The interactions between hypothalamic-pituitary-adrenal axis activity, testosterone, insulin-like growth factor I and abdominal obesity with metabolism and blood pressure in men

Abstract

OBJECTIVE: To examine potential interactions between abdominal obesity, endocrine, metabolic and hemodynamic perturbations. SUBJECTS: A subgroup of 284 men from a population sample of 1040 at the age of 51 y. MEASUREMENTS: Anthropometric measurements included body mass index (BMI, kgam 2 ), waistahip circumference ratio (WHR) and abdominal sagittal diameter (D). Endocrine measurements were a modi®ed, low dose (0.5 mg) dexamethasone suppression test (Dex), testosterone (T) and insulin-like growth factor I (IGF-I). Overnight fasting values of blood glucose, serum insulin, triglycerides, total, low and high density lipoprotein cholesterol, as well as resting heart rate and blood pressure were also determined. RESULTS: Arbitrary subdivisions of the men were performed to obtain subgroups of low T and IGF-I values (lowest decile, borderlines 13.13 nmolal and 128.80 m mgal, respectively) and normal or blunted Dex. Signi®cant relationships with BMI, WHR or D, and abnormal metabolic and hemodynamic factors, usually with the exception of total and low density lipoprotein cholesterol, were then found in subgroups with different endocrine pro®les. 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 or IGF-I values. In addition, a group with isolated low Dex suppression, as well as another group without endocrine abnormalities, showed such relationships. These ®ndings suggest that, in men, obesity factors are associated with metabolic and hemodynamic complications with or without the presence of perturbations of hypothalamic-pituitaryadrenal axis (HPA) regulation or low T or growth hormone secretion. In order to generate hypotheses concerning the nature of the impact of the endocrine perturbations in abdominal obesity and its metabolic complications, path analyses were performed, testing different models. These models 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 metabolic perturbations). The results showed a satisfactory ®t (goodness-of-®t index: 0.945 ± 1.0) for the path diagrams: Dex ? TaIGF-I ? WHR or D ? insulin ? triglycerides with additional direct input of blunted Dex on insulin values (see Figure 1). With BMI as determinant, essentially the same results were found with the addition of a direct 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 determined endocrine variables. CONCLUSIONS: The results suggest that abdominal obesity with or without endocrine abnormalities exerts a major impact on abnormalities in metabolic and hemodynamic variables. Abdominal obesity seems to be dependent on endocrine abnormalities, which in turn show direct or indirect relationships to the metabolic and circulatory variables, including a direct pathway between HPA-axis perturbations and accumulation of total body fat as ind...

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“…This is occurring with, but also without evidence for HPA axis involvement. 23 This is in accordance with case-control studies of men with isolated growth hormone or testosterone de®ciencies, which show such abnormalities, which are nearly or totally normalized upon optimal hormonal substitutions. 21,22 In addition, both testosterone and growth hormone de®ciencies are risk factors for the development of diabetes cardiovascular disease and premature mortality.…”

Hypothalamic-Pituitary-Adrenal Axis Function: Relative Contributions of Perceived Stress and Obesity in Women

“…This dysregulated HPA axis pattern has been implicated in the observed relationship between cortisol secretion and risk factors for CVD and type 2 diabetes. 23,24 Low SES has been found to be associated with chronically elevated cortisol levels. 25,26 This social gradient may be a result of chronic stress associated with difficult living conditions or lifestyle behaviors, such as diet and physical inactivity.…”

Hypoglycemia, But Not Insulin, Acutely Decreases LH and T Secretion in Men

“…Additionally, decreased T levels in patients with the metabolic syndrome could be a direct consequence of perturbed function of the hypothalamic-pituitary-adrenal (HPA) axis (9,10). It is known that a counterregulatory response of the HPA axis, including cortisol release, to hypoglycemia begins at normoglycemic ranges in poorly controlled type 2 diabetes (11), and the epinephrine response during hypoglycemia is enhanced (12).…”