Body mass index stratification in hospitalized Italian adults with congenital heart disease in relation to complexity, diagnosis, sex and age.

BACKGROUND AND AIMS: Adults with congenital heart disease (ACHD) are at risk of overweight and obesity, two major health problems, though underweight can be a negative prognostic factor too. Awareness of the body mass index (BMI) in ACHD is very limited. The present study describes the use and prevalence of BMI in Italian symptomatic hospitalized ACHD patients in relation to complexity by Bethesda system classification, diagnosis, sex and age. METHODS AND RESULTS: We classified 1388 ACHD patients, aged 18-69 years, on the basis of their BMI, and compared them to the Italian reference population. In our total ACHD population we found a significantly higher prevalence of underweight compared to the Italian reference population (6.34% vs 3.20%). ACHD women were more underweight than men. Underweight decreased with age. Overweight was significantly less frequent in the total ACHD population (26.73% compared to 31.70%) in the Italian reference population. Men were more likely to be overweight than women. In statistical terms obesity was similar in the Italian reference population (10.50%) and our ACHD population (9.58%). Both overweight and obesity increased with age. Results were comparable using a diagnostic anatomical-functional classification and the Bethesda system classification. CONCLUSIONS: In our cohort of ACHD the prevalence of underweight was double that of the Italian reference population. The prevalence of overweight was lower, while obesity was similar. Since BMI does not account for differences in body fat distribution, a future aim will be to quantify the visceral component of the adipose tissue in ACHD patients and examine their body composition in order to reflect their risk of acquired cardiovascular disease better, and either to maintain or achieve an adequate visceral component.

Epicardial adipose tissue inflammation is related to vitamin D deficiency in patients affected by coronary artery disease.

BACKGROUND AND AIMS: Alterations in epicardial adipose tissue (EAT) biology (i.e. increased fat thickness and inflammation) have been described in coronary artery disease (CAD) patients. In addition to its classic role in the regulation of calcium-phosphate homeostasis, vitamin D may exert immune-regulatory and anti-inflammatory effects. Whether EAT inflammation may be linked to vitamin D deficiency is still unknown. In the present study we evaluated plasma 25-hydroxycholecalciferol (25OHD) level in CAD patients and its relationship with EAT ability to locally metabolize vitamin D, EAT expression of inflammation-related molecules and EAT thickness. METHODS AND RESULTS: Plasma 25OHD level was quantified by an immunoluminometric assay. EAT expression of inflammation-related molecules (MCP-1, PTX3, TNFα, IL-6, adiponectin), vitamin D receptor (VDR), CYP27B1 (25OHD-activating enzyme) and CYP24A1 (1,25-dihydroxycholecalciferol-metabolizing enzyme) was performed by microarray. EAT thickness was quantified by echocardiography. Median plasma 25OHD level was 10.85 ng/mL and 83% of CAD patients displayed 25OHD level below 20 ng/mL. At decreasing plasma 25OHD concentration, we observed a down-regulation in CYP27B1 and CYP24A1 level and an increased expression of VDR and pro-inflammatory cytokines (MCP-1, PTX3, TNFα, IL-6) at EAT level. No correlation was observed between plasma 25OHD level and EAT thickness. CONCLUSION: Our data suggest an increased activation of inflammatory pathways at EAT level possibly related to systemic and local vitamin D deficiency in CAD patients. Whether maintaining an optimal vitamin D status may be helpful to reduce EAT inflammation and to prevent CAD and its progression needs further investigation.

IL-18 level in patients undergoing coronary artery bypass grafting surgery or valve replacement: which link with epicardial fat depot?

