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Purpose: Detection of antipituitary antibodies (APA) at high levels and with a particular immunofluorescence pattern in patients with autoimmune polyendocrine syndromes may indicate a possible future autoimmune pituitary involvement. This longitudinal study was aimed at characterizing in patients with a single organ-specific autoimmune disease the pituitary cells targeted by APA at start, verifying whether this characterization allows to foresee the kind of possible subsequent hypopituitarism. Methods: Thirty-six APA positive and 40 APA negative patients with isolated autoimmune diseases participated in the study. None of them had pituitary dysfunction at entry. Characterization by four-layer immunofluorescence of pituitary cells targeted by APA in APA positive patients at entry and study of pituitary function in all patients were performed every 6 months during a 5 year follow-up. Results: Antipituitary antibodies immunostained selectively one type of pituitary-secreting cells in 21 patients (58.3 %, group 1), and several types of pituitary cells in the remaining 15 (41.7 %, group 2). All patients in group 1 showed subsequently a pituitary insufficiency, corresponding to the type of cells targeted by APA in 18 of them (85.7 %). Only 8 out of 15 patients in group 2 (53.3 %) showed a hypopituitarism, isolated in 7 and combined in the other one. None of APA negative patients showed hypopituitarism. Conclusions: The characterization of pituitary cells targeted by APA in patients with isolated autoimmune diseases, when the pituitary function is still normal, may help to foresee the kind of subsequent hypopituitarism, especially when APA immunostained selectively only one type of pituitary cells. A careful follow-up of pituitary function in these patients is advisable to allow an early diagnosis of hypopituitarism, even in subclinical phase and a consequent timely replacement therapy. [ABSTRACT FROM AUTHOR]

Oxidative stress and inflammation, which disrupt nitric oxide (NO) production directly or by causing resistance to insulin, are central determinants of vascular diseases including ED. Decreased vascular NO has been linked to abdominal obesity, smoking and high intakes of fat and sugar, which all cause oxidative stress. Men with ED have decreased vascular NO and circulating and cellular antioxidants. Oxidative stress and inflammatory markers are increased in men with ED, and all increase with age. Exercise increases vascular NO, and more frequent erections are correlated with decreased ED, both in part due to stimulation of endothelial NO production by shear stress. Exercise and weight loss increase insulin sensitivity and endothelial NO production. Potent antioxidants or high doses of weaker antioxidants increase vascular NO and improve vascular and erectile function. Antioxidants may be particularly important in men with ED who smoke, are obese or have diabetes. Omega-3 fatty acids reduce inflammatory markers, decrease cardiac death and increase endothelial NO production, and are therefore critical for men with ED who are under age 60 years, and/or have diabetes, hypertension or coronary artery disease, who are at increased risk of serious or even fatal cardiac events. Phosphodiesterase inhibitors have recently been shown to improve antioxidant status and NO production and allow more frequent and sustained penile exercise. Some angiotensin II receptor blockers decrease oxidative stress and improve vascular and erectile function and are therefore preferred choices for lowering blood pressure in men with ED. Lifestyle modifications, including physical and penile-specific exercise, weight loss, omega-3 and folic acid supplements, reduced intakes of fat and sugar, and improved antioxidant status through diet and/or supplements should be integrated into any comprehensive approach to maximizing erectile function, resulting in greater overall success and patient satisfaction, as well as improved vascular health and longevity. [ABSTRACT FROM AUTHOR]

This study was designed to evaluate the prevalence and correlates of ED in a population of diabetic men. Consecutive patients with type 2 diabetes were recruited among outpatients regularly attending Diabetes Clinics. Inclusion criteria for the initial selection of patients were a diagnosis of type 2 diabetes for at least 6 months but less than 10 years, age 35–70 years, body mass index (BMI) of 24 or higher, HbA1c of 6.5% or higher: a total of 555 (90.8%) of the 611 men were analyzed in this study. ED was assessed by the IIEF-5 instrument. Approximately, 6 in 10 men in our sample of diabetic men had varying degrees of erectile dysfunction: mild 9%, mild to moderate 11.2%, moderate 16.9% and severe 22.9%. The prevalence of severe ED increased with age. Higher hemoglobin A1c (HbA1c) levels were associated with ED; similarly, the presence of metabolic syndrome, hypertension, atherogenic dyslipidemia (low levels of HDL-cholesterol and high levels of triglycerides) and depression was associated with ED. Physical activity was protective of ED; men with higher levels of physical activity were 10% less likely to have ED as compared with those with the lowest level. In conclusion, among subjects with type 2 diabetes glycemic control and other metabolic covariates were associated with ED risk, whereas higher level of physical activity was protective. These results encourage the implementation of current medical guidelines that place intensive lifestyle changes as the first step of the management of type 2 diabetes. [ABSTRACT FROM AUTHOR]

