP tested. It's been eight years since my Very Smart Doctor tested it. I was told my CRP was normal back then, but because I don't have the lab sheets I don't know whether it was "normal" as in <3 mg/L or "normal" as in 1-2.99 mg/L. As you can see from the findings of that first study, the mid range for CRP is does not look to be anywhere near normal for women though it might be for men.

What Is Correct Response to Finding Markers of Inflammation?

If CRP is elevated, the question we should be asking is not "what drug can I take to lower CRP" so much as "What is inflamed, why, and what can I do to reverse that inflammation?"

For starters you'll want to get to work on eliminating infection--CRP rises the most in response to bacterial rather than viral infection. Taking a drug to suppress inflammation without getting rid of any bacteria that might be causing that inflammation is like turning off your smoke alarm instead of turning off the burner under a smoking pot.

Once you have eliminated the obvious sources of bacterial inflammation like gum disease, there are some strategies you can pursue to lower inflammation which we will discuss in upcoming blog posts.

In any event, it looks like the CRP test is one everyone with diabetes should have performed, if they can afford it.

March 27, 2009

When The Doc Says Lowering A1c Below 7% is Dangerous

I've been receiving a depressing amount of email from readers whose doctors or diabetes nurses have warned them that recent studies have proved it is dangerous to lower A1c below 7.0%.

I've blogged about this before. You can read why doctors are giving this advice--and why it is flawed--here:

A Giant Step Backwards: Misinterpreting ACCORD Harms People with Diabetes

Why Doctors are Telling Type 2s Not to Lower Blood Sugar--And Why They Are Wrong

But what I want to do in this post is different. I want to give you a brief list of questions to ask the doctor or diabetes nurse who tells you that lowering A1c is dangerous.

Ask these questions and suggest that these supposed professionals read the studies this flawed advice was based on before they give their patients advice that will enhance their risk of neuropathy, blindness and kidney failure.

Questions Ask Your Doctor Who Discourages You From Attaining A Normal Blood Sugar

1. Are you aware that the ADVANCE study, which was larger and lasted longer than the ACCORD study, found no increase in cardiovascular death when people lowered A1c to 6.5%?

2. Are you aware that the major difference between ADVANCE and ACCORD is that people in ACCORD were older and sicker and that ADVANCE did not use TZD drugs (Actos or Avandia) used in ACCORD, drugs which have both been shown to cause heart failure in people who did not have it before starting these drugs?

3. Are you aware that ACCORD and ADVANCE both found that lowering A1c to 6.5% lowered the incidence of kidney failure and other microvascular diabetic complications?

4. Are you aware that the Veterans study being used to support the idea that lowering A1c is useless for people with diabetes involved people who were substantially older and sicker than most newly diagnosed people with Type 2 diabetes--who had already developed irreversible heart disease after decades of maintaining extremely high A1cs, so that their experience is not applicable to recently diagnosed younger Type 2s? Do you also know that they were put on the high carb diet combined almost certainly with the outdated sliding scale insulin protocols that are known to lead to hypos?

5. Are you aware that in all these studies the subjects were eating hhigh carbohydrate diets and counteracting the high blood sugars this caused using a cocktail of drugs, all of which have known, dangerous side effects?

6. Do you know that no study has followed people with Type 2 diabetes who lower their A1c using diet alone, most specifically by cutting carbohydrates out of their diet, though what data we have shows that doing this drops A1c dramatically, improves lipids, and lowers blood pressure without side effects?

7. Did you know that the study showing intensive care patients do worse with tight control reflects the fact most hospitals still dose insulin using the dangerously inaccurate "sliding scale" method that bases dose on pre-meal blood sugar, not carbs consumed per meal, and almost guarantees hypos?

As these questions. If your doctor doesn't respond positively, find a new doctor.

It's tragic to think how many people are going to suffer blindness, amputation, and kidney failure because their doctors only read newsletter summaries of these studies, rather than the studies themselves.

Even more frightening is the fact that insurers will seize on this to cut costs by claiming it is a waste of money to pay for strips or insulin for people whose A1cs are lower than 8%.

What these studies really show is this: If you've had Type 2 for 30 years, there probably isn't much you can do about the advanced heart disease you've developed but at least lowering blood sugar may mean you don't have to go on dialysis or go blind.

If you eat a high carb diet that raises your blood sugar unnecessarily high and then take a cocktail of drugs including TZDs along with huge doses of insulin prescribed without reference to your carb intake, you may suffer cardiac side effects and hypos.

But if you are newly diagnosed, have no complications at diagnosis, and lower your A1c by cutting out carbohydrates and normalizing blood sugar, lipids, and blood pressure, there is NO research that suggests you can't have completely normal health.