Interleukin-18 (IL-18) is a member of the interleukin-1 family of cytokines produced constitutively by different cell types and by adipose tissue. Due to the link between obesity, inflammation and cardiovascular diseases, we aimed to measure IL-18 circulating level in patients undergoing open-heart surgery both for elective coronary artery bypass grafting (CABG) or for valve replacement (VR), and we also evaluated whether epicardial adipose tissue (EAT) depot may be a potential source of IL-18. Circulating IL-18 protein was quantified by enzyme-linked immunosorbent assay. IL-18, IL-18 receptor 1 (IL-18 R1) and IL-18 receptor accessory protein (IL-18-RAP) gene expression in EAT depot were evaluated by one colour microarray platform. EAT thickness was measured by echocardiography. In this study we found that all cardiovascular patients (CABG and VR) have increased circulating IL-18 level compared to healthy control subjects (p < 0.0001), but no statistical significant difference was observed between CABG and VR groups (p = 0.35). A great increase in the gene expression of IL-18 (p < 0.05), IL-18 R1 (p < 0.01) and IL-18 RAP (p < 0.001) was observed in EAT samples obtained from CABG vs VR patients. In conclusion, CABG and VR patients had similar increased level of circulating IL-18 protein, but in EAT depots isolated from CABG gene expression of IL-18, IL-18 R1 and IL-18-RAP resulted higher than in VR patients. Future investigation on local IL-18 protein production, its autocrine-paracrine effect and its correlation with plasmatic IL-18 level could give more information on the relationship between IL-18 and coronary artery disease.

Effects of treatment strategy on endothelial function.

A large body of evidence indicates that endothelial dysfunction is a characteristic of patients with arterial hypertension. As functional abnormalities lead to impaired endothelium-dependent vasodilation, this early step of atherogenesis is potentially reversible. In addition to reducing blood pressure, the major families of anti-hypertensive drugs have a number of pleiotropic effects that could improve endothelial function. In particular, the renin-angiotensin system plays an important role in the pathogenesis of both arterial hypertension and endothelial dysfunction, and so drugs capable of limiting the dangerous effects of this hormonal axis, such as angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers and renin inhibitors, could help prevent/delay/reverse the atherosclerotic process. New third-generation ß-blockers and 5-phosphodiesterase inhibitors may affect endothelial function. Furthermore, the HMGCoA-reductase inhibitors currently used to reduce cholesterol levels have major pleiotropic anti-inflammatory and anti-hypertensive effects. The preservation or recovery of endothelial function in hypertensive patients is crucial to inhibit the development of atherosclerosis and the onset of cardiovascular events. This review focuses on the ancillary effects of hypertensive drugs and HMGCoA-reductase inhibitors that go beyond lowering blood pressure and cholesterol levels.

Relationship of thyroid function with body mass index and insulin-resistance in euthyroid obese subjects.

BACKGROUND AND AIMS: It is recognized that overt thyroid dysfunction is associated with weight changes, but the influence of a minor alteration of thyroid function remains unclear. This study aimed to further investigate the relationship between obesity and thyroid function and to examine the possible role of insulin resistance on the hypothalamic-pituitary- thyroid axis. METHODS AND RESULTS: Serum TSH and free T4 (FT4) levels, anthropometric and metabolic parameters were evaluated in 581 obese patients. In all patients TSH values progressively increased according to the severity of obesity and were positively correlated with body mass index (p=0.001, r=0.13) and waist circumference (p=0.02, r=0.11). Patients with insulin resistance showed higher TSH (1.8±1.0 vs 1.6±0.9 µUI/l; p=0.03) and lower FT4 levels (13.8±2.3 vs 15.0±2.2 pmol/l; p<0.001), as compared with patients with normal insulin sensitivity. Moreover, TSH was positively correlated with fasting insulin (p<0.001, r=0.152) and homeostasis model assessment of insulin resistance (HOMA-IR; p<0.001, r=0.148), and negatively correlated with Quantitative Insulin Sensitivity Check Index (QUICKI; p<0.001, r=-0.148); FT4 was negatively associated with fasting insulin (p<0.001, r=-0.287) and HOMA-IR (p<0.001, r=-0.295), and positively associated with QUICKI (p<0.001, r=0.295). CONCLUSIONS: A relationship between thyroid function and overweight/ obesity condition seems to exist, mainly influenced by insulin resistance. Whether variations in TSH and/or thyroid hormones, within a normal range, can influence body weight or whether obesity per se can alter thyroid function cannot be stated so far. Further studies are needed to assess the link between thyroid function and body weight, by considering not only changes in thyroid hormones, but also body fat distribution, obesity duration and low-grade inflammation.

