Insulin resistance and lipid profiles in HIV-infected Thai children receiving lopinavir/ritonavir-based highly active antiretroviral therapy
Abstract
Background: Lopinavir/ritonavir (LPV/r) is associated with insulin resistance (IR). We aim to determine the prevalence of IR, dyslipidemia and their inter-relationships with adipokines in HIV-infected children treated with LPV/r-based highly active antiretroviral therapy (HAART).
Methods: Twenty-eight children were enrolled. Fasting glucose, insulin, lipid profiles, adipokines, and oral glucose tolerance tests were performed.
Results: The prevalence of IR, pre-diabetes mellitus, and hypertriglyceridemia was 42.9(12/28), 10.7(3/28), and 75.0(21/28)% respectively. No case met the definition for diabetes mellitus (DM) and lipodystrophy. Children with IR had higher BMI z-score, triglyceride levels but unchanged leptin or adiponectin levels compared to those without IR. Longer duration of LPV/r-based HAART was associated with increased levels of triglyceride and total cholesterol.
Conclusions: We describe high prevalence of IR, pre-diabetes mellitus, and dyslipidemia among HIV-infected children receiving LPV/r-based HAART. Pre-diabetes mellitus or DM or IR screening might be important for early diagnosis and intervention in these children.
Acknowledgments
This study was funded by the National Research University Program, Chiang Mai University.
Conflict of interest statement: None
References
1. Eyzaguirre F, Mericq V. Insulin resistance markers in children. Horm Res 2009;71:65–74.10.1159/000183894Search in Google Scholar PubMed
2. Feeney ER, Mallon PW. Insulin resistance in treated HIV infection. Best Pract Res Clin Endocrinol Metab 2011;25:443–58.10.1016/j.beem.2010.11.002Search in Google Scholar PubMed
3. Taylor SA, Lee GA, Pao VY, Anthonypillai J, Aweeka FT, et al. Boosting dose ritonavir does not alter peripheral insulin sensitivity in healthy HIV-seronegative volunteers. J Acquir Immune Defic Syndr 2010;55:361–4.10.1097/QAI.0b013e3181e6a7d9Search in Google Scholar PubMed PubMed Central
4. Lee GA, Lo JC, Aweeka F, Schwarz JM, Mulligan K, et al. Single-dose lopinavir-ritonavir acutely nhibits insulin-mediated glucose disposal in healthy volunteers. Clin Infect Dis. 2006;43:658–60.10.1086/505974Search in Google Scholar PubMed PubMed Central
5. Noor MA, Parker RA, O’Mara E, Grasela DM, Currie A, Hodder SL, et al. The effects of HIV protease inhibitors atazanavir and lopinavir/ritonavir on insulin sensitivity in HIV-seronegative healthy adults. AIDS 2004;18:2137–44.10.1097/00002030-200411050-00005Search in Google Scholar PubMed
6. Hruz PW. Molecular mechanisms for insulin resistance in treated HIV-infection. Best Pract Res Clin Endocrinol Metab 2011;25:459–68.10.1016/j.beem.2010.10.017Search in Google Scholar PubMed PubMed Central
7. Mulligan K, Grunfeld C, Tai VW, Algren H, Pang M, et al. Hyperlipidemia and insulin resistance are induced by protease inhibitors independent of changes in body composition in patients with HIV infection. J Acquir Immune Defic Syndr 2000;23:35–43.10.1097/00126334-200001010-00005Search in Google Scholar PubMed
8. Carr A, Samaras K, Burton S, Law M, Freund J, et al. A syndrome of peripheral lipodystrophy, hyperlipidaemia and insulin resistance in patients receiving HIV protease inhibitors. AIDS 1998;12:F51–8.10.1097/00002030-199807000-00003Search in Google Scholar PubMed
