Glucose lowering strategies and cardiovascular disease in type 2 diabetes - teachings from the TOSCA.IT study.

TOSCA.IT is an institutional, non-industry-supported, head-to-head study comparing long term cardiovascular effects, efficacy and safety of two antidiabetes drugs (pioglitazone vs sulphonylureas) used in combination with metformin in patients with type 2 diabetes mellitus. The study results show that in the absence of clinically evident cardiovascular disease both treatment strategies represent suitable alternatives; however, in consideration of the greater durability of the metabolic effects, the lower risk of hypoglycemia and the potential benefit on atherosclerotic cardiovascular disease, the combination of metformin and pioglitazone may be considered as the preferential therapeutic option. In this review the study is critically evaluated against the background of the evidence accumulated over the last decade on the impact of different glucose lowering drugs on cardiovascular events in people with type 2 diabetes.

Dietary intake and major food sources of polyphenols in people with type 2 diabetes: The TOSCA.IT Study.

PURPOSE: Proper evaluation of polyphenols intake at the population level is a necessary step in order to establish possible associations with health outcomes. Available data are limited, and so far no study has been performed in people with diabetes. The aim of this work was to document the intake of polyphenols and their major food sources in a cohort of people with type 2 diabetes and in socio-demographic subgroups. METHODS: We studied 2573 men and women aged 50-75 years. Among others, anthropometry was measured by standard protocol and dietary habits were investigated by food frequency questionnaire (EPIC). The intake of polyphenols was evaluated using US Department of Agriculture and Phenol-Explorer databases. RESULTS: The mean total polyphenol intake was 683.3 ± 5.8 mg/day. Non-alcoholic beverages represented the main food source of dietary polyphenols and provided 35.5% of total polyphenol intake, followed by fruits (23.0%), alcoholic beverages (14.0%), vegetables (12.4%), cereal products and tubers (4.6%), legumes (3.7%) and oils (2.1%); chocolate, cakes and nuts are negligible sources of polyphenols in this cohort. The two most important polyphenol classes contributing to the total intake were flavonoids (47.5%) and phenolic acids (47.4%). Polyphenol intake increased with age and education level and decreased with BMI; furthermore, in the northern regions of Italy, the polyphenol intake was slightly, but significantly higher than in the central or southern regions. CONCLUSIONS: The study documents for the first time the intake of polyphenols and their main food sources in people with diabetes using validated and complete databases of the polyphenol content of food. Compared with published data, collected in people without diabetes, these results suggest a lower intake and a different pattern of intake in people with diabetes.

Incidence, prevalence, costs and quality of care of type 1 diabetes in Italy, age 0-29 years: The population-based CINECA-SID ARNO Observatory, 2002-2012.

BACKGROUND AND AIMS: To assess temporal trend in incidence (2003-12) and prevalence (2002-12) of type 1 diabetes in children and young adults, direct costs and selected indicators of quality of care under the coverage of the universalistic Italian National Health System (NHS). METHODS AND RESULTS: The ARNO Observatory, a healthcare monitoring system based on administrative data, identified a population-based multiregional cohort of subjects aged 0-29 years. Type 1 diabetes was defined by at least two prescriptions of insulin over 12 months and continuous insulin-treatment in the following year. Indicators of quality of care and directs costs were assessed in persons with diabetes and in people without diabetes, individually matched for age, gender and health unit (1:4 ratio). We identified 2357 incident cases of type 1 diabetes aged 0-29 years (completeness of ascertainment, 99%). Incidence rates were similar in ages 0-14 (15.8, 95% CI 14.9-16.8) and 15-29 years (16.3, 15.4-17.2), with no significant trend. Prevalence increased from 137 to 166.9/100,000, particularly in the age 15-29 years. Direct costs accounted for € 2117 in persons with diabetes and € 292 in control individuals. A statistically significant decreasing trend in hospitalization for acute complications was evident (p < 0.001), which was almost completely due to ketoacidosis. People with at least one HbA1c measurement over the year were 48.5%. CONCLUSION: We showed high incidence and increasing prevalence of type 1 diabetes in young adults in Italy, which impact on direct costs under the universalistic coverage of the NHS.

