Does ageing increase vulnerability to hypoglycaemia and hyperglycaemia? A systematic review of physiological and cognitive responses.

Abstract

Clinical guidelines relax glycaemic targets for older adults with diabetes on the assumption that ageing increases vulnerability to hypoglycaemia, an evidence base not formally appraised. We assessed whether ageing alters physiological, cognitive and behavioural responses to experimentally induced hypoglycaemia and hyperglycaemia. We searched PubMed, Embase and Web of Science from inception to 15 February 2025, updated to 15 September 2026, for studies comparing an older with a younger adult group as designated by the study authors, and reporting awareness, counter-regulatory hormone, cognitive or glucose-handling outcomes. Risk of bias was assessed with ROBINS-E, certainty with GRADE, and findings synthesised narratively. Fourteen studies (1985-2009; nine hypoglycaemia, five hyperglycaemia) met criteria; eleven enrolled healthy adults without diabetes, none at low risk of bias. Four of five awareness studies found reduced symptom perception in older adults; three of six glucagon studies showed attenuation; catecholamine findings were mixed; three of four cognition studies found comparable impairment. Each hyperglycaemia study identified a different impaired mechanism, none replicated; certainty was very low throughout. Very-low-certainty evidence suggests reduced symptom perception in older adults, with heterogeneous findings for counter-regulation and hyperglycaemia. This evidence base is too limited to determine appropriate glycaemic targets. PROSPERO: CRD420250654327.