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Severe insulin resistance contrasting with mild anthropometric changes in the adipose tissue of HIV-infected children with lipohypertrophy

Abstract

BACKGROUND: The HIV-associated lipodystrophic syndrome (HIV-LDS) combines redistribution of fat mass with insulin resistance and hyperlipidemia. We have previously reported that HIV-LDS prevails in children in a comparable pattern as in adults. The metabolic activity itself of the lipodystrophic adipose tissue in HIV infection has been poorly studied.

AIM AND METHODS: To assess in situ the insulin sensitivity of the lipohypertrophic subcutaneous abdominal adipose tissue using the microdialysis technique in HIV-infected children. Insulin sensitivity, assessed by the inhibition of glycerol release, was measured in the abdominal subcutaneous adipose tissue during a standard oral glucose tolerance test (OGTT) in six HIV-infected children under multi-therapy with abdominal lipohypertrophy (supra-iliac skinfold thickness >97th percentile) (HIV/LH+), in six obese children (obese group) and in eight HIV-infected children without lipodystrophy (HIV/LH−).

RESULTS: Glucose tolerance was normal in all subjects. Mean insulin areas under the curve (IAUC) were significantly higher in the obese and HIV/LH+ groups than in HIV/LH− (8769±5429, 8161±4552 and 3618±2222 mU min l−1, respectively; P=0.04 for the three groups comparison by the Kruskal–Wallis test), reflecting insulin resistance in the two former groups independent of a significant difference in percentage fat mass (37.2±4.7, 22.8±10.9 and 20.7±7.1%, respectively; P= 0.006). The crude inhibition of glycerol release, expressed as the relative change in dialysate glycerol concentration between baseline and 120 min, was not statistically different between the three groups (14% in obese, −38±14% in HIV/LH+ and −51±17% in HIV/LH− groups; P=0.3). The inhibition of glycerol release with respect to the circulating insulin level (expressed by IAUC) was similar in HIV/LH+ and obese groups (−6±5×10−3 and −7±5×10−3 l mU−1 min−1, respectively, P=0.4 for two-groups comparison by the U-Mann–Whitney test) and four-fold less than in the HIV/LH− group (−24±25×10−3 l mU−1 min−1; P=0.02).

CONCLUSION: These data argue in favor of insulin resistance in the adipose tissue of lipohypertrophies associated with HIV infection.

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References

  1. Carr A, Samaras K, Burton S, Law M, Freund J, Chisholm DJ & Cooper DA . A syndrome of peripheral lipodystrophy, hyperlipidaemia and insulin resistance in patients receiving HIV protease inhibitors. AIDS 1998; 12: F51–58.

    Article  CAS  PubMed  Google Scholar 

  2. Hadigan C, Meigs JB, Corcoran C, Rietschel P, Piecuch S, Basgoz N, Davis B, Sax P, Stanley T, Wilson PW, D'Agostino RB & Grinspoon S . Metabolic abnormalities and cardiovascular disease risk factors in adults with human immunodeficiency virus infection and lipodystrophy. Clin Infect Dis 2001; 32: 130–139.

    Article  CAS  PubMed  Google Scholar 

  3. Mynarcik DC, McNurlan MA, Steigbigel RT, Fuhrer J & Gelato MC . Association of severe insulin resistance with both loss of limb fat and elevated serum tumor necrosis factor receptor levels in HIV lipodystrophy. J AIDS 2000; 25: 312–321.

    CAS  Google Scholar 

  4. Paparizos VA, Kyriakis KP, Botsis C, Papastamopoulos V, Hadjivassiliou M & Stavrianeas NG . Protease inhibitor therapy-associated lipodystrophy, hypertriglyceridaemia and diabetes mellitus. [Letter.] AIDS 2000; 14: 903–905.

    Article  CAS  PubMed  Google Scholar 

  5. Safrin S & Grunfeld C . Fat distribution and metabolic changes in patients with HIV infection. [Editorial.] AIDS 1999; 13: 2493–2505.

    Article  CAS  PubMed  Google Scholar 

  6. Thiebaut R, Daucourt V, Mercie P, Ekouevi DK, Malvy D, Morlat P, Dupon M, Neau D, Farbos S, Marimoutou C & Dabis F . Lipodystrophy, metabolic disorders, and human immunodeficiency virus infection: Aquitaine Cohort, France, 1999. Groupe d'Epidemiologie Clinique du Syndrome d'Immunodeficience Acquise en Aquitaine. Clin Infect Dis 2000; 31: 1482–1487.

    Article  CAS  PubMed  Google Scholar 

  7. Vigouroux C, Gharakhanian S, Sahli Y, Nguyen TH, Chevenne D, Capeau J & Rozenbaum W . Diabetes, insulin resistance and dyslipidaemia in lipodystrophic HIV-infected patients on highly active antiretroviral therapy (HAART). Diabet Metab 1999; 25: 225–232.

    CAS  Google Scholar 

  8. Martinez E, Mocroft A, Garcia-Viejo MA, Pérez-Cuevas JB, Blanco JL, Mallolas J, Bianchi L, Conget I, Blanch J, Phillips A & Gatell JM . Risk of lipodystrophy in HIV-1-infected patients treated with protease inhibitors: a prospective cohort study. Lancet 2001; 357: 592–598.

    Article  CAS  PubMed  Google Scholar 

  9. Goujard C, Boufassa F, Deveau C, Laskri D & Meyer L . Incidence of clinical lipodystrophy in HIV-infected patients treated during primary infection. AIDS 2001; 15: 282–284.

    Article  CAS  PubMed  Google Scholar 

  10. Jaquet D, Levine M, Ortega_Rodriguez E, Faye A, Polak M, Vilmer E & Levy-Marchal C . Clinical and metabolic presentation of the lipodystrophic syndrome in HIV-infected children. AIDS 2000; 14: 2123–2128.

