Radon concentration in self-bottled mineral spring waters as a possible public health issue.

Since 2013, the Council Directive 2013/51/Euratom has been regulating the content of radioactive substances in water intended for human consumption. However, mineral waters are exempted from this regulation, including self-bottled springs waters, where higher radon concentration are expected. Therefore, a systematic survey has been conducted on all the 33 mineral spring waters of Lazio (a region of Central Italy) in order to assess if such waters, when self-bottled, may be of concern for public health. Waters have been sampled in two different ways to evaluate the impact of bottling on radon concentration. Water sampling was possible for 20 different spring waters, with 6 samples for each one. The results show that 2 (10%) of measured mineral spring waters returned radon concentrations higher than 100 Bq L-1, i.e., the parametric value established by the Council Directive. These results, if confirmed by other surveys involving a higher number of mineral spring waters, would suggest regulating also these waters, especially in countries like Italy for which: (i) mineral water consumption is significant; (ii) mineral concession owners generally allow the consumers to fill bottles and containers, intended for transport and subsequent consumption, directly from public fountains or from fountains within the plant; (iii) the consumers' habit of drinking self-bottled mineral water is widespread.

Is dermolipectomy effective in improving insulin action and lowering inflammatory markers in obese women?

OBJECTIVE: Obesity is a major risk factor for coronary heart disease, and surgical treatment of obese patients as part of a multidisciplinary approach seems to provide faster results than diet therapy. The aim of this study was to evaluate the effect of dermolipectomy on insulin action and inflammatory markers in 20 obese women. PATIENTS: At baseline and 40 days after dermolipectomy, 20 obese women underwent indirect calorimetry and hyperinsulinaemic glucose clamp. Twenty obese nonsmoking females (age range 25--40 years) volunteered for the study. All subjects had a stable body weight for 2 months before the study. No patient was affected by cardiovascular and/or pulmonary disease, type 2 diabetes, thyroid dysfunction, acute or chronic hepatitis, renal insufficiency or cancer. No patients was receiving any drug therapy and all measurements were made during the follicular phase of the menstrual cycle. RESULTS: At baseline, fat mass (FM) correlated with plasma triglycerides (r=.58, P<0.009), free fatty acids (FFA) (r=0.73, P<0.001), insulin (r=0.70, P<0.002), leptin (r=0.55, P<0.01), adiponectin (r=-0.32, P<0.02) and resistin (r=0.31, P<0.01), insulin sensitivity (IS) (r=-0.59, P<0.005) and respiratory quotient (Rq) (r=0.62, P<0.002). With regard to inflammatory markers, FM was significantly correlated with plasma interleukin (IL)-6 (r=0.71, P<0.001), IL-10 (r=-0.67, P<0.002), tumour necrosis factor-alpha (TNF-alpha) (r=0.78, P<0.001) and soluble IL-6 receptor (sIL-6r) (r=-0.65, P<0.003). Dermolipectomy resulted in a significant decline in total FM of 2.3+/- 0.2 kg. A significant decline in BMI was also observed (30.0+/- 0.08 vs. 31.1+/- 0.7 kg/m(2)). After 40 days a significant decline in plasma resistin (P<0.001) and inflammatory markers and an increase in plasma adiponectin (P<0.03) were observed. Those metabolic changes were accompanied by a significant improvement in insulin-mediated glucose uptake (P<0.001), substrate oxidation and degree of inflammation. Changes in FM following dermolipectomy correlated with the changes in IS (P<0.01), substrate oxidation and FFA (P<0.001). CONCLUSIONS: In obese patients, dermolipectomy is associated with weight lost, improved glucose handling and lower inflammatory markers.

Resting metabolic rate and respiratory quotient in human longevity.

