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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.

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.

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.

Objectives: Little is known about the specific comorbidities contributing to higher costs in patients with type-2 diabetes mellitus (T2DM), particularly in older cases. We aimed to evaluate the prevalence, type, and cost of comorbidities occurring in older T2DM patients versus older non-T2DM patients, and the factors associated with high cost (HC) T2DM patients.Methods: Retrospective cohort study using information from the Campania Region healthcare database. People aged ≥65 years who received ≥2 prescriptions for antidiabetic drugs were identified as “T2DM patients.” Comorbidities among T2DM and non-T2DM groups were assessed through the RxRiskV Index (modified version). T2DM individuals were classified according to the total cost distribution as HC or “non-high cost.” Two sub-cohorts of HC T2DM patients were assessed: above 90th and 80th percentile of the total cost. Age- and sex-adjusted logistic regression models were created.Results: Among the T2DM cohort, concordant and discordant comorbidities occurred significantly more frequently than in the non-T2DM cohort. Total mean annual cost per T2DM patient due to comorbidities was €7,627 versus €4,401 per non-T2DM patient. Among T2DM patients identified as being above 90th and 80th percentiles of cost distribution, the total annual costs were >€19,577 and >€2,563, respectively. The hospitalization cost was higher for T2DM cases. Strongest predictors of being a HC T2DM patient were having ≥5 comorbidities and renal impairment.Conclusion: HC patients accrued >80% of the total comorbidities cost in older T2DM patients. Integrated care models, with holistic and patient-tailored foci, could achieve more effective T2DM care.

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.

Background: We evaluate whether the Pro12Ala polymorphism of peroxisome proliferator-activated receptor γ2 (PPARγ2) has a role in the progression of diabetes by modulating the occurrence of treatment failure to glucose-lowering drugs. Methods: We studied 215 patients with type 2 diabetes participating in the Thiazolidinediones Or Sulphonylureas and Cardiovascular Accidents Intervention Trial study. All participants were insufficiently controlled (glycated haemoglobin [HbA1c] 7.0%-9.0%) with metformin 2 g/day and were randomly allocated to add-on pioglitazone or a sulfonylurea. Treatment failure was defined as HbA1c ≥8% on two consecutive visits, 3 months apart. Results: Carriers or non-carriers of the polymorphism had similar age, body mass index, and diabetes duration. Ala carriers had lower fasting plasma insulin, better insulin sensitivity (Homeostasis Model Assessment [HOMA]2-%S), and worse beta cell secretion (HOMA2-%B) than non-carriers. During 24 months of follow-up, 32.5% among the Ala carriers and 8.6% among non-carriers (P < 0.001) developed treatment failure with a cumulative incidence of 18.6 vs 4.6/100 person-years. Those patients who developed treatment failure were older, had a younger age at diabetes diagnosis (48 ± 10 vs 52 ± 7 years; P = 0.032), higher HbA1c (8.1 ± 0.5 vs 7.7 ± 0.5%; P < 0.001), and lower HOMA2-%B (30 ± 12 vs 46 ± 29; P = 0.015) at study entry, as compared to those who did not develop treatment failure. At multivariate analysis, the Pro12Ala polymorphism was significantly associated with treatment failure (hazard ratio [HR] 4.45; 95% confidence interval [CI] 1.79-11.1; P < 0.001); HbA1c at study entry was the other independent predictor of failure in this study population. Conclusion: The Pro12Ala polymorphism is associated with a greater insulin sensitivity, reduced beta cell function and a substantially increased risk of treatment failure.

Aims To document in recent cohorts the degree of control of major cardiovascular (CV) risk factors according to diabetes status and prior CV disease in different settings. Methods We studied men and women aged 50–75 years of whom 3028 with type 2 diabetes mellitus (T2DM) managed at diabetes clinics participants of the TOSCA.IT (NCT00700856) study recruited in 2008–2014; 742 with T2DM managed mainly in primary care and 6753 without diabetes participating in the Moli-sani (NCT03242109) study and recruited in 2005–2010 from an adult general population. Results Among people without a prior CV event people with diabetes managed at diabetes clinics have lower LDL-cholesterol and blood pressure and a more frequent use of lipid-lowering and antihypertensive medications as compared to people with diabetes managed mainly in primary care and to people without diabetes. The proportions achieving the recommended treatment targets are respectively 47.4% vs 33.4% vs 29.5% for LDL-cholesterol and 42.6% vs 9.5% vs 47.4% for blood pressure. Figures for the participants with prior CV events were 26.8% vs 15.1% vs 42.5% for LDL-cholesterol and 43.8% vs 8.5% vs 43.6% for blood pressure. Conclusions The study documents that in modern cohorts a large proportion of people with or without diabetes does not achieve the treatment targets for LDL-cholesterol and blood pressure, both in primary and secondary CV prevention. People with diabetes attending diabetes clinics achieve a better control of major CV risk factors than those managed mainly in primary care, thus highlighting the relevant role of a structured model of care.

