Search

Objectives To identify the predictive value on time to onset of heart failure (HF) or cardiac death of clinical, radiographic, and echocardiographic variables, as well as cardiac biomarkers N-terminal pro brain natriuretic peptide (NT-proBNP) and cardiac troponin I in dogs with preclinical myxomatous mitral valve disease (MMVD). Animals One hundred sixty-eight dogs with preclinical MMVD and left atrium to aortic root ratio ≥1.6 (LA:Ao) and normalized left ventricular end-diastolic diameter ≥1.7 were included. Methods Prospective, randomized, multicenter, single-blinded, placebo-controlled study. Clinical, radiographic, echocardiographic variables and plasma cardiac biomarkers concentrations were compared at different time points. Using receiving operating curves analysis, best cutoff for selected variables was identified and the risk to develop the study endpoint at six-month intervals was calculated. Results Left atrial to aortic root ratio >2.1 (hazard ratio [HR] 3.2, 95% confidence interval [95% CI] 1.9–5.6), normalized left ventricular end-diastolic diameter > 1.9 (HR: 6.3; 95% CI: 3.3–11.8), early transmitral peak velocity (E peak) > 1 m/sec (HR: 3.9; 95% CI: 2.3–6.7), and NT-proBNP > 1500 ρmol/L (HR: 5.7; 95% CI: 3.3–9.5) were associated with increased risk of HF or cardiac death. The best fit model to predict the risk to reach the endpoint was represented by the plasma NT-proBNP concentrations adjusted for LA:Ao and E peak. Conclusions Logistic and survival models including echocardiographic variables and NT-proBNP can be used to identify dogs with preclinical MMVD at higher risk to develop HF or cardiac death.

Introduction: Efficacy of renin-angiotensin-aldosterone system (RAAS) blockade using angiotensin-converting enzyme inhibitors (ACEi) in dogs with preclinical myxomatous mitral valve disease (MMVD) is controversial. Hypothesis: Administration of spironolactone (2-4 mg q 24 h) and benazepril (0.25-0.5 mg q 24 h) in dogs with preclinical MMVD, not receiving any other cardiac medications, delays the onset of heart failure (HF) and cardiac-related death. Moreover, it reduces the progression of the disease as indicated by echocardiographic parameters and level of cardiac biomarkers N-terminal pro brain natriuretic peptide (NT-proBNP) and cardiac troponin I (cTnI). Animals: 184 dogs with pre-clinical MMVD and left atrium-to-aortic root ratio (LA:Ao) >= 1.6 and normalized left ventricular end-diastolic diameter (LVEDDn) >= 1.7. Methods: This is a prospective, randomized, multicenter, single-blinded, placebo-controlled study. Primary outcome variable was time-to-onset of first occurrence of HF or cardiac death. Secondary end points included effect of treatment on progression of the disease based on echocardiographic and radiographic parameters, as well as variations of NT-proBNP and cTnI concentrations. Results: The median time to primary end point was 902 days (95% confidence interval (CI) 682-not available) for the treatment group and 1139 days (95% CI 732-NA) for the control group (p = 0.45). Vertebral heart score (p = 0.05), LA:Ao (p < 0.001), LVEDDn (p < 0.001), trans-mitral E peak velocity (p = 0.011), and NT-proBNP (p = 0.037) were lower at the end of study in the treatment group. Conclusions: This study failed in demonstrating that combined administration of spironolactone and benazepril delays onset of HF in dogs with preclinical MMVD. However, such treatment induces beneficial effects on cardiac remodeling and these results could be of clinical relevance. (C) 2020 The Authors. Published by Elsevier B.V.

Background and aim: The objective of this cross-sectional study was to evaluate the degree of glycaemic control and the frequency of diabetic complications in Italian people with diabetes who were treated with continuous subcutaneous insulin infusion (CSII). Methods and results: Questionnaires investigating the organisation of diabetes care centres, individuals’ clinical and metabolic features and pump technology and its management were sent to adult and paediatric diabetes centres that use CSII for treatment in Italy. Information on standard clinical variables, demographic data and acute and chronic diabetic complications was derived from local clinical management systems. The sample consisted of 6623 people with diabetes, which was obtained from 93 centres. Of them, 98.8% had type 1 diabetes mellitus, 57.2% were female, 64% used a conventional insulin pump and 36% used a sensor-augmented insulin pump. The median glycated haemoglobin (HbA1c) level was 60 mmol/mol (7.6%). The HbA1c target (i.e. 18 years) was achieved in 43.4% of paediatric and 23% of adult participants. Factors such as advanced pump functions, higher rate of sensor use, pregnancy in the year before the study and longer duration of diabetes were associated with lower HbA1c levels. The most common chronic complications occurring in diabetes were retinopathy, microalbuminuria and hypertension. In the year before the study, 5% of participants reported ≥1 episode of severe hypoglycaemic (SH) episodes (SH) and 2.6% reported ≥1 episode of ketoacidosis. Conclusions: Advanced personal skills and use of sensor-based pump are associated with better metabolic control outcomes in Italian people with diabetes who were treated with CSII. The reduction in SH episodes confirms the positive effect of CSII on hypoglycaemia. Clinical trial registration number: NCT 02620917 (ClinicalTrials.gov).

