Wednesday, November 21, 2012

Does lowering A1c result in increased hypoglycemia risk


The take home message from the previous discussion a few days ago.
    Epinephrine produces the early warning symptoms of a dropping blood sugar. The loss of the
    epinephrine response to a falling glucose results in " hypoglycemia unawareness " and the 
    progression to the more severe stages of hypoglycemia.

Questions:
   #1-  Does lowering A1c result in increased risk of hypoglycemia in type 1 and type 2 diabetes ?

  Answer:
              Generally the answer is yes for patients with type 1 and type 2 diabetes but their are some
              interesting  caveats.

             The association of hypoglycemia with A1c  test below 7 occurs more often
             in people with type 1 diabetes .

             The association is a little different for people with type 2 diabetes and is , I believe 
              related the severity of their insulin deficiency. 

          Low risk
              Some people , with diet control ,  and those taking* Glucophage , *Byetta , *Victoza  or a
              *DPP4 inhibitor,  can achieve an A1c of 6 with minimal risk of hypoglycemia.

          Higher risk
              Hypoglycemia risk increases for patients taking *sulfonylureas .

              The risk increases depending on the  type of insulin needed to control their glucose levels .
              The addition of a basal insulin such as Lantus or levemir to oral medications
              ( metformin and/ or Byetta, Victroza , or  **DPP4 inhibitors ) does not add much  risk.
           
            Highest risk 
             The addition of  insulin to the treatment regimin of a peson taking a sulfonylurea.

                 The risk goes definitely increases when short acting insulin ( Humalog ,Novologi,Aphidra )
                  is needed to control meal time  glucose increases.

             
  The take home messages


         The difficulty of controlling  blood glucose levels increases with with the duration of type 2

         diabetes and the associated  increasing insulin deficiency. 
          

          An older person  with a longer duration of diabetes struggling  to control a high A1c is usually 
          at a greater risk of hypoglycemia than a younger person who easily achieves and A1c of less
          than 7 .
        
      Have fun, Be Smart  and remember A1c target goals depend on each individuals 
      circumstance
      David Calder, MD

Question #2 tomorrow.       
   #2 --Does age effect a persons awareness of hypoglycemia ?

   #3 --74% of unrecognized hypoglycemia occurs at night .       True or false

For your review .

****************What is GPL-1 ?   , DPP4 inhibitors , Sulfonylureas ****************

What is GPL-1 (Glucagon like peptide -1 )

Type 2 Diabetes is a complex game with many players.
Most of us are aware of  Beta cell dysfunction and failure causing insulin deficiency and we are familier with the term insulin resistance and its association with weight gain and obesity.
 We are less familier with the dysfunction of the pancreatic alpha cells and inappropriate Glucagon releasetriggering the liver to release glucose resulting in higher fasting and after meal glucose levels

GPL-I
The , newest member of  this group  , is a deficiency of a hormone made in our intestineGlucagon like Peptide -1 (GPL-1 ). 
This hormone is released in response to eating and has a powerful influence on our ability to manage  blood glucose levels.

Effects of GPL-1
 #1  Glucose - Dependent insulin secretion. This hormone allows insulin secreting Beta Cells to
        produce insulin in response to an increase in glucose levels.
  #2  Decreases glucagon levels resulting in lower fasting and after meal glucose levels
  #3   Appetite suppression and Slows  gastric emptying

Products Available to replace GLP-1 deficiency

GLP-1 agonist
 Exenatide ( Byetta )     a twice daily injection
 Liraglutide ( Victoza )  one injection per day
 Exenatide ( Bydureon ) weekly injection

Chart summary
                                        GLP1 agonist      DPP4 inhibitors    acarbose   Insulin    sulfonylureas

Effectively reduce A1c           YES                      YES                  YES       YES          YES

Preserve Beta cell function    YES                      ?                       NO        NO            NO

Promotes weight loss             YES                      No                     + -          NO            NO

Promotes weight gain              NO                      NO                     + -         YES           YES

Do not cause hypoglycemia   YES                     YES                   YES        NO            NO

Once a week injection             YES                     NO                     NO          NO           NO

Glucagon suppression            YES                     YES                   NO         NO           NO

Most expensive                         YES                        +-                     NO          + -            NO



1 comment:

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Your comments and questions are appreciated. David Calder,MD