Significant changes in body composition, body fat distribution, and resting metabolic rate (RMR) occur with aging. Interestingly, studies on human longevity pointed out that long-lived subjects are less prone to the anthropometrics and metabolic derangement normally observed in the elderly. Indeed, the relationship between energy expenditure and longevity has been poorly investigated. Thus, energy expenditure parameters of 28 long-lived subjects were assessed and compared with those of 26 adults and 27 younger elderly. All subjects enrolled were female. In the whole population, RMR was negatively correlated with age (P < 0.05), waist to hip ratio (WHR) (P < 0.001), fat mass (P < 0.001), and percent body fat (P < 0.03); respiratory quotient (Rq) displayed an age-related decrease (P < 0.001) and was negatively correlated with WHR (P < 0.001) and fat-free mass (FFM) (P < 0.006). In multivariate analysis, both RMR and Rq had FFM, WHR, but not body mass index as significant and independent determinants. Splitting the whole study group into subgroups according to age, long-lived subjects had oxygen volume, carbon dioxide volume, and Rq significantly higher than aged subjects but lower than adult subjects. In addition, long-lived subjects had total volume of expired air and RMR greater than aged subjects but not different from ones found in adults. In long-lived subjects, Rq was negatively correlated with percent body fat (P < 0.02), plasma glucose (P < 0.05), free fatty acid (P < 0.05), and WHR (P < 0.05), whereas RMR was negatively correlated with WHR (P < 0.05). No significant associations of RMR and Rq with FFM were found. In conclusion, our data demonstrate that human longevity seems protected toward an age-related decline. It is likely that the lack of the anthropometrics derangement may preserve long-lived subjects from the age-related decrease in energy metabolism.

Cardiovascular risk in type 2 diabetics and pharmacological regulation of mealtime glucose excursions.

In type 2 diabetic patients mealtime glucose fluctuations are important determinants of overall glucose control and overall risk of diabetes cardiovascular complications. In fact, acute elevation of plasma glucose concentrations trigger an array of tissue response that may contribute to development of such vascular complications since it may result in a thrombophilic condition, causes endothelial dysfunction (possibly through a reduction of nitric oxide availability) and is responsible for non-enzymatic glycation and production of free- radicals with ensuing oxidative stress. To keep post-prandial glucose with narrow range, metiglinide analogues drugs have been developed. In particular, repaglinide and nateglinide seem the most useful ones. In fact, both drugs improve 1(st) phase insulin release but they do not affect the total daily amount of insulin released by the pancreas. Due to the mechanism of action and to pharmacokinetic properties, repaglinide and nateglinide allow diabetic patients to get a more tight metabolic glucose control with a contemporary reduction in the cases of severe hypoglycaemia. In conclusions, repaglinide and nateglinide are new and powerful pharmacological tools not only for achieving a better metabolic glucose control but also for preventing the development of diabetes-related cardiovascular complications.

New aspects of the insulin resistance syndrome: impact on haematological parameters.

AIM/HYPOTHESIS: Previous studies have shown that insulin has an important in vitro role in the regulation of human erythropoiesis. We investigated whether in vivo hyperinsulinaemia/insulin resistance affects haematological parameters. METHODS: A total of 608 subjects between 22 and 99 years of age were enrolled in the Chianti study, an epidemiological study of factors affecting mobility in old age. The degree of insulin resistance was assessed using the homeostasis model. RESULTS: We found a correlation between insulin resistance and red blood cell count, (r = 0.14 p < 0.001), plasma haemoglobin (r = 0.16 p < 0.001), haematocrit (r = 0.15 p < 0.001) and plasma iron (r = 0.1 p < 0.05) concentrations. Red blood cell count was also associated with the other biological markers of insulin resistance syndrome. Subjects with higher insulin resistance (4 degrees quartile) had higher red blood cell count, plasma triglycerides and low density lipoproteins (LDL) cholesterol concentrations and lower high density lipoproteins (HDL) cholesterol concentrations then subjects at the lowest quartiles of insulin resistance. Insulin resistance and BMI were significant and independent predictors of red blood cell count even when the analysis was adjusted for age, sex, waist-to-hip ratio, plasma iron and drug intake. CONCLUSION/HYPOTHESIS: Our findings provide in vivo evidence of a relation between hyperinsulinaemia/insulin resistance, the main variables of insulin resistance syndrome and erythropoiesis. Increased red blood cell count could be considered as a new aspect of the insulin resistance syndrome that could contribute to the increased risk of developing cardiovascular problems.

Role of free fatty acids on cardiac autonomic nervous system in noninsulin-dependent diabetic patients: effects of metabolic control.