Studies assessing sexual dysfunction in type 2 diabetic women are scanty. This study was designed to evaluate the prevalence and correlates of female sexual function in a quite large population of diabetic women. A total of 595 women with type 2 diabetes completed a questionnaire of self-report measures of sexual dysfunction and were analyzed in this study. Their age was 57.9±6.9 (mean and s.d.), duration of diabetes was 5.2±1.5 years and mean hemoglobin A1c (HbA1c) level was 8.3±1.3%. Female sexual dysfunction (FSD) was assessed by the Female Sexual Function Index instrument with a cut-off score of 23. The overall prevalence of FSD among the diabetic women was 53.4%, significantly higher in menopausal women (63.9%), as compared with nonmenopausal women (41.0%, P<0.001). There was no association between HbA1c, duration of diabetes, hypertension, or cigarette smoking status and FSD; on the contrary, age, metabolic syndrome and atherogenic dyslipidemia were significantly associated with FSD. Both depression and marital status were independent predictors of FSD, while physical activity was protective. Further studies are needed to elucidate in full the mechanisms underlying the evident differences between male and female sexual function. In the meantime, evaluation of female sexuality should become a routine evaluation in women with type 2 diabetes, such as other diabetic complications. [ABSTRACT FROM AUTHOR]

Obesity has become a worldwide public health problem of epidemic proportions, as it may decrease life expectancy by 7 years at the age of 40 years: excess bodyweight is now the sixth most important risk factor contributing to the overall burden of disease worldwide. Overweight and obesity may increase the risk of erectile dysfunction (ED) by 30–90% as compared with normal weight subjects. On the other hand, subjects with ED tend to be heavier and with a greater waist than subjects without ED, and also are more likely to be hypertensive and hypercholesterolemic. The metabolic syndrome, characterized by a clustering of risk factors associated with insulin resistance and abdominal obesity, associates with ED. Moreover, women with the metabolic syndrome have an increased prevalence of sexual dysfunctions as compared with matched control women. Lifestyle changes aimed at reducing body weight and increasing physical activity induce amelioration of both erectile and endothelial functions in obese men. Moreover, preliminary evidence suggests that a Mediterranean-style diet might be effective in ameliorating sexual function in women with the metabolic syndrome. Lifestyle changes, mainly focussing on regular physical activity and a healthy diet, are effective and safe ways to reduce cardiovascular diseases and premature mortality in all population groups; they may also prevent and treat sexual dysfunctions in both sexes.International Journal of Impotence Research (2008) 20, 358–365; doi:10.1038/ijir.2008.9; published online 10 April 2008 [ABSTRACT FROM AUTHOR]

The role of postprandial hyperglycaemia in contributing to the risk of both micro- and macrovascular complications in patients with diabetes mellitus is being increasingly recognized. In type 2 diabetes, there is a progressive shift in the relative contributions of postprandial and fasting hyperglycaemia to the overall glycaemic control as the disease progresses. For patients with fairly good glycaemic control (glycosylated hemoglobin [HA1c] <8.5%). postprandial hyperglycaemia makes a relatively greater contribution to the overall glycaemic load than fasting hyperglycaemia, but in patients with poorer control, the relative contribution of the two states to the overall glycaemic load is reversed. This finding, coupled with epidemiological evidence that elevated postprandial glucose concentration is an independent risk factor for cardiovascular disease (CVD), and is associated with a greater CVD risk than elevated fasting glucose, points to the need to monitor and target postprandial glucose, as well as fasting glucose and HbA1c levels, when optimizing insulin therapy for patients with type 2 diabetes. When insulin therapy becomes necessary in patients with type 2 diabetes who can no longer be controlled with oral antihyperglycaemic therapy, use of short-acting insulin analogues with a rapid onset of action and capable of controlling postprandial glycaemic excursions when injected immediately before a meal, has advantages over regular human insulin in that they provide a more favourable time-action profile that mimics normal physiological insulin secretion. Among the available rapid-acting insulin analogues, insulin lispro has been shown to reduce postprandial glucose concentrations to a significantly greater degree than regular human insulin in patients with type 2 diabetes. Moreover, premixed combinations of insulin lispro with the longer acting analogue neutral insulin lispro protamine suspension in 25% : 75% or 50% : 50% combinations are significantly more effective in towering postprandial blood glucose concentrations than premixed regular human insulin plus neutral protamine Hagedorn (NPH) 30%) : 70%. The premixed insulin lispro combinations offer the advantage of fewer daily injections than intensive insulin therapy, and the convenience of not having to mix insulin preparations manually. Although it has yet to be conclusively established that targeting postprandial hyperglycaemia reduces CVD risk, the potential benefits of improved postprandial and interprandial hyperglycaemia favour the use of newer insulin analogues, such as insulin lispro and insulin lispro mixes, over conventional insulin therapy, whenever insulin therapy becomes necessary in patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

