Laura Franzini

Women show worse control of type 2 diabetes and cardiovascular disease risk factors than men: Results from the MIND.IT Study Group of the Italian Society of Diabetology.

BACKGROUND AND AIMS The study explores the degree of control of hyperglycaemia and cardiovascular (CV) disease risk factors in men and women with type 2 diabetes and the impact thereon of obesity, central adiposity, age and use of medications. METHODS AND RESULTS A cross-sectional survey was conducted at 10 hospital-based outpatients diabetes clinics. 1297 men and 1168 women with no previous CV events were studied. Women were slightly (only one year) older and more obese than men: average BMI was respectively 30.7 ± 5.7 vs 28.6 ± 4.1 kg/m(2) (p < 0.001), and prevalence of abdominal obesity was 86% vs 44% (p < 0.001). Women smoked less, but had higher HbA1c, LDL cholesterol, non-HDL cholesterol, systolic blood pressure and serum fibrinogen than men. Accordingly optimal targets for HbA1c (<7%), LDL cholesterol (<100 mg/dL), HDL cholesterol (>40 for men, >50 for women, mg/dL), and systolic blood pressure (<130 mmHg) were less frequently achieved by women than men (respectively 33.8% vs 40.2%; 14.6% vs 19.2%; 34.1% vs 44.5%; 68.8% vs 72%; p < 0.05 for all). Findings were confirmed after stratification for waist circumference (< or ≥ 88 cm for women; < or ≥ 102 cm for men), BMI (< or ≥ 25 kg/m(2)) or age (< or ≥ 65 years). As for treatment, women were more likely than men to take insulin, alone or in combination with oral hypoglycaemic drugs, to be under anti-hypertensive treatment, whereas the use of lipid lowering drugs was similar in men and women. CONCLUSIONS Control of hyperglycaemia and major CVD risk factors is less satisfactory in women than men. The gender disparities are not fully explained by the higher prevalence of total and central obesity in women; or by a less intensive medical management in women.

ADMA is independently related to flow-mediated vasodilation in subjects at low cardiovascular risk.

Background  Increased plasma concentrations of asymmetric dimethylarginine (ADMA) contribute to impair endothelial function in patients with established cardiovascular disease (CVD) and/or individuals with clinical syndromes known to increase CVD. However, the impact of ADMA on endothelial function in apparently healthy individuals has not been determined.

The total antioxidant capacity of the diet is an independent predictor of plasma β -carotene

Objective:To investigate the contribution of the total antioxidant capacity (TAC) of the diet to plasma concentrations of β-carotene.Design:Cross-sectional study.Setting:Department of Public Health and Department of Internal Medicine and Biomedical Sciences, University of Parma.Subjects:A total of 247 apparently healthy adult men (n=140) and women (n=107).Methods:A medical history, a physical exam including height, weight, waist circumference and blood pressure measurements, a fasting blood draw, an oral glucose tolerance test and a 3-day food record.Results:We observe a negative trend across quartiles of plasma β-carotene for most biological variables clustering in the insulin resistance syndrome, as well as for traditional and new risk factors for type II diabetes and cardiovascular disease (CVD), including C-reactive protein and γ-glutamyltranspeptidase (P<0.05). Regarding dietary characteristics, energy-adjusted intake of fat, fiber, fruits, vegetables, β-carotene, vitamin C, vitamin E and dietary TAC significantly increased with increasing plasma β-carotene (P<0.05), whereas alcohol intake decreased (P=0.013). Adjusted geometric means (95% confidence interval) of plasma β-carotene significantly increased across quartiles of dietary TAC, even when single dietary antioxidants were considered in the model (QI=0.087 mg/dl (0.073–0.102); QII=0.087 mg/dl (0.075–0.103); QIII=0.114 mg/dl (0.098–0.132) and QIV=0.110 mg/dl (0.093–0.130); P for linear trend=0.026). When the population was divided on the basis of alcohol consumption, this trend was also observed in subjects drinking <20 g alcohol/day (P=0.034), but not in those with higher alcohol intake (P=0.448).Conclusions:Dietary TAC is an independent predictor of plasma β-carotene, especially in moderate alcohol drinkers. This may explain, at least in part, the inverse relationship observed between plasma β-carotene and risk of chronic diseases associated to high levels of oxidative stress (i.e., diabetes and CVD), as well as the failure of β-carotene supplements alone in reducing such risk.Sponsorship:Supported by the European Community IST-2001–33204 ‘Healthy Market’, the Italian Ministry of University and Research COFIN 2001 and the National Research Council CU01.00923.CT26 research projects.