The relative burden of diabetes complications on healthcare costs: The population-based CINECA-SID ARNO Diabetes Observatory.

BACKGROUND AND AIMS: In the present population-based study, we aimed to describe the per patient annual healthcare cost of people with diabetes in 2007-2012, to assess the relative burden of diabetes complications and other potential determinants on healthcare costs in the 2012 cohort, and to describe and analyse the determinants of the cost of incident cases diagnosed in 2012. METHODS AND RESULTS: We analysed data from a retrospective cohort of residents in four Italian areas that were served by Local Health Units participating in the ARNO Observatory. Per patient annual healthcare costs (Euros) were estimated as the sum of all the resources supplied during that year (drugs, outpatient care, and hospitalisations). The mean per patient annual healthcare cost increased from €2752 in 2007 to €3191 in 2010, before decreasing to €2791 in 2012. The largest component of these costs was represented by hospitalisations (around €1550, on average; 51.7% of total cost), followed by outpatient care (€422; 14.6%) and drugs (€973; 33.7%). In 2012, the most relevant cost determinants were chronic diabetes complications, with an additional cost due to nephropathy/end stage renal disease (€4683), amputations (€5042), lower extremity revascularization (€4808), and cerebrovascular diseases (€3861). Costs associated with incidence cases were higher than those associated with prevalent. CONCLUSION: The present study provides evidence on the excess of healthcare costs due to diabetes complications in both prevalent and incident cases.

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.

The combination of UCP3-55CT and PPARγ2Pro12Ala polymorphisms affects BMI and substrate oxidation in two diabetic populations.

BACKGROUND AND AIM: To evaluate the combined contribution of UCP3-55CT and PPARγ2 Pro12Ala polymorphisms as correlates of BMI, energy expenditure (REE) and substrate oxidation in people with type 2 diabetes. METHODS AND RESULTS: Two independent population with type 2 diabetes were studied: population A, n = 272; population B, n = 269. Based on both UCP3 and PPARγ2 genotypes three groups were created. Carriers of the PPARγ2 Pro12Ala in combination with the CC genotype of UCP3 (ProAla/CC, group 1); carriers of only one of these genotypes (either CC/ProPro or CT-TT/ProAla, group 2); people with neither variants (CT-TT/ProPro, group 3). In both populations BMI (kg/m(2)) was highest in group 1, intermediate in group 2 and lowest in group 3, independent of energy intake (i.e 35.3 ± 6.7 vs 33.4 ± 5.4 vs 31.8 ± 3, p < 0.02, population A; 32.4 ± 4.2 vs 31.7 ± 3.8 vs 30.1 ± 2.7; p < 0.03, population B). People with the ProAla/CC genotype (group 1) showed similar REE, but lower lipid oxidation (10.9 vs 13.9 g/kg fat free mass/day; p = 0.04) and higher carbohydrate oxidation (23.6 vs 15.6 g/kg fat free mass/day; p = 0.02) than carriers of other genotypes. CONCLUSIONS: The combination of UCP3-55 CC and PPARγ2 Pro12Ala genotypes is associated with significantly higher BMI than other PPARγ2-UCP3 genotype combinations, partly due to a reduced ability in lipids oxidation. The relative importance of these mechanism(s) may be different in non diabetic people.

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.

Under-treatment of migrants with diabetes in a universalistic health care system: the ARNO Observatory.

