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In many patients with severe primary IGF-I deficiency (SPIGFD) defined by low IGF-I (less than 3 SDS or the 2.5 th percentile), severe short stature (Height SDS less than 3), normal GH secretion and absence of acquired insensitivity to GH (discussed below) genetic defects may be absent

Additionally, the metabolic pathway which produces NAD+ can be inhibited by chronic inflammation, high fat diets and, oxidation which can further negate the levels of NAD+ in the body

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