Clusters of adipose tissue dysfunction in adults with type 2 diabetes identify those with worse lipidomic profile despite similar glycaemic control.

AIMS: To investigate clusters of adipose tissue dysfunction, that is, with adipose tissue insulin resistance (ADIPO-IR) and large waist circumference (WC), identify a worse lipidomic profile characterised by a high proportion of lipids rich in saturated fatty acids (SFA). MATERIALS AND METHODS: Hierarchical clustering based on WC and ADIPO-IR (calculated as fasting plasma non-esterified fatty acids times fasting plasma insulin, FFA×INS), was performed in 192 adults with overweight/obesity and type 2 diabetes (T2D) treated with metformin (HbA1c = 7.8%). Free fatty acid composition and lipidomic profile were measured by mass spectrometry (GC-MS and LC-MSQTOF). Indexes of fatty acid desaturation (stearoyl-coA desaturase-1 activity, SCD116 = palmitoleic acid/palmitic acid and SCD118 = oleic acid/stearic acid) and of insulin resistance (HOMA-IR) were also calculated. RESULTS: Three clusters were identified: CL1 (ADIPO-IR = 4.9 ± 2.4 and WC = 96±7 cm, mean ± SD), CL2 (ADIPO-IR = 6.5 ± 2.5 and WC = 114 ± 7 cm), and CL3 (ADIPO-IR = 15.0 ± 4.7 and WC = 107 ± 8 cm). Insulin concentrations, ADIPO-IR, and HOMA-IR significantly increased from CL1 to CL3 (all p < 0.001), while fasting glucose concentrations, HbA1c, dietary lipids and caloric intake were similar. Moreover, CL3 showed significantly higher concentrations of monounsaturated free fatty acids, oleic and palmitoleic acids, triglycerides (TAG) rich in saturated FA and associated with de novo lipogenesis (i.e., TAG 46-50), higher SCD116, SCD118, ceramide (d18:0/18:0), and phosphatidylcholine aa(36:5) compared with CL1/CL2 (all p < 0.005). CONCLUSIONS: High ADIPO-IR and large WC identify a worse lipid profile in T2D characterised by complex lipids rich in SFA, likely due to de novo synthesis given higher plasma monounsaturated FFA and increased desaturase activity indexes. REGISTRATION NUMBER TRIAL: ID NCT00700856 https://clinicaltrials.gov.

Feasibility of a Type 2 Diabetes Prevention Program at Nationwide Level in General Practice: A Pilot Study in Italy.

BACKGROUND: Lifestyle interventions halt the progression of prediabetes to frank type 2 diabetes (T2D). However, the feasibility of a diabetes prevention program promoting tailored interventions on a national scale and conducted by primary care physicians is unclear. METHODS: General practitioners located in ten different regions throughout Italy enrolled random subjects without known metabolic diseases to identify individuals with prediabetes and prescribe them an intervention based on physical activity. Using a simple stepwise approach, people referring to their primary care physician for any reason were screened for their diabetes risk with a web-based app of the Findrisc questionnaire. Those at risk for T2D, i.e., with a Findrisc score >9, were invited to come back after overnight fasting to measure fasting glycaemia (FG). Those with 100 ≤ FG < 126 mg/dL were considered as people with prediabetes and compiled the Physical Activity Readiness Questionnaire (PAR-Q) to then receive a personalised prescription of physical activity. RESULTS: Overall, 5928 people were enrolled and compiled the questionnaire. Of these, 2895 (48.8%) were at risk for T2D. Among these, FG was measured in 2168 subjects (participation rate 75%). The numbers of individuals with undetected prediabetes and T2D according to FG were 755 and 79 (34.8% and 3.6% of those assessing FG), respectively. Of the 755 subjects in the prediabetes range, 739 compiled the PAR-Q and started a personalised program of physical activity (participation rate 97%). Physicians involved in the study reported a mean of 6 min to perform the screening. CONCLUSIONS: Overall, these data suggest the feasibility of a national diabetes prevention program developed by general practitioners using a simple stepwise approach starting from a web app to intercept individuals with prediabetes.

MG53 does not mark cardiovascular risk and all-cause mortality in subjects with type 2 diabetes: A prospective, observational study.

