Brand New Gestational Diabetes Cutoffs Point to Safe Levels

The cutoffs for diagnosing gestational diabetes--the kind that occurs during pregnancy--have always been more stringent than those used to diagnose the general population. Now a large study that matched maternal blood sugars with the outcome of the pregnancy has documented that even more stringent blood sugar limits are necessary to avoid diabetic problems during pregnancy.

Not so surprisingly, the new blood sugar targets they urge are very similar to those that are emerging from research connecting blood sugar levels with complications with diabetes in people who are NOT pregnant. (Details HERE.)

Here, from the report in Science Daily are the findings:

Based on a study of more than 23,000 women in nine countries, Metzger and an international group of 50 experts concluded a fasting blood sugar level of 92 or higher, a one-hour level of 180 or higher on a glucose tolerance test or a two-hour level of 153 or higher on a glucose tolerance test constitute serious risks to the mother and baby.

Science Daily: Gestational Diabetes: Blood Sugar Levels Once Considered Normal Are Not Safe for Baby, Mother

Compare these findings to the results in non-pregnant people that found that the presence in young men of a fasting blood sugar over 92 mg/dl predicted the development of diabetes a decade later, and that cardiovascular risk takes a major step up once the one hour glucose tolerance test result goes over 155. (Details HERE.)

Since complications kick in at these levels you would want to keep your blood sugar a bit lower, which is why I continue to suggest that you shoot for the "Five Percent Club" blood sugar targets. Note that the fasting number in our targets is higher, largely because so many people with diabetes will find the fasting number the hardest to lower. Most research, however, points to the post-meal numbers as being those that produce the complications.

The values before are for first thing in the morning fasting blood sugar and one and two hours after eating meals.

Yes: Actos and Avandia Cause a Huge Increase in Fracture Risk

I've blogged about the way Avandia and Actos cause osteoporosis and broken bones before. I've also documented this on the page where I summarize all the research that makes it clear how dangerous both these drugs are, which you can read HERE.

But I wanted to bring your attention to a new cohort study involving 19,070 patients with diabetes, which was published in the Journal of Clinical Endocrinology and Metabolism. It quantifies just how big the fracture risk of these drugs really is.

Thiazolidinedione Use and the Longitudinal Risk of Fractures in Patients with Type 2 Diabetes Mellitus Zeina A. Habib et al. JClinEndo&Metab Vol. 95, No. 2 592-600 doi:10.1210/jc.2009-1385

As summarized in the newsletter, Endocrine Today, researchers

... studied 19,070 patients at Henry Ford Hospital in Detroit between January 2000 and May 2007. The study group included 9,620 women and 9,450 men.

During the study period, 4,511 patients had at least one prescription filled for a TZD. The investigators used electronically maintained medical claims data to identify nontraumatic bone fractures.

TZD use was associated with an increased risk for fracture in the overall cohort (adjusted HR=1.35; 95% CI, 1.05-1.71) and in women (HR=1.57; 95% CI, 1.16-2.14). Men, regardless of age, were not at an increased risk for fractures (HR=1.05; 95% CI, 0.70-1.58).

Women aged 65 years and older appeared to be at the greatest risk for fracture (HR=1.72; 95% CI, 1.17-2.52).

They found that the increased risk for fracture in women appeared after approximately one year of TZD use.

Before you conclude that this means this is a safe drug for men and younger women, you need to remember that fractures due to osteoporosis only occur after bone has been significantly weakened. Older women already have weak bones so any factor that weakens them further will stand out.

But the chances are very good that these drugs are causing osteoporotic changes in patients with denser bones and that over time they too will find themselves with dangerously fragile bones.

The reason we know this is that we know WHY these drugs cause osteoporosis. It is because the mechanism they use transforms stems cells that would normally become baby bone cells into baby fat cells. You can read more about this mechanism HERE.

With what we already know about how these drugs cause edema and promote heart failure in people who did not have it before they started the drug this latest very large study should make it crystal clear that this is not a good drug to take. Once you've rotted out your long bones, you face a lifetime of limited mobility that undoes any minor change in blood sugar they may make. And they only make a very small change in blood sugar. Not enough to take this kind of risk.

If your doctor still insists this is a safe drug, print out the information you'll find HERE and for an explanation of why you should be ignoring it.