And if you are recently diagnosed but diet alone is not enough to control your blood sugar it is completely possible to normalize blood sugar by adding metformin and/or insulin to your low carb regimen. Type 2s who control carbohydrates and learn how to dose insulin properly do not need to experience hypos.

March 25, 2009

That Meat Study Also Found Red Meat Associated with Accidental Death in Older Men

A study published this week is garnering a lot of attention in the press because it confirms what the health establishment would like to believe is true, that red meat--especially fatty red meat--is dangerous. But as usual, a closer look at the study calls this into question.

This study is currently available for free online. You can read it or download the PDF here:

Meat Intake and Mortality: A Prospective Study of Over Half a Million People. Rashmi Sinha, et al.Arch Intern Med. 2009;169(6):562-571.

It's worth looking at the whole study, because without reading the whole thing, you won't really understand what this study did and did not find.

The researchers in this study administered a dietary questionnaire to 617,119 AARP members aged between 50 and 71 years old in 1995. The questionnaire asked them to try to remember how many portions of various kinds of foods they'd eaten over the past month. The respondants were then followed up for ten years and the number of deaths and causes of death were determined by looking people up in the Social Security Administration Death Master File. Verification of vital status, and the cause of death information was provided by follow-up searches of the National Death Index (NDI).

After adjusting their data for factors known to affect mortality, such as smoking, physical activity, social indicators, age and BMI the authors write:
CVD mortality, as well as all other deaths in both men (Table 2) and women (Table 3) in the highest compared with the lowest quintile of red meat intake in the fully adjusted model. There was an increased risk associated with death from injuries and sudden death with higher consumption of red meat in men but not in women.
You may notice that this is not quite what you read in your newspaper. Your paper did not report, "Eating red meat increases likelihood of injury in older men but not women" because your response to that conclusion would have been to say, "Sounds like red meat must be a marker for something this study neglected to measure."

Later on, in the discussion section, the authors brush off this latter finding by explaining that the number of accidental and sudden deaths was low so perhaps the finding wasn't that significant.

After that, they explain why eating red meat causes the excess heart disease and cancer deaths they they believe they found. It is important to note that nothing in this study points to any of these causes being involved. These are, basically, religious beliefs common in the nutritional community. Here's what they wrote:
There are various mechanisms by which meat may be related to mortality. In relation to cancer, meat is a source of several multisite carcinogens, including heterocyclic amines and polycyclic aromatic hydrocarbons, which are both formed during high-temperature cooking of meat, as well asN-nitroso compounds. Iron in red meat may increase oxidative damage and increase the formation of N-nitroso compounds.Furthermore, meat is a major source of saturated fat, which has been positively associated with breast and colorectal cancer.
This last part of the study has been quoted in the press as if it had been proven in the study. This is not true.

In fact, as Dr. Eades points out in his blog today two other significant, well-conducted studies released at the same time as the red meat study debunked the meat/colorectal cancer connection. One found no relationship between colorectal cancer and meat consumption, the other found no significant differences in mortality between vegetarians and meat eaters in the UK.

You can read the details of those studies in Dr. Eades' blog with links to the studies so I won't reproduce them here.

What Dr. Eades did not mention is the glaring omission in the red meat study. The participants were asked to remember how much meat of various kinds they had eaten over the past month. They were asked about their fruit and vegetable consumption. But they were not asked anything about their carbohydrate consumption.

So we don't know whether the people eating the most meat were also those eating the most french fries with their red meat, or the most hot dog buns with their processed meat, or the most supersized Cokes with their burgers.

This is not a trivial omission. We know there is a very strong relationship between A1c and heart disease and without the carbohydrate intake figures, it is impossible to know if it is the higher portions of carbohydrates consumed along with higher portions of meat that is raising those mortality figures.

We also know that high blood sugars turn off the immune system at the same time as they provide glucose to tumors, which may help explain the connection found in this study between a slight increase in cancers and eating more red meat. Since the other studies Dr. Eades cites found no correlation when meat eating is more carefully quantified, it's possible that this study really found something completely different from what it's researchers thought they were finding because they did not ask the right questions. Remember that in 1995 when this study began it was an article of religious belief that carbohydrates were the healthiest kind of food a person could eat and that fat and meat caused disease.

I don't know about you, but I'm going to keep eating red meat and I'll keep eating it without fries or sugary soda. And if steak prices go down because people who read health news uncritically avoid it, all the better!

The two studies that Dr. Eades points to confirm what I've observed in my own circle which is filled with "health food" fanatics who eat nothing but vegetarian organic foods. Over the decades I've known them, they have developed an alarming number of autoimmune diseases and cancers.

What you want to do with this data is up to you. But I hope it includes writing a letter to the editor of your local newspaper asking why they reported on the study that linked cancer and meat but didn't mention the other two equally well conducted studies that found no such links.

