THE INTERACTIONS BETWEEN HYPOTHALAMIC-PITUITARY-ADRENAL AXIS ACTIVITY, TESTOSTERONE, INSULIN-LIKE-GROWTH-FACTOR-I AND ABDOMINAL OBESITY WITH METABOLISM AND BLOOD-PRESSURE IN MEN

OBJECTIVE: To examine potential interactions between abdominal obesity , endocrine, metabolic and hemodynamic perturbations. SUBJECTS: A subg roup of 284 men from a population sample of 1040 at the age of 51 y. M EASUREMENTS: Anthropometric measurements included body mass index (BMI , kg/m(2)), waist/hip circumference ratio (WHR) and abdominal sagittal diameter (D). Endocrine measurements were a modified, low dose (0.5 m g) dexamethasone suppression test (Dex), testosterone (T) and insulin- like growth factor I (IGF-I). Overnight fasting values of blood glucos e, serum insulin, triglycerides, total, low and high density lipoprote in cholesterol, as well as resting heart rate and blood pressure were also determined. RESULTS: Arbitrary subdivisions of the men were perfo rmed to obtain subgroups of low T and IGF-I values (lowest decile, bor derlines less than or equal to 13.13 nmol/l and less than or equal to 28.80 mu g/l, respectively) and normal or blunted Dex. Significant rel ationships with BMI, WHR or D, and abnormal metabolic and hemodynamic factors, usually with the exception of total and low density lipoprote in cholesterol, were then found in subgroups with different endocrine profiles. These included men with a blunted Dex test with low T or IGF -I values, as well as men with a normal Dex test and low or normal T o r ICE-I values. In addition, a group with isolated low Dex suppression , as well as another group without endocrine abnormalities, showed suc h relationships. These findings suggest that, in men, obesity factors are associated with metabolic and hemodynamic complications with or wi thout the presence of perturbations of hypothalamic-pituitary-adrenal axis (HPA) regulation or low T or growth hormone secretion. In order t o generate hypotheses concerning the nature of the impact of the endoc rine perturbations in abdominal obesity and its metabolic complication s, path analyses were performed, testing different models. These model s included the endocrine measurements (Dex test, T and IGF-I), the WHR and D (representing abdominal distribution of fat), BMI (representing obesity), as well as insulin and triglyceride values (representing me tabolic perturbations). The results showed a satisfactory fit (goodnes s-of-fit index: 0.945 - 1.0) for the path diagrams: Dex --> T/IGF-I -- > WHR or D --> insulin --> triglycerides with additional direct input of blunted Dex on insulin values (see Figure I). With BMI as determina nt, essentially the same results were found with the addition of a dir ect pathway between Dex and BMI as well as between IGF-I-T and insulin (Figure 2). There was no evidence for pathways where WHR or BMI deter mined endocrine variables. CONCLUSIONS: The results suggest that abdom inal obesity with or without endocrine abnormalities exerts a major im pact on abnormalities in metabolic and hemodynamic variables. Abdomina l obesity seems to be dependent on endocrine abnormalities, which in t urn show direct or indirect relationships to the metabolic and circula tory variables, including a direct pathway between HPA-axis perturbati ons and accumulation of total body fat as indicated by the BMI. It is therefore suggested that endocrine perturbations are followed by obesi ty and by storage of an elevated proportion of fat in visceral depots, followed by metabolic and hemodynamic abnormalities. This is statisti cal evidence which is supported by evidence of mechanistic links in pr evious studies, suggesting the possibility of causal relationships. Th e results also indicate subgroups of abdominal obesity and its associa ted metabolic and hemodynamic abnormalities, which might be due to the input of different pathogenetic factors.