The hypoglycemia associated autonomic failure triggered by exercise in the patients with "brittle" diabetes and the strategy for prevention.

Exercise is a fundamental component of diabetes management. However, choosing inappropriate type or timing of exercise is associated with mild or severe hypoglycemia either during exercise or several hours after exercise. Several studies have shown that impaired counterregulatory responses triggers hypoglycemia. Therefore, in this investigation, we explored the appropriate intensity and time of exercise in patients with diabetes. The mechanisms of counterregulatory responses and hypoglycemia associated autonomic failure (HAAF), as well as the strategies for preventing episodes of hypoglycemia after exercise were also investigated. In this study, we obtained the following results: 1) High intensity interval exercise is more suitable for diabetic patients. 2) Morning exercise reduces nocturnal hypoglycemia risks compared with midday, afternoon and evening exercise. 3) Hypoglycemia can be prevented by dietary approach, reduction or suspension of insulin dose, use of mini dose glucagon, caffeine, mitigation methods, prediction algorithm, autonomic feedback controlled close-loop insulin delivery, real time continuous glucose monitoring. Based on these results we concluded that exercise may cause severe hypoglycemia or induce blunted response in patients with diabetes. For Diabetes Mellitus (DM) patients, the intensity and time of exercise influence the occurrence of hypoglycemia. This review summarizes the clinical characteristics of different types of exercises and time of exercise that can be potentially used to educate and guide patients regarding the role of exercise in standard of care.

Possible Ameliorative Effect of Ivabradine on the Autonomic and Left Ventricular Dysfunction Induced by Doxorubicin in Male Rats.

Heart failure is a common adverse effect associated with doxorubicin treatment. The aim of this study is to investigate the effect of ivabradine treatment on doxorubicin-induced heart failure in conscious rats. Rats were treated with doxorubicin (2.5 mg/kg/d) or ivabradine (10 mg/kg/d) alone or along with doxorubicin injections. Changes in heart rate variability (HRV), baroreflex sensitivity, left ventricular (LV) function, serum cardiac troponin T, and cardiac histological features were taken as index parameters for the development of heart failure. Ivabradine significantly reduced the elevated heart rate; normalized the parameters of LV function, dP/dtmax and the relaxation time constant (Tau); reduced the elevated serum level of cardiac troponin T; and minimized the cardiac structural abnormalities in doxorubicin-treated rats. Moreover, ivabradine significantly increased the diminished time domain parameters of HRV, SDNN and rMSSD, and decreased the elevated low frequency power and the low frequency/high frequency while having no effect on the reduced high frequency power. Consistently, ivabradine significantly lowered the elevated baroreflex sensitivity measured by sodium nitroprusside. In conclusion, ivabradine ameliorated the LV dysfunction induced by doxorubicin. Moreover, ivabradine increased the overall HRV and restored the autonomic balance by reducing the sympathetic over activation. Therefore, ivabradine may have a possible therapeutic potential against doxorubicin-induced heart failure.

Position of draining venous cannula in extracorporeal membrane oxygenation for respiratory and respiratory/circulatory support in adult patients.

Extracorporeal membrane oxygenation (ECMO) is used in critically ill patients with severe pulmonary and/or cardiac failure. Blood is drained from the venous system and pumped through a membrane oxygenator where it is oxygenated. For pulmonary support, the blood is returned to the patient via a vein (veno-venous ECMO) and for pulmonary/circulatory support it is returned via an artery (veno-arterial ECMO).Veno-venous ECMO can be performed either with a single dual-lumen cannula or with two separate single-lumen cannulas. If the latter is chosen, flow direction can either be from the inferior caval vein (IVC) to the right atrium or the opposite. Earlier research has shown that drainage from the IVC yields less recirculation and therefore the IVC to right atrium route has become the standard in most centers for veno-venous ECMO with two cannulas. However, recent research has shown that recirculation can be minimized using a multistage draining cannula in the optimal position inserted via the right internal jugular vein and with blood return to the femoral vein. The clinical results with this route are excellent.In veno-arterial ECMO the most common site for blood infusion is the femoral artery. If venous blood is drained from the IVC, the patient is at risk of developing a dual circulation (Harlequin syndrome, North-South syndrome, differential oxygenation) meaning a poor oxygenation of the upper part of the body, while the lower part has excellent oxygenation. By instead draining from the superior caval vein (SVC) via a multistage cannula inserted in the right internal jugular vein this risk is neutralized.In conclusion, the authors argue that draining blood from the SVC and right atrium via a multistage cannula inserted in the right internal jugular vein is equal or better than IVC drainage both in veno-venous two cannula ECMO and in veno-arterial ECMO with blood return to the femoral artery.