Background Quantitative and semiquantitative methods have been proposed for the assessment of MR severity, and though all are associated with limitations. Measurement of vena contracta width (VCW) has been used in clinical practice. Objective To measure the VCW in dogs with different levels of MR severity. Animals Two hundred and seventy‐nine dogs were classified according to 5 levels of MR severity. Methods This was a retrospective study. EROA and regurgitant volume calculated by the PISA method, were measured and indexed to BSA. Descriptive statistics were calculated for VCW and VCW index for all categories of MR severity. Spearman's rank correlation coefficients (ρs) were calculated to compare the results of the different methods (VCW and VCW index vs RV PISA, RV PISA index, EROA, EROA index), and between VCW and VCW index versus MR severity. Results All Spearman's rank correlation coefficients were significant (P

The study was initiated to evaluate the ability of hyperinsulinemia (as a surrogate measure of insulin resistance) to predict the development in a previously healthy population of three putative outcomes of this abnormality--glucose intolerance, hypertension, and coronary heart disease (CHD). The study involved defining the incidence at which these changes occurred between 1981 and 1993 to 1996 in 647 individuals who were free of any disease when initially studied. The study population consisted of approximately 90% of the subjects evaluated in 1981, divided into quartiles on the basis of the plasma insulin response to a glucose challenge as determined in 1981. The results indicated that the 25% of the population with the highest insulin response in 1981 had significant (P < .001) increases in the incidence of impaired glucose tolerance (IGT) or type 2 diabetes (eightfold), hypertension (twofold), or CHD (threefold). Furthermore, the ability of hyperinsulinemia to predict the three clinical endpoints was independent of differences in age, gender, or body mass index (BMI). Finally, if CHD is considered the clinical endpoint, multiple logistic regression analysis indicates that the values for plasma triglyceride (TG) and mean arterial blood pressure ([MAP] as measured in 1981) also predict the development of CHD. These results indicate that the untoward clinical effects of insulin resistance and/or compensatory hyperinsulinemia, glucose intolerance, hypertension, and CHD clearly can develop in less than 15 years.

Objective: To investigate weight loss expectations (Expected One-Year BMI Loss, Dream and Maximum Acceptable BMI) in obese patients seeking treatment and to examine whether expectations differ by sex, weight, diet and weight history, age, psychological factors, and primary motivations for weight loss. Research Methods and Procedures: 1,891 obese patients seeking treatment in 25 medical Italian centers (1,473 females; age, 44.7 ± 11.0 years; BMI, 38.2 ± 6.5 kg/m2) were evaluated. Diet and weight history, weight loss expectations, and primary motivation for seeking treatment (health or improving appearance) were systematically recorded. Psychiatric distress, binge eating and body image dissatisfaction were tested by self-administered questionnaires (Symptom CheckList-90, Binge Eating Scale and Body Uneasiness Test). Results: In 1,011 cases (53.4%), one-year expected BMI loss was ? 9 kg/m2. Dream BMI was 26.0 ± 3.4 kg/m2 (corresponding to a 32% loss), Maximum Acceptable BMI was 29.3 ± 4.4 kg/m2 (-23%). BMI and age were the strongest predictors of weight goals. Weight loss necessary to reach the desired targets was largely in excess of weight loss observed during previous dieting. Psychiatric distress, body dissatisfaction and binge eating did not significantly predict weight loss expectations. The primary motivation for weight loss was concern for future or present health; women seeking treatment to improve appearance had a lower grade of obesity, were younger, and had first attempted weight loss at a younger age. Discussion: Obese Italian patients have unrealistic weight loss expectations, similar to those reported by American patients. There are significant disparities between patients’ perception and physicians’ weight loss recommendation of desirable treatment outcome.

RIASSUNTO Nonostante gli sforzi per diffondere e implementare le raccomandazioni nutrizionali per il trattamento del diabete, la loro applicazione nella pratica clinica è ancora largamente insufficiente. Tra le possibili ragioni va considerato il fatto che le abitudini alimentari risentono molto delle tradizioni gastronomiche locali. Lo studio si propone di valutare le abitudini alimentari delle persone con diabete in tre macroaree geografiche italiane, nord, centro e sud, per studiare in che misura le tradizioni gastronomiche locali possano influenzare l'adesione alle raccomandazioni nutrizionali. Sono stati studiati 1786 pazienti diabetici di tipo 2; le abitudini alimentari sono state indagate con un questionario alimentare semiquantitativo di frequenza validato (EPIC, European Prospective Investigation on Cancer and Nutrition). L'introito energetico è sovrapponibile nelle 3 macroaree geografiche, ma gli alimenti che contribuiscono alla composizione della dieta sono diversi a seconda della locazione geografica: al nord si osserva un maggiore consumo di carne, salumi e grassi animali; al sud, un maggiore consumo di pane integrale e legumi. Questo si traduce in una differente composizione in nutrienti della dieta: il consumo di grassi totali, grassi saturi e polinsaturi risulta significativamente più basso al sud e al centro rispetto al nord (p < 0,05); il contrario si osserva, invece, per i carboidrati totali e la fibra alimentare (p < 0,05). Infine, la proporzione di pazienti che aderiscono alle raccomandazioni nutrizionali è generalmente scarsa sia per il consumo di fibra, mediamente inferiore rispetto a quanto raccomandato, sia per il consumo di grassi saturi, mediamente superiore ai livelli consigliati. In conclusione, le raccomandazioni nutrizionali sono scarsamente seguite su tutto il territorio nazionale; si osservano, tuttavia, significative differenze geografiche verosimilmente dovute all'influenza delle tradizioni gastronomiche locali che vanno tenute in conto per migliorare l'adesione dei pazienti alle raccomandazioni dietetiche.