Decreased heart rate variability (HRV) is a risk factor for cardiovascular mortality. Elevated plasma free fatty acid (FFA) levels decrease HRV in healthy subjects. Thus, we investigated the effect of changes in plasma FFA levels on HRV, in non-insulin-dependent diabetes (NIDDM) patients. Thirty NIDDM patients free from diabetic neuropathy volunteered for a study made by two phases. In study A, changes in HRV along a 10% lipid emulsion infusion + heparin (n = 15) or saline infusion (control study; n = 15) were investigated. In study B, all patients (n = 30) underwent further determination of HRV after 3 months of improved metabolic control achieved by intensified insulin treatment. In study A, lipid emulsion infusion increased plasma FFA (P < 0.001) and catecholamine concentrations (P < 0.005), mean arterial blood pressure (P < 0.005), low frequency/high frequency (LF/HF) ratio (P < 0.001). Delta plasma FFA levels correlated with delta LF/HF ratio (r = 0.57; P < 0.02). Along with saline infusion, metabolic and cardiovascular parameters remained unchanged throughout the test. In study B, improved metabolic control lowered fasting plasma glucose (P < 0.005), FFA (P < 0.001), norepinephrine (P < 0.02), epinephrine (P < 0.04), and glycosylated hemoglobin levels (P < 0.001), mean arterial blood pressure(P < 0.05), and LF/HF ratio (P < 0.001). Again percent decline in plasma FFA correlated with the percent change in LF/HF ratio (r = 0.72; P < 0.001). In a multivariate analysis, percent changes in LF/HF ratio were associated with percent changes in plasma FFA independently of gender and percent changes in body mass index, waist/hip ratio, plasma norepinephrine, epinephrine, glycosylated hemoglobin, and daily insulin therapy. Our study demonstrates that changes in plasma FFA levels may have a parallel effect on cardiac sympathetic/parasympathetic nervous system balance in NIDDM patients.

Chronic administration of pharmacologic doses of vitamin E improves the cardiac autonomic nervous system in patients with type 2 diabetes.

BACKGROUND: Type 2 diabetes is associated with elevated oxidative stress and declines in antioxidant defense. The disease is also characterized by an imbalance in the ratio of cardiac sympathetic to parasympathetic tone. Antioxidants, vitamin E in particular, may have beneficial effects on the cardiac autonomic nervous system through a decline in oxidative stress. OBJECTIVE: We investigated the possible effects of vitamin E on the cardiac autonomic nervous system, as assessed by analysis of heart rate variability, in patients with type 2 diabetes and cardiac autonomic neuropathy. DESIGN: In a double-blind randomized controlled trial, 50 patients with type 2 diabetes were assigned to treatment with vitamin E (600 mg/d) or placebo for 4 mo. RESULTS: The anthropometric characteristics of the patients remained unchanged throughout the study. Chronic vitamin E administration was associated with decreases in concentrations of glycated hemoglobin (P < 0.05), plasma insulin (P < 0.05), norepinephrine (P < 0.03), and epinephrine (P < 0.02); a lower homeostasis model assessment index (P < 0.05); and improved indexes of oxidative stress. Furthermore, vitamin E administration was associated with increases in the R-R interval (P < 0.05), total power (P < 0.05), and the high-frequency component of heart rate variability (HF; P < 0.05) and decreases in the low-frequency component (LF; P < 0.05) and the ratio of LF to HF (P < 0.05). Finally, change in the plasma vitamin E concentration was correlated with change in the LF-HF ratio (r = -0.43, P < 0.04) independently of changes in the homeostasis model assessment index and plasma catecholamines concentrations. CONCLUSIONS: Chronic vitamin E administration improves the ratio of cardiac sympathetic to parasympathetic tone in patients with type 2 diabetes. Such an effect might be mediated by a decline in oxidative stress.

Elevated plasma fatty acid concentrations stimulate the cardiac autonomic nervous system in healthy subjects.

BACKGROUND: Fatty acids have been shown to stimulate the sympathetic nervous system in rats. Power spectral analysis of heart rate variability (HRV) is a safe and useful tool with which to evaluate cardiac autonomic nervous system (ANS) activity. Whether changes in plasma fatty acid concentrations affect the sympathetic nervous system or HRV in humans is unknown. OBJECTIVE: We investigated the possible changes in HRV after a significant increase in plasma fatty acid concentration. DESIGN: Subjects were randomly assigned to receive an infusion of lipid emulsion (10% triacylglycerol emulsion for 180 min) + heparin (a bolus of 200 U followed by 0.2 U*min(-)(1)*kg body wt(-)(1); n = 20) or 0.9% NaCl (for 180 min; n = 10). RESULTS: Lipid emulsion + heparin infusion was associated with a rise in plasma epinephrine and norepinephrine concentrations. The rise in plasma fatty acid concentration was associated with a significant decline in the RR interval (P: < 0.03) and in total power (P: < 0.03). Analysis of the different components of HRV showed that lipid emulsion + heparin infusion stimulated low- frequency (LF) components (P: < 0.03 at the second hour and P: < 0. 01 at the third hour) and inhibited high-frequency (HF) components (P: < 0.03 at the second and third hours). Consequently, the LF-HF ratio was significantly stimulated (P: < 0.03 at the second hour and P: < 0.01 at the third hour). Such results persisted, although attenuated, when the study was repeated in association with a propranolol infusion (n = 8). CONCLUSION: Elevated plasma fatty acid concentrations may stimulate cardiac autonomic nervous system activity.

