Abstract
To clarify the mechanism underlying the described U-shaped relation of both low and high levels of IGF-1 with cardiovascular disease this study explores the effect of decreasing and increasing growth hormone dose in GH deficient adults on (micro)vascular function, body composition and insulin resistance. In this randomized clinical trial, thirty-two subjects receiving GH therapy with an IGF-1 concentration between −1 and 1 SD score (SDS) for at least one year were randomized to receive either a decrease (IGF-1 target level of −2 to −1 SDS) or an increase of their daily GH dose (IGF-1 target level of 1 to 2 SDS) for a period of 24 weeks. Microvascular endothelium (in)dependent vasodilatation and vasomotion, vascular stiffness by pulse wave analysis, and HOMA-IR were measured. At the end of the study 30 subjects (65.6% men, mean age 46.6 (SD 9.9) years) were analyzed. There was a favorable effect of increasing the IGF-1 level on waist circumference compared to decreasing the IGF-1 level (p=0.05), but a detrimental effect on insulin resistance (p=0.03). Decreasing IGF-1 level significantly lowered the endothelial domain of vasomotion (p=0.03), whereas increasing IGF-1 level increased the contribution of the neurogenic domain (p=0.05). This change was related to the favorable change in waist circumference. In conclusion, increasing IGF-1 levels was beneficial for body composition but detrimental with respect to insulin resistance. The contribution of the neurogenic vasomotion domain increased in parallel, and could be explained by the favorable change in waist circumference.Clinical Trial RegistrationClinicalTrials.gov, identifier NCT01877512.
Highlights
Epidemiological evidence for a bidirectional link between serum IGF-1 concentrations and cardiovascular disease (CVD) has been repeatedly demonstrated
To clarify the mechanism underlying the described U-shaped relation of both low and high levels of IGF-1 with cardiovascular disease this study explores the effect of decreasing and increasing growth hormone dose in GH deficient adults onvascular function, body composition and insulin resistance
Growth hormone (GH) deficient adults are characterized by an adverse lipid profile and altered body composition with increased fat mass which may put them on an increased risk for cardiovascular disease [1, 2]
Summary
Epidemiological evidence for a bidirectional link between serum IGF-1 concentrations and cardiovascular disease (CVD) has been repeatedly demonstrated. High levels of IGF-1 such as observed in acromegaly are associated with an adverse cardiovascular risk profile and a higher prevalence of CVD [6]. These data suggest a U-shaped relationship between IGF-1 concentrations and CVD, which was corroborated by the finding of a U-shaped relationship with cardiovascular mortality in a Dutch cohort of healthy older people [7]. It is unclear whether such a U-shaped association exists in GH deficient adults treated with GH. Insulin resistance itself has been linked to a lower capillary density and a change in vasomotion, the rhythmic change in vascular diameter, which is thought to influence capillary perfusion [14]
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