Elevated concentrations of free fatty acids are associated with increased insulin response to standard glucose challenge in human immunodeficiency virus-infected subjects with fat redistribution

Gary Meininger, Colleen Hadigan, Michael Laposata, Joanne Brown, Jessica Rabe, Joseph Louca, Negar Aliabadi, Steven Grinspoon

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

Fat redistribution, defined by both increased abdominal visceral fat and/or decreased abdominal, extremity, and facial subcutaneous fat, is increasingly recognized among human immunodeficiency virus (HIV)-infected patients treated with combination antiretroviral therapy. Fat redistribution in this population is associated with insulin resistance and dyslipidemia and is often referred to as the HIV lipodystrophy syndrome (LIPO). Fatty acids are known to modulate insulin resistance in other disease states, but a comprehensive evaluation of fatty acids has not been undertaken among HIV-infected patients with fat redistribution. In this study, we investigated fatty acid concentrations in 64 HIV-infected individuals (45 men and 19 women) with evidence of fat redistribution (LIPO) in comparison to 30 HIV-infected individuals (20 men and 10 women) without evidence of fat redistribution (NONLIPO) and 32 HIV-negative healthy control subjects (C) (21 males and 11 females) of similar age and body mass index (BMI). Glucose, insulin, and free fatty acid (FFA) levels were measured in response to a 75-g oral glucose tolerance test (OGTT) in the LIPO, NONLIPO, and C subjects. In addition, fasting lipids were obtained, and body composition was determined by anthropometric measurements and dual-energy x-ray absorptiometry (DXA). Fasting FFA concentrations were significantly increased in the LIPO group as compared with NONLIPO and C subjects (0.74 ± 0.03 v 0.60 ± 0.04 [mean ± SEM] mmol/L, P = .002, LIPO v NONLIPO; 0.74 ± 0.03 v 0.59 ± 0.03 mmol/L, P = .001, LIPO v C). In contrast, fasting FFA concentrations were not increased in the NONLIPO group (0.60 ± 0.04 v 0.59 ± 0.03, P = .909, NONLIPO v C). Similarly, fasting triglycerides and 120-minute OGTT FFA were significantly increased in the LIPO group as compared with the NONLIPO and C group. FFA decreased in HIV-infected LIPO, NONLIPO, and C subjects in response to OGTT, but the 120-minute FFA concentrations remained significantly elevated in LIPO patients compared with NONLIPO and C subjects. In a multivariate regression model of LIPO patients, fasting FFA (P = .027) was a strong independent predictor of insulin area under the curve (AUC), controlling for age, BMI, gender, and body composition (r2 for model = .31). No differences were observed in FFA concentrations in the LIPO group in an analysis based on current protease inhibitor (PI) use. These data suggest that FFA concentrations are increased in HIV-infected patients with fat redistribution. Increased fasting concentrations of fatty acids are associated with abnormal insulin responses to standard glucose challenge in HIV-infected patients with fat redistribution. Further studies are necessary to determine the mechanism of increased fatty acid concentrations and the role played by increased FFA in mediating insulin resistance in this population.

Original languageEnglish (US)
Pages (from-to)260-266
Number of pages7
JournalMetabolism: Clinical and Experimental
Volume51
Issue number2
DOIs
StatePublished - 2002
Externally publishedYes

Fingerprint

Lipodystrophy
Nonesterified Fatty Acids
Fats
HIV
Insulin
Glucose
Fasting
Fatty Acids
Glucose Tolerance Test
Insulin Resistance
Body Composition
Body Mass Index
Intra-Abdominal Fat
Subcutaneous Fat
Dyslipidemias
Protease Inhibitors
Population
Area Under Curve
Healthy Volunteers
Triglycerides

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Elevated concentrations of free fatty acids are associated with increased insulin response to standard glucose challenge in human immunodeficiency virus-infected subjects with fat redistribution. / Meininger, Gary; Hadigan, Colleen; Laposata, Michael; Brown, Joanne; Rabe, Jessica; Louca, Joseph; Aliabadi, Negar; Grinspoon, Steven.

In: Metabolism: Clinical and Experimental, Vol. 51, No. 2, 2002, p. 260-266.

