Hypothalamic-pituitary-adrenal activity in type 2 diabetes mellitus: role of autonomic imbalance

University of Milan, Milano, Lombardy, Italy
Metabolism (Impact Factor: 3.89). 08/2006; 55(8):1135-40. DOI: 10.1016/j.metabol.2006.04.010
Source: PubMed


Symptomatic diabetic neuropathy has been found to be associated with hypothalamus-pituitary-adrenal (HPA) axis hyperfunction, but no data are available about HPA activity in diabetic patients with asymptomatic autonomic imbalance. To evaluate HPA axis activity in patients with type 2 diabetes mellitus (T2DM) in relation to the presence or the absence of subclinical parasympathetic or sympathetic neuronal dysfunction, we performed an observational study on 59 consecutive type 2 diabetic patients without chronic complications and/or symptoms of neuropathy or hypercortisolism. The following were measured: serum cortisol at 08:00 am and at midnight (F8 and F24, respectively), post-dexamethasone suppression cortisol, 24-hour urinary free cortisol (UFC), and morning corticotropin (ACTH). Deep-breathing (DB) and LS (LS) autonomic tests were performed to assess the parasympathetic function; postural hypotension test was performed to evaluate sympathetic activity. Patients were subdivided into 4 groups: subjects with parasympathetic failure (group A), sympathetic failure (group B), both para- and sympathetic failure (group C), and without autonomic failure (group D). Hypothalamus-pituitary-adrenal activity was increased in group A compared with group D (UFC, 48.6 +/- 21.4 vs 21.6 +/- 9.8 microg/24 h, P < .0001; ACTH, 27.0 +/- 8.6 vs 15.7 +/- 5.7 pg/dL, P < .01; F8, 20.4 +/- 4.5 vs 13.6 +/- 3.8 microg/dL, P < .05; post-dexamethasone suppression cortisol, 1.2 +/- 0.4 vs 0.8 +/- 0.6 microg/dL, P < .05, respectively) and group B (UFC, 26.3 +/- 11.0 microg/24 h, P < .0001; ACTH, 19.9 +/- 8.0 pg/dL, P < .05). Regression analysis showed that UFC levels were significantly associated with the deep-breathing test (beta = -0.40, P = .004) and tended to be associated with the lying-to-standing test (beta = -0.26, P = .065), whereas body mass index, glycated hemoglobin, and duration of disease were not. Type 2 diabetic patients with asymptomatic parasympathetic derangement have increased activity of HPA axis, related to the degree of the neuronal dysfunction.

