| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
From the Clinical Research Centers |
Neuroendocrine Unit (K.M., C.C., S.G.), Combined Program in Pediatric Gastroenterology and Nutrition (C.H.), General Clinical Research Center (E.A.) and Infectious Disease Unit (N.B.), Massachusetts General Hospital, Children’s Hospital and Harvard Medical School, Boston, Massachusetts 02114
Address all correspondence and requests for reprints to: Steven Grinspoon, M.D., Neuroendocrine Unit, Bulfinch 457B, Massachusetts General Hospital, Boston, Massachusetts 02114. E-mail: sgrinspoon{at}partners.org
 |
Abstract |
|---|
 Top Abstract IntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
|
Introduction |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
Although abnormal fat redistribution and other changes in body composition (including breast enlargement) have been reported in HIV-infected women (6), a comprehensive investigation of regional body composition, insulin, and lipid parameters has not been performed in this expanding population of HIV-infected patients. In this report, we analyze regional body composition, insulin, and lipid levels from a cohort of HIV-infected women. Our data demonstrate significant fasting hyperinsulinemia and increased insulin-to-glucose ratio, which are present even at very low body weight and are unrelated to PI usage. These data suggest underlying metabolic abnormalities in HIV-infected women, which may be further exacerbated by weight gain and increased adiposity resulting from successful antiviral treatment. These data highlight the need for further studies to determine the mechanism and the long-term consequences of hyperinsulinemia among HIV-infected women.
|
Subjects and Methods |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
Seventy-five women (mean age, 36 ± 1 yr; range, 25–46 yr) with documented HIV infection were evaluated between 1994–1997 for AIDS-related wasting. Both wasted [n = 59; i.e. individuals who were less than 90% of ideal body weight (IBW) or who had lost more than 10% of their pre-illness body weight] and nonwasted (n = 16) women were evaluated. Subjects with a history of diabetes mellitus, acute opportunistic infection within the past 4 weeks, severe diarrhea (>6 stools/day), hemoglobin less than 8 g/dL, creatinine greater than 3.0 mg/dL, or active substance abuse were excluded from the evaluation. Subjects were recruited from the multidisciplinary HIV practice at the Massachusetts General Hospital and from advertisements, and they were studied in the early follicular phase. Twenty-four percent of HIV-infected women were amenorrheic, based on the absence of menstrual periods for the 3 months before evaluation. An additional group of 30 healthy, eumenorrheic, weight-matched, premenopausal women (mean age, 24 ± 1 yr; range, 18–32 yr) served as controls and underwent similar metabolic assessment in the early follicular phase. Written informed consent was obtained from each subject, and the study was approved by the subcommittee on human studies of the Massachusetts General Hospital.
Hormonal and body composition data, in response to transdermal testosterone administration, were previously reported in a subset of the patients (7). In addition, cross-sectional data on whole-body composition (8) and energy expenditure (9) were reported in a second subset of patients. In this study, previously unpublished data on regional body composition, insulin, and lipid levels are reported. All data presented are cross-sectional, obtained before any therapeutic intervention.
Materials and methods
After a screening examination and medical history, all subjects were evaluated in the General Clinical Research Center at the Massachusetts General Hospital. Blood samples were obtained to measure insulin, glucose, cholesterol, low-density lipoproteins (LDL), high-density lipoproteins (HDL) and triglycerides, CD4 count, and HIV viral load after an overnight fast. Cholesterol LDL, HDL, triglycerides, glucose, and urinary free cortisol were determined using previously described methods (10). Insulin levels were determined in duplicate for each subject, by RIA (Linco Research Inc., St. Louis, MO). The detection limit of the assay is 2 µU/mL, with intraassay CVs ranging from 2.3–8.6%. Testosterone was measured by RIA [Endocrine Sciences, Inc., Calabasas Hills, CA (7)]. The free testosterone concentration was determined as the product of the percent free testosterone, measured by equilibrium dialysis, and the total testosterone concentration (7). Estradiol was measured by RIA [Endocrine Sciences, Inc. (7)]. CD4 cell counts were measured by flow cytometry using FACS lysing solution and a FACSscan analyzer (Burton Dickinson Immunohistochemistry Systems, San Jose, CA). Viral load was determined by RT-PCR analysis using the Roche Amplicor HIV-1 Monitor Test (Roche Molecular Biochemicals, Branchberg, NJ). Insulin and lipid data are presented only in subjects in whom an overnight fast was confirmed (n = 70).
