Adiponectin- Hormone responsible for putting out small fires.
The body is constantly under attack from the abuse of living. Internally there are all these injuries occurring at the molecular level, causing damage that spreads like wildfire until it is out of control. Metabolic syndrome is an example of this. What is it? This is a term used to describe a group of conditions that put patients at higher risk of developing type two diabetes and/or heart disease. Patients having three or more of the following are considered to have Metabolic Syndrome:
- High fasting glucose (greater than 5.6 mmol/L)
- High Blood Pressure (130/85 of higher)
- High Triglyceride (> 1.7 mmol/L)
- Decreased HDL (<1.0 in men, <1.3 in women) (A trick to remember which cholesterol is which is that HDL is the Healthy one, LDL is the Lousy one )
- Abdominal obesity or too much fat around the waist (>102 cm (40 inches) for men, >88 cm (35 inches) for women)
There is some debate on what causes Metabolic Syndrome. Is it due to increased insulin resistance, genetics, old age or life style? Wouldn’t it be nice if there was a diligent fulltime fighter in the human body that went around putting out the little brush fires these conditions caused before they became five alarm threats to our health?
Researchers have discovered a hormone that does this and it is from an unlikely source.
After studying the cells found in adipose (fatty) tissue called adipocytes, it was discovered that forty percent of the expressed genes were unknown or novel genes, even the gene that was most abundant and specific for an adipocyte. Further research identified a protein produced by adipocytes termed adiponectin.
Logic would determine that the more adipose tissue you have the more adipocytes present would result in increased levels of adiponectin, correct?
Wrong. To everyone’s surprise the higher the body mass index (BMI) the lower the adiponectin levels. Healthy patients with low levels of body fat had higher levels of adiponectin. Patients with Metabolic Syndrome and diabetes also had low levels of adiponectin.
So what does adiponectin exactly do?
It can help prevent atherosclerosis in blood vessels. Atherosclerosis is damage to cell walls caused by accumulation of fatty materials, such as LDL cholesterol and white blood cells called monocytes. Adiponectin has been found to prevent this kind of cell wall damage by having inhibitory affect against molecules that cause LDL and monocytes from sticking to vessel walls. This protein once secreted by adipocytes enters into the blood stream and looking for damaged cells lining vessel walls to repair, putting out small fires before they burn out of control.
The bad news is that measurement of adiponectin is not routinely done in the medical lab... yet. But when it does, it will help determine which patients will be at risk of developing Metabolic Syndrome. A good article to read about this can be found at :
http://atvb.ahajournals.org/cgi/reprint/24/1/29
Thank you for taking the time to read my posting. I look forward to your thoughts and comments.
Regards,
Mark Hawkins
Sunday, December 20, 2009
Wednesday, December 2, 2009
Tight Glycemic Control
One of the complications of critically ill patients is developing hyperglycemia, high glucose levels, even when they are not diabetic. Controlling the glucose level presents an added challenge to the care of these patients since it has been postulated that high glucose levels can lead to more complications such as septicemia, neuropathy and death. The conventional therapeutic approach has been to monitor the patients glucose and to treat when the plasma glucose level is greater than 11.9 mmol/L (215mg/dL) by insulin infusion and then try to maintain it between 10.0 to 11.0 mmol/L (180-200 mg/dL). Although this does work, the question has been would trying to have tighter glycemic control improve patient outcomes?
In 2001, the New England Journal of Medicine published a study by Dr. Greet Van den Berghe that tried to answer that question. In her study (which can be found at:
http://content.nejm.org/cgi/content/short/345/19/1359) 1548 ICU patients receiving mechanical ventilation were given intense insulin therapy, put insulin infusion to maintain their glucose levels between 4.4-6.0 mmol/L (80-110 mg/dl). Glucose was measured using whole blood with an ABL700 at 1 to 4 hour intervals.
The results were impressive. Bloodstream infections were reduced by 46%, acute renal failure by 41%, RBC transfusions by 50% and critical illness polyneuropathy by 44%. Most impressive of all was the mortality rate being halved from 8.0% to 4.6%.