Improving Managers' Psychophysical Well-Being: Effectiveness of Respiratory Sinus Arrhythmia Biofeedback.

High work stress has been consistently associated with disturbed autonomic balance, specifically, lowered vagal cardiac control and increased sympathetic activity, which may lead to increased cardiovascular risk. Stress management procedures have been proposed to reduce autonomic dysfunctions related to work stress in different categories of workers exposed to heightened work demands, while a limited number of studies addressed this issue in managers. The present study was aimed at evaluating the effectiveness of a respiratory sinus arrhythmia (RSA) biofeedback (BF) intervention on psychological and physiological outcomes, in managers with high-level work responsibilities. Thirty-one managers leading outstanding private or public companies were randomly assigned to either a RSA-BF training (RSA-BF; N = 16) or a control group (N = 15). The RSA-BF training consisted of five weekly 45 min sessions, designed to increase RSA, whereas controls had to provide a daily stress diary once a week. After the training, managers in both groups reported reduced heart rate at rest, lower anxiety levels and improvement in health-related quality of life. More importantly, managers in the RSA-BF group showed increased vagal control (as indexed by increased RSA), decreased sympathetic arousal (as indexed by reduced skin conductance and systolic blood pressure) and lower emotional interferences, compared to managers in the control group. Results from this study showed that RSA-BF training was effective in improving cardiac autonomic balance at rest. Moreover, findings from this study underline the effectiveness of biofeedback in reducing psychophysiological negative outcomes associated with stress in managers.

The Selective Cardiac Late Sodium Current Inhibitor GS-458967 Suppresses Autonomically Triggered Atrial Fibrillation in an Intact Porcine Model.

INTRODUCTION: The anti-atrial fibrillation (AF) effects of GS-458967 (GS-967), a selective, potent inhibitor of cardiac late Na(+) current (I(Na)), were evaluated in a novel model of AF induction that does not require electrical stimuli. METHODS AND RESULTS: In 6 closed-chest anesthetized pigs, AF was induced by intrapericardial acetylcholine (1 mL of 100 mM solution) followed within 1 minute by epinephrine (20 µg/kg, i.v., bolus over 1 min). Effects of GS-967 (0.4 mg/kg, i.v., infused over 30 min) on inducibility and duration of AF were analyzed. Administration of acetylcholine followed by epinephrine elicited spontaneous AF that persisted for 12.03 ± 1.22 minutes (mean ± SEM) in all 6 pigs. Following GS-967, AF did not occur in 5 of 6 pigs when plasma concentration was 383 ± 150 nM. In the single animal in which AF could still be induced, the arrhythmia lasted 6.3 minutes. Partial return of AF inducibility occurred in 2 of 6 animals at 90 minutes, when plasma concentration of GS-967 was 228 ± 35 nM. GS-967 reduced the QT interval (P = 0.004), consistent with cardiac late I(Na) inhibition, but did not affect heart rate, mean arterial pressure, QRS duration, or PR interval. Epinephrine infusion alone, tested in a separate group (N = 6), did not provoke AF. CONCLUSION: Selective cardiac late I(Na) inhibition with GS-967 suppresses spontaneous induction of AF in a novel model that does not require provocative electrical stimuli. Because this mode of action has only a mild on effect on contractility, it offers an advantage over contemporary anti-AF agents, which can have negative inotropic actions.

Assessment of the relationship between hypoglycaemia awareness and autonomic function following islet cell/pancreas transplantation.

BACKGROUND: This study assesses the autonomic function of patients who have regained awareness of hypoglycaemia following islet cell or whole pancreas transplant. METHODS: Five patients with type 1 diabetes and either islet cell (four patients) or whole pancreas (one patient) transplant were assessed. These patients were age-matched and gender-matched to five patients with type 1 diabetes without transplant and preserved hypoglycaemia awareness and five healthy control participants without diabetes. All participants underwent (i) a battery of five cardiovascular autonomic function tests, (ii) quantitative sudomotor axonal reflex testing, and (iii) sympathetic skin response testing. RESULTS: Total recorded hypoglycaemia episodes per month fell from 76 pre-transplant to 13 at 0- to 3-month post-transplant (83% reduction). The percentage of hypoglycaemia episodes that patients were unaware of decreased from 97 to 69% at 0-3 months (p < 0.001, Fisher's exact test) and to 20% after 12 months (p < 0.0001, Fisher's exact test). This amelioration was maintained at the time of testing (mean time: 4.1 years later, range: 2-6 years). Presence of significant autonomic neuropathy was seen in all five transplanted patients (at least 2/3 above modalities abnormal) but in only one of the patients with diabetes without transplantation. CONCLUSIONS: The long-term maintenance of hypoglycaemia awareness that returns after islet cell/pancreas transplantation in patients with diabetes is not prevented by significant autonomic neuropathy and is better accounted for by other factors such as reversal of hypoglycaemia-associated autonomic failure.