AIMS: To assess whereas prevalence, treatment and direct costs of drug-treated diabetes were similar in migrants and in people of Italian citizenship under the universalistic Italian health care system. METHODS AND RESULTS: Drug-treated diabetic individuals were identified in the population-based multiregional ARNO Observatory on the basis of 2010 prescriptions. Migrants were identified by the country-of-birth code on the fiscal identification code. Diabetes prevalence was calculated for Italians (n = 7,328,383) and migrants (n = 527,965). To assess the odds of migrants of having diabetes compared to Italians, we individually matched all migrants to Italians for major confounders (age, sex and place of residence). Finally, all migrants with diabetes were individually matched for confounders to Italians with diabetes to compare prescriptions, hospitalization rates, services use and direct costs for the National Health System. We identified 368,797 subjects with diabetes among Italians and 10,336 among migrants, giving prevalence of 5.03% and 1.96%, respectively. Migrants with diabetes were younger than Italians (52 ± 13 years vs. 68 ± 14 years, P < 0.001); after matching, their risk of disease was higher (odds ratio, 1.55, 95% confidence interval, 1.50-1.60). The total cost was 27% lower in migrants, due to lower cost of drugs (-29%), hospital admission (-27%) and health services (-22%). The number of packages/treated person-year of all glucose-lowering drugs was also lower in migrants (-15%) (P < 0.001). CONCLUSIONS: Compared to subjects of Italian ancestry, migrants to Italy show a higher risk of diabetes but less intense treatment. Inequalities in health care use are likely and are maintained also in a universalistic system.

The energy intake modulates the association of the -55CT polymorphism of UCP3 with body weight in type 2 diabetic patients.

BACKGROUND: Previous association studies of the -55CT polymorphism of the uncoupling protein 3 (UCP3) gene with body mass index (BMI) have provided inconsistent results. The study aim is twofold: (1) to evaluate the association of the -55CT polymorphism of UCP3 with BMI in two independent populations to verify the reproducibility of the finding; (2) to evaluate whether this association is modulated by energy intake. METHODS: Study participants are 736 males and females with type 2 diabetes belonging to independent populations (N=394 population 1; N=342 population 2). Anthropometry and laboratory parameters were measured; in population 2, energy intake and physical exercise were also assessed. RESULTS: The -55CT polymorphism was associated with a significantly lower BMI in population 1 (27.8±3.9 vs 28.9±4.6 kg m(-2); P<0.02), the finding was confirmed in population 2 (that is, 30.3±6.0 vs 32.1±5.9 kg m(-2); P<0.01) independent of gender, age, HbA1c, use of drugs and energy intake. To evaluate the role of diet in population 2, the study participants were stratified by genotype and tertiles of energy intake. In both genotype groups, BMI increased with increasing caloric intake with a significant trend (P<0.001), the BMI difference between the two genotype groups was large and statistically significant in the lower tertile (27.6 vs 31.2 kg m(-2); P<0.001), intermediate in the second tertile and negligible in the upper tertile (32.8 vs 32.9; kg m(-2); nonsignificant). The multivariate regression analysis confirmed a significant interaction between genotype and energy intake as correlates of BMI independent of age, gender, glucose control, physical activity and medications for diabetes (P=0.004). CONCLUSIONS: The study replicates in two independent populations the association between the -55CT polymorphism of UCP3 and a lower BMI. This association was modulated by energy intake, thus suggesting that the unmeasured effect of diet may partly account for inconsistencies of prior association studies.

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.

Addition of either pioglitazone or a sulfonylurea in type 2 diabetic patients inadequately controlled with metformin alone: impact on cardiovascular events. A randomized controlled trial.

BACKGROUND AND AIMS: Metformin is the first-line therapy in type 2 diabetes. In patients inadequately controlled with metformin, the addition of a sulfonylurea or pioglitazone are equally plausible options to improve glycemic control. However, these drugs have profound differences in their mechanism of action, side effects, and impact on cardiovascular risk factors. A formal comparison of these two therapies in terms of cardiovascular morbidity and mortality is lacking. The TOSCA.IT study was designed to explore the effects of adding pioglitazone or a sulfonylurea on cardiovascular events in type 2 diabetic patients inadequately controlled with metformin. METHODS: Multicentre, randomized, open label, parallel group trial of 48 month duration. Type 2 diabetic subjects, 50-75 years, BMI 20-45 Kg/m(2), on secondary failure to metformin monotherapy will be randomized to add-on a sulfonylurea or pioglitazone. The primary efficacy outcome is a composite endpoint of all-cause mortality, nonfatal myocardial infarction, nonfatal stroke, and unplanned coronary revascularization. Principal secondary outcome is a composite ischemic endpoint of sudden death, fatal and non-fatal myocardial infarction and stroke, endovascular or surgical intervention on the coronary, leg or carotid arteries, major amputations. Side effects, quality of life and economic costs will also be evaluated. Efficacy, safety, tolerability, and study conduct will be monitored by an independent Data Safety Monitoring Board. End points will be adjudicated by an independent external committee. CONCLUSIONS: TOSCA.IT is the first on-going study investigating the head-to-head comparison of adding a sulfonylurea or pioglitazone to existing metformin treatment in terms of hard cardiovascular outcomes. REGISTRATION: Clinicaltrials.gov ID NCT00700856.