Peripheral insulin-like factor 3 concentrations are reduced in men with type 2 diabetes mellitus: effect of glycemic control and visceral adiposity on Leydig cell function.

BACKGROUND AND AIM: Hypogonadism frequently occurs in men with type 2 diabetes mellitus (T2DM), while the role of glycemic control and visceral obesity is still unclear. This study aimed to assess the Leydig cell function, including the new sensitive marker insulin-like factor 3 (INSL3), in T2DM patients without overt hypogonadism and the influence of either glycemic control or visceral adiposity. SUBJECTS AND METHODS: Thirty T2DM patients (age 57.1+/-6.2 years, body mass index (BMI) 28.0+/-4.3) without overt hypogonadism and 30 age- and BMI-matched controls were studied. Anthropometric, glycometabolic parameters and testosterone, SHBG, LH, INSL3 levels, bioavailable and free testosterone (BT and cFT) were evaluated. The human chorionic gonadotrophin (hCG) test was also performed. RESULTS: Patients had lower total testosterone (452.6+/-130.0 vs 512.6+/-117.3 ng/dl, P=0.06), BT (189.7+/-36.4 vs 237.1+/-94.1 ng/dl, P=0.002), cFT (8.1+/-1.6 vs 10.1+/-4.0 ng/dl, P=0.002), and higher LH levels (3.5+/-1.6 vs 2.6+/-1.2 mU/ml, P=0.01) versus controls. Serum INSL3 concentrations were also lower in patients (1.1+/-0.3 vs 1.5+/-0.7 ng/ml, P=0.01). These hormonal parameters, including INSL3, did not differ between T2DM patients with poor or good glycemic control (HbA1c>9 or <7% respectively). In patients, waist circumferences (97.9+/-12.4 cm) negatively correlated with INSL3 (P=0.03) and basal, as well as hCG-stimulated testosterone levels (P=0.04 and 0.004 respectively). Basal or stimulated hormonal levels and INSL3 concentrations were not different between patients with (40%) or without erectile dysfunction. CONCLUSIONS: An early impairment of the overall Leydig cell function is present in men with T2DM, mainly related to visceral adiposity rather than to glycemic control.

Echocardiographic alterations in patients with non-functioning adrenal incidentaloma.

OBJECTIVE: While left ventricular (LV) dysfunction has been described in patients with Cushing's syndrome (CS), data concerning morphologic and functional cardiac alterations in patients with incidentally discovered adrenal masses [adrenal "incidentaloma" (AI)], without overt hypercortisolism, are lacking. In this study the echocardiographic characteristics of patients with AI were evaluated and then compared with those of lean and obese normotensive subjects. SUBJECTS AND METHODS: Twenty-one patients with AI, without clinical or subclinical hypercortisolism, 18 normotensive obese subjects matched for gender and body mass index (BMI) and 20 normotensive lean subjects were studied. Echocardiography was performed in all subjects. In all patients plasma ACTH, serum cortisol, and DHEA-S levels were measured. RESULTS: Patients with AI showed greater impairment of several echocardiographic indices of LV hypertrophy and diastolic dysfunction compared to normotensive lean subjects (p<0.05), but did not differ from those in obese subjects. Hypertensive AI patients showed a greater alteration of echocardiographic parameters (p<0.05) and higher BMI (p<0.01) and cortisol values (p<0.05) than normotensive ones. Plasma ACTH and serum cortisol were similar in AI patients and in obese controls, while DHEA-S levels were lower in AI (p<0.05). No correlations between cortisol secretion and echocardiographic parameters were found. CONCLUSION: In patients with non-functioning AI there is an impairment of cardiac morphology and function. These data suggest that patients with AI should be carefully screened also by means of echocardiographic studies.

Anthropometric, hormonal and biochemical differences in lean and obese women before and after menopause.

