DeFronzo Dethrones ADA Protocol for Type 2 Diabetes

An altered approach could protect beta cells.

Theresa Garnero By Theresa Garnero, APRN, BC-ADM, MSN, CDE

Imagine having over 500 research articles to your name and NIH funding every year for the past 36 years. Mind-boggling!

It's no small wonder that Dr. Ralph DeFranzo of the University of Texas, San Antonio, received the highest honor bestowed by the American Diabetes Association (ADA), the Banting Award (named after Frederick Grant Banting, the surgeon credited with discovering and isolating insulin, which won him the Nobel Prize in Medicine in 1923).

Dr. DeFronzo amazed an audience of more than 6,000 with the science behind his recommendations for dramatically changing current practice guidelines for type 2 diabetes during the Banting Lecture at the 68th Annual Scientific Sessions of the ADA in San Francisco, California. He nicely recapped the ‘triumvirate' triad of type 2 diabetes, with beta cell failure (pancreas isn't able to make enough insulin), increased liver production of glucose, and decreased glucose uptake from muscles. These three issues associated with type 2 diabetes are common knowledge in the diabetes community, and something he researched in the 1970s.

DeFronzo then revealed one system defect after another in type 2 diabetes. He led attendees to believe there were now four defects, then he showed more data and added the fifth, then more research and the sixth, then the seventh, all humorously named and finally ended with the eighth, the Ominous Octet. The eight is enough problems are:
1. Decreased insulin secretion
2. Increased liver production of glucose
3. Decreased muscle absorption of glucose
4. Increased free fatty acid circulation (interferes with insulin secretion and action)
5. Increased alpha cell secretion of glucagon (a hormone released from the pancreas that helps stabilize glucose)
6. Decreased gut hormones GLP-1 and GIP (known as the incretin effect that helps regulate glucose)
7. Increased ability of the kidneys to reabsorb glucose (normally, they filter 162 grams of glucose per day)
8. Decreased neurotransmitter function from the brain (affects appetite control)

What does this all mean? DeFronzo pointed out some key findings, most notably, that by the time someone gets diagnosed with type 2 diabetes, 80 percent of beta cell function is lost. In addition, up to 10 percent of people with impaired glucose tolerance (non-fasting glucose above 140) already have neuropathy and retinopathy (complications of the nerves and eyes). The good news? Muscle resistance counts for 80 percent of insulin resistance. If you are able bodied, exercise is the right medication for you! It will help your body use the insulin you are making much more efficiently.

His decades of research suggest we need to take an approach that is based on known pathogenic abnormalities, not just those that reduce A1C levels. Since only 20 percent of beta cell function is left at diagnosis, he laid the groundwork for hitting diabetes hard and fast with the three medications that are known to address the physiologic deficits: metformin (Glucophage), thiazolidinediones (Actos or Avandia), and the incretin mimetic GLP-1, exenetide (Byetta). That's in addition to lifestyle modification.

How this will play out in the real world of living with diabetes is yet to be determined. Many issues come to mind, from the individual who is shell shocked with the diagnosis who wouldn't want three drugs at once (one of which is an injection), to dealing with clinical inertia (some medical professionals practice the "wait and see" / not treat aggressively approach), to battling with insurance companies to cover the drugs (if you are lucky enough to be covered or can afford them).

He doesn't present himself as a rebel, even though his lecture was somewhat scandalous (who else could categorically refute ADA recommendations?). He's a passionate researcher and a personable genius. Dr. Fronzo received thunderous applause and a well-deserved standing ovation. This was a historic lecture that will have ripple effects for years to come.

The bottom line is to take action. Don't wait — protect your remaining beta cells. Exercise if you can. Talk with your healthcare team about what changes should be made.

Thank you, Dr. DeFronzo.

Read Theresa's bio here.

Read more of Theresa Garnero's columns.

NOTE: The information is not intended to be a replacement or substitute for consultation with a qualified medical professional or for professional medical advice related to diabetes or another medical condition. Please contact your physician or medical professional with any questions and concerns about your medical condition.

Last Modified Date: May 17, 2013

All content on is created and reviewed in compliance with our editorial policy.

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by Brenda Bell
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