Height and weight were measured for each subject. Dual-energy x-ray absorptiometry (DEXA) was performed to determine total and regional lean body and fat mass using a Hologic-2000 densitometer (Hologic, Inc., Waltham, MA). Regions of interest (including arms, legs and trunk) were standardized (1995 Users Guide, Hologic, Inc.).
Percent body fat and percent lean body mass were calculated by dividing
the weight of fat and lean tissue by total body weight (Fig. 1
). Similarly, the percentage of truncal
fat and extremity fat were determined by dividing the weight of truncal
fat and extremity fat by the total amount of body fat. The ratio of
percent truncal fat to extremity fat was calculated for the control
subjects, and the mean value was 0.59 ± 0.14. Therefore, a value
of 0.87 (mean + 2 SD) was selected to represent abnormal
fat distribution, with higher values representing increased truncal fat
relative to extremity fat. This criterion was then used to identify
HIV-infected women with regional fat distribution suggestive of
increased truncal adiposity.
|
Data from 75 HIV-infected women are included in the analysis. Descriptive statistics are represented as mean ± SE. Correlation coefficients were determined between indices of total and regional body fat, insulin, glucose, lipid concentrations, and virologic parameters. Comparisons were made between HIV-infected patients and control subjects. Within the HIV-infected group, additional comparisons were made between subjects with and without: 1) weight < 90% IBW; 2) abnormal truncal adiposity; and 3) PI use. Student’s t tests were performed to test for difference between two subject groups. Wilcoxon rank sum test was used for subanalyses to compare small groups with nonnormally distributed data. A P value of 0.05 was used to test for statistical significance, and all statistical tests were two-tailed.
|
Results |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
Baseline clinical characteristics of the study subjects are shown
in Table 1. HIV-infected subjects were
matched for weight with control subjects. The percent truncal fat
(38.5 ± 0.9 vs. 34.9 ± 1.3%, P
< 0.05) and the trunk fat to extremity fat ratio (0.70 ± 0.03
vs. 0.59 ± 0.04, P < 0.05) were
increased and the percent extremity fat decreased (56.9 ± 0.7
vs. 59.9 ± 1.1%, P < 0.05) in the
HIV-infected patients, compared with control subjects. Although the
percent total body fat was significantly less (21.1 ± 1.6
vs. 27.0 ± 1.5%, P < 0.001) in the
low-weight HIV-infected subjects (%IBW < 90), compared with
controls, the percent truncal fat was not significantly reduced in this
group (33.4 ± 1.5 vs. 34.9 ± 1.2%,
P = 0.44, low-weight HIV vs. control).
|
Compared with the control subjects in whom weight was similar, the
mean insulin level was significantly increased in the HIV-infected
patients (15.9 ± 1.5 vs. 7.5 ± 0.6 µU/mL,
P < 0.001, HIV vs. controls) and above the
published normal range for the assay (5–15 µU/mL) in 30% of
HIV-infected patients (Table 2, Fig. 2). Insulin levels remained significantly
different when the groups were age-matched (18.1 ± 3.8
vs. 6.8 ± 4.8 µU/mL, HIV vs. control,
Wilcoxon rank sum, P < 0.001). No correlation was
observed between age and insulin levels among the HIV-infected women
(r = 0.07, P = 0.6).
|
|
Thirteen subjects demonstrated abnormal fat distribution, based on the definition of trunk-to-extremity fat ratio more than 2 SD above the mean ratio for the control subjects (see Subjects and Methods). Among these subjects, insulin was significantly increased and more than twice that of HIV-infected women with more normal fat distribution (28.2 ± 3.2 vs. 13.2 ± 1.5 µU/mL, P < 0.001). The insulin-to-glucose ratio was also significantly increased in the HIV-infected subjects with relative truncal adiposity, compared with HIV-infected subjects with a normal ratio of trunk to extremity fat (0.32 ± 0.04 vs. 0.17 ± 0.02, P < 0.01).
Lipid concentrations
HIV-infected women demonstrated significant hypertriglyceridemia (144 ± 15 vs. 66 ± 23 mg/dL, P < 0.01 vs. controls), which was present even among low-weight patients (148 ± 32 mg/dL, P < 0.001 vs. controls). In contrast, neither HDL, LDL, nor cholesterol levels were different between the HIV-infected and control subjects.
