A1c and High Post-Meal Blood Sugars Predict Heart Attack

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A1c and Post-Meal Blood Sugars Predict Heart Attack
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If you need any more motivation to pursue normal blood sugars consider this:Heart attack risk more than doubles at blood sugar levels considered to be "prediabetic."

Post-Meal Blood Sugar and A1c Predict Cardiovascular Events and Deaths

A study conducted in Italy which analyzed 14 years of blood sugar data taken from people recently diagnosed with Type 2 diabetes concluded "A1C and blood glucose 2 h after lunch but not FBG [fasting blood glucose] predict cardiovascular events and all-cause mortality." The reason only sugars after lunch were cited here is that the study did not analyze post-dinner readings, only pre-dinner readings. The methodology of this study was crude--basically they compared people who met the anemic ADA blood sugar targets with those who didn't, classifying those with post-meal readings under 180 mg/dl (10 mmol/L) as "good" and comparing them with those that were over and hence "bad." Even with this crude filter, the post-meal reading was predictive.

Postprandial Blood Glucose Predicts Cardiovascular Events and All-Cause Mortality in Type 2 Diabetes in a 14-Year Follow-Up Lessons from the San Luigi Gonzaga Diabetes StudyFranco Cavalot et al. Diabetes Care October 2011 vol. 34 no. 10 2237-2243.doi: 10.2337/dc10-2414

A study links post-meal blood sugars to artery thickening

An Italian team published a study in January of 2008 where they report that over five years the increase in the thickness of the carotid artery correlated directly with the amount that blood sugars rose after meals in people with diabetes measuring their blood sugar at home.

They found dangerously high rises in 95% of people with diabetes in their study, probably because they were encouraged to eat the extremely high carbohydrate, ADA-recommended diet and attempt to counter the resulting post-meal high blood sugars with oral drugs--which the study found, did not control the peaks.

Postmeal glucose peaks at home associate with carotid intima-media thickness in type 2 diabetes Katherine Esposito, et. al. J Clin Endo doi:10.1210/jc.2007-2000

One Hour OGTT Result over 155 mg/dl(8.6 mmol/L) Correlates with Markers for Cardiovascular Disease

Interesting things happen when we get away from studies that confirm the wisdom of the ADA's much-too-high blood sugar targets. For example, a study published in November of 2009 linked blood sugar readings one hour after ingesting glucose with high fibrinogen and leukocytes count (WBC), which point to subclinical inflammation, and with abnormal lipid ratios, and insulin sensitivity in a population of 1062 participants with normal glucose tolerance or prediabetes. "Normal" glucose tolerance as defined by doctors and researchers means a 2 hour blood sugar reading of under 140 mg/dl on an oral glucose tolerance test.

This study found
Elevated 1hPG [one hour plasma glucose] in NGT [people with normal glucose tolerance] and pre-DM subjects is associated to subclinical inflammation, high lipid ratios and insulin resistance. Therefore, 1hPG >155 mg/dl could be considered a new 'marker' for cardiovascular risk.
This strongly supports the message I have been emphasizing on this web site since 2004 that it is essential to keep one hour blood sugar reading after meals under 140 mg/dl.

The reliance of doctors on two hour glucose tolerance test results allows people to live for years with blood sugars high enough to promote complications long before they are diagnosed even pre-diabetes.

Inflammation markers and metabolic characteristics of subjects with one-hour plasma glucose levels. Gianluca Bardini et al. Diabetes Care Published online before print November 16, 2009, doi: 10.2337/dc09-134

A1c Accurately Predicts Heart Attack Risk

This was discovered a few years ago in a large-scale study called EPIC-Norfolk. What's particularly valuable about this study is that they weren't looking for causes of heart disease. They were studying cancer and they were looking at blood sugar because of the belief that it might be related to cancer incidence, which turned out not to be the case. The finding that A1c predicted heart disease in people with supposedly normal blood sugar was a shocker.

