Impact of migration on diabetes burden: audit in the metropolitan area of Bologna, Italy.

PURPOSE: To investigate the impact of diabetes in immigrants on the Italian healthcare system, as well as their compliance with standard protocols of control and treatment. METHODS: The prevalence of immigrants with diabetes living in the metropolitan area of Bologna (about 1 million inhabitants) in 2019 was investigated using a database containing all subjects in active follow-up for diabetes, based on antidiabetic drug use, disease-specific copayment exemption, ICD-9 codes, continuous care in diabetes units. Country of origin was derived from fiscal code. RESULTS: The overall prevalence of diabetes (n = 53,941; 51.8% males, median age 64) was 6.1% in both Italy-born and immigrant cohorts. Immigrant prevalence was 12.4%, moderately higher than that observed in the total population (12.2%). Diabetes risk was increased in the whole immigrant cohort (odds ratio (OR) 1.74; 95% Confidence Interval (CI) 1.69-1.79). Among cases with incident diabetes, the proportion of immigrants (median age, 49 vs. 65 in Italy-born individuals) increased progressively from 11.7% to 26.5% from 2011 to 2019 (males, 8.9-21.0%; females, 14.9-32.8%) in all age groups, particularly in young adults, but also in older subjects. Metabolic control was lower in immigrants, as was adherence to shared diagnostic and therapeutic protocols, without systematic differences in antidiabetic drug use, but much lower use of drugs for comorbid conditions. CONCLUSIONS: The population with diabetes in the metropolitan area of Bologna is rapidly changing. Quality improvement initiatives are needed to reduce the burden for the universalistic Italian health care system generated by the rapidly-growing high-risk immigrant population.

Management of dairy heifers: Can operant conditioning be an effective and feasible tool to decrease stress and ease animals' close contact and handling?

Besides health monitoring, a regular check of dairy heifers' growth rate is desirable, but it is rarely done because procedures that require restraint and handling can be associated with substantial stress for both animals and farmers. Inexperienced heifers, especially if they are highly responsive to humans, may find restraint and handling potentially aversive. This study investigated whether training heifers of different age and responsiveness toward humans (RTH), through operant conditioning, could reduce stress in animals, ease close contact and handling, and be feasible in terms of farmers' effort. We assessed 60 Holstein heifers of 2 age classes (young, n = 29, 291 ± 39 d; old, n = 31, 346 ± 62 d) according to the avoidance distance test and classified them as confident (n = 20), neutral (n = 21), or nonconfident (n = 19). Half of the heifers of each age and RTH class were trained (n = 29), whereas the other half was not (n = 31). The trained heifers were subjected to target training for 8 sessions and positively reinforced with feed to allow being touched on the muzzle, rump, and perineum. If a heifer refused positive reinforcement, the trainer stepped back as negative reinforcement. In the last week of the experiment, the effect of training on the reaction to handling was assessed in all heifers. We measured heart rate, root mean square of successive interbeat interval differences (RMSSD), and fecal cortisol metabolites (FCMet). The presence of behavioral distress signs was recorded as well. The avoidance distance test was performed a second time 24 h after the measuring session. All of the trained heifers, regardless of RTH class, successfully accomplished the target training task in 6 sessions, each spending on average 25.3 s per session. All of the trained heifers allowed touches on the rump and perineum at the end of the fourth session. Training nonconfident heifers required more time compared with the others. Trained heifers showed higher RMSSD than nontrained heifers (14.2 vs. 16.9 ms, respectively), indicating a lower vagal tone, and thus, a slightly lower stress level than nontrained heifers. Training did not lead to differences in HR, FCMet, or presence of stress behavioral signs. Nonconfident heifers had the highest mean baseline FCMet values compared with neutral and confident heifers (38.4 vs. 30.3 vs. 29.1 ng/g, respectively). Nonconfident heifers also showed the lowest value of FCMet 12 h after the measuring session (36.7 vs. 44.6 vs. 49.7 ng/g), likely due to a decreased responsiveness of the adrenal gland to a stressor. The average avoidance distance decreased between the beginning and the end of the experiment, especially for neutral and nonconfident heifers, regardless of whether they were trained or not. These results show how using operant conditioning on some heifers not only decreased their vagal tone, but also reduced the responsiveness to humans of all the animals, trained and not trained; in the latter case, this reduction was through nonassociative learning, such as habituation.