PI use
Seventeen subjects among the entire patient group were receiving PI therapy for a minimum of 2 weeks. The average duration of PI therapy for this group was 6.4 ± 0.8 months; 16 subjects were on indinavir, and 1 subject was treated with nelfinavir. No differences in truncal fat distribution (0.75 ± 0.05 vs. 0.68 ± 0.03, P = 0.3), insulin (14.0 ± 3.2 vs. 16.5 ± 1.7 µU/mL, P = 0.5), insulin-to-glucose ratio (0.20 ± 0.02 vs. 0.17 ± 0.04, P = 0.5), or triglyceride levels (154 ± 20 vs. 109 ± 37 mg/dL, P = 0.3) were seen among the PI-treated patients (compared with non-PI-treated patients, respectively). Only 4 of the 13 patients who met the criteria for abnormal fat distribution were receiving PI therapy, with a duration of therapy ranging from 0.5–5 months.
Menstrual function and hormonal parameters
Although weight, total body fat, truncal fat, and total and free testosterone were not different among the amenorrheic (24%, n = 18), compared with eumenorrheic HIV-infected patients (76%, n = 57), insulin (23.1 ± 3.1 vs. 13.9 ± 1.7 µU/mL, P = 0.01, amenorrheic vs. eumenorrheic) and the insulin-to-glucose ratio (0.29 ± 0.04 vs. 0.17 ± 0.02, P = 0.01) were significantly increased in the amenorrheic (compared with eumenorrheic) HIV-infected subjects. Estradiol levels tended to be reduced in amenorrheic vs. eumenorrheic subjects (8.8 ± 2.7 vs. 14.2 ± 1.9 pg/mL, P = 0.1), but this difference did not reach statistical significance. Serum total testosterone (25.3 ± 1.8 ng/dL; normal range, 10–55 ng/dL) and free testosterone (1.95 ± 0.2 pg/mL; normal range, 1.1–6.3 pg/mL) levels were decreased in 6% and 37% of HIV-infected patients, respectively, but were not different in comparison by wasting status, truncal adiposity, or PI usage within the HIV-infected patients (data not shown). Testosterone levels did not correlate with insulin or insulin-to-glucose ratio (data not shown). Twenty-four-hour urine free cortisol levels were available in a subset of 20 patients. Cortisol levels were significantly lower in the HIV-infected vs. control subjects, although the mean level in each group was within the normal range (48.9 ± 3.3 vs. 27.8 ± 3.9 µg/day, P < 0.001; normal range, 20–90 µg/day). Among the subgroup in whom cortisol levels were available, insulin levels were significantly increased (16.2 ± 1.6 vs. 7.5 ± 1.3 µU/mL, P < 0.001 HIV-infected vs. control subjects).
Regression analysis
Among the entire group of HIV-infected patients, insulin and glucose levels correlated with body mass index (BMI) (r = 0.36 for insulin; r = 0.37 for glucose, P < 0.01), whereas glucose (r = 0.26, P < 0.05), but not insulin, correlated with percent total body fat. In contrast, insulin levels correlated with truncal adiposity (percent trunk fat, r = 0.27, P < 0.05 and trunk fat-to-extremity fat ratio r = 0.26, P < 0.05). Percent truncal fat correlated with cholesterol (r = 0.26, P < 0.05), but not triglyceride, levels (r = 0.11, P = 0.4). Significant inverse correlations were observed between viral load and BMI (r = -0.23, P < 0.05) and between viral load and percent truncal fat (r = -0.26, P < 0.05). In contrast, positive associations were observed between viral load and triglyceride level (r = 0.29, P < 0.05) and between duration of PI use and triglyceride level (r = 0.61, P < 0.01).
|
Discussion |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
Our data demonstrate significant fasting hyperinsulinemia and an increased insulin-to-glucose ratio in HIV-infected women. The mean insulin level was more than twice the level in weight-matched control subjects and above the reference range of the assay in 30% of HIV-infected subjects. Of note, increased insulin and insulin-to-glucose ratio were seen even among patients with low weight, less than 90% IBW (mean 82 ± 3%), in whom reduced insulin would be expected. These data are generally in agreement with the recent data of Walli et al. (2), suggesting insulin resistance in HIV-infected men. However, previous data suggest an increased prevalence of abnormalities in glucose homeostasis among PI-treated patients, in whom over 50% demonstrate abnormal oral glucose tolerance testing. Furthermore, Mulligan et al. (13) have shown that initiation of PI therapy results in increased insulin and glucose levels. In contrast, these data suggest increased insulin and insulin-to-glucose ratio even among significantly wasted HIV-infected women, as well as patients not receiving PI therapy. Further prospective studies are needed to determine the effect of PI therapy on glucose homeostasis in HIV-infected patients. The potential consequence of hyperinsulinemia in this group is unknown but may predispose such patients to glucose intolerance and increased risk of long-term cardiovascular morbidity.
