Conversely, within non-diabetic populations, periods of IER (75 - 85 % ER on restricted days) do not typically affect fasting glucose
levels 37, 41, 45, 48 or HbA1c 41, 48; results of which can often be replicated by short term CER studies.62 - 65These findings are unsurprising given that frank hyperglycaemia within the T2DM diagnostic range is effectively a late - stage manifestation of IR, which along with compensatory increases insulin secretion, can precede the onset of T2DM by many years.66, 67 Findings from one large scale prospective cohort study, Whitehall II, reveal a sharp increase in the trajectory towards fasting hyperglycaemia which is only detectable three years prior to diagnosis with T2DM.67 Consequently, it can be argued that changes in
circulating insulin concentrations, fasting (hepatic) insulin sensitivity and glucose uptake / clearance are more sensitive markers of deteriorating glucose
control than fasting glycaemia in non - diabetics.68 - 70
Patients with advanced AD show higher plasma but lower CSF insulin concentrations than healthy
controls.40 Clearly, then, the lower concentration of insulin in the brain is not a result of reduced
circulating levels in the blood.
This strategy is effective in
controlling blood sugar
levels and preventing the appearance of the symptoms of diabetes, but the rise in
circulating insulin creates a challenge that the medical world is now calling the «Metabolic Syndrome» or «Syndrome X».