Thursday, December 29, 2011

Merry Christmas and a happy New Year

Merry Christmas and happy New Year. I have been enjoying my family this week, 3 children and 5 grand children. I will get my blog going again Jan. 2nd.  My best to you and your family .   Dr. Calder

Wednesday, December 21, 2011

Tell us about the benefits of NMR and A1C testing...pleazzzzzzz. Thank you!

  Carl Old Sr said...
Tell us about the benefits of NMR and A1C testing...pleazzzzzzz. Thank you!

 NMR lipid profile is a test that measures the number and size of lipoproteins  such as LDL and HDL. This can be useful when trying to evaluate someones LDL cholesterol when they have an elevation of their Triglyceride level over 150mg/dl.
    LDL is made in the liver and is produced is a spectrum of sizes varying from small  to large LDL particles. The smaller size LDL is associated with increased risk of heart disease . Triglyceride elevation which is common in people with Type 2 diabetes is associated with an increase is the small dense LDL particles .
     Apo b test is another way of  this problem. See my blog Dec.14

 
 What are the Benefits of A1c testing ?

      This is a great question.

 Glucose in blood binds to  hemoglobin in  red blood cells  and remains attached for the life of the  cell which is about  3 months.  Higher glucose levels are associated with more glucose attachment . The chart below will give you an idea of how A1c results correlate with mean glucose test results..
  
                                        Mean plasma glucose
A1C (%)
                                         mg/dl               mmol/l
6                                          126                     7.0

7                                          154                      8.6

8                                          183                    10.2
9                                          212                    11.8
10                                        240                    13.4
11                                        269                    14.9

    The A1c test is a predictor of the risk for developing diabetes complications. Two classic studies, the DCCT study in Type 1 Diabetes and  the UKPDS  done with Type 2 Diabetes demonstrated a significant   reduction in eye , nerve and kidney damage by reducing  the A1c  to 7. There was about a 30 % reduction in risk for  a 1 % point drop in A1c. There was also a nonsignificant 16% reduction in cardiovascular risk  by reducing The A1c from 8 to 7 in the UKPDS .
 These two large studies  and another one called the Kumamoto study provided the evidence for establishing an A1c result of < 7 as the recommended target goal
         Thanks again for the good question. Dr. Calder

Monday, December 19, 2011

Diabetes Office visit App iTunes add update

I have revised my iTunes  explanation of  the Diabetes Office  Visit App.  Comments ,corrections and discussion is welcome .



The only comprehensive diabetes management App - see more 
**CREATED BY David Calder MD to provide an always at your finger tips comprehensive diabetes management tool , that will simplify your diabetes care and help you preserve your good health. 
                                         "  Diabetes Office Visit app.  " is designed to help you , 
                                             Set goals> reach goals> and prevent complication 
                                          :" Diabetes office visit app " is designed specifically to deal with all risk 
                                             associated with having Diabetes. 
                                        
                                            Diabetes control is more than just controlling blood glucose levels. 
                                            Cardiovascular disease is the major risk for people with Diabetes and 
                                            pre -diabetes.
  "DIABETES OFFICE VISIT APP"  includes
     " RISK MANAGEMENT SECTION "     provides the tools for tracking and managing the risk factors ( Blood 
                                                            Pressure , LDL cholesterol , HDL cholesterol , Triglycerides , Apo b 
                                                            levels and albumin/ creatinine ratio ) associated with Diabetes and 
                                                            heart disease.
                                                           
                                                         

      "GOAL SETTING SECTION "             provides you with the recommend target goals and the ability to 
                                                             adjust those goals to meet your specific situation.
                                                             Having target goals makes diabetes care much simpler. If you know
                                                             the target goals- then any thing that is not meeting that goal is a
                                                             reason for discussion with your physician
                                                            .
  
                                      ” YOU FAIL TO ACHIEVE 100% OF THE GOALS YOU DON'T SET”. 
     " GLUCOSE MANAGEMENT SECTION " is designed by me to present the the information needed by you
                                                                and your physician to make management decisions . Collecting 
                                                                and presenting the right  data to your health care provider is 
                                                                crucial to making the correct glucose management decisions. 
                                                              
                                                               You can follow just your glucose results or add carbohydrate 
                                                               intake, exercise or medications if needed.
                                                               The ebook discusses when to test and how to  present your data to
                                                                your health care provider. 
                                                             
     " e BOOK SECTION "                          Provides all of the above tools , plus a better understanding of 
                                                               treatment goals and a light hearted look at our diet problems and 
                                                               geezerhood treatment decisions and diabetes .
                                                             
