Influence of dietary fat and carbohydrates proportions on plasma lipids, glucose control and low-grade inflammation in patients with type 2 diabetes-The TOSCA.IT Study.

PURPOSE: The optimal macronutrient composition of the diet for the management of type 2 diabetes is debated, particularly with regard to the ideal proportion of fat and carbohydrates. The aim of the study was to explore the association of different proportions of fat and carbohydrates of the diet-within the ranges recommended by different guidelines-with metabolic risk factors. METHODS: We studied 1785 people with type 2 diabetes, aged 50-75, enrolled in the TOSCA.IT Study. Dietary habits were assessed using a validated food-frequency questionnaire (EPIC). Anthropometry, fasting lipids, HbA1c and C-reactive protein (CRP) were measured. RESULTS: Increasing fat intake from <25 to ≥35 % is associated with a significant increase in LDL-cholesterol, triglycerides, HbA1c and CRP (p < 0.05). Increasing carbohydrates intake from <45 to ≥60 % is associated with significantly lower triglycerides, HbA1c and CRP (p < 0.05). A fiber intake ≥15 g/1000 kcal is associated with a better plasma lipids profile and lower HbA1c and CRP than lower fiber consumption. A consumption of added sugars of ≥10 % of the energy intake is associated with a more adverse plasma lipids profile and higher CRP than lower intake. CONCLUSIONS: In people with type 2 diabetes, variations in the proportion of fat and carbohydrates of the diet, within the relatively narrow ranges recommended by different nutritional guidelines, significantly impact on the metabolic profile and markers of low-grade inflammation. The data support the potential for reducing the intake of fat and added sugars, preferring complex, slowly absorbable, carbohydrates.

Sex differences in food choices, adherence to dietary recommendations and plasma lipid profile in type 2 diabetes - The TOSCA.IT study.

BACKGROUND AND AIMS: Diabetic women have a more adverse plasma lipid profile than men. Sex differences in dietary habits may play a role, but are little investigated. The study evaluates the quality of diet, adherence to the nutritional recommendations of the Diabetes and Nutrition Study Group and their relation with plasma lipid in men and women with diabetes. METHODS AND RESULTS: We studied 2573 people, aged 50-75, enrolled in the TOSCA.IT study (clinicaltrials.gov; NCT00700856). Plasma lipids were measured centrally. Diet was assessed with a semi-quantitative food frequency questionnaire. Women had a more adverse plasma lipid profile than men. Women consumed significantly more legumes, vegetables, fruits, eggs, milk, vegetable oils, and added sugar, whereas men consumed more starchy foods, soft drinks and alcoholic beverages. This stands for a higher proportion (%) of energy intake from saturated fat and added sugar (12.0 ± 2.4 vs 11.5 ± 2.5 and 3.4 ± 3.2 vs 2.3 ± 3.2, P < 0.04), and a higher intake of fiber (11.2 ± 2.8 vs 10.4 ± 2.6 g/1000 Kcal/day) in women. Adherence to the recommendations for saturated fat and fiber consumption was associated with significantly lower LDL-cholesterol regardless of sex. Adherence to the recommendations for added sugars was associated with significantly lower triglycerides and higher HDL-cholesterol in men and women. CONCLUSIONS: Men and women with diabetes show significant differences in adherence to nutritional recommendations, but sex differences in plasma lipid profile are unlikely to be explained by nutritional factors. Adherence to the nutritional recommendations is associated with a better plasma lipid profile regardless of sex, thus reinforcing the importance of substituting saturated for unsaturated fat sources, increasing fiber and reducing added sugar intake.

Impact of three phthalate esters on the sexual reproduction of the Monogonont rotifer, Brachionus calyciflorus.