Markedly elevated insulin levels were seen among the subset of HIV-infected patients with relative truncal adiposity, defined using a DEXA criterion obtained from healthy normal control subjects in whom the ratio of percent truncal fat to percent extremity fat was determined. An advantage of this index is that it takes into account relative fat loss in the extremities, as well as increased truncal fat. Using this criterion, we were able to identify a subset of patients in whom insulin, but not overall percent fat mass, was significantly increased. In addition, the insulin-to-glucose ratio was significantly increased in such patients. In a regression analysis of the entire cohort of HIV-infected patients, a significant correlation between truncal adiposity and insulin levels was observed.
Although the HIV-infected patients demonstrated increased truncal adiposity and reduced extremity fat, no significant differences in truncal fat or in the relative ratio of trunk to extremity fat were observed in the PI-treated patients. These data suggest that there may be underlying changes in regional body composition among HIV-infected women that are independent of PI therapy. In agreement with this finding, Kotler et al. (14) noted an increased waist-to-hip ratio, in a retrospective study among HIV-infected patients before the widespread use of PI therapy.
Triglyceride levels were significantly increased in our female patients, consistent with prior reports in HIV-infected men (15). In this regard, a positive association was observed between triglyceride levels and viral load. Hellerstein et al. (16) have previously shown increased hepatic very-low-density lipoprotein synthesis and decreased triglyceride clearance in HIV-infected patients. However, recent studies suggest that PI therapy may exacerbate hypertriglyceridemia in HIV-infected patients and may directly effect fat metabolism (17). Data from Mulligan et al. and others (13) demonstrate increased lipid levels within 12 weeks after the initiation of PI therapy. Carr et al. (17) suggest that PI therapy may inhibit: 1) chylomicron and triglyceride uptake by the endothelial LRP-lipoprotein lipase complex; and 2) CRABP-1 effects on peripheral adipocyte differentiation and apoptosis, resulting in increased peripheral fat deposition and redistribution. Elevated LDL, combined with low HDL levels, have been reported in men using PIs and who exhibit signs of lipodystrophy (3). The majority of our patient population had a history of wasting, which may account for the lack of such a finding in this study.
In contrast, no significant difference in triglyceride levels was detected among patients receiving PI therapy in this study, in whom the average duration of therapy was 6 months. Although no difference in triglyceride levels was observed in the PI-treated group, a strong association was noted between duration of PI use and triglyceride levels (r = 0.61, P < 0.001). Therefore, it is possible that the relatively short duration of PI use was insufficient to result in increased triglyceride levels in the PI-treated subset of patients. Furthermore, PI-treated patients demonstrated a significant amount of weight loss in this study, and further elevations in triglyceride might occur with weight gain. Finally, in contrast to the data of Miller et al. (4), we found no relationship between truncal adiposity and triglyceride levels. Instead, we observed only a significant correlation between truncal adiposity and cholesterol. However, the computed tomography scan technique used by Miller et al. (4) is better able to assess visceral adiposity, in contrast to the DEXA technique used in this study, in which only the relative proportion of trunk-to-extremity adiposity is determined.
We assessed hormonal factors that may potentially contribute to the lipodystrophy syndrome. Increased insulin levels were observed in both the eumenorrheic and amenorrheic HIV-infected subjects, compared with control subjects. However, significantly increased insulin and insulin-to-glucose ratios were seen among amenorrheic (compared with eumenorrheic) HIV-infected patients. Neither weight, truncal fat mass, nor testosterone levels were increased among amenorrheic HIV-infected subjects, to potentially explain the observation of hyperinsulinemia. Further studies are needed to investigate the potential relationship among menstrual function, insulin, and glucose homeostasis in HIV-infected patients.