With such positive patient outcomes, many hospitals have started using tight glycemic control and have reported similar impressive results. Logic would conclude that tight glycemic works.
However in March 2009 the NEJM released a the results of the NICE-SUGAR (Normoglycemic in Intensive Care-Survival Using Glucose Algorithm Regulation) study that evaluated hospitals using tight glycemic control on critically ill patients.
It was a huge multinational study that examined the outcomes of 6000 patients. In this study (http://content.nejm.org/cgi/content/short/360/13/1283?ssource=mfv), the opposite was found, that tight glycemic control did not decrease mortality, but increased it.
So where does that leave the critically ill patient? The day after the NICE-SUGAR study was released, a joint statement was released by the American Diabetes Association and the American Association of Clinical Endocrinologists stating that tight glycemic control should not be abandoned, but be up to the clinician on whether or not the patient would benefit from it. This statement can be found at:
http://newswise.com/articles/joint-statement-on-the-nice-sugar-study-on-intensive-versus-conventional-glucose-control-in-critically-ill-patients?ret=/articles/list&category=latest&page=1&search[billing_institution_id]=0&search[date_range]=&search[institution_name
Dr. Van den Berghe’s groundbreaking study has shown that keeping glucose levels tightly controlled can improve patient outcomes while the NICE-SUGAR study illustrates that before a hosptital jumps on the tight glycemic control bandwagon it has to have the infrastructure in place. The cornerstone to this is accurate and precise measurement of blood glucose levels. In order for this to happen, the lab will have to be involved. Why?
On the surface it looks like the lab has no role in tight glycemic control since it is done by nurses. All that is required is for a single drop of blood placed on a test strip that is then stuck in the small bedside monitor and wait for the result to be displayed. It doesn’t get any simpler than that.
The same could be said about driving a car. There have been news stories of children as young as five taking their parents car for a spin down the freeway. That doesn’t mean the driving age should be dropped to six. The same could be said for any health care professional performing bedside glucose monitoring. Before anyone can operate them, they have to be trained on not only how to use them, but the institution’s standard operating procedures as well. This is where the lab can be a vital resource, providing training and making sure that the instruments used are properly working.
If anyone involved in the NICE-SUGAR is reading this posting, would it be possible if you could answer this simple question regarding the operators. Was there any external proficiency testing done?
What is external proficiency testing? It is standard in all labs, where an outside agency sends specimens that the lab has to analyze and send the result in. The labs performance is then evaluated depending on how accurate the results were. If the lab consistently produces good results, it passes. However if the lab is inconsistent in its performance, its accreditation can be taken away.
External proficiency testing is not cheap. But neither is quality.
Another reason the lab can be involved is if the doctor wants to check other analytes, such as electrolytes and ketone bodies. Patients who are dehydrated and are on certain medications can have spurious results on the bedside glucose monitors, and may require a different analyzer to measure their glucose level.
Some labs actually do the bedside glucose testing with very good consistent results. An example of this is the program run by Brenda Franks at Nebraska Methodist Hospital in Omaha where phlebotomists do the bedside glucose testing. An article on their success can be found at:
http://www.cap.org/apps/cap.portal?_nfpb=true&cntvwrPtlt_actionOverride=%2Fportlets%2FcontentViewer%2Fshow&_windowLabel=cntvwrPtlt&cntvwrPtlt%7BactionForm.contentReference%7D=cap_today%2F0909%2F0909f_POC_leader_spreads.html&_state=maximized&_pageLabel=cntvwr
Bottom line, tight glycemic controls works, but it’s not perfect. The lab should be used as an excellent resource if the organization wants to pursue this for their critically sick patients.
In 2001, the New England Journal of Medicine published a study by Dr. Greet Van den Berghe that tried to answer that question. In her study (which can be found at:
http://content.nejm.org/cgi/content/short/345/19/1359) 1548 ICU patients receiving mechanical ventilation were given intense insulin therapy, put insulin infusion to maintain their glucose levels between 4.4-6.0 mmol/L (80-110 mg/dl). Glucose was measured using whole blood with an ABL700 at 1 to 4 hour intervals.