Phthalate esters are widespread contaminants that can cause endocrine disruption in vertebrates. Studies showed that molecules with hormonal activities in vertebrates and invertebrates can affect asexual and sexual reproduction in rotifers. We investigated the impact of di-hexylethyl phthalate (DEHP), di-butyl phthalate (DBP) and butylbenzyl phthalate (BBP), on the asexual and sexual reproduction of the freshwater monogonont rotifer Brachionus calyciflorus in order to determine a potential environmental risk for sexual reproduction. We observed that DEHP has no significant impact on both asexual and sexual reproduction up to 2 mg/L. DBP has a positive effect on asexual reproduction at concentrations from 0.05 to 1 mg/L, but depresses it at 2 mg/L. Sexual reproduction is only affected at 2 mg/L and the impact observed is negative. BBP displayed a negative impact on both asexual and sexual reproduction at 1 and 2 mg/L. However we showed that the impacts of BBP on mixis and fertilization rates observed are due to the decrease in population growth rates at these concentrations and not to a direct impact of BBP on the mixis and the fertilization processes. Our results show that sexual reproduction in B. calyciflorus is not more sensitive than asexual reproduction to any of the substances tested which indicates the mode of action of these molecules is related to general toxicity and not to an interference with potential endocrine regulation of sexual reproduction. Comparison of effect concentrations and surface water contamination by phthalate esters suggests these compounds do not constitute a risk for primary consumers in these environments.

Functionally thrombasthenic state in normal platelets following the administration of ticlopidine.

To elucidate the bleeding tendency that follows the administration of ticlopidine, we investigated the skin bleeding time and some ex vivo functions of platelets obtained from eight healthy volunteers before and 1 wk after daily administration of 500 mg of ticlopidine. We found the following: ticlopidine significantly (P less than 0.001) prolonged the skin bleeding time and impaired the binding of radiolabeled fibrinogen and von Willebrand Factor, the clot retraction and the aggregation of platelets in response to ADP, epinephrine, thrombin, ionophore A23187, collagen, or arachidonic acid. In contrast, the administration of this drug did not affect intraplatelet levels of cAMP, agglutination and binding of von Willebrand Factor in response to ristocetin, shape change in response to ADP, collagen, thrombin, or arachidonic acid, or binding of prostaglandin E1 to resting platelets. Secretion of ATP in response to ADP or epinephrine was completely inhibited, whereas secretion as well as thromboxane synthesis in response to high concentrations of collagen, arachidonic acid, calcium ionophore A23187, or thrombin was unaffected. Studies with monoclonal antibodies showed that the glycoprotein IIb-IIIa complex (the putative receptor for fibrinogen and von Willebrand Factor on the surface of platelets exposed to naturally occurring aggregating agents) was quantitatively unaffected by ticlopidine. This observation was further confirmed by densitometric scannings of Periodic Acid-Schiff-stained gels of platelet suspensions. The onset, as well as the cessation of the inhibitory effect of ticlopidine on platelets was very slow, and reached a maximum after a 3-5-d administration. In addition, ticlopidine appeared to be a much more potent inhibitor when administered to subjects than when added in vitro to platelets. Finally, abnormalities comparable to those found in volunteers taking ticlopidine were observed when platelets from untreated subjects were incubated in the plasma of ticlopidine-treated subjects. We conclude that ticlopidine induces a thrombasthenic state in normal platelets without affecting the glycoprotein IIb-IIIa complex quantitatively. Furthermore, our data suggest that one or more active metabolites rather than the native drug mediate the abnormalities of platelet function observed in ticlopidine-treated subjects.

Nutrient determinants of postprandial triglyceride response in a population-based sample of type II diabetic patients.

BACKGROUND: Nutrient determinants of postprandial triglyceride (TG) are matter of debate, especially for type II diabetes. OBJECTIVE: This study was performed to evaluate the impact of dietary habits on postprandial TG response in a population-based sample of type II diabetic patients. DESIGN: One-hundred and forty type II diabetic patients (63 men/77 women, age 45-70 years) referring to the same health district, not on hypolipidemic drugs and without any other chronic disease, performed four TG profiles (at fasting, before, 2 and 3 h after lunch) with a specific device (Accutrend GCT, Roche Diagnostics Mannheim, Germany) validated previously. Dietary habits were recorded by a dietitian utilizing a previously validated semiquantitative questionnaire. RESULTS: Triglyceride values (mmol/l, mean +/- s.d.) were 2.22 +/- 0.93 at fasting, decreased before lunch (2.03 +/- 0.81), reached peak values 3 h after lunch (2.73 +/- 1.11). Postprandial TG increments (3 h after lunch minus pre-lunch concentration) significantly correlated with the intake (g/day) of animal protein (r = 0.20, P < 0.02), total fat (r = 0.21, P < 0.01), animal fat (r = 0.19, P < 0.03) and vegetable fat (r = 0.19, P < 0.03), also after adjusting for fasting TG and high-density lipoprotein cholesterol levels. Expressing nutrient intake as percentage of total calorie intake, total and animal fat remained significantly and directly related to postprandial TG increment (r = 0.21, P < 0.01 for total fat; r = 0.19, P < 0.03 for animal fat) whereas the percentage of carbohydrates was inversely related (r = -0.23, P < 0.007). CONCLUSIONS: Fat intake seems the major nutritional determinant of postprandial TG response in type II diabetic patients.