In the present study, we tested the effect of a Mediterranean-style diet on sexual function in women with the metabolic syndrome. Women were identified in our database of subjects participating in controlled trials evaluating the effect of lifestyle changes and were included if they had a diagnosis of female sexual dysfunction (FSD) associated with a diagnosis of metabolic syndrome, a complete follow-up in the study trial and an intervention focused mainly on dietary changes. Fifty-nine women met the inclusion/exclusion criteria; 31 out of them were assigned to the Mediterranean-style diet and 28 to the control diet. After 2 years, women on the Mediterranean diet consumed more fruits, vegetables, nuts, whole grain and olive oil as compared with the women on the control diet. Female sexual function index (FSFI) improved in the intervention group, from a mean basal value of 19.7±3.1 to a mean post-treatment value of 26.1±4.1 (P=0.01), and remained stable in the control group. C-reactive protein (CRP) levels were significantly reduced in the intervention group (P<0.02). No single sexual domain (desire, arousal, lubrication, orgasm, satisfaction, pain) was significantly ameliorated by the dietary treatment, suggesting that the whole female sexuality may find benefit from lifestyle changes. A Mediterranean-style diet might be effective in ameliorating sexual function in women with metabolic syndrome.International Journal of Impotence Research (2007) 19, 486–491; doi:10.1038/sj.ijir.3901555; published online 2 August 2007 [ABSTRACT FROM AUTHOR]

Sexual difficulties in women appear to be widespread in society; the relationship between female sexual function and obesity is unclear. This study aimed to investigate the relationship between body weight, the distribution of body fat and sexual function in women. Fifty-two, otherwise healthy women with abnormal values of female sexual function index (FSFI) score (23) were compared with 66 control women (FSFI >23), matched for age and menopausal status. All women were free from diseases known to affect sexual function. FSFI strongly correlated with body mass index (BMI) (r=–0.72, P=0.0001), but not with waist-to-hip ratio (r=–0.09, P=0.48), in women with sexual dysfunction. Of the six sexual function parameters, desire and pain did not correlate with BMI, while arousal (r=–0.75), lubrication (r=–0.66), orgasm (r=–0.56) and satisfaction (r=–0.56, all P<0.001) did. FSFI score was significantly lower in overweight women as compared with normal weight women, while cholesterol and triglyceride levels were higher. On multivariate analysis, both age and BMI explained about 68% of FSFI variance, with a primacy of BMI over age (ratio 4:1). In conclusion, obesity affects several aspects of sexuality in otherwise healthy women with sexual dysfunction.International Journal of Impotence Research (2007) 19, 353–357; doi:10.1038/sj.ijir.3901548; published online 8 February 2007 [ABSTRACT FROM AUTHOR]

Cell-derived microparticles are supposed to be involved in endothelial dysfunction and atherogenesis. This study aimed to evaluate circulating microparticles in diabetic subjects with erectile dysfunction (ED) and their relation with endothelial dysfunction. Thirty diabetic men with ED and 20 age-matched control subjects without ED were assessed for circulating microparticles and endothelial dysfunction. Flow cytometry was used to assess microparticles by quantification of circulating endothelial (EMP, CD31+/CD42b−) and platelet (PMP, CD31+/CD42b+) microparticles in peripheral blood. Endothelium-dependent flow-mediated dilation (FMD) was evaluated in the right brachial artery after reactive hyperemia. Compared with non-diabetic subjects, diabetic men presented significantly higher numbers of EMP (P=0.001), and reduced FMD (P=0.01), with a significant inverse correlation between the number of circulating EMP and the International Index of Erectile Function (IIEF) score (r=−0.457, P=0.01). Multivariate analysis correcting for age, anthropometric indices, glucose and lipid parameters, FMD and PMP identified EMP as the only independent predictor for IIEF score (P=0.03). EMP are elevated in impotent diabetic subjects and independently involved in the pathogenesis of ED.International Journal of Impotence Research (2007) 19, 161–166. doi:10.1038/sj.ijir.3901500; published online 10 August 2006 [ABSTRACT FROM AUTHOR]

The role of dietary factors in erectile dysfunction (ED) has never been addressed. In the present case–control study, we investigated the relation of the Mediterranean diet with ED. A total of 100 men with ED were compared with 100 age-matched men without ED. A scale indicating the degree of adherence to the Mediterranean diet was constructed: the total Mediterranean diet score ranged from 0 (minimal adherence to the Mediterranean diet) to 9 (maximal adherence). The percentage of physical inactivity was greater in the ED group (35 vs 19%, P=0.04), whereas the diet score was lower (4.7±0.5 vs 5.4±0.5, P<0.01), indicating a reduced adherence to the Mediterranean diet. In analyses adjusted for the prevalence of associated risk factors (hypertension, hypercholesterolemia), body mass index, waist, physical inactivity and total energy intake, the intake of fruits and nuts, and the ratio of monounsaturated lipids to saturated lipids remained the only individual measures associated with ED. In conclusion, the results of the present study show that dietary factors may be important in the development of ED: adoption of healthy diets would hopefully help preventing ED.International Journal of Impotence Research (2006) 18, 370–374. doi:10.1038/sj.ijir.3901438; published online 5 January 2006 [ABSTRACT FROM AUTHOR]