 

TCF7L2, What this Very Common Type 2 Diabetes Gene Does

Many of you have been sold a bill of goods about how you "caused your diabetes" with unhealthy lifestyle choices. The media are full of articles telling us that diabetes is caused by obesity and failure to exercise which cause insulin resistance. You might have been told that while people with Type 1 Diabetes don't secrete insulin, people with Type 2 Diabetes secrete too much insulin. Though doctors repeat this misinformation, it turns out not to be true.

High quality research suggests very strongly that most Type 2 Diabetes results from genetic damage. This damage may be inherited or it may be caused by environmental pollutants like arsenic, PCBs, pesticides and popular prescription drugs. The environment of the womb can also permanently alter the expression of certain genes in ways that promote the development of Type 2 Diabetes.

Since the research has made it clear that most Type 2 is inherited, scientists have been using the new, cheap tools for studying the genome, to search for the gene variants that are common among people with Type 2 diabetes and absent in the rest of the population.

The single most common Type 2 Diabetes gene they've found in populations of people with Western European heritages is a variant of TCF7L2. A study published in this month's edition of the journal Diabetes sheds much light on why this gene is so closely associated with (i.e. causes) Type 2 Diabetes. You can find the study here:

TCF7L2 Variant rs7903146 Affects the Risk of Type 2 Diabetes by Modulating Incretin Action
Dennis T. Villareal et al. Diabetes Diabetes February 2010 vol. 59 no. 2 479-485, doi: 10.2337/db09-1169

First off, ignore the article's title. As is becoming more and more common, the titles of research studies are being slanted to appeal to whatever the fashionable belief of the year might be in diabetes research. And as is also common, that fashionable belief is heavily influenced by the mechanisms used by whatever new drugs are being peddled by Big Pharma. Since right now incretin drugs are the hottest (i.e. most expensive) new drugs, the researchers pitched this article as if it was a study documenting the effect of the defective TCF7L2 gene on incretin hormones. In fact, its results show something else entirely.

What the researchers did here was take eight subjects with the specific variant of the TCF7L2 gene that has been linked to Type 2 diabetes and compare them to a group of 10 controls lacking this gene variant. The tool used was a fancy 5 hour glucose tolerance test. (Yes, I know this is a pitifully small sample which makes its result suspect, and thanks for noticing.)

As described in the study the subjects:

underwent 5-h oral glucose tolerance test (OGTT), isoglycemic intravenous glucose infusion, and graded glucose infusion (GGI).

The isoglycemic infusion is one where glucose levels are maintained at a constant level. In the graded glucose infusion the glucose amount is raised in steps in amounts that are usually calculated as a function of the subject's body weight. This is because glucose raises blood sugar in inverse proportion to the subject's body weight: the more a person weighs, the less rise there is with each additional gram of glucose.

Note that the researchers made no direct measurement of the incretin hormones, GLP-1 and GIP in the course of the study. They drew their conclusions about incretin hormones after applying a mathematical model to the glucose tolerance test results.

As stated in the study:

The incretin effect was assessed from ratios of the insulin secretory rates (ISR) during oral and isoglycemic glucose infusions.

This strikes me as an odd way to determine the effect of incretin hormones. I'm sure the model was based on the findings of some other study, but without direct measurement of the incretin hormones the conclusion has to be labeled, at best, "speculative".

So let's ignore that for now, and see what we can safely conclude from this fancy glucose tolerance test. And it turns out that it is something worth noting. The study found that

β-cell responsivity to oral glucose was 50% lower (47 ± 4 vs. 95 ± 15 × 109 min−1; P = 0.01) in the group of subjects with risk-conferring TCF7L2 genotypes compared with control subjects.

This means the TCF7L2 gene carried by so many people with Type 2 diabetes damages the ability of the beta cell to secrete insulin in response to rising blood sugars.

If so, we can define TCF7L2-related Type 2 Diabetes as a disease of insulin insufficiency, NOT, as we are usually told, a disease caused by insulin resistance.

The headlined conclusion of this study, based on the estimates of "incretin effect" derived from the mathematical model is that:

The TCF7L2 variant rs7903146 appears to affect risk of type 2 diabetes, at least in part, by modifying the effect of incretins on insulin secretion. This is not due to reduced secretion of GLP-1 and GIP but rather due to the effect of TCF7L2 on the sensitivity of the β-cell to incretins.

This translates into saying that normal amounts of incretin hormones are being made, but the beta cell isn't responding to them. Given that this conclusion is drawn without any measuring of incretin hormone levels, the only part of this statement that is reliable is the "at least in part" which translates into, "Perhaps, maybe."

