Relationship between plasma aldosterone levels and arterial stiffness parameters in hypertensive patients with subclinical vascular damage.

Purpose: Aldosterone plays important role in cardiovascular damage. Aim was to evaluate arterial subclinical damage through arterial stiffness parameters in patients with Essential Hypertension (EH) and Primary Aldosteronism (PA). Methods: From 2018 to 2019 we consecutively enrolled 82 subjects (37 males and 45 women), distinguished in two groups: 60 EH [systolic blood pressure (SBP) 143.4 ± 16.7 mmHg, diastolic blood pressure (DBP) 89.5 ± 12.1 mmHg] and 22 PA (SBP 149 ± 19.5 mmHg, DBP 92.7 ± 12.4 mmHg) [5 with aldosterone-secreting adrenal adenoma(APA), 17 with idiopathic aldosteronism(IHA)]; 40 matched normotensive subjects (NS) were enrolled (SBP 109.7 ± 6.2 mmHg, DBP 71.3 ± 9.7 mmHg). We used non-invasive applanation tonometer to acquire pressure waveform. Results: PA patients showed higher µ-Albuminuria (UAE) (65.7 ± 11.0mg/24 h) than EH and NS (21.5 ± 7.0 mg/24 h and 21.5 ± 7.0 mg/24 h, respectively); APA group showed increased levels of arterial stiffness index (11.7 ± 4.8 m/s; p < 0.02) compared to EH subjects (8.3 ± 3 m/s) and NS subjects (7.2 ± 1.7 m/s) as well as higher carotid intima-media thickness (c-IMT); APA patients showed significant reduction of subendocardial viability ratio (SEVR) and travel time of the reflected waves (TI) respect EH and NS. PA groups showed high percentage of augmented "worsening age" (60%), compared to EH (38%) and NS (37%). PAC was positively correlated with Arterial Stiffness Index. Performing multiple linear regression analysis (evaluating anthropometric and biochemical parameters), we found UAE as predictor of Augmentation Index, Arterial Stiffness Index and Travel Time of reflected waves in the enrolled population. Conclusion: PA patients showed higher cardiovascular subclinical damage respect to EH; UAE excretion had significant correlation with aldosterone, resulting best marker of subclinical vascular remodeling.

Work-related stress and cortisol levels: is there an association? Results of an observational study.

OBJECTIVE: Chronic exposure to work-related stress (WRS) stimulates the hypothalamic-pituitary-adrenal (HPA) axis to increase glucocorticoid secretion, including cortisol, and these hormones can be measured both in serum and urine. The Health Safety Executive Toolkit (HSE) questionnaire is used to assess WRS risk objectively. The scope of our study is to investigate whether serum or urinary cortisol levels could be used as alternative objective indicators of WRS, specifically in those subjects who are chronically exposed to it. PATIENTS AND METHODS: 130 patients (75 males and 55 females, mean age 47.7 ± 11.3 years) were evaluated at a specialized Centre for Secondary Hypertension, where both their serum (8 AM) and 24-hours urinary cortisol were measured and they were asked to complete two questionnaires: one questionnaire to collect data about their socio-demographic and job characteristics, and the HSE questionnaire to evaluate WRS. RESULTS: Multiple linear regression analysis showed an association of urinary cortisol with several variables: tobacco smoke (ß = 69.6; p = 0.003); female gender (ß = -37.3; p = 0.041); exposure to physical risks (ß = 51.8; p = 0.032); control score (ß = -22.7; p = 0.039); role score (ß= 39.3; p = 0.020). Age was the only variable associated with serum cortisol levels (ß = -3.6; p = 0.042). CONCLUSIONS: Urinary cortisol levels, but not serum levels, are associated with variables linked to WRS (score control and role) and to socio-demographic variables, namely gender and tobacco smoke. Thus, urinary cortisol can be considered a useful and non-invasive biological indicator to quantify WRS.

Vitreous and plasma changes of endothelin-1, adrenomedullin and vascular endothelium growth factor in patients with proliferative diabetic retinopathy.