Association of Hemoglobin A1c with Cardiovascular Disease and Mortality in Adults: The European Prospective Investigation into Cancer in Norfolk. Kay-Tee Khaw, MBBChir FRCP; Nicholas Wareham, MBBS, FRCP; Sheila Bingham, PhD; Robert Luben, BSc; Ailsa Welch, BSc; and Nicholas Day, PhD. Annals of Internal Medicine, 9/21/2004, Vol 141, no 6, 413-420

Here's the summary from that paper's conclusions:
In men and women, the relationship between hemoglobin A1c and cardiovascular disease (806 events) and between hemoglobin A1c and all-cause mortality (521 deaths) was continuous and significant throughout the whole distribution. The relationship was apparent in persons without known diabetes. Persons with hemoglobin A1c concentrations less than 5% had the lowest rates of cardiovascular disease and mortality. An increase in hemoglobin A1c of 1 percentage point was associated with a relative risk for death from any cause of 1.24 (95% CI, 1.14 to 1.34; P < 0.001) in men and with a relative risk of 1.28 (CI, 1.06 to 1.32; P < 0.001) in women. These relative risks were independent of age, body mass index, waist-to-hip ratio, systolic blood pressure, serum cholesterol concentration, cigarette smoking, and history of cardiovascular disease.
Another study which drew similar conclusions discovered an even tighter correlation between A1c and heart disease risk that began as A1c rose above 4.6%, a level that corresponds to a blood sugar level of 86 mg/dl (4.8 mmol/l)!

Glycemic Control and Coronary Heart Disease Risk in Persons With and Without Diabetes. The Atherosclerosis Risk in Communities Study. Elizabeth Selvin,et. al. Arch Intern Med. 2005;165:1910-1916.

To quote what that study found:
In nondiabetic adults, HbA1c level was not related to CHD risk below a level of 4.6% but was significantly related to risk above that level (P<.001). In diabetic adults, the risk of CHD increased throughout the range of HbA1c levels. In the adjusted model, the Risk Ratio of CHD for a 1 percentage point increase in HbA1c level was 2.36 (95% CI, 1.43-3.90) in persons without diabetes but with an HbA1c level greater than 4.6%. In diabetic adults, the Risk Ratio was 1.14 (95% CI, 1.07-1.21) per 1 percentage point increase in HbA1c across the full range of HbA1c values.
In short, it isn't whether you have diabetes that decides your risk, it's whether you have abnormal blood sugars, and the more abnormal, the more the risk. But "abnormal" blood sugars are those that doctors now treat as normal!

A study presented by Dr Esther van 't Riet at the EASD meeting in Sept, 2007, confirmed that even for people without diabetes A1c closely matches heart attack risk.

Here is a summary of the EASD report from Diabetes in Control:

Diabetes in Control: Even in nondiabetics, increased HbA1c levels are associated with a significantly increased risk of nonfatal cardiovascular disease after other cardiovascular risk factors are accounted for.

This study turned up information that needs further discussion. It found that though A1c matched cardiac risk, 2 hour oral glucose tolerance test (OGTT) results did not.

I have proposed a common sense explanation for why that might be HERE. In brief, it is my belief that the OGTT--as anyone who has taken one knows--because it uses a huge dose of pure glucose that all hits the bloodstream within fifteen minutes does NOT mimic the action of high carbohydrate food on our blood sugar.

When people have a blood sugar response in the 5-6% A1c range, 75 grams of glucose will produce a very high reading at 1 hour and then the blood sugar drops back very swiftly giving a normal or mildly impaired reading at 2 hours--the time used in this study to compare OGTT results with heart attack risk.

In real life, however, eating 75 grams of carbs in a meal of slower digesting food will produce--in the same person who got the moderate OGTT result--2-3 hours of damagingly high blood sugars which are what causes the heart disease.

Given that people with 5% A1cs often see peaks at one hour after eating which drop dramatically at 2 hours, I speculate that looking at post-meal (not OGTT) blood sugar values in people with 5% A1cs using a high carb meal would show a correlation between 1 hour values and heart attack risk.