March 23, 2009

When You Need to Go to The Emergency Room with High Blood Sugars

My uncle, like all his family, was a bit of a cheapskate. He hated to spend money unless it was absolutely necessary. He was thin and active, having only recently given up a career as a singer and dancer performing weekly on a nationally televised variety show. So when he felt unwell one weekend night, he turned down his wife's suggestion that she drive him to the emergency room and told her he'd wait til Monday when he could see his family doctor. Why waste all that money on an ER visit that was probably unnecessary?

As it turned out, he didn't need to see his doctor on Monday. He died that night. He was a few years younger than I am now and the fatal heart attack he experienced was the first symptom he had of our family's odd form of inherited diabetes.

But this is why, even though I've inherited the family "cheap" gene, if there's any possibility something dangerous is going on, I head for the ER.

Usually it is a waste of money. I was in a small car accident a few weeks ago that left me with nerve pain running up and down my arms and legs. I sat for four hours at our local ER, saw the doctor for five minutes, and was sent home. The diagnosis, whiplash. The treatment, wait and see if it gets worse. The bill? Over $900.

I went to the ER because I'd called my family doctor's office and they told me to. Whiplash usually resolves on its own, but occasionally it can cause swelling in your neck that can kill you. I'm not equipped to judge what kind I had, and unlike my uncle, I wasn't about to gamble.

So with this in mind, you can understand my reaction when a stranger contacted me recently, after reading my web page, and told me that his blood sugar, which had been normal until very recently, was testing in the 500s on his meter except when his meter wasn't able to give him a number. Cutting the carbs out of his diet was not lowering his blood sugar, either. He'd been told to go to the ER, but didn't have insurance. This is an ugly situation, but being alive without insurance is a whole lot better than leaving a tidy estate. I told him to go to the ER too.

A blood sugar over 500 mg/dl is an emergency. Especially if you aren't already diagnosed with diabetes or under a doctor's care. It's an emergency not because those very high blood sugars will lead to complications. They will, but it takes more than a few days of exposure to high blood sugars to cause complications. It's an emergency because the are two different disorders that can occur when your blood sugar is very high that can kill you within hours.

One is diabetic ketoacidosis (DKA). This is a condition that usually occurs in people who are not making any insulin at all. Usually this means someone with a diagnosis of Type 1 diabetes. But it is also diagnosed in people with Type 2, probably because many people who develop diabetes late in life are misdiagnosed with Type 2 when they really have some form of autoimmune diabetes that is killing off their beta cells.

DKA occurs when people have no insulin in their bodies to counteract their rising blood sugars. Unable to burn glucose without insulin, their cells begin to starve even as their blood sugar rises extremely high. The body survives by burning stored fat which produces ketones. If high levels of ketones build up in their bloodstream, which is already filled with unprocessed glucose, the acidity of the blood rises to a point where, if not treated, it damages tissues irreversibly and causes death.

The symptoms of DKA are high blood sugars (300 mg/dl or higher ) and: excessive thirst, frequent urination, nausea and vomiting, Abdominal pain, loss of appetite, Weakness or fatigue, shortness of breath, fruity-scented breath, and confusion.

The occurrence of DKA is often what triggers a Type 1 diagnosis. Estimates of its fatality range from 1% to 10% but if you get to a hospital when you develop DKA you can be rescued with intravenous insulin and fluids.

The other dangerous condition associated with very high blood sugars is the hyperosmolar hyperglycemic State.(HHS) Untreated this condition leads to coma and death.

It happens when people with Type 2 diabetes become severely dehydrated at the same time that they are experiencing very high blood sugars. This can happen when they have a serious diarrhea and vomiting syndrome like that caused by norovirus or e coli, or in elderly people who are prone to dehydration. With HHS, the patient will not be spilling ketones. But if it occurs it is more likely to be fatal than DKA. Estimates of its fatality range from 10-20%.

HHS may develop over a course of days or weeks, unlike DKA which develops suddenly. Symptoms include very high blood sugar (over 600 mg/dl) and: drowsiness and lethargy, delirium, coma, seizures, visual changes or disturbances, hemiparesis (one sided paralysis), and sensory deficits. Patients with HHS do not typically report abdominal pain, which is often seen in DKA.

What these conditions have in common is that if you develop them, you can go from fine to dead very quickly though they can be treated successfully with intravenous insulin and fluids at the ER.

Not everyone whose blood sugar goes over 500 mg/dl develops either condition. And if you have been diagnosed with diabetes of either type and see an occasional reading over 300 mg/dl, which most people will, it isn't likely to kill you. Nor does one very high reading mean you have to head for the emergency room if you have tools at hand that you have used in the past that you know will lower your blood sugar.