Research output: Contribution to journalArticle

@article{99856659fe11411db6e3b9828ff04ff5,
title = "Elevated concentrations of free fatty acids are associated with increased insulin response to standard glucose challenge in human immunodeficiency virus-infected subjects with fat redistribution",
abstract = "Fat redistribution, defined by both increased abdominal visceral fat and/or decreased abdominal, extremity, and facial subcutaneous fat, is increasingly recognized among human immunodeficiency virus (HIV)-infected patients treated with combination antiretroviral therapy. Fat redistribution in this population is associated with insulin resistance and dyslipidemia and is often referred to as the HIV lipodystrophy syndrome (LIPO). Fatty acids are known to modulate insulin resistance in other disease states, but a comprehensive evaluation of fatty acids has not been undertaken among HIV-infected patients with fat redistribution. In this study, we investigated fatty acid concentrations in 64 HIV-infected individuals (45 men and 19 women) with evidence of fat redistribution (LIPO) in comparison to 30 HIV-infected individuals (20 men and 10 women) without evidence of fat redistribution (NONLIPO) and 32 HIV-negative healthy control subjects (C) (21 males and 11 females) of similar age and body mass index (BMI). Glucose, insulin, and free fatty acid (FFA) levels were measured in response to a 75-g oral glucose tolerance test (OGTT) in the LIPO, NONLIPO, and C subjects. In addition, fasting lipids were obtained, and body composition was determined by anthropometric measurements and dual-energy x-ray absorptiometry (DXA). Fasting FFA concentrations were significantly increased in the LIPO group as compared with NONLIPO and C subjects (0.74 ± 0.03 v 0.60 ± 0.04 [mean ± SEM] mmol/L, P = .002, LIPO v NONLIPO; 0.74 ± 0.03 v 0.59 ± 0.03 mmol/L, P = .001, LIPO v C). In contrast, fasting FFA concentrations were not increased in the NONLIPO group (0.60 ± 0.04 v 0.59 ± 0.03, P = .909, NONLIPO v C). Similarly, fasting triglycerides and 120-minute OGTT FFA were significantly increased in the LIPO group as compared with the NONLIPO and C group. FFA decreased in HIV-infected LIPO, NONLIPO, and C subjects in response to OGTT, but the 120-minute FFA concentrations remained significantly elevated in LIPO patients compared with NONLIPO and C subjects. In a multivariate regression model of LIPO patients, fasting FFA (P = .027) was a strong independent predictor of insulin area under the curve (AUC), controlling for age, BMI, gender, and body composition (r2 for model = .31). No differences were observed in FFA concentrations in the LIPO group in an analysis based on current protease inhibitor (PI) use. These data suggest that FFA concentrations are increased in HIV-infected patients with fat redistribution. Increased fasting concentrations of fatty acids are associated with abnormal insulin responses to standard glucose challenge in HIV-infected patients with fat redistribution. Further studies are necessary to determine the mechanism of increased fatty acid concentrations and the role played by increased FFA in mediating insulin resistance in this population.",
author = "Gary Meininger and Colleen Hadigan and Michael Laposata and Joanne Brown and Jessica Rabe and Joseph Louca and Negar Aliabadi and Steven Grinspoon",
year = "2002",
doi = "10.1053/meta.2002.29999",
language = "English (US)",
volume = "51",
pages = "260--266",
journal = "Metabolism: Clinical and Experimental",
issn = "0026-0495",
publisher = "W.B. Saunders Ltd",
number = "2",

}

TY - JOUR

T1 - Elevated concentrations of free fatty acids are associated with increased insulin response to standard glucose challenge in human immunodeficiency virus-infected subjects with fat redistribution