Marker of Damage to Heart Muscle Rises with Rising A1cs in the Normal Range

A study published in February 2012 found that when a new high-sensitivity test that detects tiny amounts of a protein associated with heart muscle damage, troponin T, was used, study subjects were 24% more likely to have high cardiac troponin T if their A1c was between 5.7%-6.4%, compared to those whose A1c was below 5.7%. When their A1cs were over 6.4% that likelihood doubled. This suggests high blood sugars in the upper part of the range most doctors consider normal directly damage heart muscle.

Chronic Hyperglycemia and Subclinical Myocardial Injury.
Jonathan Rubin et al. J.Am.Col.Cardiology,Volume 59, Issue 5, 31 January 2012, Pages 484489 http://dx.doi.org/10.1016/j.jacc.2011.10.875,

Risk Quantified For Non-Diabetic A1cs and Heart Attack Risk

The Atherosclerosis Risk in Communities study tracked 11,092 black or white adults who did not have a history of diabetes or cardiovascular disease. for 15 years. It found no association between fasting blood sugar and risk of heart disease, but A1c was a different story. The table below summarizes the correlation of baseline A1c with the risk of developing cardiovascular disease.

Multivariate-Adjusted Hazard Ratio

5%: 0.96 (0.74-1.24)
5% to < 5.5%: 1.00 (reference)
5.5% to < 6%:1.23 (1.07-1.41)
6% to < 6.5%:1.78 (1.48-2.15)
= 6.5%: 1.95 (1.53-2.48)

Glycated Hemoglobin, Diabetes, and Cardiovascular Risk in Nondiabetic Adults. Elizabeth Selvin et al.NEJMVolume 362:800-811. March 4, 2010 Number 9.

Keep in mind that because these subjects were probably diagnosed as "non-diabetic" using a fasting glucose test many of those with the higher A1cs probably were diabetic at the study outset based on post-meal values. If you are recently diagnosed with diabetes and have no signs of heart disease, your risk/A1c ratio should be similar if not identical to those shown here.

A1c Rises with Advancing Age

A study which looked at the A1cs of two different large groups of people who participated in long term health studies and who did not have either impaired fasting glucose [fasting blood sugar over 110 mg/dl (6 mmol/L)] or impaired glucose tolerance [2 hr Glucose Tolerance Test result > 140 mg/dl (7.7 mmol/L)]discovered for these "normal" people, A1c rose at the rate of .01 unit per year.

Among those under 40 years old, the top end of the normal A1c was 5.6% to 6.0% (depending on the study cited) but for people who were 70 the normal range was 6.2% to 6.6% (again depending on the study cited).

It is not clear from the abstract whether these studies used the same method for calculating A1c, so the absolute A1c value given is open to interpretation, but the finding that A1c rises over time-- about .6% from age 40 to age 70 in normal people is worth considering.

This may have something to do with age-related changes in the characteristics of the red blood cells that are measured by this test. Whether these changes in the red blood cell, independent of blood sugar levels, make people more prone to heart attacks is a question that has not yet been answered by research.

However, since there is other data linking blood sugar levels after meals to heart attack, and since the definition of "normal" was based on having a Glucose Tolerance Test value of 139 mg/dl or less--a test result that usually translates into higher post-meal blood sugars, it is also possible that "normal" in these studies had post meal (as opposed to 2 hour glucose tolerance test results) significantly higher than those of younger people.

Effect of Aging on A1c Levels in Individuals without Diabetes: Evidence from the Framingham Offspring Study and the NHANES 2001-2004.Lydie N. Pani et. al, Diabetes Care 31:1991-1996, 2008.

Can Normalizing A1c Reduce Cardiac Risk?

It sure looks like it. Since the relationship between blood sugar level and cardiac risk is so clear cut it looks like people with diabetes don't get heart attacks because diabetes does something special to the heart. Instead, it looks like they get heart attacks because doctors tell them to maintain A1c levels near 7%--A1cs that are 2.4 percentage points above that 4.6% normal.

Something about having abnormally blood sugars, even ones that are considered normal by today's doctors, is what kills!

New Insight: Gene Raises Cardiac Risk in People With Diabetes and Poor Control

A study published in JAMA in November of 2008 found that people with a specific genetic error, a single-nucleotide polymorphism at 9p21 (rs2383206) had a much higher risk of heart disease than people who did not have this gene variant. Not only that, but people who had inherited two defective copies of this gene had twice the risk of those with one copy.