If your high blood occurred because you forgot to take your insulin, because your insulin spoiled due to exposure to high temperatures, or because your needle or cannula got blocked and the insulin you used didn't get into your body, all you may need is another dose of insulin, possibly one from a new vial or a new cannula for your pump.

But if your blood sugar does not come down swiftly in response to your usual techniques, or if your blood sugar is over 300 mg/dl and you are vomiting and cannot keep down liquids, or having a lot of diarrhea, you do need to head to the ER.

And if you are new to diabetes and your meter is reading "HI" or in the 500s and you don't feel well, you most certainly need to head to the ER.

It's possible you'll end up being told your high blood sugar isn't a crisis and leave, as I did, with a huge bill. This is what eventually happened to the gentleman who contacted me. The ER confirmed that his blood sugar was very high, gave him an emergency shot of insulin, told him he had Type 2 diabetes, prescribed metformin, and referred him to a doctor. I don't know what labs were done, but I would hope assume his urine was checked for ketones.

He may be thinking that his trip to the ER was a mistake, but it wasn't. He was feeling unwell and until a doctor determined he wasn't going into DKA or HHS, with the high blood sugars he was experiencing there was a significant risk he might.

You don't want to end up like my uncle. Much better to guess wrong and end up with an ER bill than to guess wrong and end up dead.

March 17, 2009

Parsing the Alzheimers-Diabetes Scare Headlines

The AP carried a story this week that has appeared in many newsletters. More Evidence Links Diabetes to Alzheimer's Risk.

Since I've learned that these kinds of media reports are often based on poor understanding of studies, I tracked down several of the studies cited to see what they really said and learned that as I thought their findings were quite different from what you read in this press story.

Then I found another study, published in Archives of Neurology along with one of the cited studies, which turned out to have far more substantive information than the cited studies and answers many of our questions about the link between diabetes, Alzheimers, and dementia.

So what do these studies really say?

One of the more detailed studies finds a stronger association between diabetes and vascular dementia in people whose average age was the mid-80s. Vascular dementia is a different condition from Alzheimer's that has a different pattern of progressing. It is characterized by the occurrence of mini-stokes in the brain.

This study, not cited in the media, quantified the heightened incidence of dementia in people with diabetes diagnoses. In it, 26% of the 125 people whose brains were autopsied who died in their 80s without dementia were diagnosed with diabetes while 36% of the 71 who were demented had been diagnosed with diabetes.

The researchers doing this study had access to the A1cs and fasting blood sugars of the group as a whole, as well as their medication history. Based on this they noted that the A1cs of those people with diabetes who had not developed dementia were lower than that of those who did--(7.4% compared to 7.8%). This is similar to the finding of another study we cited in an earlier blog post. Though it is worth noting that 63% of those who developed dementia did not have diabetes.

On close examination of these people's brains the researchers found:

Most interstingly, "Individuals without DM but with dementia (DM−/dementia+) had a greater amyloid-beta peptide load and increased levels of F2-isoprostanes in the cerebral cortex, while DM+/dementia+ patients had more microvascular infarcts and an increased cortical IL-6 (interleukin 6) concentration. The number of microvascular
infarcts was greater in deep cerebral structures in patients with dementia whose diabetes was treated, whereas amyloid plaque load tended to be greater for untreated
diabetic patients with dementia.
This means found fewer Alzheimer-like plaques and tangles among the people with diabetes than among people without, and also more IL-6 in the cortex. IL-6 is a marker for inflammation. They also found more sub-cortical lesions in people with diabetes--strokes deep in the brain which may have to do with the nature of the blood supply to those regions.

But what is really interesting is that the people "with diabetes" in this group, who were not "treated" i.e. medicated, had brains more like those of people without diabetes in terms of the amount of beta-amyloid plaques and tangles. The researchers comment that the drop in beta amyloid tangles is,
a result consistent with a recent report from a large autopsy series that showed that decreased senile plaque burden was associated with insulin therapy.
But the researchers also note that they found more evidence of deep brain strokes in the treated group which they note had much higher A1cs than the nonmedicated diabetics. (6.3% unmedicated, 8.6% medicated.)

Unfortunately, the researchers also explain, "A weakness of our study was the limited numbers of DM+/dementia+ cases available for analysis of treatment effects, which made it impossible to analyze specific diabetes treatments."

Another weakness not cited by the researchers but revealed in the data is that the group who were not demented had a slightly lower average age. Since the people (including diabetics) with vascular dementia were two years older on average than those without, and since vascular dementia can arise and kill very quickly (I've seen this in our extended family) the increased amount of vascular dementia may be partially explained by greater age.

Still, this study suggests that there is a slightly higher likelihood of developing dementia among people with diabetes, especially among those with Average A1cs of 8.6% and that this appears to be due to their propensity for having tiny deep brain strokes and brain inflammation. At the same time--what the news reports ignore is that this study, like most, shows that the overwhelming majority of people who develop dementia do not have diabetes.

