Exactly Why Does Diabetes Increase the Risk of Heart Disease?

[jimmydasaint]

Having checked out a few websites which suggest that diabetes increases the rate of heart disease, I am none the wiser. What is the mechanism that increases heart disease and is it diabetes Type I or II which is worse for a person's heart.

[Marat]

The whole area of the etiology of diabetic complications is vastly complex, since autoimmune and genetic factors play a role in their genesis along with hyperglycemia, and it is difficult to determine how much of the problem comes from each factor, or whether it is the interaction among the factors which is key. After the DCCT, there was fixation on the idea that all the complications were caused by hyperglycemia, but now after the ACCORD study it is evident that for type 2 patients more normalization of blood glucose levels is harmful, rather than helpful, as the theory would predict. Another confusing factor is that type 2 patients have a much easier time controlling blood sugar levels than type 1 patients, yet type 2 patients develop the classic diabetic complications much sooner after diagnosis than type 1 patients do. Is this because the type 2 patients go undiagnosed for much longer than the type 1 patients do, is it because their age of onset is typically older, or is it because their disease is different in some unknown way?

 

Many of the complications of diabetes, even though perhaps caused by hyperglycemia, are best controlled not by addressing the hyperglycemia per se but rather by addressing related risk factors. Thus for example, trying to prevent diabetic nephropathy by blood sugar control is not very effective, but controlling blood pressure in the presence of developing diabetic nephropathy is important.

[jimmydasaint]

I agree that there is a multifactorial explanation. I have found an article dating to 1984 which may cut through some complications:

 

As the degree of atherosclerosis appears to be greater

in diabetic patients, even shortly after diagnosis, it is

conceivable that atherosclerosis itself may predispose to

the development of diabetes [14], though there is no direct

evidence to support this hypothesis. It is more likely

that atherosclerosis and diabetes share a number of

antecedents, the balance between them determining the

clinical outcome. One pre-existing factor which may

sway the balance in the direction of diabetes is obesity,

which has a much stronger relationship in prospective

studies to the incidence of diabetes than to that of CHD

[31]. The common antecedents date back to adolescence

or before, for association between levels of blood pressure,

blood glucose and plasma lipids have been demonstrated

in the young as well as in adults [32-34]. For

both serum cholesterol and blood pressure, there is evidence

of tracking of level with increasing age [35, 36].

Thus, an adolescent with a 'normal' blood pressure level,

but towards the upper end of the distribution, is likely

to remain there and by middle-age to have entered

the hypertensive 'at risk' range. If the analogy is correct,

the newly-diagnosed diabetic patient of age 45 years

may have 30 or more years of exposure to factors which

promote atherogenesis. The final decompensation of

blood glucose control which we recognise as diabetes,

though generating the risk of microvascular disease,

does not add to the risk of CHD.

 

Chicken or egg explanation

 

In short, although I am over-simplifying somewhat, obese people tend to get diabetes Type II. The obesity itself also predisposes to potential atheroma formation, vascular disease and subsequent cardiac problems.

[zapatos]

Having checked out a few websites which suggest that diabetes increases the rate of heart disease, I am none the wiser. What is the mechanism that increases heart disease and is it diabetes Type I or II which is worse for a person's heart.

"In people with diabetes, sugar (glucose) accumulates in the blood to very high levels. The excess glucose can attach to proteins in the blood vessels and alter their normal structure and function. One effect of this is that the vessels become thicker and less elastic, making it hard for blood to squeeze through."

 

"High blood sugar damages blood vessels and can lead to blockage. In the heart, this blockage can cause heart attacks."

 

http://www.genetichealth.com/dbts_consequences_of_diabetes.shtml

Edited December 23, 2010 by zapatos

[jimmydasaint]

"In people with diabetes, sugar (glucose) accumulates in the blood to very high levels. The excess glucose can attach to proteins in the blood vessels and alter their normal structure and function. One effect of this is that the vessels become thicker and less elastic, making it hard for blood to squeeze through."

