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Euglycemic hyperinsulinemia alters the response to orthostatic stress in older adults with type 2 diabetes.

Madden KM, Tedder G, Lockhart C, Meneilly GS - Diabetes Care (2008)

Bottom Line: 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.This could contribute to orthostatic hypotension in combination with other factors such as hyperthermia, hypovolemia, and adverse effects from medications.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Division of Geriatric Medicine, University of British Columbia, Vancouver, British Columbia, Canada. kmmadden@interchange.ubc.ca

ABSTRACT

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 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.

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Related in: MedlinePlus

Heart rate response to low- and high-dose tilts. Despite the drop in blood pressure seen during the high-dose tilt, there was no significant difference in the heart rate response (low-dose tilt P = 0.979; high-dose tilt P = 0.273) between the insulin and saline sessions (Fig. 3). •, low-dose insulin; ○, low-dose placebo; ▴, high-dose insulin; ▵, high-dose-placebo.
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f2: Heart rate response to low- and high-dose tilts. Despite the drop in blood pressure seen during the high-dose tilt, there was no significant difference in the heart rate response (low-dose tilt P = 0.979; high-dose tilt P = 0.273) between the insulin and saline sessions (Fig. 3). •, low-dose insulin; ○, low-dose placebo; ▴, high-dose insulin; ▵, high-dose-placebo.

Mentions: When these subjects were excluded from the analysis, there was no significant effect of insulin on the response of systolic (P = 0.992), mean (P = 0.962), or diastolic (P = 0.959) blood pressure compared with placebo (by two-way AVOVA with repeated measures) during the low-dose tilt (Table 1). During the high-dose tilt, subjects demonstrated a significantly larger drop in mean (P = 0.005) and diastolic (P = 0.008) blood pressure over time. As shown in Fig. 1, this drop in blood pressure became significant during the 8th and 9th min (t8 and t9). The difference between the two sessions with respect to systolic blood pressure approached, but did not reach, statistical significance (P = 0.014) for the high-dose tilt. Despite the increased orthostatic drop with insulin during the high-dose tilt, there was no significant difference in the heart rate response (P = 0.979, low-dose tile; P = 0.273, high-dose tilt) between the insulin and saline sessions (Fig. 2). As shown in Fig. 3, there was also no significant difference in total peripheral resistance during the euglycemic-hyperinsulinemic clamp compared with placebo (P = 0.047) during the high-dose tilt or low-dose tilt (P = 0.897).


Euglycemic hyperinsulinemia alters the response to orthostatic stress in older adults with type 2 diabetes.

Madden KM, Tedder G, Lockhart C, Meneilly GS - Diabetes Care (2008)

Heart rate response to low- and high-dose tilts. Despite the drop in blood pressure seen during the high-dose tilt, there was no significant difference in the heart rate response (low-dose tilt P = 0.979; high-dose tilt P = 0.273) between the insulin and saline sessions (Fig. 3). •, low-dose insulin; ○, low-dose placebo; ▴, high-dose insulin; ▵, high-dose-placebo.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2571046&req=5

f2: Heart rate response to low- and high-dose tilts. Despite the drop in blood pressure seen during the high-dose tilt, there was no significant difference in the heart rate response (low-dose tilt P = 0.979; high-dose tilt P = 0.273) between the insulin and saline sessions (Fig. 3). •, low-dose insulin; ○, low-dose placebo; ▴, high-dose insulin; ▵, high-dose-placebo.
Mentions: When these subjects were excluded from the analysis, there was no significant effect of insulin on the response of systolic (P = 0.992), mean (P = 0.962), or diastolic (P = 0.959) blood pressure compared with placebo (by two-way AVOVA with repeated measures) during the low-dose tilt (Table 1). During the high-dose tilt, subjects demonstrated a significantly larger drop in mean (P = 0.005) and diastolic (P = 0.008) blood pressure over time. As shown in Fig. 1, this drop in blood pressure became significant during the 8th and 9th min (t8 and t9). The difference between the two sessions with respect to systolic blood pressure approached, but did not reach, statistical significance (P = 0.014) for the high-dose tilt. Despite the increased orthostatic drop with insulin during the high-dose tilt, there was no significant difference in the heart rate response (P = 0.979, low-dose tile; P = 0.273, high-dose tilt) between the insulin and saline sessions (Fig. 2). As shown in Fig. 3, there was also no significant difference in total peripheral resistance during the euglycemic-hyperinsulinemic clamp compared with placebo (P = 0.047) during the high-dose tilt or low-dose tilt (P = 0.897).

Bottom Line: 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.This could contribute to orthostatic hypotension in combination with other factors such as hyperthermia, hypovolemia, and adverse effects from medications.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Division of Geriatric Medicine, University of British Columbia, Vancouver, British Columbia, Canada. kmmadden@interchange.ubc.ca

ABSTRACT

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 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.

Show MeSH
Related in: MedlinePlus