PMID- 37951842
OWN - NLM
STAT- MEDLINE
DCOM- 20240318
LR  - 20240318
IS  - 1945-7197 (Electronic)
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 109
IP  - 4
DP  - 2024 Mar 15
TI  - Impact of Free Fatty Acids on Vascular Insulin Responses Across the Arterial 
      Tree: A Randomized Crossover Study.
PG  - 1041-1050
LID - 10.1210/clinem/dgad656 [doi]
AB  - CONTEXT: Vascular insulin resistance is commonly observed in obesity and 
      diabetes; yet, insulin action across the vascular tree and the relationship 
      between insulin responses at different vascular locations remains incompletely 
      defined. OBJECTIVE: To elucidate the impact of elevated free fatty acids (FFAs) 
      on insulin action across the arterial tree and define the relationship among 
      insulin actions in the different arterial segments. METHODS: This randomized 
      crossover study assigned healthy lean adults to 2 separate admissions with 
      euglycemic insulin clamp superimposed for the final 120 minutes of 5-hour lipid 
      or matched-volume saline infusion. Vascular measures including peripheral and 
      central arterial blood pressure, brachial artery flow-mediated dilation (FMD), 
      carotid femoral pulse wave velocity (cfPWV), augmentation index (AIx), pulse wave 
      separation analysis, subendocardial viability ratio (SEVR), and skeletal and 
      cardiac muscle microvascular perfusion were determined before and after insulin 
      clamp. Insulin-mediated whole body glucose disposal was calculated. RESULTS: 
      Insulin enhanced FMD, AIx, reflection magnitude, and cardiac and skeletal muscle 
      microvascular perfusion. Elevation of plasma FFA concentrations to the levels 
      seen in the postabsorptive state in people with insulin resistance suppressed 
      SEVR, blunted insulin-induced increases in FMD and cardiac and skeletal muscle 
      microvascular blood volume, and lowered insulin's ability to reduce AIx and 
      reflection magnitude. In multivariate regression, insulin-mediated muscle 
      microvascular perfusion was independently associated with insulin-mediated FMD 
      and cfPWV. CONCLUSION: Clinically relevant elevation of plasma FFA concentrations 
      induces pan-arterial insulin resistance, the vascular insulin resistance outcomes 
      are interconnected, and insulin-mediated muscle microvascular perfusion 
      associates with cardiovascular disease predictors. Our data provide biologic 
      plausibility whereby a causative relationship between FFAs and cardiovascular 
      disease could exist, and suggest that further attention to interventions that 
      block FFA-mediated vascular insulin resistance may be warranted.
CI  - (c) The Author(s) 2023. Published by Oxford University Press on behalf of the 
      Endocrine Society. All rights reserved. For permissions, please e-mail: 
      journals.permissions@oup.com.
FAU - Love, Kaitlin M
AU  - Love KM
AD  - Division of Endocrinology and Metabolism, Department of Medicine, University of 
      Virginia Health System, Charlottesville, VA 22908, USA.
FAU - Jahn, Linda A
AU  - Jahn LA
AD  - Division of Endocrinology and Metabolism, Department of Medicine, University of 
      Virginia Health System, Charlottesville, VA 22908, USA.
FAU - Hartline, Lee M
AU  - Hartline LM
AD  - Division of Endocrinology and Metabolism, Department of Medicine, University of 
      Virginia Health System, Charlottesville, VA 22908, USA.
FAU - Aylor, Kevin W
AU  - Aylor KW
AD  - Division of Endocrinology and Metabolism, Department of Medicine, University of 
      Virginia Health System, Charlottesville, VA 22908, USA.
FAU - Liu, Zhenqi
AU  - Liu Z
AUID- ORCID: 0000-0001-5077-0941
AD  - Division of Endocrinology and Metabolism, Department of Medicine, University of 
      Virginia Health System, Charlottesville, VA 22908, USA.
LA  - eng
GR  - K23 DK131327/DK/NIDDK NIH HHS/United States
GR  - R01DK102359/NH/NIH HHS/United States
PT  - Journal Article
PT  - Randomized Controlled Trial
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (Fatty Acids, Nonesterified)
RN  - 0 (Insulin)
SB  - IM
CIN - J Clin Endocrinol Metab. 2024 Jan 05;:. PMID: 38181432
MH  - Adult
MH  - Humans
MH  - *Insulin Resistance/physiology
MH  - Fatty Acids, Nonesterified
MH  - Cross-Over Studies
MH  - Pulse Wave Analysis
MH  - *Cardiovascular Diseases
MH  - Insulin
MH  - Muscle, Skeletal/physiology
MH  - *Hyperinsulinism
MH  - Brachial Artery
MH  - *Vascular Stiffness
PMC - PMC10940257
OTO - NOTNLM
OT  - arterial stiffness
OT  - endothelium
OT  - flow-mediated dilation
OT  - free fatty acids
OT  - insulin
OT  - microvasculature
EDAT- 2023/11/12 00:42
MHDA- 2024/03/18 06:43
PMCR- 2024/11/10
CRDT- 2023/11/11 22:13
PHST- 2023/08/21 00:00 [received]
PHST- 2024/11/10 00:00 [pmc-release]
PHST- 2024/03/18 06:43 [medline]
PHST- 2023/11/12 00:42 [pubmed]
PHST- 2023/11/11 22:13 [entrez]
AID - 7407978 [pii]
AID - dgad656 [pii]
AID - 10.1210/clinem/dgad656 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2024 Mar 15;109(4):1041-1050. doi: 
      10.1210/clinem/dgad656.