AIMS: Subjects with type 2 diabetes (T2D) are characterized by a high cardiovascular morbidity and mortality. MG53, a marker of peripheral insulin resistance, has been linked with impaired ß-cell function and decreased ß-cell survival, and its circulating levels are increased in T2D. Its relationship with the cardiovascular risk profile and mortality in T2D is currently unknown. METHODS: In this longitudinal study, MG53 was measured in serum samples collected at baseline for 296 Caucasian participants in the MIND.IT study, relating its circulating levels with the cardiovascular risk profile and all-cause mortality over a 17-years follow up. RESULTS: As compared to a reference cohort of 234 healthy subjects, MG53 levels were higher in T2D individuals (p < 0.001), and higher in T2D women than in men (p = 0.001). In the whole study cohort, MG53 levels were directly related to HbA1c (r2 0.029; p = 0.006) and systolic blood pressure (r2 0.032; p = 0.004). There was no difference in baseline MG53 levels between deceased and alive participants, neither predict all-cause mortality. CONCLUSIONS: MG53 does not mark the cardiovascular risk profile neither predict long-term mortality in Caucasian T2D individuals.

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.

Good for the heart, good for the Earth: proposal of a dietary pattern able to optimize cardiovascular disease prevention and mitigate climate change.

BACKGROUND AND AIMS: Human and planetary health are inextricably interconnected through food systems. Food choices account for 50% of all deaths for cardiovascular diseases (CVD) - the leading cause of death in Europe - and food systems generate up to 37% of total greenhouse gas (GHG) emissions. METHODS AND RESULTS: Based on a systematic revision of meta-analyses of prospective studies exploring the association between individual foods/food groups and the incidence of CVD, we identified a dietary pattern able to optimize CVD prevention.. This dietary pattern was compared to the current diet of the European population. The nutritional adequacy of both diets was evaluated according to the European Food Safety Authority (EFSA) recommended nutrient intake for the adult population, and their environmental impact was evaluated in terms of carbon footprint (CF). As compared to the current diet, the desirable diet includes higher intakes of fruit, vegetables, wholegrains, low glycemic index (GI) cereals, nuts, legumes and fish, and lower amounts of beef, butter, high GI cereals or potatoes and sugar. The diet here identified provides appropriate intakes of all nutrients and matches better than the current Europeans' one the EFSA requirements. Furthermore, the CF of the proposed diet is 48.6% lower than that of the current Europeans' diet. CONCLUSION: The transition toward a dietary pattern designed to optimize CVD prevention would improve the nutritional profile of the habitual diet in Europe and, at the same time, contribute to mitigate climate change by reducing the GHG emissions linked to food consumption almost by half.

Consumption of different animal-based foods and risk of type 2 diabetes: An umbrella review of meta-analyses of prospective studies.

We performed an umbrella review of dose-response meta-analyses of prospective studies reporting the incidence of type 2 diabetes associated with the consumption of animal-based foods. A systematic search was conducted in PubMed, Web of Science, Scopus, and Embase according to PRISMA. Thirteen meta-analyses are included in the study providing 175 summary risk ratio estimates. The consumption of 100 g/day of total or red meat, or 50 g/day of processed meat, were associated with an increased risk; RR and 95 % CI were respectively 1.20, 1.13-1.27; 1.22, 1.14-1.30 and 1.30, 1.22-1.39. White meat (50 g/day) was associated with an increased risk, but of lesser magnitude (RR 1.04, 95 % CI 1.00-1.08). A risk reduction was reported for 200 g/day of total dairy (RR 0.95, 95 % CI 0.92-0.98) or low-fat dairy (RR 0.96, 95 % CI 0.92-1.00) or milk (RR 0.90, 95 % CI 0.83-0.98), or 100 g/day of yogurt (RR 0.94, 95 % CI 0.90-0.98). No association with diabetes risk was reported for fish or eggs. In conclusions animal-based foods have a different association with diabetes risk. To reduce diabetes risk the consumption of red and processed meat should be restricted; a moderate consumption of dairy foods, milk and yogurt, can be encouraged; moderate amounts of fish and eggs are allowed.

Performance of 2019 ESC risk classification and the Steno type 1 risk engine in predicting cardiovascular events in adults with type 1 diabetes: A retrospective study.