Type 2 diabetes treatment and progression of chronic kidney disease in Italian family practice.

AIMS: Progressive chronic kidney disease represents a dreadful complication of type 2 diabetes mellitus (T2DM). We tested the pattern of use and the renal effects of old glucose-lowering drugs in T2DM patients cared for by Italian general practitioners (GPs). METHODS: Data of 2606 T2DM patients were extracted from the databases of GPs, who do not have access to the most recent glucose-lowering drugs in Italy. The rate of kidney function decline was calculated by CKD-EPIcr, based on two consecutive creatinine values. RESULTS: Metformin was used in 55% of cases, either alone or with sulfonylureas/repaglinide, across the whole spectrum of CKD (from 66% in stage G1 to only 8% in G4). Sulfonylurea use peaked at 21-22% in stage G2-G3a, whereas repaglinide use significantly increased from 8% in G1 to 22% in G4. The median rate of CKD decline was - 1.64 mL/min/1.73 m2 per year; it was higher in G1 (- 3.22 per year) and progressively lower with CKD severity. 826 cases (31.7%) were classified as fast progressors (eGFR decline more negative than - 5 mL/min/1.73 m2 per year). The risk of fast progressing CKD was associated with increasing BMI, albuminuria, and sulfonylurea use, alone (OR, 1.47; 95% confidence interval, 1.16-1.85), or in association with metformin (OR, 1.40; 95% CI 1.04-1.88). No associations were demonstrated for metformin, cardiovascular and lipid lowering drug use. CONCLUSION: In the setting of Italian family practice, sulfonylurea use is associated with progressive CKD in patients with T2DM. Metformin, at doses progressively reduced according to CKD stages, as recommended by guidelines, is not associated with fast progression.

Pharmacovigilance of sodium-glucose co-transporter-2 inhibitors: What a clinician should know on disproportionality analysis of spontaneous reporting systems.

Sodium-glucose co-transporter-2 inhibitors (SGLT2-Is) have consistently demonstrated a clinically significant reduction of cardiovascular mortality. However, their safety in clinical practice is still incompletely characterized, and post-marketing monitoring is required considering the expected increase in clinical use. Different analyses of international spontaneous reporting systems, known as disproportionality analyses (DAs), have highlighted the occurrence of ketoacidosis, amputations, acute renal failure and skin toxicity. In this viewpoint, we critically appraise these pharmacovigilance data on SGLT2-Is, with the aim of supporting clinicians in proper interpretation of these studies, and discussing their risk-benefit profile. To this aim, we offer a broad perspective on basic technical aspects subtending DAs of spontaneous reporting databases (describing peculiarities of the Food and Drug Administration Adverse Event Reporting System), their common and evolving uses, key pitfalls in presenting study results (in terms of "risk" or "association") and relevant strategies to account for major confounders. This will also facilitate reviewers and editors in proper evaluation of DAs, and prompt pharmacovigilance experts in converging towards a set of minimum requirements in standardization of design, performance and reporting of DAs. A consensus on quality assessment of DAs will finally establish their transferability to clinical practice. It is anticipated that DAs cannot be used per se as a standalone approach to assess a drug-related risk and cannot replace clinical judgment in the individual patient.

Sense of coherence, self-esteem, and health locus of control in subjects with type 1 diabetes mellitus with/without satisfactory metabolic control.