Lower endothelial progenitor cell number, family history of cardiovascular disease and reduced HDL-cholesterol levels are associated with shorter leukocyte telomere length in healthy young adults

BACKGROUND AND AIMS Leukocyte telomere length (LTL) is a novel marker of cardiovascular (CV) risk. The aim of the study was to investigate the major determinants of LTL in a healthy young population at very low CV risk. METHODS AND RESULTS LTL was determined in 82 healthy subjects (49M/33F; age37 ± 9yrs), normotensive and not taking any medication with different family history of cardiovascular disease (CVD) (24yes/58no). Fasting blood samples were drawn in all subjects for the determination of lipid profile, high sensitive C-reactive protein, uric acid, Plasminogen Activator Inhibitor-1 (PAI-1), LTL and Endothelial Progenitor Cell (EPC) number. LTL was assessed with a specific real-time PCR reaction in leukocyte DNA samples. LTL resulted inversely correlated with family history of CVD (t = 2.70; p = 0.009), age (r = -0.238; p = 0.032), waist circumference (r = -0.256; p = 0.02), triglycerides (r = -0.218; p = 0.049), PAI-1 (r = -0.288; p = 0.009) and directly correlated with HDL-cholesterol (r = 0.316; p = 0.004) and EPC number (r = 0.358; p = 0.002). At a multivariate analysis, family history of CVD (p = 0.013), EPC count (p = 0.003), and HDL-cholesterol (p = 0.017) were independently associated with LTL (r = 0.62). CONCLUSION LTL is independently associated to CV risk factors also in healthy young adults.

Intake of the plant lignans matairesinol, secoisolariciresinol, pinoresinol, and lariciresinol in relation to vascular inflammation and endothelial dysfunction in middle age-elderly men and post-menopausal women living in Northern Italy

BACKGROUND AND AIMS It has been suggested that lignan intake may decrease the risk for cardiovascular disease (CVD) by modifying traditional risk factors as well as aortic stiffness. However, the role of dietary lignans on the vascular system is largely unknown. The objective was to investigate whether dietary intake of plant lignans in a free-living population was associated with markers of vascular inflammation and function. METHODS AND RESULTS We performed a cross-sectional study in 242 (151 males) men and post-menopausal women. Anthropometric characteristics and lignan intake were evaluated. Soluble intercellular adhesion molecule-1 (sICAM-1), insulin, high-sensitive C-reactive protein, glucose, total cholesterol, HDL-cholesterol and triacylglycerols were measured in fasting blood samples. Brachial flow-mediated dilation (FMD) measurements were available for 101 subjects (56 males). Median (interquartile range) daily intake of matairesinol (MAT), secoisolariciresinol (SECO), pinoresinol (PINO), lariciresinol (LARI), and total lignans was 20.9 microg (17.4), 335.3 microg (289.1), 96.7 microg (91.1), 175.7 microg (135.8), and 665.5 microg (413.7), respectively, as assessed by 3-day weighed food record. Plasma concentrations of sICAM-1 (whole sample) significantly decreased (mean (95%CI) = 358 microg/L (320-401), 276 microg/L (252-303), 298 microg/L (271-326), and 269 microg/L (239-303), P per trend 0.013) and FMD values (FMD sub-group) significantly increased (4.1% (2.2-6.0), 5.7% (4.3-7.2), 6.4% (4.9-7.8), and 8.1% (6.3-10.0), P per trend 0.016) across quartiles of energy-adjusted MAT intake, even after adjustment for relevant clinical and dietary variables. Intake of SECO was also inversely related to plasma sICAM-1 (P per trend 0.018), but not to FMD values. No relationship between intake of PINO, LARI or total lignans and either sICAM-1 or FMD values was observed. CONCLUSIONS Higher MAT intakes in the context of a typical Northern Italian diet are associated to lower vascular inflammation and endothelial dysfunction, which could have some implications in CVD prevention.