Backgrounds and aims To investigate relevant indicators of quality of care in a large population-based sample of people with diabetes representative of clinical practice in Italy in 2018. Methods and results We analyzed data from 11,300,750 subjects. All administrative healthcare claims collected in 2018 were scrutinized to identify subjects with diabetes and investigate several indicators of quality of care. Subjects with diabetes were identified by anti-hyperglycemic drug prescriptions, disease-specific co-payment exemption and hospital discharge codes. Indicators of quality of care pertained to monitoring (HbA1c, creatinine, lipid profile, microalbuminuria, eye examination, ECG, ultrasonography of carotid and lower limb arteries) and diabetes treatment (anti-hyperglycemic agents in subjects with cardiovascular disease, CVD). Subjects attending and nonattending Diabetes Clinics were compared. We identified 697,208 individuals with diabetes. HbA1c was assessed at least once in the year in 62.7%, creatinine in 62.3%, total cholesterol in 59.6%, microalbuminuria in 34.3%. Frequency of eye examination was 8.2%, ECG 23.5%, carotid ultrasonography 14.3%, lower limb ultrasonography 7.6%. Among anti-hyperglycemic drugs, SGLT-2 inhibitors were prescribed to ~5% and GLP-1 receptor agonists to ~5% although the proportion of subjects with CVD was ~45%. Subjects attending Diabetes Clinics had higher figures for all these monitoring and treatment indicators. Conclusions The implementation of national and international guidelines regarding disease monitoring and treatment is far from being satisfactory, especially among subjects nonattending Diabetes Clinics. Further efforts and investments are needed for better disseminating guidelines, more efficaciously engaging healthcare professionals and more strongly empowering the healthcare system to improve diabetes care.

IntroductionDiabetes is a highly prevalent disease worldwide and represents a challenge for patients and healthcare systems. This population-based study evaluated diabetes burden in Italy in 2018 by assessing all aspects of outpatient and hospital care.Research design and methodsWe investigated data of 11 300 750 residents in local health districts contributing to ARNO Diabetes Observatory (~20% of Italian inhabitants). All administrative healthcare claims were analyzed to gather information on access to medical resources. Subjects with diabetes, identified by antihyperglycemic drug prescriptions, disease-specific copayment exemption and hospital discharge codes, were compared with age, sex and residency-matched non-diabetic individuals.ResultsWe identified 697 208 subjects with ascertained diabetes, yielding a prevalence of 6.2% (6.5% in men vs 5.9% in women, p2-fold higher in subjects with diabetes, mainly driven by hospitalizations and outpatient care related to chronic complications rather than to glucose-lowering drugs, diabetes-specific devices, or metabolic monitoring.ConclusionsThe burden of diabetes in Italy is particularly heavy and, as a systemic disease, it includes all aspects of clinical medicine, with consequent high expenses in all areas of healthcare.

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.

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.

Context Hypoglycemic drugs with proven cardiovascular (CV) benefits are recommended for patients with type 2 diabetes and CV disease. Whether the beneficial effects extend to those at lower risk remains unclear. Aim We investigated the long-term CV effects of pioglitazone or sulfonylureas (SUs) across the spectrum of pretreatment CV risk. Methods Among 2820 participants of the TOSCA.IT trial, four subgroups with different risk of outcome-a composite of all-cause death, nonfatal myocardial infarction, nonfatal stroke, urgent coronary revascularization-were identified by the RECursive Partitioning and AMalgamation (RECPAM) method. Within each group, the effect of SUs or pioglitazone on the outcome was evaluated. Results Sex was the first splitting variable, followed by urinary albumin-to-creatinine ratio (UACR) (>9 mg/g or ≤9 mg/g) and body mass index (BMI) (>28.7 or ≤28.7 kg/m2). Female patients had the lowest risk (reference); male patients with UACR >9 mg/g and BMI >28.7 kg/m2 had the highest risk [hazard ratio (HR), 5.58; 95% CI, 3.32 to 9.69]. Patients in this group present a cluster of conditions suggestive of marked insulin resistance (higher BMI, waist circumference, triglycerides, blood pressure, and UACR and lower high-density lipoprotein cholesterol) than the other groups. Treatment with pioglitazone in this group was associated with a significantly lower occurrence of the outcome than SUs (HR, 0.48; 95% CI, 0.25 to 0.76). No significant difference between study treatments was observed in the other RECPAM classes. Conclusions It is possible to identify patients with type 2 diabetes early in the stage of their disease and who are largely free from evident CV disease in whom add-on pioglitazone to metformin confers CV protection as compared with SUs.

Aims: Type 2 diabetes (DM2) is associated to oxidative modifications of high-density lipoproteins (HDL), which can interfere with their function. Pioglitazone has proved effective in raising HDL cholesterol (HDL-C) and lowering small dense low-density lipoprotein (LDL), but no clinical studies have examined its effect on lipoprotein oxidation in patients with DM2. Methods: We assessed the effect of pioglitazone vs glimepiride after 1 year on HDL oxidation, expressed as relative abundance of peptides containing Met 112 O in ApoA-I (oxApoA-I) estimated by mass spectrometry (MALDI/TOF/TOF), in 95 patients with DM2. The oxLDL and AGE were quantified by ELISA. Results: Patients receiving pioglitazone showed a significant increase in the concentration of ApoA-I (Δ = 7.2 ± 14.8 mg/dL, p < 0.02) and a reduction in oxApoA-I (Δ = − 1.0 ± 2.6%, p < 0.02); this reduction was not significantly different from glimepiride. oxLDL showed a slight, but not significant increase in both treatment groups. Regression analysis showed a correlation between ΔoxApoA-I and ΔAGE (r = 0.30; p = 0.007) in all patients, while both of these parameters were unrelated to changes in HbA1c, HDL-C, duration of illness, or use of statins. Conclusions: Long-term treatment with pioglitazone was effective in reducing the oxidation of HDL, but not LDL in patients with DM2, while glimepiride didn’t. This finding seems to be associated to the change of glyco-oxidation status, not to any improvement in glycemic control or lipid profile. Trial registration: NCT00700856, ClinicalTrials.gov Registered June 18, 2008.