AU - Meininger, Gary

AU - Hadigan, Colleen

AU - Laposata, Michael

AU - Brown, Joanne

AU - Rabe, Jessica

AU - Louca, Joseph

AU - Aliabadi, Negar

AU - Grinspoon, Steven

PY - 2002

Y1 - 2002

N2 - Fat redistribution, defined by both increased abdominal visceral fat and/or decreased abdominal, extremity, and facial subcutaneous fat, is increasingly recognized among human immunodeficiency virus (HIV)-infected patients treated with combination antiretroviral therapy. Fat redistribution in this population is associated with insulin resistance and dyslipidemia and is often referred to as the HIV lipodystrophy syndrome (LIPO). Fatty acids are known to modulate insulin resistance in other disease states, but a comprehensive evaluation of fatty acids has not been undertaken among HIV-infected patients with fat redistribution. In this study, we investigated fatty acid concentrations in 64 HIV-infected individuals (45 men and 19 women) with evidence of fat redistribution (LIPO) in comparison to 30 HIV-infected individuals (20 men and 10 women) without evidence of fat redistribution (NONLIPO) and 32 HIV-negative healthy control subjects (C) (21 males and 11 females) of similar age and body mass index (BMI). Glucose, insulin, and free fatty acid (FFA) levels were measured in response to a 75-g oral glucose tolerance test (OGTT) in the LIPO, NONLIPO, and C subjects. In addition, fasting lipids were obtained, and body composition was determined by anthropometric measurements and dual-energy x-ray absorptiometry (DXA). Fasting FFA concentrations were significantly increased in the LIPO group as compared with NONLIPO and C subjects (0.74 ± 0.03 v 0.60 ± 0.04 [mean ± SEM] mmol/L, P = .002, LIPO v NONLIPO; 0.74 ± 0.03 v 0.59 ± 0.03 mmol/L, P = .001, LIPO v C). In contrast, fasting FFA concentrations were not increased in the NONLIPO group (0.60 ± 0.04 v 0.59 ± 0.03, P = .909, NONLIPO v C). Similarly, fasting triglycerides and 120-minute OGTT FFA were significantly increased in the LIPO group as compared with the NONLIPO and C group. FFA decreased in HIV-infected LIPO, NONLIPO, and C subjects in response to OGTT, but the 120-minute FFA concentrations remained significantly elevated in LIPO patients compared with NONLIPO and C subjects. In a multivariate regression model of LIPO patients, fasting FFA (P = .027) was a strong independent predictor of insulin area under the curve (AUC), controlling for age, BMI, gender, and body composition (r2 for model = .31). No differences were observed in FFA concentrations in the LIPO group in an analysis based on current protease inhibitor (PI) use. These data suggest that FFA concentrations are increased in HIV-infected patients with fat redistribution. Increased fasting concentrations of fatty acids are associated with abnormal insulin responses to standard glucose challenge in HIV-infected patients with fat redistribution. Further studies are necessary to determine the mechanism of increased fatty acid concentrations and the role played by increased FFA in mediating insulin resistance in this population.

AB - Fat redistribution, defined by both increased abdominal visceral fat and/or decreased abdominal, extremity, and facial subcutaneous fat, is increasingly recognized among human immunodeficiency virus (HIV)-infected patients treated with combination antiretroviral therapy. Fat redistribution in this population is associated with insulin resistance and dyslipidemia and is often referred to as the HIV lipodystrophy syndrome (LIPO). Fatty acids are known to modulate insulin resistance in other disease states, but a comprehensive evaluation of fatty acids has not been undertaken among HIV-infected patients with fat redistribution. In this study, we investigated fatty acid concentrations in 64 HIV-infected individuals (45 men and 19 women) with evidence of fat redistribution (LIPO) in comparison to 30 HIV-infected individuals (20 men and 10 women) without evidence of fat redistribution (NONLIPO) and 32 HIV-negative healthy control subjects (C) (21 males and 11 females) of similar age and body mass index (BMI). Glucose, insulin, and free fatty acid (FFA) levels were measured in response to a 75-g oral glucose tolerance test (OGTT) in the LIPO, NONLIPO, and C subjects. In addition, fasting lipids were obtained, and body composition was determined by anthropometric measurements and dual-energy x-ray absorptiometry (DXA). Fasting FFA concentrations were significantly increased in the LIPO group as compared with NONLIPO and C subjects (0.74 ± 0.03 v 0.60 ± 0.04 [mean ± SEM] mmol/L, P = .002, LIPO v NONLIPO; 0.74 ± 0.03 v 0.59 ± 0.03 mmol/L, P = .001, LIPO v C). In contrast, fasting FFA concentrations were not increased in the NONLIPO group (0.60 ± 0.04 v 0.59 ± 0.03, P = .909, NONLIPO v C). Similarly, fasting triglycerides and 120-minute OGTT FFA were significantly increased in the LIPO group as compared with the NONLIPO and C group. FFA decreased in HIV-infected LIPO, NONLIPO, and C subjects in response to OGTT, but the 120-minute FFA concentrations remained significantly elevated in LIPO patients compared with NONLIPO and C subjects. In a multivariate regression model of LIPO patients, fasting FFA (P = .027) was a strong independent predictor of insulin area under the curve (AUC), controlling for age, BMI, gender, and body composition (r2 for model = .31). No differences were observed in FFA concentrations in the LIPO group in an analysis based on current protease inhibitor (PI) use. These data suggest that FFA concentrations are increased in HIV-infected patients with fat redistribution. Increased fasting concentrations of fatty acids are associated with abnormal insulin responses to standard glucose challenge in HIV-infected patients with fat redistribution. Further studies are necessary to determine the mechanism of increased fatty acid concentrations and the role played by increased FFA in mediating insulin resistance in this population.

UR - http://www.scopus.com/inward/record.url?scp=0036182863&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036182863&partnerID=8YFLogxK

U2 - 10.1053/meta.2002.29999

DO - 10.1053/meta.2002.29999

M3 - Article

VL - 51

SP - 260

EP - 266

JO - Metabolism: Clinical and Experimental

JF - Metabolism: Clinical and Experimental

SN - 0026-0495

IS - 2

ER -