Plasma fibrinogen: a new factor of the metabolic syndrome. A population-based study.

OBJECTIVE: To evaluate whether hyperfibrinogenemia represents a component of the metabolic syndrome. RESEARCH DESIGN AND METHODS: A cross-sectional study was conducted on the relation between fibrinogen and the metabolic syndrome in a working population of 1,252 nondiabetic men, aged 35-64 years, randomly selected among all men participating in a health screening. We measured anthropometric characteristics, blood pressure, fasting plasma fibrinogen, cholesterol (total, LDL, and HDL), triglycerides, glucose, and insulin. Individuals with two or more metabolic abnormalities (defined as being in the highest quartile of the distribution of diastolic blood pressure, plasma glucose, or triglycerides or being in the lowest quartile of HDL cholesterol) were considered to have the metabolic syndrome. RESULTS: Age-adjusted fibrinogen levels correlated significantly with BMI, waist-to-hip ratio, systolic and diastolic blood pressure, plasma total cholesterol, LDL cholesterol, triglycerides, insulin, and HDL cholesterol (inversely). Subjects with the metabolic syndrome had significantly higher plasma fibrinogen levels than those without (285.1 +/- 1.9 vs. 300.2 +/- 3.0 mg/dl, mean +/- SE, P = 0.0001). Plasma fibrinogen concentrations and the prevalence of hyperfibrinogenemia (defined as > or = 350 mg/dl) increased progressively from 279 to 307 mg/dl (P = 0.0001) and from 9 to 22% (P = 0.0024), respectively, across categories with an increasing number of metabolic disorders characterizing the syndrome (only one, any two, three or more). In multivariate analyses, both plasma insulin and the metabolic syndrome were significantly and independently associated with plasma fibrinogen. CONCLUSIONS: The finding suggests that hyperfibrinogenemia may be considered a component of the metabolic syndrome. This may also explain the increased cardiovascular risk associated with hyperinsulinemia/insulin resistance.

Prevention of early-morning hyperglycemia in IDDM patients with long-acting zinc insulin.

OBJECTIVE: To evaluate whether an insulin regimen with a long-acting zinc insulin (Ultratard HM) could help control fasting hyperglycemia in insulin-dependent diabetes mellitus (IDDM) patients. RESEARCH DESIGN AND METHODS: A randomized sequential crossover trial with 6-wk treatment periods was used. Ten IDDM patients from the diabetes clinic at the Medical School who had persistent fasting hyperglycemia (greater than 10 mmol/L) were studied. Patients with nocturnal hypoglycemia were excluded. All patients completed the study. Insulin regimens consisted of three daily injections of a short-acting insulin (Actrapid HM) before meals and either a long-acting zinc insulin (Ultratard HM) or an intermediate isophane insulin (Protaphane HM) before the evening meal. Each regimen was followed for 6 wk. RESULTS: Fasting blood glucose levels (at 06:00 and 08:00) were significantly lower after the long-acting insulin regimen (6.26 +/- 0.88 vs. 10.82 +/- 4.27 mM, P less than 0.05 and 9.26 +/- 1.02 vs. 14.03 +/- 1.08 mM, P less than 0.05, respectively). Plasma-free insulin levels mirrored blood glucose concentrations because they were significantly higher at 06:00 and 08:00 after the long-acting insulin regimen (49.5 +/- 10.1 vs. 20.1 +/- 4.3 pM, P less than 0.05 and 31.6 +/- 5.0 vs. 16.5 +/- 3.4 pM, P less than 0.05, respectively). At any other time of the day, blood glucose and plasma insulin levels were not significantly different with either one of the two insulin regimens. CONCLUSIONS: A long-acting zinc human insulin injected before the evening meal can help to control persistent fasting hyperglycemia in IDDM patients.