Certain features of the lipodystrophy syndrome, including dorsocervical and truncal fat accumulation and insulin resistance, are consistent with Cushing’s syndrome. However, other more specific features (such as muscle weakness, striae, and bruising) are not observed. In this regard, serum and urine cortisol levels have been shown to be elevated in only a minority of patients with the lipodystrophy syndrome and to adequately suppress with dexamethasone in such patients (5). Furthermore, facial fat atrophy, seen in some patients, is not a usual feature of Cushing’s syndrome. In this study, we did not formally investigate the relationship between the HPA axis and insulin. Increased insulin levels were noted, however, among a subset of patients, in whom normal urine free cortisol levels were observed, suggesting that factors other than hypercortisolemia contributed to hyperinsulinemia in this subset of patients. In addition, these data do not rule out a paracrine effect of glucocorticoid in specific fat depots, independent of systemic steroid levels.
This study has a number of potential limitations. These data are cross-sectional and, therefore, do not permit investigation of the time course of development of hyperinsulinemia or changes in weight or adiposity. Nonetheless, our data demonstrate the degree to which hyperinsulinemia occurs among HIV-infected women, even at low body weight. Furthermore, we established a normative range of truncal adiposity in healthy women, using DEXA scanning in control subjects, and applied these standards to the HIV-infected patients. Markedly increased insulin levels were seen in subjects with increased truncal adiposity, suggesting the potential utility of this index, if validated in larger prospective studies, as a phenotypic marker for the lipodystrophy syndrome. Although the control population was relatively younger, the differences in insulin persisted even after age-matching the groups, and insulin levels were above the normal range for the assay in 30% of the HIV-infected patients studied. Additionally, no relationship was found between age and insulin levels in the HIV-infected patients.
These data, obtained in a relatively large cohort of HIV-infected women, demonstrate fasting hyperinsulinemia and increased truncal adiposity. Taken together, these data suggest underlying metabolic disturbances related to HIV infection independent of PI usage. Nonetheless, hyperinsulinemia and insulin resistance may be exacerbated by PI use, either by a direct effect of PI therapy on fat metabolism or in association with weight gain and increased fat mass with disease recovery. Further research into the underlying mechanisms of hyperinsulinemia and the potential effect of PI therapy in HIV-infected women is needed. In this regard, prospective studies are necessary to determine the effects of PI therapy on body composition, fat redistribution, and glucose homeostasis in HIV-infected patients.
|
Acknowledgments |
|---|
|
Footnotes |
|---|
Received December 30, 1998.
Revised February 17, 1999.
Accepted February 17, 1999.
|
References |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
This article has been cited by other articles:
 |
|
 |
|
  J. B Albu, S. Kenya, Q. He, M. Wainwright, E. S Berk, S. Heshka, D. P Kotler, and E. S Engelson Independent associations of insulin resistance with high whole-body intermuscular and low leg subcutaneous adipose tissue distribution in obese HIV-infected women Am. J. Clinical Nutrition, July 1, 2007; 86(1): 100 - 106. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Falasca, M. R. Manigrasso, D. Racciatti, P. Zingariello, M. Dalessandro, C. Ucciferri, P. Mancino, M. Marinopiccoli, C. Petrarca, P. Conti, et al. Associations between Hypertriglyceridemia and Serum Ghrelin, Adiponectin, and IL-18 Levels in HIV-infected Patients. Ann. Clin. Lab. Sci., December 1, 2006; 36(1): 59 - 66. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. H. Tang, J. S. Sheffield, J. Grimes, B. McElwee, S. W. Roberts, V. Laibl, D. D. McIntire, and G. D. Wendel Jr Effect of protease inhibitor therapy on glucose intolerance in pregnancy. Obstet. Gynecol., May 1, 2006; 107(5): 1115 - 1119. