IGF1 levels as predictor factor of metabolic derangement in adult patients with severe GH deficiency
Valentina Gasco1, Guglielmo Beccuti1, Silvia Rovere1, Filippa Marotta1, Gianluca Aimaretti2, Mauro Maccario1, Silvia Grottoli1 & Ezio Ghigo1
GH deficiency (GHD) in adults leads to impairment in body composition and function, as well as to deranged lipoprotein and carbohydrate metabolism implying increased cardiovascular morbidity. The morphologic and metabolic alterations in GHD syndrome are more marked in patients with the most severe GHD, even when evaluated by maximal provocative test such as GHRH + arginine. IGF1 synthesis and secretion are function of the GH status but also of major metabolic factors such as insulin. In fact, even in a big population of normal subjects, IGF1 levels in lower quartile are associated with increased risk for metabolic and cardiovascular disease. Nevertheless, in GHD adults the severity of GHD is not strictly associated to IGF1 levels. In fact, IGF1 levels in severe GHD adults are often within the normal range. We retrospectively evaluated the relationship between total IGF1 levels and metabolic parameters in a large populations of adults with severe GHD (139 M, 107 F; age (mean±S.D.): 48.3±16.6 years). We evaluated the correlation of IGF1 SDS with BMI, glucose, HbA1c, total cholesterol, triglyceride, HDL, LDL, non-HDL cholesterol levels, bone T score and Z-score.
BMI adjusted for age was higher in the lower quartiles (P< 0.0001). Similarly, after adjusting for age and BMI, the lowest IGF1 SDS quartiles associated with highest levels of glucose (P< 0.0001), HbA1c (P< 0.0004), total cholesterol (P< 0.0001), HDL (P< 0.0001), LDL (P< 0.007), non-HDL cholesterol (P< 0.003). IGF1 SDS levels did not associate to triglyceride levels. On the other hand, the highest IGF1 SDS quartiles associated with the highest levels of either bone T (P< 0.04) or Z-score (P< 0.0004) adjusted for BMI.
In conclusion, this study shows that more severe impairment of the IGF1 status is associated to more marked derangement in glucose and lipid metabolism.