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Glucotoxicity and Lipotoxicity: Reasons for Use of Insulin in Type 2 Patients

Oct 13, 2014

Typically when we diagnose a type 2 patient we start on the normal pathway of metformin and “diet and exercise” modifications. For many of our patients this regimen makes a significant improvement in their glucose levels and A1c values….

But for those patients who don’t improve, we are then forced to add more medications and this has been shown to improve A1c’s but often times the patient will find it difficult to adhere to the regimen and so long term values will begin to rise.

Glucotoxicity refers to the structural and functional damage in the beta cells and target tissues of insulin, caused by chronic hyperglycemia. These alterations cause a lower hormonal secretion and action (insulin resistance).

Lipotoxicity refers to the damage caused by persistently high free fatty acid levels, as a consequence of triacylglycerol catabolism.

This toxicity can be implicated in the pathogenesis of type 2 diabetes and in the secondary failure of oral hypoglycemic drugs.

Since many of our patients present with this apparent glucose toxicity, it is important to treat to target as quickly as possibly and this is where many clinicians are choosing short term use of insulin to reduce both the average glucose levels and reduce the associated glucose toxicity….

Del Prato et al at the Department of Endocrinology and Metabolism, Section of Metabolic Diseases and Diabetes, University of Pisa, Pisa, Italy found that short term use of insulin improved both glucose levels and insulin resistance.

We know that lipotoxicity also contributes to the loss of glucose control and to explain how that occurs we have a video from Dr. Philipp Scherer, Professor and Director of the Touchstone Diabetes Center at the University of Texas Southwestern Medical Center in Dallas, which you can find here.

The use of insulin for both glucotoxicity and lipotoxicity is often only temporary and if used aggressively enough will work to reverse some of the damage done by the high glucose level.