Fasting APO B48 levels are associated with microalbuminuria in patients with type 2 diabetes.

In view of the high incidence of macrovascular diseases in patients with type 2 diabetes mellitus and microalbuminuria, the study evaluates the association of microalbuminuria with fasting plasma Apo B48 levels, a marker of the residual presence of intestinally derived TRLs lipoproteins, thought to be highly atherogenic. We studied 50 patients with type 2 diabetes aged 35-75 years. Exclusion criteria were overt macrovascular disease, overt nephropathy (Glomerular filtration rate (GFR) <45 ml/min/1.73 m(2)), or use of hypolipidemic agents. Anthropometry, fasting plasma lipids, plasma creatinine, and HbA1c were measured. Urinary albumin excretion was measured on a morning urine sample with the ELISA and expressed as albumin/creatinine ratio. GFR was estimated using the MDRD formula. The plasma fasting Apo B48 was measured by ELISA. Age, gender distribution, fasting plasma lipids, HbA1c, smoking status, plasma creatinine, estimate GFR, and the proportion of patients treated with insulin or antihypertensive drugs were similar for patients with or without microalbuminuria. People with microalbuminuria had longer diabetes duration (borderline significance) and significantly higher Apo B48 (1.765 ± 1.379 µg/ml vs. 1.022 ± 0.692 µg/ml, p = 0.01) than those without microalbuminuria. Multivariate logistic regression analysis confirmed that fasting Apo B48 levels were significantly associated with microalbuminuria independent of major confounders measured in the study. In patients with type 2 diabetes, microalbuminuria is associated with elevated Apo B48 levels, independent of major confounders; this may partly explain the excess cardiovascular risk of these patients.

Cardiovascular risk in women with diabetes.

Women with diabetes have a high risk of cardiovascular disease that, almost completely eliminates the gender difference in cardiovascular morbidity and mortality between non-diabetic men and women. In this chapter we have reviewed data showing that cardiovascular risk factors are more common, more likely to cluster, or more severe in diabetic women than men; this may be due to biological or behavioural factors. Disparities in accessibility, quality and, possibly, effectiveness of care further disadvantage diabetic women. Based on available data it can be concluded that a large number of CVD deaths are preventable in diabetic women; therefore special attention should be paid to risk factors detection and correction, as well as timely CHD diagnosis and treatment in diabetic women. To meet these needs gender specific guidelines and implementation measures may be in order.

Measurement of the intrarenal arterial resistance index for the identification and prediction of diabetic nephropathy.

BACKGROUND AND AIMS: High intrarenal resistance index (RI) predicts renal function in several conditions; its use in the prediction of diabetic nephropathy (DN) is little explored. We aimed (1) to compare RI in diabetic and non diabetic hypertensive patients, and (2) to evaluate whether high RI is associated with clinical signs of DN and its progression over time. DESIGN: observational, prospective. PARTICIPANTS: 92 type 2 diabetic patients and 37 non-diabetic controls aged 40-70, with hypertension and normal renal function. We measured ultrasound RI and, among others, creatinine, estimated glomerular filtration rate and urinary albumin excretion rate (AER) at baseline and after 4.5 years follow-up. Progression of albuminuric state (i.e., transition from baseline normo-microalbuminuria to follow-up micro-macroalbuminuria) was evaluated. RI was significantly higher in diabetic than non-diabetic participants (0.69+/-0.05 vs 0.59+/-0.05, p<0.001). Diabetic patients with RI>or=0.73, i.e., above the 80th percentile of the RI distribution, had significantly higher baseline AER and a more frequent progression of the albuminuric state compared to patients with RI<0.73 (27.7microg/mg [12.1-235.4] vs 15.1microg/mg [8.6-33.4]; 52.9% vs 9.5%, respectively). AER increased significantly from baseline to follow-up in patients with RI>or=0.73 (from 27.7microg/mg [12.1-235.4] to 265.0microg/mg [23.8-1018.1], p<0.01), but not in those with RI<0.73 (from 15.1microg/mg [8.6-33.4] to 16.1microg/mg [10.7-67.2], ns). OR for progression of albuminuric state, adjusted for established predictors of DN, including baseline AER, was 5.01 (1.4-17.7, 95% CI) for patients with RI>or=0.73 vs <0.73. Findings were confirmed in patients with normoalbuminuria at baseline. CONCLUSIONS: In diabetic patients, high RI (>or=0.73) is associated with features of DN and its progression over time, independent of albuminuria.