Objectives. To define the effect of asymptomatic hyperuricaemia on various facets of glucose, insulin, and lipoprotein metabolism. Design. Case control study in health volunteers. Setting. The volunteers for this study were selected on the basis of their laboratory results from a larger population participating in a general survey in one large factory. Subjects. The study population consisted of 40 healthy males: 20 with asymptomatic hyperuricaemia (serum uric acid concentration equal to or greater than 420 mmol l−1) and 20 with normal serum uric acid concentrations (180–320 mmol l−1). The two groups were similar in terms of age, general obesity (estimated by body mass index), smoking and alcohol intake, and estimate of work and leisure time activity. Interventions. All subjects received a 75 g oral glucose challenge, with blood taken before and at frequent intervals thereafter. Main outcome measures. Fasting plasma glucose, insulin, and lipid concentrations and plasma glucose and insulin responses to the oral glucose challenge. Results. By selection, mean (± sem) serum uric acid concentration was higher in the hyperuricaemic individuals (454 ± 7 vs. 274 ± 12 mmol l−1). In addition, the plasma insulin response to oral glucose was increased in individuals with asymptomatic hyperuricaemia (P < 0.005) as were both systolic (136 ± 3 vs. 126 ± 3 mmHg, P < 0.05) and diastolic (91 ± 1 vs. 82 ± 1, P < 0.01) blood pressure. Furthermore, subjects with asymptomatic hyperuricaemia were dyslipidaemic (higher plasma TG and cholesterol and lower HDL-cholesterol concentrations) as compared to the normouricaemic control group (P < 0.07–0.005). Conclusions. These results provide a possible explanation for the well-known association of hyperuricaemia with coronary heart disease, as well as suggesting that hyperuricaemia be added to the cluster of metabolic and haemodynamic abnormalities associated with insulin resistance and/or hyperinsulinaemia and designated as Syndrome X.

Background Recent advances in technology have provided the opportunity for off-line analysis of digital video-clips of two-dimensional (2-D) echocardiographic images. Commercially available software that follows the motion of cardiac structures during cardiac cycle computes both regional and global velocity, strain, and strain rate (SR). The present study aims to evaluate the clinical applicability of the software based on the tracking algorithm feature (studied for cardiology purposes) and to derive the reference values for longitudinal and circumferential strain and SR of the left ventricle in a normal population of children and young adults. Methods 45 healthy volunteers (30 adults: 19 male, 11 female, mean age 37 ± 6 years; 15 children: 8 male, 7 female, mean age 8 ± 2 years) underwent transthoracic echocardiographic examination; 2D cine-loops recordings of apical 4-four 4-chamber (4C) and 2-chamber (2C) views and short axis views were stored for off-line analysis. Computer analyses were performed using specific software relying on the algorithm of optical flow analysis, specifically designed to track the endocardial border, installed on a Windows™ based computer workstation. Inter and intra-observer variability was assessed. Results The feasibility of measurements obtained with tissue tracking system was higher in apical view (100% for systolic events; 64% for diastolic events) than in short axis view (70% for systolic events; 52% for diastolic events). Longitudinal systolic velocity decreased from base to apex in all subjects (5.22 ± 1.01 vs. 1.20 ± 0.88; p < 0.0001). Longitudinal strain and SR significantly increased from base to apex in all subjects (-12.95 ± 6.79 vs. -14.87 ± 6.78; p = 0.002; -0.72 ± 0.39 vs. -0.94 ± 0.48, p = 0.0001, respectively). Similarly, circumferential strain and SR increased from base to apex (-21.32 ± 5.15 vs. -27.02 ± 5.88, p = 0.002; -1.51 ± 0.37 vs. -1.95 ± 0.57, p = 0.003, respectively). Values of global systolic SR, both longitudinal and circumferential, were significantly higher in children than in adults (-1.3 ± 0.2, vs. -1.11 ± 0.2, p = 0.006; -1.9 ± 0.6 vs. -1.6 ± 0.5, p = 0.0265, respectively). No significant differences in longitudinal and circumferential systolic velocities were identified for any segment when comparing adults with children. Conclusion This 2D based tissue tracking system used for computation is reliable and applicable in adults and children particularly for systolic events. Measured with this technology, we have established reference values for myocardial velocity, Strain and SR for both young adults and children.

Obesity dietetic treatment produces a residual bulk reduction that is easily responsible of constipation. Fiber addiction improves bowel transit. To avoid some unpleasant effects of high molecular weight fibers, a research was made on a colloidal cellulose microfibers (MCC) product, that for its low molecular weight and its phytic acid lack, can limit these problems. Influence on constipation, blood and chemical analysis and satiation has been studied.Research was made on obese patients. One group (studied for 4 weeks) of 30 subjects, 25 affected by simple obesity, and 5 obese, with hyperlipemia and non insulin dependent diabetes. The other group (studied for 8 weeks) of 10 subjects affected by simple obesity. The product was in tablets containing MCC 0.600 mg each, to be taken daily in dose of 4/6. Weight, BMI, total and fractionated cholesterol, triglycerides, A and B lipoproteins, uric acid, glucose and glycosylated hemoglobin (in diabetic patients), blood count and plasma iron level (in the second group of patients) had been determined. Each subject reported on a record evacuations, collaterals symptoms, sense of satiation.83% in the first group of patients and 90% in the second group showed defecation improvement. No changes were found in controlled parameters. MCC effect has been constipation correction.This fiber can be suggested in obese subjects when diet caused a slow bowel transit. Supplement can be protracted because it doesn't interfere with iron absorption.

