Impact of adult growth hormone deficiency on metabolic profile and cardiovascular risk [Review]

Giovannini, Lara; Tirabassi, Giacomo; Muscogiuri, Giovanna; Somma, Carolina Di; Colao, Annamaria; Balercia, Giancarlo

doi:10.1507/endocrj.ej15-0337

Cited by 45 publications

(34 citation statements)

References 116 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Consistent beneficial effects of GHT were variously reported on body composition, metabolism and cardiovascular risk factors [29][30][31][32], although the prevalence of the metabolic syndrome in GHD patients was found to be increased when compared to healthy controls even after GHT, likely due to the discordant data about anthropometric parameters and glucose metabolism [32][33][34]. Therefore, if the beneficial effect of GHT on lipid profile is well established, other cardiovascular risk factors may continue to deteriorate during GHT, leading to a concern about the net beneficial effects of GHT.…”

Section: Discussionmentioning

confidence: 54%

The visceral adiposity index is associated with insulin sensitivity and IGF-I levels in adults with growth hormone deficiency

2016

View full text Add to dashboard Cite

The visceral adiposity index, based on anthropometric and metabolic parameters, has been shown to be related to adipose tissue function and insulin sensitivity. We aimed to evaluate the performance of the visceral adiposity index in adult patients with growth hormone deficiency. We enrolled 52 patients(mean age 51 ± 13 years) with newly diagnosed growth hormone deficiency and 50 matched healthy subjects as controls at baseline. At baseline and after 12 and 24 months of treatment we evaluated anthropometric measures, lipid profile, glucose and insulin during an oral glucose tolerance test, hemoglobin A1c, homeostasis model assessment estimate of insulin resistance, quantitative insulin sensitivity check index, insulin sensitivity index Matsuda, insulin-like growth factor-I and visceral adiposity index. At baseline growth hormone deficiency patients showed higher waist circumference (p < 0.001), low-density lipoprotein cholesterol (p < 0.001) and visceral adiposity index (p = 0.003) with lower insulin sensitivity index (p = 0.007) and high-density lipoprotein cholesterol (p = 0.001) than controls. During growth hormone treatment we observed a significant increase in insulin-like growth factor-I (p < 0.001), high-density lipoprotein (p < 0.001) with a trend toward increase in insulin sensitivity index (p = 0.055) and a significant decrease in total cholesterol (p < 0.001) and visceral adiposity index (p < 0.001), while no significant changes were observed in other clinical and metabolic parameters. The visceral adiposity index was the only parameter that significantly correlated with growth hormone peak at diagnosis (p < 0.001) and with insulin-like growth factor-I and insulin sensitivity index both at diagnosis (p = 0.009 and p < 0.001) and after 12 (p = 0.026 and p = 0.001) and 24 months (p < 0.001 and p = 0.001) of treatment. The visceral adiposity index, which has shown to be associated with both insulin-like growth factor-I and insulin sensitivity, proved to be the most reliable index of metabolic perturbation, among the most common indexes of adiposity assessment and a marker of benefit during treatment in adult growth hormone deficiency patients.

show abstract

Section: Discussionmentioning

confidence: 54%

The visceral adiposity index is associated with insulin sensitivity and IGF-I levels in adults with growth hormone deficiency

2016

View full text Add to dashboard Cite

show abstract

“…Through a complex process of visceral fat accumulation and insulin resistance, GHD causes abnormal body composition, dyslipidemia, diabetes mellitus, low-grade chronic inflammation, and, collectively, an increased risk of cardiovascular disease and mortality (11). Given the lipolytic effect of GH, GH replacement results in a reduction in fat mass, particularly in the abdomen (12).…”

Section: Discussionmentioning

confidence: 99%

A Randomized Phase 2 Study of Long-Acting TransCon GH vs Daily GH in Childhood GH Deficiency