OBJECTIVE: To assess vitreous and plasma changes of vascular endothelial growth factor A (VEGF-A), adrenomedullin (ADM) and endothelin-1 (ET-1) in proliferative diabetic retinopathy (PDR). PATIENTS AND METHODS: 9 patients with PDR in type 2 diabetes (T2DM) and 11 age-matched non-diabetic patients were enrolled. The levels of VEGF-A, ADM and ET-1 were measured using an enzyme (ELISA) and a radioimmunoassay (RIA) both in vitreous and plasma samples. RESULTS: Vitreous ADM and VEGF-A levels were significantly higher in PDR patients (p=0.04 and p=0.02), whereas no differences were found in ET-1 levels (p=0.29). Plasma ADM levels were significantly higher in the PDR group (p<0.01), whereas no significant differences were found in the plasma ET-1 and VEGF-A levels (p=0.30 and p=0.37). The ADM vitreous/plasma ratio was significantly reduced in PDR group. CONCLUSIONS: The role of ET-1 in advanced PDR is still controversial; it has been supposed a role limited to induce hypoxic state and promote angiogenesis in the early phases. Once the neo-angiogenic process starts, other mediators are mainly involved as VEGF and ADM. Our findings suggest that ADM is an important marker of advanced PDR as well as VEGF. Conversely, ET-1 is not significantly involved in the advanced stage of PDR.

Enhanced Soluble Serum CD40L and Serum P-Selectin Levels in Primary Aldosteronism.

Primary aldosteronism (PA) is one of the most frequent forms of secondary hypertension, associated with atherosclerosis and higher risk of cardiovascular events. Platelets play a key role in the atherosclerotic process. The aim of the study was to evaluate the platelet activation by measuring serum levels of soluble CD40L (sCD40L) and P-selectin (sP-selectin) in consecutive PA patients [subgroup: aldosterone-secreting adrenal adenoma (APA) and bilateral adrenal hyperplasia (IHA)], matched with essential hypertensive (EH) patients. The subgroup of APA patients was revaluated 6-months after unilateral adrenalectomy. In all PA group, we measured higher serum levels of both sP-selectin (14.29±9.33 pg/ml) and sCD40L (9.53±4.2 ng/ml) compared to EH patients (9.39±5.3 pg/ml and 3.54±0.94 ng/ml, respectively; p<0.001). After removal of APA, PA patients showed significant reduction of blood pressure (BP) values, plasma aldosterone (PAC) levels and ARR-ratio, associated with a significant reduction of sP-selectin (16.74±8.9 pg/ml vs. 8.1±3.8 pg/ml; p<0.01) and sCD40L (8.6±1 ng/ml vs. 5.24±0.94 ng/ml; p<0.001). In PA patients, we found a significant correlation between sP-selectin and sCD40L with PAC (r=0.52, p<0.01; r=0.50, p<0.01, respectively); this correlation was stronger in APA patients (r=0.54; p<0.01 r=0.63; p<0.01, respectively). Our results showed that PA is related to platelet activation, expressed as higher plasma values of sCD40L and sP-selectin values. Surgical treatment and consequent normalization of aldosterone secretion was associated with significant reduction of sCD40L and sP-selectin values in APA patients.

Epicardial Fat Thickness and Primary Aldosteronism.

Primary aldosteronism (PA) is associated with increased cardiovascular risk and left ventricle (LV) changes. Given its peculiar biomolecular and anatomic properties, excessive epicardial fat, the heart-specific visceral fat depot, can affect LV morphology. Whether epicardial fat can be associated with aldosterone and LV mass (LVM) in patients with PA is unknown. We performed ultrasound measurement of the epicardial fat thickness (EAT) in 79 consecutive newly diagnosed patients with PA, 59 affected by bilateral adrenal hyperplasia (IHA), 20 aldosterone-producing adenoma (APA), and 30 patients with essential hypertension (low renin hypertension) (EH). The 3 groups did not differ by age, sex distribution, body mass index (BMI), waist circumference (WC), or blood pressure values. EAT showed a trend of increase in both APA and IHA groups when compared to patients with EH (8.3±1.8 vs. 7.9±1.3 vs. 7.8±2 mm, respectively). EAT was significantly correlated with indexed LVM in the IHA group (r=0.35, p<005), better than BMI or WC were. Interestingly, EAT was highly associated with plasma aldosterone concentrations (PAC) and PAC/plasma renin activity (PRA) (PAC/PRA) in the APA group (p=0.58, p=0.37, p<0.01, for both), whereas BMI and WC were not. EAT was also correlated with PRA in the IHA group (p=-0.28, p<0.05). Our study indicates a novel and interesting interaction of EAT with PA, independent of obesity, abdominal fat and blood pressure control. EAT can locally affect LVM, at least in patients with IHA. Further studies in larger population will be required to confirm these findings.

