Hello again everyone! For week 2 of obesity/diabetes, I focused on the paper that discussed the supposed increase in proinflammatory cytokines in diabetic women with some sort of cardiovascular disease, which included a heart attack, coronary artery bypass surgery, stroke, or coronary angioplasty.
The paper looked
specifically at IL-6, TNF-alpha, and IL-1 beta.
The study itself consisted
of four different groups: 1) the healthy control group without diabetes or
cardiovascular disease, 2) women with only cardiovascular disease, 3) women with only
diabetes, and 4) women with diabetes and cardiovascular disease, (which was the
group of interest).
Blood samples were taken
from the subjects, and ELISA was used to measure the amount of the 3 different
cytokines in the blood.
They
found that IL-6 levels were significantly increased in women with diabetes and cardiovascular disease. TNF-alpha was also highest in the group with diabetes and
cardiovascular disease, BUT the increase was not statistically significant. IL-1 beta showed no significant pattern or increase so the authors
concluded that it is not one of the cytokines that is chronically higher in
patients with diabetes and cardiovascular disease.
One very important point that Dr. Cohen brought up in class was the significance of significance!! The data for TNF-alpha did not show a statistically significant increase in any of the groups over the control. And yet, the authors discussed the effects and mechanisms of TNF-alpha at length, and treated their data as if it was significantly increased in subjects with diabetes and cardiovascular disease. We cannot make claims from data without them being significant, because that data doesn't officially prove or support the hypothesis.
In my opinion, the article should have been entirely focused on IL-6, since it did show a statistically significant increase in the subjects.
IL-6
drives B cell differentiation and stimulation, as well as promotes inflammation
and fever. In addition to its immunoregulatory actions, IL-6 has been proposed
to affect glucose homeostasis and metabolism directly and indirectly by action
on skeletal muscle cells, adipocytes, hepatocytes, pancreatic beta-cells, and
neuroendocrine cells. Genetic studies have shown type 2 diabetes may be
associated with an over-expression of the gene for the IL-6 receptor, which
means increased levels of IL-6 would be able to effectively bind and promote inflammatory
processes. The paper mentions a study that was done where IL-6 was given
exogenously to mice and it was shown to enhance fatty lesion buildup in
atherosclerosis. IL-6 was also increased after a heart attack and is associated
with a lower ejection fraction, which is a measurement of how well the heart is
pumping out blood.
The article also brings up the point that
the increased cytokines, such as IL-6, in diabetes are primarily secreted from cells not in
the circulation, such as adipocytes and endothelial cells in blood vessels, not from immune cells. Last week, we
talked about adipocytes’ role in promoting inflammation with their secretion of
leptin and adiponectin. I think this just goes to show the damaging role that
obesity plays in inflammation, since adipocyte hyperplasia and hypertrophy can
lead to such damaging inflammatory effects.
The
article also makes the point that diabetes is a stronger risk factor for
coronary heart disease in women than in men. Diabetes is associated with a 3-7 times greater cardiovascular disease risk among women compared with a 2-3 times greater risk among men. So I wanted to ask you guys, why do you think that is? What would make
diabetes so much worse for women in terms of acquiring cardiovascular disease? As a woman with cardiovascular disease and diabetes running in my family, this is particularly relevant to me!
I have been trying to find some research on your question of why women have a greater cardiovascular disease risk than men with diabetes, but everything I have found on it has said that the cause for this isn't completely understood. One possible reason I found is simply that diabetes might have a greater effect on risk factors for heart disease in women than in men.
ReplyDeleteThe Texas Heart Institute has a lot of good information about heart disease and talks about the risk with having diabetes. A reason for pre-menopausal women to be at greater risk than men is that diabetes in overweight, less active women cancels out the protective effects of estrogen. Estrogen is associated with higher levels of HDL and lower levels of LDL, so women with lower levels of estrogen leads to lower good cholesterol and higher bad cholesterol which is most likely a factor of why women have such a greater risk because they have less estrogen after menopause as well.
http://www.texasheartinstitute.org/HIC/Topics/HSmart/women.cfm
I had the same problem finding information on why women have a greater risk, which I thought was interesting because they put such an emphasis on making that point, and then they don't even give a clear reason why!
ReplyDeleteThe estrogen explanation was really interesting; I didn't know that low estrogen is associated with higher LDL levels.
My theory on this is that estrogen could very well be the key. Prior to menopause, estrogen is thought to provide some protection to women against heart disease. However, women that smoke or have diabetes may not be adequately protected by estrogen because diabetes and smoking are major risk factors for heart disease. In terms of the cardiovascular system, estrogen partially works to keep a woman's arteries free from atherosclerotic plaque by improving the ratio of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol. Estrogen increases the amount of HDL cholesterol, which helps clear LDL cholesterol from the bloodstream. However, after menopause estrogen levels are much lower and now the higher LDL levels are a major risk in developing coronary heart disease. On top of that some women in menopause are more prone to accumulating fat as a survival feature because fat produces estrogen and other hormones. That extra fat can be problematic and can only farther disrupt hormonal metabolism, balance, and increase inflammation throughout the body. So naturally I thought that hormone replacement therapy must be the answer, but, as I found out today, large clinical trials found that the treatment actually posed more health risks than benefits so it is no longer recommended, with a few exceptions.
ReplyDelete