                                                              Diabetes office visit deals one of the biggest diabetes associated
                                                              risk , COMPLACENCY .
                                                                       (the feeling of quite security often while unaware of a 
                                                                        potential danger )
    " DIABETES OFFICE VISIT WEB SITE "   This web site and "The Doctor is in"  section is designed to answer 
                                                               any diabetes related questions and includes a almost daily blog 
                                                               focused on improving your understanding of basic management 
                                                               concepts.  The 10 minute App training video will help you find and
                                                               use all of this app's features.
                                                            
                                                                www.diabetesofficevisit.com 
      You and I , as patients ,are ultimately responsible for managing all of the aspects of diabetes care. 
       Imagine what could happen if, each of us accepted the privilege and responsibility for   
       maintaining our own good health. Diabetes Office Visit App. provides you with the tools to make this 
       this happen 

       You can also reach me  email          info@diabetesofficevisit.com           
                                                               dcalder@diabetesofficevisit.com 
                                            Regular mail —- Diabetes office Visit PO BOX 1170 Creswell, Oregon 97426 
I will do my best to make this app work for you.
One of the technical issues we had in development was the inability of me to make test and corrections prior to its release. This resulted in 8 updates over 3 to 4 months as I found and corrected Items that did not meet my goals. I apologize for that problem 
If you are unhappy with the app for any reason i will refund your money . 
                                                 
                 Thank you , have fun  and be smart . You can defeat diabetes
                                                                                                                  David Calder, MD 
This eBook and App is written by David Calder,MD  , a diabetes specialist with over 35 years of experience , who worked hands on to design this app to help patients better manage all aspects of 
their diabetes care. This app taps the knowledge and experience of Dr. Calder to  help you get more out of each doctor's visit .


Friday, December 16, 2011

What is Non-HDL cholesterol ? Why should I care ?

We have discussed using LDL cholesterol and Apo b test  to help evaluate  our risk for developing heart disease. Today we are discussing another tool  that is gaining in popularity , Non-HDL Cholesterol .

 Non -HDL Cholesterol  is based on a simple idea . Elevated levels of any thing other than HDL is not in our best interest.

 Calculation is easy;
      Total cholesterol - HDL  =  Non - HDL Cholesterol

 Recommended  Target Goals by;    ADA ( American Diabetes association )
                                                          ACC ( American college of cardiology )


                              LDL            Apo b          Non-HDL cholesterol
                                mg/dl           mg/dl               mg/dl

no risk factors        <100            <90                 <130
+ 1 risk factor         <70             <80                 < 100


  risk factors include High Blood Pressure ,smoking , family history of premature heart disease.

  This is an easy test to do on your own lab.  and may help you and you physician make management decisions
                          Have  fun      Dr. Calder

Wednesday, December 14, 2011

Your heart and your Apo b test

Yesterday we discussed some of the problems associated with evaluating our LDL test results. We know that an increase in our Triglycerides  effects the mathematical calculation of LDL  and is also associated with an increase of small dense LDL particles .

We do have another way of evaluating LDL cholesterol .
It is possible to measure a protein , called  Apo-b .
Apo-b lipoprotein is an integral part of each  LDL particle regardless of it's size.

 Recommended Goals  2009
                          ACC( American college of cardiology )
                          ADA ( American Diabetes Association )
           
      LDL <100 mg/dl           Apo b   < 90 mg/dl

       LDL < 70 mg/dl            Apo b   <80  mg/dl

  Combining this test with your LDL result  is another tool helping you and your doctor  reduce your risk of heart disease.

What is non-HDL cholesterol ?   Find out tomorrow .
     
       Have fun.   Dr. Calder

 


Tuesday, December 13, 2011

Triglycerides , LDL cholesterol and your risk of heart disease

 I think most of us have had a LIPID panel done.  This test usually includes ;
     Total  Cholesterol
     Triglyceride
      LDL cholesterol
      HDL cholesterol

 Many of us are satisfied with a call from our doctors office reporting that " every thing looks OK " .

I would like to encourage you to not accept that answer and use a different approach.
      #1  always ask for a copy of your lab. reports
      #2  Know what the recommended goals are for each test
      #3  Any test not at the recommended goal is a reason to make an appointment and discuss the result
            with your doctor
      #4    Read and learn as much as you can about the test in question before seeing your doctor. Your
              doctor is a wonderful source of wisdom and understanding if you just ask for the help.

