Legume Consumption and Blood Pressure Control in Individuals with Type 2 Diabetes and Hypertension: Cross-Sectional Findings from the TOSCA.IT Study.

BACKGROUND: Our aims were to evaluate the relationship of habitual legume consumption with blood pressure (BP) control in a large cohort of people with T2D and hypertension, and to investigate whether specific nutritional components of legumes or other foods may contribute to regulate BP levels. METHODS: We studied 1897 participants with T2D and hypertension. Dietary habits were assessed through a validated food frequency questionnaire. Sex-specific quartiles of legume consumption were created. RESULTS: Higher legume consumption was associated with a lower intake of energy, carbohydrates, glycaemic load, alcohol, and sodium, and a significantly greater intake of proteins, fat, monounsaturated, polyunsaturated, fibre, potassium, and polyphenols. Significantly lower systolic and diastolic BP values were observed in the highest vs. lowest quartile of legume consumption (132.9 ± 6.7 vs. 137.3 ± 7.0 mmHg, p < 0.001; 78.9 ± 4.1 vs. 81.0 ± 4.2 mmHg, p = 0.002; respectively), as well as the proportion of people meeting the treatment targets (61.3% vs. 37.4% and 71.3% vs. 52.4%, respectively, p < 0.01). This association was independent from other foods whose consumption is associated with the high legume intake. CONCLUSIONS: In people with T2D and hypertension, three servings of legumes per week are associated with significantly better BP control. This gives further support to current dietary guidelines in recommending the frequent consumption of legumes, as a "ready-to-use" dietary strategy to achieve optimal BP control.

Association between Diet Quality and Index of Non-Alcoholic Steatohepatitis in a Large Population of People with Type 2 Diabetes: Data from the TOSCA.IT Study.

Background: There are still open questions with respect to the optimal dietary treatment in patients with type 2 diabetes (T2D) and coexisting non-alcoholic steatohepatitis (NASH). The aim of this study is to investigate, in patients with T2D, the association between NASH, dietary component intake, food groups and adherence to the Mediterranean diet. Methods: Cross-sectional analysis of 2026 people with T2D (1136 men and 890 women). The dietary habits were assessed with the European Prospective Investigation into Cancer and Nutrition (EPIC) questionnaire. NASH was identified by the Index Of NASH (ION). Based on the cluster analysis two dietary patterns were identified: the NASH and the NO-NASH pattern. Results: The macronutrient composition of the diet was similar in the two patterns. However, the NASH pattern compared with the NO-NASH pattern was characterized by a significantly lower content of fibre (p < 0.001), ß-carotene (p < 0.001), vitamin C (p < 0.001), vitamin E (p < 0.001), polyphenols (p = 0.026) and antioxidant capacity (p < 0.001). With regard to food consumption, the NASH pattern compared with NO-NASH pattern was characterized by higher intake of rice (p = 0.021), potatoes (p = 0.013), red (p = 0.004) and processed meat (p = 0.003), and a lower intake of wholegrain bread (p = 0.019), legumes and nuts (p = 0.049), vegetables (p = 0.047), fruits (p = 0.002), white meat (p = 0.001), fatty fish (p = 0.005), milk and yogurt (p < 0.001). Conclusions: NO-NASH dietary pattern was characterized by a food consumption close to the Mediterranean dietary model, resulting in a higher content of polyphenols, vitamins, and fibre. These finding highlight the potential for dietary components in the prevention/treatment of NASH in people with T2D.

Effectiveness on major cardiovascular risk factors of an educational program to promote a Mediterranean type of diet among the employees of the company FCA Italia S.p.A.

