bluuebunny/crossref_metadata_2025_split huggingface dataset:
Persistent C-Peptide Levels and Proliferative Retinopathy in Childhood-Onset Type 1 Diabetes (T1D)
Authors: WILLIAMS KATHERINE , COSTACOU TINA , BECKER DOROTHY J. , ORCHARD TREVOR J. 
Published: June 2018

Persistent C-peptide levels may protect against complications in T1D. To test this hypothesis, 185 subjects from the Pittsburgh Epidemiology of Diabetes Complications (EDC) study, a 30-year prospective study of childhood onset (&lt;17 years) T1D, had serum C-peptide levels measured by Mercodia ultra-sensitive ELISA at their 25 year exam. Eighteen (9.7%) subjects had detectable C-peptide levels. Those with and without detectable C-peptide did not differ in age (51.8 vs. 51.1 years, p=0.70), age of onset (9.7 vs. 8.1 years, p=0.12), diabetes duration (42.1 vs. 43.0 years, p=0.61), or HbA1c at either baseline (8.1 vs. 8.5%, p=0.22) or 25 years (7.8 vs. 7.8%, p=0.91). In those with detectable C-peptide, non-HDL cholesterol levels were lower at baseline (104.4 vs. 124.1 mg/dl, p=0.01), but not 25 years (112.6 vs. 119.5 mg/dl, p=0.44) and pump use was marginally lower at 25 years (31.2% vs. 55.3%, p=0.07). Proliferative retinopathy was lower in those with detectable C-peptide levels (33.5% vs. 55.1%, p=0.08) and this difference remained marginally significant (p=0.08) after controlling for duration of T1D, HbA1c and non-HDL cholesterol. No significant differences in overt nephropathy (5.6% vs. 22.7%, p=0.13), peripheral neuropathy (61.1% vs. 77.2%, p=0.15), or renal failure (0 vs. 4.2%, p=1.00) were found between the two groups when analyzed separately. When those with either retinopathy or nephropathy were combined, those with detectable C-peptide levels had lower rates of these complications (33.3% vs. 58.1%, p=0.045). This association remained significant in logistic regression after controlling for duration of diabetes and HbA1c with a statistically significant odds ratio 0.39 (95% CI: 0.08-0.94). When those with neuropathy were added to the overall microvascular complication group, no significant differences were found (p=0.13). These findings are consistent with the hypothesis that proliferative retinopathy and possibly nephropathy in T1D may be influenced by persistent C-peptide secretion.

Disclosure
K. Williams: None. T. Costacou: None. D.J. Becker: None. T.J. Orchard: None.
Impact of Vitamin B6 Intake on the Risk of Diabetic Retinopathy—Analysis from Multicenter Prospective Study of Japanese Patients with Type 2 Diabetes
Authors: HORIKAWA CHIKA , AIDA REI , TANAKA SHIRO , YOSHIMURA YUKIO , KAWASAKI RYO , MORIYA TATSUMI , ARAKI ATSUSHI , SONE HIROHITO 
Published: June 2018

Vitamin B6 has been expected to prevent the progression of diabetic retinopathy. Previous studies reported that treatment with vitamin B6 protected against capillary dropout in a mouse model of diabetes and low serum vitamin B6 levels were associated with retinal vein occlusion in healthy individuals. However, data on this topic in patients with diabetes are sparse. As part of a nationwide cohort study we investigated the relationship between vitamin B6 intake and the incidence of diabetic retinopathy in Japanese patients with type 2 diabetes aged 40-70 years with HbA1c≥6.5%. The present analysis was conducted among 22Japanese patients with type 2 diabetes from outpatient clinics in 59 university and general hospitals in Japan. Analyzed were 1516 responders to a baseline dietary survey assessed by the Food Frequency Questionnaire based on food groups. Primary outcome was the 8-year risk of a diabetic retinopathy event. Cox regression analyses estimated hazard ratios (HRs) for dietary intake adjusted for age, gender, body mass index, HbA1c, smoking, energy intake, and other confounders. Mean vitamin B6 intake in quartiles ranged from 0.9 to 2.0 mg/day and half of participants had vitamin B6 intake less than the recommended dietary allowance according to dietary reference intakes in Japan (males 1.4 mg/day; females 1.2 mg/day). Patients in higher quartiles included those with significantly high energy, vegetable, meat and fish intakes (p for trend&lt; 0.01, &lt; 0.01, &lt; 0.01, and &lt; 0.01, respectively). After adjusting for confounders, hazard ratios for diabetic retinopathy in the 2nd, 3rd, and 4th quartiles of vitamin B6 intake compared with the 1st quartile were 1.2 (95% confidence interval 0.8-1.7, p=0.36), 0.9 (0.6-1.3, p=0.51), and 0.51 (0.31-0.88, p=0.01), respectively. We clarified that the decreased incidence of diabetic retinopathy in Japanese patients with type 2 diabetes was associated with high vitamin B6 intake.

