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Cited by 109Adipokines, Inflammation, and Metabolic DiseasesDiabetes, Cardiovascular Risks, and LipoproteinsAdipose Tissue and Metabolism

The DOI matches its Crossref record; 52 of the 52 references it cites were found in a registry or an index.

Sustained Reduction in Plasma Free Fatty Acid Concentration Improves Insulin Action without Altering Plasma Adipocytokine Levels in Subjects with Strong Family History of Type 2 Diabetes

Bajaj, Mandeep, Suraamornkul, Swangjit, Kashyap, Sangeeta, Cusi, Kenneth, Mandarino, Lawrence, DeFronzo, Ralph A.·2004·The Journal of Clinical Endocrinology & Metabolism
DOI 10.1210/jc.2004-0224
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Abstract

To investigate the effect of a sustained (7-d) decrease in plasma free fatty acid (FFA) concentration in individuals genetically predisposed to develop type 2 diabetes mellitus (T2DM), we studied the effect of acipimox, a potent inhibitor of lipolysis, on insulin action and adipocytokine concentrations in eight normal glucose-tolerant subjects (aged 40 +/- 4 yr, body mass index 26.5 +/- 0.8 kg/m(2)) with at least two first-degree relatives with T2DM. Subjects received an oral glucose tolerance test (OGTT) and 120 min euglycemic insulin clamp (80 mU/m(2).min) with 3-[(3)H] glucose to quantitate rates of insulin-mediated whole-body glucose disposal (Rd) and endogenous (primarily hepatic) glucose production (EGP) before and after acipimox, 250 mg every 6 h for 7 d. Acipimox significantly reduced fasting plasma FFA (515 +/- 64 to 285 +/- 58 microm, P < 0.05) and mean plasma FFA during the OGTT (263 +/- 32 to 151 +/- 25 microm, P < 0.05); insulin-mediated suppression of plasma FFA concentration during the insulin clamp also was enhanced (162 +/- 18 to 120 +/- 15 microm, P < 0.10). Following acipimox, fasting plasma glucose (5.1 +/- 0.1 vs. 5.2 +/- 0.1 mm) did not change, whereas mean plasma glucose during the OGTT decreased (7.6 +/- 0.5 to 6.9 +/- 0.5 mm, P < 0.01) without change in mean plasma insulin concentration (402 +/- 90 to 444 +/- 102 pmol/liter). After acipimox Rd increased from 5.6 +/- 0.5 to 6.8 +/- 0.5 mg/kg.min (P < 0.01) due to an increase in insulin-stimulated nonoxidative glucose disposal (2.5 +/- 0.4 to 3.5 +/- 0.4 mg/kg.min, P < 0.05). The increment in Rd correlated closely with the decrement in fasting plasma FFA concentration (r = -0.80, P < 0.02). Basal EGP did not change after acipimox (1.9 +/- 0.1 vs. 2.0 +/- 0.1 mg/kg.min), but insulin-mediated suppression of EGP improved (0.22 +/- 0.09 to 0.01 +/- 0.01 mg/kg.min, P < 0.05). EGP during the insulin clamp correlated positively with the fasting plasma FFA concentration (r = 0.49, P = 0.06) and the mean plasma FFA concentration during the insulin clamp (r = 0.52, P < 0.05). Plasma adiponectin (7.1 +/- 1.0 to 7.2 +/- 1.1 microg/ml), resistin (4.0 +/- 0.3 to 3.8 +/- 0.3 ng/ml), IL-6 (1.4 +/- 0.3 to 1.6 +/- 0.4 pg/ml), and TNFalpha (2.3 +/- 0.3 to 2.4 +/- 0.3 pg/ml) did not change after acipimox treatment. We concluded that sustained reduction in plasma FFA concentration in subjects with a strong family history of T2DM increases peripheral (muscle) and hepatic insulin sensitivity without increasing adiponectin levels or altering the secretion of other adipocytokines by the adipocyte. These results suggest that lipotoxicity already is well established in individuals who are genetically predisposed to develop T2DM and that drugs that cause a sustained reduction in the elevated plasma FFA concentration may represent an effective modality for the prevention of T2DM in high-risk, genetically predisposed, normal glucose-tolerant individuals despite the lack of an effect on adipocytokine concentrations.

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Metadata

Authors
Bajaj, M., Suraamornkul, S., Kashyap, S., Cusi, K., Mandarino, L., & DeFronzo, R. A.
Affiliations
The University of Texas at San Antonio Health Science Center (US)
ORCID
Venue
The Journal of Clinical Endocrinology & Metabolism
Publisher
The Endocrine Society
Published
2004-09
Volume
89
Issue
9
Pages
4649-4655
ISSN
  • 0021-972X (ISSN-L)
  • 1945-7197
DOI
10.1210/jc.2004-0224
OpenAlex
W2074390251
Cited by
109
References
52
Citations by year
2026: 1 · 2024: 1 · 2023: 3 · 2022: 1 · 2021: 4 · 2020: 2 · 2019: 3 · 2018: 6 · 2017: 5 · 2016: 2 · 2015: 5 · 2014: 4 · 2013: 10 · 2012: 11
FWCI
5.75
Type
journal article
Language
en
Open access
closed
Locations
  • The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK 24092, F32DK061189)
  • National Center for Research Resources (M01RR01346, M01RR001346)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
  • Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
Keywords
free fatty acids, acipimox, lipolysis inhibition, insulin action, insulin resistance, type 2 diabetes risk, genetic susceptibility, adipokines, adiponectin, leptin, adiponectin/leptin ratio, glucose disposal, hepatic glucose production, hyperinsulinemic-euglycemic clamp, oral glucose tolerance test, nonoxidative glucose disposal
MeSH terms
Adult, Diabetes Mellitus, Type 2, Fatty Acids, Nonesterified, Female, Glucose, Glucose Tolerance Test, Humans, Insulin, Male, Proteins, Pyrazines, Tumor Necrosis Factor-alpha, Interleukin-6, Intercellular Signaling Peptides and Proteins, Adiponectin

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