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.


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 x m(-2) x min(-1) (low dose) and 2 h at 80 mU x m(-2) x min(-1) (high dose), and each was followed by a head-up tilt table test at 70 degrees 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.
Madden
Kenneth M
KM
Department of Medicine, Division of Geriatric Medicine, University of British Columbia, Vancouver, British Columbia, Canada. kmmadden@interchange.ubc.ca
Tedder
Gale
G
Lockhart
Chris
C
Meneilly
Graydon S
GS
D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D001794:Blood Pressure / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000503:physiopathology*; D005260:Female; D015309:Glucose Clamp Technique / Q000379:methods*; D006801:Humans; D006946:Hyperinsulinism / Q000503:physiopathology*; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects; D007024:Hypotension, Orthostatic / Q000139:chemically induced / Q000503:physiopathology*; D007328:Insulin / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D013312:Stress, Physiological; D018667:Tilt-Table Test
D007004:Hypoglycemic Agents; D007328:Insulin