Long-term effects of fish oil on insulin resistance and plasma lipoproteins in NIDDM patients with hypertriglyceridemia.

OBJECTIVE: The aim of this study was to evaluate the long-term (6-month) effects of moderate fish oil supplementation on insulin sensitivity and plasma lipoproteins in NIDDM patients with hypertriglyceridemia. RESEARCH DESIGN AND METHODS: The study has been performed according to a randomized double-blind placebo-controlled design with a parallel group sequence. After a washout period of 4 weeks and a run-in period of 3 weeks, 16 NIDDM patients with hypertriglyceridemia (triglyceride [TG], 2.25-5.65 mmol/l) were randomly assigned to either fish oil (2.7 g/day eicosapentaenoic plus docosahexaenoic acid for 2 months, then 1.7 g/day for 4 more months) (n = 8) or placebo (n = 8). Diet and hypoglycemic drugs remained unchanged throughout the whole experiment. At baseline and after 6 months, insulin sensitivity was measured by euglycemic hyperinsulinemic clamp (insulin infused, 2.0 mIU.kg-1 body wt.min-1). At the same time, blood glucose control, fasting and postprandial serum insulin and nonesterified fatty acid (NEFA) concentrations, and fasting plasma lipoprotein concentrations were evaluated. RESULTS: In the group treated with fish oil compared with the baseline, there was: 1) a significant reduction in both plasma TG (2.92 +/- 0.23 vs. 3.85 +/- 0.32 [mean +/- SE] mmol/l, P < 0.001) and VLDL-TG (2.35 +/- 0.24 vs. 4.25 +/- 0.66 mmol/l, P < 0.01), without significant changes in blood glucose control; 2) a significant reduction in fasting NEFA concentrations (572 +/- 100 vs. 825 +/- 131 mumol/l, P < 0.01); and 3) a significant enrichment in long-chain omega-3 fatty acids of erythrocyte membrane phospholipids. In the placebo group, there were no changes in any of the variables analyzed. The insulin-mediated glucose uptake was unchanged in both groups (fish oil, 4.04 +/- 0.82 mg.kg-1.min-1 at baseline and 3.96 +/- 0.50 mg.kg-1.min-1 at 6 months; placebo, 3.51 +/- 0.62 mg.kg-1.min-1 at baseline and 4.09 +/- 0.49 mg.kg-1.min-1 at 6 months). CONCLUSIONS: In NIDDM patients with hypertriglyceridemia, moderate amounts of fish oil induce a long-term significant reduction in plasma triglycerides, VLDL triglycerides, and NEFA and a significant enrichment in the erythrocyte phospholipid content of long-chain omega-3 fatty acids, without deteriorating blood glucose control. However, this amount of omega-3 fatty acids was unable to improve insulin sensitivity in this group of patients.

Metabolic consequences of feeding a high-carbohydrate, high-fiber diet to diabetic patients with chronic kidney failure.

The aim of this study was to compare the metabolic effects of a high-carbohydrate (CHO), high-fiber diet with only moderate protein restriction with those of a low-CHO, low-fiber diet with a low protein content in six diabetic patients with moderate chronic renal failure. The high-CHO, high-fiber diet induced a significant improvement in blood glucose control, a significant decrease in serum cholesterol, and a significant increase in fecal nitrogen losses. Other variables evaluated were not significantly different between the two diets, except for a significant increase in serum phosphorus during the high-CHO, high-fiber diet. N balance was not significantly different from 0 at the end of either dietary period and was very similar for both diets. The high-CHO, high-fiber diet presents many beneficial metabolic effects in diabetic patients with chronic renal failure.

A controlled study on the effects of n-3 fatty acids on lipid and glucose metabolism in non-insulin-dependent diabetic patients.