9. Stanley TL, Grinspoon SK. Body composition and metabolic changes in HIV-infected patients. J Infect Dis 2012;205 Suppl 3:S383–90.10.1093/infdis/jis205Search in Google Scholar PubMed PubMed Central
10. Dube MP, Cadden JJ. Lipid metabolism in treated HIV Infection. Best Pract Res Clin Endocrinol Metab 2011;25:429–42.10.1016/j.beem.2011.04.004Search in Google Scholar PubMed
11. Lee GA, Seneviratne T, Noor MA, Lo JC, Schwarz JM, et al. The metabolic effects of lopinavir/ritonavir in HIV-negative men. AIDS. 2004;18:641–9.10.1097/00002030-200403050-00008Search in Google Scholar
12. Calza L, Manfredi R, Farneti B, Chiodo F. Incidence of hyperlipidaemia in a cohort of 212 HIV-infected patients receiving a protease inhibitor-based antiretroviral therapy. Int J Antimicrob Agents 2003;22:54–9.10.1016/S0924-8579(03)00100-6Search in Google Scholar
13. Strehlau R, Coovadia A, Abrams EJ, Martens L, Arpadi S, et al. Lipid profiles in young HIV-infected children initiating and changing antiretroviral therapy. J Acquir Immune Defic Syndr 2012;60:369–76.10.1097/QAI.0b013e318243760bSearch in Google Scholar PubMed PubMed Central
14. Rhoads MP, Lanigan J, Smith CJ, Lyall EG. Effect of specific ART drugs on lipid changes and the need for lipid management in children with HIV. J Acquir Immune Defic Syndr 2011;57:404–12.10.1097/QAI.0b013e31821d33beSearch in Google Scholar PubMed
15. Molina JM, Andrade-Villanueva J, Echevarria J, Chetchotisakd P, Corral J, et al. Once-daily atazanavir/ritonavir compared with twice-daily lopinavir/ritonavir, each in combination with tenofovir and emtricitabine, for management of antiretroviral-naive HIV-1-infected patients: 96-week efficacy and safety results of the CASTLE study. J Acquir Immune Defic Syndr 2010;53:323–32.10.1097/QAI.0b013e3181c990bfSearch in Google Scholar PubMed
16. Kosalaraksa P, Bunupuradah T, Engchanil C, Boonrak P, Intasan J, et al. Double boosted protease inhibitors, saquinavir, and lopinavir/ritonavir, in nucleoside pretreated children at 48 weeks. Pediatr Infect Dis J 2008;27:623–8.10.1097/INF.0b013e31816b4539Search in Google Scholar PubMed
17. Ananworanich J, Kosalaraksa P, Hill A, Siangphoe U, Bergshoeff A, et al. Pharmacokinetics and 24-week efficacy/safety of dual boosted saquinavir/lopinavir/ritonavir in nucleoside-pretreated children. Pediatr Infect Dis J 2005;24:874–9.10.1097/01.inf.0000180578.38584.daSearch in Google Scholar PubMed
18. Vigano A, Zuccotti GV, Cerini C, Stucchi S, Puzzovio M, et al. Lipodystrophy, insulin resistance, and adiponectin concentration in HIV-infected children and adolescents. Curr HIV Res. 2011;9:321–6.10.2174/157016211797635946Search in Google Scholar PubMed
19. Resino S, Palladino C, Lorente R, Micheloud D, Bellon JM, et al. Association between lipodystrophy and leptin in human immunodeficiency virus-1-infected children receiving lopinavir/ritonavir-based therapy. Pediatr Infect Dis J. 2010;29:774–7.10.1097/INF.0b013e3181db741bSearch in Google Scholar PubMed
20. Centers for Disease Control and Prevention. 1994 Revised classification system for human immunodeficiency virus infection in children <13 years of age. Official authorized addenda: human immunodeficiency virus infection codes and official guidelines for coding and reporting ICD-9-CM. Morb Mortal Wkly Rep 1994;43:1–10.Search in Google Scholar