Men with the metabolic syndrome demonstrate an increased prevalence of erectile dysfunction (ED). In the present study, we tested the effect of a Mediterranean-style diet on ED in men with the metabolic syndrome. Men were identified in our database of subjects participating in controlled trials evaluating the effect of lifestyle changes and were included if they had a diagnosis of ED associated with a diagnosis of metabolic syndrome, complete follow-up in the study trial, and intervention focused mainly on dietary changes. Sixty-five men with the metabolic syndrome met the inclusion/exclusion criteria; 35 out of them were assigned to the Mediterranean-style diet and 30 to the control diet. After 2 years, men on the Mediterranean diet consumed more fruits, vegetables, nuts, whole grain, and olive oil as compared with men on the control diet. Endothelial function score and inflammatory markers (C-reactive protein) improved in the intervention group, but remained stable in the control group. There were 13 men in the intervention group and two in the control group (P=0.015) that reported an IIEF score of 22 or higher. Mediterranean-style diet rich in whole grain, fruits, vegetables, legumes, walnut, and olive oil might be effective per se in reducing the prevalence of ED in men with the metabolic syndrome.International Journal of Impotence Research (2006) 18, 405–410. doi:10.1038/sj.ijir.3901447; published online 5 January 2006 [ABSTRACT FROM AUTHOR]

Sexual problems in both sexes appear to be widespread in society, influenced by both health-related and psychosocial factors, and are associated with impaired quality of life. Epidemiological studies suggest that modifiable health behaviors, including physical activity and leanness, are associated with a reduced risk for erectile dysfunction (ED) among men. Data from other surveys also indicate a higher prevalence of impotence in obese men. Obesity may be a risk factor for sexual dysfunction in both sexes; the data for the metabolic syndrome are very preliminary and need to be confirmed in larger epidemiologic studies. The high prevalence of ED in patients with cardiovascular risk factors suggests that abnormalities of the vasodilator system of penile arteries play an important role in the pathophysiology of ED. We have shown that one-third of obese men with ED can regain their sexual activity after 2 y of adopting health behaviors, mainly regular exercise and reducing weight. Western societies actually spend a huge part of their health care costs on chronic disease treatment and interventions for risk factors. The adoption of healthy lifestyles can reduce the prevalence of obesity and the metabolic syndrome, and hopefully the burden of sexual dysfunction.International Journal of Impotence Research (2005) 17, 391–398. doi:10.1038/sj.ijir.3901333; published online 19 May 2005 [ABSTRACT FROM AUTHOR]

Aims/hypothesis. Oxidative stress is involved in the pathogenesis of microangiopathic and macroangiopathic diabetic complications. The results of recent trials suggest that type 1 angiotensin II (AT-1) receptor blockers may prevent or delay nephropathy and cardiovascular disease in diabetic patients, independently of their anti-hypertensive action. There is evidence that AT-1 receptor blockers can work as intracellular antioxidants. This study investigated whether the AT-1 receptor blocker irbesartan is able to reduce nitrotyrosine formation in non-hypertensive diabetic patients under fasting conditions and during acute hyperglycaemia. Methods. A total of 40 non-hypertensive, non-microalbuminuric Type 2 diabetic patients and 20 healthy, normotensive subjects were recruited for this study. Diabetic patients followed a randomised, doubleblind, placebo-controlled, crossover protocol, taking either irbesartan (150 mg orally, twice daily) or placebo for 60 days. Fasting glucose and nitrotyrosine were measured at baseline and at the end of each treatment period. An OGTT was also performed at the same time intervals, during which plasma glucose and nitrotyrosine levels were monitored. Results. Compared with baseline measurements, treatment with irbesartan (0.57±0.4 vs 0.35±0.3 µmol/l, p<0.01) but not placebo (0.58±0.3 vs 0.59±0.2 µmol/l) significantly reduced fasting nitrotyrosine levels. Irbesartan also significantly reduced nitrotyrosine formation during the OGTT. Conclusions/interpretation. This study demonstrates that irbesartan reduces plasma levels of nitrotyrosine in diabetic patients and is effective in counterbalancing nitrotyrosine formation during acute hyperglycaemia. Our results may help to elucidate how AT-1 receptor blockers exert their beneficial effect independently of their BP-lowering activity. [ABSTRACT FROM AUTHOR]