Genetic mapping of major genes and quantitative traits loci (QTLs) for many important agricultural traits is increasing the integration of biotechnology with the conventional breeding process. Exploitation of the information derived from the map position of traits with agronomical importance and of the linked molecular markers, can be achieved through marker assisted selection (MAS) of the traits during the breeding process. However, empirical applications of this procedure have shown that the success of MAS depends upon several factors, including the genetic base of the trait, the degree of the association between the molecular marker and the target gene, the number of individuals that can be analyzed and the genetic background in which the target gene has to be transferred. MAS for simply inherited traits is gaining increasing importance in breeding programs, allowing an acceleration of the breeding process. Traits related to disease resistance to pathogens and to the quality of some crop products are offering some important examples of a possible routinary application of MAS. For more complex traits, like yield and abiotic stress tolerance, a number of constraints have determined severe limitations on an efficient utilization of MAS in plant breeding, even if there are a few successful applications in improving quantitative traits. Recent advances in genotyping technologies together with comparative and functional genomic approaches are providing useful tools for the selection of genotypes with superior agronomical performancies.

The activity of the hypothalamic-GH-insulin-like growth factor (IGF) network declines with age. It has recently been shown that increased cardiovascular mortality occurs in adults with GH deficiency. As hypercholesterolemia is common in GH-deficient adults, and because there is experimental evidence that GH may play a role in regulating plasma cholesterol, we decided to investigate the activity of the GH-IGF axis in an elderly population by measuring serum IGF-I, IGF-II, and IGF-binding protein-3 (IGFBP-3) levels and to study their relationship with blood lipid levels. One hundred and thirty-two elderly subjects, 52 men and 80 women, were studied (age range, 60-91 yr). Men had significantly lower levels of IGFBP-3, high density lipoprotein cholesterol (HDL-C) and apoprotein A1 (ApoA1) compared to the women, whereas IGF-I and IGF-II were only slightly lower. Using linear regression analysis, we observed an inverse relationship of age with IGF-I (r = -0.35; P0.001), IGF-II (r = 0.40; P0.001), IGFBP-3 (r = 0.52; P0.001), body mass index, and lipid levels. Univariate regression analysis showed a strong and positive correlation of both IGF-I and IGFBP-3 with HDL-C and ApoA1. Partial correlation analysis, after adjustment for age and body mass index, showed that IGFBP-3 and IGF-II were still significantly and positively related to HDL-C and ApoA1. Furthermore, a strong association was documented among IGF-I, IGF-II, and IGFBP-3. These data demonstrate that even in an elderly population, further aging is accompanied by a progressive decline in circulating IGF-I, IGF-II, and IGFBP-3, suggesting a continuing diminution of the GH-IGF axis throughout aging. Moreover, the strong correlation between HDL-C and an index of GH secretion, such as IGFBP-3, suggests that GH might play an important role in lipid metabolism in healthy elderly subjects.

Objectives. To see if the cluster of metabolic and haemodynamic variables defined as comprising Syndrome X varied as a function of urinary albumin excretion (UAE) rate in a healthy population. Design. A cross-sectional, population-based study. Setting. A factory in Italy. Subjects. Two hundred and twenty-five healthy volunteers, 115 men and 110 women. Outcome measures. Measurements were made of the plasma glucose and insulin responses to oral glucose, fasting triglyceride (TG) and high density lipoprotein (HDL)-cholesterol concentrations, blood pressure, and UAE rates. Results. Only five of the 225 volunteers had microalbuminuria, defined as a UAE rate >2 μg min-1, and the UAE rate was

Objective. The major aim of this study was to compare various aspects of carbohydrate, insulin, and lipoprotein metabolism, serum uric acid concentration, and blood pressure in normal subjects stratified on the basis of both plasma insulin concentration and degree of obesity. The hypothesis to be tested was that hyperinsulinaemia, per se, was associated with relative glucose intolerance, higher triglyceride and uric acid concentrations, lower high-density lipoprotein cholesterol concentration and higher blood pressure, irrespective of degree of obesity. Design. This represents a case-control study, in which normal volunteers were subdivided into four equal groups based upon degree of obesity and plasma insulin response to a 74 g oral glucose challenge. Setting. The study was performed in the out-patient clinic of a university hospital. Subjects. Sixty-four individuals were recruited for this study, subdivided into four groups based upon their plasma insulin concentration and body mass index. Subjects were classified as hyperinsulinaemic if their plasma insulin concentrations in response to an oral glucose challenge were more than two standard deviations above the mean of 732 volunteers previously studied [1]. Obesity was defined as a body mass index of > 30 kg m-2, and individuals were classified as non-obese if their body mass index was < 27.0 kg m-2. Based upon these criteria, four experimental groups were created: (i) non-obese hyperinsulinaemic (NOB hyper); (ii) obese hyperinsulinaemic (OB hyper); (iii) non-obese normo-insulinaemic (NOB normo); and (iv) obese normo-insulinaemic (OB normo). Main outcome measures. Subject groups were compared on the basis of the integrated plasma glucose response to a 75 g oral glucose challenge, fasting plasma triglyceride, cholesterol, high-density lipoprotein cholesterol, and uric acid concentrations, and blood pressure. Results. Mean (± standard error of the mean) integrated plasma glucose response area for 2 h following a 75 g oral glucose load was significantly higher (13.4 ± 0.4 vs. 11.0 ± 0.4 mmol 1-1, P < 0.001) in the hyperinsulinaemic group, as were the fasting triglyceride levels (2.4 ± 0.2 vs. 1.4 ± 0.1 mmol 1-1, P < 0.001) and uric acid (5.3 ± 0.2 vs. 4.4 ± 0.2 mmol 1-1, P < 0.05) concentrations. In contrast, high-density lipoprotein concentrations were lower in the hyperinsulinaemic group (1.06.0.05 vs. 1.32 ± 0.05 mmol 1-1, P < 0.001). In addition, blood pressure was higher in the hyperinsulinaemic group (136 ± 5/87 ± 2 vs. 123 ± 2/82 ± 1 mmHg, P < 0.05). Furthermore, when each of the two groups were divided into obese (n = 16) and non-obese (n = 16) groups, all of the differences outlined above persisted. These changes were independent of age, gender distribution, generalized and abdominal obesity, cigarette smoking, and estimated physical activity. Conclusions. The cluster of changes subsumed under the heading of syndrome X are closely associated with hyperinsulinaemia (and presumably insulin resistance), and can be discerned irrespective of degree of obesity.