Disclosure
C. Horikawa: None. R. Aida: None. S. Tanaka: None. Y. Yoshimura: None. R. Kawasaki: None. T. Moriya: None. A. Araki: None. H. Sone: Research Support; Self; Novo Nordisk Inc., Eli Lilly and Company, MSD K.K., Chugai Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Development Center Asia, Pte. Ltd., Daiichi Sankyo Company, Limited, Ono Pharmaceutical Co., Ltd., Kyowa Hakko Kirin Co., Ltd., Sanofi, Kowa Pharmaceuticals America, Inc., Eisai Inc..
Knowledge, Attitudes, and Practices Related to Diabetes Eye Complications among Diabetes Mellitus Patients at a Referral Hospital in Zimbabwe
Authors: SITHOLE MELLISA , MATIMBA ALICE , WOODWARD RICHMOND 
Published: June 2018

Information related to knowledge, attitudes, and practices of people with diabetes is especially important in resource-limited settings such as Zimbabwe, where medications to treat diabetes are costly and capacity to treat complications is limited, making observance of appropriate self-care practices that may delay or prevent complications vital to patient and public health. As a start to understanding the level of knowledge of diabetes eye complications, attitudes towards self-care practices, and utilization of available health care resources among diabetes patients, we conducted face-to-face interviews with 189 diabetes patients (133 female, 56 male, mean age 62.7 years) attending a referral hospital in Zimbabwe’s second largest city. A structured questionnaire was administered to each patient to document knowledge, attitudes, and practices that had 13, 11, and 12 questions in each section respectively. Knowledge results revealed the total knowledge score of diabetes and associated eye complications is associated with patients' self-report of seeing clearly or not, indicating patients not seeing all the time have a higher score then patients self-reporting they do see clearly all the time, x2=24.5815, df=11, p=0.0105. Attitude results revealed 74% of participants viewed consulting a pharmacist as a very important health care step compared to 96% who viewed consulting a physician as a very important health care step. Results indicating patients with diabetes who see clearly have less knowledge about diabetes and related eye complications suggests that reinforcing self-care steps should be directed towards this group. At the same time, patient attitude results suggest this gap could be filled by emphasizing the role of pharmacists in fostering good diabetes self-care practices and providing education for individuals with diabetes, especially early in the course of disease before vision impairment may occur.

Disclosure
M. Sithole: None. A. Matimba: None. R. Woodward: None.
A Whole-Grain Diet Confers Metabolic Advantages in Glucose Metabolism Compared to a Macronutrient-Matched, Refined-Grain Diet
Authors: MEY JACOB T. , HARI ADITHYA , GODIN JEAN-PHILIPPE , ROSS ALASTAIR , KIRWAN JOHN P. 
Published: June 2018

