Summary
It is postulated that hyperglycaemia influences the natural history of Type 1 (insulin-dependent) and Type 2 (non-insulin-dependent) diabetes mellitus. Hyperglycaemia, even when mild, can attenuate the secretory response of pancreatic β and α cells to increments in glucose and can impair insulin-mediated glucose transport, thus impeding its own correction and initiating a cycle of progressive self-exacerbation and metabolic deterioration. Both reduced islet function and insulin action may be the consequence of a generalized down-regulation and/or occupation of glucose transporters by hyperglycaemia so that the islets respond less to further increments in glycaemia. The postulated hyperglycaemic cycle can be initiated by any environmental perturbation that increases insulin demand in previously normoglycaemic patients in whom insulin secretion has already reached a maximum level of compensation for peripheral insulin resistance (as in obese pre-Type 2 diabetes) or for a reduced β-cell mass (as in pre-Type 1 diabetes). Elimination of hyperglycaemia by any means can halt this cycle of progressive metabolic deterioration and may restore transiently metabolic recompensation both in Type 1 and Type 2 diabetes. There is experimental evidence that long-standing severe hyperglycaemia may irreversibly damage β cells.
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Unger, R.H., Grundy, S. Hyperglycaemia as an inducer as well as a consequence of impaired islet cell function and insulin resistance: implications for the management of diabetes. Diabetologia 28, 119–121 (1985). https://doi.org/10.1007/BF00273856
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DOI: https://doi.org/10.1007/BF00273856