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

Aims: To assess whereas prevalence, treatment and direct costs of drug-treated dia-betes 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 Z 7,328,383) and migrants (n Z 527,965). To assess the odds of migrants of having diabetes compared to Italians, we individually matched all migrants to Italians for major con-founders (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 sub-jects 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, 1.50e1.60). 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.

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.

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.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) (p0.001), and prevalence of abdominal obesity was 86% vs 44% (p0.001). 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%; p0.05 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.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.

The paper presents a post-hoc analysis of the intensity of dyslipidaemia care operated in the first 2 years of Multiple-Intervention-in-type-2-Diabetes.ITaly (MIND.IT) study.MIND.IT is a multicentric, randomized, two-parallel arm trial involving 1461 type 2 diabetic patients at high cardiovascular (CV) risk. The study compares the usual care (UC) of CV prevention with a multifactorial intensive care (IC) approach aiming at achieving target values for the main CV risk factors according to a step-wise treat-to-target approach.Proportion of patients on target for low-density lipoprotein cholesterol (LDL-C) was about 10% at baseline and increased significantly more with IC than UC (43 vs. 27%; p 0.001). However, the majority (57%) of patients, in this intended intensively treated cohort, failed to achieve the proposed target. Average LDL-C decreased from 144 ± 35 to 108 ± 31 mg/dl with IC and from 142 ± 28 to 118 ± 32 with UC (p-for-interaction0.0001). IC was associated with a significantly greater increase in statin prescription and lower withdrawal from treatment than UC (43 vs. 11% and 28 vs. 61%, respectively; both p 0.001). However, the new treatments were characterized in both groups by the use of low starting doses (≤ 10 mg of atorvastatin, equivalent dose in more than 90% of patients) without increase in case of missed target.The application of a multifactorial treat-to-target intervention is associated with a significant improvement in LDL-C beyond usual practice. However, the change in LDL-C appears to be more related to an increased number of treated patients and a decreased treatment withdrawal than to a true treat-to-target approach.

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.

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 50e75, 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.

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).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%.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.

OBJECTIVE—We explore the relationship among BMI, habitual diet, and the Pro12Ala polymorphism in the peroxisome proliferator–activated receptor (PPAR)γ2. RESEARCH DESIGN AND METHODS—The Pro12Ala variant was characterized in 343 unrelated type 2 diabetic patients who were consecutively seen at the outpatient clinic of a health district of the province of Naples. Anthropometric and laboratory parameters were measured; habitual diet was assessed by a validated semiquantitative food frequency questionnaire. RESULTS—The overall frequency of Ala12 was 12% (n = 42). BMI was significantly higher in Ala carriers than non-Ala carriers, whereas total daily energy intake or macronutrient composition of the diet were similar in the two groups. For further analysis, participants were stratified according to genotype and sex-specific quartiles of energy intake. BMI increased in both genotype groups with increasing energy intake (P < 0.03). BMI was similar in Ala carriers and non-Ala carriers (30.0 vs. 30.1 kg/m2, P > 0.10) in the lower quartile of energy intake but significantly higher in Ala carriers in the upper quartile (36.0 vs. 32.1 kg/m2, P < 0.001). Average daily energy intake and diet composition were comparable within each quartile for carriers or noncarriers of the Ala allele. Relative to the noncarriers, Ala carriers had a significantly lower energy intake per kilogram body weight, thus suggesting that the Ala allele is associated with a higher food efficiency. The confounding role of medications, glucose control, and physical exercise was ruled out. CONCLUSIONS—This study provides evidence of a differential susceptibility to fat accumulation, and, hence, weight gain, in response to habitual high energy intake for Ala carriers compared with Pro/Pro homozygotes.

The aim of this article is to evaluate food properties able to influence specific physiological targets that may be helpful for the prevention and management of overweight and diabetes.Observational and intervention studies have clearly shown that type 2 diabetes can be prevented by lifestyle measures, including reduced energy intake to induce a modest but sustained weight reduction, together with changes in diet composition.Foods can be regarded as functional if proven to affect beneficially one or more target functions in the body, beyond adequate nutritional effects, in a way relevant to improved state of health and well-being, reduction of risk of diseases, or both. Functional foods might have a particularly high impact for prevention or treatment of overweight and diabetes for which, more than in many other fields, the link between nutrition, biological responses and diseases is clearly established. Functional foods for obesity should be able to influence the energy balance equation regulated by the control of energy intake or of energy dissipated as heat (thermogenesis). For prevention of type 2 diabetes, several unmodified foods with functional properties have already been identified (low saturated fat products, vegetables, fruit, wholegrain foods, low glycemic index starchy foods). Overall, the available evidence on functional foods so far identified in this field is incomplete: the major gap is the lack of diet-based intervention trials of sufficient duration to be relevant for the natural history of diseases like overweight and diabetes.