AIMS: The study compares the performance of the European Society of Cardiology (ESC) risk criteria and the Steno Type 1 Risk Engine (ST1RE) in the prediction of cardiovascular (CV) events. METHODS: 456 adults with type 1 diabetes (T1D) were retrospectively studied. During 8.5 ± 5.5 years of observation, twenty-four patients (5.2%) experienced a CV event. The predictive performance of the two risk models was evaluated by classical metrics and the event-free survival analysis. RESULTS: The ESC criteria show excellent sensitivity (91.7%) and suboptimal specificity (64.4 %) in predicting CV events in the very high CV risk group, but a poor performance in the high/moderate risk groups. The ST1RE algorithm shows a good predictive performance in all CV risk categories. Using ESC classification, the event-free survival analysis shows a significantly higher event rate in the very high CV risk group compared to the high/moderate risk group (p < 0.0019). Using the ST1RE algorithm, a significant difference in the event-free survival curve was found between the three CV risk categories (p < 0.0001). CONCLUSIONS: In T1D the ESC classification has a good performance in predicting CV events only in those at very high CV risk, whereas the ST1RE algorithm has a good performance in all risk categories.

Relations between the Consumption of Fatty or Lean Fish and Risk of Cardiovascular Disease and All-Cause Mortality: A Systematic Review and Meta-Analysis.

Fish consumption is associated with a reduced risk of cardiovascular diseases (CVDs) partly ascribed to the high content of long-chain (LC) n-3 PUFAs; however, not all fish types are equally rich in these components. To date, it is not clear whether the beneficial effects of fish consumption are shared by fatty and lean fish. Therefore, the aim of this meta-analysis was to synthesize knowledge regarding the relation between the intake of fatty fish or lean fish and the risk of cardiovascular events and all-cause mortality. We conducted a systematic search in PubMed, Web of Science, and Embase until May 2021 for full text with a prospective design involving humans providing data for the highest compared with the lowest fish consumption categories. Summary risk ratios (RRs) and 95% CIs were estimated using a random-effects model. Out of 1902 articles retrieved from the literature search, 19 reports met the criteria for inclusion in the meta-analysis. Altogether, studies on fatty fish comprised 1,320,596 person-years of follow-up, 20,531 incident coronary heart disease (CHD) cases, 9256 incident CVD cases, and 104,763 total deaths. Studies on lean fish comprised 937,362 person-years of follow-up, 21,636 incident CHD cases, 7315 incident CVD cases, and 16,831 total deaths. An inverse association was present for fatty fish with CHD incidence (RR: 0.92; 95% CI: 0.86, 0.97), CHD mortality (RR: 0.83; 95% CI: 0.70, 0.98), and total mortality (RR: 0.97; 95% CI: 0.94, 0.99). This was not the case for lean fish. The summary estimates for CVD incidence and mortality did not show significant association with both fatty fish and lean fish consumption. The study findings are innovative in highlighting that the health benefits so far linked to fish consumption are, in fact, driven by fatty fish.

Consumption of Dairy Foods and Cardiovascular Disease: A Systematic Review.

Limited consumption of dairy foods and use of low-fat products is recommended for cardiovascular (CV) prevention; however, other features besides fat content modulate their metabolic effects. We analyze updated evidence on the relationship of different dairy products (low/full-fat dairy, milk, cheese, yogurt) with CVD by reviewing meta-analyses of cohort studies and individual prospective cohort studies with CV hard endpoints (CVD/CHD incidence/mortality), together with meta-analyses of randomized controlled trials exploring the effect of dairy on major CV risk factors. The analyses provide evidence that moderate dairy consumption (up to 200 g/day, globally) has no detrimental effects on CV health and that their effect depends more on the food type (cheese, yogurt, milk) than on the fat content. These data expand current knowledge and may inform revision of current guidelines for CVD prevention.

Dietary recommendations for prevention of atherosclerosis.

