Improved Triglycerides and Insulin Sensitivity with 3 Months of Acipimox in Human Immunodeficiency Virus-infected Patients with Hypertriglyceridemia

Hadigan, Colleen; Liebau, James; Torriani, Martin; Andersen, Rebecca; Grinspoon, Steven

doi:10.1210/jc.2006-1174

Cited by 41 publications

(31 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…During stage 2 (high insulin dose), lipolysis was totally blocked by insulin, which is most likely the reason for no detectable effect of acipimox on glucose metabolism. The response of R a FFAs to acute acipimox during high-dose insulin is similar to the response of R a FFAs to chronic acipimox (12).…”

Section: Discussionmentioning

confidence: 63%

“…In other insulin-resistant states (e.g., obesity and type 2 diabetes), increased rates of lipolysis and plasma FFA concentration are related to the degree of insulin resistance (8 -10). Both acute and chronic suppression of lipolysis can improve insulin sensitivity in HIV lipodystrophy (11,12). However, the nature of improved insulin resistance (i.e., whether due to changes in hepatic or peripheral insulin sensitivity) has not been determined, and the molecular mechanism behind FFA-induced insulin resistance is still incompletely understood.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Inhibition of Lipolysis Stimulates Peripheral Glucose Uptake but Has No Effect on Endogenous Glucose Production in HIV Lipodystrophy

et al. 2007

View full text Add to dashboard Cite

HIV-infected patients with lipodystrophy (HIV lipodystrophy) are insulin resistant and have elevated plasma free fatty acid (FFA) concentrations. We aimed to explore the mechanisms underlying FFA-induced insulin resistance in patients with HIV lipodystrophy. Using a randomized, placebo-controlled, cross-over design, we studied the effects of an overnight acipimox-induced suppression of FFAs on glucose and FFA metabolism by using stable isotopelabeled tracer techniques during basal conditions and a two-stage euglycemic-hyperinsulinemic clamp (20 and 50 mU insulin/m 2 per min, respectively) in nine patients with nondiabetic HIV lipodystrophy. All patients received antiretroviral therapy. Biopsies from the vastus lateralis muscle were obtained during each stage of the clamp. Acipimox treatment reduced basal FFA rate of appearance by 68.9% (95% CI 52.6 -79.5) and decreased plasma FFA concentration by 51.6% (42.0 -58.9) (both, P < 0.0001). Endogenous glucose production was not influenced by acipimox. During the clamp, the increase in glucose uptake was significantly greater after acipimox treatment compared with placebo (acipimox: 26. 85 , decreased phosphorylation of glycogen synthase (GS) site 3a ؉ b, and increased GS activity (percent I-form) in skeletal muscle (P < 0.01). Acipimox decreased phosphorylation of GS (site 3a ؉ b) (P < 0.02) and increased GS activity (P < 0.01) in muscle. The present study provides direct evidence that suppression of lipolysis in patients with HIV lipodystrophy improves insulin-stimulated peripheral glucose uptake. The increased glucose uptake may in part be explained by increased dephosphorylation of GS (site 3a ؉ b), resulting in increased GS activity.

show abstract

Section: Discussionmentioning

confidence: 63%

mentioning

confidence: 99%

Inhibition of Lipolysis Stimulates Peripheral Glucose Uptake but Has No Effect on Endogenous Glucose Production in HIV Lipodystrophy

et al. 2007

View full text Add to dashboard Cite

show abstract

“…The increased levels of FFAs play an important role in the insulin resistance appearing in HALS, and lipolysis inhibition attained through pharmacological means has been reported to ameliorate insulin sensitivity in HALS patients. 105 Similarly to other events already mentioned, activation of lipolysis appears to be due to a complex combination of HIV-1 infection and HAART-mediated events. In fact, enhanced lipolysis has been reported in HIV 1-infected patients irrespective of HAART.…”

Section: The Paradox Of the Common Inflammation Status In Adipose Tismentioning

confidence: 77%

Lipodystrophy in HIV 1-infected patients: lessons for obesity research

2007

View full text Add to dashboard Cite

“…10,28 Studies in HIV-positive subjects demonstrated that inhibition of lipolysis by acipimox resulted in a signifi cant reduction in lipolysis and NEFA levels. 29 Furthermore, a recent study using a high-fat meal showed that increased postprandial NEFA levels were associated with insulin resistance (HOMA-IR) and lipoatrophy in HIV-positive subjects. 30 In our study, we observed a dynamic pattern in NEFA levels with a >50% rapid reduction in response to a physiologic meal following a 12-hour fasting period.…”

Section: Discussionmentioning

confidence: 99%

Relationship of Postprandial Nonesterified Fatty Acids, Adipokines, and Insulin Across Gender in Human Immunodeficiency Virus–Positive Patients Undergoing Highly Active Antiretroviral Therapy

Thomas-Geevarghese

Anuurad

et al. 2009

Metabolic Syndrome and Related Disorders

View full text Add to dashboard Cite

Background: Metabolic derangements are common in human immunodefi ciency virus (HIV)-positive subjects undergoing antiretroviral therapy, but little is known about postprandial conditions. Methods: We investigated the relationship between leptin, adiponectin, nonesterifi ed fatty acids (NEFA), and insulin in response to a day-long meal pattern and evaluated gender differences in HIV-positive men (n = 12) and women (n = 13) undergoing highly active antiretroviral therapy (HAART). Results: For both men and women, a signifi cant decrease in postprandial NEFA levels was observed following breakfast (0.53 vs. 0.22 mmol/L, P < 0.001, baseline and at 3 hours, respectively), whereas day-long postprandial leptin and adiponectin levels showed small nonsignifi cant oscillations. In contrast to NEFA and adiponectin, postprandial leptin levels were signifi cantly higher among women compared to men (P < 0.05). Postprandial NEFA levels correlated positively with fasting insulin levels (r 2 = 0.25, P = 0.016), and the postbreakfast decrease in NEFA levels correlated signifi cantly with the postbreakfast increase in insulin levels (r 2 = 0.17, P = 0.038). No signifi cant association between postprandial adipokines and insulin was observed. Conclusions: In HAART-treated, HIV-infected men and women, levels of NEFA, but not adipokines, showed signifi cant postprandial variation. Furthermore, food intake resulted in signifi cant NEFA suppression in proportion to the food-stimulated insulin increase.

show abstract

Improved Triglycerides and Insulin Sensitivity with 3 Months of Acipimox in Human Immunodeficiency Virus-infected Patients with Hypertriglyceridemia

Cited by 41 publications

References 43 publications

Inhibition of Lipolysis Stimulates Peripheral Glucose Uptake but Has No Effect on Endogenous Glucose Production in HIV Lipodystrophy

Inhibition of Lipolysis Stimulates Peripheral Glucose Uptake but Has No Effect on Endogenous Glucose Production in HIV Lipodystrophy

Lipodystrophy in HIV 1-infected patients: lessons for obesity research

Relationship of Postprandial Nonesterified Fatty Acids, Adipokines, and Insulin Across Gender in Human Immunodeficiency Virus–Positive Patients Undergoing Highly Active Antiretroviral Therapy

Contact Info

Product

Resources

About