Background There is no definite consensus on which indexation of left ventricular mass (LVM) should be used to better identify left ventricular hypertrophy (LVH). Left ventricular mass has been adjusted to height, to height 2.7 (h 2.7 ) and to body surface area (BSA). The aims of the present study were to evaluate the prevalence of LVH according to different indexations and different cut-offs and to identify the most useful indexation of LVM to detect hypertension-related LVH. Methods Echocardiographic LVH was defined as LVM to h 2.7 , LVM to BSA, LVM to height, LVM values in the upper 5th percentile of our gender-related LVM distribution, using different partition values suggested in previous population-based studies. Results Prevalence of LVH in the general population was 32% using the less restrictive criterion (LVH 49.2/46.7 g/m 2.7 ), 15% with the criterion of LVH 116/104 g/m 2 , and 3.8% with the most restrictive one (LVH 134/110 g/m 2 ). Prevalence of LVH in hypertensive subjects was almost twice than in normotensive subjects with all criteria. Only 20 subjects out of the 707 evaluated were found to have LVH with all six criteria. In multiple regression analysis SBP was independently associated with nonindexed LVM and was indexed to both BSA and h 2.7 . On the other hand, fat-free mass was a poweful predictor of nonindexed LVM or of LVM to BSA, whereas body mass index was the strongest predictor of LVM to h 2.7 . Conclusions The indexation of LVM to BSA, possibly with the cut-off of LVH 116/104, is probably the best criterion for identifying blood pressure–related LVH.

Postprandial lipaemia is considered an emerging risk factor for cardiovascular disease also in the Type 2 diabetic population. However, little information exists on the daily triglyceride profile of these patients, especially during everyday life. The aim of the study was to evaluate the daily triglyceride profile of Type 2 diabetic patients during their everyday life.145 Type 2 diabetic patients (66 men/79 women, age range 45-65 years) at a health district near Naples, Italy, participating in a screening survey for the evaluation of diabetic complications, and 30 non-diabetic subjects of the same area underwent four daily capillary triglyceride profiles by Accutrend (Roche)-a previously validated method.Triglyceride values (mmol/l; Means +/- SE) were 2.22+/-0.08 at fasting, decreased before lunch (2.03+/-0.07), reached a peak 3 h after lunch (2.73+/-0.09) and remained substantially high before dinner (2.47+/-0.09) (all p0.001 vs fasting). The triglyceride profile of non-diabetic subjects was significantly lower at each point (average difference of 0.73 mmol/l). The percentage of patients with values above 2.25 mmol/l was 61% 3 h after lunch and 49% before dinner. Moreover, in 30% of patients with optimal fasting values (1.69 mmol/l) triglyceride concentrations 3 h after lunch ranged between 1.69 and 2.25 mmol/l, and in 31% they were above 2.25 mmol/l.Most Type 2 diabetic patients have postprandial triglycerides above optimal concentrations for several hours after meals. Moreover, optimal fasting concentrations are not always a good predictor of postprandial triglycerides.

Summary objective To analyse the association of the UCP2 gene, alone or in combination with the PPARγ2 gene, with obesity. design Cross-sectional, case–control study. study population From a working population of 4500 Italian Caucasian employees of the Italian telephone company participating in a firm-sponsored health screening programme, we selected all those with obesity [n = 122; body mass index (BMI) ≥ 30 kg/m2]. For each case, three nonobese age- and sex-matched individuals were selected as controls from the same population (n = 374). Included in the study were also 76 severely obese (BMI ≥ 40 kg/m2) patients consecutively admitted to the obesity clinic of the department. Diabetic individuals were excluded. measurements The −866G/A UCP2 and the Pro12Ala PPARγ2 polymorphisms were determined on genomic DNA of the studied individuals. Several metabolic and anthropometric measures were also obtained, like plasma glucose, insulin, triglycerides, total cholesterol, high-density lipoprotein (HDL) cholesterol and BMI. results BMI, plasma glucose, insulin, triglycerides, total and HDL cholesterol were not significantly different in carriers and noncarriers of the −866G/A variant. No significant association was observed between the −866G/A UCP2 gene polymorphism and moderate or severe obesity. This was also observed when the UCP2 polymorphism was analysed in combination with the PPARγ2 polymorphisms. conclusions The −866G/A variants of the UCP2 gene are not associated with either obesity or other features of the metabolic syndrome in the studied groups of the Italian population. This negative finding is not modified after a combined analysis of the UCP2 polymorphism and the Pro12Ala polymorphism of PPARγ2.