This review aims at summarizing updated evidence on cardiovascular disease (CVD) risk associated with consumption of specific food items to substantiate dietary strategies for atherosclerosis prevention. A systematic search on PubMed was performed to identify meta-analyses of cohort studies and RCTs with CVD outcomes. The evidence is highly concordant in showing that, for the healthy adult population, low consumption of salt and foods of animal origin, and increased intake of plant-based foods-whole grains, fruits, vegetables, legumes, and nuts-are linked with reduced atherosclerosis risk. The same applies for the replacement of butter and other animal/tropical fats with olive oil and other unsaturated-fat-rich oil. Although the literature reviewed overall endorses scientific society dietary recommendations, some relevant novelties emerge. With regard to meat, new evidence differentiates processed and red meat-both associated with increased CVD risk-from poultry, showing a neutral relationship with CVD for moderate intakes. Moreover, the preferential use of low-fat dairies in the healthy population is not supported by recent data, since both full-fat and low-fat dairies, in moderate amounts and in the context of a balanced diet, are not associated with increased CVD risk; furthermore, small quantities of cheese and regular yogurt consumption are even linked with a protective effect. Among other animal protein sources, moderate fish consumption is also supported by the latest evidence, although there might be sustainability concerns. New data endorse the replacement of most high glycemic index (GI) foods with both whole grain and low GI cereal foods. As for beverages, low consumption not only of alcohol, but also of coffee and tea is associated with a reduced atherosclerosis risk while soft drinks show a direct relationship with CVD risk. This review provides evidence-based support for promoting appropriate food choices for atherosclerosis prevention in the general population.

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.

Initial treatment of diabetes in Italy. A nationwide population-based study from of the ARNO Diabetes Observatory.

BACKGROUND AND AIMS: To investigate diabetes treatment initiation and continuation in the next sixth months in newly diagnosed Italian subjects. METHODS AND RESULTS: We analyzed administrative claims of 11,300,750 Italian residents. Subjects with incident diabetes were identified by glucose lowering drug prescriptions, disease-specific co-payment exemptions and hospital discharge codes occurring in 2018 but not in 2017. Incident cases were 65,932 of whom 91.4% received the prescription of a glucose lowering drug. Among the latter, those receiving a prescription of a noninsulin medication but no insulin were 84.8%, those receiving a prescription of insulin only were 9.4%, and those receiving prescriptions of both insulin and noninsulin drugs were 5.8%. Metformin was the most frequently drug initially prescribed in noninsulin treated subjects (~85%) and sulphonylurea receptor (SUR) agonists collectively ranked as second (~13%). Lispro (35%) and glargine (34%) were the most frequently prescribed molecules in subjects who were insulin treated. Differences in prescriptions were found in age categories, with increased use of SUR agonists across decades. In the first six months, as many as 50% of noninsulin treated patients continued with the initial drug, ~15% added a second agent, ~5% switched to another medication, and ~30% discontinued any glucose lowering treatment. CONCLUSIONS: These data document that current guidelines are often neglected because prescriptions of SUR agonists as first agent are still quite common and insulin is prescribed more than expected. They point out the urgent need to improve the dissemination and implementations of guidelines in diabetes care.

Pioglitazone even at low dosage improves NAFLD in type 2 diabetes: clinical and pathophysiological insights from a subgroup of the TOSCA.IT randomised trial.

AIMS: Non-Alcoholic Fatty Liver Disease (NAFLD) and type 2 diabetes (T2D) share pathophysiological mechanisms and possible therapeutic strategies. We evaluated the effects of 1-year treatment with pioglitazone or sulphonylureas on indirect indices of NAFLD in people with T2D and the role of insulin-resistance and glucotoxicity in determining these effects. METHODS: Patients with T2D (n = 195) aged 50-75 years, poorly controlled with metformin 2 g/day, were randomly allocated to add-on pioglitazone (n = 98) or sulphonylureas (n = 97) within the TOSCA.IT trial. Plasma insulin, glucose, and liver enzymes were measured at baseline and after 1-year. Indirect indices of NAFLD (Liver Fat Equation [LFE], Hepatic Steatosis Index [HSI], and Index of NASH [ION]), and insulin resistance (HOMA-IR, Visceral Adiposity Index [VAI] and adipose tissue Insulin Resistance [ADIPO-IR]) were calculated. RESULTS: Indices of NAFLD improved after pioglitazone, but not after sulphonylureas; differences between changes (1-year minus baseline) were respectively: -1.76 ± 3.84 vs. 0.28 ± 3.75 for LFE; -1.35 ± 2.78 vs. -0.27 ± 2.63 for HSI; -9.75 ± 43 vs. 3.24 ± 31 for ION; p < 0.05 for all. Indices of insulin resistance decreased after pioglitazone, but not after sulphonylureas: -0.95 ± 4.57 vs. 0.37 ± 3.34 for HOMA-IR, p = 0.032; -1.25 ± 4.11 vs. 1.36 ± 5.43 for ADIPO-IR, p = 0.001; -0.53 ± 1.88 vs. 0.03 ± 2.36 for VAI, p = 0.074. Changes in NAFLD indices were similar with different doses of pioglitazone (15, 30, or 45 mg/day), and were independent of blood glucose control. CONCLUSIONS: One-year treatment with pioglitazone even at low dosage significantly improved liver steatosis and inflammation, systemic and adipose tissue insulin resistance in patients with T2D. The beneficial effects of pioglitazone on NAFLD were independent of blood glucose control.