Association between -308 G/A TNF-α polymorphism and appendicular skeletal muscle mass index as a marker of sarcopenia in normal weight obese syndrome.

BACKGROUND AND AIM: Normal weight obese (NWO) syndrome is characterized by normal body mass index (BMI), but high amount of fat mass and reduced lean mass. We evaluated allelic frequency of the G/A -308 TNF-α polymorphism and prevalence of sarcopenia in NWO. METHODS: We enrolled 120 Italian healthy women, distinguished into 3 groups: normal weight (NW); NWO, and preobese-obese (PreOB/OB) and evaluated anthropometric parameters, body composition by dual X-ray absorptiometry, blood tests, and genotyping of G/A -308 TNF-α polymorphism. RESULTS: We found a positive association between sarcopenic obesity and -308 TNF-α polymorphism. All obese women were sarcopenic and were no carrier of mutation (G/G). Among all G/G, NWO showed significant differences in lean mass and total body lean mass (TBLean) with respect to NW and PreOB/OB (P < 0.001). Regarding appendicular skeletal muscle mass index values, 4.21% of NW were sarcopenic (50% G/G and 50% G/A); the same percentage was observed in NWO subjects (100% G/G). Moreover, 2.10% of PreOB/OB were sarcopenic and all were G/G. CONCLUSION: Our study suggests that TNF-α polymorphism contributes to sarcopenic obesity susceptibility, in association with body composition. This is the first study that shows the importance of TNF-α polymorphism to determine TBLean variation in NWO syndrome.

A giant hemorragic adrenal pseudocyst: contrast-enhanced examination (CEUS) and computed tomography (CT) features.

INTRODUCTION: Adrenal pseudocysts are rare cystic masses that arise from the adrenal gland and which are usually non-functional and asymptomatic. We report a rare case of a giant hemorrhagic adrenal pseudocyst presenting with abdominal pain and we discussed the radiological features. PRESENTATION OF CASE: A 75 year old man was admitted with acute abdominal pain post mild-trauma. Computed tomography (CT) of abdomen revealed a hemorrhagic mass measuring 18 cm located in the right suprarenal region, displacing the right kidney and liver. He subsequently underwent to contrast enhancement ultrasound (CEUS), which showed features suggestive for hemorrhagic adrenal pseudocyst. A complete endocrine working didn't show any hormonal hypersecretion. The patient underwent laparotomy and right adrenal mass was excised. Histological examination revealed giant hemorrhagic adrenal pseudocyst. The abdominal pain resolved after surgery. CONCLUSIONS: to the best our knowledge, this is the first case studied with CEUS reported in the literature.

Adrenal ganglioneuroma incidentally discovered in a patient with dysuria: a case report.

A case of adrenal ganglioneuroma incidentally discovered during an abdominal ultrasound examination in a 26 year-old woman patient with recurrent episodes of dysuria. After a diagnostic work-up with laboratory and abdomen CT scan, the patient uderwent a laparotomic removal of the adrenal lesion. Histopathological examination of the adrenal mass confirmed the diagnosis.

Primary aldosteronism due to adrenocortical adenoma with concurrent ileum carcinoid tumor: case report.

Primary aldosteronism (PA) with synchronous carcinoid syndrome is extremely rare occurrence. In this article, we describe a case of PA due to adrenocortical adenoma ("aldosteronoma") and concurrent malignant carcinoid tumor of ileum. The patient was treated with synchronous right adrenalectomy and resection of the ileum. This case is an example of concomitant presence of two types of tumors, effectively managed surgically. We report a case of a nonclassical form of multiple endocrine neoplasia type 1 (MEN 1) syndrome.

Renin-angiotensin-aldosterone system in patients with sleep apnoea: prevalence of primary aldosteronism.