Aims/hypothesis. This study aimed to evaluate the effects of hyperglycaemia on the evolution of myocardial infarction and the expression of the transcriptional factor for angiogenesis hypoxia-inducible factor 1α (HIF-1α) in the rat. Methods. We studied the effects of streptozotocin induced diabetes on infarct size and HIF-1α gene expression. These parameters were also evaluated in isolated hearts of non-diabetic rat, in condition of high glucose concentration. Results. In streptozotocin (STZ)-diabetic rats (in vivo study), myocardial infarct size was greater (p<0.01) in hyperglycaemic rats (22 mmol/l) than in normoglycaemic (7 mmol/l) or non-diabetic rats. In euglycaemic conditions, basal expression of HIF-1α mRNA was not appreciable, but increased steadily after ischaemia (762±86%, p<0.001); this response was blunted in hyperglycaemic STZ-rats (6.8±6% of the control, p<0.001) and improved in euglycaemic STZ-rats (58±10%). The changes in myocardial Rac1 mRNA expression paralleled those of HIF-1α. In isolated hearts from non-diabetic rats (in vitro study), perfusion with high glucose (33 mmol/l) produced an infarct size (58±2% of the area at risk) not different from that obtained in hyperglycaemic STZ-rats (57±2%). Similar changes in the expression of HIF-1α and Rac1, which were prevented by glutathione infusion (0.3 mmol/l) were also observed. Conclusion/interpretation. Both hyperglycaemia and high glucose concentrations increased basal HIF-1α and Rac1 expression, suggesting a state of pseudohypoxia. These findings show that myocardial infarct size in the rat is increased in hyperglycaemic conditions and is associated with a reduced expression of the HIF-1α gene. These changes are reversed, totally or partially, by normoglycaemia or glutathione suggesting a role for reactive oxygen species generation brought about by hyperglycaemia. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: The aim of this study was to evaluate the relation between erectile dysfunction and endothelial functions, coagulation activation, peripheral and autonomic neuropathy in men with Type II (non-insulin-dependent) diabetes mellitus. Methods: We studied 30 Type II diabetic patients with symptomatic erectile dysfunction and 30 potent diabetic patients matched for age and disease. Endothelial functions were assessed with the l-arginine test, plasma thrombomodulin and cell adhesion molecules circulating concentrations. Haemostasis was evaluated with markers of thrombin activation and fibrinolysis. Quantitative sensory testing (vibratory, warming, and heat-pain thresholds), cardiovascular reflex tests and 24-h blood pressure monitoring were used to assess peripheral or autonomic neuropathy. Results: Mean erectile score and HbA1 c were 10.5 ± 5.8 and 8.3 ± 1.6 % in patients with erectile dysfunction, and 24.0 ± 0.7 and 6.8 ± 1.4 % in those without erectile dysfunction, respectively (p < 0.001); there was a significant relation between HbA1 c and erectile function score in patients with erectile dysfunction (r = –0.45, p = 0.02). The decrease in blood pressure and platelet aggregation in response to l-arginine was lower (p < 0.05–0.02) in patients with erectile dysfunction, whereas soluble thrombomodulin, P-selectin and intercellular cell ahhesion molecule-1 concentrations were higher (p < 0.05–0.02). Indices of coagulation activation (F1 + 2 and d-dimers) and reduced fibrinolysis (PAI-1) were also found to be higher in erectile dysfunction patients. Heat-pain and warm perception thresholds, as well as cardiovascular reflex tests, were most commonly abnormal in patients with erectile dysfunction (p < 0.05). In multivariate analysis, HbA1 c, MBP response to l-arginine, P-selectin, indices of coagulation, and quantitative sensory testing were independent predictors of erectile function score. Conclusion/interpretation: Erectile dysfunction in diabetic men correlates with endothelial dysfunction. A reduced nitric oxide activity might provide a unifying explanation. [Diabetologia (2001) 44: 1155–1160] [ABSTRACT FROM AUTHOR]

Aims/hypothesis. To investigate cardiac repolarization time in streptozotocin-induced diabetic rats and isolated hearts perfused with high glucose concentration. Methods. We studied the effects of streptozotocin-induced diabetes on the cardiac repolarisation time (Q-T interval) in Sprague-Dawley rats during a 4-day period of hyperglycaemia and a subsequent 4-day period of normoglycaemia. The Q-T interval was also evaluated in isolated hearts of non-diabetic rats, in condition of high glucose concentration. Results. Hyperglycaemia in streptozotocin rats increased mean blood pressure and led to a significant (p < 0.001) prolongation of Q-T values, which normalized after 4 days of normoglycaemia with intravenous insulin infusion. Perfusion of isolated hearts in condition of high glucose concentration caused a significant prolongation of Q-T values and increased coronary perfusion pressure (p < 0.001). The effects of high glucose were completely prevented by glutathione and almost completely by l-arginine, the natural precursor of nitric oxide. In a condition of normal glucose, l-NAME, an inhibitor of endogenous nitric oxide synthesis, increased both Q-T and CPP values to levels similar to those induced by high glucose (p < 0.001). Verapamil completely prevented Q-T lengthening and reduced by about two-thirds CPP values (p < 0.001). Conclusion/Interpretation. Streptozotocin-diabetes in rats produces significant haemodynamic and electric perturbations that are reversed by normoglycaemia. Moreover, high glucose increases Q-T and CPP values in the isolated hearts of non-diabetic rats. The latter effects are reversed by glutathione and l-arginine, partially reversed by verapamil and mimicked by l-NAME. By increasing the production of free radicals, high glucose could reduce nitric oxide availability to target cells inducing a state of increased vasomotor tone and ventricular instability. [Diabetologia (2001) 44: 464–470] [ABSTRACT FROM AUTHOR]

