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Gender-related differences in counterregulatory responses to antecedent hypoglycemia in normal humans.
J Clin Endocrinol Metab. 2000 Jun; 85(6):2148-57.JC

Abstract

Compared to men, inherent counterregulatory responses are reduced in healthy and type 1 diabetic women. Despite this, the prevalence of hypoglycemia in patients with type 1 diabetes (type 1 DM) is gender neutral. The aim of this study was to determine the in vivo mechanism(s) responsible for this apparent clinical paradox. The central importance of antecedent hypoglycemia in causing subsequent counterregulatory failure is now established. We, therefore, hypothesized that a gender-related difference to the blunting effects of prior hypoglycemia may exist, and this could explain why type 1 DM women do not have an increased prevalence of hypoglycemia despite reduced counterregulatory responses. Fifteen healthy male and female individuals (eight men and seven women) underwent four separate 2-day experimental protocols in a randomized fashion. Day 1 involved identical morning and afternoon 2-h hyperinsulinemic (9 pmol/kg x min) glucose clamp studies with 5.1 +/- 0.1, 3.9 +/- 0.1, 3.3 +/- 0.1, or 2.9 +/- 0.1 mmol/L. Day 2 consisted of a single 2-h hypoglycemic clamp of 2.9 +/- 0.1 mmol/L. Insulin levels were similar on both days of each protocol in men and women. After day 1 euglycemia (5.1 +/- 0.1 mmol/L), day 2 counterregulatory responses were significantly increased (P < 0.01) in men relative to women. In women, counterregulatory responses were resistant to the effects of day 1 hypoglycemia. Antecedent hypoglycemia of 3.9, 3.3, and 2.9 +/- 0.1 mmol/L produced 3 +/- 2%, 5 +/- 2%, and 25 +/- 4% aggregate reductions in day 2 neuroendocrine, muscle sympathetic nerve activity, and metabolic counterregulatory responses. In marked contrast, identical day 1 hypoglycemia of 3.9, 3.3, and 2.9 +/- 0.1 mmol/L in men produced significantly greater reductions in day 2 counterregulatory responses of 30 +/- 6%, 39 +/- 6%, and 52 +/- 6%, respectively. The net effect of the differential gender effects of antecedent hypoglycemia was to overcome the usually increased (50%) sympathetic nervous system (SNS) counterregulatory responses to hypoglycemia found in men. We conclude that 1) antecedent hypoglycemia produces less blunting of counterregulatory responses to subsequent hypoglycemia in women relative to men; 2) two episodes of antecedent hypoglycemia can overcome the greater SNS response to hypoglycemia usually found in men; and 3) the reduced susceptibility of women to the blunting effects of antecedent hypoglycemia may be the mechanism explaining why, despite inherently reduced SNS counterregulatory responses, female type 1 DM patients have a similar prevalence of hypoglycemia compared to men.

Authors+Show Affiliations

Davis SN
Department of Medicine, Vanderbilt University School of Medicine and Veterans Affairs Medical Center, Nashville, Tennessee 37232-6303, USA.
Shavers C
No affiliation info available
Costa F
No affiliation info available

MeSH

Activity CyclesAdultBlood GlucoseDiabetes Mellitus, Type 1EpinephrineFemaleGlucagonGlucose Clamp TechniqueHormonesHuman Growth HormoneHumansHydrocortisoneHyperinsulinismHypoglycemiaInfusions, IntravenousInsulinMaleMuscle, SkeletalNorepinephrinePancreatic PolypeptidePeroneal NerveReference ValuesSex CharacteristicsSympathetic Nervous System

Pub Type(s)