Unraveling the mechanism of neuroprotection of curcumin in arsenic induced cholinergic dysfunctions in rats.

Earlier, we found that arsenic induced cholinergic deficits in rat brain could be protected by curcumin. In continuation to this, the present study is focused to unravel the molecular mechanisms associated with the protective efficacy of curcumin in arsenic induced cholinergic deficits. Exposure to arsenic (20mg/kg body weight, p.o) for 28 days in rats resulted to decrease the expression of CHRM2 receptor gene associated with mitochondrial dysfunctions as evident by decrease in the mitochondrial membrane potential, activity of mitochondrial complexes and enhanced apoptosis both in the frontal cortex and hippocampus in comparison to controls. The ultrastructural images of arsenic exposed rats, assessed by transmission electron microscope, exhibited loss of myelin sheath and distorted cristae in the mitochondria both in the frontal cortex and hippocampus as compared to controls. Simultaneous treatment with arsenic (20mg/kg body weight, p.o) and curcumin (100mg/kg body weight, p.o) for 28 days in rats was found to protect arsenic induced changes in the mitochondrial membrane potential and activity of mitochondrial complexes both in frontal cortex and hippocampus. Alterations in the expression of pro- and anti-apoptotic proteins and ultrastructural damage in the frontal cortex and hippocampus following arsenic exposure were also protected in rats simultaneously treated with arsenic and curcumin. The data of the present study reveal that curcumin could protect arsenic induced cholinergic deficits by modulating the expression of pro- and anti-apoptotic proteins in the brain. More interestingly, arsenic induced functional and ultrastructural changes in the brain mitochondria were also protected by curcumin.

Hodgkin lymphoma and hypothermia: case report and review of the literature.

We report the development of hypothermia in a patient with Hodgkin lymphoma which resolved with chemotherapy administration. A review of the literature revealed 16 previous reports of hypothermia in patients with Hodgkin lymphoma. Overall prognosis seems to be unfavorable. To the best of our knowledge this is the first report of hypothermia in a patient with Hodgkin lymphoma transforming from chronic lymphocytic leukemia (Richter's syndrome). A possible pathophysiology could be paraneoplastic autonomic neuropathy. Physicians should be aware that Hodgkin lymphoma can present with hypothermia and should carefully monitor newly diagnosed patients with advanced disease for this complication. Likewise, patients with Hodgkin lymphoma who develop hypothermia should be screened for signs of autonomic neuropathy.

Impact of early detection and treatment of diabetes on the 6-year prevalence of cardiac autonomic neuropathy in people with screen-detected diabetes: ADDITION-Denmark, a cluster-randomised study.

AIMS/HYPOTHESIS: There is limited evidence on how multifactorial treatment improves outcomes of diabetes when initiated in the lead time between detection by screening and diagnosis in routine clinical practice. Cardiac autonomic neuropathy (CAN) in people with diabetes indicates widespread damage to the autonomic nervous system, which may severely affect health and quality of life. We examined effects of early detection and subsequent intensive treatment of type 2 diabetes in primary care on the prevalence of CAN at the 6-year follow-up examination in a pragmatic cluster-randomised parallel group trial. METHODS: One hundred and ninety general practices were randomised to deliver either intensive multifactorial treatment (IT) or routine care (RC) as recommended by national guidelines to patients with type 2 diabetes, identified through a stepwise screening programme in the primary care setting. 1533 people (IT, n = 910; RC, n = 623) were identified and included. At the 6-year follow-up examination, measures of CAN were applied in an unselected subsample of 777 participants using heart rate variability analysis and standard tests of CAN. RESULTS: At the 6-year follow-up examination, the prevalence of early CAN was 15.1% in the RC group and 15.5% in the IT group, while manifest CAN was present in 7.1% and 7.3%, respectively. We found no statistically significant effect of intensive treatment on the prevalence of CAN compared with routine care. CONCLUSIONS/INTERPRETATION: In the Danish arm of the ADDITION Study, signs of CAN were highly prevalent 6 years after a screening-based diagnosis of type 2 diabetes. Intensive multifactorial treatment did not significantly affect the prevalence of CAN compared with routine care. However, at follow-up the level of medication was also high in the RC group.