BACKGROUND: Despite intensive training, a few individuals with Type 1 diabetes mellitus (T1DM) fail to reach the desired metabolic targets. AIM: To evaluate the association between disease-related emotional and cognitive aspects and metabolic control in subjects with T1DM. SUBJECTS AND METHODS: Health locus of control (HLOC), sense of coherence (SOC), and self-esteem were assessed in T1DM subjects using validated questionnaires. Sixty-seven consecutive subjects who did not attain the desired HbA1c target (mean HbA1c, 8.3% [67 mmol/mol]) were compared with 30 cases in satisfactory metabolic control (HbA1c levels <7%-53 mmol/mol). RESULTS: In the overall population, SOC was negatively associated with BMI and average HbA1c, as was the association of self-esteem with HbA1c. Subjects attaining the desired metabolic target were characterized by higher SOC scores, higher Internal HLOC and prevalent Internal vs. Powerful-others HLOC. Compared to subjects in good metabolic control, subjects with unsatisfactory control had lower scores of SOC, Internal HLOC and Self-esteem, with no difference in Powerful others, or Chance HLOC. In the same group, SOC in the upper tertile was significantly associated with self-esteem (OR 1.35; 95% CI 1.08-1.69) and PHLOC (OR 1.24; 95% CI 1.03-1.49), after adjustment for age, sex, educational level, and comorbidities. CONCLUSIONS: Patients who fail to reach a satisfactory metabolic control tend to rely on significant others, trusting in the physicians' skills or on the efficiency of the health-care system. Strategies aimed at increasing self-efficacy and SOC, based on personal ability, are eagerly awaited to help patients improve diabetes care.

Adverse events with sodium-glucose co-transporter-2 inhibitors: A global analysis of international spontaneous reporting systems.

BACKGROUND AND AIMS: We assessed post-marketing safety of sodium-glucose co-transporter-2 inhibitors (SGLT2-Is) by analyzing adverse events (AEs) reported in international pharmacovigilance databases. METHODS AND RESULTS: Eudravigilance, WHO-Vigibase (as of Feb 25, 2017) and the FDA Adverse Event Reporting System (FAERS, from 2004 to 2016 second quarter) were queried to extract AEs recording SGLT2-Is as suspect. Disproportionality analyses (case/non-case method) were performed in FAERS by calculating the reporting odds ratios (RORs) from System Organ Classes (SOCs) to Preferred Terms (PTs) (precise clinical entities). Potential signals were defined by statistically-significant ROR (lower limit of the 95% confidence interval - LL95%CI - >1) undetected by literature analysis (as of December 2016). SGLT2-Is were recorded in 7972, 19,775, 11,137 reports (Eudravigilance, WHO-Vigibase and FAERS, respectively); in FAERS, statistically significant ROR emerged for the following SOCs: "infections and infestations" (N = 2162; LL95%CI = 3.25), "metabolism and nutrition disorders" (2278; 1.36), "renal and urinary disorders" (1665; 2.31), "reproductive system and breast disorders" (471; 4.85), "skin and subcutaneous tissue disorders" (1136; 1.52). Skin toxicity emerged as potential signal (e.g., rash, photosensitivity, urticaria as PTs), both for SGLT2-Is as a class and as individual drugs. Severe adverse skin events (81 reports, 7% of the skin cases) mainly occurred in females aged 18-65 using SGLT2-Is as single antidiabetic regimen. CONCLUSION: Among antidiabetics, SGLT2-Is are associated with higher reporting of infections, metabolism, renal and reproductive AEs, corroborating clinical trial evidence. Their large reporting patterns and the unexpected signal of skin toxicity justify active vigilance by clinicians and "real-time" monitoring by pharmacovigilance experts.

Dipeptidyl peptidase-4 inhibitors and heart failure: Analysis of spontaneous reports submitted to the FDA Adverse Event Reporting System.

BACKGROUND AND AIMS: We tested the possible association between dipeptidyl peptidase-4 inhibitors (DPP-4-I) use and heart failure (HF) occurrence by assessing the publicly available US-FDA Adverse Event Reporting System (FAERS). METHODS: FAERS data reporting HF and DPP-4-Is use in the period from the fourth quarter of 2006 through 2013 were extracted, using the Standardized MedDRA Query "Cardiac failure". Disproportionality (case/non-case method) was implemented by calculating Reporting Odds Ratios (RORs) with 95% Confidence Interval (CI): (1) exploratory analysis on the entire FAERS (using rosiglitazone as positive control); (2) consolidated analyses by therapeutic area (within antidiabetics), correcting for event- and drug-related competition bias and adjusting for co-reported drugs as confounders. RESULTS: HF during DPP4-I use was recorded in 390 reports (4.4% of total reports). In exploratory analysis, statistically significant ROR emerged for DPP-4-I as a class (ROR = 1.17; 95% CI = 1.05-1.29), saxagliptin (1.68; 1.29-2.17), vildagliptin (2.39; 1.38-4.14), and rosiglitazone (13.98; 13.30-14.70). In consolidated analyses, the ROR for saxagliptin (2.60; 1.92-3.50) and vildagliptin (4.07; 2.28-7.27) increased, and became also significant for sitagliptin (1.61; 1.40-1.86). Concomitant drugs were reported in more than 50% of cases; the adjusted RORs of saxagliptin (2.30; 1.70-3.10), vildagliptin (3.15; 1.76-5.63), and sitagliptin (1.48; 1.28-1.71) were nonetheless significant. CONCLUSION: FAERS data are consistent with clinical studies on a possible association between saxagliptin and HF. The disproportionate reporting of HF with sitagliptin, conflicting with a recent phase IV trial, suggests that cardiovascular safety requires close post-marketing vigilance by clinicians of individual DPP-4-I in the community until the issue of class effect is solved.