Clinical Trial
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

10852444

Citation

Davis, S N., et al. "Gender-related Differences in Counterregulatory Responses to Antecedent Hypoglycemia in Normal Humans." The Journal of Clinical Endocrinology and Metabolism, vol. 85, no. 6, 2000, pp. 2148-57.
Davis SN, Shavers C, Costa F. Gender-related differences in counterregulatory responses to antecedent hypoglycemia in normal humans. J Clin Endocrinol Metab. 2000;85(6):2148-57.
Davis, S. N., Shavers, C., & Costa, F. (2000). Gender-related differences in counterregulatory responses to antecedent hypoglycemia in normal humans. The Journal of Clinical Endocrinology and Metabolism, 85(6), 2148-57.
Davis SN, Shavers C, Costa F. Gender-related Differences in Counterregulatory Responses to Antecedent Hypoglycemia in Normal Humans. J Clin Endocrinol Metab. 2000;85(6):2148-57. PubMed PMID: 10852444.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Gender-related differences in counterregulatory responses to antecedent hypoglycemia in normal humans. AU - Davis,S N, AU - Shavers,C, AU - Costa,F, PY - 2000/6/14/pubmed PY - 2000/7/6/medline PY - 2000/6/14/entrez SP - 2148 EP - 57 JF - The Journal of clinical endocrinology and metabolism JO - J Clin Endocrinol Metab VL - 85 IS - 6 N2 - Compared to men, inherent counterregulatory responses are reduced in healthy and type 1 diabetic women. Despite this, the prevalence of hypoglycemia in patients with type 1 diabetes (type 1 DM) is gender neutral. The aim of this study was to determine the in vivo mechanism(s) responsible for this apparent clinical paradox. The central importance of antecedent hypoglycemia in causing subsequent counterregulatory failure is now established. We, therefore, hypothesized that a gender-related difference to the blunting effects of prior hypoglycemia may exist, and this could explain why type 1 DM women do not have an increased prevalence of hypoglycemia despite reduced counterregulatory responses. Fifteen healthy male and female individuals (eight men and seven women) underwent four separate 2-day experimental protocols in a randomized fashion. Day 1 involved identical morning and afternoon 2-h hyperinsulinemic (9 pmol/kg x min) glucose clamp studies with 5.1 +/- 0.1, 3.9 +/- 0.1, 3.3 +/- 0.1, or 2.9 +/- 0.1 mmol/L. Day 2 consisted of a single 2-h hypoglycemic clamp of 2.9 +/- 0.1 mmol/L. Insulin levels were similar on both days of each protocol in men and women. After day 1 euglycemia (5.1 +/- 0.1 mmol/L), day 2 counterregulatory responses were significantly increased (P < 0.01) in men relative to women. In women, counterregulatory responses were resistant to the effects of day 1 hypoglycemia. Antecedent hypoglycemia of 3.9, 3.3, and 2.9 +/- 0.1 mmol/L produced 3 +/- 2%, 5 +/- 2%, and 25 +/- 4% aggregate reductions in day 2 neuroendocrine, muscle sympathetic nerve activity, and metabolic counterregulatory responses. In marked contrast, identical day 1 hypoglycemia of 3.9, 3.3, and 2.9 +/- 0.1 mmol/L in men produced significantly greater reductions in day 2 counterregulatory responses of 30 +/- 6%, 39 +/- 6%, and 52 +/- 6%, respectively. The net effect of the differential gender effects of antecedent hypoglycemia was to overcome the usually increased (50%) sympathetic nervous system (SNS) counterregulatory responses to hypoglycemia found in men. We conclude that 1) antecedent hypoglycemia produces less blunting of counterregulatory responses to subsequent hypoglycemia in women relative to men; 2) two episodes of antecedent hypoglycemia can overcome the greater SNS response to hypoglycemia usually found in men; and 3) the reduced susceptibility of women to the blunting effects of antecedent hypoglycemia may be the mechanism explaining why, despite inherently reduced SNS counterregulatory responses, female type 1 DM patients have a similar prevalence of hypoglycemia compared to men. SN - 0021-972X UR - https://www.unboundmedicine.com/medline/citation/10852444/Gender_related_differences_in_counterregulatory_responses_to_antecedent_hypoglycemia_in_normal_humans_ DB - PRIME DP - Unbound Medicine ER -