Emerging drugs for autonomic dysfunction in Parkinson's disease.

INTRODUCTION: Autonomic dysfunction, including orthostatic hypotension (OH), sialorrhea, sexual dysfunction, urinary dysfunction and constipation is a common feature of Parkinson's disease (PD). Even though its treatment has been recognized as a major unmet need in PD, there is a paucity of clinical trials to assess their treatment. AREAS COVERED: Evidence about the efficacy and safety of available treatments for autonomic dysfunction is summarized. Potential targets for upcoming therapies are then discussed in light of what is currently known about the physiopathology of each disorder in PD. Proof-of-concept trials and circumstantial evidence about treatments for autonomic dysfunction as well as upcoming clinical trials are discussed. Finally, critical aspects of clinical trials design are considered. EXPERT OPINION: Botulinum toxin (BTX) or glycopyrrolate might be used for sialorrhea whereas macrogol could be useful in constipation. There is preliminary evidence suggesting that fludrocortisone, domperidone, droxidopa or fipamezole may be effective for the treatment of OH. Tropicamide, clonidine or radiotherapy are under development for sialorrhea. Sildenafil may be effective for the treatment of erectile dysfunction; BTX or behavioral therapy for urinary incontinence and lubiprostone and probiotics for constipation. Sound clinical trials are needed in order to allow firm evidence-based recommendations about these treatments.

A randomized controlled trial of exercise training on cardiovascular and autonomic function among renal transplant recipients.

BACKGROUND: There are conflicting data regarding the effects of renal transplantation (RT) on uraemic autonomic dysfunction. Moreover, no study has examined the impact of physical training on the cardiac autonomic function in RT patients. Thus, we studied the effects of exercise training on heart rate variability (HRV) and arterial baroreflex sensitivity (BRS), which are sensitive markers of cardiac autonomic outflow, in RT recipients. METHODS: Eleven patients (Exercise group-aged 52.1 ± 5.6 years) were studied before and after 6 months of exercise training. Twelve age- and sex- matched RT patients (Sedentary) and 12 healthy sedentary individuals (Healthy), who remained untrained, served as controls. At baseline and follow-up, all the subjects underwent cardiopulmonary exercise testing for the evaluation of peak oxygen consumption (VO2peak), a tilt test for the evaluation of BRS and baroreflex effectiveness index (BEI) and an ambulatory 24-h Holter monitoring for time- and frequency-domain measures of HRV. RESULTS: In the exercise group, VO2peak increased by 15.8% (P < 0.05) and all depressed HRV and BRS indices were significantly improved after training. Specifically, the standard deviation of all normal-to-normal (NN) intervals (SDNN) significantly increased by 92.5%, the root-mean-square of the differences between consecutive NN intervals by 45.4%, the percentage value of NN50 count by 58.2%, the high-frequency by 74.8% and low-frequency spectral power by 41.6%, BRS by 43.7% and BEI by 57.3%. None of the variables studied was altered over time in either control group. CONCLUSIONS: The increased cardiorespiratory fitness by exercise training was associated with an improved BRS function and a modification of the sympathovagal control of HRV towards a persistent increase in parasympathetic tone. These alterations may lead to a better cardiovascular prognosis in RT recipients.

Sleep disordered breathing improvement prevents worsening of autonomic dysfunction in children with Down syndrome.

BACKGROUND: Resolution of sleep disordered breathing (SDB) in typically developing children normalises heart rate variability (HRV), a measure of autonomic control, to that of non-snoring controls. Children with Down Syndrome (DS) have dampened heart rate variability (HRV) but the effect of treatment is not known. To assess the effect of improvement of SDB on autonomic control we compared HRV in children with DS whose SDB improved over 2 y, to those whose SDB did not improve. METHODS: 24 children (3-19 y) had a baseline and follow-up polysomnographic study 2 y later. Improved SDB was defined as a reduction in obstructive apnea hypopnea index (OAHI) to ≤ 50% of baseline. Children were grouped into Improved (n = 12) and Unimproved (n = 12). Power spectral analysis of the ECG determined low frequency (LF), high frequency (HF) power and the LF/HF ratio. Seven children in the Improved and 2 in the Unimproved group were treated following the baseline study. RESULTS: In the Unimproved group at follow-up, LF power was lower compared to baseline during N3 and Total Sleep (p < 0.05 for both). HF power was lower during REM (p < 0.05). HRV remained unchanged between studies in the Improved group. CONCLUSION: Autonomic control worsened as indicated by lower LF and HF power in children whose SDB was not improved. In contrast, in those children with improved SDB, autonomic control remained the same, suggesting improvement in SDB severity prevents further worsening of autonomic control in children with DS.