Costs associated with emergency care and hospitalization for severe hypoglycemia.

BACKGROUND AND AIMS: We aimed to determine the direct economic cost of the management of severe hypoglycemia among people with diabetes in Italy. METHODS AND RESULTS: Data of cases with an acceptance diagnosis of hypoglycemia between January 2011 and June 2012 were collected in 46 Emergency Departments (EDs). Emergency care costs were computed by estimating the average cost per ambulance service, ED visit and short-term (<24 h) observation period. Hospitalization expenditure was estimated using the average cost reimbursed by the Italian healthcare system for hospital admission per patient with diabetes in a specific hospital ward. We retrieved 3516 hypoglycemic episodes occurring in subjects with diabetes. Half the cases (51.8%) required referral to EDs by means of the emergency ambulance services. A total of 1751 cases (49.8%) received an ED visit followed by discharge; 604 cases (17.2%) received a short-term observation period; 1161 (33.1%) were hospitalized. Unit costs for emergency care management were estimated at €205 for an ambulance call, €23 for an ED visit, and €220 for a short-term observation. The mean hospitalization cost was estimated at €5317; the average cost per each severe hypoglycemic event totaled €1911. From a base case assumption, the total direct cost of severe hypoglycemia in patients with diabetes in Italy was estimated to be approximately €23 million per year. CONCLUSION: Severe hypoglycemia in patients with diabetes constitutes a remarkable economic burden for national healthcare systems. Measures for preventing hypoglycemia are mandatory in diabetes management programs considering the impact on patients and on health spending.

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.

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 management of severe hypoglycemia by the emergency system: the HYPOTHESIS study.

BACKGROUND AND AIMS: Severe hypoglycemia is not rare in diabetes and markedly impacts on health resource use. We aimed to describe the characteristics of patients attending emergency departments (EDs) following a severe episode of hypoglycemia, the factors associated with the management of events and the final outcome. METHODS AND RESULTS: We carried out a retrospective analysis of cases attending 46 Italian EDs for hypoglycemia from January 2011 to June 2012. A total of 3753 records were retrieved from the databases of the participating centers, part of a network repeatedly involved in collaborative studies; 3516 episodes occurred in subjects with diabetes (median age, 76 years; range, 1-102). Comorbidities were recorded in 2320 (65.9%) diabetes cases; association with trauma or road accidents in 287 (8.2%) and 47 (1.3%), respectively. Patients were treated with insulin (49.8%), oral agents (31.4%), or combination treatment (15.1%). The event required assistance by the out-of-hospital Emergency services in 1821 cases (51.8%). Following the ED visit, admission to hospital departments was deemed necessary in 1161 cases (33.1%). Diabetes treatment (oral agents: OR, 1.63; 95% confidence interval (CI), 1.37-1.94), increasing age (OR, 1.39; 95% CI, 1.31-1.48) and the number of comorbidities (OR, 1.51; 95% CI, 1.38-1.66) were the main drivers of admission. The in-hospital death rate was 10%, associated with the number of comorbidities (OR, 1.28; 95%CI, 1.01-1.63). CONCLUSION: Severe hypoglycemia requiring referral to EDs is associated with a significant work-up of the Emergency services and a remarkable in-hospital death rate in frail individuals with diabetes.

Drug utilization, safety, and effectiveness of exenatide, sitagliptin, and vildagliptin for type 2 diabetes in the real world: data from the Italian AIFA Anti-diabetics Monitoring Registry.