AIMS: The educational program implemented at the Pratola Serra (Avellino, Italy) facility of the company FCA (Fiat Chrysler Automobiles), had as its goal to raise awareness among people to adopt behaviors inspired by the principles of a Mediterranean diet, physical activity and prevention of the main cardiovascular risk factors. METHODS: The educational program was implemented in two different ways in order to compare, according to an intervention-control scheme, the performance of the subgroups and the effect of the types of intervention. On both groups measurements of the vital parameters were carried out and compared by means of statistical probabilistic tests. RESULTS: The educational intervention was shown to be effective in: encouraging healthy food choices both in the workplace and at home (with a statistically significant reduction in caloric intake, animal protein, saturated fatty acids, cholesterol and glycemic load and an increase in vegetable proteins), significantly increasing physical activity and reducing body weight, body mass index, waist circumference, total cholesterol, LDL cholesterol and blood glucose in the participants. CONCLUSIONS: The educational campaign proved effective in increasing the well-being of the participants, confirming the effectiveness of a multifactorial intervention based on the promotion of a dietary model rather than individual foods.

Dietary inflammatory index score, glucose control and cardiovascular risk factors profile in people with type 2 diabetes.

We examined the relationships between the dietary inflammatory index (DII®), dietary habits and cardiovascular risk factor profiles in people with type 2 diabetes mellitus (T2DM). Energy-adjusted DII (E-DII™) scores were calculated from a Food Frequency Questionnaire in 2568 T2DM patients from different parts of Italy. Analyses were conducted according to quartiles of sex-specific E-DII scores. Higher, more pro-inflammatory, (quartile 4) E-DII scores were associated with overall poor quality of the diet characterised by higher content of refined carbohydrates, added sugars, saturated fat and cholesterol and lower unsaturated fat, fibre and polyphenols compared to quartile 1. Higher E-DII scores also were associated with higher waist circumference (105.4 vs. 103.5 cm; p = 0.002), triglycerides (154.6 vs. 146.1 mg/dL; p = 0.005), diastolic blood pressure (80.05 vs. 78.6 mmHg; p = 0.04) and lower HDL-cholesterol (45.3 vs. 47.4 mg/dL; p = 0.04). In conclusion, E-DII is a potent marker of overall quality of the diet and is associated with an unfavourable cardiovascular risk factor profile.

Pasta Consumption and Connected Dietary Habits: Associations with Glucose Control, Adiposity Measures, and Cardiovascular Risk Factors in People with Type 2 Diabetes-TOSCA.IT Study.

BACKGROUND: Pasta is a refined carbohydrate with a low glycemic index. Whether pasta shares the metabolic advantages of other low glycemic index foods has not really been investigated. The aim of this study is to document, in people with type-2 diabetes, the consumption of pasta, the connected dietary habits, and the association with glucose control, measures of adiposity, and major cardiovascular risk factors. METHODS: We studied 2562 participants. The dietary habits were assessed with the European Prospective Investigation into Cancer and Nutrition (EPIC) questionnaire. Sex-specific quartiles of pasta consumption were created in order to explore the study aims. RESULTS: A higher pasta consumption was associated with a lower intake of proteins, total and saturated fat, cholesterol, added sugar, and fiber. Glucose control, body mass index, prevalence of obesity, and visceral obesity were not significantly different across the quartiles of pasta intake. No relation was found with LDL cholesterol and triglycerides, but there was an inverse relation with HDL-cholesterol. Systolic blood pressure increased with pasta consumption; but this relation was not confirmed after correction for confounders. CONCLUSIONS: In people with type-2 diabetes, the consumption of pasta, within the limits recommended for total carbohydrates intake, is not associated with worsening of glucose control, measures of adiposity, and major cardiovascular risk factors.

Impact of a Mediterranean Dietary Pattern and Its Components on Cardiovascular Risk Factors, Glucose Control, and Body Weight in People with Type 2 Diabetes: A Real-Life Study.