Blockage of the afferent sensitive pathway prevents sympathetic atrophy and hemodynamic alterations in rat portal hypertension.

BACKGROUND AND AIMS: Portal hypertension causes arterial vasodilation and sympathetic atrophy in the splanchnic area. We aimed to demonstrate a relationship between hemodynamic alterations and sympathetic atrophy by investigating a pathway from sensitive afferent signals to mesenteric sympathetic ganglia. METHODS: Experiments were conducted in sham and portal vein ligated (PVL) adult and neonatal rats treated with vehicle or capsaicin. Hemodynamic parameters, and immunohistochemistry, immunofluorescence and Western blot of different tissues were analysed. RESULTS: cFos expression in the brain supraoptic nuclei was used to confirm abrogation of the afferent signal in capsaicin-treated PVL rats (effectively afferent blocked). Neonatal and adult PVL afferent blocked rats showed simultaneous prevention of hemodynamic alterations and sympathetic atrophy (measured by tyrosine hydroxylase expression in nerve structures of splanchnic vasculature). Not effectively afferent blocked rats showed none of these effects, behaving as PVL vehicle. All capsaicin treated animals presented loss of calcitonin gene-related peptide in superior mesenteric artery and ganglia, whereas neuronal nitric oxide synthase remained unaffected. Neuronal markers semaphorin-3A, nerve growth factor, its precursor and p75 neurotrophic receptor, were significantly over-expressed in the PVL sympathetic ganglia compared with sham, but not in effectively afferent blocked rats. Semaphorin-3A staining in mesenteric ganglia co-localized with vesicular acetylcholine transporter, but not with adrenergic, nitrergic and sensory axons, suggesting that semaphorin-3A might originate in preganglionic neurons. CONCLUSION: These results indicate that the nervous system has a central role in the genesis of the circulatory abnormalities of portal hypertension, and support that mesenteric sympathetic atrophy contributes to splanchnic arterial vasodilation.

ß-Blockers for traumatic brain injury: A systematic review and meta-analysis.

BACKGROUND: Paroxysmal sympathetic hyperactivity (PSH) and catecholamine surge, which are associated with poor outcome, may be triggered by traumatic brain injury (TBI).ß Adrenergic receptor blockers (ß-blockers), as potential therapeutic agents to prevent paroxysmal sympathetic hyperactivity and catecholamine surge, have been shown to improve survival after TBI. The principal aim of this study was to investigate the effect of ß-blockers on outcomes in patients with TBI. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, EMBASE, and Cochrane Library databases from inception to September 25, 2020, for randomized controlled trials, nonrandomized controlled trials, and observational studies reporting the effect of ß-blockers on the following outcomes after TBI: mortality, functional measures, and cardiopulmonary adverse effects of ß-blockers (e.g., hypotension, bradycardia, and bronchospasm). With use of random-effects model, we calculated pooled estimates, confidence intervals (CIs), and odds ratios (ORs) of all outcomes. RESULTS: Fifteen studies with 12,721 patients were included. Exposure to ß-blockers after TBI was associated with a significant reduction in adjusted in-hospital mortality (OR, 0.39; 95% CI, 0.30-0.51; I2 = 66.3%; p < 0.001). ß-Blockers significantly improved the long-term (≥6 months) functional outcome (OR, 1.75; 95% CI, 1.09-2.80; I2 = 0%; p = 0.02). Statistically significant difference was not seen for cardiopulmonary adverse events (OR, 0.91; 95% CI, 0.55-1.50; I2 = 25.9%; p = 0.702). CONCLUSION: This meta-analysis demonstrated that administration of ß-blockers after TBI was safe and effective. Administration of ß-blockers may therefore be suggested in the TBI care. However, more high-quality trials are needed to investigate the use of ß-blockers in the management of TBI. LEVEL OF EVIDENCE: Systematic review and meta-analysis, level III.