In any case, this is not the first study to find that the common genes associated with Type 2 Diabetes cause failure to secrete insulin, NOT insulin resistance. The more research done into these genes, the more the balance is shifting to finding that Type 2 Diabetes is often an insulin deficiency disease.

You can read about the research that had identified the common Type 2 Diabetes genes in this excellent summary:

NIH News: Newly Identified Genes Influence Insulin and Glucose Regulation: Five of these variants raise type 2 diabetes risk.

Note this extremely interesting statement from the lead researcher in this large scale effort to find Type 2 Diabetes genes:

"The hallmarks of type 2 diabetes are insulin resistance and impaired beta cell function. We were intrigued to find that most of the newly found variants influence insulin secretion rather than insulin resistance. Only one variant, near IGF1, is associated with insulin resistance," said lead author Inês Barroso, Ph.D., of the Wellcome Trust Sanger Institute, Cambridge, England.

You can read about much more research that links Type 2 Diabetes to genetic flaws both inherited and caused by environmental pollutants on the web page,

You Did Not Eat Your Way to Diabetes.

If you have been blaming yourself for causing your diabetes, I urge you to take a look at that page. You'll feel a lot better about yourself after you do.

 

Inflammation Raises Blood Sugar

Many people diagnosed with Type 2 diabetes are not aware that the presence of significant inflammation anywhere in the body can raise their blood sugar. But this is a very important finding. In rare cases, people can lower their blood sugar significantly by eliminating the inflammation.

Unfortunately, because high blood sugar weakens the immune system, diabetes can create a vicious circle where inflammation raises blood sugar which deactivates the immune system components that should fight the inflammation, allowing the inflammation to increase, and further raising blood sugar.

A very common site for inflammation that can have this kind of effect is the gum. Dr. Richard K. Bernstein, author of Dr. Bernstein's Diabetes Solution: The Complete Guide to Achieving Normal Blood Sugars has long preached about the importance of eliminating the infection associated with gum disease.

The usual way dentists approach treating gum disease is to treat it with antibacteria mouthwashes and gum surgeries until, inevitably, the teeth all have to be removed. Dr. Bernstein suggests treating it with a long-term aggressive course of antibiotic therapy. This is controversial because of the side effects of long term antibiotic use, but he reports that this approach is successful and lowers his patients' blood sugars. He doesn't comment on whether it allows them to keep their teeth, which would be worth knowing.

A meta study published in this month's edition of the journal, Diabetes Care reviewed the research on the relationship between periodontal treatment and A1c and concluded that such treatment appeared to lower the A1c. Unfortunately, because this is a meta study, the definition of "periodontal treatment" is different from study to study, which limits its usefulness and keeps the metastudy's finding from being "robust."

You can see that study here:

Effect of Periodontal Treatment on Glycemic Control of Diabetic Patients: A systematic review and meta-analysis. Wijnand J. Teeuw et al. Diabetes Care February 2010 vol. 33 no. 2 421-427. doi: 10.2337/dc09-1378

It is worth noting that other studies have linked the presence of gum disease with the development of heart disease. This association may or may not be independent fact that blood sugars in the "prediabetic range" also raise the risk of heart disease. The incidence of heart disease increases dramatically as blood sugars rise into the "pre-diabetic" range and hit 155 mg/dl (8.6 mmol/L) one hour after glucose challenge. (I blogged about the study documenting that HERE.) It is not known whether eliminating the bacteria associated with gum disease after it has occured lowers the risk of heart disease.

Smoking greatly increases the incidence of gum disease, by damaging the tiny capillaries that should bring immune system cells to the gum where they can fight off the infections. This may have something to do with why smoking increases the risk of heart attack.

Gum disease is only one kind of inflammation that can raise blood sugar. Systemic autoimmune inflammatory conditions like Rheumatoid Arthritis and Lupus can also have an impact on blood sugar and I have received anecdotal reports from people who have found dietary ways of controlling their RA which also lowered their blood sugar.

It is possible that the inflammatory effect of gluten on many people who have forms of celiac disease may explain why the elimination of grains from the diet has such a powerful effect on the blood sugar of some people with diabetes beyond the fact that cutting out grains lowers carbohydrates.

There is some evidence that obesity may be associated with an inflammatory state in the fat cells. You can read a summary of research on this topic HERE.