The menopausal status is associated with an increased risk of metabolic and cardiovascular diseases. Since the post-menopausal modifications have not been clearly investigated in obese women, we evaluated the influences of menopausal status on anthropometric, hormonal and biochemical characteristics in selected groups of normal-weight and obese women. We studied 92 female outpatients: 24 normal-weight pre-menopausal (Pre-NW) [body mass index (BMI) 23.6 +/- 0.48, age 44.8 +/- 0.68], 24 normal-weight post-menopausal (Post-NW) (BMI 23.7 +/- 0.44, age 55.5 +/- 0.69), 24 obese pre-menopausal (pre-OB) (BMI 32.3 +/- 0.45, age 44.6 +/- 0.75), 20 obese post-menopausal women (Post-OB) (BMI 32.9 +/- 0.57, age 55.2 +/- 0.82). All the subjects were non smokers and free from hypertension, diabetes or impaired glucose tolerance (IGT). Anthropometric parameters, body composition, 17 beta-estradiol, LH, FSH, androstenedione, SHBG, testosterone and leptin were determined. Free androgen index (FAI) and insulin resistance index (HOMA) were calculated. In comparison with Pre-OB, Post-OB had higher values of waist circumferences (p < 0.02), while Post-NW showed no difference. Total and LDL-cholesterol were high in Post-NW women, whereas in the obese subjects they were already elevated in the premenopausal period. SHBG levels declined and FAI increased in Post-OB in comparison with Pre-OB. SHBG levels showed an inverse correlation with BMI, waist and waist-to-hip ratio (WHR), while FAI positively correlated with waist values. Serum leptin levels were higher in Post-OB than in Pre-OB, whereas they were similar in normal-weight women. The rise of leptin levels may be related to the greater abdominal fat deposition. In addition, menopausal status of uncomplicated obese women is associated with a greater abdominal fat deposition and with higher values of free androgen index, which may be considered as factors of cardiovascular risk.

Diagnosis and management of Addison's disease during pregnancy.

Although primary adrenal failure is considered a rare condition, recent epidemiological studies indicate a rising incidence of the disease owing to the increase of autoimmune disorders. Addison's disease may be a life-threatening condition and the occurrence of pregnancy has been considered as a dangerous event. Nowadays, adrenal insufficiency during pregnancy is associated with high incidence of serious fetal and maternal complications, as fetal death in utero and post-partum adrenal crises, only if the disorder is not recognized and adequately treated. In this article pathophysiological aspects, clinical features and guidelines of management of pregnancy in Addison's disease are reviewed.

Relationship of visceral fat distribution to angiographically assessed coronary artery disease: results in subjects with or without diabetes or impaired glucose tolerance.

BACKGROUND AND AIM: To evaluate the relationship between the degree of coronary artery disease (CAD) and the amount of visceral fat deposition in a mixed population of CAD patients with or without diabetes or impaired glucose tolerance (IGT), and with different body weights. METHODS AND RESULTS: A total of 55 patients undergoing coronary angiography (43 men and 12 women with a mean age of 58.9 +/- 1.1 years, range 37-70, and a mean body mass index [BMI] of 27.9 +/- 0.4, range 21.3-38.7) were studied in order to establish whether the coronary damage exclusively depends on intra-abdominal adipose tissue per se, or may be influenced by the coexistence of diabetes or IGT. Twenty-one subjects were non-diabetic, 13 had type 2 diabetes, and 21 IGT. Hypertension was found in 47% and dyslipidemia in 55%; 69% were smokers. The angiographic evaluation of CAD was made using the method of Gensini, and computed tomography (CT) was used to estimate the amount of visceral adipose tissue (VAT) based on a single scan at L4 level. Clinical, anthropometric, biochemical and hormonal variables, as well as smoking and alcohol consumption were determined. In the study population as a whole, the coronary score did not correlate with VAT, but only with smoking. However, both univariate and multivariate regression analysis showed that CAD significantly correlated with VAT in the non-diabetic patients, particularly in those with VAT of > 130 cm2. This correlation did not appear in the diabetic or IGT patients, nor when the group of patients with VAT > 130 cm2 was extended to include diabetic or IGT patients. No relationship was found between CAD and BMI or the other considered variables. CONCLUSIONS: In a mixed population of CAD patients with or without diabetes, CAD correlates with VAT only in the absence of diabetes or IGT, and especially when VAT exceeds 130 cm2 at an L4 CT scan, regardless of weight or obesity. Diabetes or IGT therefore seem to contribute towards the development of CAD regardless of the amount of VAT.

