A1c and the Progression of Coronary Artery Calcification Among Adults Without Diabetes

Abstract

OBJECTIVE

Higher levels of hemoglobin A1c (HbA1c) are associated with increased cardiovascular disease risk among individuals without diabetes and may also be positively associated with coronary artery calcification (CAC). This study investigated the association of HbA1c with CAC progression in the Coronary Artery Risk Development in Young Adults study.

RESEARCH DESIGN AND METHODS

We included 2,076 participants with HbA1c and noncontrast computed tomography (CT) assessed at baseline (2005–2006), and CT repeated 5 years later (2010–2011). CAC progression was defined as 1) incident CAC (increase >0 Agatston units among those with no CAC at baseline), 2) any CAC progression (increase >10 Agatston units between examinations), and 3) advanced CAC progression (increase >100 Agatston units between examinations).

RESULTS

During the 5-year follow-up period, 12.9% of participants without baseline CAC developed incident CAC; among all participants, 18.2% had any CAC progression and 5.4% had advanced CAC progression. Higher HbA1c was associated with incident CAC (risk ratio [RR] = 1.45; 95% CI 1.02, 2.06), any CAC progression (RR = 1.51; 95% CI 1.16, 1.96), and advanced CAC progression (RR = 2.42; 95% CI 1.47, 3.99) after adjustment for sociodemographic factors. Additional adjustment for cardiovascular risk factors attenuated the associations of HbA1c with incident CAC (RR = 1.05; 95% CI 0.74, 1.49) and any CAC progression (RR = 1.13; 95% CI 0.87, 1.47). In contrast, the association of HbA1c with advanced CAC progression persisted in multivariable adjusted models (RR = 1.78; 95% CI 1.08, 2.95).

CONCLUSIONS

Higher HbA1c was independently associated with advanced CAC progression among individuals without diabetes, while the associations with incident CAC and any CAC progression were accounted for by other established cardiovascular risk factors

Full paper here http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4274774/

graham64 wrote:Abstract

OBJECTIVE

Higher levels of hemoglobin A1c (HbA1c) are associated with increased cardiovascular disease risk among individuals without diabetes and may also be positively associated with coronary artery calcification (CAC). This study investigated the association of HbA1c with CAC progression in the Coronary Artery Risk Development in Young Adults study.

RESEARCH DESIGN AND METHODS

We included 2,076 participants with HbA1c and noncontrast computed tomography (CT) assessed at baseline (2005–2006), and CT repeated 5 years later (2010–2011). CAC progression was defined as 1) incident CAC (increase >0 Agatston units among those with no CAC at baseline), 2) any CAC progression (increase >10 Agatston units between examinations), and 3) advanced CAC progression (increase >100 Agatston units between examinations).

RESULTS

During the 5-year follow-up period, 12.9% of participants without baseline CAC developed incident CAC; among all participants, 18.2% had any CAC progression and 5.4% had advanced CAC progression. Higher HbA1c was associated with incident CAC (risk ratio [RR] = 1.45; 95% CI 1.02, 2.06), any CAC progression (RR = 1.51; 95% CI 1.16, 1.96), and advanced CAC progression (RR = 2.42; 95% CI 1.47, 3.99) after adjustment for sociodemographic factors. Additional adjustment for cardiovascular risk factors attenuated the associations of HbA1c with incident CAC (RR = 1.05; 95% CI 0.74, 1.49) and any CAC progression (RR = 1.13; 95% CI 0.87, 1.47). In contrast, the association of HbA1c with advanced CAC progression persisted in multivariable adjusted models (RR = 1.78; 95% CI 1.08, 2.95).

CONCLUSIONS

Higher HbA1c was independently associated with advanced CAC progression among individuals without diabetes, while the associations with incident CAC and any CAC progression were accounted for by other established cardiovascular risk factors

Full paper here http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4274774/

Hi Graham,
Could it be Hba1c is not always an adequate measurement of damage even with lowish values?
According to Dr.Kraft those with hyperinsulinemia can have an OK Hba1c but high insulin does the damage. He reckoned over 90% of heart attacks were caused by high insulin levels.
regards
Derek

Yep. That is what I understand. Hyperinsulinemia causes vascular damage long before it causes diabetes and its first symptom is hypertension. That's why diabetics should not just focus on glucose. They also need to reduce insulin and insulin resistance (IR).