This study evaluates the relation of a Mediterranean dietary pattern and its individual components with the cardiovascular risk factors profile, plasma glucose and body mass index (BMI) in people with type 2 diabetes. We studied 2568 participants at 57 diabetes clinics. Diet was assessed with the EPIC (European Prospective Investigation into Cancer and Nutrition) questionnaire, adherence to the Mediterranean diet was evaluated with the relative Mediterranean diet score (rMED). A high compared to a low score was associated with a better quality of diet and a greater adherence to the nutritional recommendations for diabetes. However, even in the group achieving a high score, only a small proportion of participants met the recommendations for fiber and saturated fat (respectively 17% and 30%). Nonetheless, a high score was associated with lower values of plasma lipids, blood pressure, glycated hemoglobin, and BMI. The relationship of the single food items components of the rMED score with the achievement of treatment targets for plasma lipids, blood pressure, glucose, and BMI were also explored. The study findings support the Mediterranean dietary model as a suitable model for type 2 diabetes and the concept that the beneficial health effects of the Mediterranean diet lie primarily in its synergy among various nutrients and foods rather than on any individual component.

Effects on the incidence of cardiovascular events of the addition of pioglitazone versus sulfonylureas in patients with type 2 diabetes inadequately controlled with metformin (TOSCA.IT): a randomised, multicentre trial.

BACKGROUND: The best treatment option for patients with type 2 diabetes in whom treatment with metformin alone fails to achieve adequate glycaemic control is debated. We aimed to compare the long-term effects of pioglitazone versus sulfonylureas, given in addition to metformin, on cardiovascular events in patients with type 2 diabetes. METHODS: TOSCA.IT was a multicentre, randomised, pragmatic clinical trial, in which patients aged 50-75 years with type 2 diabetes inadequately controlled with metformin monotherapy (2-3 g per day) were recruited from 57 diabetes clinics in Italy. Patients were randomly assigned (1:1), by permuted blocks randomisation (block size 10), stratified by site and previous cardiovascular events, to add-on pioglitazone (15-45 mg) or a sulfonylurea (5-15 mg glibenclamide, 2-6 mg glimepiride, or 30-120 mg gliclazide, in accordance with local practice). The trial was unblinded, but event adjudicators were unaware of treatment assignment. The primary outcome, assessed with a Cox proportional-hazards model, was a composite of first occurrence of all-cause death, non-fatal myocardial infarction, non-fatal stroke, or urgent coronary revascularisation, assessed in the modified intention-to-treat population (all randomly assigned participants with baseline data available and without any protocol violations in relation to inclusion or exclusion criteria). This study is registered with ClinicalTrials.gov, number NCT00700856. FINDINGS: Between Sept 18, 2008, and Jan 15, 2014, 3028 patients were randomly assigned and included in the analyses. 1535 were assigned to pioglitazone and 1493 to sulfonylureas (glibenclamide 24 [2%], glimepiride 723 [48%], gliclazide 745 [50%]). At baseline, 335 (11%) participants had a previous cardiovascular event. The study was stopped early on the basis of a futility analysis after a median follow-up of 57·3 months. The primary outcome occurred in 105 patients (1·5 per 100 person-years) who were given pioglitazone and 108 (1·5 per 100 person-years) who were given sulfonylureas (hazard ratio 0·96, 95% CI 0·74-1·26, p=0·79). Fewer patients had hypoglycaemias in the pioglitazone group than in the sulfonylureas group (148 [10%] vs 508 [34%], p<0·0001). Moderate weight gain (less than 2 kg, on average) occurred in both groups. Rates of heart failure, bladder cancer, and fractures were not significantly different between treatment groups. INTERPRETATION: In this long-term, pragmatic trial, incidence of cardiovascular events was similar with sulfonylureas (mostly glimepiride and gliclazide) and pioglitazone as add-on treatments to metformin. Both of these widely available and affordable treatments are suitable options with respect to efficacy and adverse events, although pioglitazone was associated with fewer hypoglycaemia events. FUNDING: Italian Medicines Agency, Diabete Ricerca, and Italian Diabetes Society.

Polyphenol intake and cardiovascular risk factors in a population with type 2 diabetes: The TOSCA.IT study.

