JamesLHollyMD.com | EPM Tools | Progression to Diabetes - Lipotoxicity

	James L. Holly, M.D.

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EPM Tools - Progression to Diabetes - Lipotoxicity

Diabetes is a global metabolic disorder that is also characterized by changes in fat and protein metabolism

Data in animal models suggest that lipid changes may contribute to the development of B-cell dysfunction.

Westernization and the accompanying increase in dietary fat intake may contribute to alterations in B-cell function.

Increase in dietary carbohydrate and decrease in dietary fat resulted in improved glucose tolerance as a result of an increase in insulin secretion and an improvement in insulin sensitivity in older subjects and individuals with type 2 diabetes.

As the development of obesity commonly results in increased intra-abdominal fat that appears to be metabolically active fat depot it is possible that factors emanating from fat may be the critical mediator.

Free fatty acids is one candidate.
Fluctuations of FFA are known to be critical to B-cell function.
Chronic increases of FFA may be deleterious to B-cell function

This seems to result not only in a decline in insulin release but also may have an effect to reduce the efficiency of proinsulin to insulin conversion within the B-cell.

Other candidate molecules from fat may play a role in B-cell function decrease:

Leptin
Cytokine TNF-alpha

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