The clinical reality of guidelines for primary prevention of cardiovascular disease in type 2 diabetes in Italy.

INTRODUCTION AND AIM: Guidelines for cardiovascular prevention in diabetes have been issued by the national and international scientific societies. No audit as ever been performed to evaluate the implementation of these documents in clinical practice in Italy. The study evaluates the prevalence, treatment, and control of major cardiovascular risk factors in type 2 diabetic patients, to assess the clinical practice of primary cardiovascular prevention in type 2 diabetes. PATIENTS AND METHODS: Two thousand four hundred and sixty-five men and women with type 2 diabetes, aged 50-75 and free of cardiovascular events were recruited on a consecutive basis at 10 hospital based outpatients diabetes clinics. Clinical variables were measured by standard protocol. Biochemical parameters were evaluated at each centre. The laboratories were monitored by an external quality control assessment in order to reach and maintain a standard of quality and traceability among the participating centres. RESULTS: A minority of patients (5%) met the recommended targets for LDL cholesterol, blood pressure, glycated haemoglobin and smoking habits, whereas the vast majority (66%) had unsatisfactory control of three or more of the above. Achievement of desirable control of risk factors differed according to gender and known diabetes duration. Lipid lowering and, to a lesser extent, antihypertensive medications were under-used and their titration insufficiently target-driven. Prophylactic use of antiplatelet agents was scarce, only one out of five patients was treated independent of absolute cardiovascular risk. CONCLUSION: In clinical practice there is poor adherence to national and international guidelines for primary cardiovascular prevention in type 2 diabetes in Italy. The study underlines the great potential for prevention, particularly in women and in high-risk patients.

Dietary habits in type II diabetes mellitus: how is adherence to dietary recommendations?

OBJECTIVE: To clarify adherence of type II diabetic patients to dietary recommendations. SUBJECTS AND METHODS: The dietary habits of a group of 540 patients, with type II diabetes (male 322/female 218, mean age 61+/-5 years, body mass index (BMI) 29.7+/-5.2 kg/m(2); mean+/-s.d.) referring to six Italian diabetes centres were evaluated by means of a 3-day diet record (2 workdays, 1 holiday). Diet records were analysed according to Italian food composition tables and compared with the dietary recommendations of the Diabetes and Nutrition Study Group of the European Association for the study of Diabetes. RESULTS: Calorie intake was 1725+/-497 kcal (1800 for men, 1610 for women). Mean intake for each nutrient was close to the recommended amount, except for fibre (12/1000 vs 20 g/1000 kcal). Calculating the percentage of patients who complied with each recommendation, the intakes of saturated fat and fibre least reflected the dietary target: in 43% of patients saturated fat was >10% of total calories, in only 6% was fibre intake > or =20 g/1000 kcal (considered ideal), and in 25% it was > or =15 g/1000 kcal (acceptable). CONCLUSIONS: These results indicate that compliance to dietary recommendations is not completely satisfactory, even in Italy. Calorie intake is a bit elevated, given the high BMI of our diabetic population. As to dietary composition, there are two crucial issues: the high intake of saturated fat and--most importantly--the low intake of fibre. All strategies aiming to a proper implementation of guidelines should take these results into due account.

The PEA15 gene is overexpressed and related to insulin resistance in healthy first-degree relatives of patients with type 2 diabetes.