  Lets take a closer look at your lipid panel.

  Your  total cholesterol is made up of components of each of the other test.

      Total cholesterol = 1/5 of triglycerides + HDL + LDL

       Triglycerides-    triglycerides are often the sleeper with a major impact on our other test results
                                   

        LDL Cholesterol
                  LDL cholesterol is made in our liver and
                  LDL is produced in various sizes ,varying from small dense particles to larger fatter particles.

                 The size of the LDL particles changes with our triglyceride levels
                  High triglycerides are associated with an increase in small dense LDL particles and increased
                  risk of heart disease.

                  LDL cholesterol is usually not measured and instead is a calculated number.
                  for example:

                  LDL   =   Cholesterol  -  1/5 of triglycerides   -  HDL
                        Changes in triglyceride levels have a major effect on your LDL test results
                        Higher triglycerides  increase small dense LDL and lower appearing LDL results
           
         Compare the LDL result by changing triglycerides from 150 mg/dl  to 300 mg/dl

                  Total Cholesterol   -  1/5 triglycerides   -     HDL       = LDL Cholesterol


                         200mg/dl       -    150/5 ( 30 )                  -       40         =    130mg/dl

                          200 mg/dl      -     300/5 (60)                 -       40         =     100 mg/dl

            The decision to recommend a statin becomes a little more complex when elevated triglycerides are
             included in the pictures. This is a common every day problem for people with type 2 diabetes.
             The most common lipid profile for patients with Type 2 diabetes is a slight increase in  total
             cholesterol , LDL and triglycerides.

         What about a Apo-b test.   find out tomorrow.

                                  Have fun      Dr. Calder
                 

           
               
       

Monday, December 12, 2011

Goals for LDL cholesterol. Is there a level of optimal benefit ?


   



What are  the recommended goals for LDL cholesterol for people with diabetes?

American Diabetes Association 2010

For individuals "without  overt "cardiovascular disease  the primary goal is an LDL < 100 mg/dl (2.6 mm/l)
For individuals "with overt" cardiovascular disease, a lower goal of < 70 mg/dl (1.8mm/l)


My thoughts on these targets starts with questions .

Is an LDL result of < 70 mg/dl the level of optimal benefit ?
     Recent clinical trials have demonstrated that reducing LDL  levels minimally above 100mg/dl  by about 30 to 40 
    %  to effective in reducing cardiovascular events. 
    This is especially true for people with acute coronary syndromes.
   
   

How do we know who does and who does not have silent coronary artery disease ?


                               We don't know because it is silent !
                             

      Coronary calcium deposits can be detected with special CT scans and  intra-coronary artery ultrasound procedures  can detect hidden vascular disease. However there is  increased cost and risk  that prevent there use in our routine screening test. 
     I did have the a coronary calcium CT assessment  done and was happy to know that I had negligible coronary artery calcium. However I also realize that the test did not completely rule out silent coronary disease. The test did detect  asymptomatic significant coronary calcium in a friend  who subsequently had coronary bypass surgery.


    Also our known risk factors have not been shown to predict who does or does not have coronary heart disease. 
 reported that 22% 
   The Diad Study published in Diabetes Care August 8 2004 ;1954-1961 reported that 22 % of asymptomatic
    patients with diabetes were found to have silent myocardial ischemia with extensive testing. 

My thoughts;
      We know who is at risk .
      We know what the risk factors are for heart disease.
      We know that we can correct the risk factors and reduce the risk of developing heart disease.
      We know that we have safe effective medications  for reducing risk.
      I believe that most of us would prefer to not have overt cardiovascular disease. 
    
      Why not use these amazing tools and treat to a level of optimal benefit ( LDL < 70mg/dl ) and


      reduce everyones risk of developing heart disease? 


There are some things to consider . 
   
     
        Is age or  type of diabetes a factor  in making the decision ?

           Most of the risk factor management  for people with diabetes is about " reducing long term risk ".  
           You may have noticed that long term becomes a little shorter as we approach Geezerhood .

         (check out  Diabetes Office visit chapter 8 page 53 ,The definition of long term from an old geezers 
              perspective, for a lighter look at this problem. Diabetes Office visit , is a lighter look at simplifying the complex
               issues of diabetes care. )
      
         How does  HDL and Triglyceride test results effect my  treatment decision ?  
       
         Would checking  my  Apo- b level help in making my treatment decision ?
       My LDL has improved but is still well above the recommended goals. Should I stay on the 
        medication ?
I will continue this discussion on lipids and diabetes . Your questions and opinions are welcome . 
                     Have fun            Dr. Calder 
       

Recommended goals for LDL cholesterol. Is there a level of optimal benefit ?