Eight male non-insulin-dependent diabetic patients participated in a double-blind randomized cross-over study (2 weeks for each period) evaluating the effects of 10 g/day fish oil dietary supplementation on glucose and lipid metabolism. Fasting serum triglyceride concentrations were decreased by fish oil because of a reduction in VLDL (1.4 +/- 0.2 vs. 1.9 +/- 0.2 mmol/l, P less than 0.025). LDL cholesterol concentration was instead increased (3.4 +/- 0.3 vs. 2.8 +/- 0.3 mmol/l, P less than 0.025) and net changes in VLDL triglyceride and in LDL cholesterol were inversely correlated (r = -0.86, P less than 0.01). Plasma free fatty acids concentrations and turnover rate [( 3H]palmitate method) were similar after fish oil and placebo. Fish oil supplement did not induce significant changes in fasting blood glucose (8.1 +/- 1.1 vs. 8.5 +/- 1.2 mmol/l) and average daily blood glucose (BG) (9.4 +/- 3.2 vs. 9.3 +/- 3.5 mmol/l). Glucose stimulated plasma insulin response during a hyperglycemic clamp was not significantly influenced by fish oil both in the early phase and during steady state. Insulin sensitivity (M/I index) was also unchanged. In conclusion, this study shows that a dietary supplement of fish oil decreases plasma triglyceride levels in non-insulin-dependent diabetic patients, an increased conversion rate of VLDL to LDL playing a role in this change. With this dosage of fish oil no relevant variations in glycemic control, insulin secretion and insulin sensitivity occurred.

Long-term effects of fish oil on lipoprotein subfractions and low density lipoprotein size in non-insulin-dependent diabetic patients with hypertriglyceridemia.

The effects of fish oil on lipoprotein subfractions and low density lipoprotein (LDL) size in non-insulin-dependent diabetes mellitus (NIDDM) patients with hypertriglyceridemia are unknown. To elucidate this, 16 NIDDM hypertriglyceridemic patients (plasma triglyceride 2.25- 5.65 mmol/l, plasma cholesterol < or = 7.75 mmol/l) were randomly assigned to a 6-month period with either moderate amounts of fish oil (n = 8) or placebo (n = 8) after 4 weeks of wash-out and 3 weeks of run-in. Diet and hypoglycemic treatment were unchanged throughout the experiment. LDL size were evaluated at baseline and after 6 months. Three VLDL and LDL subfractions were measured at the end of the two periods. The total lipid concentration of all very low density lipoprotein (VLDL) subfractions was lower at the end of fish oil treatment compared with placebo (large VLDL 124.3 +/- 19.7 mg/dl vs 156.7 +/- 45.5 mg/dl; intermediate VLDL 88.5 +/- 9.5 mg/dl vs 113.9 +/- 23.2 mg/dl; small VLDL 105.9 +/- 9.7 mg/dl vs 128.9 +/- 40.7 mg/dl) (mean +/- SEM), although the difference was not statistically significant. Moreover, at the end of the two treatments, the percentage distribution of VLDL subfractions was very similar (large 37.5 +/- 3.3% vs 37.6 +/- 2.6%, intermediate 27.6 +/- 0.9% vs 31.0 +/- 2.4%; small 34.9 +/- 3.7% vs 31.4 +/- 2.1%). Concerning LDL, no significant change in LDL size was observed after the two treatments (255.4 +/- 2.2 A vs 254.2 +/- 1.7 A, fish oil; 253.7 +/- 2.0 A vs 253.3 +/- 1.7 A, placebo). LDL subfraction distribution was also very similar (large 17 +/- 3% vs 17 +/- 2%; intermediate 62 +/- 3% vs 65 +/- 3%; small 21 +/- 3% vs 18 +/- 2%), at the end of the two periods, confirming the lack of effects on LDL size. In conclusion, our study indicates that in NIDDM patients with hypertriglyceridemia, fish oil does not induce any improvement in LDL distribution and LDL size despite its positive effects on plasma triglycerides.

Lipoprotein(a) concentrations in non-insulin-dependent diabetes mellitus and borderline hyperglycemia: a population-based study.

