Euglycemic Hyperinsulinemia Alters the Response to Orthostatic Stress in Older Adults With Type 2 Diabetes

Abstract

Objective: Insulin has opposing influences on blood pressure by simultaneously increasing adrenergic activity and vasodilatating peripheral blood vessels. This study sought to determine if hyperinsulinemia affects tilt table responses in older adults with Type 2 diabetes not complicated by orthostatic hypotension.

Research design and methods: 22 older adults (mean age 71.7±1.1) with diet-controlled or oral hypoglycemic-controlled Type 2 diabetes were recruited. All subjects with orthostatic hypotension, diabetic nephropathy and sensory neuropathy were excluded. Subjects underwent euglycemic hyperinsulinemic clamp and placebo “sham clamp” sessions. Sequential euglycemic hyperinsulinemic clamps were performed for 2 hours at 40 mU/M²/min (Low Dose) and 2 hours at 80 mU/M²/min (High Dose) and each followed by a head-up tilt table test at 70 degrees for 10 minutes.

Results: There were no incidents of presyncope during the “sham clamp”, while there were 4 presycopal events during both the Low Dose and High Dose tilts. Although the Low Dose clamp showed no difference in the response between sessions (2-way ANOVA), subjects demonstrated a significantly larger decrease in MAP (p=0.005) and DBP (p=0.08) during the High Dose tilt. Doppler measures of Middle Cerebral Artery velocity were no different between the two sessions at either dose.

Conclusions: The vasodilatatory response to insulin can unmask orthostatic intolerance in older adults with Type 2 diabetes, resulting in presyncopal symptoms. This could contribute to orthostatic hypotension in combination with other factors such as hyperthermia, hypovolemia and adverse effects from medications.