BACKGROUND: The role of polyphenol intake on cardiovascular risk factors is little explored, particularly in people with diabetes. AIM: To evaluate the association between the intake of total polyphenols and polyphenol classes with the major cardiovascular risk factors in a population with type 2 diabetes. METHODS: Dietary habits were investigated in 2573 males and females participants of the TOSCA.IT study. The European Prospective Investigation on Cancer and Nutrition (EPIC) questionnaire was used to assess dietary habits. In all participants, among others, we assessed anthropometry, plasma lipids, blood pressure, C-reactive protein and HbA1c following a standard protocol. The USDA and Phenol-Explorer databases were used to estimate the polyphenol content of the habitual diet. RESULTS: Average intake of polyphenols was 683.3 ± 5.8 mg/day. Flavonoids and phenolic acids were the predominant classes (47.5% and 47.4%, respectively). After adjusting for potential confounders, people with the highest intake of energy-adjusted polyphenols (upper tertile) had a more favorable cardiovascular risk factors profile as compared to people with the lowest intake (lower tertile) (BMI was 30.7 vs 29.9 kg/m2, HDL-cholesterol was 45.1 vs 46.9 mg/dl, LDL-cholesterol was 103.2 vs 102.1 mg/dl, triglycerides were 153.4 vs 148.0 mg/dl, systolic and diastolic blood pressure were respectively 135.3 vs 134.3 and 80.5 vs 79.6 mm/Hg, HbA1c was 7.70 vs 7.67%, and C-reactive Protein was 1.29 vs 1.25 mg/dl, p < .001 for all). The findings were very similar when the analysis was conducted separately for flavonoids or phenolic acids, the two main classes of polyphenols consumed in this population. CONCLUSIONS: Polyphenol intake is associated with a more favorable cardiovascular risk factors profile, independent of major confounders. These findings support the consumption of foods and beverages rich in different classes of polyphenols particularly in people with diabetes. CLINICAL TRIAL: http://www.clinicaltrials.gov; Study ID number: NCT00700856.

How Well Can We Control Dyslipidemias Through Lifestyle Modifications?

The role for lifestyle modifications to correct dyslipidemia(s) is reviewed. Dietary composition is crucial. Replacing saturated fat with MUFA or n-6 PUFA lowers plasma low-density lipoproteins (LDL) cholesterol and ameliorates the LDL/HDL ratio. Replacing saturated fat with carbohydrates has diverging effects due to the heterogeneity of carbohydrate foods. Diets rich in refined carbohydrates increase fasting and postprandial triglycerides, whereas the consumption of fiber-rich, low GI foods lowers LDL cholesterol with no detrimental effects on triglycerides. The role of polyphenols is debated: available evidence suggests a lowering effect of polyphenol-rich foods on postprandial triglycerides. As for functional foods, health claims on a cholesterol lowering effect of psyllium, beta-glucans and phytosterols are accepted by regulatory agencies. The importance of alcohol intake, weight reduction, and physical activity is discussed. In conclusion, there is evidence that lifestyle affects plasma lipid. A multifactorial approach including multiple changes with additive effects is the best option. This may also ensure feasibility and durability. The traditional Mediterranean way of life can represent a useful model.

The PPARγ2 Pro12Ala variant is protective against progression of nephropathy in people with type 2 diabetes.

OBJECTIVE: Cross-sectional studies suggest the association between diabetic nephropathy and the PPARγ2 Pro12Ala polymorphism of the peroxisome proliferator-activated receptor γ2 (PPARγ2). Prospective data are limited to microalbuminuria and no information on renal function is available to date. The present study evaluates the association between the Pro12Ala polymorphism of PPARγ2 and the progression of albuminuria and decay in glomerular filtration rate (GFR) in type 2 diabetes. PATIENTS AND MEASUREMENTS: We studied 256 patients with an average 5-year follow-up. Among others, urinary albumin excretion rate (UAER) was measured on spot sample, GFR was estimated with the CKD-EPI Equation. RESULTS: Baseline UAER and GFR were similar for carriers or non-carriers of the polymorphism. At follow-up no significant changes from baseline were observed for UAER or eGFR in carriers of the Pro12Ala polymorphism whereas a significant increase in UAER [17 (11.3-37.9) versus 24.5 (13.8-49.9) µg/mg, p < 0.006)] and a significant reduction in the eGFR (82.8 ± 14.5 versus 80.3 ± 17.3 ml/min/1.73, m(2) p = 0.02), were observed in non carriers of the Pro12Ala polymorphism. Progression of nephropathy - defined according to a combined end point of UAER and eGFR- i.e. doubling of baseline UAER to at least 100 µg/mg, or new onset microalbuminuria, or progression from micro to macroalbuminuria, or 25% reduction of eGFR, or annualized eGFR decline >3 ml/min/year - was significantly less frequent in Ala carriers than non carriers (11.4% vs 35.8%; p < 0.01); HR adjusted for baseline age, AER, eGFR, HbA1c, diabetes duration and blood pressure was 0.32 (0.12-0.80). CONCLUSIONS: This study found that among patients with type 2 diabetes, the PPARγ2 Pro12Ala polymorphism is protective against progression of nephropathy and decay of renal function independent of major confounders.

