Is exogenous insulin inevitable for diabetics?
Endogenous insulin production ceases with the loss of pancreatic islet β-cells, caused by autoimmune antibodies 1, 2, 3 and fatty acids 4, 5. Thus the presence of high-titre islet cell antibodies may foreshadow loss of residual β-cell function and subsequently reduced (endogenous) insulin production 6. Given that insulin, and its precursors, is the initial antigen 2, 7, metabolic circumstances resulting in hyperinsulinism may lead to overt diabetes via both antibody production and dislipidemia.
Reports that long-term insulin dependence does not eliminate endogenous insulin secretion completely 8, that β-cells may undergo significant cell proliferation 9, and that at least some antibodies have limited persistence 1, 3, suggests that preventing continued autoimmune antibody production may ultimately restore normal insulin activity.
An alternative to managing diabetes with exogenous insulin is to reduce the glycemic load appropriate to the residual insulin activity still available 10. In early stages of diabetes, it seems logical that removing the antigen trigger (excess insulin in the β-cells) may allow a natural decline in antibodies and thus extend the timeframe to overt diabetes or potentially even prevent β-cell loss. Could a similar pathway also reverse long-term insulin-dependent diabetes?