The effect of known diabetes on in-hospital mortality from ischemic stroke is still debated whereas the role of unknown diabetes is virtually unexplored. This study evaluates the impact of known and unknown diabetes on in-hospital mortality from ischemic stroke.We have retrospectively evaluated the records of 286 consecutive cases of ischemic stroke hospitalized from January 1998 to December 2000 at the Department of Internal Medicine of the General Hospital located in the western area of Naples. Fasting plasma glucose level7 mmol/L identified non diabetic subjects. Known diabetes mellitus was diagnosed by history of diabetes and/or hypoglycemic therapy, unknown diabetes was defined as a random plasma glucose levelor = 11 mmol/L and/or in-hospital fasting glucoseor = 7 mmol/L on two or more occasions. Severity of stroke was defined using the Canadian Neurological Score (CNS). According to these criteria, 144 subjects were non diabetics, 99 had known diabetes and 43 had unknown diabetes. Subjects with known diabetes showed a higher prevalence of female sex, hypertension and increased triglyceride levels as compared with non diabetic subjects (p0.01). Subjects with unknown diabetes were older (p0.01) and showed a more severe CNS (3.4 +/- 2.7) than non diabetic and diabetic subjects (5.8 +/- 2.6 and 5.8 +/- 2.6, respectively; p0.01). In-hospital mortality was significantly higher in the unknown diabetic group (44%) as compared with known diabetic (15%) and non diabetic groups (12%) (p0.001). This finding was independent of neurological deficit, age, atrial fibrillation and history of previous stroke.Our study shows that unknown diabetes, more than known diabetes, is a strong risk factor for in-hospital mortality in subjects with acute ischemic stroke.

Summary background There is substantial but not conclusive evidence that insulin resistance is related to left ventricular mass (LVM) in hypertensive individuals. To what extent this association is mediated by the relationship between plasma insulin and body size and build is still debated, and is poorly explored in nonhypertensive people. objective To explore the relationship between insulin or insulin resistance and LVM in a population-based sample of nonhypertensive participants of the Gubbio Study. method Echocardiographic LVM was determined in 91 nondiabetic, nonhypertensive individuals aged 45–54 years, participating in a population-based screening. LVM normalized for height2·7 was used in the analyses; LV hypertrophy was defined as a value of ≥ 50 g/m2·7 in men or ≥ 47 g/m2·7 in women. Fasting plasma insulin and glucose were measured and the Homeostasis Model Assessment (HOMA) index was used as a measure of insulin resistance. results LVM was positively and significantly correlated with body mass index (BMI) (P

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.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.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.Fasting ApoB48 was independently associated with asymptomatic PAD in patients with type 2 diabetes.

Summary background The Pro12Ala polymorphism of the peroxisome proliferator-activated receptor (PPAR) γ gene has been associated in some, but not all, studies with lower body mass index (BMI) and improved insulin sensitivity; how an altered transcriptional activity of PPARγ2 could influence insulin sensitivity is currently unclear. The free fatty acids (FFAs) released from adipose tissue triglycerides via lipolysis are key mediators of impaired insulin sensitivity; however, no study has described the relationship of the Pro12Ala mutation with circulating levels of FFAs under physiological conditions. objective To investigate in a population-based sample of Caucasians the relation of the Pro12Ala polymorphism with plasma concentrations of FFAs and other markers of lipid and glucose metabolism described as components of the insulin resistance syndrome. subjects Four hundred and thirty-eight nondiabetic employees of the Italian Telephone Company, aged 35–65 years, randomly selected from a total population of 3900 participants in a company-sponsored health screening. measurements The Pro12Ala polymorphism of the PPARγ was studied together with plasma FFAs, insulin, glucose, triglycerides, high density lipoprotein (HDL) cholesterol, blood pressure and anthropometry. The Homeostatic Model Assessment (HOMA) index was calculated as a measure of insulin resistance. results Carriers and noncarriers of the Pro12Ala polymorphism showed very similar circulating levels of FFA (0·46 ± 0·2 vs. 0·47 ± 0·2, NS); plasma glucose, triglycerides, HDL cholesterol and blood pressure were also similar in the two groups with or without the polymorphism. To allow for the possible confounding effect of obesity, a separate analysis was conducted in overweight (BMI ≥ 25 kg/m2) and normal-weight people (BMI

Background To estimate cardiovascular disease (CVD) mortality in relation to obesity and gender. Methods Data from 11 prospective cohorts from four European countries including 23 629 men and 21 965 women, aged 24 to 99 years, with a median follow-up of 7.9 years were analyzed. Hazards ratios (HR) for CVD mortality in relation to baseline body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR) were estimated using Cox proportional hazards models with age as the timescale. Results Men had higher CVD mortality than women in all four BMI categories (

The aim of this report is to perform a systematic review and qualitative synthesis of the literature to address whether, and to what extent, diet modulates the effects of the Pro12Ala polymorphism of peroxisome proliferator-activated receptor gamma 2 (PPARγ2) on body weight and other measures of adiposity. A systematic search of the literature was conducted, wherein both observational and experimental studies of adults were reviewed. Overall, the results of the observational studies show little consistency. Methodological differences in their design, conduct and analysis may largely account for the apparently discrepant findings. This notwithstanding, the main picture that emerges is that the energy content and composition of the diet may affect BMI, body composition and metabolic parameters in Ala allele carriers more than in Pro/Pro homozygotes. In most studies, carriers of the Ala allele with an obesogenic lifestyle (i.e. high-energy, high-carbohydrate and, to some extent, high-fat diets) are more obese than Pro homozygotes. Well-designed intervention studies with a sufficiently large sample size consistently show that carriers of the Ala allele are more prone to weight loss when exposed to a healthy lifestyle; however, these individuals do not seem to retain these benefits when returning to a sedentary lifestyle and inadequate dieting behaviours. Some key questions in this area of research have emerged. Carefully designed and adequately powered studies are needed, particularly involving the development and validation of standardized tools for the assessment of dietary exposure, including the use of biomarkers, to move the field forward.