Plasma triglyceride concentrations were shown to be higher in hypertensive (153 +/- 2 mm Hg) male Dahl salt-sensitive rats than in control Sprague-Dawley rats (122 +/- 2 mm Hg). These differences in triglyceride concentrations were seen when blood was drawn at 9 AM from unfasted animals (229 +/- 27 versus 111 +/- 8 mg/dL), at 1 PM after a 4-hour fast (186 +/- 13 versus 88 +/- 4 mg/dL), or at 9 AM after a 13-hour fast (151 +/- 6 versus 90 +/- 6 mg/dL), all p < 0.001. Total triglyceride secretion was also compared in groups of rats by determining the increment in plasma triglyceride concentration for 2 hours after blocking triglyceride removal from plasma by injecting Triton. Studies performed at 1 PM and 9 AM, after the 4- and 13-hour fast, demonstrated that total triglyceride secretion was greater (p < 0.05) in Dahl rats only when studied at 1 PM. Direct estimates of hepatic triglyceride secretion at 1 PM also demonstrated a significant (p < 0.02) increase in secretion rate by perfused livers from Dahl rats, due in part to their increased liver size. In addition, removal of prelabeled very low density lipoprotein-triglyceride in the intact rat was significantly (p < 0.05) decreased in Dahl rats. Lipoprotein lipase activity measured in skeletal muscle, heart, and adipose tissue was also significantly decreased at 9 AM and 1 PM (after 0 and 4 hours of fasting) in tissue from Dahl rats. These data confirm that Dahl rats have higher plasma triglyceride concentrations than Sprague-Dawley rats. Since both total and hepatic triglyceride secretion were somewhat greater in Dahl rats, in association with a decrease in both removal of very low density lipoprotein from plasma and decreased muscle and adipose tissue lipoprotein lipase activity, it seems likely that hypertriglyceridemia in Dahl rats results from a combination of increased triglyceride secretion and decreased triglyceride removal.

A total of 41 patients with hypertension were identified in a survey of 732 healthy factory workers. Twenty-three of these individuals were receiving antihypertensive medication, whereas 18 cases were newly discovered. Plasma glucose and insulin responses to oral glucose and fasting plasma triglyceride (TG), cholesterol, and high-density-lipoprotein (HDL) cholesterol concentrations of these 41 individuals were compared with those of 41 other factor workers, with normal blood pressure, matched with the hypertensive group in terms of gender, age, degree of obesity, job in the factory, and leisure-time activity. Patients with hypertension had significantly higher plasma glucose (P less than 0.05) and insulin (P less than 0.05) concentrations in response to oral glucose, as well as a higher plasma TG concentration (P less than 0.05). Similar findings were obtained when the treated and untreated hypertensive groups were analysed separately and compared with their respective control groups. However, there were no differences between the treated and untreated hypertensive groups. Ninety per cent of the normotensive group had a plasma insulin concentration of less than 500 pmol l-1 2 h after the glucose load. Using this value as the criterion for definition of hyperinsulinaemia, 41% of the patients with high blood pressure were hyperinsulinaemic. In addition to meeting this cut-off point, the patients with hypertension and hyperinsulinaemia were also glucose intolerant and dyslipidaemic. In conclusion, approximately 50% of an unselected group of patients with hypertension were hyperinsulinaemic. Insulin levels were comparable in treated and untreated patients with high blood pressure, and hyperinsulinaemic patients also tended to be glucose intolerant and dyslipidaemic.

Plasma glucose, insulin, triglyceride, and cholesterol concentrations were measured in male rats of the Milan hypertensive strain (MHS) and compared to the Milan normotensive strain (MNS) of the same body weight. Both blood pressure (P less than .001) and left ventricular weight (P less than .005) were higher in rats of the MHS. Although plasma glucose concentrations were similar in both groups, mean (+/- SEM) plasma insulin concentration were significantly higher (P less than .01) in MHS as compared to MNS rats (30 +/- 4 v. 13 +/- 5 microU/mL). In addition mean (+/- SEM) plasma triglyceride concentrations were higher (P less than .01) in MHS rats (112 +/- 9 mg/dL) than in MNS rats (81 +/- 6 mg/dL), as were plasma cholesterol concentrations (114 +/- 3 v 100 +/- 2 mg/dL, P less than .001). These data demonstrate the presence of hyperinsulinemia and hypertriglyceridemia in another genetic model of rat hypertension.

The effect of streptozotocin-induced diabetes mellitus on maximal insulin-stimulated glucose uptake in the rat was studied in isolated adipocyte, perfused hindlimb, and the intact organism. Basal glucose transport per fat cell was reduced by approximately two-thirds (P less than 0.001), being associated with a similar decrease in glucose oxidation per fat cell (P less than 0.001). There was also a significant decrease (P less than 0.001) in basal glucose uptake by perfused hindlimb of diabetic rats of approximately 40%. Furthermore, maximal insulin-stimulated glucose transport and oxidation were approximately 50% lower (P less than 0.001) in fat cells of diabetic as compared with control rats. In contrast, maximal insulin-stimulated glucose disposal by perfused hindlimbs from diabetic and control rats was similar, and this was also true of the ability of insulin to maximally stimulate glucose uptake in the intact normal and diabetic rat. These findings indicate that variation exists in the manner in which insulin-sensitive tissues respond to experimentally induced insulin deficiency and support the view that total body glucose disposal is primarily related to insulin action on muscle.