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Moriconi, M. Kraenzlin, B. Muller, U. Keller, C. P. G. Nusbaumer, S. Stohr, M. Tamm, and J. J. Puder Body Composition and Adiponectin Serum Concentrations in Adult Patients with Cystic Fibrosis J. Clin. Endocrinol. Metab., April 1, 2006; 91(4): 1586 - 1590. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J. Puder, S. Varga, M. Kraenzlin, C. De Geyter, U. Keller, and B. Muller Central Fat Excess in Polycystic Ovary Syndrome: Relation to Low-Grade Inflammation and Insulin Resistance J. Clin. Endocrinol. Metab., November 1, 2005; 90(11): 6014 - 6021. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Johnsen, S. E. Dolan, K. V. Fitch, K. M. Killilea, J. L. Shifren, and S. K. Grinspoon Absence of Polycystic Ovary Syndrome Features in Human Immunodeficiency Virus-Infected Women Despite Significant Hyperinsulinemia and Truncal Adiposity J. Clin. Endocrinol. Metab., October 1, 2005; 90(10): 5596 - 5604. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Mayer, B T. Walsh, R. N Pierson Jr, S. B Heymsfield, D. Gallagher, J. Wang, M. K Parides, R. L Leibel, M. P Warren, E. Killory, et al. Body fat redistribution after weight gain in women with anorexia nervosa Am. J. Clinical Nutrition, June 1, 2005; 81(6): 1286 - 1291. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Koutkia, B. Canavan, J. Breu, and S. Grinspoon Effects of Growth Hormone-Releasing Hormone on Bone Turnover in Human Immunodeficiency Virus-Infected Men with Fat Accumulation J. Clin. Endocrinol. Metab., April 1, 2005; 90(4): 2154 - 2160. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Koutkia, B. Canavan, J. Breu, and S. Grinspoon Growth Hormone (GH) Responses to GH-Releasing Hormone-Arginine Testing in Human Immunodeficiency Virus Lipodystrophy J. Clin. Endocrinol. Metab., January 1, 2005; 90(1): 32 - 38. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Koutkia, B. Canavan, J. Breu, M. Torriani, J. Kissko, and S. Grinspoon Growth Hormone-Releasing Hormone in HIV-Infected Men With Lipodystrophy: A Randomized Controlled Trial JAMA, July 14, 2004; 292(2): 210 - 218. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. T. Brown, M. D. Ruppe, R. Kassner, P. Kumar, T. Kehoe, A. S. Dobs, and J. Timpone Reduced Bone Mineral Density in Human Immunodeficiency Virus-Infected Patients and Its Association with Increased Central Adiposity and Postload Hyperglycemia J. Clin. Endocrinol. Metab., March 1, 2004; 89(3): 1200 - 1206. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. G. Albert and A. D. Mooradian Low-Dose Recombinant Human Growth Hormone as Adjuvant Therapy to Lifestyle Modifications in the Management of Obesity J. Clin. Endocrinol. Metab., February 1, 2004; 89(2): 695 - 701. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Johnson, J. B. Albu, E. S. Engelson, S. K. Fried, Y. Inada, G. Ionescu, and D. P. Kotler Increased systemic and adipose tissue cytokines in patients with HIV-associated lipodystrophy Am J Physiol Endocrinol Metab, February 1, 2004; 286(2): E261 - E271. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. M Hendricks, K. R Dong, A. M Tang, B. Ding, D. Spiegelman, M. N Woods, and C. A Wanke High-fiber diet in HIV-positive men is associated with lower risk of developing fat deposition Am. J. Clinical Nutrition, October 1, 2003; 78(4): 790 - 795. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. E. Yarasheski, P. Tebas, S. Claxton, D. Marin, T. Coleman, W. G. Powderly, and C. F. Semenkovich Visceral adiposity, C-peptide levels, and low lipase activities predict HIV-dyslipidemia Am J Physiol Endocrinol Metab, October 1, 2003; 285(4): E899 - E905. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. N. Reeds, B. Mittendorfer, B. W. Patterson, W. G. Powderly, K. E. Yarasheski, and S. Klein Alterations in lipid kinetics in men with HIV-dyslipidemia Am J Physiol Endocrinol Metab, September 1, 2003; 285(3): E490 - E497. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Misra, L. A Soyka, K. K Miller, S. Grinspoon, L. L Levitsky, and A. Klibanski Regional body composition in adolescents with anorexia nervosa and changes with weight recovery Am. J. Clinical Nutrition, June 1, 2003; 77(6): 1361 - 1367. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. K. S. Leow, C. L. Addy, and C. S. Mantzoros Human Immunodeficiency Virus/Highly Active Antiretroviral Therapy-Associated Metabolic Syndrome: Clinical Presentation, Pathophysiology, and Therapeutic Strategies J. Clin. Endocrinol. Metab., May 1, 2003; 88(5): 1961 - 1976. [Full Text] [PDF]