 

http://www.genetichealth.com/dbts_consequences_of_diabetes.shtml

 

This is why diabetics often have issues with eyes, kidneys, nerves, and heart.

 

That is what I thought to start with, excess glucose leads to the glycosylation of many proteins that would not normally have glucose attached:

Glycosylation What is it, how it affects patients with diabetes and what you c

Glycosylation refers to the covalent bonding of blood glucose to the red blood cells. Normally, only a small percentage of blood glucose, usually between 4.5%- 6%, is covalently linked to the red blood cells in hemoglobin of the non diabetes population.

Advertisement This value is commonly referred to as glycosylated hemoglobin or more specifically hemoglobin A1c. The quantification for hemoglobin A1c is based on the total accumulation and reaction between glucose and red blood cells over their life span of 90-120 days. Apparently, short term or hourly elevations in blood sugar levels do not seem to acutely affect the total hemoglobin A1c value. This may be due possibly to the suspected slow rate in which glucose and hemoglobin combine.

 

Nevertheless, the increased amount and duration of glucose in the blood allows more glycosylation to occur, not only with hemoglobin, but with proteins and this can have systemic ramifications.[ii] The excessive cleavage of glucose, especially with important protein amino groups, can affect cell function and structure and create an inbalance which leads to cell destabilization.[iii] [iv]

 

This condition seems to target organs and tissues that are not dependent on insulin for their absorption of glucose. Kidneys, blood vessels, peripheral nerves and lenses of the eye are more susceptible to damage from periods of hyperglycemia than other organs due to their lack of insulin dependence.

 

There appears to be a particular enzyme implicated in the corruption of these cell structures. It is called aldose reductase. Aldose reductase is responsible for converting sugars to their corresponding alcohols namely sorbitol. Since a diabetes patient has higher than normal serum glucose levels, susceptible cells exposed to aldose reductase accumulate larger amounts of these converted alcohols. It is known as the polyol pathway.[v]

 

 

Link to article

 

With the replies received, I can start to piece together a couple of conclusions. Obesity may be important to cause diabetes Type II. Obesity also can predispose to coronary heart disease. However, the high levels of sugar in the blood, from uncontrolled diabetes Type I or Type II, can also cause proteins to become glycosylated that would not normally be covalently attached to glucose. The covalent attachment could affect blood vessels in a way that would damage them and make thrombosis or atheroma formation more possible.

 

Atheroma

 

Thrombosis

Edited December 23, 2010 by jimmydasaint

[Marat]

The whole question of what exactly causes diabetic complications is a complex one. It is puzzling, for example, that certain animals, such as hummingbirds, live their entire lives with a very high blood sugar level and never develop the least histological trace of diabetic complications. It is also difficult to explain why some diabetics develop severe complications very quickly despite minimal hyperglycemia, while others with massive hyperglycemia fail to develop complications for decades. Some diabetics present with complications at diagnosis, even when the onset of their diabetes, as in the case of type 1 diabetics, is quite acute, so there is fairly good evidence that some of the complications develop independently of the characteristic hyperglycemia of the disease.

 

Part of this explanation might have to do with how well the body is equipped with the necessary enzymes for metabolizing excess glucose to its ultimately harmful form, the advanced glycation endproducts. There is now a harmless pro-vitamin, benfotiamine, which has been demonstrated to block three of the four metabolic pathways by which hyperglycemia results in advanced glycation endproducts, and this has great promise in preventing diabetic complications.

 

Some of the complications seem to be pre-programmed by genes inherited along with the gene cluster which predisposes people to develop type 1 or type 2 diabetes. Some of the vascular and neurological damage is caused by the autoimmune processes which initally attack the beta cells of the pancreas in type 1 diabetes, and to this extent hyperglcemia is a concommitant but not a cause of the complications of diabetes. Since insulin is either not produced at all, or only produced in insufficient amounts in type 1 diabetes, some of the complications in type 1 diabetics may be caused by lack of c-peptide, which is normally produced along with insulin. Since c-peptide cannot pass through the cell walls in type 2 diabetes, this ineffectiveness of c-peptide may also play a role in causing the complications of type 2 diabetes.

