A randomized, open‐label study to compare the effects of two different doses of recombinant human growth hormone on fat reduction and fasting metabolic parameters in HIV‐1‐infected patients with lipodystrophy

Abstract

Several studies have shown beneficial effects of recombinant human growth hormone (r-hGH) in reducing visceral adipose tissue (VAT) in HIV-1-infected patients with lipodystrophy. MethodsPatients were randomized to r-hGH 4 mg daily (group A) or three times per week (group B) over 12 weeks, followed by a 2 mg daily maintenance dose for 12 weeks. Magnetic resonance imaging (MRI) scans were performed to assess body composition. ResultsA total of 26 subjects were included in the study. VAT was reduced overall by 35.1 cm 2 (29.5%) at week 12 and by 49 cm 2 (39.9%) at week 24, respectively, compared with baseline (Po0.001 for both comparisons). By week 12, VAT was reduced by 27 and 29% (A vs B; P 5 0.47) while facial fat was reduced by 3.3 and 2.6 cm 2 in groups A and B, respectively (P 5 0.96). Over 24 weeks, VAT was reduced by 42 and 38% (P 5 0.35) and facial fat by 3.2 and 2.4 cm 2 in groups A and B, respectively (P 5 0.91), compared with baseline. There was a greater increase in high-density lipoprotein (HDL) in group A than in group B (4.9 vs 2.4 mg/dL in week 12 and 7.1 vs À 0.4 mg/dL in week 24; P 5 0.03). Fasting insulin levels increased, whereas glucose and insulin measured in oral glucose tolerance tests remained unchanged. Drug-related side effects were transient and reversible, but more common in group A (67%) than in group B (29%). ConclusionsThis study confirms reports that r-hGH effectively reduces VAT, with a relatively small reduction of facial and limb fat.Keywords: growth hormone, lipodystrophy, magnetic resonance imaging, visceral adipose tissue, visceral adiposity IntroductionIn recent years, HIV-associated lipodystrophy syndrome has become a major challenge in the treatment of HIV disease. This syndrome involves intra-abdominal (visceral) adiposity, development of antero-and dorsocervical fat pads (buffalo hump), breast enlargement and symmetric lipomatosis as signs of fat accumulation, and loss of subcutaneous fat from the face, limbs, trunk and buttocks [1][2][3][4][5]. All of these changes can occur alone or in combination. To date, the exact pathogenesis of the broad spectrum of these common, disfiguring body shape changes, which can occur at any stage of treated HIV 397 infection, is not completely understood. Visceral adiposity, one of the hallmarks of HIV-associated lipodystrophy syndrome, is a known independent risk factor for insulin resistance and cardiovascular complications [6][7][8] and is therefore a major concern as a potential long-term complication of highly active antiretroviral therapy (HAART). Recent studies suggest an increase of cardiovascular and cerebrovascular events associated with the duration of HAART, although some results are contradictory [9][10][11][12][13][14][15][16]. Several studies using various antiretroviral treatment strategies failed to completely resolve or prevent HIV-associated lipodystrophy. Furthermore, expensive and time-consuming three-dimensional imaging techniques such as computed tomography or magnetic resonance imaging (MRI) are needed to disting...

GH/GHRH axis in HIV lipodystrophy

“…Initial studies using a GH dose of 6 mg daily in lipodystrophy showed dramatic reductions in VAT along with decreased insulin sensitivity and relatively frequent treatment-limiting side effects, including arthralgias, myalgias, hypoesthesia, and fluid retention, likely related to the supraphysiological IGF-I levels achieved [55,57]. A relatively lower GH dose of 4 mg daily decreases VAT by approximately 20% or more, but this dose also worsens glucose tolerance and causes side effects in a significant percentage of patients [58,59,62,63]. Alternate day dosing (4 mg every other day) appears to yield similar benefits in terms of VAT reduction while causing fewer side effects [58,59,62].…”

“…In patients with HIVassociated weight loss, subcutaneous GH administration at a very high dose of 6 mg daily has been used to overcome GH resistance and to increase body weight [47][48][49][50][51][52][53], build lean body mass [48,[50][51][52][53], and decrease protein oxidation [47,54]. The effects of GH to increase lean mass and decrease abdominal adiposity have also made it an attractive potential treatment for HIV lipodystrophy, and numerous clinical trials confirm that GH improves body composition and lipid parameters in patients with HIV lipodystrophy (Table 1) [55][56][57][58][59][60][61][62][63][64][65][66][67][68][69]. In the two largest of these trials, GH 4 mg daily for 12 weeks decreased visceral fat by approximately 20%, lowered total cholesterol levels, and increased HDL cholesterol [58,59,63].…”

“…A relatively lower GH dose of 4 mg daily decreases VAT by approximately 20% or more, but this dose also worsens glucose tolerance and causes side effects in a significant percentage of patients [58,59,62,63]. Alternate day dosing (4 mg every other day) appears to yield similar benefits in terms of VAT reduction while causing fewer side effects [58,59,62]. Significantly lower, physiologic GH doses designed to maintain IGF-I levels in the normal range have been studied in three small trials, all of which show modest effect on body composition but, importantly, do not demonstrate worsened insulin sensitivity [60,61,66].…”

Safety and Metabolism of AOD9604, a Novel Nutraceutical Ingredient for Improved Metabolic Health

“…Accordingly, systemic hGH treatment in rodents and humans influences fat distribution, particularly abdominal fat, and reduces body fat mass [15][16][17][18][19][20]. However side effects can include glucose intolerance, diabetes and insulin resistance, acromegaly, cancer, edema and hypertension [4,16,[21][22][23][24].…”

Treatment for lipoatrophy: facing the real costs

“…In some studies, but not all, thiazolidinediones have been shown to result in modest recovery in fat volume [5]. The use of human growth hormone can improve visceral adiposity, but may worsen facial or peripheral lipoatrophy [6].…”