Observational studies suggest diets high in whole grains (WG) may confer metabolic benefits over diets based on refined grains (RG) for overweight/obese individuals, thus preventing the development of type 2 diabetes (T2D). However clinical data have been inconclusive, in part due to metabolic heterogeneity. Therefore, we investigated a WG and RG diet in individuals at high risk (HR) or low risk (LR) of developing T2D based on 1 hour glycemic level during an OGTT (oral glucose tolerance test). We conducted a double-blind randomized crossover trial in 15 overweight/obese adults. Participants were administered a 4 hour, 75g OGTT and stratified as HR or LR of developing T2D (HR: 1 hour OGTT glucose (GLU) ≥155 mg/dl; LR: 1 hour OGTT GLU &lt;155 mg/dl). Isocaloric WG and RG diets were provided for two 8 week periods with 10 week washout. Macronutrients were matched except for WG or RG (50g/1000 kcal). Fifteen subjects completed the trial, 10 HR (38±3 years, 33±2 kg/m2, 1 hour OGTT GLU 201±8 mg/dl) and 5 LR (38±4 years, 35±2 kg/m2, 1 hour OGTT GLU 126±5 mg/dl). Groups differed only by 1 hour OGTT (p&lt;0.05). Weight loss was similar but only HR reached statistical significance (-2.1 kg, p&lt;0.05). HR-WG improved insulin sensitivity (Matsuda Index, +21%, p&lt;0.05). Further, HR-RG had a significant negative association between change in BMI and Matsuda Index vs. WG (r2=0.41, p&lt;0.01). LR-RG reduced GLU clearance (iAUC 180 minutes, +27%, p&lt;0.05 vs. WG). In agreement, LR-RG increased OGTT insulin (iAUC p&lt;0.05 at 120, 180 and 240 minutes) and c-peptide (iAUC p&lt;0.05 at 60 and 120 minutes). Interestingly, 1 hour OGTT GLU predicted change in waist circumference in WG (n=15, r2=0.36, p=0.02), suggesting those with more impaired GLU tolerance may acquire greater benefit from WG. We observed differential effects of a WG and RG diet in overweight/obese adults. These data suggest a WG diet may improve measures of glucose metabolism in individuals at high risk of developing T2D, whereas a RG diet may impair glucose metabolism in lower risk individuals.

Disclosure
J.T. Mey: None. A. Hari: None. J. Godin: Employee; Self; Nestlé. Employee; Spouse/Partner; Nestlé. A. Ross: None. J.P. Kirwan: None.
Ranibizumab-Induced Diabetic Retinopathy Improvement—Results from Patients at High Risk for Vision Loss in RIDE/RISE and Protocol S
Authors: HERSHBERGER VRINDA , HILL LAUREN F. , TUOMI LISA L. , GHANEKAR AVANTI 
Published: June 2018

Purpose: To examine diabetic retinopathy (DR) outcomes in patients (pts) at high risk for negative outcomes using data from RIDE/RISE and Protocol S. In RIDE/RISE, pts with moderately severe to severe nonproliferative DR (NPDR) at baseline were assessed due to their high risk for progression to proliferative disease (ETDRS Report 12. Ophthalmology. 1991). In Protocol S, the majority of pts had proliferative DR (PDR) at baseline, which is associated with vision loss (Moss. Ophthalmology. 1998), and DR outcomes were assessed according to diabetic macular edema (DME) status at baseline.
Methods: In the randomized phase 3 RIDE (NCT00473382)/RISE (NCT00473330) studies, pts with DME (N = 759) received monthly ranibizumab (RBZ) (0.3 mg or 0.5 mg) or sham treatment through the month (M) 24 primary end point. In the randomized phase 3 Protocol S (NCT01489189) study, eyes with and without DME received either prompt pan-retinal photocoagulation or RBZ 0.5 mg (as needed after 3 monthly treatments) (N = 394 eyes). M24 DR outcomes are retrospectively evaluated herein.
Results: In RIDE/RISE, ∼ 30% of pts in each arm had high-risk NPDR at baseline (DR severity level 47/53) (35.9%, 30.0%, and 33.9% for RBZ 0.3 mg, RBZ 0.5 mg, and sham, respectively). A significant majority of these pts (78.4% and 81.1% of RBZ 0.3 mg- and 0.5 mg-treated, respectively) achieved ≥ 2-step DR improvement at M24 vs. only 11.6% of sham-treated pts (P &lt; .0001). Notably, these rates of ≥ 2-step DR improvement with RBZ were more than 2 times higher than the overall population at M24 (37.2% and 35.9% for RBZ 0.3 mg and 0.5 mg, respectively) (Ip. Arch Ophthalmol. 2012). In Protocol S, 87% of eyes had PDR and 22% of eyes had DME at baseline. At M24, RBZ treatment resulted in ≥ 2-step DR improvement in eyes with (58.5%) and without (37.8%) DME at baseline.
Conclusions: RBZ treatment was effective at significantly improving DR in pts at high risk for DR-related vision loss, irrespective of baseline DME status.