Obstructive sleep apnoea (OSA) is a sleep disorder characterized by recurrent episodes of oxygen desaturation during sleep, representing an independent risk factor for cardiovascular disease, such as myocardial infarction, stroke, congestive heart failure and resistant hypertension. Several neurohormonal mechanisms have been suggested to account for blood pressure increases, such as sympathetic nervous system hyperactivity, oxidative stress, renin-angiotensin-aldosterone system (RAAS) activation, endothelin system activation, and endothelial dysfunction. The aim of this study was to evaluate the behaviour of RAAS and the presence of primary aldosteronism (PA) in these patients and possible correlations between RAAS and the severity of OSA. From October 2007 to November 2008 we studied 325 consecutive newly diagnosed hypertensive patients; 71 patients (21.8%) presented with clinical signs of sleep disorders, evaluated also through a specific questionnaire (Epworth Sleepiness Scale). In hypertensive patients with sleep disorders, 53 patients were affected by OSA; in this group 18 patients were affected by PA (five with aldosterone-producing adenoma (APA) and 13 with bilateral hyperplasia (IHA)); obesity was also demonstrated (BMI > 30 kg/m(2)). Overall, in patients with OSA PRA levels correlated positively with apnoea/hypopnoea index (AHI; r = 0.35; p<0.01), and in all groups the waist circumference and the neck circumference were correlated positively with AHI (r = 0.3 p<0.02 and r = 0.3 p<0.03, respectively). We revealed a high prevalence of PA in patients with OSA, and we can conclude that patients with hypertension and OSA, especially those who are newly diagnosed, must be evaluated for PA.

Parathyroidectomy erase increased myocardial electrical vulnerability in patients with primary hyperparathyroidism.

BACKGROUND: Patients with primary hyperparathyroidism (pHPT) show an increased bioelectrical risk not related to cardiovascular complications, this risk seems to persist after surgery and this last finding is still controversial and probably related to follow-up length. METHODS: The aim of the study is to evaluate QT parameters in 11 patients with primary hyperparathyroidism (pHPT) 18 months after parathyroid surgery using computed standard 12-leads ECG compared to those of 29 healthy subjects (HS). RESULTS: In pHPT patients, 4 months after parathyroidectomy QT and QTc dispersion persist significantly higher than HS. 18 months after surgery, QT and QTc dispersion resulted comparable with HS. QT dispersion was found significantly higher in pHPT at 4 months respect 18 months after parathyroidectomy. CONCLUSIONS: ECG alteration after parathyroidectomy gradually return within normal limits and we can affirm that surgery erase bioelectrical risk in pHPT.

Hyperhomocysteinemia: a biochemical link between bone and cardiovascular system diseases?

Homocysteine (HCY) is a sulfur-containing amino acid involved in two metabolic pathways, catalized by cystathionine-B-synthase and methionine synthase, depending on vitamin (vit) B6, B12, and folate levels and enzymatic activity of methylenetetrahydrofolate. High HCY levels (HHCY) are associated with cardiovascular (CV) and bone diseases, in particular osteoporosis (OP)/hip fracture. As regards the mechanisms involved in the link between HHCY, CV diseases (CVD), and OP, it has been proposed the role of lysyl-oxydase inhibition that might interfere with collagen crosslink formation. Some studies suggested the dysregulation of the osteoprotegerin/receptor activator of nuclear factor-kappaB (RANK) ligand/RANK axis, others the involvement of oxidative stress. These mechanisms may act both on bone and CV system, but whether the common denominator is HCY itself or HCY is merely a marker, remains to be clearly established. Folate, vit B6, and B12 supplementation is associated with HCY reduction, but is unable to certainly reduce the incidence of OP/fracture and CVD, probably because, in the majority of patients, HCY is only moderately increased.

Epicardial adipose tissue and intracoronary adrenomedullin levels in coronary artery disease.

The aim of the study was to test 1) whether chronic and stable coronary artery disease (CAD) could downregulate epicardial fat adrenomedullin synthesis and secretion, and decrease intracoronary plasma adrenomedullin levels, and 2) whether intracoronary plasma adrenomedullin levels could be related to epicardial adipose tissue adrenomedullin gene and protein expression in subjects with CAD. We examined 12 patients with CAD who required coronary artery bypass graft (CABG) and 10 patients with non-CAD who underwent cardiac surgery for valve replacement. Plasma levels of adrenomedullin were measured in peripheral vein circulation, in left coronary artery (LCA) and coronary sinus (CS) during coronary angiography. Epicardial adipose tissue biopsy for Reverse Transcription and Real-Time PCR (RT-PCR) adrenomedullin mRNA analysis and Western Blotting (WB) protein expression was performed during cardiac surgery in all subjects. Peripheral, LCA, and CS plasma adrenomedullin levels were significantly lower in CAD patients than in those with non-CAD (3.0+/-0.9 vs. 4.4+/-0.9 pg/ml p<0.01; 2.9+/-1 vs. 4.05+/-0.8 pg/ml, p<0.01, 3.1+/-0.9 vs. 3.98+/-0.9 pg/ml p=0.04, respectively). However, CS adrenomedullin levels were not statistically different than those in LCA suggesting that adrenomedullin was not secreted from epicardial fat into the coronary artery lumen. Epicardial fat adrenomedullin mRNA levels and protein expression were lower in patients with CAD than in those with non-CAD (p<0.01 for both). We conclude that 1) epicardial fat adrenomedullin gene and protein expression can be downregulated in CAD subjects, and 2) intracoronary adrenomedullin levels are lower in CAD. No evidence that epicardial adipose tissue really contributes intracoronary adrenomedullin can be provided at this time.