This may be depressing, but there is some good news buried in this study: blood sugar control made a big difference in the severity of the heart disease experienced by the people in this study. Those with poor control had twice the risk of heart disease than those with the same genes who had good blood sugar control. The impact of the gene became more pronounced as the years went by.

But there is something even more important that is left out of the reporting of this study: while better control halved the risk of heart disease in these people with Type 2 diabetes, "good control," as usual, was defined as an A1c of 7%. There is no data about the fate of people with this ugly gene who maintained their blood sugar in the normal range--the 5% A1c range. Given that lowring blood sugar to a still dangerously high 7% cut their risk in half, it is likely that lowering it further would provide even greater improvement.


Interaction Between Poor Glycemic Control and 9p21 Locus on Risk of Coronary Artery Disease in Type 2 Diabetes
Alessandro Doria et al. JAMA, 2008;300(20):2389-2397.

Because this is a gene, the heart attack risk associated with it runs in families, so if you have a family history of heart attack, this is all the more reason to work as hard as possible to lower your blood sugar to the safe zone using safe techniques: a lower carbohydrate diet and the diabetes drug that has been proven to be cardioprotective: Metformin.

Glycated LDL May Be The Culprit

An intriguing study published in May, 2011 may explain both why measuring cholesterol gives such confusing correlations with heart disease and why the A1c predicts it so much better.

The study is Glycation of LDL by Methylglyoxal Increases Arterial Atherogenicity: A Possible Contributor to Increased Risk of Cardiovascular Disease in Diabetes. Naila Rabbani et al. Diabetes. Published online before print May 26, 2011, doi: 10.2337/db11-0085

You can read a good explanation of what this study means here:

Science Daily: Super-Sticky 'Ultra-Bad' Cholesterol Revealed in People at High Risk of Heart Disease

In brief the finding is this: LDL becomes dangerous when it becomes glycated--i.e. when sugar molecules become bonded to it. When that happens it is more likely to stick to the artery walls. It is very likely given the correlation between heart attack and A1c that LDL becomes dangerously glycated at a rate that corresponds to the rate at which hemoglobin becomes glycosylated--which is what the A1c measures. (Glycosylation is permanent glycation.)

What Can You Do To Reduce Risk?

Your first step should be to stop worrying about total cholesterol and LDL, instead look at your A1c and triglycerides. If they are high, you know you need to cut back on carbohydrates.

  • If your A1c is between 4.8% and 5.4% your risk is beginning to rise.

    Cut down on how much starch and sugar you eat. Just eliminating junk carbs will probably normalize your blood sugar. Think twice before you eat bread, potatoes, baked goods, pasta and sugary drinks of all kinds. You are probably eating a hundred grams of junk carbohydrate a day. Cut them out and you should see dramatic improvements in your blood sugar--and cardiovascular--health.


  • If your A1c is between 5.4% and 6.0% your cardiac risk is becoming significant.

    Though your doctor might tell you these are normal readings, the evidence you read above suggests they arent. So take this as a wake-up call.

    With an A1c over 5.4% it is likely that your post-meal blood sugars are in the so-called prediabetic range that is associated with increased heart attack risk.

    Your first step should be to buy a blood sugar meter and test your blood sugar using the technique discussed here:

    Am I Diabetic, how to test your own blood sugar to find out.

    If you see your blood sugars rising over Normal Blood Sugar levels use the following technique to bring them back down to the levels that do not correlate with heart disease:

    How to Get Your Blood Sugar Under Control.

    If dietary change cannot give you normal readings, it may be time to ask your doctor for help. Metformin has been shown to be an effective and appropriate drug for prediabetes. In addition, the followup study to the UKPDS found that metformin is by far the most effective diabetes drug in terms of its ability to reduce cardiovascular risk over time.

    10-Year Follow-up of Intensive Glucose Control in Type 2 Diabetes. Rury R. Holman et al. NEJM,Volume 359:1577-1589, October 9, 2008, Number 15


  • If your A1c is over 6% you are almost certainly diabetic and your risk of heart disease is significant.