A 19 year follow-up of a woman with lipoprotein lipase deficiency treated with biliopancreatic diversion.

We show the long-term efficacy and safety of modified biliopancreatic diversion for the treatment of LPL-deficiency. How this option compares with gene therapy is difficult to evaluate due to limited experience. Surgery may be the first option in patients in whom medical therapy is ineffective and gene therapy not applicable.

Iron deficiency and cardiovascular disease: an updated review of the evidence.

Body iron status has been suggested to be related to the development of cardiovascular disease (CVD). Biologically plausible mechanisms for this association have been described, however epidemiological studies on iron status and CVD risk have provided conflicting results. The lack of consistency is likely explained by differences in the study design, the measures used for the assessment of iron status, the definition of outcomes, and adjustment for confounders. To help clarify the available evidence, we report a systematic review of published cross-sectional, longitudinal, and intervention studies evaluating the relationship between different measures of iron status and CVD risk. The most likely scenario that emerges from the available studies is that, in the reference range, iron status has a neutral effect. Extreme conditions of iron deficiency, as well as of iron overload, are associated with modestly increased CVD risk, although with different proposed mechanisms.

Fasting apolipoprotein B48 is associated with asymptomatic peripheral arterial disease in type 2 diabetic subjects: a case-control study.

OBJECTIVE: To test whether there is an association between fasting ApoB48 level, a marker of the residual presence of intestinally derived TRLs lipoproteins, thought to be highly atherogenic, and peripheral artery disease (PAD) in type 2 diabetic patients independent of fasting plasma lipids. METHODS: We studied 87 patients with type 2 diabetes: 34 with asymptomatic PAD (ankle/brachial index < 0.9) and 53 without PAD matched on age (±2 years), gender and BMI (±2 kg/m(2)). The plasma fasting ApoB48 was measured by ELISA. RESULTS: Patients with PAD had significantly higher ApoB48 levels (1.529 ± 1.253 vs 1.095 ± 0.667 µg/ml p = 0.04) than those without PAD independent of major confounders, such as duration of diabetes, smoking status, HbA1c, systolic blood pressure and fasting plasma lipids. CONCLUSIONS: Fasting ApoB48 was independently associated with asymptomatic PAD in patients with type 2 diabetes.

Uncoupling protein 2 G(-866)A polymorphism: a new gene polymorphism associated with C-reactive protein in type 2 diabetic patients.