Epicardial adipose tissue adiponectin expression is related to intracoronary adiponectin levels.

The role of adiponectin and epicardial adipose tissue in coronary artery disease (CAD) is a subject of debate. Whether plasma adiponectin concentration in the coronary circulation is locally modulated by the epicardial fat is still unexplored. We evaluated the hypothesis whether intracoronary plasma adiponectin levels are related to adiponectin expression in epicardial adipose tissue in vivo in patients with CAD and without CAD (non-CAD). We examined 12 patients with CAD who required CABG and 10 patients with non-CAD who underwent cardiac surgery for valve replacement. Plasma levels of adiponectin were measured in peripheral vein circulation and in left coronary artery (LCA) during coronary angiography. Epicardial adipose tissue biopsy for adiponectin protein extraction was performed during cardiac surgery in both CAD and non-CAD subjects. Adiponectin protein expression in epicardial adipose tissue was lower in patients with CAD than in those with non-CAD (0.45+/-0.4 vs. 1.1+/-1.0, p<0.05). LCA plasma adiponectin levels significantly correlated with epicardial adipose tissue adiponectin protein expression (r=0.68, p=0.02) in all subjects. Peripheral adiponectin levels and epicardial fat adiponectin protein expression were the best correlates of LCA adiponectin, r (2)=0.49, p<0.01, p<0.05, respectively). Our study showed that intracoronary adiponectin levels reflect systemic adiponectin levels. Epicardial adipose tissue could partially contribute to adiponectin levels in the coronary circulation.

Cushing's syndrome patient who exhibited congestive heart failure.

Cushing's Syndrome (CS) may sometimes lead to dilated cardiomyopathy, even though this condition can be partially or completely reversed after treatment. In this article we report the case of a 28-yr-old woman with CS secondary to adrenal adenoma who exhibited congestive heart failure as an initial symptom. Two weeks before being admitted to our hospital, the patient started complaining of shortness of breath, orthopnea, paroxysmal nocturnal dyspnea and generalized edema. A physical examination did not reveal signs of hypercortisolism. Chest auscultation revealed bilateral diffused crepitation; blood pressure was 180/120 mmHg with heart rate of 90 beats/min. A chest X-ray showed a cardiac shade enlargement due to congestive heart failure. Transthoracic echocardiography demonstrated a dilated left ventricle and an impaired left ventricular systolic function. The patient's urinary cortisol excretion was elevated and circadian rhythm of cortisol was absent. ACTH level was low. In addition, plasma cortisol failed to decrease after administration of dexamethasone. An abdominal magnetic resonance imaging scan showed a 7-cm right adrenal mass. The patient was administered oxygen, spironolactone, ACE-inhibitor and the signs and symptoms of heart failure gradually improved. A laparoscopic right adrenalectomy was performed and pathological examination of the gland showed a benign adrenocortical adenoma. After the adrenalectomy the patient was started on hydrocortisone therapy and 5 months later the wall thickness of the left ventricle was within normal range and the patient's blood pressure was 130/80 mmHg. In conclusion we report the case of heart failure as the main clinical symptom in CS secondary to adrenal adenoma.

Adrenal pheochromocytoma and jejunal neurofibroma in type 1 neurofibromatosis: report of a case.