Aims/hypothesis. Prolongation of heart rate-adjusted QT (QTc) is associated with an increased risk of coronary heart disease and sudden death. The objective of this study was to investigate whether acute increases of plasma glucose concentrations in healthy subjects could influence QTc and QTc dispersion. Methods. Plasma glucose concentrations were quickly raised to 15 mmol/l in 20 healthy subjects (10 men/10 women) and maintained for 2 h. On another occasion, and in random order, all subjects underwent the same hyperglycaemic clamp as above and an infusion of the somatostatin analogue octreotide (25 μg as iv bolus followed by a 0.5 g/min infusion) to block the release of endogenous insulin. Results. Systolic and diastolic blood pressures, heart rate and plasma catecholamine concentrations showed significant increases (p < 0.05) starting after 60 min of hyperglycaemia. QTc, QTc dispersion and PR interval also showed significant increments at 120 min of the hyperglycaemic clamp. The infusion of octreotide did not influence QTc duration, QTc dispersion, PR interval and the haemodynamic effects of acute hyperglycaemia. Conclusion/interpretation. The results show that acute hyperglycaemia produces significant increments of QTc and QTc dispersion in normal subjects. In this context, endogenously released insulin during acute hyperglycaemia seems to play a minor part. [Diabetologia (2000) 43: 571–575] [ABSTRACT FROM AUTHOR]

The efficacy and safety of metformin in the treatment of obese, non-insulin-dependent, diabetic subjects poorly controlled by insulin after secondary failure to respond to sulphonylureas has been investigated. Fifty insulin-treated, obese diabetics participated in this prospective, randomised double-blind six-month trial. After a four-week run-in period, during which all patients were given placebo (single-blind), patients were randomly assigned to continue to receive placebo or to active treatment with metformin. At six months, there was a relevant and significant improvement in glycaemic control in diabetics receiving the combined insulin-metformin treatment (decrease in glucose −4.1 mmol·l; glycosylated haemoglobin A decrease −1.84%). No significant changes were seen in diabetics receiving insulin and placebo. There was a significant decrease in blood lipids (trygliceride and cholesterol), an increase in HDL-cholesterol and a reduction in blood pressure in diabetics taking metformin. These postive findings were most marked in the 14 diabetics who experienced a good response to metformin (glucose profile <10 mmol·l), and were less marked but still significant in the remaining 13 diabetics, whose response to therapy was not so good (glucose profile >10 mmol·l). The fasting insulin level was significantly lower after six months of combined insulin-metformin treatment as shown by a 25% reduction in the daily dose of insulin (−21.6 U/day). Metformin was well tolerated by all diabetics. Combining metforming with insulin in obese, insulin-treated and poorly controlled diabetics may represent a safe strategy to achieve better glycaemic control with a reduction in certain metabolic risk factors associated with the increased incidence of cardiovascular disease in diabetes mellitus. [ABSTRACT FROM AUTHOR]

The effect of the calcium antagonist nicardipine on insulin secretion and glucose homoeostasis was investigated in elderly hypertensives with and without diabetes mellitus; 15 patients with essential hypertension for at least 10 years and normal glucose tolerance according to standard criteria (Group I) and 15 elderly hypertensive patients affected by Type 2 diabetes mellitus and on treatment with diet or oral drugs (Group 2). In the basal state, all patients were submitted to an oral glucose tolerance test (OGTT, 75 g) and an iv arginine test (30 g), on two different days and in random order. The same tests were repeated after one month of treatment with nicardipine 60 mg/day, in three spaced doses, the last being given 1 h before the post-treatment test. Nicardipine did not change overall glucose homoestasis, as assessed by haemoglobin Alc and fructosamine, nor did it significantly affect the plasma insulin response either to glucose or arginine in Groups 1 and 2. Only the glucagon response to arginine was significantly reduced in diabetic hypertensives. Small, non-significant variations in the metabolic and hormonal parameters were seen in additional two groups of patients (Groups 3 and 4), matched with Groups 1 and 2 for age, sex and diseases, who took capsules containing placebo. Thus, nicardipine did not produce any significant over-all alteration in glucose homoestasis when given to elderly diabetic or nondiabetic hypertensive subjects. [ABSTRACT FROM AUTHOR]