    Though your doctor may tell you than at A1c under 7% is "great control," the data above should make it clear it is great control only if you don't care about dropping dead from what is the number one killer of people with diabetes--heart attack.

    The good news is that no matter how rotten your A1c right now, you can get it back into control.

    To normalize your diabetic blood sugar, start out with the technique described HERE. If that doesn't work, add metformin. And if metformin doesn't get you to normal levels, talk to your doctor about insulin. Insulin is the one drug that always lowers blood sugars, when dosed correctly.

    Your doctor may tell you that major studies have found that lowering A1c in people with diabetes did not lower heart attack risk, however the studies he is citing were studies where people took other drugs--sulfonylureas, Avandia, and Actos along with high carbohydrate diets and, in some cases, huge doses of insulin needed to neutralize the very high carbohydrate intake. There is no data about the effect of combining a lower carb intake with metformin or insulin, but anecdotal evidence from those of us on the web who pursue this strategy has been that it is very effective.

New Data: Blood Sugar Post Meal Spikes Correlate with Heart Disease in NON-Diabetic People, Too

Though heart disease is more common among people with diabetes, it is a major killer of supposedly "normal" people too.

Now an intriguing study has found a strong correlation between post-challenge blood sugar (i.e. the blood sugar spike you get for an hour or two after eating carbs) and heart disease in a group of "normal" women. While there was no relationship between their fasting blood sugars and the rate at which they developed coronary artery disease over a period of about 3.5 years, there was a strong relationship between their scores on a glucose tolerance test and the degree to which they developed coronary artery disease.

Post-challenge glucose predicts coronary atherosclerotic progression in non-diabetic, post-menopausal women P. B. Mellen, V. Bittner, D. M. Herrington Diabetic Medicine 24 (10), 1156-1159.

If you do have diabetes, what does this mean for you? It means that the best thing you can do to avoid getting heart disease or to slow its development if you are in the early stages is to prevent your post-meal blood sugars from rising over normal limits. That means doing what you can to keep your blood sugar under 140 mg/dl (7.8 mmol/L) after every meal. To do this, you will have to cut down on carbohydrates. No drug will do this for you.

Also, this finding should encourage you to limit the carbs everyone in your family eats, because it's almost certain some of the supposedly "normal" people around you are getting the high post-meal high blood sugars that produce heart disease though they are not getting diagnosed thanks to their normal fasting blood sugars. The fasting blood sugar test is the only test most American doctors use to evaluate blood sugar health.

NOTE: When Your A1c May Be Inaccurate

Doctors have a touching faith that the A1c reflects your blood sugar control. Unfortunately, it is misplaced.

The A1c will not reflect your actual blood sugars if:
  • You have anemia. When you are anemic the A1c will be much lower than the value corresponding to the actual concentrations of glucose in your bloodstream


  • If you are on dialysis. If you are on dialysis your A1c will also be much lower than the value that reflects your actual blood sugars.


  • If you have certain genetic variants of the red blood cell. Genetic oddities in your hemoglobin can cause to a much lower than expected A1c.

You should never rely on the A1c alone to monitor your control. Test your blood sugar with a meter after meals frequently enough that you get a good idea of what your blood sugars are doing. If your A1c is much higher or lower than you expect, discuss this with your doctor. If you test after meals and consistently see high blood sugars, trust your meter readings over a low A1c If this happens to you, the fructosamine test may give you a more valid measurement of long term control.

Because there is a growing amount of evidence that it is blood sugars spikes after eating that damage your organs not only the glycation of proteins reflected in the A1c, it is dangerous to think a low A1c means you have nothing to worry about if your post-meal blood sugars are going into the damage zone.

But what about Cholesterol?

With so much evidence pointing to the predictive value of post-meal blood sugar and A1c why do most doctors continue to focus on cholesterol test values and prescribe statins rather than urge you to lower your post meal blood sugars (which will lower your A1c)?
Drug companies have sold doctors and the public on the idea that they can prevent heart attacks by lowering LDL--even though this is far from what the data actually prove. In fact, at least 1/3 and possibly a half of all people who have a first heart attack have normal cholesterol, and giving statins to people who have not had heart attacks and does not decrease their incidence of heart attacks.