 

But to say that the development of complications in diabetes is directly proportional to the degree of hyperglycemia is much too simple.

[jimmydasaint]

The whole question of what exactly causes diabetic complications is a complex one. It is puzzling, for example, that certain animals, such as hummingbirds, live their entire lives with a very high blood sugar level and never develop the least histological trace of diabetic complications. It is also difficult to explain why some diabetics develop severe complications very quickly despite minimal hyperglycemia, while others with massive hyperglycemia fail to develop complications for decades. Some diabetics present with complications at diagnosis, even when the onset of their diabetes, as in the case of type 1 diabetics, is quite acute, so there is fairly good evidence that some of the complications develop independently of the characteristic hyperglycemia of the disease.

 

Part of this explanation might have to do with how well the body is equipped with the necessary enzymes for metabolizing excess glucose to its ultimately harmful form, the advanced glycation endproducts. There is now a harmless pro-vitamin, benfotiamine, which has been demonstrated to block three of the four metabolic pathways by which hyperglycemia results in advanced glycation endproducts, and this has great promise in preventing diabetic complications.

 

Some of the complications seem to be pre-programmed by genes inherited along with the gene cluster which predisposes people to develop type 1 or type 2 diabetes. Some of the vascular and neurological damage is caused by the autoimmune processes which initally attack the beta cells of the pancreas in type 1 diabetes, and to this extent hyperglcemia is a concommitant but not a cause of the complications of diabetes. Since insulin is either not produced at all, or only produced in insufficient amounts in type 1 diabetes, some of the complications in type 1 diabetics may be caused by lack of c-peptide, which is normally produced along with insulin. Since c-peptide cannot pass through the cell walls in type 2 diabetes, this ineffectiveness of c-peptide may also play a role in causing the complications of type 2 diabetes.

 

But to say that the development of complications in diabetes is directly proportional to the degree of hyperglycemia is much too simple.

 

Thank you for such a thoughtful and detailed reply Marat.

 

So, to summarise, there are the following elements, that affect the pathology of diabetes:

 

a.) genetics; genetics and diabetes

b.) behavioural (including diet); Diet and diabetes

c.)AGE (advanced glycosylation end products) AGE and diabetes

and

d.) possibly hyperglycaemia, although the evidence for this is inconsistent. Article on Hyperglycaemia

 

There are additional complications that you have mentioned and there should be a distinction made between juvenile onset diabetes (Type I and caused by the body's immune response to its own pancreatic cells ) and late onset diabetes (Type II) caused by body tissues become less responsive to insulin, especially skeletal muscle. Damage to blood vessels, as a possible consequence of diabetes, also considering complicating factors, could lead to the development of heart disease.

 

I hope this is reasonably accurate so far.

Edited December 26, 2010 by jimmydasaint

[Marat]

The only clarification I would suggest is that behavioral factors such as diet and exercise are usually emphasized in relation to the onset of type 2 diabetes in those genetically predisposed to it, since in those people, obesity and indolence can cause that disease. The trigger for type 1 diabetes remains speculative, since even in monozygotic twins there is only a 50% concordance for type 1 diabetes, although they are genetically identical and their environments are also usually almost identical. Type 2 diabetes is more genetically conditioned than type 1, and so many massively obese individuals never develop type 2 diabetes, while some of those who do become type 2 diabetics are thin and active.

 

Medicine alternates between emphasizing the similarities between types 1 and 2 (up until around the mid-1960s) and insisting on their total distinction (mid-1960s to today), although some recent research is once again indicating that there may be more genetic similarities between the two conditions than previously imagined.