As a result of becoming more aware of the insulin role, I've now concluded that an optimal treatment for diabetes is a ketogenic diet (reduces both glucose and insulin to minimal levels) plus metformin (reduces IR) and an ACE Inhibitor or ARB (reduces IR). And it has also been shown that Sildenafil (better known as Cialis) improves IR.

See

http://www.tuitnutrition.com/2015/09/its-the-insulin-1.html

http://www.hindawi.com/journals/ijhy/2013/230868/

http://vmj.sagepub.com/content/17/5/330.full

http://press.endocrine.org/doi/10.1210/jc.2015-3415?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub%3Dpubmed&

Yes agreed hyperinsulinemia is the problem as Kraft demonstrated, wonder just how many who have passed a GTT are already starting with complications including vascular problems.

This is the reason all type two diabetics need to get control as soon as possible. It has been proved damage has been happening for many years before diagnosis of diabetes in the majority of cases. It also highlights why injected insulin or drugs that induce more output of natural insulin is dangerous. So few including many medics fail to realise many type diabetics are over producing insulin, more insulin is the last thing type two's need. Many also fail to realise excess plasma insulin is arguably more damaging than elevated BG numbers. Insulin is the growth hormone it is also the ageing hormone. Hence why the carb up and shoot up so many feel is cool just because they can hold 'reasonable' BG numbers is to be avoided. Good BG numbers are necessary for long term good health, but as we have said so often, it's how good numbers are achieved is just as important.

Thanks for the " heads up" @graham64  I am following a ketogenic diet since the waterfast before Christmas, in order to prevent any calcium plaque build up in my cardiovascular system. I appear to be clear of CAC, according to a recent echocardiogram, which I put down to luck. It is terrifying how many adverse conditions are simmering away, ready to boil over once pre diabetes is diagnosed. Eternal vigilance seems necessary, but really, it is also necessary to live a life, isn't it, without falling into the hypocaust of hypochondria?
And OldTech, I keep looking for ways to steer clear of hyperinsulinaemia without resorting to medications which may help many, but I do not feel that I am there yet, but I note your suggestions.
And thank you for the very informative links.
Eddie, I agree that getting control is paramount, but it does go beyond control of BGLs, which many T2Ds think is the holy Grail. Difficult times ahead.

"Eddie, I agree that getting control is paramount, but it does go beyond control of BGLs, which many T2Ds think is the holy Grail. Difficult times ahead."

I hear what you are saying, but there are limits to what we can achieve. We diabetics are damaged permanently. All we can do is minimise and in some cases reverse complications if caught earlier enough. The sad fact is so many diabetics never even achieve safe BG numbers, let alone anything else. It seems to me to be the case get your BG numbers in order and many other numbers improve.

The real sad fact in all this is type two diabetes used to be an old man's disease, now ever more young people including teenagers are becoming type two's. I believe T2 will reduce all our length of lives to some degree. Not so bad when you become a diabetic at sixty of seventy years of age. What chance of getting to the biblical three score years and ten for so many young people, poor I reckon.

I agree there are limits to how much we can control. Still, we can do quite a lot to control BGLs, insulin, and insulin resistance. Keto helps with all three, and strenuous exercise helps with all three, but as Eddie says we have damaged bodies.

I use to think that the ideal goal was to control BGLs with natural methods and to get off of all meds. Now I think that is foolish unless you are pre-pre-diabetic because it does not fully address IR. To reduce IR, we need the effective meds. For example, the ACE Inhibitor is targeted at the process that causes IR in the vascular system.

Keto is great but does have it's problems. When I started low carb I went down to 30 carbs per day max. Checking with keto sticks ever day. I was eating three meals a day and calories down to around 1300 per day. To start with it was great, I lost 50 lbs in 3 months easily. The trouble for me was I lost so much weight people around me thought I was terminally ill. I never felt hungry or tired because I was burning my own body fat for energy. What happens when you do not want to lose more weight, you have to up the calories. Obviously you have to eat more calories, getting that balance right can be hard to do. Some real star diabetics I know can do it, but it seems to me for some of them diabetes has become a full time job. I know I could get better numbers, but at my age I have taken the decision to accept good control rather than optimum control. Each person must set their own targets. The younger a person is the more the need for optimum control. The big problem is the establishment are telling people very poor control is good. The NICE guidelines are nowhere near good control. As always the waters are muddied with all sorts of misinformation. Much the same way the descriptions quoted for what low carb is.