What are the recommended goals for LDL cholesterol for people with diabetes? American Diabetes Association 2010 For individuals "without overt "cardiovascular disease the primary goal is an LDL < 100 mg/dl (2.6 mm/l) For individuals "with overt" cardiovascular disease, a lower goal of < 70 mg/dl (1.8mm/l) My thoughts on these targets starts with questions . Is an LDL result of < 70 mg/dl the level of optimal benefit ? Recent clinical trials have demonstrated that reducing LDL levels minimally above 100mg/dl by about 30 to 40 % to effective in reducing cardiovascular events. This Treatment is especially true for people with acute coronary syndromes. How do we know who does and who does not have silent coronary artery disease ? Coronary calcium deposits can be detected with special CT scans and intra-coronary artery ultrasound procedures can detect hidden vascular disease. However there is increased cost and risk that prevent there use in our routine screening test. I did have the a coronary calcium CT assessment done and was happy to know that I had negligible coronary artery calcium. However I also realize that the test did not completely rule out silent coronary disease. The test did detect asymptomatic significant coronary calcium in a friend who subsequently had coronary bypass surgery. I believe that we are generally not good at making a diagnosis of silent coronary artery disease in any one with out the use of invasive and risky procedures. Also our known risk factors have not been shown to predict who does or does not have coronary heart disease. THe Diad Study published in Diabetes Care 2004 found that 22% of asymptomatic patients with diabetes were found to have silent myocardial ischemia with extensive testing. My thoughts; I believe that most of us would prefer to not have overt cardiovascular disease. We also know that we have limited tools to accurately determine who does and does not have silent coronary artery disease We also have safe effective medications ( statins and others) that can reduce our risk of developing overt cardiovascular disease Why not use these amazing tools and treat to a level of optimal benefit ( LDL < 70mg/dl ) and reduce everyone risk of developing heart disease ? Is age a factor ? Most of the risk factor management for people with diabetes is about " reducing long term risk ". You may have noticed that long term becomes a little shorter as we approach Geezerhood . check out Diabetes Office visit chapter 8 page 53 ,The definition of long term from an old geezers perspective, for a lighter look at this problem. Diabetes Office visit , is a lighter look at simplifying the complex issues of diabetes care. How does HDL and Triglyceride test results effect my decision ? Would checking my Apo- b level help in making my treatment decision ? My LDL has improved but is still well above the recommended goals. Should I stay on the medication ? I will continue this discussion on lipids and diabetes . Your questions and opinions are welcome . Have fun Dr. Calder

Saturday, December 10, 2011

Reducing heart disease risk is your choice

In a recent article in medscape,Dr. John Betterridge(university of London,UK )discussed the evidence for the use of Statins as part of our treatment program for people with diabetes.He pointed out that trials such as the CARDS Study have proven the benefit of Statins in reducing the risk of vascular disease in people with type 2 diabetes. The CARDS study , for example, used Lipitor(atorvastatin) and reduce LDL cholesterol by 40 % and was associated with a 37% reduction in cardiovascular events and a halving of the stroke rate in 4 years.
He refered to another study the Cholesterol treament Trailists'Colalaboration which showed that women and people with type 1 diabetes over the age of 40 benefited from the use of statins.

I like final sentence in the CARDS study.

"THe debate about whether all patients with type 2 diabetes warrant statin treatment should now focus on whether any patient can reliably be identified as sufficiently low risk for this safe and efficacious treatment to be withheld" .



Upcoming topics on cholesterol. The > good , the < bad = < ugly outcome

How low to go with LDL cholesterol ( bad cholesterol ) ? Is there a level of optimal benefit ?

LDL is made in our___?____ . LDL cholesterol comes in small , medium and large sizes. What would you like to order ?

Is my LDL test results measured or just a calculated number?

Where are your triglycerides tonight ? Why should you care ?

My HDL ( good cholesterol )is 65 mg/dl. Why should I care about my LDL result ?

Will taking a " Statin drug " completely protect me from a heart attack ?


You can reduce your risk for developing heart disease and stroke. Become your doctors #1 assistant in maintaining your good health.

Reducing your heart disease risk is a game of numbers . Play hard ,understand your numbers , and win one day at a time ?

Have fun. Dr. Calder






Dr. Calder

Tuesday, December 6, 2011

Teenagers- great home test results - elevated A1c continued.