1096 www.thelancet.com Vol 384 September 20, 2014 Holman and colleagues raise the possibility that metformin showed some effi cacy in the UKPDS34 trial, which only compared 342 patients with 411 controls, yet their review strategy only included randomised clinical trials with more than 1000 patients. This efficacy was limited to a subgroup of overweight patients and was not significant at the 1% level as planned in the protocol. Moreover, in a meta-analysis, the efficacy of metformin was not proven. The comparison of a metformin–sulfonylurea combination with sulfonylurea alone showed an increase in all cause and cardiovascular mortality, similarly to that reported in UKPDS34, yet Holman and colleagues did not comment on this point. We fi nd it peculiar that the whole of the medical community judges metformin as a gold-standard treatment when its effi cacy on clinical endpoints is based on one result, obtained in a subgroup and with a low-level proof. With regards to the long-term control of glycaemia, Holman and colleagues quoted the 10 year follow-up of the UKPDS, which does not have strong evidence, without mentioning the ACCORD post-trial follow-up in which some excess mortality persisted. The time has come to measure the effi cacy of antidiabetics on clinically important outcomes and not to limit research to safety studies.

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.

OBJECTIVE Insulin resistance plays a part in diabetic nephropathy (DN). The association between the peroxisome proliferator–activated receptor γ Pro to Ala alteration at codon 12 (Pro12Ala) polymorphism and the risk of insulin resistance has been confirmed. The association between the polymorphism and DN risk has also been widely studied recently, but no consensus was available up to now. RESEARCH DESIGN AND METHODS A systematic search of electronic databases (MEDLINE, Embase, and China National Knowledge Infrastructure) and reference lists of relevant articles was carried out, and then 18 case-control studies involving 3,361 DN cases and 5,825 control subjects were identified. RESULTS In the overall analysis, the Ala12 variant was observed to be significantly associated with decreased DN risk (odds ratio 0.76 [95% CI 0.61–0.93]). Some evidence of heterogeneity among the included studies was detected, which could be explained by the difference of ethnicity and stage of DN. Subgroup analyses stratified by ethnicity and stage of DN were performed, and results indicated the Pro12Ala polymorphism was associated with the risk of DN in Caucasians but no similar association was observed in Asians. Additionally, we observed that Ala12 was associated with decreased risk of albuminuria. With only a few of subjects were available, we failed to detect statistically significant association between the polymorphism and end-stage renal disease (ESRD). CONCLUSIONS Our results indicated that the Ala12 variant is a significantly protective factor for DN. Future research should focus on the effect of Pro12Ala polymorphism on ESRD and gathering data of Africans.

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)

1. Parillo M, Riccardi G. Diet composition and the risk of type 2 diabetes: epidemiological and clinical evidence. Br J Nutr 2004;92(1):7–19. 2. Riccardi G, Aggett P, Brighenti F, et al. PASSCLAIM—body weight regulation, insulin sensitivity and diabetes risk. Eur J Nutr 2004;43(Suppl 2):II7–II46. 4. Wirth A, Krause J. Long-term weight loss with sibutramine. JAMA 2001;286:1331–1339. 5. Van Gal LF, Rissanen AM, Scheen AJ, et al; RIOEurope Study Group. Effects of the cannabinoid-1 receptor blockers rimonabant on weight reduction and cardiovascular risk factors in overweight patients: 1year experience from the RIO-Europe study. Lancet 2005;365:1389–1397. 6. Vessby B, Uusitupa M, Hermansen K, et al. Substituting dietary saturated for monounsaturated fat impairs insulin sensitivity in healthy men and women: the KANWU study. Diabetologia 2001;44:312–319. 7. Fernandez de la Puebla RA, Fuentes F, Perez-Martinez P, et al. A reduction in dietary saturated fat decreases body fat content in overweight, hypercholesterolemic males. Nutr Metab Cardiovas Dis 2003;13:273–278. 9. World Health Organization. Obesity: preventing and managing the global epidemic, WHO technical report series no. 894 edition. Geneva: WHO; 1999. 10. Tuomilehto J, Undstrom J, Eriksson JG, et al. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. New Engl J Med 2001;344:1343–1350. 11. Diabetes Prevention Program Research Group Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. New Engl J Med 2002;346:393–403. 13. American Dietetic Association. Position of the American Dietetic Association: fat replacers. J Am Diet Assoc 2005;105(2):266–75. 14. Mann JI, De Leeuw I, Hermansen K, et al. Diabetes Nutrition Study Group. Evidence-based nutritional approaches to the treatment and prevention of diabetes mellitus. Nutr Metab Cardiovasc Dis 2004;14: 373–94. 15. Riccardi G, Giacco R, Rivellese AA. Dietary fat, insulin sensitivity and the metabolic syndrome. Clin Nutr 2004;23(4):447–56. 16. Caprio S, Weiss R. The metabolic phenotype of prediabetes in obese youth. Nutr Metab Cardiovasc Dis 2004;14:270–5. 17. Goh SY, Cooper ME. Clinical review: The role of advanced glycation end products in progression and complications of diabetes. J Clin Endocrinol Metab 2008 Apr;93(4):1143–52. 18. Riccardi G, Rivellese AA, Giacco R. Role of glycemic index and glycemic load in the healthy state, in prediabetes, and in diabetes. Am J Clin Nutr 2008 Jan;87(1):269S–74S. 19. Klein S, Sheard NF, Pi-Sunyer X, et al. Weight management through lifestyle modification for the prevention and management of type 2 diabetes: rationale and strategies: a statement of the American Diabetes Association, the North American Association for the Study of Obesity, and the American Society for Clinical Nutrition. Diabetes Care 2004;27(8):2067–73. 21. Pereira MA, Jacobs DR jr, Van Horn L, et al. Dairy consumption, obesity and the insulin resistance syndrome in young adults: the CARDIA Study. JAMA 2002;287:2081–9. 23. Hu FB, Manson JE, Stampfer MJ, et al. Diet, lifestyle, and the risk of type 2 diabetes mellitus in women. N Engl J Med. 2001 Sep 13;345(11):790–7.