Plasma lipid, lipoprotein, and apoprotein concentrations were measured in 169 patients with non-insulin-dependent diabetes mellitus (NIDDM), 78 with normal blood pressure, and 91 diagnosed and receiving drug treatment for hypertension. Plasma triglyceride, cholesterol, low-density lipoprotein-cholesterol, and apoprotein B concentrations were significantly higher (p = less than 0.05 to less than 0.001) in the hypertensive group. In addition, the ratios of high-density to low-density lipoprotein-cholesterol and of apoprotein A-1 to apoprotein B were significantly reduced (p less than 0.01) in patients with hypertension. The changes noted were independent of differences in sex distribution, degree of obesity, and level of glycemic control. These results indicate that substantial differences in plasma lipid, lipoprotein, and apoprotein concentrations are seen when normotensive patients with NIDDM are compared with patients who are also being treated for hypertension, and that all of the changes noted would increase the risk of coronary artery disease in the hypertensive group. Since all patients with hypertension were receiving anti-hypertensive medications, it is not clear if it is hypertension per se, or its treatment, that is responsible for the observed changes in lipid metabolism.

Multiple risk factors for coronary artery disease were determined in 50 healthy, non-diabetic persons with an oral glucose tolerance test result that could not be classified as normal by current criteria and 50 sex-, age-, and weight-matched persons with normal oral glucose tolerance. The results indicated that persons with abnormal oral glucose tolerance were hyperinsulinemic, as well as hypercholesterolemic and hypertriglyceridemic. In addition, patients with abnormal results in glucose tolerance tests had significantly elevated systolic blood pressure and heart rates. These data suggest that a cluster of risk factors for coronary artery disease exists in non-diabetic persons with abnormal oral glucose tolerance.

Prazosin was administered by intraperitoneal injection (0.3 or 3.0 mg/kg) to normal chow-fed male rats for 14 days. Mean +/- SEM plasma triglyceride levels were lower (p less than 0.001) in the prazosin-treated rats (74 +/- 12 mg/dl and 72 +/- 9 mg/dl) than in saline-injected control rats (115 +/- 11 mg/dl). This effect was associated with commensurate reductions in very low density lipoprotein-triglyceride secretion in prazosin-treated rats. No changes were noted in either plasma total or high density lipoprotein cholesterol concentrations. In addition, prazosin was capable of reducing by approximately 50% the elevation in plasma triglyceride concentration produced by a high glucose diet in control rats. The mechanism of the observed effect of prazosin on very low density lipoprotein metabolism in the rat remains to be defined.

Administration of pyridoxine-alpha-ketoglutarate (PAK) to a group of insulin-independent non-ketotic diabetics decreased (p less than 0.01) the plasma concentration of lactate response to isometric exercise. The mechanism of action of PAK could be interpreted as a consequence of changes induced by the drug on the Krebs' cycle with a subsequent reduction of lactate production.

Adipocytes contain adenosine receptors, termed A1 receptors, which inhibit lipolysis by decreasing adenylate cyclase activity. The inhibition of lipolysis by adenosine agonists in vivo acutely suppresses the plasma concentrations of free fatty acids (FFA) and triglycerides. We have found that infusions of the adenosine receptor agonist phenylisopropyladenosine (PIA) initially decreases plasma FFA concentrations; however, with prolonged exposure (6 d), rats become very tolerant to the effects of the drug. Adipocytes isolated from epididymal fat pads from PIA-infused rats have altered lipolytic responses. When lipolysis is stimulated with a relatively high concentration of isoproterenol (10(-7) M), PIA does not inhibit lipolysis in adipocytes from the infused animals. However, PIA inhibits isoproterenol-stimulated cyclic AMP (cAMP) accumulation in adipocytes from the infused rats although with decreased sensitivity compared with controls. The explanation for the impaired antilipolytic effect appears to be due to the fact that isoproterenol-stimulated cAMP accumulation is markedly increased in cells from infused rats. Indeed, basal lipolysis and lipolysis stimulated with lower concentrations of isoproterenol (10(-9), 10(-8) M) are effectively inhibited by PIA. cAMP accumulation is greatly increased in adipocytes from infused rats when stimulated by isoproterenol, ACTH, and forskolin. The results have some striking analogies to changes induced in nerve cells by prolonged exposure to narcotics. These data suggest that tolerance to PIA develops in adipocytes as a consequence of enhanced cAMP accumulation.

Plasma insulin and C-peptide levels in the fasting state and after a 2-h 75 g oral glucose tolerance test (OGTT) in a large number of healthy subjects are reported. 247 volunteers (134 males, 113 females), aged 13-69 years, who had a negative history of diabetes, no history of significant disease, normal physical examination, normal body weight, normal glucose tolerance, normal blood tests, and who were taking no drugs were studied. Results, mean +/- SEM (range): fasting glucose concentration = 4.64 +/- 0.03 mmol/l (3.10 - 6.10), 1-h glucose concentration = 5.23 +/- 0.10 mmol/l (2.20 - 9.90), 2-h glucose concentration = 4.11 +/- 0.06 mmol/l (2.00 - 6.80); fasting insulin level = 0.088 +/- 0.002 nmol/l (0.03 - 0.28), 1-h insulin level = 0.45 +/- 0.01 nmol/l (0.06 - 1.63), 2-h insulin level = 0.24 +/- 0.01 nmol/l (0.05 - 1.12); fasting C-peptide concentration = 0.60 +/- 0.01 nmol/l (0.14 - 1.34), 1-h C-peptide concentration = 2.17 +/- 0.05 (0.63 - 8.56), 2-h C-peptide concentration = 1.77 +/- 0.04 nmol/(0.35 - 5.74). Fasting insulin and fasting C-peptide concentrations correlated to post-glucose insulin and C-peptide concentrations, respectively. At each sampling-point insulin concentration correlated to C-peptide concentration. After glucose ingestion, both insulin and C-peptide plasma levels correlated significantly with the corresponding glucose levels. During fasting, C-peptide but no insulin level correlated to glucose level.(ABSTRACT TRUNCATED AT 250 WORDS)