Most of the time parents of children with diabetes are are somewhat reluctant but also happy when their child takes over glucose testing and insulin shots.

There can sometimes be problems as the child assumes responsibility for this part of their life. Teenagers often seem to be very mature and at the same time have residual childhood behavior that can lead to making unwise decisions.

The problem of children especially teenage children providing false glucose test data to their parents and doctors is not unusual. How to deal with this sensitive issue is a problem for parents and health care providers.

My approach evolved over time. I believe that dealing with diabetes day to day can overwhelm any one, especially a child. I also think that diabetes can beat up a child but it cannot beat up a child and their parents working as a team.

Recognizing and accepting the problem is the first goal. Explaining to the parents and child very openly that this type of behavior is a common way of dealing with an unpleasant overwhelming job. It is no ones fault and may just be a way your child is asking for help.

Let the child know that you love them and that this type of behavior is not in his or her best interest. Explain that becoming independent is a part of growing up and that independence often proceeds our readiness to accept all of the responsibility of being independent. Let the child know that is nothing is seriously wrong and that this is a type of behavior and we have all experienced this to some degree. The child also needs to understand that the behavior is not in their best interest and that you will do anything to help them find another way of dealing with day to day requirements of having diabetes.

My mother raised 6 children with some occasional back up by my dad. They only went to the 5th and 6th. grade in school but were very wise. Mom or dad believed in hard work and independence but also encouraged enjoying being a child. Mom explained that childhood is brief and that being a responsible adult is a much longer part of our lives.

In summary, I suggest encouraging a teenager with diabetes management problems to enjoy being a child just a little longer and allow mom and dad to help them slowly accept the responsibility of dealing with this disease . Dr. Calder

Sunday, December 4, 2011

Teenagers- great home test results - elevated A1c

Teenagers with diabetes – great home glucose test- high A1c


Teenage children with diabetes present a number of issues for parents and their doctors. I would like to stress the word children because they are. They may have a grown up looking body and developing independence but still have many of the thought processes of a child.
This combination often presents some delicate issues for their parents and health care providers.

The mismatch of A1c and home glucose test results is not unusual. Teen agers may bring in great looking home glucose test results and then the lab. finds an elevated A1c result.

The desire to believe the home glucose results is very strong with parents and doctors. I have been fooled more times than I would like to remember by sweet young girls. The girls would often bring in neat clean glucose records with what appeared to be expected variation. we would discuss and make management plans based on their results .Then the A1c would come back at 12 or 14. This resulted in phone calls and disbelief by the parents . It is common to first think that the A1c test is incorrect or that the child has some other problem causing the elevation.
My ability to deal with this issue improved after we started doing office testing of A1c and had immediate results.

I cannot think of many causes for false elevations of the A1c. Lab error is rare and ruled out by a repeat test. Iron deficiency may cause a very slight elevation, but generally when you hear hoof beats coming you can expect to see a horse

There are also subtle clues to made up numbers. Girls will often have very neat results all written with the same pen. if you look at the last digit of the results there will be a pattern of using the same number such as 0 or 5. Boys were often a little different with less desire to please their parents or doctor with good results. Some kids would provide sloppy unreadable test results or no results at all.

How to manage this problem is a problem for parents and healthcare providers .

I will give you my opinion tomorrow. Dr. Calder


Friday, December 2, 2011

What if ! you are empowered to become your doctors number one assistant caring for your diabetes.

Wow ! why not become the number one medical assistant in caring for my diabetes.


Your doctor , diabetes educators and dietitians have the knowledge and wisdom to direct your diabetes care. They provide you with the tools and it is up to you to use those tools.


Many people with diabetes rely on their doctor or other health care provider to remind them when a test is needed and are satisfied when they are told every thing looks OK. You may say that understanding all of those test is just to difficult. I am here to tell you that all of the diabetes test results are just numbers. The recommended goals for those numbers is available from the American Diabetes Association or your doctors office.

All of our life situations are different and the recommended goals may not be the best goal for you . Your doctor can help you adjust the recommended goals to your specific situation. You and your doctor decide on specific target goals. "Just numbers". Now any number that is not at its recommended level is a reason for discussion with your doctor.


I would like to go back to our imaginary statistical primary care doctor from a few days ago who has 72.5 patients with diabetes and 223 patients with pre-diabetes and trying to track and manage 3546 test.

Your doctor could now have 295.5 trained diabetes medical assistants . As one of those assistants your job will be to track and manage 12 test on the person who is the most interested in their own health. You


Great things can happen with you being the number one medical assistant responsible for winning this game of numbers. Review this information from the National Institutes of Health and you decide if it is worth the effort.