BACKGROUND AND AIMS: In Italy, the reimbursed use of incretin mimetics and incretin enhancers was subject to enrollment of patients into a web-based system recording the general demographic and clinical data of patients. We report the utilization data of glucagon-like peptide 1 (GLP1) receptor agonists and dipeptidylpeptidase-4 (DPP4) inhibitors in clinical practice as recorded by the Italian Medicines Agency (AIFA) Monitoring Registry. METHODS AND RESULTS: From February 2008 to August 2010, 75,283 patients with type 2 diabetes were entered into the registry and treated with exenatide, sitagliptin, or vildagliptin. The treatment was administered to patients in a wide range of ages (≥75 years, n = 6125 cases), body mass index (BMI) (≥35 kg/m(2), n = 22,015), and metabolic control (HbA(1c) ≥ 11% ((96 mmol/mol), n = 3151). Overall, 1116 suspected adverse drug reactions were registered, including 12 cases of acute pancreatitis (six on exenatide). Hypoglycemic episodes mainly occurred in combination with sulfonylureas. Treatment discontinuation for the three drugs (logistic regression analysis) was negatively associated with the male gender and positively with baseline HbA1c, diabetes duration, and, limitedly to DPP-4 inhibitors, with BMI. Treatment discontinuation (including loss to follow-up, accounting for 21-26%) was frequent. Discontinuation for treatment failure occurred in 7.7% of cases (exenatide), 3.8% (sitagliptin), and 4.1% (vildagliptin), respectively, corresponding to 27-40% of all discontinuations, after excluding lost to follow-up. HbA1c decreased on average by 0.9-1.0% (9 mmol/mol). Body weight decreased by 3.5% with exenatide and by 1.0-1.5% with DPP-4 inhibitors. CONCLUSIONS: In the real world of Italian diabetes centers, prescriptions of incretins have been made in many cases outside the regulatory limits. Nevertheless, when appropriately utilized, incretins may grant results at least in line with pivotal trials.

Effect of feeding fine maize particles on the reticular pH, milk yield and composition of dairy cows.

The particle size of cereal grains has been found to modulate the rate of passage from the rumen and the digestibility of starch and neutral detergent fibre (NDF), but few studies have examined its impact on reticular pH. The study aimed to evaluate the effect of feeding finely ground maize on the risk of ruminal acidosis, milk yield and composition. Twelve Holstein-Friesian cows were assigned to one of two experimental groups and fed according to a cross-over design. Diets were isoenergetic and isonitrogenous and were characterised by the same NDF and ADF, differing only in maize particle size. In the control diet (Ct), the maize meal was ground to 1.0 mm, whereas in the experimental diet, it was finely ground (Fg) to 0.5 mm. The pH and temperature of the reticulum were continuously measured in eight cows throughout the trial using indwelling sensors. Dry matter intake was higher in cows offered Fg diet than in Ct (19.0 vs. 20.3 kg/day; p = 0.067). However, milk yield (p = 0.855) and the 3.5% fat-corrected milk (FCM) (p = 0.724) did not show any differences between the diets. Casein (2.48 vs. 2.57%; p = 0.035) and crude protein (CP) (3.18 vs. 3.31%; p = 0.021) resulted higher in Fg. Similarly, starch digestibility increased in animals offered Fg diet versus Ct (0.94 vs. 0.98; p = 0.078). Among the reticular parameters, the Fg-fed cows spent a significantly higher time below the 5.5 pH threshold (15 vs. 61 min/day; p = 0.047) and had an average daily variation in reticular pH characterised by a lower nadir pH (5.95 vs. 5.72; p < 0.001) and a higher pH range (0.79 vs. 0.94; p = 0.003). In this study, grain particle size affected the risk of the onset of ruminal acidosis. Therefore, it should be carefully considered when formulating rations.

High sCD36 plasma level is associated with steatosis and its severity in patients with genotype 1 chronic hepatitis C.