I am not certain that the obesity is causing this inflammation, however, since I know for a fact that in Type 2 Diabetes, the elevated blood sugar or abnormal level of genetically caused insulin resistance is present long before the individual becomes obese. It is quite possible that in humans the inflammation of fat cells precedes the development of obesity. Inflammation may do this by damaging the receptors the fat cells use to take in the circulating peptides the body uses to regulate fat storage and fat burning.

Another area of the body that is prone to low level inflammation that is very difficult to diagnose and treat is the urinary tract. Because the urine of people with diabetes can be full of glucose which feeds invasive bacteria, people with diabetes are very prone to get urinary tract infections.

Unfortunately, the bacteria that cause these infections form bacterial mats which can make these infections very difficult to eliminate. The antibiotics given for urinary tract infections tend to knock back the bacteria rather than eliminate them and over time repeat antibiotic use can breed drug resistant superbugs.

Even worse, these bacterial mats may keep bacteria bound up and prevent them from showing up in cultures in numbers high enough to provide a diagnosis. This is particularly true when the bacteria have colonized the urethrea.

If you have an ongoing problem with recurring urethral symptoms that don't culture, do not jump to the conclusion that you have a non-infectious condition such as Interstitial Cystitis, until you have tried several long term treatments with powerful antibiotics that are known to reach the urethra. Not all drugs routinely prescribed for urinary tract infection reach the urethra. Macrodantin (nitrofurantoin) does not.

One area where treating inflammation may worsen insulin resistance is heart disease. We know now that statins have a positive effect on the subset of people elevated cardiac-specific C Reactive Protein (CRP), which is an index to inflammation in the blood vessels. This effect appears to have little to do with the fact these drugs lower LDL cholesterol and everything to do with the fact that they appear to decrease inflammation in the blood vessels.

But statins do not appear to lower insulin resistance in humans, though they might do this in rodents. In fact there is some evidence that statins increase insulin resistance in humans. I have blogged about that finding HERE.

 

The Lancet Study: Old Patients Victimized By Poor Treatment Die of Hypos from 70/30 Insulin Regimens

The latest outrage perpetrated on the diabetes community is a study published recently in the Lancet which is being widely reported in the media as proving that the 6.5% A1c is dangerous and that the "safest" A1c for people with diabetes is one of 7.5%.

The 7.5% A1c corresponds to an average blood sugar of 169 mg/dl (9.4 mmol/L). To get an average that high a person would typically be seeing blood sugars rising into the middle 200s after every meal, a level that the ADA has confirmed is associated with the development of retinopathy and eventually, blindness. That A1c also guarantees you will develop neuropathy. Two previous studies, ACCORD and ADVANCE both found that lowering A1c to 6.5 lowered neuropathy significantly.

The abstract of this study can be found here:

Survival as a function of HbA1c in people with type 2 diabetes: a retrospective cohort study. Dr Craig J Currie. The Lancet, Early Online Publication, 27 January 2010. doi:10.1016/S0140-6736(09)61969-3

Unfortunately, this study can only be understood by reading the full text which is NOT available for free. Someone sent me a copy so I was able to read it, and I will summarize the most important points that the full text makes for you. Save them off somewhere, because it is almost certain your doctor, who does not have access to the full text will NOT understand the conclusions of this study and will use it to deny you the treatment you need to keep your A1c in the low, safe zone that will prevent you from getting complications.

I am going to keep this brief to make it easy for you to grasp the concepts you will need to know to counter the arguments your doctor might make.

1. WHO WAS STUDIED: This Study analyzed records of about 50,000 British Patients Dating Back to 1986. In this study there were two and a half times as many patients with A1cs of near 11% as there were patients with A1cs near 7%. This reflects the abysmal treatment patients in the UK received during this period which was characterized by treatment that let them maintain very high A1cs for years before being offered insulin.

The average age of the patients with 11% A1cs was 59.7. The average age of those with the lowest A1cs was 67.4. This again reflects the fact that people in the UK had to spend years with very high blood sugars before being given insulin to lower blood sugars. The study methodology suggests very strongly that these people with 6.5% A1cs had low A1cs because they had been put on insulin, and that they had been put on insulin only after experiencing years of extremely high A1cs.

One reason for these very high blood sugars is that British patients, even today, are usually not given blood sugar meters until they have had uncontrolled diabetes for long enough to produce serious complications. They are never told that they can lower their blood sugars by cutting back on carbohydrates. Instead they are told to cut back on fat with the implication that fat is what raises their blood sugars.