But before you get too excited about this finding, consider the findings of another study. It found a much stronger link than the one shown in the study we just discussed between vascular dementia and the presence of so-called "metabolic syndrome" in people 92% of whom did not have elevated blood sugars.

In that study, which examined "4895 older women (mean age, 66.2 years)
A total of 497 women (10.2%) had the metabolic syndrome and, of these, 36 (7.2%) developed cognitive impairment compared with 181 (of 4398 or 4.1%) without the syndrome (age-adjusted odds ratio, 1.66; 95% confidence interval, 1.14-2.41).
The incidence of dementia was almost twice as high in the group with metabolic syndrome, though it was low overall probably because this group was younger than the group studied above. But given that less than 8% of this group had elevated blood sugars, one wonders about the extent to which the microvascular damage in either study was due to blood sugar rather than high blood pressure and high triglycerides which were strongly predictive factors in this second study, independent of blood sugar.

And the ambiguity of the results gets worse, because yet another study this one a cohort study of a large number of 2798 people followed from 1992-1999 comes up with this odd result:
In evaluations of midlife obesity, an increased risk of dementia was found for obese (BMI >30) vs normal-weight (BMI 20-25) persons, adjusted for demographics (hazard ratio [HR], 1.39; 95% confidence interval [CI], 1.03-1.87) and for cardiovascular risk factors (1.36; 0.94-1.95). The risk estimates were reversed in assessments of late-life BMI. Underweight persons (BMI <20) had an increased risk of dementia (1.62; 1.02-2.64), whereas being overweight (BMI >25-30) was not associated (0.92; 0.72-1.18) and being obese reduced the risk of dementia (0.63; 0.44-0.91) compared with those with normal BMI.
In short, as you get older the fatter you are, the less likely you are to develop dementia, though if you are middle aged being overweight is more highly associated with dementia.

This is not a freak result, as NHANES data has long supported the finding that after age 70, any weight loss correlated with a higher likelihood of death and that people in the overweight category seem to do better, long term as they age than people of so-called normal weight.

So what should we conclude from all this? Are the headlines unnecessarily alarmist? I'd say, yes. In fact there is no connection here between classic Alzheimer's disease and diabetes. In fact, the opposite seems to be true. People using insulin appear to have less Alzheimer's.

Uncontrolled high blood sugars do seem to slightly up your chance of developing vascular dementia, but not any more than does being overweight in middle age, and having high blood pressure and high triglyceride levels.

Looking at the broader picture, none of these factors make that much of a difference in your risk of developing dementia, because the overwhelming number of people who develop dementia do not have diabetes and more importantly, as people get older, the overweight that is so demonized by doctors appears to protect people from developing dementia rather than promoting it.

Bottom line: There is much you cannot control when it comes to dementia, but to make a slight improvement in your chances, keep your blood sugars under control, keep your blood pressure normal. Keep your triglycerides down. You can lower triglycerides by keeping your carbohydrate intake low because triglycerides are produced when you eat more dietary dietary glucose than your body can burn right away.

If you have diabetes, you can normalize your risk of diabetes-associated dementia by keeping your A1c in the normal range. Your risk for dementia goes way up if you maintain an A1c in the 8% range.

A Last Bit of Good News

The first study cited above gave us some numbers for the blood sugar of "normal" people whose risk for dementia was lower than those with diabetes. Their average A1c was 5.9% and their average fasting glucose was 105 mg/dl (5.8 mmol/L).

These are VERY attainable numbers for all people with diabetes so if the association of "diabetes" with dementia worries you, shoot for those numbers.

March 13, 2009

How to Reverse Fatty Liver

Two recent studies have come up with some useful information about what it takes to reverse nonalcoholic fatty liver disease.

This is a condition where fat accumulates in the liver. It is often considered "benign"--that is not associated with any adverse health effects. But in rare cases it can lead to liver damage and, very rarely, this damage may lead to liver failure.

Fatty liver disease is caused by--or found in association with--the taking of certain medications, gastric bypass surgery, high cholesterol, high levels of triglycerides in the blood, malnutrition, metabolic syndrome, obesity, rapid weight loss, toxins and chemicals, such as pesticides, Type 2 diabetes, and Wilson's disease.

The drugs reported as causing fatty liver include total parenteral nutrition, methotrexate (Rheumatrex), griseofulvin (Grifulvin V), tamoxifen (Nolvadex), steroids, valproate (Depakote), and amiodarone (Cordarone).

However, most people with Type 2 diabetes who develop fatty liver probably develop it because of exposure to the very high triglycerides that result from uncontrolled high sugars.

If you are diagnosed with fatty liver, you will probably be told that losing weight will reverse fatty liver, and this appears to be true.

