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

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
Open this paper in CoChat — free account

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.

Integrity signals

Registry

Crossref · 10.1210/jc.2004-0224

Cites

52 of 52 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Reducing plasma free fatty acid concentration in insulin-resistant individuals, such as type 2 diabetic subjects, augments insulin-stimulated glucose disposal in skeletal muscle, and the improvement in insulin sensitivity is closely associated with a reduction in intramyocellular fatty acyl-CoA concentration.

    “Conversely, reduction of plasma FFA concentration in insulin resistant individuals, for example, type 2 diabetic subjects, augments insulin-stimulated glucose disposal in skeletal muscle [69–72], and the improvement in insulin sensitivity is closely associated with a reduction in intramyocellular FACoA concentration [69].”

    From Pathogenesis of insulin resistance in skeletal muscle (2010) · cites this paper as [70]

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

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 › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
  • Health Sciences › Medicine › Physiology › 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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review