Incidence of diabetes mellitus in Italy in year 2018. A nationwide population-based study of the ARNO Diabetes Observatory.

BACKGROUNDS AND AIMS: To assess incidence of diabetes in Italy in 2018 by the use of administrative claims from several million residents. Differences in rates in men and women across decades of age were investigated. Incident rates of insulin or noninsulin treated subjects were also examined. METHODS AND RESULTS: We analyzed administrative healthcare claims of 11,300,750 subjects monitored by the ARNO Diabetes Observatory. Incident cases of diabetes were identified by glucose lowering drug prescriptions, disease-specific co-payment exemptions and hospital discharge codes related to diabetes occurring in 2018 but not in 2017. We identified 697,208 subjects with ascertained diabetes. Incident cases were 65,932, with a rate of 5.83 per 1000 person-years (p-y). Incidence of drug-treated diabetes (n = 60,271) was 5.33 per 1000 p-y. Subjects receiving only insulin prescriptions were 5652 (rate 0.50 per 1000 p-y) and those receiving only prescriptions of noninsulin medications were 51,085 (rate 4.52 per 1000 p-y). Incidence rates progressively increased across decades until age 80 and then dropped by 25-30%. Overall, incident rates were generally higher in women aged 11-40 and in men aged ≥51. CONCLUSIONS: Recent cases represented ~10% of the population of diabetic subjects. Incidence of noninsulin-treated diabetes was almost 10-fold higher than incidence of insulin-treated diabetes. Substantial differences in incidence rates were observed in men and women of several decades of age: women more affected in adolescence and young adult age, men more affected in mature and advanced age. These data provide further understanding on the epidemiological burden of the disease in Italy.

White Meat Consumption, All-Cause Mortality, and Cardiovascular Events: A Meta-Analysis of Prospective Cohort Studies.

The association of meat consumption with mortality and morbidity for non-communicable diseases has been extensively studied. However, the relation of white meat consumption with health outcomes remains controversial. The present meta-analysis was conducted to comprehensively analyze the available evidence on the consistency and strength of the association between the consumption of white meat, death from any cause and incidence of fatal and non-fatal cardiovascular (CV) events. PubMed, Web of Science, Scopus and Embase databases were searched for articles published up to April 30, 2020. We included prospective cohort studies reporting relative risks and pertinent 95% confidence intervals (CI) for all-cause mortality and/or CV events (fatal or non-fatal). A total of 22 studies were included in the meta-analysis. Eleven studies (14 data sets) reported data on all-cause mortality, 10 studies (15 datasets) on cardiovascular disease (CVD) mortality and 10 studies (11 datasets) on non-fatal CV events. When comparing the highest versus the lowest consumption of white meat, the pooled OR and pertinent 95% CI were 0.94 (0.90, 0.97, p < 0.001) for all-cause mortality, 0.95 (0.89, 1.01, p = 0.13) for CV mortality, and 0.99 (0.95, 1.02, p = 0.48) for non-fatal CV events. In conclusion, the study shows for the first time a robust and inverse association between white meat consumption and all-cause mortality and a neutral association with CV mortality and morbidity. This highlights the importance of differentiating the meat types for what concerns their health effects and suggests that white meat might be a healthier alternative to read and processed meat consumption.