For me low carb is 50 carbs per day or less. Good BG control is HbA1c 6 or less, excellent BG control is 5 or less. The NHS audited stats prove so few get close, and they never will until dietary recommendations change. I know, I am a broken record. On another blog I read a few days ago, a member that used to post here big time, recently stated our forum was low carb or nothing. That's true, because nothing else works. On this other blog the ex member from here was ridiculed harshly, that never ever happened here. And one thing is for sure, I am not going to change the way I control diabetes until someone can show me a better way. I will wait a long time for that to happen.

Low carb is not perfect for everyone, but it's the best we have got until a true cure for all diabetics is found. Also, the old chestnut of eat as much as you like as long as it's low carb and you will not put on weight is complete bunkum. That's another lie the low carb antis like to say we preach. Jeez I have also seen recently from another ex member here, that the less she eats the more weight she puts on. Good luck with that theory.

The betus, it's a funny old game. I suspect it will ever be thus.

Yes agree with all of the above. My A1c was never above 6 because the amount of time I spent with BG up to 11 was balanced with the amount of time I spent hypoglycemic. Now I've been told that high postprandial BG is "perfectly normal". No you clueless dolt, it has become COMMON but that doesn't make it NORMAL. Even our massively obese doctor wouldn't claim she was normal just because obesity has become common.

EPIC-Norfolk (Kay-Tee Khaw) and the five year followup, and a truly massive New Zealand study (Elley et al) showed a linear relationship between A1c and cardiovascular risk starting at truly normal A1c of below 5%. Other studies (probably listed on Blood Sugar 101) show the correlation between A1c and microvascular disease and also the relationship between postprandial spikes and macrovascular disease to be quite distinct mechanisms.

This study is another poke in the eye for the Lipid Hypothesis and the Diet-Heart Hypothesis and especially for ACCORD. I predict NICE/NHS Evidence will ignore it just as they did the above listed studies, and carry on recommending low fat diets.

[quote="chris c"]Yes agree with all of the above. My A1c was never above 6 because the amount of time I spent with BG up to 11 was balanced with the amount of time I spent hypoglycemic. Now I've been told that high
randial BG is "perfectly normal". No you clueless dolt, it has become COMMON but that doesn't make it NORMAL. Even our massively obese doctor wouldn't claim she was normal just because obesity has become common.

EPIC-Norfolk (Kay-Tee Khaw) and the five year followup, and a truly massive New Zealand study (Elley et al) showed a linear relationship between A1c and cardiovascular risk starting at truly normal A1c of below 5%. Other studies (probably listed on Blood Sugar 101) show the correlation between A1c and microvascular disease and also the relationship between postprandial spikes and macrovascular disease to be quite distinct mechanisms.

This study is another poke in the eye for the Lipid Hypothesis and the Diet-Heart Hypothesis and especially for ACCORD. I predict NICE/NHS Evidence will ignore it just as they did the above listed studies, and carry on recommending low fat diets.[/qu

Insulin puts up b.p and causes us to pee out potassium,
We pee out sodium when we low carb and this puts bp down...it is believed.
D.

From what I understand, the first order effect of insulin is to suppress NO which prevents the vascular system from relaxing thus causing hypertension. Of course, insulin also has other effects.

And yes I agree that very low carb reduces sodium for diabetics. Or, at least, it does for me. I have to eat additional salt to prevent leg cramps and restless legs.

OldTech wrote:From what I understand, the first order effect of insulin is to suppress NO which prevents the vascular system from relaxing thus causing hypertension. Of course, insulin also has other effects.

And yes I agree that very low carb reduces sodium for diabetics. Or, at least, it does for me. I have to eat additional salt to prevent leg cramps and restless legs.

