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.


CarolynC said...


Thanks for another informative blog entry. With regard to affordability, Landmark has a blood spot hs-CRP (hs = high sensitivity) test for about $35/test. You collect the blood spot at home on a card and send it off for analysis.

I did this last June after reading about the importance of CRP. My results came back with a reading of <0.3 mg/mL. I was very pleased.

I'm a 52 year old female who was diagnosed with type II diabetes 13 years ago. My father suffers from both type II diabetes and heart disease and diabetes is common in both sides of my family. I don't have any other health issues (although my HDL is lower than desired and my LDL is higher and I'm still about 20 pounds overweight). My blood sugar is usually well controlled with diet and exercise and metformin, although I'm currently struggling greatly with the dawn phenomenon. (I find post-prandial blood sugar much easier to control than fasting blood sugar.) I've begun to wonder if that is being made worse by menopause.


Anne said...

I had a very high hs-CRP - it was found to be over 13 back in 1996 when I first started having problems with my coronary arteries. Over the years this number has slowly come down. I feel this number has dropped because of my lifestyle changes and supplements. I was not able to tolerate statins. My latest test was 2.19. Not optimal, but I am thrilled with getting it under 3.

I think some of my recent lifestyle changes made the biggest difference. Yes, I do have a problem with blood sugar too. Checking my blood glucose as suggested by Jenny, showed fasting is normal, but post prandial jumped over 200. A low carb, no grain diet has lowered my A1c to 5.3

I have wondered if my sore, bleeding gums figured in to my heart disease. I am happy to say that my gums don't bleed anymore and look much more healthy ever since I stopped eating wheat(gluten) 6 years ago.

Anonymous said...

I think one very important thing to remember about the CRP is that it is NON specific. With this said, it seems to be a very important lab that is too often not ordered.
I just got mine done last month. It's 1.3 My endo was surprised based upon my history. So now it's something to watch.
Reading the post above...I'm gluten free also and it's be 'Just the BEST' :-)

Diabeteshormone said...

Very informative blog about Daibetes.But it is found that Women with higher CRP levels were more likely to have heart problems.

CRP levels were lower in social drinkers (people who drink occasionally but not every day) than in those who didn’t drink and heavy drinkers.

CRP levels were similar in smokers and nonsmokers. They were also similar in heavy and light smokers.

Trinkwasser said...

Yet another test we csn't get here "unless you already have an inflammatory condition" said the GP. I didn't bother to point out the connection between Type 2 and inflammation as I'm sure she knows that perfectly well, only the accountants don't. It looks likely to me also that the CRP like the lipids is a function of high BG and/or high insulin, controlling which *before* reaching the diagnostic point for "diabetes" may well slow or stop your progression in terms of beta cell damage as well as the cardiovascular risk.

Anne said...

There are two CRP tests. One is the CRP and that is for general inflammation. The other is more specific for heart disease and is the high sensitivity CRP or hs-CRP.

Jenny said...


I'm almost certain these journal articles were referring to the high sensitivity CRP. The reference range is identical.