21. Aurpibul L, Puthanakit T, Lee B, Mangklabruks A, Sirisanthana T, et al. Lipodystrophy and metabolic changes in HIV-infected children on non-nucleoside reverse transcriptase inhibitor-based antiretroviral therapy. Antivir Ther 2007;12:1247–54.10.1177/135965350701200811Search in Google Scholar
22. Reaven GM, Chen YD, Hollenbeck CB, Sheu WH, Ostrega D, et al. Plasma insulin, C-peptide, and proinsulin concentrations in obese and nonobese individuals with varying degrees of glucose tolerance. J Clin Endocrinol Metab 1993;76:44–8.Search in Google Scholar
23. Valerio G, Licenziati MR, Iannuzzi A, Franzese A, Siani P, et al. Insulin resistance and impaired glucose tolerance in obese children and adolescents from Southern Italy. Nutr Metab Cardiovasc Dis 2006;16:279–84.10.1016/j.numecd.2005.12.007Search in Google Scholar PubMed
24. Yeckel CW, Taksali SE, Dziura J, Weiss R, Burgert TS, et al. The normal glucose tolerance continuum in obese youth: evidence for impairment in beta-cell function independent of insulin resistance. J Clin Endocrinol Metab 2005;90:747–54.10.1210/jc.2004-1258Search in Google Scholar PubMed
25. Inzucchi SE. Clinical practice. Diagnosis of diabetes. N Engl J Med 2012;367:542–50.10.1056/NEJMcp1103643Search in Google Scholar PubMed
26. Kwiterovich PO Jr. Recognition and management of dyslipidemia in children and adolescents. J Clin Endocrinol Metab 2008;93:4200–9.10.1210/jc.2008-1270Search in Google Scholar PubMed
27. Ten S, Maclaren N. Insulin resistance syndrome in children. J Clin Endocrinol Metab 2004;89:2526–39.10.1210/jc.2004-0276Search in Google Scholar PubMed
28. Levy-Marchal C, Arslanian S, Cutfield W, Sinaiko A, Druet C, et al. Insulin resistance in children: consensus, perspective, and future directions. J Clin Endocrinol Metab 2010;95: 5189–98.10.1210/jc.2010-1047Search in Google Scholar PubMed PubMed Central
29. Keskin M, Kurtoglu S, Kendirci M, Atabek ME, Yazici C. Homeostasis model assessment is more reliable than the fasting glucose/insulin ratio and quantitative insulin sensitivity check index for assessing insulin resistance among obese children and adolescents. Pediatrics 2005;115:e500–3.10.1542/peds.2004-1921Search in Google Scholar PubMed
30. Yeckel CW, Weiss R, Dziura J, Taksali SE, Dufour S, et al. Validation of insulin sensitivity indices from oral glucose tolerance test parameters in obese children and adolescents. J Clin Endocrinol Metab 2004;89:1096–101.10.1210/jc.2003-031503Search in Google Scholar PubMed
31. dos Reis LC, de Carvalho Rondo PH, de Sousa Marques HH, de Andrade SB. Dyslipidaemia and insulin resistance in vertically HIV-infected children and adolescents. Trans R Soc Trop Med Hyg 2011;105:197–203.10.1016/j.trstmh.2011.01.005Search in Google Scholar PubMed
32. Rosso R, Parodi A, d’Annunzio G, Ginocchio F, Nicolini L, et al. Evaluation of insulin resistance in a cohort of HIV-infected youth. Eur J Endocrinol 2007;157:655–9.10.1530/EJE-07-0414Search in Google Scholar PubMed
33. Geffner ME, Patel K, Miller TL, Hazra R, Silio M, et al. Factors associated with insulin resistance among children and adolescents perinatally infected with HIV-1 in the pediatric HIV/AIDS cohort study. Horm Res Paediatr 2011;76:386–91.10.1159/000332957Search in Google Scholar
