Six low-function (20%) and 6 high-function (13%) subjects were obese based on BMI, and 4 low-function (13%) but no high-function subjects were underweight. BMI was not significantly different between low-function (geometric mean 25.5 kg/m2, 95% CI: 24.0 to 27.1 kg/m2) and high-function groups (24.2 kg/m2, 95% CI: 22.4 to 26.0 kg/m2, P = 0.25). Relative body fat was slightly higher among low-function (28.2% ± 1.6%) than high-function persons (25.0% ± 1.4%), but this was not significant after adjusting for CD4, current protease inhibitor use, or any use of zidovudine, didanosine, or stavudine (P = 0.14). Fat mass, fat index, fat distribution, and the fat mass ratio were not associated with greater odds of being low function (Table 3). In general and as expected, women had higher median percentage of body fat than men (33% vs 23%). When considering all subjects and adjusting for functional status, age, gender, and time since HIV diagnosis, demographics, smoking or alcohol use, or class of ART were not significantly associated with increased odds of higher relative body fat (all P ≥ 0.11).
Lower IGF-1 and IGFBP-3 were associated with significantly greater odds of being low function (Table 3). Among all subjects and adjusting for functional status, age, gender, and duration of HIV diagnosis, hepatitis B or C was associated with greater odds of having low IGF-1 or IGFBP-3 (OR: 3.5, 95% CI: 1.2 to 10.2, P = 0.03; OR: 6.6, 95% CI: 2.0 to 22.0, P = 0.002) and alcohol use was associated with greater odds of low IGFBP-3 (OR: 15.7, 95% CI: 2.8 to 88.5, P = 0.002).
The frequency of low muscle mass was particularly surprising given the relatively young age (mean: 52 years) of the cohort and similar to what is commonly reported among persons 10–25 years older than the participants in our study.34,35 The implications of this finding are concerning because low muscle mass and sarcopenia are associated with functional dependence and increased mortality among both HIV-infected and HIV-uninfected adults.12,26,36
Low functional status was associated with low serum IGF-1 and IGFBP-3 concentrations in our cohort. Indeed, levels of IGF-1 in our low-function group (99 ± 8 ng/mL) were comparable with those reported in healthy men 70–80 years of age (125 ± SD of 48 ng/mL)44 and frail women 70–79 years of age (104 ± SD of 2 ng/mL).45 An age-related decline in the GH/IGF-1-axis has been well described,46,47 but the unexpectedly low levels of IGF-1 in our cohort, even after adjusting for potential confounders, may represent early somatopause as a manifestation of premature aging in HIV-1 infection. Whether low IGF-1 in our physically impaired group is due to an age-related decrease in GH–releasing hormone, impaired pituitary release of GH, impaired IGF-1 production, or related to hypothalamic infiltration of HIV or side effects of ART is not known.48–51
In our cohort, BMI and measures of fat were not significantly different between low- and high-functioning groups. This finding contrasts to findings from a cohort of “frail” (defined by at least 2 deficits in physical performance test, peak oxygen uptake, activities of daily living, or instrumental activities of daily living), HIV-infected subjects in the Rochester, New York area that demonstrated higher BMI, waist circumference, fat mass, and trunk fat than HIV-infected nonfrail controls.52 The discordance between studies may reflect the lower prevalence of obesity in Colorado compared with New York. In county-specific data collected by the Centers for Disease Control, 30.3% of adults in Monroe County, New York are obese compared with less than 20% of adults in counties of the Denver metropolitan area.53 Indeed, the average BMI of our cohort was 25 kg/m2 compared with 29 kg/m2 in the Rochester cohort.52
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