The objective of the study was to compare lipoprotein(a) [Lp(a)] concentrations in population-based samples of individuals with non-insulin-dependent diabetes mellitus (NIDDM), borderline hyperglycemia, and normoglycemia. From 2,740 male Italian Telephone Company employees aged 40 to 59 years participating in a health screening, we selected all those with NIDDM (n = 100) plus a random sample of 950 nondiabetic individuals. Diabetes was defined as fasting plasma glucose (FPG) of at least 140 mg/dL or current use of hypoglycemic drugs. Among nondiabetic individuals, 854 were defined as normoglycemic (FPG < 115 mg/dL) and 95 were defined as borderline hyperglycemic (115 < FPG < 140 mg/dL). Lp(a) level was measured on frozen plasma by enzyme-linked immunosorbent assay. Lp(a) concentrations were similar in people with NIDDM, borderline hyperglycemia, and normoglycemia: 11.2 +/- 14, 14.1 +/- 20, and 13.9 +/- 18 mg/dL, respectively (F = 1.03). Accordingly, the proportion of subjects with Lp(a) levels of at least 30 mg/dL was comparable in the three groups (12%, 15%, and 14%; chi 2 = 3.95, P = .41). Results were not confounded by differences in age, body mass index (BMI), waist to hip ratio, plasma lipids, alcohol consumption, physical activity, and use of drugs. Furthermore, within the diabetic group Lp(a) levels were not significantly different for those on diet only versus those on oral agents (10.8 +/- 14.1 v 11.7 +/- 14.7, P = .7) or for people with FPG of at least 180 as compared with people with FPG less than 180 mg/dL (9.9 +/- 12.8 v 11.5 +/- 14.8, P = .5).(ABSTRACT TRUNCATED AT 250 WORDS)

Self-monitoring of plasma triglyceride levels to evaluate postprandial response to different nutrients.

Self-monitoring of plasma triglycerides (TG) may be a very useful tool to monitor, on a daily basis, the TG responses to different nutrients, particularly carbohydrates (CHO) and fat, whose influence on postprandial TG levels is not very well known. Therefore, the aim of the present study was to evaluate the TG response of hypertriglyceridemic patients to a similar amount of calories deriving from different sources of CHO and fat. Thirty-nine hypertriglyceridemic patients were randomly assigned to 1 of 2 experimental groups. In 1 group (the fat group), patients were given a standard meal plus a fat supplement of 300 kcal derived from different types of fat (butter, sunflower margarine, olive oil) for dinner, once a week for 3 weeks. In the other group (the CHO group), patients consumed the same standard meal plus a supplement of 300 kcal derived from different types of CHO (bread, coke, fruit). In both groups, patients measured their plasma TG before and 3 hours after each meal by Accutrend GCT (ROCHE, Mannheim, Germany). A subgroup of patients (n = 18) also performed TG determinations 2 hours after the test meals. The 3-hour TG increments were not significantly different between the different test meals (f = 0.671; P =.52); instead, the TG increments induced by fat supplements were significantly higher than those induced by the CHO supplements (f = 14.31; P =.0001). Similar results were also obtained 2 hours after the test meals. In conclusion, this study shows that the 2- and 3-hour TG responses to fat are higher compared with that induced by carbohydrate. This point, especially if confirmed by experiments with more frequent after meal measurements and of longer duration, should be taken into account in defining the best dietary approach to lower plasma TG levels throughout the whole day.

Responses of serum insulin and blood pressure to cold and handgrip in obese patients.

A close correlation between body weight and blood pressure has been frequently observed in both clinical and epidemiological studies. The aim of this clinical trial was to evaluate whether, in obese patients, there is any relationship between blood pressure, at rest or during sympathetic stimulation, and blood glucose and serum insulin, both while fasting and during an oral glucose challenge. Twenty obese patients (age 26-65 years, body weight 97 +/- 16 kg, 11 normotensive and 9 hypertensive) entered the study. After a 4-week run-in period on an isocaloric diet with normal intake of sodium, blood pressure and heart rate were measured at rest and during sympathetic stimulation induced by cold and isometric testing. Responses of glucose and insulin to a standardized 75 g oral glucose tolerance test were also evaluated. The responses of glucose and insulin to glucose challenge were not statistically different in normotensive and hypertensive obese patients. Levels of insulin in the serum in the serum in the fasting state and during glucose load were significantly correlated with the response of blood pressure to cold and isometric exercise, but not to blood pressure at rest. The response of heart rate to cold was closely related to insulin only in the subgroup of normotensives. The present findings support the hypothesis that the sympathetic nervous system, which influences secretion of insulin and regulation of blood pressure, is involved in the pathophysiology of the association of obesity and hypertension.