Most of the patients in this study were not diagnosed with until their fasting blood sugar was 140 mg/dl (7.7 mmol/L) as this was the diagnostic standard until 1998. The Hoorn Study showed that fully half of all people diagnosed with this fasting blood sugar cut off already have significant neuropathy on the day of diagnosis. This means they probably had undiagnosed diabetes--post- meal blood sugars over 200 mg/dl (11 mmol/L) for as long as a decade before diagnosis.

The patients who'd been put on intensive therapy already had 2.5 times much severe diabetic kidney damage diagnosed by high creatinine levels as did the younger patients. Keep in mind that the younger patients also had the very high A1cs guaranteed to give them kidney problems as they grew older.

CONCLUSION: The people with low A1cs in this study were those who had spent many years with damagingly high blood sugars, both before and after diagnosis. Many had spent nearly a decade with A1cs near 11%. They were not put on insulin until they had already developed serious diabetic complications.

2. HOW WERE THEY TREATED: The patients given oral treatment were all given sulfonylurea drugs. Since this study goes back to the 1980s, this means they were given the first generation sulfonylurea drugs--the ones now known to promote heart attack. There is a black box warning on all sulfonylurea drugs in the US because of their proven association with increased heart attack death.

The full text of this study makes it clear that the patients with the 6.5% A1cs were those who had been put on insulin after many years of being out of control.

The study does not break out the kinds of insulin or the regimens used. After reading the diabetes discussion boards for years I can tell you what the typical UK insulin treatment was during the time of this study. It was a 70/30 insulin twice a day. 70/30 insulin is a combination of long acting and short acting insulin, usually in the UK involving NPH as the "long acting" insulin. The fast action portion cannot be matched to carbohydrate intake and NPH is notorious for its unpredictable activity curve and ability to provoke severe hypos.

The 70/30 insulin regimen is the one most likely to cause severe hypos, and from the discussion in this study, that appears to be exactly what it did. The group with the low A1cs had a very high rate of hypo. As stated in the study:

In this study, mortality was three times higher in patients in either the conventional or intensive treatment groups who had severe hypoglycaemia than in those who did not have severe hypoglycaemia.

One factor not discussed in this study is the damage caused by a high degree of blood sugar variation. It is now understood that large fluctuations in blood sugar--for example, a blood sugar that rises from 100 to 300 after a meal and then plunges down to 70 three hours later--are more damaging to tissues than blood sugars that stay stable.

When you give one or two fixed dose shots of 70/30 NPH based insulin to people who are eating high carbohydrate diets you guarantee just that kind of blood sugar variability. The 6.5% A1c will result from a blood sugar that goes high and then drops very low because it is an average.

The Kumamoto Study made it very clear that if A1cs are attained by keeping peaks low rather than going high and then low, far fewer complications result.

Finally, because the people in this study had been out of control for years, they were prone to autonomic neuropathy--damage to the nerves that control the systems the body uses to fight hypo. This made it more likely that if they started to have hypos, they would develope "Hypo unawareness" which causes the severe hypos that damage the brain and body. These are more likely in older Type 2s, which is the group put on the poorly designed insulin regimens used in the UK.

CONCLUSION: The low A1cs in this study were due not to good control but to the dangerous combination of blood sugar highs followed by severe hypos. Both these factors are known to increase mortality.

3. WHAT TO DO IF YOUR DOCTOR URGES YOU TO SHOOT FOR A "SAFE" 7.5 A1C.

Explain that this study is irrelevant to patients who achieve a lower A1c by using a blood sugar meter to monitor their blood sugars and who keep their blood sugar in a narrow normal in a way that does not cause hypos.

Explain that this study is irrelevant to patients diagnosed before they have developed serious complications who avoid sulfonylurea drugs and use modern insulins less likely to provoke hypo.

Explain that doctors who only read one line summaries of studies may inadvertently harm patients. The authors of this study made clear its many limitations, but the reporting of this study even in the medical press is focusing only on its conclusions without citing the many cautions that the authors provided in the text.

Explain to your doctor that there is a large body of research that makes it clear that it is high post meal blood sugars, not A1c that cause neuropathy, retinopathy, and kidney damage, and that you intend to avoid developing any of these horrible complications by maintaining a safe, healthy blood sugar, as measured by blood sugar testing after meals, rather than relying on the A1c test to determine how you are doing.

You are fortunate in that you have read this information here. Sadly most people with diabetes will not, and it is very likely that their doctors will use this irrelevant result to deprive them of the treatment that could prolong their life and prevent them developing life-ruining complications. Insurers love this kind of study too as it justifies them in denying patients expensive care.