Food-related sensory stimuli are able to promote pancreatic polypeptide elevation without evident cephalic phase insulin secretion in human obesity.

The data concerning the cephalic phase of insulin secretion (CPIS) in human obesity are controversial. We investigated the effect of a variety of sensory challenges on CPIS in 17 non-diabetic obese patients (four males, 13 females, mean age 41.1 years, mean BMI 38.7). Water, saccharin, and lemon juice were used as oral stimuli, and a complete meal was simply presented as visual and olfactory stimulations. Twelve healthy normal-weight subjects (four men, eight women, mean age 39.9, mean BMI 22.5) also underwent oral stimulation as controls, and the patients who underwent the sight and smell stimulations were also tested for pancreatic polypeptide (PP) changes in order to verify the occurrence of truly cephalic reflex during the test. Insulin levels were measured before and after each stimulation (every min for the first 5 min, and then after 10, 20, and 30 min). None of the stimuli (saccharin, lemon juice or water retained in the mouth for 2 min and were then spat out; the combined and separate sight and smell of a meal for 2 min) led to a significant increase in insulin in the obese patients (except in the case of one woman after oral stimulation). The oral stimuli led to a variable CPIS in one female and three male controls. Despite the absence of CPIS, the five obese patients undergoing all three sensory stimulations related to the meal (combined sight and smell, sight alone and smell alone) showed an early and significant increase in plasma PP concentrations within the first 3 min; this was more pronounced after the combined than after the separate exposure. Although only preliminary, these results underline the variability but substantial lack of CPIS in obese patients, thus suggesting that it can be considered a relatively rare and unrelevant event even in the presence of a true brain-mediated reflex revealed by the rapid and consistent increase in PP found in our experiments.

The role of central fat distribution in coronary artery disease in obesity: comparison of nondiabetic obese, diabetic obese, and normal weight subjects.

OBJECTIVE: To investigate the degree of coronary artery disease (CAD) in relation to obesity and fat distribution in obese patients with normal glucose tolerance, in comparison with CAD of diabetic obese patients and of normal weight subjects with CAD. DESIGN: Patients listed for coronary angiography with different body mass index (BMI) with or without diabetes: study of the correlation between severity of coronary damage and fat distribution. SUBJECTS: 92 patients subdivided into: 30 normal glucose tolerant obese (BMI 31.7+/-0.5, aged 53+/-1.7 y), 28 type 2 diabetic obese (BMI 30.7+/-0. 3, aged 57+/-1.2 y), and 34 normal weight patients (BMI 23.1+/-0.3, aged 54+/-1.7 y). MEASUREMENTS: CAD assessed by angiography and evaluated according to the method of Gensini. Fat mass and fat distribution assessed by bioelectrical impedance and anthropometry. Clinical, biochemical and hormonal variables, as well as smoking habits and alcohol intake. RESULTS: The angiographic coronary scores were similar in nondiabetic obese and in diabetic obese patients, and were significantly higher than those of normal weight subjects. In the entire population coronary score correlated with indices of abdominal fat distribution. In the stepwise analysis of each group separately, waist hip ratio (WHR) correlated with coronary score only in normal weight nondiabetic patients. CAD was inversely associated with BMI only in nondiabetic obese patients. CONCLUSION: CAD of obese patients: 1) is similar to that of diabetic obese patients; 2) is more severe than that of normal weight individuals; and 3) is inversely correlated with BMI. CAD appears to be associated with WHR, not with BMI, only in nondiabetic patients with normal body weight. On the contrary, CAD of diabetic obese patients is unrelated to BMI and parameters of fat distribution, but is associated with smoking habits.

Diabetes and complications after cardiac surgery: comparison with a non-diabetic population.