The two studies I want to discus here tell us two things: how much weight you have to lose to reverse your fatty liver and what the most effective diet might be for doing that.

How Much Weight Loss Reverses Fatty Liver

The first study Orlistat for overweight subjects with nonalcoholic steatohepatitis: A randomized, prospective trial. was another drug company supported trial that hoped to prove that the drug, Orlistat, which blocks the digestion of fat would reverse steatohepatitis, which is the term for the inflammatory liver condition that develops in some people with fatty liver.

In fact, the study found that Orlistat neither enhanced weight loss or made any positive changes in the laboratory markers relating to the inflamed liver. However, what it did discover was that when patients managed to lose weight--using any technique--their liver disease improved. Beyond that, the study quantified how much weight loss was needed to achieve this.

Their findings were these:
...subjects who lost 5% of body weight over 9 months improved insulin resistance and steatosis [liver inflammation], and those subjects who lost 9% also achieved improved hepatic histologic changes [liver cell changes visible on microscopic exam].
In short, inflammation started to recede when 5% of the starting weight had been lost and when subjects lost 9% or more of their starting weight and maintained that loss over a period of nine months, the damage that had been done to their livers started to improve.

This is good news, because it turns out that 10% to 20% of starting weight is about as much weight as most people can lose without obsessional dieting, so it's good to know that losing only 20 lbs when you weigh 200 lbs though it isn't enough to make you comfortable wearing a bikini, is enough to reverse any liver damage you might have sustained.

Which Diet Burns Liver Fat Best?

The second study is Alterations in hepatic glucose and energy metabolism as a result of calorie and carbohydrate restriction.

To understand this study which is quite technically complex, I'd suggest you read the article about this study that was posted on Diabetes in Control: Low-Carb Diet Burns More Excess Liver Fat Than Low-Calorie Diet.

In brief, this study assigned 7 overweight people to a low calorie diet, 7 overweight people to a low carbohydrate diet, and used a group of 7 lean people eating normally as controls. Though the numbers are very small, that is because of the high expense of the techniques employed. And I already like this study, because of the inclusion of controls. This is a factor so often lacking in diet studies.

After two weeks, they studied their livers using advanced imaging techniques. They found that the liver behaved differently in people on a low carbohydrate diet. To quote Diabetes in Control,
“We saw a dramatic change in where and how the liver was producing glucose, depending on diet,” said Dr. Browning. Researchers found that participants on a low-carbohydrate diet produced more glucose from lactate or amino acids than those on a low-calorie diet. “Understanding how the liver makes glucose under different dietary conditions may help us better regulate metabolic disorders with diet,” Dr. Browning said.
In addition,
people on a low-calorie diet got about 40 percent of their glucose from glycogen, which is comes from ingested carbohydrates and is stored in the liver until the body needs it.

The low-carbohydrate dieters, however, got only 20 percent of their glucose from glycogen. Instead of dipping into their reserve of glycogen, these subjects burned liver fat for energy. [emphasis mine]
This latter finding is the one of most interest to those with fatty liver disease. The doctors who conducted the study believe it may point to the superiority of eating low carb diet when attempting to reverse fatty liver disease and will be doing more research to look into this.

By the same token, if you don't already have fatty liver disease, eating the low carbohydrate diet that has been shown repeatedly to lower triglycerides may prevent you from developing it.

March 11, 2009

FDA Approves Apidira SoloStar Disposable Pen!

I just read in Diabetes in Control that the FDA has finally approved the disposable Apidra pen.

I've been using Apidra for almost six months and for me it is by far the most phyiological fast acting insulin. Injected at the time I eat, it peaks exactly when my food peaks, and it's gone in about 2 hours. If I eat something that digests slowly, I may split my dose and do another small booster shot at 2 hours.

Until now, Apidra was only available in vials or cartridges that you use with the huge somewhat clumsy OptiClick pen. I like that the Opticlick displays the dose you've injected for a few minutes. But I don't like that if anything goes wrong with the pen you have to get a new one, in my case, from a doctor as the pharmacies don't stock them here, which could leave you high and dry if it broke during a weekend.

This availability in the new disposable pen makes Apidra more competitive with Novolog, too. The pen is the same one used for Lantus--though I never understood why you would need to dispense once a day insulin via pen. Especially since most people using Lantus use large enough doses that they'd go through a pen in a few days.

Unfortunately, the insurers in my region don't cover pens unless you are blind, and my own insurer doesn't cover Apidra at all. But when a new product like this is released, doctors get a lot of free samples, so if nothing else, more people may be trying Apidra and perhaps the drug reps will turn their intensive marketing efforts to getting the insurance company to cover Apidra along with Novolog and Humalog. It doesn't cost any more than they do.