34. Esmailzadeh N, Wongsabut J, Petwijit T, Kosalaraksa P, Suntarattiwong P, et al. Prevalence of insulin resistance and metabolic syndrome among HIV-infected children receiving lopinavir/ritonavir-based antiretroviral therapy [Abstract no. MOPDB0102]. In: 7TH IAS Conference on HIV Pathogenesis, Treatment and Prevention. Jun 30 to Jul 03, 2013. Kuala Lumpur, Malaysia.Search in Google Scholar
35. Bunupuradah T, van der Lugt J, Kosalaraksa P, Engchanil C, Boonrak P, et al. Safety and efficacy of a double-boosted protease inhibitor combination, saquinavir and lopinavir/ritonavir, in pretreated children at 96 weeks. Antivir Ther 2009;14:241–8.10.1177/135965350901400218Search in Google Scholar
36. Ramos JT, De Jose MI, Duenas J, Fortuny C, Gonzalez-Montero R, et al. Safety and antiviral response at 12 months of lopinavir/ritonavir therapy in human immunodeficiency virus-1-infected children experienced with three classes of antiretrovirals. Pediatr Infect Dis J 2005;24:867–73.10.1097/01.inf.0000180574.18804.90Search in Google Scholar
37. Eckel RH, Grundy SM, Zimmet PZ. The metabolic syndrome. Lancet. 2005;365:1415–28.10.1016/S0140-6736(05)66378-7Search in Google Scholar
38. Luo L, Zhang L, Tao M, Qiu Z, Xie J, et al. Adiponectin and leptin levels in Chinese patients with HIV-related lipodystrophy: A 30-month prospective study. AIDS Res Hum Retroviruses 2009;25:1265–72.10.1089/aid.2009.0072Search in Google Scholar PubMed
39. Dzwonek AB, Novelli V, Schwenk A. Serum leptin concentrations and fat redistribution in HIV-1-infected children on highly active antiretroviral therapy. HIV Med 2007;8:433–8.10.1111/j.1468-1293.2007.00490.xSearch in Google Scholar PubMed
©2014 by Walter de Gruyter Berlin/Boston
Articles in the same Issue
- Frontmatter
- Original articles
- Assessment of hearing in children with type 1 diabetes mellitus
- Insulin resistance and lipid profiles in HIV-infected Thai children receiving lopinavir/ritonavir-based highly active antiretroviral therapy
- Increased hunger and speed of eating in obese children and adolescents
- Glucagon and insulin cord blood levels in very preterm, late preterm and full-term infants
- Thyroid function in late preterm infants in relation to mode of delivery and respiratory support
- Prevalence of vitamin D deficiency and its related factors in children and adolescents living in North Khorasan, Iran
- Asymmetric dimethyl L-arginine, nitric oxide and cardiovascular disease in adolescent type 1 diabetics
- A combined nutritional-behavioral-physical activity intervention for the treatment of childhood obesity – a 7-year summary
- The effect of earlier puberty on cardiometabolic risk factors in Afro-Caribbean children
- Prevalence of risk of deficiency and inadequacy of 25-hydroxyvitamin D in US children: NHANES 2003–2006
- Serum uric acid: relationships with biomarkers in adolescents and changes over 1 year
- Psychological impact on parents of children with congenital adrenal hyperplasia: a study from Sri Lanka
- Investigation of adropin and leptin levels in pediatric obesity-related nonalcoholic fatty liver disease
- Diseases accompanying congenital hypothyroidism
- Molecular diagnosis of a Chinese pedigree with α-mannosidosis and identification of a novel missense mutation
- Are the characteristics of thyroid cancer different in young patients?