This is probably because the true effect of statins is to lower vascular inflammation, not LDL.

Why Cholesterol and LDL Poorly Predict Heart Attack Risk

You would never know it from the statin ads, but half of all people who have heart attacks have no known risk factors--which means, among other things, that they have completely normal cholesterol.

Fifty percent of patients with coronary artery disease do not have any of the conventional risk factors. Futterman LG, Lemberg L.Am J Crit Care. 1998 May;7(3):240-4

A large epidemiological study published in 2012, which tracked 52,087 Norwegians for ten years, found that their total cholesterol levels did not predict heart attacks--or any other kind of death--and that for women, the higher their cholesterol, the less likely they were to die of heart attack. Indeed, total cholesterol levels up to about 271 mg/dl appeared to be protective against heart disease.

Is the use of cholesterol in mortality risk algorithms in clinical guidelines valid? Ten years prospective data from the Norwegian HUNT 2 study. Halfdan Petursson, et al. Journal of Evaluation in Clinical Practice. 2012 February; 18(1): 159168.
doi: 10.1111/j.1365-2753.2011.01767.x

Among that half of people who have heart disease who have high cholesterol, the Framingham heart study data confirms that it isn't total cholesterol that predict heart attack--or LDL.

Lipids, risk factors and ischaemic heart disease. Castelli WP. Framingham Cardiovascular Institute, Atherosclerosis. 1996 Jul;124 Suppl:S1-9.

Here's an except from that study:
Two simple tests for determining plasma lipid levels can be used to identify those individuals with an atherogenic lipid profile and who are, therefore, at increased risk for CVD. Firstly, the ratio of total cholesterol to high density cholesterol (HDL cholesterol) should be determined, followed by measurement of plasma triglyceride concentrations.
This states clearly that the only cholesterol measurements shown to be mildly associated with heart attack and thus useful in prediction are:
  • The ratio of Total Cholesterol/HDL, which should be under 3
  • Triglycerides which should be under 100

What Improves The Framingham Lipid Risk Factors?

To lower triglycerides, you need to lower dietary carbohydrate. The more carbs you eat, especially those that circulate in your blood stream as high blood sugar, the higher your triglycerides will be.

The drug, Metformin, which has been shown to have a cardioprotective effect will also significantly lower triglycerides.

Furthermore, a study published in Sept, 2007 found that in people who have low LDL it is the level of HDL (not affected by statins) that predicts heart attack risk.

HDL Cholesterol, Very Low Levels of LDL Cholesterol, and Cardiovascular Events. Philip Barter, e. al NEJM Volume 357:1301-1310 September 27, 2007, Number 13.

What raises HDL? Cutting carbohydrates out of your diet.

What does all this suggest? That the significant cholesterol fractions--if they mean anything, risk-wise--are those that point to high blood sugar.

Triglycerides in Heart Muscle may Be At Fault

A study published in the September 4, 2007 issue of Circulation comes up with a novel observation that may explain why high post-meal blood sugars are associated with heart attacks in people with diabetes. The study found that "lipid overstorage in human cardiac myocytes is an early manifestation in the pathogenesis of type 2 diabetes mellitus." This means that lipds are overstored in heart muscle very early in the progress of diabetes.

Cardiac Steatosis in Diabetes Mellitus: A 1H-Magnetic Resonance Spectroscopy Study. Jonathan M. McGavock,et al. Circulation 2007;116:1170-1175.

The specific lipid stored is triglyceride, which is the form of fat that the body creates out of glucose when blood sugar is high.This appears to occur at the blood sugar levels only slightly over normal--those associated with "impaired glucose tolerance"

Cutting back carbohydrates is a very effective way of normalizing those blood sugars and it is also well known to lower the concentration of triglycerides in the bloodstream, It is possible that lowering blood sugar to normal prevents the deposit of fat molecules in the hear and may explain why A1c correlates so closely with heart attack risk with or without a diabetes diagnosis.

 

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