March 10, 2009

Study Identifies Virus Linked to Both Type 1 and Type 2 Diabetes

Last week's Science News directed my attention to a fascinating new study. I could not find the actual study posted online, but I did find this excellent article provided by the UK NHS which gives more information about it than you will find in the abstract when it comes out:

NHS: Diabetes Linked to Virus

This study replicated findings of an earlier study linking the finding of enterovirus on autopsy in human pancreases of people with Type 1 diabetes but not those without it. The enterovirus is a stomach virus that causes vomiting.

This new study went beyond the earlier study in quantifying how frequently this virus was found in people with and without Type 1 diabetes and looking at where the virus was found in the pancreas.

The researchers used sophisticated techniques to hunt for viral proteins in the pancreases of 72 young people diagnosed with diabetes who had died on average 8 months after diagnosis and of 39 children who had died at the same age who did not have diabetes.

They found that 61% of the children recently diagnosed with Type 1 diabetes showed signs of pancreatic infection with the enterovirus. Furthermore, when they looked at where the protein was being expressed, they discovered that it was being expressed almost entirely in the beta cells found in the pancreas islets that further testing showed had been still producing insulin at the time of death. The researchers also found an antiviral protein, PKR in these same islets.

In contrast, only about 8% of the pancreases of children who had died of other causes were found to have viral proteins from enterovirus, and their pancreases did not have any antiviral PKR protein in their islets.

This association of the virus and the anti-viral protein is very interesting, and may suggest an explanation for why, even though we know there is a genetic profile associated with Type 1 diabetes, some people with that profile get Type 1 and others do not. This is true even in identical twins, which has always suggested that there must be some environmental factor that causes someone with a certain genetic make-up to develop Type 1.

But, as they say on the infomercials, That's Not All!

These brilliant researchers went on to use the same techniques to examine the pancreases of a group of adults who had been diagnosed with Type 2 diabetes and then compared them with the pancreases of a group of adult controls who did not have Type 2 diabetes. Here's what they found: Forty percent of the pancreases from adults with type 2 diabetes contained the enterovirus protein. But it was found in only 13% of the normal adult pancreases. The incidence of enterovirus in pancreases of people diagnosed with Type 2 was three times higher than in those without it.

They did not, apparently, check the Type 2 pancreases for the antiviral protein PKR. That is a shame because it would be important to know if the people without Type 2 diabetes who harbored enteroviruses in their pancreases also lacked the PKR that was lacking in those children with enterovirus in their pancreases who did not develop Type 1 diabetes.

The most important thing about this study is that hints very strongly that both Type 1 and Type 2 diabetes may be related to infection with this common gut virus.

Though it is important that the study confirms the earlier finding that the virus is linked to Type 1 diabetes and found that further implication of the PKR anti-viral protein, finding the link between enterovirus and Type 2 strikes me as being the real news here--one that appears to have eluded those writing the reports about this study in the media.

If you've been reading my blog and web site you know that I'm convinced that Type 2 diabetes is no more "caused by obesity" than Type 1 is. There is a huge amount of evidence accumulating that suggests that while "prediabetes" is common among people who are overweight, people, no matter how overweight do not develop full fledged Type 2 diabetes unless they have one of dozens of specific underlying genetic conditions that have been linked in research study after research study with Type 2 diabetes. Even then, as was the case with Type 1 genes, you need some environmental factor to turn the genetic profile into actual diabetes.

We already knew from other research, that these environmental factors may include exposure to pharmaceutical drugs like Zyprexa and some SSRIs, exposure to pesticides or PCBs, and plastics like Bisphenol-A. Now we have found another possible culprit. A common virus your children are likely to bring home from elementary school.

The good news is that it may be possible to create a vaccine against this particular virus and if that happens, it might eliminate one factor that pushes beta cells towards failure.

March 5, 2009

The Supreme Court Hands Patients a Win!

From Reuters:

WASHINGTON, March 4 (Reuters) - The U.S. Supreme Court on Wednesday ruled against the drugmaker Wyeth in a closely watched case, holding that pharmaceutical companies can be held liable for harm from medicines which carry warnings approved by federal regulators.

By a 6-3 vote, the high court ruled that labeling approvals by the U.S. Food and Drug Administration does not preempt state laws and shield companies from legal damages as part of liability claims.

This is huge. If this case had gone the other way, the same drug companies that get their drugs approved by the FDA by submitting cherry picked studies and heavily massaged data, the FDA run by executives who go right back to the drug industry when they leave the FDA, would have been protected from lawsuits from those patients their drugs harmed.

Instead, the court ruled that the company still has a responsibility to protect the people who use their drugs no matter what the FDA says.


While the business press is treating this as a victory for trial lawyers, it is worth noting that trial lawyers don't take cases unless someone has been seriously maimed or killed. If they are maimed or killed by a drug because the company that provides that drug omitted to mention that the drug could maim or kill in the information it gives doctors, the drug company should pay a price. It will be far less than that paid by the victims of their negligence.