Background. Insulin resistance has a role in diabetic nephropathy. The A12 variant of the PPARc2 P121A polymorphism has been firmly associated with reduced risk of insulin resistance, while its role on the risk of albuminuria in patients with type 2 diabetes is uncertain. This study investigated whether the PPARc2 P12A polymorphism modulates the risk of albuminuria in these patients. Methods. We tested the association between the A12 variant and albuminuria in three new case–control studies in diabetic patients from Italy (n ¼ 841, n ¼ 623 and n ¼ 714 patients, respectively) and then performed a meta-analysis of all studies available to date. The nine studies we meta-analysed (six previously published and three presented here) comprised a total of 2376 cases and 4188 controls. Results. In none of the three new studies was a significant association observed with odds ratio (OR) [95% confidence intervals (95% CI)] being 1.115, 0.799 and 0.849 (P ¼ 0.603, 0.358 and 0.518, respectively). At meta-analysis, the overall OR (95% CI) for association between A12 and albuminuria was 0.694 (0.528–0.912). A significant heterogeneity of the genetic effect was observed (P ¼ 0.026), which was totally explained by the different method of urine collection and albuminuria definition utilized across the studies. In fact, most of the effect was observed in the four studies determining albumin excretion rate rather than in those using albumin concentration in a single spot (OR, 95% CI: 0.529, 0.397–0.706, P ¼ 0.0000164 and 0.919, 0.733–1.153, P ¼ 0.47, respectively). Conclusion. The present study shows that the PPARc2 Ala12 variant is significantly associated with a reduced risk of albuminuria among patients with type 2 diabetes.

Cerebrovascular reserve capacity (CVRC) was investigated in 13 insulin-dependent diabetic (IDDM) patients with clinical microangiopathy and in 12 healthy subjects. CVRC was assessed by transcranial Do

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.

OBJECTIVE To explore the relationship of one versus two postload plasma glucose measurements to 19-yr mortality in men in the Chicago Peoples Gas Company Study. RESEARCH DESIGN AND METHODS One-hour postload plasma glucose was measured twice (1.4 yr apart, 1965–1967) for 873 nondiabetic men 34–65 yr of age. Serum cholesterol, blood pressure, height, and weight were measured. Data on smoking habits were obtained. Mortality follow-up was complete through July 1986, 19 yr after second glucose load. RESULTS In prospective analyses, with each of three glucose values—first, second, and mean of first and second—coronary, cardiovascular, and all-cause age-adjusted mortality rates were higher in quintiles 3, 4, and 5 compared with quintile 1, with a significant linear trend. Multivariate analyses with glycemia as a continuous variable confirmed a positive independent association between plasma glucose and mortality endpoints with first measurement and mean of two values but not with second. With dichotomization of plasma glucose (≥ 11.2 mM [≥ 200 mg/dl]) for 30 men hyperglycemic both times, CHD and CVD death rates were significantly higher (odds ratios 2.3–2.7) compared with those for 758 men consistently nonhyperglycemic. In contrast, for those hyperglycemic once only, death rates were not significantly higher. Results of multivariate analyses were consistent with these findings. CONCLUSIONS These data indicate a significant relationship of asymptomatic hyperglycemia on repeat examinations to coronary and cardiovascular mortality independent of other factors measured in the study.

