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Mechanisms of altered hemodynamic and metabolic responses to insulin in patients with insulin-dependent diabetes mellitus and autonomic dysfunction.
J Clin Endocrinol Metab. 1998 Feb; 83(2):468-75.JC

Abstract

Patients with autonomic neuropathy are more susceptible to insulin-induced hypotension than normal subjects, but the mechanisms are unclear. We quantitated the hemodynamic and metabolic effects of two doses of i.v. insulin (1 and 5 mU/kg.min, 120 min each) and several aspects of autonomic function in 28 patients with insulin-dependent diabetes mellitus (IDDM) and in 7 matched normal subjects under standardized normoglycemic conditions. The autonomic function tests included those predominantly assessing the integrity of vagal heart rate control (the expiration inspiration ratio during deep breathing and high frequency power of heart rate variability) and tests measuring sympathetic nervous function (reflex vasoconstriction to cold and blood pressure responses to standing and handgrip). During hyperinsulinemia, heart rate increased less (2 +/- 1 vs. 6 +/- 2 beats/min; P < 0.04) and diastolic blood pressure fell more (-3.1 +/- 1.2 vs. 0.9 +/- 2.1; P = NS) in the patients with IDDM than in the normal subjects. Forearm vascular resistance decreased significantly in the patients with IDDM [by -7.1 +/- 1.4 mm Hg/(mL/dL.min); P < 0.001 for high vs. low dose insulin], but not in the normal subjects (-0.1 +/- 2.5 mm Hg/(mL/dL.min; P = NS). Reflex vasoconstriction to cold was inversely correlated with the decreases in diastolic (r = -0.51; P < 0.005) and systolic (r = -0.59; P < 0.001) blood pressure and forearm vascular resistance (r = -0.53; P < 0.005), but not with the change in heart rate. The expiration inspiration ratio was, however, directly correlated with the insulin-induced change in heart rate (r = 0.63; P < 0.001), but not with diastolic or systolic blood pressure or forearm vascular resistance. Whole body (48 +/- 2 vs. 67 +/- 5 mumol/kg.min; P < 0.005) and forearm (44 +/- 4 vs. 67 +/- 8 mumol/kg.min; P < 0.05) glucose uptake were significantly lower in the IDDM patients than in the normal subjects. The latter could be attributed to a defect in the forearm glucose arterio-venous difference (1.5 +/- 0.1 vs. 2.2 +/- 0.2 mmol/L, respectively; P < 0.01), but not in blood flow. We conclude that both impaired vagal heart rate control and sympathetic nervous dysfunction exaggerate the hemodynamic effects of insulin in patients with IDDM and could contribute to insulin-induced hypotension.

Authors+Show Affiliations

Department of Medicine, Helsinki University Central Hospital, Finland.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9467559

Citation

Mäkimattila, S, et al. "Mechanisms of Altered Hemodynamic and Metabolic Responses to Insulin in Patients With Insulin-dependent Diabetes Mellitus and Autonomic Dysfunction." The Journal of Clinical Endocrinology and Metabolism, vol. 83, no. 2, 1998, pp. 468-75.
Mäkimattila S, Mäntysaari M, Schlenzka A, et al. Mechanisms of altered hemodynamic and metabolic responses to insulin in patients with insulin-dependent diabetes mellitus and autonomic dysfunction. J Clin Endocrinol Metab. 1998;83(2):468-75.
Mäkimattila, S., Mäntysaari, M., Schlenzka, A., Summanen, P., & Yki-Järvinen, H. (1998). Mechanisms of altered hemodynamic and metabolic responses to insulin in patients with insulin-dependent diabetes mellitus and autonomic dysfunction. The Journal of Clinical Endocrinology and Metabolism, 83(2), 468-75.
Mäkimattila S, et al. Mechanisms of Altered Hemodynamic and Metabolic Responses to Insulin in Patients With Insulin-dependent Diabetes Mellitus and Autonomic Dysfunction. J Clin Endocrinol Metab. 1998;83(2):468-75. PubMed PMID: 9467559.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mechanisms of altered hemodynamic and metabolic responses to insulin in patients with insulin-dependent diabetes mellitus and autonomic dysfunction. AU - Mäkimattila,S, AU - Mäntysaari,M, AU - Schlenzka,A, AU - Summanen,P, AU - Yki-Järvinen,H, PY - 1998/2/19/pubmed PY - 1998/2/19/medline PY - 1998/2/19/entrez SP - 468 EP - 75 JF - The Journal of clinical endocrinology and metabolism JO - J Clin Endocrinol Metab VL - 83 IS - 2 N2 - Patients with autonomic neuropathy are more susceptible to insulin-induced hypotension than normal subjects, but the mechanisms are unclear. We quantitated the hemodynamic and metabolic effects of two doses of i.v. insulin (1 and 5 mU/kg.min, 120 min each) and several aspects of autonomic function in 28 patients with insulin-dependent diabetes mellitus (IDDM) and in 7 matched normal subjects under standardized normoglycemic conditions. The autonomic function tests included those predominantly assessing the integrity of vagal heart rate control (the expiration inspiration ratio during deep breathing and high frequency power of heart rate variability) and tests measuring sympathetic nervous function (reflex vasoconstriction to cold and blood pressure responses to standing and handgrip). During hyperinsulinemia, heart rate increased less (2 +/- 1 vs. 6 +/- 2 beats/min; P < 0.04) and diastolic blood pressure fell more (-3.1 +/- 1.2 vs. 0.9 +/- 2.1; P = NS) in the patients with IDDM than in the normal subjects. Forearm vascular resistance decreased significantly in the patients with IDDM [by -7.1 +/- 1.4 mm Hg/(mL/dL.min); P < 0.001 for high vs. low dose insulin], but not in the normal subjects (-0.1 +/- 2.5 mm Hg/(mL/dL.min; P = NS). Reflex vasoconstriction to cold was inversely correlated with the decreases in diastolic (r = -0.51; P < 0.005) and systolic (r = -0.59; P < 0.001) blood pressure and forearm vascular resistance (r = -0.53; P < 0.005), but not with the change in heart rate. The expiration inspiration ratio was, however, directly correlated with the insulin-induced change in heart rate (r = 0.63; P < 0.001), but not with diastolic or systolic blood pressure or forearm vascular resistance. Whole body (48 +/- 2 vs. 67 +/- 5 mumol/kg.min; P < 0.005) and forearm (44 +/- 4 vs. 67 +/- 8 mumol/kg.min; P < 0.05) glucose uptake were significantly lower in the IDDM patients than in the normal subjects. The latter could be attributed to a defect in the forearm glucose arterio-venous difference (1.5 +/- 0.1 vs. 2.2 +/- 0.2 mmol/L, respectively; P < 0.01), but not in blood flow. We conclude that both impaired vagal heart rate control and sympathetic nervous dysfunction exaggerate the hemodynamic effects of insulin in patients with IDDM and could contribute to insulin-induced hypotension. SN - 0021-972X UR - https://www.unboundmedicine.com/medline/citation/9467559/Mechanisms_of_altered_hemodynamic_and_metabolic_responses_to_insulin_in_patients_with_insulin_dependent_diabetes_mellitus_and_autonomic_dysfunction_ L2 - https://academic.oup.com/jcem/article-lookup/doi/10.1210/jcem.83.2.4541 DB - PRIME DP - Unbound Medicine ER -