Dietary antioxidants and glucose metabolism.

Purpose of reviewOxidative stress seems to play a pathogenic role in the vicious circle linking obesity, insulin resistance and type 2 diabetes. Hypothetically, dietary antioxidants should decrease oxidative stress and therefore improve glucose metabolism. However, many interventional trials evaluating the effect of antioxidant supplementation on insulin resistance, plasma glucose levels and risk of type 2 diabetes gave inconsistent results. Recent findingsMany studies have recently demonstrated a positive effect of vitamin supplementation and of food enriched in antioxidant (seafood, whole nut, etc.) on markers of oxidative stress, insulin resistance, fasting plasma glucose and incidence of diabetes. The present paper critically reviews the consolidated notions on dietary antioxidant in view of the recent evidences. SummaryAlthough a definitive estimation of the impact of dietary antioxidants on glucose metabolism is still lacking, food with high antioxidant concentrations seems to have a protective effect, improving oxidative stress-mediated detrimental effects on the vicious circle among obesity, insulin resistance and redox imbalance.

Ability of a high-total antioxidant capacity diet to increase stool weight and bowel antioxidant status in human subjects

There is limited knowledge about the possible effect of unabsorbed dietary antioxidants that reach the large intestine on bowel habits. The aim of the present study was to investigate whether a dietary recommendation directed to increase diet total antioxidant capacity (TAC) is able to affect gut function in human subjects. In this cross-over intervention, nineteen subjects followed a high-TAC (HT) and a low-TAC (LT) diet for 2 weeks, which were comparable for energy, macronutrient, total dietary fibre and alcohol contents. At the end of each intervention period, the 48 h stool output was recorded. In the faecal samples obtained from a subset of nine subjects, moisture, pH, ammonia content, Lactobacillus and Bifidobacterium counts, faecal water antioxidants and genotoxicity were measured. A 3 d weighed food record was used to assess the diet composition during HT and LT diet intake. Significant increases in the intake of TAC, vitamins E and C and phenolic compounds were observed during the HT diet intake. The higher intake of antioxidants led to increased 48 h stool output (324 (SD 38) g in HT v. 218 (SD 22) g in LT), and to higher TAC and total phenolic concentrations in faecal water. No significant variation in the other measured parameters was observed between the diets. In conclusion, a diet selected to raise the intake of dietary antioxidants is able to increase stool bulk and antioxidant content of faeces.

Feasibility and Effectiveness in Clinical Practice of a Multifactorial Intervention for the Reduction of Cardiovascular Risk in Patients With Type 2 Diabetes The 2-year interim analysis of the MIND.IT study: a cluster randomized trial