The study evaluates whether data concerning drug prescriptions available from the National Health System (NHS) can be used to provide an estimate of the prevalence and pattern of treatment of diabetes in a well defined health district in southern Italy. In Italy virtually all drug prescriptions are obtained through the NHS. For a period of three consecutive months all prescriptions of insulin, hypoglycemic agents and strips for blood and urine testing were monitored in a well defined area near Naples. 2958 cases were thus identified giving a prevalence of drug treated diabetes mellitus of 2.01%; prevalence was higher in females than in males (2.68 vs 1.35%) and increased with age from 0.05% in the age group below 9 years to 13.67 in the age group over 70 years. This case-finding procedure was validated by cross-check with independent sources of cases. To evaluate the sensitivity of the method a list of 820 "known" cases of drug treated diabetes mellitus was obtained from a random sample of local general practitioners (GPs) and diabetic clinics: 73.5% of these cases were also detected through the analysis of drug prescriptions. To evaluate the probability of misclassification a random subsample of 602 cases identified through prescriptions was submitted to the GPs working in the study area, for 517 the diagnosis of diabetes was confirmed, thus yielding a positive predictive value of 85.9%. After correction for sensitivity and probability of misclassification the prevalence of drug treated diabetes in our population was 2.52%. The pattern of prescriptions in this population is also given.(ABSTRACT TRUNCATED AT 250 WORDS)

OBJECTIVE There is debate over the most appropriate adiposity markers of obesity-associated health risks. We evaluated the relationship between fat distribution and high-sensitivity C-reactive protein (hs-CRP), independent of total adiposity. RESEARCH DESIGN AND METHODS We studied 350 people with abdominal adiposity (waist-to-hip ratio [WHR] ≥0.9 in male and ≥0.85 in female subjects) and 199 control subjects (WHR RESULTS Participants with abdominal adiposity had BMI similar to that in control subjects (24.8 ± 2.5 vs. 24.7 ± 2.2 kg/m2, respectively), but significantly higher waist circumference (96.4 ± 6.0 vs. 83.3 ± 6.7 cm; P < 0.01) and WHR (1.07 ± 0.08 vs. 0.85 ± 0.05; P < 0.001). Compared with the control subjects, participants with abdominal adiposity had an adverse cardiovascular risk factor profile, significantly higher hs-CRP (1.96 ± 2.60 vs. 1.53 ± 1.74 mg/dl; P < 0.01), and a twofold prevalence of elevated CRP values (>3 mg/dl). CONCLUSIONS In nonobese people, moderate abdominal adiposity is associated with markers of subclinical inflammation independent of BMI.

Studies have been inconsistent regarding whether lipoprotein particle subfraction measures are useful indicators of cardiovascular risk. The present study evaluated the relation between lipoprotein particle concentrations and size, analyzed using nuclear magnetic resonance spectroscopy and measures of carotid atherosclerosis in a population with high cardiovascular risk but little hyperlipidemia. In this cross-sectional, population-based sample of Alaska Eskimosor=35 years old (n = 656), a greater carotid intimal medial thickness was associated with greater low-density lipoprotein (LDL) cholesterol (p = 0.03) and total LDL particle concentration (p = 0.04), independently of other traditional risk factors. The effects of LDL cholesterol and LDL particle concentration on intimal medial thickness were additive (p = 0.015). Carotid plaque was associated with greater levels of LDL cholesterol (p = 0.01), greater concentrations of large LDL particles (p = 0.003), and a reduction in the size of the very-low-density lipoprotein particles (p = 0.03). The effects of LDL cholesterol and large LDL particles on the plaque score were additive. In conclusion, the carotid intimal medial thickness was associated with greater LDL particle concentrations. The association was strongest in those with greater LDL cholesterol levels. Plaque was associated with greater concentrations of LDL cholesterol, large LDL particles, and smaller very-low-density lipoprotein particles. It might be beneficial to determine the lipoprotein subfractions in populations with little hyperlipidemia.

Thirty patients with intermittent claudication (IC) and treated diabetes melllitus and 30 age- and gender-matched nondiabetic claudicants underwent a vascular examination by noninvasive ultrasound methods (continuous-wave Doppler, duplex scanner). The ankle/arm systolic pressure index did not differ in the two groups. Diabetic patients with IC had more (p < .001) non-flow-reducing stenoses (lumen reduction < 50%) and fewer (p 50 % ) of the iliac arteries than nondiabetics had. These data are consistent with a preferentially distal (below the inguinal ligament) localization of arterial stenoses in diabetic patients, whereas iliac artery diseases are relatively more severe in nondiabetics.

Peroxisome proliferator-activated receptor (PPAR)-gamma is a major regulator of adipogenesis and insulin sensitivity. The PPAR-gamma gene generates two isoforms through alternative splicing, PPAR-gamma1 and -gamma2, the latter having an additional stretch of 28 amino acids at its NH2-terminus in the ligand-independent activation domain. This extension renders PPAR-gamma2 more sensitive to insulin action. Since there is a Pro12Ala substitution in this domain, we tested whether it is related to type 2 diabetes or insulin resistance. Therefore, 131 type 2 diabetic patients and 312 normoglycemic control subjects were screened for the presence of the mutation and for major clinical and metabolic features. The frequency of the mutation did not differ significantly between diabetic patients and control subjects. BMI, insulin, and other metabolic and anthropometric variables were also not associated with the mutation. Although the study was carried out on a sufficiently large sample, the conclusions do not support a major role for the Pro12Ala substitution of the PPAR-gamma gene in the etiology of type 2 diabetes.