Preventing Diabetes Complications. This information was taken from the, National Institute Of Diabetes,Digestive and Kidney Disease .

Glucose Control

  • Studies in the United States and abroad have found that improved glycemic control benefits people with either type 1 or type 2 diabetes. In general, every percentage point drop in A1C blood test results, for example, from 8.0 to 7.0 percent, can reduce the risk of microvascular complications—eye, kidney, and nerve diseases—by 40 percent. The absolute difference in risk may vary for certain subgroups of people.
  • In patients with type 1 diabetes, intensive insulin therapy has long-term beneficial effects on the risk of cardiovascular disease.

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Blood Pressure Control

  • Blood pressure control reduces the risk of cardiovascular disease—heart disease or stroke—among people with diabetes by 33 to 50 percent and the risk of microvascular complications—eye, kidney, and nerve diseases—by about 33 percent.
  • In general, for every 10 mmHg reduction in systolic blood pressure, the risk for any complication related to diabetes is reduced by 12 percent.
  • No benefit of reducing systolic blood pressure below 140 mmHg has been demonstrated in randomized clinical trials.
  • Reducing diastolic blood pressure from 90 mmHg to 80 mmHg in people with diabetes reduces the risk of major cardiovascular events by 50 percent.

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Control of Blood Lipids

  • Improved control of LDL, or bad, cholesterol can reduce cardiovascular complications by 20 to 50 percent.

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Preventive Care Practices for Eyes, Feet, and Kidneys

  • Detecting and treating diabetic eye disease with laser therapy can reduce the development of severe vision loss by an estimated 50 to 60 percent.
  • About 65 percent of adults with diabetes and poor vision can be helped by appropriate eyeglasses.
  • Comprehensive foot care programs—ones that include risk assessment, foot-care education and preventive therapy, treatment of foot problems, and referral to specialists—can reduce amputation rates by 45 to 85 percent.
  • Detecting and treating early diabetic kidney disease by lowering blood pressure can reduce the decline in kidney function by 30 to 70 percent. Treatment with particular medications for hypertension called angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) is more effective in reducing the decline in kidney function than is treatment with other blood pressure lowering drugs.
  • In addition to lowering blood pressure, ARBs and ACE inhibitors reduce proteinuria, a risk factor for developing kidney disease, by about 35 percent.




Having diabetes is not all bad. You know your enemy and you have the tools to win the battle. Pick up those tools and go to work. Your doctor and other health care providers are your best partners in this battle.

Dr. Calder





Thursday, December 1, 2011

More on aspirin - to take or not to take

The question of when and if we should take an aspirin a day has not been completely answered. The article below may help with your understanding of the problem. I suggest that you read the highlighted areas first and then read the whole article if you want more detail. Dr. Calder


