Too much insulin means increased clotting, CV risk
Mass General study may explain high CV rate
Increased blood clotting due to elevated fasting insulin levels may help explain why diabetics are so susceptible to heart attacks and strokes, say researchers at Massachusetts General Hospital.
Impaired fibrinolysis or blood clotting may be an important link between hyperinsulinemia, insulin resistance, and the increased risk of cardiovascular disease in people with glucose intolerance, theorizes the team led by James B. Meigs, MD, MPH, an internal medicine specialist at Massachusetts General Hospital in Boston.
This may point out a flaw in the standard approach to the treatment of Type 2 diabetes by increasing amounts of insulin as the disease progresses, says Meigs.
"That [escalating insulin dosages] may not really help reduce cardiovascular events because it may be cranking up the insulin levels, causing more clotting and working against the intention to improve CVD risk, says Meigs.
Yet, he conjectures, exercise may hold a key to neutralizing the effects of excess insulin.
"Regular physical exercise is absolutely critical here," he says. "Because exercise makes the body more receptive to the effects of insulin, it may improve a person’s ability to dissolve blood clots and possibly lower the risk of heart attacks and strokes that kill 75% of all Type 2 diabetics."
The study, published in the Jan. 11 issue of the Journal of the American Medical Association, studied 3,000 people in the Framingham Offspring Study between 1991 and 1995. The subjects included diabetics, people with impaired glucose tolerance (IGT), and nondiabetics. They closely matched the estimated prevalence in the general population: 80.2% with normal glucose tolerance, 15.2% with IGT, and 4.7% with previously undiagnosed diabetes.
Investigators found that nondiabetics who had elevated insulin levels also had elevated levels of the PAI-1 antigen, a chemical that impairs blood’s ability to dissolve clots. In diabetics and those with IGT, the levels of insulin and PAI-1 were even higher.
"What this means is that the presence of insulin tips the blood’s balance toward clots forming and staying," theorizes Meigs. "Something is wrong with the lining of the blood vessels, and the endothelium is dying, which raises PAI-1 levels and causes insulin resistance."
Be aware of the dangers
The findings, says Meigs, should make clinicians more aware of the dangers of IGT and consider medications to treat IGT earlier, even before it becomes full-blown diabetes. Particularly, he suggests using thiazolidinediones to lower insulin levels, which may help lower the risk of cardiovascular disease.
"We don’t know if thiazolidinediones improve fibrinolysis capacity, that’s our next area of research," says Meigs.
He urges clinicians to encourage their patients to exercise at least three times a week, a regimen widely recommended to reduce all risks of complications by improving glycemic control. He also recommends that clinicians pay the utmost attention to all means of reducing cardiovascular risks, including diet, cholesterol and blood pressure lowering, and appropriate medications.
It is difficult to sort out the contribution of various risk factors, like impaired fibrinolysis, to the total burden of cardiovascular risk, says Andreas Festa, MD, a research fellow in clinical epidemiology studies on clotting and insulin resistance at the University of Texas Health Science Center at San Antonio.
Festa says people with insulin resistance syndrome (IRS) — high insulin resistance, high blood pressure, visceral obesity, dyslipidemia — also have high PAI-1 levels, whether they are diabetic or nondiabetic, and therefore have a high risk of cardiovascular disease.
He agrees that exercise, weight control, and controlling triglycerides and increasing HDL cholesterol may help lower PAI-1 levels, adding to protections against other diabetic complications.
Since there is currently no consensus as to what constitutes normal PAI-1 levels or pathological, so measurement of these risk factors "seems questionable at this point but will conceivably be meaningful in the near future," says Festa. The laboratory technique is relatively easy to perform and can be standardized, he adds.
There are some data to show that insulin sensitizing medications like metformin also may provide an effective treatment for elevated PAI-1 levels. However, he says, "By treating insulin resistance, you may expect improvement of impaired fibrinolysis, but it is not clear whether this improvement adds to the benefit in cardiovascular outcome you might expect in successfully treating people with insulin-resistant syndrome."
Glycemic control, while important in the larger picture of diabetes treatment, will "certainly add to the benefit, but to what extent is largely unknown," Festa concludes.
[For more information, contact James Meigs at (617) 726-8157 and Andreas Festa at [email protected].]
You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
- Award-winning Medical Content
- Latest Advances & Development in Medicine
- Unbiased Content