The real benefit of this decision is not for trial lawyers. It is for you, the patient. The drug companies have known all along about the studies they have kept hidden from the FDA and from the public. They also know how the data has been massaged to hide certain findings when they earned product approval. We saw this when Avandia's connection with heart attack finally was made public many years after the company had suppressed this information. We just saw this in the case against the makers of Seroquel who also hid data showing their drug to be less effective than older drugs and more likely to cause diabetes in people who otherwise would not have gotten it.

Now thd drug companies whose drugs' hidden dangers have not been revealed have been put on warning. They will be subject to ruinous law suits if they don't do something to protect the public against the dangers that they already know their drugs present.

Like, for example, the likelihood that Januvia's inhibition of DPP-4 is turning off the tumor suppressor gene you need to survive prostate cancer, melanoma, lung cancer, and ovarian cancer.

There are studies that could be done to determine if this is the case. They have not been done. The only screening done currently when the FDA approves a drug, to rule out that it causes cancer, is screening to see if the drug causes cancer in test tube cells or rodents. No one is saying Januvia causes cancers, only that it turns off our cancer fighting mechanism.

Most of us develop one or two cancerous cells many times throughout our lifetimes, but our tumor suppressor genes kill them. There is no research to see what happens to people harboring one or two cancerous cells when you give a drug that turns off the anti-cancer genes, and that is exactly what Januvia is doing.

It may take ten years until the Januvia-related cancer epidemic becomes evident. At least, with this latest Supreme Court case decided, the company selling it, whose scientists must know of the tumor suppressant features of DPP-4 will not be able to say, "The FDA approved Januvia, so we're off the hook."

March 3, 2009

Extremely Bad Science: HEART2D "Proves" Fast Acting Insuiln is Worthless

Sometimes you see a study published that is so poorly conceived it leaves you wondering how lab chimpanzees were able to take over the department that ran the study and how they got into the journal office that published it.

The most recent study that falls into this category was published in this month's Diabetes Care.

Effects of Prandial Versus Fasting Glycemia on Cardiovascular Outcomes in Type 2 Diabetes: The HEART2D trial

It is very important that you pay attention to what is wrong with this study, because it is yet another study whose outcome is going to be used to justify denying you the care that could prevent you from developing complications.

The idea behind this study was to see if lowering post-meal blood sugars would be more effective in preventing heart attacks than using a strategy of lowering fasting blood sugar alone.

Okay. That sounds reasonable. Why am I trashing this study?

Here's why: The study took a group of people who had already had a heart attack. It assigned them to two groups. One received three shots a day of Humalog (Lispro). The other received either 2 shots a day of NPH or one shot of Lantus.

Do you see the problem with this study? Of course you do! They gave no basal insulin to the people who were given the post-meal insulin. But all these people started out with very high A1cs which tells you that their fasting blood sugar control was shot. So when those three shots of fasting insulin wear off, their blood sugar will go right back up.

That, apparently, is exactly what happened. At the time the study was stopped both groups of patients had nearly the same average A1cs: 7.7 ± 0.1 (Humalog) and 7.8 ± 0.1% (basal insulin.) The people using fast acting only would have had their blood sugars rise any time they were in the fasting state. The people using basal only had their blood sugars shoot up any time they were in the post-meal state.

No group was given insulin to control their blood sugars in both states. Brilliant, eh?

Endocrinologists do not prescribe post-meal insulin alone. They prescribe it in combination with basal insulin. That researchers in a major study involving 1,115 patients were so ignorant that they set up their experiment in a way that violated everything doctors know about blood sugar control is criminal. That the editors of Diabetes Care considered this study worthy of publication is even more so.

Criminal? That's a strong word. But it is probably not strong enough. Because you can be certain this study will be used by insurance companies as "Evidence Based Medicine" that justifies withholding expensive fast acting insulin from patients.

In fact, all this study really proved is that if you maintain your blood sugar at levels high enough to produce a 7.7% A1c and already have severe heart disease you have a one in three chance of having another heart attack.

This is not news. EPIC-Norfolk data already showed conclusively, drawing on a huge number of study subjects, that people with A1cs well over 7% have three times the risk of heart attack as those with an A1c of 5.5%-6% and between 4 and 5 times higher than those with an A1c of 4-5.4%.

So in addition to proving that using fast acting insulin without basal insulin is ineffective in people with very high blood sugars. this study also proves only that allowing patients who have already had a heart attack to maintain average blood sugars at levels known to quadruple cardiovascular risk in anyone will not change their risk.

But try telling that to your insurer when they tell you they are no longer paying for your fast acting insulin because "studies show it doesn't do anything.