When you low carb sodium is released, hence telling people to drink lots of water is a no no. Very often when going low carb and eating whole fresh foods instead of highly processed salt laden junk or takeaways the salt in the diet can drop big time.

Some words from Dr. Jay Wortman a lowcarb expert and type two diabetic on lowcarb and salt.

“When you cut the carbs your kidneys will release sodium. This is why people lose some water initially and why blood pressure also tends to get better on low-carb. If you are not careful to replace the lost sodium sufficiently by adding salt to your food, you will experience the effects of mild hypo-natremia. These are: headache, constipation, weakness, fatigue, low-blood pressure, othostatic hypotension and possibly leg cramps. If you get a blood test you may find that your potassium is low, too. Unfortunately, there is no reliable blood test for magnesium but it may also be low. Supplementing with salt should correct these problems. You don't need to take a potassium supplement, it will correct if you eat enough salt. Some people will have a persistent magnesium deficiency that will require supplements. This would be manifested by leg cramps and hyper-reflexia (something your doctor can check). To correct this you should take a slow-release Mg++ supplement daily.

Many people make the mistake of restricting salt and drinking lots of water when on a low carb diet. This is virtually guaranteed to cause problems. When you look carefully at the studies that report equivocal results with a low-carb diet, this is invariably one of the reasons.”

OldTech wrote:From what I understand, the first order effect of insulin is to suppress NO which prevents the vascular system from relaxing thus causing hypertension. Of course, insulin also has other effects.

And yes I agree that very low carb reduces sodium for diabetics. Or, at least, it does for me. I have to eat additional salt to prevent leg cramps and restless legs.

I am surprised you need sodium your kidneys will pee it out again to maintain stasis. It is usual low potassium causes cramps.

Some tribal people existed on less than 100mg of sodium per day. Sodium puts up bp and potassium puts it down.
Insulin and glucose are given for potassium overdose.
Show me the u&e results that shows low carb causes low blood sodium?
D.

I don't have a reference, but it seems that it is common knowledge especially during low carb initiation (that of course does not make it true). And in my case, it seems true. My blood work shows low sodium. Calcium was also low, but I have hypoparathyroidism, so I now supplement with both calcium and calcitriol. Magnesium (also supplemented) and potassium are within normal ranges. I only drink when I am thirsty and only eat homemade foods without extra sodium.

And I cannot see that the extra salt makes any difference in my blood pressure. My blood pressure is usually below 120/80 and around 110/70 when I wake up. It only goes above 130 when I exercise (especially weights). For the times that I have checked, it is not lower when I have cramps or restless legs.

As I said above I think that hypertension and CVD are caused by excess insulin and especially hyperinsulinemia that is the hallmark of type 2 diabetes.

OldTech wrote:I don't have a reference, but it seems that it is common knowledge especially during low carb initiation (that of course does not make it true). And in my case, it seems true. My blood work shows low sodium. Calcium was also low, but I have hypoparathyroidism, so I now supplement with both calcium and calcitriol. Magnesium (also supplemented) and potassium are within normal ranges. I only drink when I am thirsty and only eat homemade foods without extra sodium.

And I cannot see that the extra salt makes any difference in my blood pressure. My blood pressure is usually below 120/80 and around 110/70 when I wake up. It only goes above 130 when I exercise (especially weights). For the times that I have checked, it is not lower when I have cramps or restless legs.

As I said above I think that hypertension and CVD are caused by excess insulin and especially hyperinsulinemia that is the hallmark of type 2 diabetes.

Unless you overload your system with water or sodium it won't make any difference your bp is regulated by aldosterone from your adrenals. You'll just pee it out. You shouldn't be needing sodium we all have plenty in our diet. I have Conn's syndrome and I have restricted sodium intake to very low indeed, and I never got cramp.
It is dangerous advice to blanket tell low carbers to take in sodium, they may have faulty adrenals, all you can say its OK for you.
But for heart failure patients on spironolactone who have to block aldosterone and need to lose sodium the advice will render their meds useless.
If you suspect you have low sodium you should get your doctor to do U & E's. You may have had them done?68 Personally I think low carbers lack proof but if you like the stuff and your adrenals work OK take as much as you like.
D.

