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 Presentation

"The Role of Increased Free Fatty Acids in the Metabolic Derangementís of Type 2 DM"

Dr. Meredith Hawkins (biography)
English - 2003-05-23 - 50 minutes
(30 slides)
(7 questions)

Summary :
The role of circulating free fatty acids (FFAs) in insulin resistance is many-fold, as it affects the major organs controlling glucose metabolism and homeostasis: increased levels of FFAs cause impaired insulin secretion from the pancreas, diminished glucose uptake in skeletal muscle and inappropriate levels of glucose output from the liver. Just how much does this increased hepatic glucose output affect hyperglycemia in type 2 DM? Here we show that a chronic increase in FFAs contributes substantially to this problem. We also make the connection between the increased FFA and PAI-1 levels seen in diabetics, and finally we see new evidence and examine the implications of the increased plasma levels of adiponectin observed in the course of TZD therapy.

Learning objectives :
The participant will review some new data from Dr M Hawkins and colleagues which provide insights into:

- the mechanism whereby increased FFAs affect hyperglycemia in type 2 DM
- the relationship between FFA and PAI-1 levels
- the importance of increased plasma adiponectin levels arising in TZD therapy


- Chronic increases in FFA availability contribute substantially to the loss of regulation of glucose production by hyperglycemia per se in DM2.

- Lowering plasma FFA levels in DM2 is potentially of therapeutic benefit in restoring normal effectiveness of glucose to regulate hepatic glucose fluxes.

- It has been demonstrated for the first time in humans that increased circulating FFA levels can contribute substantially to the inappropriately elevated plasma PAI-1 levels seen in type 2 diabetes mellitus and thus in turn to the prothrombic state.

- Given the time course and magnitude of effect, it is likely that increases in plasma levels of the fat-derived peptide adiponectin may contribute importantly to the beneficial effects of thiazolidinediones on insulin action in people with type 2 diabetes mellitus.

Bibliographic references :
Lam TK, Carpentier A, Lewis GF, van de Werve G, Fantus IG, Giacca A. 2003.Mechanisms of the free fatty acid-induced increase in hepatic glucose production. Am J Physiol Endocrinol Metab 284(5):E863-73.

   


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