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    • "These individuals also present an abnormal feedback of the hypothalamus pituitary axis by sexual steroids, either due to reduced pituitary sensitivity or because of inefficient steroid transport into effector cells (Baccetti et al., 2002; Dong et al., 1991). These alterations have a direct effect on the overall testicular functioning, particularly on spermatogenesis, spermiogenesis and sperm metabolism (Ballester et al., 2004; Chiodini et al., 2006). Ultrastructural alterations in the testis (Cameron et al., 1985), sexual disorders such as erectile dysfunction (De Young et al., 2004), retrograde ejaculation, impotence or decreased libido (Schoeffling et al., 1963) and abnormal sperm parameters are problems commonly described in diabetic men (Bartak, 1979; Padron et al., 1984; Ranganathan et al., 2002). "
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    ABSTRACT: ndividuals with Diabetes Mellitus (DM) present marked reduction in sperm quality and higher DNA damage in spermatozoa, evidencing that this metabolic disorder impairs male fertility. These effects are related to defective testicular metabolic pathways and signaling, resulting in altered sperm metabolism. Spermatozoa metabolize several substrates to ensure energy supplies and any alteration in this feature compromises sperm quality. For ATP production, spermatozoa require substrate availability and the involvement of specific hexoses membrane carriers. DM is known to modulate the spermatozoa substrate consumption and/or production due to altered glycolytic behavior. In fact, glucose uptake and metabolism is highly deregulated in diabetic individuals. Herein, we present an overview of the implications of DM in sperm glucose uptake and metabolism. The understanding of these processes is essential to identify key mechanisms associated with DM-related male (in)fertility. Moreover, it may contribute to the development of therapeutics to counteract the dysfunction induced by DM in sperm metabolism.
    Full-text · Article · Aug 2014 · Molecular and Cellular Endocrinology
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    • "These alterations are probably due to reduced relative feedback sensitivity to glucocorticoids in different parts of the axis, changes in 11- beta hydroxysteroid dehydrogenase (11B-HSD) enzyme activity, and increased expression of corticotropin-releasing hormone in hypothalamus [4]. In this regard, it has been shown that there is an increase in cortisol secretion and adrenocortical hypertrophy in type 2 diabetic patients who suffer parasympathetic neuropathy, compared with type 1 diabetics with sympathetic neuropathy [5]. Thus, it seems that the degree of HPA axis dysfunction in diabetic patients is associated with the damage of neuronal pathway of the HPA axis and weakening response of glucocorticoids negative feedback [6]. "
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    ABSTRACT: Diabetes is one of the most common endocrine disorders characterized by hyperglycemia due to defects in insulin secretion, insulin function, or both. Causing dysfunction in the body general metabolism, diabetes-induced chronic hyperglycemia leads to alterations in those endocrine glands involved in regulating the body metabolism. In this line, the present study has been conducted to investigate the effects of type 1 and type 2 diabetes on the structural changes and hormonal output of the adrenal cortex in male Wistar rat. Eighteen male Wistar rats were divided into three groups including control, experimental type 1 diabetes (subcutaneous injection of 135 mg/kg alloxan) and experimental type 2 diabetes (8 weeks treatment with drinking water containing 10% fructose). Two months after the induction of both types of diabetes, the level of blood biochemical factors (glucose, insulin, cortisol, triglycerides, cholesterol, LDL, and HDL) were measured. Structural changes of the adrenal cortex were then evaluated, using stereological techniques. Serum biochemical analysis showed significant difference in the levels of glucose, triglycerides, insulin and cortisol in experimental groups, compared to the control. The results of structural alterations were also indicative of increase in adrenal cortex volume in both types of diabetes. Probably through increasing HPA axis activity, type1 diabetes-induced hyperglycemia leads to adrenal hypertrophy and increase the hormonal output of adrenal gland.
    Full-text · Article · Jan 2013 · Journal of Diabetes and Metabolic Disorders
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    • "Thus, special care must be taken in account when discussing the overall effects of DM in any relevant physiological condition because the spectrum of development stages of this disease is very complex [29]. It is also well known that DM alters the hypothalamic–pituitary–gonadal axis, which is responsible for some of the problems related to DM, such as impotence [16] [30]. Earlier studies reported elevated pituitary gonadotrophins in diabetic rats [31] and altered levels of LH and FSH [32] [33]. "
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    ABSTRACT: Diabetes Mellitus (DM) is one of the greatest public health threats in modern societies. Although during a few years it was suggested that DM had no significant effect in male reproductive function, this view has been challenged in recent years. The increasing incidence of DM worldwide will inevitably result in a higher prevalence of this pathology in men of reproductive age and subfertility or infertility associated with DM is expected to dramatically rise in upcoming years. From a clinical perspective, the evaluation of semen parameters, as well as spermatozoa DNA integrity, are often studied due to their direct implications in natural and assisted conception. Nevertheless, recent studies based on the molecular mechanisms beyond glucose transport in testicular cells provide new insights in DM-induced alterations in male reproductive health. Testicular cells have their own glucose sensing machinery that react to hormonal fluctuations and have several mechanisms to counteract hyper- and hypoglycemic events. Moreover, the metabolic cooperation between testicular cells is crucial for normal spermatogenesis. Sertoli cells (SCs), which are the main components of blood-testis barrier, are not only responsible for the physical support of germ cells but also for lactate production that is then metabolized by the developing germ cells. Any alteration in this tied metabolic cooperation may have a dramatic consequence in male fertility potential. Therefore, we present an overview of the clinical significance of DM in the male reproductive health with emphasis on the molecular mechanisms beyond glucose fluctuation and transport in testicular cells.
    Full-text · Article · Jan 2013 · Biochimica et Biophysica Acta
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