Increased plasma insulin and triglycerides and decreased high density lipoprotein concentrations are primary risk factors in the development of coronary artery disease. The aim of the present study was to verify whether there was an independent relationship between plasma insulin levels and both HDL cholesterol and triglyceride in a worker population of 607 subjects, 389 men and 218 women, aged 23-73 years. An oral glucose tolerance test (75 g) was performed. Plasma glucose, insulin, triglyceride and HDL cholesterol were measured at fasting, plasma glucose and insulin were determined also 1 h and 2 h after glucose load. The results, examined separately in men and women documented a significant negative relationship between plasma insulin and HDL cholesterol level, as well as pointing out that both HDL cholesterol and insulin are significantly correlated to degree of hypertriglyceridemia, degree of obesity and level of glucose tolerance. The partial correlation coefficients between HDL cholesterol and plasma insulin levels at fasting in men and post-glucose load in women, demonstrated an independent relationship between increased plasma insulin and decreased plasma HDL concentration. However, the strongest relationship, revealed by partial correlation coefficient analysis, was between the degree of hyperinsulinemia and hypertriglyceridemia.

We have studied metabolic, circulatory and vascular parameters in a group of 57 diabetics (37 affected by IDDM, 20 affected by NIDDM; 35 were males, 22 were females). Goals of present study were: 1) quantitative evaluation of the blood retinal barrier; 2) influence of the metabolic state, blood pressure, sex, type and duration of the diabetes on the ocular conditions; 3) relationship between ophthalmoscopic appearance of the retina and vitreous fluorophotometric recordings. We concluded that: a) ocular alterations depend by lipidic metabolism, blood pressure, sex, type and duration of the diabetes; b) vitreous fluorophotometry has proved a good device for early detection of retinal damages in the diabetic retinopathy.

The aim of the present study was to investigate the secretion and hepatic removal of insulin in the healthy offspring of type 2 (non-insulin-dependent) diabetic subjects. For this purpose, we examined the insulin and C-peptide responses to a 75 g oral glucose tolerance test in a group of 55 healthy subjects each having one parent with type 2 diabetes mellitus, and in a group of 55 individuals without a family history of diabetes. All the 110 subjects in the study were ambulatory volunteers, in good general health, and with normal glucose tolerance. The two groups were carefully matched for sex, age, and body weight. Glucose and insulin concentrations as well as incremental areas were similar in the two groups. C-peptide levels and incremental areas were almost identical. C-peptide to insulin molar ratios both in fasting state and after glucose load, as well as relations between C-peptide and insulin incremental areas did not differ in the two groups. In conclusion, the healthy offspring of only one non-insulin-dependent diabetic parent show a normal beta-cell response to glucose, and normal removal of insulin by the liver.

The ability of metformin to prevent carbohydrate-induced hypertriglyceridemia was studied in fructose fed rats. The results indicated that plasma triglycerides were approximately 50% reduced in the drug treated rats and the reduction was associated with lowered very low density lipoprotein-triglyceride secretion rates and plasma insulin levels. Since the drug does not affect the fructose intestinal absorption, it did not prevent normal rate of weight gain. These results provide further evidence for the existence of a causal relationship between plasma TG concentration and plasma insulin concentration; metformin is able to modify both these variables likely affecting primarily the ambient insulin level.

Activation of adenosine receptors leads to the inhibition of lipolysis in the fat cells of several species including humans. We have examined the effects of the adenosine analog phenylisopropyladenosine (PIA) on lipolysis in vivo in intact rats. PIA suppresses markedly serum-free fatty acid (FFA) concentrations when injected s.c. (-)-PIA is more potent than (+)-PIA in suppressing FFA concentrations; also, this effect of (-)-PIA is blocked by the adenosine receptor antagonist 8-(p-sulfophenyl)theophylline. (-)-PIA also suppressed plasma triglyceride (TG) concentrations by approximately 50% in these rats. Utilizing Triton WR1339 injections, we found that the decrease in serum TG concentrations was associated with a marked fall in very low density lipoprotein secretion rate. We also examined the effects of (-)-PIA on FFA and TG concentrations in two models of hypertriglyceridemia in rats: stretozotocin-induced diabetes and sucrose feeding. Both groups had elevated FFA and TG concentrations compared with controls. An injection of (-)-PIA suppressed markedly FFA concentrations and essentially normalized the serum concentration of TG in these rats. We conclude that (-)-PIA suppresses markedly lipolysis and triglyceride secretion in control and hypertriglyceridemic rats suggesting that the activation of adenosine receptors may have major metabolic effects in vivo.