From Therapeutic Advances in Chronic Disease
Recommending Aspirin for Primary Prevention in Diabetic Patients
What May We Conclude From the Data?
Antonio Nicolucci, MD
Authors and Disclosures
Posted: 05/10/2011; Ther Adv Chronic Dis. 2011;2(3):157-160. © 2011 Sage Publications, Inc.
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Abstract and Introduction
Introduction
Cardiovascular (CV) disease is the leading cause of morbidity and is responsible for premature mortality in patients with diabetes [King et al. 1998]. In addition to its association with multiple classical CV risk factors, diabetes is associated with accelerated atherosclerosis and inflammation that contribute to the pathogenesis and progression of vascular complications [Evangelista et al. 2005]. For this reason, antiplatelet therapy is considered an essential component of diabetes care to reduce ischemic risk [Angiolillo, 2009].
Aspirin has been on the market since 1899, and is still one of the most widely used medications for the treatment and prevention of CV disease. Despite such a long history of use, the role of aspirin for the primary prevention of CV events in individuals with diabetes is still a matter of debate. The new evidence made available in the last few years seems to have increased, rather than resolved, all the doubts regarding the risk–benefit profile of antiplatelet therapy. The uncertainty surrounding this topic is clearly demonstrated by the extreme heterogeneity in the recommendations issued by different scientific societies. As an example, until 2008, the American Diabetes Association recommended the use of aspirin for primary prevention of CV events in all individuals aged over 40 years or with additional risk factors [American Diabetes Association, 2008]. This recommendation was graded as A, that is, supported by evidence of the highest quality. In 2009, while maintaining the same recommendation, grading was changed to C (evidence from poorly controlled studies) [American Diabetes Association, 2009]. In 2010, the recommendation to use aspirin in the primary setting was changed to include individuals with a 10-year risk of CV events >10% (i.e. most men over 50 years of age and most women over 60 years with at least one additional risk factor). The recommendation was attributed a C grading [American Diabetes Association, 2010]. A completely different conclusion was reached by the Canadian Diabetes Association in its 2008 recommendations, where it was concluded that there is no clear evidence to support the prescription of aspirin to the vast majority of patients with diabetes, leaving aspirin use to individual clinical judgment [Bhattacharyya et al. 2008]. Guidelines issued by the Scottish Intercollegiate Guidelines Network (SIGN) in 2010 go even further, by considering the evidence on the lack of efficacy of aspirin strong enough not to recommend its use for primary prevention of CV events (A grading) [SIGN, 2010].
Then the question is: ‘what is the body of evidence leading to such divergent conclusions regarding the efficacy of aspirin in individuals with diabetes?’
In 2002, a meta-analysis (287 trials, 135,000 participants) on the efficacy of antiplatelet therapy in the prevention of major CVevents found a clear benefit of aspirin overall (22% risk reduction), but no statistically significant benefit in the subgroup of 5126 participants with diabetes (7% risk reduction) [Antithrombotic Trialists' Collaboration, 2002]. Consistent with the findings of the meta-analysis, a subgroup analysis of the Primary Prevention Project in 1031 diabetic patients showed that low-dose aspirin only marginally reduced the risk of major CV events after 3 years of follow up (relative risk [RR]=0.90; 95% confidence interval [CI] 0.50–1.62) [Sacco et al. 2003]. On the same line, results of the Women’s Health Study documented in 1027 women with diabetes that treatment with low-dose aspirin was associated with a nonsignificant 10% reduction in the risk of major CV events when compared with placebo (RR=0.90; 95% CI 0.63–1.29) [Ridker et al. 2005]. This overall effect was the net result of a reduction in the risk of stroke (RR=0.46; CI 0.25–0.85), associated with an increased risk of myocardial infarction (MI) (RR=1.48; CI 0.88–2.49).
Controversies about the role of aspirin have been refueled by the results of two recent trials. The Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes (JPAD) trial was specifically designed to address the issue of aspirin therapy for the primary prevention of CV events in diabetes [Ogawa et al. 2008]. The trial, including 2539 patients with type 2 diabetes, showed that after a median follow up of 4.37 years, aspirin therapy was associated with a nonsignificant 20% reduction (hazard rating [HR]=0.80; CI 0.58–1.10) in the risk of the primary composite endpoint, including fatal or nonfatal ischemic heart disease, fatal or nonfatal stroke, transient ischemic attack, and peripheral arterial disease. In a subgroup analysis restricted to individuals aged 65 years or older, a marginally significant reduction in the incidence of the primary endpoint was documented in patients treated with aspirin compared with controls (HR 0.68; CI 0.46–0.99). A major limitation of the study was represented by the inadequate statistical power, determined by a rate of events much lower than expected.
The Prevention of Progression of Arterial Disease and Diabetes (POPADAD) study involved 1276 patients with asymptomatic peripheral arterial disease, followed up for a median of 6.7 years [Belch et al. 2008]. The study found no evidence of benefit of aspirin on CV events and mortality, despite a baseline CV disease risk in the study population close to 3% a year. Nevertheless, the POPADAD trial was largely underpowered, due to an observed event rate less than half that hypothesized and the recruitment of 1276 patients instead of 1600 as planned. Further to this, only 50% of the patients were still taking aspirin after 5 years.
The persistence of a substantial uncertainty was further confirmed by the publication of two meta-analyses summarizing the results of trials testing aspirin in individuals with diabetes [Zhang et al. 2010; De Berardis et al. 2009]. Overall, aspirin use in primary prevention was associated with a 10% relative reduction in the risk of major CV events (CV death, nonfatal MI, nonfatal stroke). Such an effect was mainly attributable to a significant reduction in the risk of nonfatal MI in men, and to a reduction in nonfatal stroke in women. No clear effect on CV and overall mortality was documented. These findings were further confirmed by the recent Antithrombotic Trialists’ Collaboration (ATT) meta-analysis [Antithrombotic Trialists' Collaboration, 2009], based on individual patient data deriving from six large primary prevention trials. The meta-analysis showed that both in patients with and without diabetes aspirin decreased the risk of major CV events by about 10%.
Overall, these findings suggest that the benefits of aspirin in the primary prevention setting could be lower than expected on the basis of the results obtained in secondary prevention. It is therefore important to weigh the documented benefits against the risks of intracranial and gastrointestinal bleeding. It is estimated that low doses of aspirin cause one or two cases of major bleedings for 1000 individuals treated for one year [McQuaid and Laine, 2006]. Such a risk is probably higher in the real-world setting [Hernandez-Diaz and Garcia Rodriguez, 2006], and exponentially increases with age, being particularly elevated in the elderly. Further to this, the recent ATT meta-analysis suggests that diabetes per se may be associated with a 55% higher risk of gastrointestinal bleeding and a 70% higher risk of intracranial bleeding compared with individuals without diabetes [Antithrombotic Trialists' Collaboration, 2009]. Therefore, given the lack of specific safety data in individuals with diabetes, the assumption that major side effects of aspirin are rare should be taken with caution.


