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Perspectives on Diabetes Care

This is the official blog of the Association of Diabetes Care & Education Specialists where we share recent research and professional opinions on diabetes care and education.


Explore Helpful Views on Diabetes Care & Education

If you're looking for professional opinions on diabetes care and education, you're in the right place. Perspectives on Diabetes Care is the official ADCES® diabetes care and education blog that shares helpful views on diabetes care and education. 

This is where you'll find practical tips on working with people affected by prediabetes, diabetes and related cardiometabolic conditions and the latest research and viewpoints on issues facing diabetes care and education specialists and the people they serve.



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Incretins and Pathogenic Abnormalities

Nov 6, 2012, 06:00 AM

In my last blog, I shared with you what I learned at a meeting on Metformin.  I was in shock and awe when I saw that 15 kind people commented on that entry.  I hope not to bore you, but I thought I would try once more to share what I learned at an early morning breakfast meeting presented by Dr. Ralph DeFronzo (a diabetes rock star). 

According to Dr. DeFronzo -
1.  Beta cell failure occurs much earlier in the natural history of type 2 diabetes and is more severe than previously appreciated.
2.  Individuals with impaired glucose tolerance are maximally or near maximally insulin resistant, have lost approximately 80 percent of their beta cell function (DeFronzo) and have lost significant beta cell mass (Butler)
3.  Our primary goal should be to prevent beta cell failure. Interventions should target pathogenic mechanisms known to promote beta cell failure and cause insulin resistance.
4.  Treatments of type 2 dm will require multiple drugs in combination to correct multiple pathophysiologic defects, should be based upon known pathogenic abnormalities and not simply on reduction of A1c and must be started early in the natural history of type 2 dm, if progressive beta cell failure is to be prevented.
(For more detailed information, review Dr. DeFronzo’s Banting lecture on the Ominous Octet).

Dr. DeFronzo addressed incretins and how they correct multiple abnormalities
1.  Glucagon-like Peptide 1 (GLP-1) and Glucose-dependent Insulinotrophic Polypeptide (GIP) account for approximately 90 percent of the incretin effect
2.  In response to equivalent hyperglycemic stimuli, oral glucose elicits a greater insulin response than IV glucose. Thus, the gut becomes more important.
When we eat, K-cells of the intestine secrete GIP and L-cells secrete GLP-1.
GLP-1 is responsible for delaying gastric emptying, increasing satiety , increasing insulin secretion by the beta cells, and shutting off glucagon production by the pancreas.
One good point is that these drugs do not cause hypoglycemia.
4.  There are also cardiovascular benefits of the GLP-1 analogues. These include:

  • improved plasma lipid levels 
  • reduction of blood pressure
  • decreased CRP and BNP
  • improvement in endothelial dysfunction
  • reduction in infarct size – this has been shown by Robert Chilton in the cath lab

5.  In the liver, GLP-1 analogues decreased fat accumulation and hepatic glucose production.

The incretin mimetic drugs are Exenatide, Liraglutide  and Bydureon. Another drug class associated with incretins are the DPP IVs  (read DPP 4s). I am sure there are more complex explanations, but this is how I understand them to work.  DPP IV breaks down the action of GIP and GLP-1 thus causing incretins to be biologically inactive.  As stated above, you do not want the GIP and GLP-1 to be inactive because they do lots of good things to assist in controlling diabetes.  So you would give a DPP IV Inhibitor to slow the degrading action of the DPP IV - thus, the GIP and GLP-1 can remain biologically active longer and do their thing to assist in controlling glucose and diabetes.

That is my drug lesson for today.  Hope you have a wonderful holiday season!

Association of Diabetes Care & Education Specialists

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