Soluble CD36 (sCD36) plasma levels, a known marker of cardiometabolic disorders, are associated with surrogate markers of steatosis, while experimental and human studies show a link between CD36 expression in the liver and steatosis. In a cohort of patients with genotype 1 chronic hepatitis C (G1 CHC), we tested the association of sCD36 plasma levels with host and viral factors and sustained virological response (SVR). One hundred and seventy-five consecutive biopsy-proven patients were studied. sCD36 plasma levels were assessed by an in-house ELISA. All biopsies were scored by one pathologist for staging and grading (Scheuer) and graded for steatosis, which was considered moderate-severe if ≥20%. Patients underwent standard of care therapy with pegylated interferon and ribavirin. The severity of steatosis progressively increased according to sCD36 quartiles (P = 0.02); total and low-density lipoprotein (LDL) cholesterol levels were significantly higher in patients in the lower quartile compared to all the others. Gamma-glutamyl transferase (P = 0.02), homoeostasis model assessment (HOMA) score (P = 0.002) and sCD36 (P = 0.04) were independently associated with the severity of steatosis as continuous variable. Multivariate logistic regression analysis showed that HOMA (OR 1.243, 95% CI 1.04-1.484, P = 0.01) and sCD36 (OR 1.445, 95%CI 1.135-1.839, P = 0.003) were independently linked to steatosis ≥20%. No association was found between sCD36 and SVR. CD36 is linked to steatosis and insulin resistance in patients with G1 CHC, but does not predict response to treatment. The potential of sCD36 as a surrogate marker of steatosis should be further investigated.

Weight loss and clinical characteristics of young adults patients seeking treatment at medical centers: data from the QUOVADIS Study.

OBJECTIVE: To compare clinical characteristics, attrition, weight loss, and psychological changes of obese young adults and obese adults seeking treatment. MATERIALS AND METHODS: 1530 individuals seeking treatment in 18 Italian medical centers were evaluated. 382 cases (25%) were classified as young adults (age≤35 years), 1148 (75%) as adults (>35 years). Psychological distress, binge eating, body uneasiness, and attitude towards eating were evaluated, at baseline and after a 12-month weight-loss program, together with BMI changes. Weight-loss expectations and primary motivation for seeking treatment were also recorded. RESULTS: At baseline, young adults reported significantly higher BMI at age 20, weight loss expectations and body uneasiness scores than adults. A significantly higher percentage of young adults also reported improving appearance as primary reason for seeking treatment. The attrition rate was significantly larger in young adults. Among completers, the mean percent weight loss at 12 months and improvement of psychosocial variables were significantly higher in young adults than in adults. By intention to treat, BMI changes were no longer significant between groups. DISCUSSION: Obese young adults lose more weight and considerably improve psychological distress, but show a higher attrition rate after 12 months of continuous care in a real world medical setting.

TyG index, HOMA score and viral load in patients with chronic hepatitis C due to genotype 1.

The triglycerides × glucose (TyG) index is a recently proposed surrogate marker of insulin resistance (IR), calculated from fasting plasma triglyceride and glucose concentrations. We tested the host and viral factors associated with Tyg and homeostasis model assessment (HOMA) scores, comparing their associations with histological features and with sustained virological response (SVR) in patients with genotype 1 chronic hepatitis C(G1CHC). Three hundred and forty consecutive patients with G1CHC were considered. All had a liver biopsy scored by one pathologist for staging and grading (Scheuer), and graded for steatosis, which was considered moderate-severe if ≥30%. Anthropometric and metabolic measurements, including IR measured by both HOMA and TyG, were registered. By linear regression analysis, TyG was independently associated with waist circumference (WC), total cholesterol, presence of arterial hypertension, Log10 HCV-RNA and steatosis. Similarly, WC and steatosis were significantly associated with HOMA. Older age (OR, 1.036; 95%CI, 1.004-1.070, P = 0.02), higher WC (1.031; 1.004-1.060; P = 0.02) and higher TyG (11.496; 3.163-41.784; P < 0.001) were linked to moderate-to-severe steatosis (≥30%) by multiple logistic regression analysis. When TyG was replaced by HOMA-IR in the model, the latter remained significantly associated with steatosis ≥30% (1.237; 1.058-1.448; P = 0.008). Receiver operating characteristic curves showed a similar performance of TyG (AUC 0.682) and HOMA-IR (AUC 0.699) in predicting moderate-severe steatosis. No independent associations were found between both TyG and HOMA and fibrosis or SVR. In patients with G1CHC , TyG, an easy-to-calculate and low-cost surrogate marker of IR, is linked to liver steatosis and shows an independent association with viral load.