Diabetes is a well-recognized independent risk factor for mortality due to coronary artery disease. When diabetic patients need cardiac surgery, either coronary-aortic by-pass (CABP) or valve operations (VO), the presence of diabetes represents an additional risk factor for these major surgical procedures. Because of controversial data on mortality rates and post-operative complications in diabetic patients, probably due to not exactly comparable groups of patients, this retrospective study aimed to compare two homogeneous populations, which were different only for the presence or absence of diabetes. We studied 700 patients undergoing cardiac surgery: 350 with and 350 without diabetes, mean age 62 +/- 9 years (67% males); 441 underwent CABP and 259 VO. Apart from the diabetes, the two groups were strictly matched for age, body mass index, concomitant pathologies and smoking habits, except for previous neurological injuries (more frequent in diabetic patients), and for a slightly lower ejection fraction in the diabetic group. Intra- and post-operative complications or events were evaluated carefully: death, number staying in post-operative intensive care unit (ICU), renal, hepatic and respiratory complications, necessity for reoperation and hemotransfusions. Anesthesia and surgical procedures (including extra-corporeal circulation techniques) remained substantially unchanged over the period of recruitment of patients (1996-1998) and applied equally to both groups of patients. All diabetic patients were treated with insulin by using standard procedures in order to optimize metabolic control. Diabetic patients in our study, did not show higher rates of mortality in comparison with non-diabetic patients, but had more total neurological complications, more renal complications, a higher re-opening rate, more prolonged ICU stay, and they needed more blood transfusions. Diabetes remains an independent risk factor for these events even in a multivariate logistic regression model analysis. In the subgroup of diabetic patients who underwent CABP a higher rate of renal dysfunction, re-opening, need for hemotransfusions and prolonged ICU stay were confirmed. In the subgroup of diabetic patients undergoing VO we found a higher rate of renal dysfunction, reopening, prolonged ICU stay and major lung complications. In conclusion, diabetes does not seem to increase the mortality rates of cardiac surgery, but diabetic patients undergoing CABP have, on the basis of the relative risk evaluation, a 5-fold risk for renal complications, a 3.5-fold risk for neurological dysfunction, a double risk of being hemotransfused, reoperated or being kept 3 or more days in the ICU in comparison with non-diabetic patients. Moreover, diabetic patients undergoing VO have a 5-fold risk of being affected by major lung complications.

Obesity and coronary artery surgery.

OBJECTIVE: To assess whether obesity is a risk factor for morbidity and mortality in patients undergoing elective coronary artery revascularization. DESIGN: Prospective, clinical study. SETTING: University hospital. PARTICIPANTS: Three hundred forty-five consecutive patients who underwent elective coronary revascularization with cardiopulmonary bypass and without associated procedures. INTERVENTIONS: Patients were assigned to the obese group if their body mass index was greater than 30 for men and 28.6 for women, according to the World Health Organization indications. MEASUREMENTS AND MAIN RESULTS: Preoperative and intraoperative variables were collected and checked for homogeneity of the groups. Postoperative outcome was assessed on the basis of intubation time, intensive care unit (ICU) and postoperative hospital stay, mortality rate, and incidence of transfusions, reoperations, low-output syndrome, minor and major neurologic dysfunction, minor and major lung dysfunctions, renal dysfunction, and superficial and deep infections. The effect of obesity on postoperative outcome was tested with a multivariate logistic regression analysis. Obese and control patients had the same intubation time and ICU and postoperative hospital stay. Mortality and all major complications occurred with the same incidence in the two groups. Obese patients had a significantly (p < 0.05) greater rate of superficial infections and more (24.1% v 7.4%; p < 0.001) minor lung complications. Conversely, they had a significantly lower transfusion rate (27.5% v42.7%; p < 0.01). CONCLUSION: Obese patients had only minor complications after coronary artery surgery. The large body surface area because of obesity protects them against the hemodilution-related transfusion risk.

[Caloric intake and distribution of the main nutrients in a population of obese children]. / Introito calorico e ripartizione dei principali nutrienti in una popolazione infantile obesa.