AIMS/HYPOTHESIS: Overexpression of the gene encoding phosphoprotein enriched in astrocytes 15 (PEA15), also known as phosphoprotein enriched in diabetes (PED), causes insulin resistance and diabetes in transgenic mice and has been observed in type 2 diabetic individuals. The aim of this study was to investigate whether PEA15 overexpression occurs in individuals at high risk of diabetes and whether it is associated with specific type 2 diabetes subphenotypes. SUBJECTS AND METHODS: We analysed PEA15 expression in euglycaemic first-degree relatives (FDR) of type 2 diabetic subjects. RESULTS: The expression of PEA15 in peripheral blood leucocytes (PBLs) paralleled that in fat and skeletal muscle tissues. In PBLs from the FDR, PEA15 expression was two-fold higher than in euglycaemic individuals with no family history of diabetes (control subjects), both at the protein and the mRNA level (p < 0.001). The expression of PEA15 was comparable in FDR and type 2 diabetic subjects and in each group close to one-third of the subjects expressed PEA15 levels more than 2 SD higher than the mean of control subjects. Subjects with IFG with at least one type 2 diabetes-affected FDR also overexpressed PEA15 (p < 0.05). In all the groups analysed, PEA15 expression was independent of sex and unrelated to age, BMI, waist circumference, systolic and diastolic BP, and fasting cholesterol, triacylglycerol and glucose levels. However, in euglycaemic FDR of type 2 diabetic subjects, PEA15 expression was inversely correlated with insulin sensitivity (r = -557, p = 0.01). CONCLUSIONS/INTERPRETATION: We conclude that PEA15 overexpression represents a common defect in FDR of patients with type 2 diabetes and is correlated with reduced insulin sensitivity in these individuals.

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.

Clinical phenotype and beta-cell autoimmunity in Italian patients with adult-onset diabetes.

OBJECTIVE: To characterize the phenotype of a large population of Italian patients with adult onset (> or =40 years) diabetes who were attending outpatient clinics and who were screened for glutamic acid decarboxylase 65 autoantibodies (GADA), protein tyrosine phosphatase IA-2 (IA-2A) and IA-2beta/phogrin (IA-2betaA). DESIGN AND METHODS: This was a cross-sectional study comprising a total of 881 patients, aged < or = 70 years, diagnosed with type 2 diabetes after the age of 40 years, and consecutively recruited in five clinics located in different geographic areas of Italy (Milan, Florence, Rome, Naples and Catania). Their mean disease duration was 8.1 (6.9; s.d.) years. GADA, IA-2A and IA-2betaA were measured with radiobinding assays with in vitro translated S-methionine-labelled glutamic acid decarboxylase 65 (GAD65) or IA-2 or IA-2beta. Anthropometric and clinical data were collected and compared amongst patients with or without autoantibodies. RESULTS: Sixty-three (7.1%) patients had one or more autoantibodies, 58 (6.6%) had GADA, 22 (2.5%) had IA-2A, six (0.7%) had IA-2betaA and 19 (2.15%) had two or more autoantibodies. IA-2A or IA-2betaA, in the absence of GADA, were found in only five patients. Autoantibody-positive patients were more often female (63.5 vs 36.5%; P < 0.009), had higher glycated haemoglobin (Hb A1c) (P < 0.001), lower body mass index (BMI; P < 0.0005) and waist/hip ratio (WHR; P < 0.01); female gender being the main contributor to BMI and WHR. We did not observe any differences in age at diagnosis or duration of disease with respect to the presence or absence of islet autoantibodies. The proportion of patients on insulin therapy was higher in patients with two or more antibodies, compared with those with one antibody only, and no antibodies (P for trend < 0.001), and among patients with GADA, in those with higher antibody titre (73.9% in those with > 10 units vs 42.0% in those with < or = 10 units; P < 0.007). CONCLUSIONS: Patients with adult onset diabetes characterized by autoimmunity to beta-cells showed a clinical phenotype with anthropometric features that differed from those classically observed in patients with type 2 diabetes. The number and titre of autoantibodies, which reflect the severity of autoimmunity and beta-cell impairment, amplified this difference. The usefulness of autoantibody screening in adult-onset diabetes is further emphasized by these findings.