[Clinico-therapeutic experience with a new antihypertensive drug, ketanserin, in elderly patients]. / Esperienza clinico-terapeutica con un nuovo farmaco antiipertensivo, la ketanserina, in pazienti anziani.

After a placebo run-in period (one week) 32 hypertensive patients suffering also from other disorders (cardiovascular pathology, diabetes, psychic or neurotic pathology) were treated with ketanserin (20 mg twice daily p.o. for 15 days followed by 40 mg twice daily for another 65 days). The patients' (13 men, 10 women) ages ranged from 54-94 years (average 69 years). Therapeutic results became manifest gradually with significant reductions of systolic and diastolic blood pressure; heart rate, too, had decreased slightly at the end of the treatment period. Global evaluation yielded favorable results in 59% of patients. Topical and systemic tolerance was satisfactory.

[The role of anti-endomysium and anti-transglutaminase antibodies in the diagnosis and follow-up of celiac disease]. / Ruolo degli anticorpi antiendomisio e antitransglutaminasi nella diagnosi e nel follow-up della malattia celiaca.

Available, non invasive, serological tests such as the anti-endomysium antibodies (EmA) and anti-transglutaminase antibodies (Anti-tTg) has allowed better outlining of the clinical presentation as well as the pathogenesis of Coeliac Disease (CD). The aim of the study was to evaluate the reliability and concordance of EmA and anti-tTg at the diagnosis (T0) of CD and after 12 months (T12) of Gluten-Free Diet (GFD). Serum EmA and Anti-tTg were evaluated in 78 patients aged 6.3 +/- 4.7 SD yrs at diagnosis, in 56 of them at T0 and T12, as well as in a control group of 88 children aged 6.9 +/- 3.8 yrs. EmA were evaluated by indirect immunofluorescence and Anti-tTg by ELISA. All subjects had normal circulating IgA levels. In the control group, EmA and Anti-tTg resulted negative in all cases. At T0, 77/78 pts had both EmA and Anti-tTg positive, one pt (1.3%) had only EmA positive, demonstrating an overall positive concordance of 98.7%. At T12, 16 pts (28.6%) had both tests positive, 8 (14.3%) had only Anti-tTg positive (all of them were no fully compliant to GFD) and 32 (57.1%) had both tests negative. The overall concordance at T12 was 85.7%. The concordance between EmA and Anti-tTg at T0 is nearly absolute (98.7%). The higher prevalence of elevated anti-tTg than of positive EmA at T12 suggests a higher sensitivity of anti-tTg following intake of even small amounts of gluten.

Effects of beta-receptor blockade on carbohydrate metabolism.

The effects of beta-blockers on glucose tolerance, insulin secretion and peripheral insulin sensitivity were evaluated by oral glucose tolerance test and euglycaemic insulin technique in six normoglycaemic patients with primary arterial hypertension at the end of 3-week treatments with placebo (one tablet twice daily) and propranolol (80 mg twice daily). Body weight did not change during the study (83 kg at the end of placebo, 83 kg at the end of propranolol), while blood pressure (150 +/- 9/97 +/- 8 mmHg on placebo, 138 +/- 8/89 +/- 8 mmHg on propranolol, P < 0.01) and heart rate (66 +/- 9 beats/min on placebo, 60 +/- 5 beats/min on propranolol, P < 0.05) showed a significant fall on the beta-blocker. No change was observed in glucose tolerance (incremental area for glucose 3462 +/- 1149 mg/dl per min on placebo, 3209 +/- 1695 mg/dl per min on propranolol), insulin secretion (incremental area for serum insulin 7579 +/- 4380 microU/ml per min on placebo, 7934 +/- 4351 microU/ml per min on propranolol) and peripheral insulin sensitivity (metabolic clearance rate 11 +/- 4 ml/kg per min on placebo, 13 +/- 6 ml/kg per min on propranolol). These data support the hypothesis that chronic treatment with adrenergic blocking agents does not induce any significant change in insulin secretion or peripheral insulin sensitivity.