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Lack of association of apoE ε4 allele with insulin resistance

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Abstract

ApoE is a polymorphic protein involved in the metabolism of plasma lipoproteins; the ε4 allele was shown to be associated with coronary and aortic atherosclerosis in age-dependent fashion mediated by unknown mechanisms. This study was undertaken to assess whether the apoE isoforms in humans were associated with normal glucose tolerance and with metabolic and inflammatory risk factors of CVD. ApoE genotype was assessed in 365 individuals. Of those, 309 were studied in the postabsorptive conditions and 142 of them also underwent a 3h-OGTT; 56 additional subjects were studied by means of the insulin clamp in combination with [6,6-2H2] glucose infusion. ApoE genotype frequencies were similar to those previously reported and were not influenced by age and BMI. Fasting plasma glucose, insulin, FFA, the lipid profile, surrogate markers (HOMA-IR, OGTT-derived index) as well as the clamp-derived parameters or insulin sensitivity and insulin secretion were not different by apoE genotypes. Serum adipokines concentrations (leptin, adiponectin, resistin) and markers of inflammation (serum fasting hsCRP and MCP1/CCL2) were also not different by apoE genotypes. In the subgroup of young ε4 carriers which underwent the clamp procedure, a higher fasting endogenous glucose production was detected. ApoE genotype was not associated with insulin resistance or altered insulin secretion, and no abnormalities in the typical circulating endocrine, metabolic, and inflammatory features of the insulin resistance syndrome were detected.

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Abbreviations

FFA:

Free fatty acid

HOMA:

Homeostasis model assessment

OGTT:

Oral glucose tolerance test

hsCRP:

High-sensitive C-reactive protein

MCP1:

Monocyte chemotactic protein-1

DXA:

Dual-energy X-ray absorptiometry

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Acknowledgments

We wish to thank Antonella Scollo, R.N. of the Metabolic Unit of the Istituto Scientifico H San Raffaele for nursing assistance. This work was supported by grants from Italian Minister of Health (RF99.55, RF01.1831, RF030.5/199). We wish to thank the support of Laboratori Guidotti S. p. A. (grant #02027M3C-403/03).

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Authors and Affiliations

  1. Division of Metabolic and Cardiovascular Sciences, Istituto Scientifico H San Raffaele, via Olgettina 60, 20132, Milan, Italy

    Francesca Ragogna, Guido Lattuada, Giacomo Ruotolo, Livio Luzi & Gianluca Perseghin

  2. Department of Sport Sciences, Nutrition and Health, Università degli Studi di Milano, Milan, Italy

    Guido Lattuada, Livio Luzi & Gianluca Perseghin

  3. AstraZeneca R&D, Molndal, Sweden

    Giacomo Ruotolo

Authors
  1. Francesca Ragogna
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  2. Guido Lattuada
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  3. Giacomo Ruotolo
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  4. Livio Luzi
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  5. Gianluca Perseghin
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Correspondence to Gianluca Perseghin.

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Ragogna, F., Lattuada, G., Ruotolo, G. et al. Lack of association of apoE ε4 allele with insulin resistance. Acta Diabetol 49, 25–32 (2012). https://doi.org/10.1007/s00592-011-0255-3

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  • DOI: https://doi.org/10.1007/s00592-011-0255-3

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