In the presence of increased levels of fibrinopeptide A, decreased antithrombin III biological activity, and thrombin-antithrombin III complex levels are seen in diabetic patients. Induced-hyperglycaemia in diabetic and normal subjects decreased antithrombin III activity and thrombin-antithrombin III levels, and increased fibrinopeptide A plasma levels, while antithrombin III concentration did not change; heparin was shown to reduced these phenomena. In diabetic patients, euglycaemia induced by insulin infusion restored antithrombin III activity, thrombin-antithrombin III complex and fibrinopeptide A concentrations; heparin administration had the same effects. These data stress the role of a hyperglycaemia-dependent decrease of antithrombin III activity in precipitating thrombin hyperactivity in diabetes mellitus. [ABSTRACT FROM AUTHOR]

Plasma and erythrocyte magnesium levels were measured by atomic absorption spectrometry in 12 healthy subjects and 12 moderately obese patients with Type 2 (non-insulin-dependent) diabetes mellitus. Basal plasma and erythrocyte magnesium levels were significantly lower in diabetic patients than in control subjects. In vitro incubation in the presence of 100 mU/l insulin significantly increased magnesium erythrocyte levels in both control subjects ( p<0.001) and patients with diabetes ( p<0.001). However, even in the presence of 100mU/l insulin, the erythrocyte magnesium content of patients with Type 2 diabetes was lower than that of control subjects. The in vitro dose-response curve of the effect of insulin on magnesium erythrocyte accumulation was shifted to the right when red cells of diabetic patients were used, with a highly significant reduction of the maximal effect. Such reduction of the maximal effect of insulin suggests that the impairment of insulin-induced erythrocyte magnesium accumulation observed in Type 2 diabetic patients results essentially from a post-receptor defect. In the diabetic patients, the Δ increase in erythrocyte magnesium levels (calculated as the net increase between basal and 100 mU/l insulin-induced erythrocyte magnesium levels) was negatively correlated with plasma insulin levels ( r=−0.86; p<0.001) and with body mass index ( r=−0.90; p<0.001); it was positively correlated with the glucose disappearance constant K after intravenous glucose injection ( r=0.79; p<0.01), with the amount of glucose required to keep euglycaemia despite hyperinsulinaemia in a glucose clamp ( r=0.88; p<0.001), and with the metabolic clearance rate of glucose during the clamp ( r=0.82; p<0.001). These results demonstrate that insulin-induced erythrocyte magnesium accumulation is impaired in patients with Type 2 diabetes and that such defect is correlated to impaired insulin-mediated glucose disposal in these patients. [ABSTRACT FROM AUTHOR]

This study aimed at evaluating the influence of furosemide upon insulin and glucagon responses to arginine in healthy subjects. For this purpose, six normal subjects received two consecutive arginine pulses (3 g), 60 min apart, before and after the administration of furosemide (40 mg, IV). The acute insulin response (mean change from 3-10 min) to the second arginine pulse was significantly inhibited by furosemide (mean increase: 14.8 ±3.0 μU/ml versus 11.7±2.5 μU/ml, p<0.01). By contrast, the acute glucagon response was significantly increased (mean increase: 77±18 pg/ml versus 105±21 pg/ml, p<0.01). No significant changes in plasma glucose levels occurred. In control experiments, in which saline rather than furosemide was administered, the acute insulin and glucagon response to the first arginine pulse did not differ from that observed with the second pulse. The effect of furosemide on insulin and glucagon secretion might be mediated through enhanced release of endogenous prostaglandin E. [ABSTRACT FROM AUTHOR]

In 14 normal subjects, treatment with acetylsalicylic acid (ASA, 3.2 g daily for 3 days) a well known inhibitor of prostaglandin synthesis, caused a slight but significant decrease (p<0.05) in basal plasma glucose levels; by contrast, basal insulin rose from 5±1 to 8±1 μU/ml (p<0.01) after ASA. Pretreatment with ASA augmented the early insulin response to a standard IV glucose tolerance test (25 g) in 7 normal subjects (p<0.05 at 2 min; p<0.02 at 5 min; p<0.01 at 10 min). No significant changes were detected in the rate of glucose utilization. 7 additional subjects received a standard arginine test without and with ASA pretreatment. Arginine stimulated insulin levels were increased after ASA (p<0.01 at 15 min; p<0.05 at 30 min; p<0.05 at 45 min), whereas glucose values were lower than under basal conditions at all times, with significant differences at 105 (p<0.02) and 120 (p<0.05) min. A possible role of prostaglandins upon the insulin responses to glucose and arginine is discussed. [ABSTRACT FROM AUTHOR]

The effect of nifedipine, a calcium antagonist, on carbohydrate metabolism and insulin secretion was evaluated in patients who required treatment with this drug. 20 subjects underwent two oral glucose tolerance tests (100 g), one under basal conditions, and the other after ten days of treatment with nifedipine 30 mg/day by mouth, in three divided doses. 10 subjects had normal glucose tolerance; in them nifedipine administration reduced the insulin response to oral glucose in the first 60 min, but improved glucose tolerance. The other 10 subjects had impaired glucose tolerance and nifedipine treatment resulted in a further reduction both of insulin secretion and glucose tolerance. No such effects were seen in the placebo (weight- and disease-matched) group. The mechanism by which nifedipine influences carbohydrate metabolism and insulin secretion is discussed. [ABSTRACT FROM AUTHOR]