- Unsaturated fatty acids and insulin resistance in childhood obesity
- Effect of genetic subtypes and growth hormone treatment on bone mineral density in Prader-Willi syndrome
- KCNJ11 gene mutation analysis on nine Chinese patients with type 1B diabetes diagnosed before 3 years of age
- Prevalence and risk factors of metabolic syndrome in school adolescents of northeast China
- Patient reports
- A novel activating ABCC8 mutation underlying neonatal diabetes mellitus in an infant presenting with cerebral sinovenous thrombosis
- Endocrinological anomalies in a patient with 12q14 microdeletion syndrome. Completing phenotype of this exceptional short stature condition
- Acute mental status change as the presenting feature of adrenal insufficiency in a patient with autoimmune polyglandular syndrome type II and stroke
- Effect of ethosuximide on cortisol metabolism in the treatment of congenital adrenal hyperplasia
- Absence of WNT4 gene mutation in a patient with MURCS association
- Identification of a novel insulin receptor gene heterozygous mutation in a patient with type A insulin resistance syndrome
- Adrenal insufficiency in association with congenital nephrotic syndrome: a case report
- Diabetic lipemia presenting as eruptive xanthomas in a child with autoimmune polyglandular syndrome type IIIa
- A case report of nephrogenic diabetes insipidus with idiopathic Fanconi syndrome in a child who presented with vitamin D resistant rickets
- Letter to the Editor
- Hyperbilirubinemia in neonates of diabetic mothers: an indirect biomarker of organ damage?
Articles in the same Issue
- Frontmatter
- Original articles
- Assessment of hearing in children with type 1 diabetes mellitus
- Insulin resistance and lipid profiles in HIV-infected Thai children receiving lopinavir/ritonavir-based highly active antiretroviral therapy
- Increased hunger and speed of eating in obese children and adolescents
- Glucagon and insulin cord blood levels in very preterm, late preterm and full-term infants
- Thyroid function in late preterm infants in relation to mode of delivery and respiratory support
- Prevalence of vitamin D deficiency and its related factors in children and adolescents living in North Khorasan, Iran
- Asymmetric dimethyl L-arginine, nitric oxide and cardiovascular disease in adolescent type 1 diabetics
- A combined nutritional-behavioral-physical activity intervention for the treatment of childhood obesity – a 7-year summary
- The effect of earlier puberty on cardiometabolic risk factors in Afro-Caribbean children
- Prevalence of risk of deficiency and inadequacy of 25-hydroxyvitamin D in US children: NHANES 2003–2006
- Serum uric acid: relationships with biomarkers in adolescents and changes over 1 year
- Psychological impact on parents of children with congenital adrenal hyperplasia: a study from Sri Lanka
- Investigation of adropin and leptin levels in pediatric obesity-related nonalcoholic fatty liver disease
- Diseases accompanying congenital hypothyroidism
- Molecular diagnosis of a Chinese pedigree with α-mannosidosis and identification of a novel missense mutation
- Are the characteristics of thyroid cancer different in young patients?
- Unsaturated fatty acids and insulin resistance in childhood obesity
- Effect of genetic subtypes and growth hormone treatment on bone mineral density in Prader-Willi syndrome
- KCNJ11 gene mutation analysis on nine Chinese patients with type 1B diabetes diagnosed before 3 years of age
- Prevalence and risk factors of metabolic syndrome in school adolescents of northeast China
- Patient reports
- A novel activating ABCC8 mutation underlying neonatal diabetes mellitus in an infant presenting with cerebral sinovenous thrombosis
- Endocrinological anomalies in a patient with 12q14 microdeletion syndrome. Completing phenotype of this exceptional short stature condition
- Acute mental status change as the presenting feature of adrenal insufficiency in a patient with autoimmune polyglandular syndrome type II and stroke
- Effect of ethosuximide on cortisol metabolism in the treatment of congenital adrenal hyperplasia
- Absence of WNT4 gene mutation in a patient with MURCS association
- Identification of a novel insulin receptor gene heterozygous mutation in a patient with type A insulin resistance syndrome
- Adrenal insufficiency in association with congenital nephrotic syndrome: a case report
- Diabetic lipemia presenting as eruptive xanthomas in a child with autoimmune polyglandular syndrome type IIIa
- A case report of nephrogenic diabetes insipidus with idiopathic Fanconi syndrome in a child who presented with vitamin D resistant rickets
- Letter to the Editor
- Hyperbilirubinemia in neonates of diabetic mothers: an indirect biomarker of organ damage?