How should we use this information in clinical practice?

Taken together, existing evidence does not support strong recommendations to use aspirin in the primary prevention of CV events in all people with diabetes. From recent studies it can be estimated that the incidence of major CV events in people with diabetes and without prior CVevents is between 10 and 20 per 1000 person years. Assuming a RR reduction associated with aspirin treatment of about 10%, as suggested by the different meta-analyses, 1000 people need to be treated for one year to prevent one or two major CV events. Therefore, the expected benefits might not exceed the risk of major bleedings, particularly among people at low-intermediate CV risk (i.e.>15% over 10 years), or among older patients (>70 years) at high risk of bleeding. Although preventing one episode of MI or ischemic stroke can be considered far more important than provoking a transient episode of gastrointestinal bleeding, the lack of evidence of benefit of aspirin use on CV mortality might also suggest that antiplatelet therapy only prevents the less severe forms of MI or stroke.
Further to this, we completely lack information regarding the possible differential role of aspirin in individuals with type 1 and type 2 diabetes. Epidemiological data suggest a harmful effect of hyperglycemia on CV risk, not only for type 2, but also for type 1 diabetes [Turnbull et al. 2009; Juutilainen et al. 2008]. Nevertheless, given the profound differences in the pathophysiology of type 2 diabetes compared with type 1 diabetes, particularly as far as insulin resistance is concerned, the extrapolation of trials results, including mainly or exclusively individuals with type 2 diabetes, to type 1 diabetes is not warranted.


As for the dose of aspirin, evidence from the ATT collaboration meta-analysis suggests that the benefits obtained with low doses (75–162 mg/day) are similar to those obtained with higher doses (500–1500 mg/day) [Antithrombotic Trialists' Collaboration, 2002]. Although platelets from patients with diabetes have altered function, it is unclear if higher doses of aspirin are required in the patient with diabetes [Pignone et al. 2010]. In fact, many alternative pathways exist for platelet activation and aggregation that are independent of thromboxane A2 and thus not sensitive to the effects of aspirin [Evangelista et al. 2005]. Therefore, while platelet activation appears higher in patients with diabetes when measured by a variety of ex vivo and in vitro methods, these observations alone are insufficient to recommend empirically higher doses of aspirin [Pignone et al. 2010]. Furthermore, it remains to be established whether diabetes represents a specific case of ‘aspirin resistance’, related to accelerated platelet turnover making the 24-hour dosing interval inadequate to suppress completely platelet cyclo-oxygenase [Davi and Santilli, 2010].

The role of aspirin in the primary prevention of CV disease in people with diabetes will probably be clarified by ongoing trials. Two trials, A Study of Cardiovascular Events in Diabetes (ASCEND, International Standard Randomized Controlled Trial Number ISRCTN60635500) and the Aspirin and Simvastatin Combination for Cardiovascular Events Prevention Trial in Diabetes (ACCEPT-D) [De Berardis et al. 2007], will enroll more than 15,000 participants. In addition, the Japanese primary prevention project [Teramoto et al. 2010], involves 14,466 elderly patients, one third of which have diabetes. While awaiting new, firm data, it seems prudent to consider aspirin not indicated for individuals with a 10-year risk below 10%, while the decision to prescribe it in individuals with a moderate risk (i.e. 10–15%), must be taken on an individual patient basis, after a careful evaluation of the balance between the expected benefits and the significant risk of major bleeding. Finally, given the currently available limited evidence, it seems reasonable to suggest that patients at high intermediate risk (i.e. >15%) and higher, and without contraindications for aspirin, probably warrant treatment.
References