Calorie intake and the main nutrient contents were assessed in a population of 152 obese (OB) children (86 M; 66 F; age 7-11) and 153 normal weight (NW) peers (87 M; 66 F). The following method was used: a) an interview using a food dictionary to assess food intake during the 2 days prior to the study and on one holiday: and b) a weekly questionnaire. The mean food intake of OB did not exceed that of NW, but on the contrary was lower (OB: 1812.9 +/- 39.6 kcal/die; NW: 1928.5 +/- 39.4 kcal/die; p less than 0.05). The population studied consumed approximately 50% of calories as carbohydrates (CHO), 35% as fats (F) and 15% as protein (P), and no difference was noted between OB and NW. The percentage of CHO was lower than that recommended by LARN, whereas the percentages of F and P were higher. A significant increase with age was noted in F and P intake as was a significant reduction of CO. 70% of OB and 80% of NW matched or exceeded the calorie intake recommended by LARN. 30% of OB and 24% of NW consumed 30% less than the daily calorie intake recommended by LARN.

Effect of acute administration of metoclopramide on insulin secretion in man.

The effect of acute i.v. administration of 2.5 mg metoclopramide (MCP), an antidopaminergic agent with low serotoninergic activity, on blood insulin and glucose concentrations was studied in 9 healthy men. MCP was able to significantly decrease basal serum insulin levels (from 6.8 +/- 1.1 to 4.3 +/- 0.7 microU/ml in 120 min; p less than 0.025) with a parallel elevation in blood glucose (from 72.5 +/- 1.1 to 82.6 +/- 2.5 mg/dl in 120 min; p less than 0.01). These findings, which were not observed after placebo, and appeared not to be explained by the spontaneous occurrence of physiological oscillations of insulin and glucose plasma levels, are consistent with similar effects observed after administration of other antidopaminergic agents and with the stimulatory activity on insulin and glucagon release described during dopamine infusion in man.

Epidural spinal electrostimulatory system (ESES) in the management of diabetic foot and peripheral arteriopathies.

Epidural spinal electrostimulatory system (ESES) or dorsal column stimulation (DCS) may be used for the treatment of peripheral vascular diseases of the lower extremities. ESES has been used in our metabolic and surgical department as a way to ameliorate inadequate blood supply in patients suffering from diabetic foot (seven patients), painful chronic arterial narrowing, or inoperable occlusions (25 patients). The continuous stimulation by an implantable apparatus (Medtronic model Itrel, Medtronic, Inc., Minneapolis, MN, USA) led to a reduction or disappearance of pain, an improvement in plethysmographic curves, functional performance, and trophic lesions in about 75% of the patients. The system is safe and well-tolerated by patients.

Clinical and pharmacological characterization of anomalous metoclopramide-induced growth hormone secretion in insulin-dependent diabetes mellitus.

An abnormal growth hormone (GH) increase after non-specific stimuli (such as TRH, LHRH and, in a few cases, metoclopramide), has been described in insulin-dependent diabetes. Sixty-nine non-hypogonadic male insulin-dependent diabetic patients (mean age 38.6 years, range 18-54; mean duration of diabetes 11.1 years, range 1.3-28, in different degree of metabolic control, some of them with retinopathy, nephropathy and peripheral and/or autonomic neuropathy) were tested twice with 10 mg i.v. metoclopramide (MCP), an antidopaminergic agent with weak serotoninergic activity. Anomalous GH response (i.e. GH increment equal to or higher than 5 ng/ml from basal level) occurred in 33 patients (47.8%). Mean (+/- SE) MCP-induced GH release in these 'responder' patients peaked up to 17.2 +/- 1.7 ng/ml in comparison with no variation found in 'non-responders' and in 25 healthy control men. Abnormal GH secretion appeared to be unrelated to age, metabolic control, basal GH values and duration of diabetes. Moreover, it remained unmodified by pretreatments with placebo, cimetidine, meclastine, propranolol, acetylsalicylic acid and naloxone, while it was enhanced by metergoline, significantly reduced by bromocriptine and almost completely blunted by pirenzepine, a cholinergic muscarinic receptor antagonist. Neuropathy and nephropathy were equally distributed in the two groups, while retinopathy was more frequent in 'responders'. In conclusion, the exact mechanism(s) by which MCP may induce a paradoxical GH release in many insulin-dependent diabetic patients, is still unclear; it might be dependent, at least in part, on the activation of cholinergic pathways. Indeed, it seems to indicate the presence, in diabetes, of a rather complex derangement in the regulatory mechanisms of GH secretion.