Chatelain

Malievsky

Radziuk³

et al. 2017

The Journal of Clinical Endocrinology &Amp; Metabolism

View full text Add to dashboard Cite

Context: TransCon Growth Hormone (GH) (Ascendis Pharma) is a long-acting recombinant sustained-release human GH prodrug in development for children with GH deficiency (GHD).Objective: To compare the pharmacokinetics, pharmacodynamics, safety, and efficacy of weekly TransCon GH to that of daily GH in prepubertal children with GHD. Design:Randomized, open-label, active-controlled study of three doses of weekly TransCon GH versus daily Genotropin (Pfizer).Setting: Thirty-eight centers in 14 European countries and Egypt.Patients: Prepubertal male and female treatment-naïve children with GHD (n = 53).Interventions: Subjects received one of three TransCon GH doses (0.14, 0.21, or 0.30 mg GH/kg/wk) or Genotropin 0.03 mg GH/kg/d for 26 weeks.Main Outcome Measures: GH and insulinlike growth factor-1 (IGF-1) levels, growth, adverse events, and immunogenicity.Results: Both GH maximum concentration and area under the curve were similar following TransCon GH or Genotropin administration at comparable doses. A dose response was observed, with IGF-1 standard deviation scores increasing into the normal range for all three TransCon GH doses. Annualized mean height velocity for the three TransCon GH doses ranged from 11.9 cm to 13.9 cm, which was not statistically different from 11.6 cm for Genotropin. Adverse events were mild to moderate, and most were unrelated to the study drug. Injection site tolerance was good. One TransCon GH subject developed a low-titer, nonneutralizing antibody response to GH. Conclusions:The results suggest that long-acting TransCon GH is comparable to daily Genotropin for GH (pharmacokinetics) and IGF-1 (pharmacodynamics) levels, safety, and efficacy and support advancement into phase 3 development.

show abstract

“…GH deficiency contributes to visceral obesity, leading to insulin resistance and dyslipidemia (especially high LDL), diabetes mellitus and chronic inflammation (specifically increased C-reactive protein). The net result is increased atherosclerosis and reduced cardiac function with a subsequent increased risk of cardiovascular events and mortality (16). In a study by Hoffman and coworkers, 166 AGHD subjects were treated with daily GH.…”

Section: Discussionmentioning

confidence: 99%

A phase 2 trial of long-acting TransCon growth hormone in adult GH deficiency

Höybye

Pfeiffer

Ferone

et al. 2017

Endocrine Connections

View full text Add to dashboard Cite

TransCon growth hormone is a sustained-release human growth hormone prodrug under development in which unmodified growth hormone is transiently linked to a carrier molecule. It is intended as an alternative to daily growth hormone in the treatment of growth hormone deficiency. This was a multi-center, randomized, open-label, active-controlled trial designed to compare the safety (including tolerability and immunogenicity), pharmacokinetics and pharmacodynamics of three doses of weekly TransCon GH to daily growth hormone (Omnitrope). Thirty-seven adult males and females diagnosed with adult growth hormone deficiency and stable on growth hormone replacement therapy for at least 3 months were, following a wash-out period, randomized (regardless of their pre-study dose) to one of three TransCon GH doses (0.02, 0.04 and 0.08 mg GH/kg/week) or Omnitrope 0.04 mg GH/kg/week (divided into 7 equal daily doses) for 4 weeks. Main outcomes evaluated were adverse events, immunogenicity and growth hormone and insulin-like growth factor 1 levels. TransCon GH was well tolerated; fatigue and headache were the most frequent drug-related adverse events and reported in all groups. No lipoatrophy or nodule formation was reported. No anti-growth hormone-binding antibodies were detected. TransCon GH demonstrated a linear, dose-dependent increase in growth hormone exposure without accumulation. Growth hormone maximum serum concentration and insulin-like growth factor 1 exposure were similar after TransCon GH or Omnitrope administered at comparable doses. The results suggest that long-acting TransCon GH has a profile similar to daily growth hormone but with a more convenient dosing regimen. These findings support further TransCon GH development.

show abstract

Impact of adult growth hormone deficiency on metabolic profile and cardiovascular risk [Review]

Cited by 45 publications

References 116 publications

The visceral adiposity index is associated with insulin sensitivity and IGF-I levels in adults with growth hormone deficiency

The visceral adiposity index is associated with insulin sensitivity and IGF-I levels in adults with growth hormone deficiency

A Randomized Phase 2 Study of Long-Acting TransCon GH vs Daily GH in Childhood GH Deficiency

A phase 2 trial of long-acting TransCon growth hormone in adult GH deficiency

Contact Info

Product

Resources

About