Studies have shown that a high plasma non-esterified fatty acid concentration may inhibit glucose induced insulin secretion in vitro and in vivo. The effect of lowering the fatty acid concentration on the acute insulin response was investigated in first degree relatives of people with Type II diabetes in a double-blind, randomised, placebo-controlled trial. Fifty first degree relatives of people with Type II diabetes volunteered for the study. Twenty five were given acipimox (250 mg/day, four times daily) and 25 placebo. The group treated with acipimox had a lower 2-h plasma glucose concentration (6.1 ± 0.2 vs 7.7 ± 0.3 vs mmol/l, p < 0.01); better insulin-mediated glucose uptake (35.4 ± 0.5 vs 28.3 ± 0.4 μmol/kg fat free mass per min, p < 0.01), acute insulin response (68 ± 4.4 vs 46 ± 7.3 mU/l, p < 0.01) and respiratory quotient (0.81 ± 0.02 vs 0.77 ± 0.03, p < 0.05); and a rise in the plasma glucagon (164 ± 63 vs 134 ± 72 ng/l, p < 0.05), growth hormone (1.31 ± 0.13 vs 0.97 ± 0.21 μg/l, p < 0.03) and cortisol (325 ± 41 vs 284 ± 139 nmol/l, p < 0.05) concentrations. The difference in the acute insulin response persisted, even after adjustment for the 2-h plasma glucose concentration, insulin-mediated glucose uptake, the fasting plasma glucagon concentration and the growth hormone concentration ( p < 0.05). In a subgroup of eight patients acipimox was compared with acipimox plus intralipid. The acute insulin response (44 ± 5.1 vs 71 ± 5.3 mU/l, p < 0.01) and the insulin-mediated glucose uptake (27.4 ± 0.4 vs 36.7 ± 0.5 μmol/kg fat free mass per min, p < 0.003) were lower with acipimox plus intralipid treatment than with acipimox alone. It is concluded that long term acipimox treatment lowers the plasma fasting free fatty acid concentration and improves the acute insulin response and the insulin mediated glucose uptake. [Diabetologia (1998) 41: 1127–1132] [ABSTRACT FROM AUTHOR]

Female sexual dysfunction (FSD) is a significant public health problem. We assessed the prevalence of FSD in premenopausal women with the metabolic syndrome as compared to the general female population. Compared with the control group (N=80), women with the metabolic syndrome (N=120) had reduced mean full Female Sexual Function Index (FSFI) score (23.2±5.4 vs 30.1±4.7, P<0.001), reduced satisfaction rate (3.5±1.1 vs 4.7±1.2, P<0.01), and higher circulating levels of C-reactive protein (CRP: 2.2 (0.6/4.9) vs 0.8 (0.2/2.9)?mg/l, median (interquartile range), P=0.01). There was an inverse relation between CRP levels and FSFI score (r=-0.32, P=0.02). Investigation of female sexuality is suggested for patients with the metabolic syndrome.International Journal of Impotence Research (2005) 17, 224-226. doi:10.1038/sj.ijir.3901310 Published online 17 February 2005 [ABSTRACT FROM AUTHOR]

The effects of non-enzymatic glycation on heparin cofactor II activity, at glucose concentrations which might be expected in physiological or diabetic conditions have been evaluated in this study. Radiolabelled glucose incorporation was associated with a loss of heparin cofactor anti-thrombin activity. The heparin cofactor heparin and dermatan sulfatedependent inhibition of thrombin was significantly reduced, showing a remarkable decrease of the maximum second order rate constant. This study shows that heparin cofactor can be glycated at glucose concentrations found in the blood, and that this phenomenon produces a loss of heparin cofactor-antithrombin activity. These data suggest, furthermore, a possible link between heparin cofactor glycation and the pathogenesis of thrombosis in diabetes mellitus. [ABSTRACT FROM AUTHOR]

Increased factor VII levels have been reported in Type 1 (insulin-dependent) diabetic subjects. A direct correlation between fasting plasma glucose and factor VII level was found to exist in both diabetic and normal subjects. Induced-hyperglycaemia was able to increase factor VII levels in both diabetic patients and normal control subjects while, when euglycaemia was achieved in diabetic patients, factor VII values returned to normal range. This study shows that the level of factor VII may be directly conditioned by circulating blood glucose and, therefore, stresses the role of hyperglycaemia in conditioning coagulation abnormalities in diabetes mellitus. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor regarding the association of elevated post-prandial free fatty acids with cardiac sympathetic overactivity in Type II diabetic patients.