Effects of simvastatin and atorvastatin administration on insulin resistance and respiratory quotient in aged dyslipidemic non-insulin dependent diabetic patients.

One hundred and ninety-five aged (mean age: 67+/-4.8 years), non-insulin dependent diabetic patients underwent a randomised single-blind study for investigating the effect of statin administration on insulin resistance and respiratory quotient. After 4 weeks run-in period, all patients were randomised in three groups: placebo (n=67), simvastatin (10 mg/day) (n=61) and atorvastatin (5 mg/day) (n=67). Each treatment period lasted 8 weeks. At the beginning, after the run-in and at the end of the study, insulin resistance was assessed by homeostasis model assessment (HOMA) index, while respiratory quotient (Rq) was evaluated by indirect calorimetry. Statins versus placebo significantly lowered plasma total, LDL-, HDL-cholesterol and triglyceride concentrations and improved insulin resistance and Rq and metabolic control. Atorvastatin had a greater effect than simvastatin on plasma triglyceride concentration (-26.3+/-3.1 vs. -19.7+/-2.8%, P<0.03), HOMA index (-13.1+/-0.6 vs. -9.1+/-0.9%, P<0.05), Rq (5.9+/-0.4 vs. 3.1+/-0.5%, P<0.05) and glycosylated haemoglobin (-11.2+/-0.3 vs. -7. 1+/-0.4%, P<0.05). In the whole group of subjects (n=195) and at the end of the study, changes in plasma triglyceride concentrations were significantly correlated with the change in the HOMA index (r=0.44, P<0.001) and age and BMI adjusted-Rq (r=-0.32, P<0.005). Multivariate analyses demonstrated that decline in plasma triglyceride concentration was a significant determinant for explaining the effect of statin on insulin resistance and Rq. In conclusion our study demonstrates that statin administration is useful for controlling dyslipidemia in NIDDM patients and for improving the metabolic control. With regard to this latter aim, atorvastatin seems to be more powerful than simvastatin.

Chronic vitamin E administration improves brachial reactivity and increases intracellular magnesium concentration in type II diabetic patients.

Vascular disease accounts for the majority of the clinical complications in diabetes mellitus. As an exaggerated oxidative stress degree has been postulated as the link between diabetes mellitus and endothelial function, a possible positive effect of plasma vitamin E (Vit.E) administration on brachial reactivity could be postulated. Our study aims at investigating the possible effect of chronic Vit.E administration on brachial reactivity, oxidative stress indexes, and intracellular magnesium and calcium content in type II diabetic patients free of diabetic complications. Forty adult, type II diabetic patients were enrolled in the study, which was deigned as a double blind, randomized vs. placebo trial. At baseline all patients underwent the following tests: 1) anthropometric and metabolic examinations, 2) evaluation of oxidative stress indexes, 3) intracellular magnesium and calcium measurements, and 4) determination of arterial compliance and distensibility. Then, all patients were randomly assigned to Vit.E treatment at a dose of 600 mg/day (Evion Forte; n = 20) or placebo (n = 20) over 8 weeks. At the end of this treatment period, a complete reevaluation of the patients was made. Vit.E treatment was associated with a significant improvement in the percent change in brachial artery diameter (P<0.03) and oxidative stress indexes (P< 0.005). In the Vit.E group, the percent change in brachial artery diameter correlated positively with the percent change in oxidative stress indexes (oxidized/reduced glutathione, Trolox-equivalent antioxidant capacity, thiobarbituric acid reaction products, lipid peroxides) and intracellular cation content (magnesium and calcium). After adjustment for age, sex, body mass index, and wait/hip ratio, all of these correlations remained significant (P<0.03 for all). Furthermore, adjusting for glycosylated hemoglobin, plasma total cholesterol, and homeostatic model index, brachial artery diameter was still correlated with the percent change in oxidative stress indexes (P<0.04 for all). Nevertheless, the relationship between the percent change in brachial artery diameter and oxidative stress indexes was no longer significant after adjustment for intracellular Mg and Ca2+. In conclusion, our study demonstrates that chronic administration of Vit.E improves brachial artery reactivity in patients with type II diabetes mellitus. Such an effect seems mediated by a reduction in oxidative stress and a regulation of intracellular calcium and magnesium contents.