    Article  CAS  PubMed  Google Scholar 

  11. Arner P, Bolinder J, Eliasson A, Lundin A & Ungerstedt U . Microdialysis of adipose tissue and blood for in vivo lipolysis studies. Am J Physiol 1988; 255: E737–742.

    Article  CAS  PubMed  Google Scholar 

  12. Lafontan M, Sengenes C, Galitzky J, Berlan M, De Glisezinski I, Crampes F, Stich V, Langin D, Barbe P & Riviere D . Recent developments on lipolysis regulation in humans and discovery of a new lipolytic pathway. Int J Obes Relat Metab Disord 2000; 24 (Suppl 4): S47–52.

    Article  CAS  PubMed  Google Scholar 

  13. Rolland-Cachera MF, Brambilla P, Manzoni P, Akrout M, Sironi S, Del Maschio A & Chiumello G . Body composition assessed on the basis of arm circumference and triceps skinfold thickness: a new index validated in children by magnetic resonance imaging. Am J Clin Nutr 1997; 65: 1709–1713.

    Article  CAS  PubMed  Google Scholar 

  14. Rolland-Cachera MF, Sempé M, Guilloud-Bataille M, Patois E, Péquignot-Guggenbuhl F & Fautrad V . Adiposity indices in children. Am J Clin Nutr 1982; 36: 178–184.

    Article  CAS  PubMed  Google Scholar 

  15. Rolland-Cachera MF, Cole TJ, Sempé M, Tichet J, Rossignol C & Charraud A . Body Mass Index variations: centiles from birth to 87 years. Eur J Clin Nutr 1991; 45: 13–21.

    CAS  PubMed  Google Scholar 

  16. Tanner JM & Whitehouse RH . Clinical longitudinal standards for height, weight, height velocity, weight velocity and stages of puberty. Arch Dis Child 1976; 51: 170–179.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Lafontan M & Arner P . Application of in situ microdialysis to measure metabolic and vascular responses in adipose tissue. Trends Pharma Sc 1996; 17: 309–313.

    Article  CAS  Google Scholar 

  18. Moran A, Jacobs DR, Steinberger J, Hong CP, Prineas R, Luepker R & Sinaiko AR . Insulin resistance during puberty: results from clamp studies in 357 children. Diabetes 1999; 48: 2039–2044.

    Article  CAS  PubMed  Google Scholar 

  19. Wentworth JM, Burris TP & Chatterjee VK . HIV protease inhibitors block human preadipocyte differentiation, but not via the PPARgamma/RXR heterodimer. J Endocrinol 2000; 164: R7–R10.

    Article  CAS  PubMed  Google Scholar 

  20. Zhang B, MacNaul K, Szalkowski D, Li Z, Berger J & Moller DE . Inhibition of adipocyte differentiation by HIV protease inhibitors. J Clin Endocrinol Metab 1999; 84: 4274–4277.

    Article  CAS  PubMed  Google Scholar 

  21. Murata H, Hruz PW & Mueckler M . The mechanism of insulin resistance caused by HIV protease inhibitor therapy. J Biol Chem 2000; 275: 20251–20254.

    Article  CAS  PubMed  Google Scholar 

  22. Rudich A, Vanounou S, Riesenberg K, Porat M, Tirosh A, Harman-Boehm I, Greenberg AS, Schlaeffer F & Bashan N . The HIV protease inhibitor nelfinavir induces insulin resistance and increases basal lipolysis in 3T3-L1 adipocytes. Diabetes 2001; 50: 1425–1431.

    Article  CAS  PubMed  Google Scholar 

  23. Murataa H & Hruza PMM . Indinavir inhibits the glucose transporter isoform Glut4 at physiologic concentrations. AIDS 2002; 16: 859–863.

    Article  Google Scholar 

  24. Walli R, Herfort O, Michl GM, Demant T, Jäger H, Dieterle C, Bogner JR, Landgraf R & Goebel FD . Treatment with protease inhibitors associated with peripheral insulin resistance and impaired oral glucose tolerance in HIV-1-infected patients. AIDS 1998; 12: F167–173.

    Article  CAS  PubMed  Google Scholar 

  25. Noora MA, Seneviratnea T, Aweekac FT, Loa JC, Schwarza JM, Mulligana K & Schambelana MCG . Indinavir acutely inhibits insulin-stimulated glucose disposal in humans: A randomized, placebo-controlled study. AIDS 2002; 16: F1–F8.

    Article  Google Scholar 

  26. Keen H, Jarrett RJ & McCartney P . The ten-year follow-up of the Bedford survey (1962–1972): glucose tolerance and diabetes. Diabetologia 1982; 22: 73–78.

    Article  CAS  PubMed  Google Scholar 

  27. Bjorntorp P & Sjostrom L . The composition and metabolism in vitro of adipose tissue fat cells of different sizes. Eur J Clin Invest 1972; 2: 78–84.

    Article  CAS  PubMed  Google Scholar 

  28. Jacobsson B & Smith U . Effect of cell size on lipolysis and antilipolytic action of insulin in human fat cells. J Lipid Res 1972; 13: 651–656.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The study was supported by a grant from the Agence Nationale de Recherches sur le SIDA (Paris, 2000). The authors are grateful to the skillful nursing assistance of the staff of the Clinical Investigation Centre at the Robert Debré Hospital, Paris.

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Correspondence to C Lévy-Marchal.

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Beregszàszi, M., Jaquet, D., Lévine, M. et al. Severe insulin resistance contrasting with mild anthropometric changes in the adipose tissue of HIV-infected children with lipohypertrophy. Int J Obes 27, 25–30 (2003). https://doi.org/10.1038/sj.ijo.0802176

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