The anticoagulant effect of a Low Molecular Weight Heparin from Alfa Farmaceutici, Bologna, Italy, was studied in human volunteers of either sex. Assays of plasma anti Xa (S-2222) and anti IIa (cromozym TH) activities, and of PTT, were performed following single or repeated administration by intravenous (i.v.), subcutaneous (s.c.) or intramuscular (i.m.) route. Each set of experiments was carried out in groups of subjects ranging from 6 to 12. After i.v. adm. of 8000 and 16000 I.U. AXa peak level and half life in plasma of the anti Xa activity were about double than the corresponding values of anti IIa activity and the effect on PTT, when compared with the same reference material (heparin, Third Internat. Standard). Similar differences between these pharmacological effects were found in the response curves obtained after s.c. or i.m. adm. of 16000 and 8000 I.U. Appreciable anti Xa activity was found in plasma 16-20 hours after adm. of 16000 I.U., and 10 hours after 8000 I.U. After repeated i.m. or s.c. adm. for 7 days, no cumulative effect was observed with 16000 I.U. once daily. By giving 8000 b.i.d., mean peak levels of .35-.40 U/ml of anti Xa activity were reached in the first day and of .45-.55 U/ml in the following days, a residual activity in the order of .1-.2 U/ml being always detected in the samples drawn immediately before the following injection.

The level of fructose 2,6-bisphosphate (F2,6P2), a potent stimulator of 6-phosphofructo-1-kinase and inhibitor of fructose 1,6-bisphosphatase, was measured in three different muscle types (tensor fascia latae, biceps femoris, and soleus) and in the liver of normal and diabetic rats. The mean (+/- SEM) content of F2,6P2 (nanomoles per g tissue) varied among the three types of skeletal muscle in normal rats, with the biceps femoris having the highest (0.97 +/- 0.15) and the soleus the lowest (0.57 +/- 0.03) levels. However, these differences were unrelated to simultaneous estimates of skeletal muscle activity of 6-phosphofructo-1-kinase activity. The total concentration of F2,6P2 was more than 8-fold higher (8.5 +/- 0.9) in the liver, and this value fell to 5.3 +/- 0.8 (P less than 0.05) after the induction of diabetes with streptozotocin. In contrast, F2,6P2 levels did not fall in skeletal muscle of rats with streptozotocin-induced diabetes, and the concentration actually increased. Thus, the fall in hepatic F2,6P2 concentration associated with insulin deficiency was not observed in skeletal muscle.

Thyroid hormone serum concentrations, the thyrotropin (TSH) and prolactin (PRL) response to thyrotropin-releasing hormone (TRH) were evaluated in patients undergoing cardiopulmonary bypass (CPB) conducted in hypothermia. During CPB a marked decrease of thyroxine (T4) and triiodothyronine (T3) concentration with a concomitant increase of reverse T3 (rT3) were observed similarly to other clinical states associated with the 'low T3 syndrome'. Furthermore, in the present study elevated FT4 and FT3 concentrations were observed. In a group of patients, TRH administered during CPB at 26 degrees C elicited a markedly blunted TSH response. In these patients, PRL concentration was elevated but did not significantly increase after TRH. The increased concentrations of FT4 and FT3 were probably due to the large doses of heparin administered to these patients. Thus, the blunted response of TSH to TRH might be the consequence of the elevation of FT4 and FT3 in serum, however, other factors might play a role since also the PRL response to TRH was blocked.

The effect of age on glucose tolerance, as differentiated from the effects of obesity, work and leisure physical activity, family history of diabetes, and the use of drugs known to adversely affect glucose tolerance and/or insulin secretion, has been analyzed in 732 factory workers aged 22 to 73 years. Glucose tolerance, as evaluated by the plasma glucose response to 75 g of oral glucose deteriorated with age, associated with an increase in plasma insulin levels. However, the age-related decrease in glucose tolerance also correlated significantly with degree of obesity, leisure-time physical activity, and the use of potential diabetogenic drugs. Partial correlation coefficients were calculated to define the effect of age per se on glucose tolerance, controlling for the presence of these other age-related variables. When this was done, the degree of correlation between age and glucose tolerance was reduced, particularly in women, to where it became of marginal statistical significance. The effect of age on insulin response was affected to a greater degree by age-related variables, and was no longer statistically significant when these other factors were taken into consideration. These data suggest that the elevation in plasma glucose and insulin levels associated with age are to a certain extent due to age-related environmental factors, and the deterioration in glucose tolerance with age is relatively modest in magnitude in a generally healthy population.

Prazosin was administered by intraperitoneal injection (0.3 or 3.0 mg/kg) to normal chow-fed male rats for 14 days. Mean +/- SEM plasma triglyceride levels were lower (p less than 0.001) in the prazosin-treated rats (74 +/- 12 mg/dl and 72 +/- 9 mg/dl) than in saline-injected control rats (115 +/- 11 mg/dl). This effect was associated with commensurate reductions in very low density lipoprotein-triglyceride secretion in prazosin-treated rats. No changes were noted in either plasma total or high density lipoprotein cholesterol concentrations. In addition, prazosin was capable of reducing by approximately 50% the elevation in plasma triglyceride concentration produced by a high glucose diet in control rats. The mechanism of the observed effect of prazosin on very low density lipoprotein metabolism in the rat remains to be defined.

Fatty liver at ultrasounds, with/without raised plasma levels of hepatic enzymes, is common in obesity. In most cases, it is the hallmark of nonalcoholic fatty liver disease (NAFLD), a potentially progressive disease associated with insulin resistance and the metabolic syndrome. We tested the hypothesis that insulin resistance per se might be associated with hepatocellular necrosis. Alanine and aspartate aminotransferases (ALT and AST; n = 799) and gamma-glutamyltranspeptidase (GGT; n =459) were analyzed in a group of treatment-seeking obese patients recruited in 12 Italian medical centers. Insulin resistance was calculated by the homeostasis model assessment method (HOMA-IR)(n =522). Median ALT and AST increased with increasing obesity class (P =0.001 and P =0.005) and exceeded normal limits in 21.0% of cases. Also HOMA-IR increased with the obesity class (P