BACKGROUND: This study evaluated the relationship between the G(-866)A polymorphism of the uncoupling protein 2 (UCP2) gene and high-sensitivity C reactive protein (hs-CRP) plasma levels in diabetic patients. METHODS: We studied 383 unrelated people with type 2 diabetes aged 40-70 years. Anthropometry, fasting lipids, glucose, HbA1c, and hs-CRP were measured. Participants were genotyped for the G (-866)A polymorphism of the uncoupling protein 2 gene. RESULTS: Hs-CRP (mg/L) increased progressively across the three genotype groups AA, AG, or GG, being respectively 3.0 ± 3.2, 3.6 ± 5.0, and 4.8 ± 5.3 (p for trend = 0.03). Since hs-CRP values were not significantly different between AA and AG genotype, these two groups were pooled for further analyses. Compared to participants with the AA/AG genotypes, homozygotes for the G allele (GG genotype) had significantly higher hs-CRP levels (4.8 ± 5.3 vs 3.5 ± 4.7 mg/L, p = 0.01) and a larger proportion (53.9% vs 46.1%, p = 0.013) of elevated hs-CRP (> 2 mg/L). This was not explained by major confounders such as age, gender, BMI, waist circumference, HbA1c, smoking, or medications use which were comparable in the two genotype groups. CONCLUSIONS: The study shows for the first time, in type 2 diabetic patients, a significant association of hs-CRP levels with the G(-866)A polymorphism of UCP2 beyond the effect of major confounders.

Relationship between smoking habits and the features of the metabolic syndrome in a non-diabetic population.

INTRODUCTION: Cigarette smoking is a risk factor for type 2 diabetes mellitus. The effect of smoking on the pathogenic factors for the development of diabetes is little explored. We evaluate the relation of smoking with the features of the insulin resistance syndrome, insulin resistance, and insulin secretion. METHODS: 2412 non-diabetic men, aged 35-65 years, were studied. Smoking habit was investigated by questionnaire. Anthropometry, blood pressure, forced expiratory volume (FEV1), fasting glucose, triglycerides, total and HDL cholesterol, plasma free fatty acids (FFA), insulin and fibrinogen were measured. HOMA-IR and HOMA beta cell were calculated. The metabolic syndrome was defined according to ATP III criteria. RESULTS: The metabolic syndrome was more prevalent in smokers than non-smokers (OR: 1.34; 95% CI 1.01-1.77). This was mainly due to a higher prevalence of dyslipidemia - high triglycerides (46.1% vs 29.9%, p<0.001), or low HDL cholesterol (42.2% vs 30.4%, p<0.001), in smokers. In smokers, other features of insulin resistance - i.e. obesity, hypertension, and hyperglycemia were significantly less frequent and FFA were lower (p<0.001). Plasma insulin and HOMA beta cell were similar in the two groups (8.3 vs 8.0microU/ml and 80.7% vs 82.9%, respectively), but HOMA-IR was significantly lower in smokers (p<0.001) due to the lower glucose values observed in these people. CONCLUSIONS: Among the features of the metabolic syndrome, only dyslipidemia is associated with chronic smoking. Smoking in not associated with enhanced insulin resistance, or with impaired insulin secretion. Alternative hypotheses should be explored for the increased risk of diabetes in smokers.

Changing the definition of impaired fasting glucose: impact on the classification of individuals and risk definition.

OBJECTIVE: This study evaluates the impact of lowering the diagnostic threshold for impaired fasting glucose (IFG) from 6.1 to 5.6 mmol/l as proposed by the American Diabetes Association (ADA) on the prevalence of the condition, classification of individuals, and risk definition. RESEARCH DESIGN AND METHODS: A total of 1,285 employees of the Italian Telephone Company aged 35-59 years without known diabetes underwent an oral glucose tolerance test (OGTT). BMI, serum cholesterol, triglycerides, and blood pressure were measured. Medication use was recorded. RESULTS: With the new ADA criterion, the proportion of people diagnosed with IFG increased from 3.2 to 9.7%. The newly proposed IFG category identified 41% of all subjects with impaired glucose tolerance (IGT) compared with 16.2% identified with the use of the World Health Organization criterion for IFG; the improvement in accuracy has been achieved at the cost of classifying more previously "normal" subjects as having IFG (from 2.3 to 7.3%). Both IFG and IGT were associated with an unfavorable risk profile for diabetes and cardiovascular disease, with a higher estimated risk for IGT than IFG. CONCLUSIONS: Even with the revised diagnostic criterion, IFG and IGT identify distinct groups that have a different background risk. The cost/benefit of preventive measures tested in people with IGT may not apply to the new IFG category.