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Diabetes mellitus, hypertension and ageing: the ionic hypothesis of ageing and cardiovascular-metabolic diseases.

Ageing in industrialised societies is associated with an increasing prevalence of hypertension, atherosclerotic vascular diseases, reduced insulin sensitivity and non-insulin-dependent diabetes mellitus (NIDDM). It has been suggested that hyperinsulinaemia/insulin resistance and/or hyperglycaemia could play a role in determining and/or exacerbating the hypertension and vascular disease associated with diabetes mellitus and ageing. Insulin-resistant states, such as essential hypertension and NIDDM, as well as "normal" ageing, are characterised by similar intracellular ionic defects, i.e. accumulation of cytosolic free calcium and depletion of free magnesium. The importance of calcium and magnesium ions in regulating cell functions is well-known. A rise in cellular free calcium and a depletion in cellular magnesium may induce cellular insulin resistance and vasoconstriction. Ionic levels quantitatively predict the extent of elevated blood pressure, fasting blood glucose, HBA1c and hyperinsulinaemic response to oral glucose challenge. We suggest that ionic disturbance might be the missing link responsible for the frequent clinical coexistence of hypertension, atherosclerosis and metabolic disorders. Ageing cells may become more vulnerable to ion disturbances, leading to possible elevation of intracellular free calcium and concurrent magnesium depletion. The "ionic hypothesis" of ageing supposes that an alteration in the cellular mechanisms which maintain the homeostasis of cytosolic calcium concentrations may play a key role in the ageing process, and that a sustained accumulation of cellular calcium and/or the depletion of cellular magnesium may also provide the final common pathway for many ageing-associated diseases, including hypertension and NIDDM.