The results were impressive. Bloodstream infections were reduced by 46%, acute renal failure by 41%, RBC transfusions by 50% and critical illness polyneuropathy by 44%. Most impressive of all was the mortality rate being halved from 8.0% to 4.6%.
With such positive patient outcomes, many hospitals have started using tight glycemic control and have reported similar impressive results. Logic would conclude that tight glycemic works.
However in March 2009 the NEJM released a the results of the NICE-SUGAR (Normoglycemic in Intensive Care-Survival Using Glucose Algorithm Regulation) study that evaluated hospitals using tight glycemic control on critically ill patients.
It was a huge multinational study that examined the outcomes of 6000 patients. In this study (http://content.nejm.org/cgi/content/short/360/13/1283?ssource=mfv), the opposite was found, that tight glycemic control did not decrease mortality, but increased it.
So where does that leave the critically ill patient? The day after the NICE-SUGAR study was released, a joint statement was released by the American Diabetes Association and the American Association of Clinical Endocrinologists stating that tight glycemic control should not be abandoned, but be up to the clinician on whether or not the patient would benefit from it. This statement can be found at:
http://newswise.com/articles/joint-statement-on-the-nice-sugar-study-on-intensive-versus-conventional-glucose-control-in-critically-ill-patients?ret=/articles/list&category=latest&page=1&search[billing_institution_id]=0&search[date_range]=&search[institution_name
Dr. Van den Berghe’s groundbreaking study has shown that keeping glucose levels tightly controlled can improve patient outcomes while the NICE-SUGAR study illustrates that before a hosptital jumps on the tight glycemic control bandwagon it has to have the infrastructure in place. The cornerstone to this is accurate and precise measurement of blood glucose levels. In order for this to happen, the lab will have to be involved. Why?
On the surface it looks like the lab has no role in tight glycemic control since it is done by nurses. All that is required is for a single drop of blood placed on a test strip that is then stuck in the small bedside monitor and wait for the result to be displayed. It doesn’t get any simpler than that.
The same could be said about driving a car. There have been news stories of children as young as five taking their parents car for a spin down the freeway. That doesn’t mean the driving age should be dropped to six. The same could be said for any health care professional performing bedside glucose monitoring. Before anyone can operate them, they have to be trained on not only how to use them, but the institution’s standard operating procedures as well. This is where the lab can be a vital resource, providing training and making sure that the instruments used are properly working.
If anyone involved in the NICE-SUGAR is reading this posting, would it be possible if you could answer this simple question regarding the operators. Was there any external proficiency testing done?
What is external proficiency testing? It is standard in all labs, where an outside agency sends specimens that the lab has to analyze and send the result in. The labs performance is then evaluated depending on how accurate the results were. If the lab consistently produces good results, it passes. However if the lab is inconsistent in its performance, its accreditation can be taken away.
External proficiency testing is not cheap. But neither is quality.
Another reason the lab can be involved is if the doctor wants to check other analytes, such as electrolytes and ketone bodies. Patients who are dehydrated and are on certain medications can have spurious results on the bedside glucose monitors, and may require a different analyzer to measure their glucose level.
Some labs actually do the bedside glucose testing with very good consistent results. An example of this is the program run by Brenda Franks at Nebraska Methodist Hospital in Omaha where phlebotomists do the bedside glucose testing. An article on their success can be found at:
http://www.cap.org/apps/cap.portal?_nfpb=true&cntvwrPtlt_actionOverride=%2Fportlets%2FcontentViewer%2Fshow&_windowLabel=cntvwrPtlt&cntvwrPtlt%7BactionForm.contentReference%7D=cap_today%2F0909%2F0909f_POC_leader_spreads.html&_state=maximized&_pageLabel=cntvwr
Bottom line, tight glycemic controls works, but it’s not perfect. The lab should be used as an excellent resource if the organization wants to pursue this for their critically sick patients.
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