OBJECTIVE To evaluate the feasibility and effectiveness of an intensive, multifactorial cardiovascular risk reduction intervention in a clinic-based setting. RESEARCH DESIGN AND METHODS The study was a pragmatic, cluster randomized trial, with the diabetes clinic as the unit of randomization. Clinics were randomly assigned to either continue their usual care (n = 5) or to apply an intensive intervention aimed at the optimal control of cardiovascular disease (CVD) risk factors and hyperglycemia (n = 4). To account for clustering, mixed model regression techniques were used to compare differences in CVD risk factors and HbA1c. Analyses were performed both by intent to treat and as treated per protocol. RESULTS Nine clinics completed the study; 1,461 patients with type 2 diabetes and no previous cardiovascular events were enrolled. After 2 years, participants in the interventional group had significantly lower BMI, HbA1c, LDL cholesterol, and triglyceride levels and significantly higher HDL cholesterol level than did the usual care group. The proportion of patients reaching the treatment goals was systematically higher in the interventional clinics (35% vs. 24% for LDL cholesterol, P = 0.1299; 93% vs. 82% for HDL cholesterol, P = 0.0005; 80% vs. 64% for triglycerides, P = 0.0002; 39% vs. 22% for HbA1c, P = 0.0259; 13% vs. 5% for blood pressure, P = 0.1638). The analysis as treated per protocol confirmed these findings, showing larger and always significant differences between the study arms for all targets. CONCLUSIONS A multifactorial intensive intervention in type 2 diabetes is feasible and effective in clinical practice and it is associated with significant and durable improvement in HbA1c and CVD risk profile.

Intervention study with a high or low antioxidant capacity diet: effects on circulating β-carotene.

Background and objectives:A cross-sectional observation suggests that total antioxidant capacity (TAC) of the diet positively affects plasma concentrations of β-carotene independent of β-carotene intake. This study was carried out to investigate the effect of two dietary strategies, designed to be comparable in fruits, vegetables, fibre, alcohol and β-carotene intake but substantially different in their TAC, on changes in antioxidant intake and antioxidant status, and in particular in circulating β-carotene concentrations.Subjects:A randomized cross-over intervention trial involving 33 healthy participants and consisting of two 14-day dietary periods (high TAC diet, HT; low TAC diet, LT) with a 14-day washout in between was conducted.Results:Energy, macronutrient, dietary fibre, alcohol and β-carotene intake was not significantly different between LT and HT, whereas intake of other carotenoids and dietary TAC was significantly higher in the HT than in the LT (P<0.001). Circulating carotenoids (with the exception of α-carotene, which followed an inverse trend) and α-tocopherol decreased significantly during the LT and increased during the HT period. Among these, β-carotene almost doubled its concentration in plasma after the HT diet.Conclusions:The increase in circulating β-carotene along with the increase in dietary TAC suggests that plasma β-carotene could be a marker of TAC intake rather than of β-carotene intake itself. This may explain, in part, why β-carotene supplementation alone has shown no benefit in chronic disease prevention and adds to a putative beneficial role of high dietary TAC diets, which merits further investigation.

The increase in plasma PAI-1 associated with insulin resistance may be mediated by the presence of hepatic steatosis.

OBJECTIVE Recent evidence suggests that plasminogen-activator inhibitor-1 (PAI-1) is abundantly produced by the fatty liver, but it is unclear whether hepatic steatosis (HS) can mediate the increase in plasma PAI-1 induced by insulin resistance/compensatory hyperinsulinemia (IR/CH). METHODS AND RESULTS To address this issue, we cross-sectionally evaluated IR/CH as area under the curve of plasma insulin (AUC-PI) concentrations during OGTT, metabolic profile, and ultrasound degree of HS in 235 healthy volunteers (132M, age: 60+/-7 years) with normal transaminase concentrations. Circulating PAI-1 was increased in subjects with classical features of IR/CH (overweight, high fasting and post-OGTT insulin and glucose, high triglycerides (TG), and low HDL-cholesterol), and significantly correlated to prevalence and degree of HS, but not to alcohol intake. In a multivariate model, AUC-PI, TG and degree of HS were independent predictors of plasma PAI-1 (R(2)=0.32). However, AUC-PI was significantly correlated to PAI-1 only in subjects with HS, suggesting an interaction between AUC-PI and HS. In addition, in the presence of HS and IR/CH, PAI-1 concentrations were increased to a similar extent both in heavy and moderate drinkers, suggesting that metabolic and alcoholic steatosis have a similar effect on the relationship between IR/CH and PAI-1. CONCLUSION These results support the hypothesis that HS has a major impact on the relationship between IR/CH and plasma PAI-1 concentrations, and this effect seems to be unaffected by the etiology of the HS.