|
|
|
|
|
|
Q. Tong, J.-L. Sankale, C. M. Hadigan, G. Tan, E. S. Rosenberg, P. J. Kanki, S. K. Grinspoon, and G. S. Hotamisligil Regulation of Adiponectin in Human Immunodeficiency Virus-Infected Patients: Relationship to Body Composition and Metabolic Indices J. Clin. Endocrinol. Metab., April 1, 2003; 88(4): 1559 - 1564. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Chen, A. Misra, and A. Garg Lipodystrophy in Human Immunodeficiency Virus-Infected Patients J. Clin. Endocrinol. Metab., November 1, 2002; 87(11): 4845 - 4856. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. V Heath, K. J Chan, J. Singer, M. V O'Shaughnessy, J. S G Montaner, and R. S Hogg Incidence of morphological and lipid abnormalities: gender and treatment differentials after initiation of first antiretroviral therapy Int. J. Epidemiol., October 1, 2002; 31(5): 1016 - 1020. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Meininger, C. Hadigan, P. Rietschel, and S. Grinspoon Body-composition measurements as predictors of glucose and insulin abnormalities in HIV-positive men Am. J. Clinical Nutrition, August 1, 2002; 76(2): 460 - 465. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Grinspoon, L. Thomas, K. Miller, S. Pitts, D. Herzog, and A. Klibanski Changes in regional fat redistribution and the effects of estrogen during spontaneous weight gain in women with anorexia nervosa Am. J. Clinical Nutrition, May 1, 2001; 73(5): 865 - 869. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Insulin Resistance in HIV Lipodystrophy Syndrome AIDS Clinical Care, February 1, 2001; 2001(201): 7 - 7. [Full Text]
|
|
|
|
|
|
S. I. Helle, T. Ueland, D. Ekse, S. S. Frøland, J. M. P. Holly, P. E. Lønning, and P. Aukrust The Insulin-Like Growth Factor System in Human Immunodeficiency Virus Infection: Relations to Immunological Parameters, Disease Progression, and Antiretroviral Therapy J. Clin. Endocrinol. Metab., January 1, 2001; 86(1): 227 - 233. [Abstract] [Full Text]
|
|
|
|
 |
|
 P. A. Heine, J. A. Taylor, G. A. Iwamoto, D. B. Lubahn, and P. S. Cooke Increased adipose tissue in male and female estrogen receptor-alpha knockout mice PNAS, November 7, 2000; 97(23): 12729 - 12734. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Hadigan, C. Corcoran, S. Piecuch, W. Rodriguez, and S. Grinspoon Hyperandrogenemia in Human Immunodeficiency Virus-Infected Women with the Lipodystrophy Syndrome J. Clin. Endocrinol. Metab., October 1, 2000; 85(10): 3544 - 3550. [Abstract] [Full Text]
|
|
|
|
 |
|
 J. M. Lenhard, D. K. Croom, J. E. Weiel, A. Spaltenstein, D. J. Reynolds, and E. S. Furfine Dietary Fat Alters HIV Protease Inhibitor-Induced Metabolic Changes in Mice J. Nutr., September 1, 2000; 130(9): 2361 - 2366. [Abstract] [Full Text]
|
|
|
|
|
|
C. Hadigan, C. Corcoran, N. Basgoz, B. Davis, P. Sax, and S. Grinspoon Metformin in the Treatment of HIV Lipodystrophy Syndrome: A Randomized Controlled Trial JAMA, July 26, 2000; 284(4): 472 - 477. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Sesmilo, B. M.K. Biller, J. Llevadot, D. Hayden, G. Hanson, N. Rifai, and A. Klibanski Effects of Growth Hormone Administration on Inflammatory and Other Cardiovascular Risk Markers in Men with Growth Hormone Deficiency: A Randomized, Controlled Clinical Trial Ann Intern Med, July 18, 2000; 133(2): 111 - 122. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Hadigan, C. Corcoran, T. Stanley, S. Piecuch, A. Klibanski, and S. Grinspoon Fasting Hyperinsulinemia in Human Immunodeficiency Virus-Infected Men: Relationship to Body Composition, Gonadal Function, and Protease Inhibitor Use J. Clin. Endocrinol. Metab., January 1, 2000; 85(1): 35 - 41. [Abstract] [Full Text]
|
|
| ||||||