Disclosure
V. Hershberger: None. L.F. Hill: Employee; Self; Genentech, Inc. L.L. Tuomi: Employee; Self; Genentech, Inc. A. Ghanekar: Employee; Self; Roche Pharma. Stock/Shareholder; Self; Roche Pharma.
Association between Metabolic Syndrome Components and Indices of Liver Steatosis and Stiffness by Transient Elastography in Patients with Type 2 Diabetes and Imaging-Confirmed Nonalcoholic Fatty Liver Disease
Authors: HUANG ZHIMIN , LEE CHI HO , FONG HO YI , LAM KAREN S. 
Published: June 2018

Background and Aims: The index of liver steatosis, controlled attenuation parameter (CAP), is a relatively new introduction to Fibroscan, an established equipment for assessing liver fibrosis, in terms of liver stiffness measurement (LSM). The relationship between CAP and/or LSM and metabolic syndrome components in diabetic patients with nonalcoholic fatty liver disease (NAFLD) was unclear, and was addressed in this study.
Methods: A total of 224 patients with type 2 diabetes and NAFLD confirmed by ultrasonography were recruited. Anthropometric and serum biochemical parameters were collected. CAP and LSM were measured using transient elastography. The association between metabolic syndrome components and values of CAP and LSM was analyzed.
Results: The mean age of the patients was 57.9±10.2 years, their BMI was28.6± 5.5kg/m2, and the duration of diabetes was 16.6±8.3 years. Eighty-eight percent of the patients had hypertension, and 79.5% were on lipid-lowering drugs. The mean CAP was 309.3±57.9 dB/m, and median LSM was 7.9 (5.7, 10.4) kpa. There were significant rising trends in BMI, waist circumference, waist to hip ratio, white blood cell count, HbA1c, FPG, triglyceride, ALT, AST and LSM with escalating CAP tertiles, whereas age, HDL-c, AST/ALT ratio and plasma adiponectin decreased concomitantly (all p&lt;0.05). There was a larger number of metabolic syndrome components clustering in the third as compared to the first tertile of CAP (p=0.027) and LSM (p=0.035). On the other hand, with an increasing number of metabolic syndrome components, the value of CAP (p=0.001) and LSM (p=0.025) increased accordingly.
Conclusion: CAP and LSM measured by transient elastography had a strong correlation with the clustering of metabolic syndrome components in NAFLD, even in patients with long-standing type 2 diabetes.

Disclosure
Z. Huang: None. C. Lee: None. H. Fong: None. K.S. Lam: None.
Reduction of Diabetes and Cardiovascular Risk in a Workforce after Digital Behavioral Counseling
Authors: BIRSE CHARLES E. , LAGIER ROBERT J. , CHEW PAUL , JASIK CAROLYN B. , MADERO ERICA N. 
Published: June 2018