INTRODUCTION: Neurofibromatosis type 1 (NF1), known as von Recklinghausen's disease, is characterized by presence of café au lait spots, and neurofibromas in the skin or along the course of peripheral nerves. Diagnosis, despite extreme clinical variability, is defined by established diagnostic criteria. Clinical status is frequently complicated by systemic disorders and neoplasias. CASE REPORT: A case of a patient affected by NF1, with hypertension due to adrenal pheochromocytoma and with jejunal neurofibroma, is reported. DISCUSSION AND CONCLUSIONS: Variability in clinical presentation of NF1 with possible manifestation of severe systemic benign and malignant diseases requires strict follow-up and specific screening of extra-cutaneous lesions.

Pheochromocytoma associated with adrenocortical tumor in the same gland. Two case reports and literature review.

Pheochromocytomas are catecholamine-producing neuroendocrine tumours arising from chromaffin cells of the adrenal medulla or extra-adrenal paraganglionic system that show 2 distinctive features, rarity and clinical variability. Pheochromocytoma occasionally is associated with pathological lesions of the adrenal cortex. We present 2 cases of patients referred to our hospital with a finding of clinical suspected pheochromocytoma. Both of them were hypertensive; the first patient with typical symptoms of pheochromocytoma and the second patient with chest pain and hypertension resistant to pharmacological treatment. The diagnosis of pheochromocytoma was confirmed in both cases with laboratory analysis and the lesion was achieved by employing 3 imaging techniques: computed tomography (CT), magnetic resonance imaging (MRI) and scintigraphy with (123)I-metaiodobenzilguanidine (MIBG). The patients underwent adrenalectomy and in the same adrenal gland we found a pheochromocytoma associated with a nonfunctioning cortical adenoma. As far as we know few cases with this association are available in the literature.

Adrenomedullin plasma concentrations in patients with retinitis pigmentosa.

PURPOSE: To evaluate the relationship between retinitis pigmentosa (RP) and plasma adrenomedullin (ADM) levels. METHODS: Blood samples were obtained from a group of 40 consecutive patients with RP matched with 35 healthy subjects (HS) as control. We carried out a complete ophtalmological examination. The study group included 26 patients with RP and 14 patients with syndromic RP. Plasma ADM levels were determined in duplicate with a specific radioimmunoassay method. RESULTS: In the HS plasma ADM levels were 13.7 +/- 6.1 pg/mL. The mean of plasma ADM concentrations in all patients with RP (23.4 +/- 10.7 pg/mL) was significantly (P < 0.0001) higher than that of HS. Moreover, in the syndromic RP patients, plasma ADM levels (28.6 +/- 14.35 pg/ml) were higher than those of HS and RP patients (P < 0.0017). CONCLUSION: The increase of plasma ADM levels in RP patients may be a response to photoreceptor damage.

Acute hyperinsulinemia is associated with increased plasma adrenomedullin concentrations in uncomplicated obesity.

OBJECTIVE: Adrenomedullin (AM) is a potent hypotensive peptide which may be implicated in the insulin regulatory system. Acute hyperinsulinemia exerts no influence on plasma AM in normal subjects while no data on obese subjects has been reported. PURPOSE: The aim of the study was to investigate the effect of acute hyperinsulinemia on the plasma AM concentration in patients with uncomplicated obesity. RESEARCH METHODS: We measured the plasma AM levels in 23 obese subjects (BMI 41.9 +/- 9.8 kg/m2), 21 females and 2 males (mean age 31 +/- 7.2 years), before and during a euglycemic hyperinsulinemic clamp. The control group consisted of 43 healthy subjects (HS) (22 males and 21 females; mean age 38 +/- 12 years; BMI 23.3 +/- 3.2 kg/m2). RESULTS: Baseline plasma AM was found to be higher in obese subjects (20.4 +/- 8.4 pg/ml) than in normal subjects (11.3 +/- 0.8 pg/ml) (p < 0.001). A significant increase in the plasma AM levels was observed in obese subjects during acute hyperinsulinemia (from 20.4 +/- 8.4 pg/ml at 0 min to 26 +/- 8.9 pg/ml at 120 min, p < 0.02). Plasma AM concentrations were significantly correlated with insulin levels at 30 min (r = 0.44; p = 0.04) and 120 min (r = 0.40, p = 0.05) during the clamp. DISCUSSION: In conclusion, acute hyperinsulinemia induced a significant increase in the plasma levels of AM in uncomplicated obese subjects. Hyperinsulinemia may, at least in part, regulate levels of AM in obesity, explaining the high levels of the peptide in these subjects.