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

OBJECTIVE—Insulin has opposing influences on blood pressure by simultaneously increasing adrenergic activity and vasodilatating peripheral blood vessels. In this study, we sought to determine whether hyperinsulinemia affects tilt table responses in older adults with type 2 diabetes not complicated by orthostatic hypotension. RESEARCH DESIGN AND METHODS—Twenty-two older adults (mean age 71.7 ± 1.1) with diet-controlled or oral hypoglycemic drug–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 h at 40 mU · m(−2) · min(−1) (low dose) and 2 h at 80 mU · m(−2) · min(−1) (high dose), and each was followed by a head-up tilt table test at 70°C for 10 min. RESULTS—There were no incidents of presyncope during the sham clamp, whereas there were four presyncopal events during both the low-dose and high-dose tilts. Although the low-dose clamp showed no difference in the response between sessions (two-way ANOVA), subjects demonstrated a significantly larger decrease in mean arterial pressure (P = 0.005) and diastolic blood pressure (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 vasodilatory 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.