IGF-I Bioactivity in an Elderly Population

Abstract

OBJECTIVEThere is a complex relationship between IGF-I, IGF binding proteins, growth hormone, and insulin. The IGF-I kinase receptor activation assay (KIRA) is a novel method for measuring IGF-I bioactivity in human serum. We speculated that determination of IGF-I bioactivity might broaden our understanding of the IGF-I system in subjects with the metabolic syndrome. The purpose of our study was to investigate whether IGF-I bioactivity was related to insulin sensitivity and the metabolic syndrome.RESEARCH DESIGN AND METHODSWe conducted a cross-sectional study embedded in a random sample (1,036 elderly subjects) of a prospective population-based cohort study. IGF-I bioactivity was determined by the IGF-I KIRA. Categories of glucose (in)tolerance were defined by the 2003 American Diabetes Association criteria. Insulin sensitivity was assessed by homeostasis model assessment. The Adult Treatment Panel III definition of the metabolic syndrome was used.RESULTSIn subjects with normal fasting glucose and impaired fasting glucose, IGF-I bioactivity progressively increased with increasing insulin resistance, peaked at fasting glucose levels just below 7.0 mmol/l, and dropped at higher glucose levels. Mean IGF-I bioactivity peaked when three criteria of the metabolic syndrome were present and then declined significantly when five criteria of the metabolic syndrome were present.CONCLUSIONSWe observed that IGF-I bioactivity was related to insulin sensitivity, insulin levels, and the metabolic syndrome. Our study suggests that there exists an inverse U-shaped relationship between IGF-I bioactivity and number of components of the metabolic syndrome. This observation contrasts with previous results reporting an inverse relationship between total IGF-I and components of the metabolic syndrome.

Abnormal metabolic phenotype in middle-aged GH-deficient adults despite long-term recombinant human GH replacement

“…Further study is needed to identify sensitive biomarkers to monitor rhGH replacement therapy. Second, it is previously shown that there is an optimum for GH dosing with respect to insulin resistance (33). In this respect, further lowering of the GH dose is probably needed to minimize insulin resistance.…”

Aging phenotype and its relationship with IGF-I gene promoter polymorphisms in elderly people living in Catalonia

“…The somatotropic axis and its activity has claimed to be implicated both in healthy and non-healthy ageing, by virtue of which an improved or impaired IGF-I action may influence the development of diseases affecting longevity and survival with a U-shape effect [6,9]. In relation to this, circulating IGF-I levels in the upper normal range have been associated with a higher prevalence of prostate and colon cancer as well as increased muscle mass and muscle strength [20], while low levels are present in old and frail individuals with different degrees of disability [21] and premature mortality [7].…”

“…In addition, the inclusion of a younger sample of individuals would have overcome the problem of the overrepresentation of certain genotypes due to survival bias, and also, the current minority prevalence of non-carriers of 192 bp allele may have caused problems of statistical power in the sample. Additionally, the measurement of free IGF-I or IGF-I bioactivity [6,9] rather than total IGF-I would have helped to establish certain associations not found with the latter.…”

“…An impaired somatotropic axis activity has been related to a poor ageing condition and increased mortality [6,7]. Overall, population studies seem to indicate an association between high circulating levels of IGF-I and colorectal cancer, due to its positive action in the regulation of proliferative pathways [8] and a U-shaped relationship between bioactive IGF-I and cardiovascular risk, by virtue of which very high or very low IGF-I levels are linked to an excess of mortality [6,9].…”

Serum IGF1, metabolic syndrome, and incident cardiovascular disease in older people: a population-based study

“…Older persons with metabolic syndrome are more likely to experience any CVD event than subjects without metabolic syndrome (7,8). In two previous studies on the association of IGF1 with the metabolic syndrome in older populations, U-shaped relationships have been reported (9,10). Others report low IGF1 values to be related to a greater metabolic burden (11,12,13,14).…”