The direct economic cost of pharmacologically-treated diabetes in Italy-2006. The ARNO observatory.

AIMS/HYPOTHESIS: To estimate the prevalence and the direct cost of pharmacologically-treated diabetes in Italy. METHODS: The ARNO observatory database, containing the 20-year medical prescriptions of over 10 million Italian people, was used. Ten-year longitudinal data were available in 22 Local Health Districts (LHD). Subjects were classified as having diabetes when prescribed glucose-lowering drugs (oral agents or insulin) (311,979 individuals in 2006). The direct cost was calculated as the sum of drug use, financial compensation by LHD for the inpatient (hospital DRG) and outpatient activities (consultations, laboratory tests, radiology, etc.), all regulated by government contracts. Individuals with diabetes were compared with pharmacologically-treated subjects without diabetes, pair-matched for age, sex and general practitioner. RESULTS: In the 10-year period, the prevalence of pharmacologically-treated diabetes increased from 3.08% to 4.45% (P for trend, <0.001). The average pro capita cost totaled €2,589 in 2006 (95% confidence interval (CI), 2,584-2,594), corresponding to a rate ratio vs. no-diabetes of 1.54 (95% CI, 1.50-1.56). The cost of drugs was € 827 (rate ratio, 1.80 vs. no-diabetes; 95% CI, 1.79-1.82), that of service use, € 488 (rate ratio, 1.07 (0.93-1.25). Only 20% of the pharmaceutical cost was due to glucose-lowering drugs, a percentage stable through the years. The cost of any hospital admission, as defined by DRGs, was independent of diabetes, but the overall cost was much higher in diabetes due to much higher admission rates. Cardiovascular complications and renal failure accounted for the large majority of excess hospital cost. CONCLUSION: The direct economic burden of pharmacologically-treated diabetes on the National Health System is very high, due to the growing prevalence of disease and the cost of complications.

Metabolic syndrome in subjects at high risk for type 2 diabetes: the genetic, physiopathology and evolution of type 2 diabetes (GENFIEV) study.

BACKGROUND AND AIM: We evaluated the relationship between insulin resistance (IR) and insulin secretion with the metabolic syndrome (MS) in 885 subjects (377 men/508 women, age 49±11 years, BMI 29±5.2kgm(-2)) at risk of diabetes enrolled in the genetics, pathophysiology and evolution of type 2 diabetes (GENFIEV) study. METHODS AND RESULTS: All subjects underwent a 75-g oral glucose tolerance test (OGTT) for the estimation of plasma levels of glucose and C-peptide, as well as fasting insulin and lipid profile. IR was arbitrarily defined as HOMA-IR value above the 75th centile of normal glucose tolerance (NGT) subjects. Overall MS prevalence (National Cholesterol Treatment Panel-Adult Treatment Panel (NCEP-ATPIII) criteria) was 33%, 19% in subjects with NGT, 42% in impaired fasting glucose (IFG), 34% in impaired glucose tolerance (IGT), 74% in IFG+IGT subjects, and 56% in newly diagnosed diabetic patients. Prevalence was slightly higher with IDF criteria. MS prevalence was >50% in subjects with 2h glucose >7.8mmoll(-1), independently of fasting plasma glucose. IR prevalence was higher in subjects with MS than in those without (63% vs. 23%; p<0.0001) and increased from 54% to 73% and 88% in the presence of three, four or five traits, respectively. IR occurred in 42% of subjects with non-diabetic alterations of glucose homeostasis, being the highest in those with IFG+IGT (IFG+IGT 53%, IFG 45%, IGT 38%; p<0.0001). Individuals with MS were more IR irrespective of glucose tolerance (p<0.0001) with no difference in insulinogenic index. Hypertriglyceridaemia (OR: 3.38; Confidence Interval, CI: 2.294.99), abdominal obesity (3.26; CI: 2.18-4.89), hyperglycaemia (3.02; CI: 1.80-5.07) and hypertension (1.69; CI: 1.12-2.55) were all associated with IR. CONCLUSIONS: These results show that in subjects with altered glucose tolerance (in particular IFG+IGT) MS prevalence is high and is generally associated to IR. Some combinations of traits of MS may significantly contribute to identify subjects with IR.