Neuroprotective effect of herpes simplex virus-mediated gene transfer of erythropoietin in hyperglycemic dorsal root ganglion neurons.

We examined the efficacy of herpes simplex virus vector-mediated gene transfer of erythropoietin in preventing neuropathy in mouse model of streptozotocin-diabetes. A replication-incompetent herpes simplex virus vector with erythropoietin under the control of the human cytomegalovirus promoter (vector DHEPO) was constructed. DHEPO expressed and released erythropoietin from primary dorsal root ganglion neurons in vitro, and following subcutaneous inoculation in the foot, expressed erythropoietin in dorsal root ganglion neurons in vivo. At 2 weeks after induction of diabetes, subcutaneous inoculation of erythropoietin prevented the reduction in sensory nerve amplitude characteristic of diabetic neuropathy measured 4 weeks later, preserved autonomic function measured by pilocarpine-induced sweating, and prevented the loss of nerve fibres in the skin and reduction of neuropeptide calcitonin gene-related peptide in the dorsal horn of spinal cord of the diabetic mice. We further investigated whether vector-mediated local expression of erythropoietin in dorsal root ganglion neurons can protect in vivo as well as in vitro hyperglycemia-induced axonal degeneration. Our findings show that the AKT/GSK-3beta dependent pathway plays an important role in mediating the protection of erythropoietin against diabetic neuropathy. Herpes simplex virus-mediated transfer of erythropoietin to dorsal root ganglia may prove useful in treatment of diabetic neuropathy.

Autonomic changes in preoperative uncomplicated diabetic patients with postural changes.

Diabetic autonomic neuropathy is a critical complication frequently encountered in anaesthetic and surgical practice. Power spectral analysis is a noninvasive tool for monitoring frequency analysis of heart rate variability (HRV) and autonomic control of the heart. This study examined HRV changes in preoperative diabetic patients without overt signs of autonomic dysfunction and in matched controls (n=18 per group). HRV values at -15 degrees, 0 degrees, 15 degrees, 45 degrees and sitting positions were compared between groups and for each position. HRV in diabetic patients was lower than in controls at all positions (absolute units). Low-frequency power (normalized units) and the low-frequency/high-frequency ratio increased significantly at 45 degrees and in sitting positions in controls but not in diabetic patients. Pre-existing autonomic derangements in diabetic patients without overt clinical symptoms can be aggravated by high-degree tilting or sitting positions. Consequently, great care should be taken during the intra- and perioperative management of these patients.

[Programs for better health of individuals exposed to increased occupational risk].

The article deals with problems of optimizing sanatorium-and-spa programs to better health in workers exposed to vibration, through using panto-magnesium pearl baths. Examinations covered 49 individuals exposed to local vibration at work, who underwent health programs including magnetotherapy, manual massage and exercise therapy. The authors conclude that maximal effect of improved life quality was seen after panto-magnesium gas baths course auxiliary to the programs.

Impact of body fat mass extent on cardiac autonomic alterations in women.

BACKGROUND: Obesity has been associated with significant abnormalities of the cardiac autonomic regulation. However, the precise impact of increasing body weight on cardiac autonomic function and the metabolic and hormonal contributors to these changes are presently unclear. The aim of our study was to explore in subjects with increasing values of body mass index (BMI) the alterations of cardiac autonomic function and to establish the potential role of various metabolic and hormonal contributors to these alterations. MATERIALS AND METHODS: We investigated time and frequency domain heart rate variability (HRV) parameters taken from 24-h Holter recordings, and several anthropometric, metabolic and hormonal parameters (plasma glucose, insulin, triglycerides, free fatty acids, leptin and adiponectin) in 68 normoglycaemic and normotensive women (mean age of 40 +/- 3 years), subdivided according to their BMI into 15 normal body weight (controls), 15 overweight, 18 obese and 20 morbidly obese. RESULTS: Heart rate was increased and HRV was decreased in the morbidly obese group as compared with controls. In overall population, a negative association linked body fat mass (FM) to HRV indices. None of the metabolic and hormonal parameters were significantly related to the HRV indices, after they were adjusted for the body FM. CONCLUSIONS: Morbidly obese, normoglycaemic and normotensive young women have increased HR and low HRV, indicating an abnormal cardiac autonomic function and representing a risk factor for adverse cardiovascular events. A decrease of HRV parameters is associated with a progressive increase of body FM. Other metabolic and hormonal factors, characterising obesity, do not show an independent influence on these HRV alterations.