I'm another that gets low serum sodium level flagged up on my blood tests, but when I have a follow up U&E blood tests ordered by my surgery they come back within range albeit at the low end.

Originally it was thought it could be down to my BP meds as it can be a problem with certain ace inhibitors, tried a few different ones but to be honest it did not really make a lot of difference. That said it with the lab reference range of 133 - 146 mmol/L  I rarely drop below 130

Maybe I'm peeing to much out due to my tea addiction 

And it could be that it is due to insulin resistance(IR) that is interfering with the retention of sodium. It appears that insulin plays a role in the control of sodium, but when you get your glucose (and insulin) under control then you are no longer producing sufficient insulin (this is good) to overcome the IR in your kidneys. That, in turn, means that your kidneys are dumping sodium because insulin is not able to do its job.

See "Sodium-retaining effect of insulin in diabetes" at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3533616/

OldTech wrote:And it could be that it is due to insulin resistance(IR) that is interfering with the retention of sodium. It appears that insulin plays a role in the control of sodium, but when you get your
glucose (and insulin) under control then you are no longer producing sufficient insulin (this is good) to overcome the IR in your kidneys. That, in turn, means that your kidneys are dumping sodium because insulin is not able to do its job.

See "Sodium-retaining effect of insulin in diabetes" at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3533616/

that is perverse, you are saying the hyperinsulin state is correct for sodium balance in blood!

Actually the correct state is maintained by aldosterone releasing sodium via the kidneys.

More aldo and we keep more sodium, lower aldo and our sodium drops. Blood pressure is inversely proportional.
When too much sodium goes into tissue potassium comes out and is lost in urine and bp goes up.
Damage to tissue occurs due to too much sodium going into tissue. Fibrosis occurs and the heart and other organs are damaged. This why I have a pacemaker and have Afib. I had undiagnosed Conn's syndrome for 30 years.
I needn't have had HTN or diabetes if this had been diagnosed earlier, but I've have lived with 20x the normal amount of aldosterone in my blood for many years.

Derek

Just goes to show how complicated it all is and how so many things have relationships, and J curves.

Here we have VERY hard water so I am getting a LOT of calcium. When I started getting leg cramps at night I added some magnesium. My electrolytes showed bang in the middle of the range for everything so that was clearly a good decision. I've been using lo-salt (high potassium) for years, and sometimes sea salt for a change. 

The only thing that was out of range on my last but one tests was thyroid - TSH was ridiculously low and T4 and T3 very high. Since the thyroid came back down and is now borderline hypO, my LDL has shot up. Not uncommon - but what I didn't realise is that the opposite also occurs - hypERthyroid had exactly the same effect on my LDL as a statin. Who knew?

The thyroid had a massive effect on my BP and is largely responsible for Peripheral Arterial Disease - along with the BG and insulin problems I've had all my life of course. My father is one of the few other people I've known who had hyperthyroid, when young - it gave him Marty Feldman eyes and permanently damaged his heart to the extent he was "too ill" to join the army and go be killed, but not too ill to drive a fire engine in the Blitz. Nor did it stop him living to 82. I expect eating loads of lard and meat three times a day probably helped.

The downside is that taking out most of his thyroid left him hypOthyroid in his later years, which went undiagnosed.

Yet more interrelationships.

Derek wrote:
that is perverse, you are saying that hyperinsulinemia is correct for sodium balance in blood!

No. I am saying that insulin plus insulin resistance can in some cases result in normal sodium balance (a neutral state), but hyperinsulinemia causes many other problems. We are balancing two forces - the level of insulin and the degree of IR.

All I am doing is to observe that as I got my glucose and insulin levels under control (mild ketosis), I started having leg cramps and restless legs. Among the many things I tried was extra salt and that worked. Then six months ago my body seemed to adjust and I no longer needed the extra salt. Now in the past month, as I have gone into deep ketosis, my leg cramps, and restless legs have returned with a vengeance. And again I have found that adding salt fixes it.

So my speculation is that deep ketosis (3.3 mmol/l) has resulted in even lower levels of insulin (an inverse relationship) and that the lower levels of insulin are not sufficient to overcome the mild IR in my kidneys to maintain sodium levels.