Background: We asked whether the integration of digital behavioral counseling with employer-sponsored annual biometric screening could reduce the risk of obesity-related chronic disease in a U.S. workforce.
Methods: We evaluated a cohort (n=113) who participated in an employer-sponsored annual wellness program with year-end biometric screening and enrolled in a digital behavioral counseling program. Individuals were included in the analysis if they participated in the wellness program in 2015, had prediabetes (fasting glucose (FG) 100 to 125mg/dL or Hb1Ac 5.7 to 6.4%) and a BMI ≥25 kg/m2 in 2016, and agreed to participate in a digital behavioral counseling program followed by year-end biometric screening in 2017.
Results: The participants were 75% women and 61% Caucasian, 28% African American. At the 2016 year-end biometric screening, which preceded digital behavioral counseling, the characteristics of the cohort (mean± sd) were age, 50.0±9.9 years; BMI, 37.1±8.6 kg/m2; Hb1Ac, 6.1±0.6%; and FG, 106.9±24.2 mg/dL. Following behavioral counseling, 28% of the participants lost 5% or more of body weight. Hb1Ac and FG levels both fell below prediabetic thresholds for 32% of the participants. Other biometric outcome measures improved (Table).
Conclusions: Digital behavioral counseling was effective in reducing risk for both diabetes and cardiovascular disease in a workforce cohort.Change in annual biometric screening resultsThe year preceding counseling (2015 to 2016)The year counseling received (2016 to 2017)P value (paired t-Test)BMI (kg/m2)+0.66-1.18&lt;0.0001Hb1Ac (%)+0.06-0.220.001Fasting Glucose (mg/dL)+5.85-2.840.02Triglycerides (mg/dL)+12.0-17.20.0110-year ASCVD risk* (%)+1.83-0.480.01*Atherosclerotic Cardiovascular Disease risk (2013 ACC/AHA Cardiovascular Risk Guideline)

Disclosure
C.E. Birse: Employee; Self; Quest Diagnostics. Stock/Shareholder; Self; Quest Diagnostics. R.J. Lagier: Employee; Self; Quest Diagnostics. P. Chew: Employee; Self; Omada Health, Inc. C.B. Jasik: Employee; Self; Omada Health, Inc. E.N. Madero: Employee; Self; Omada Health, Inc..
ApoC-III Levels Correlate with Insulin Resistance and HbA1c in Familial Partial Lipodystrophy—Observations from the Broaden Study
Authors: MERAL RASIMCAN , DIGENIO ANDRES , NEIDERT ADAM H. , TAMI JOSEPH , ORAL ELIF A. ,   ON BEHALF OF THE BROADEN STUDY INVESTIGATORS
Published: June 2018

Familial Partial Lipodystrophy (FPLD) is a rare genetic disorder with selective loss of adipose tissue from the periphery with an increase in ectopic fat leading to severe hepatic insulin resistance, and hypertriglyceridemia. ApoC-III is a secreted liver glycoprotein associated with hypertriglyceridemia and insulin resistance. We inquired the relationship between lipid and other metabolic parameters with morphometric characteristics (including those of ectopic fat deposition) and circulating apoC-III levels in a cohort of FPLD patients who were screened for enrollment into the BROADEN study, a global trial to study efficacy of volanesorsen (an antisense mRNA apoC-III inhibitor). 28 patients are included in these analyses (age range, 28 to 65, mean 45 years; M/F, 7/21; all but one Caucasian). Table 1 shows the significant relationships observed using linear regression analyses between circulating ApoC-III levels and investigated parameters. These results reiterate the tight relationship between triglyceride levels and ApoC-III levels, and further demonstrate that circulating ApoC-III levels also correlate with insulin resistance, and HbA1c as well as important left ventricle morphometric parameters. It is plausible to hypothesize that a strategy to lower apoC-III levels may have additional benefits beyond lowering triglyceride levels.Table 1: Relationship of metabolic and echocardiogram parameters in FPLDParametersR2p-valuenParametersR2p-valuenTriglycerides* vs. ApoC-III0.63&lt;0.00128LV end systolic diameter vs ApoC-III0.260.02719HOMA-IR* vs. ApoC-III0.190.01928LV end systolic diameter vs Triglycerides*0.250.03119HOMA-IR* vs. Triglycerides*0.150.04228Left ventricle outflow tract dimension vs ApoC-III0.220.04519Insulin* vs. ApoC-III0.140.04528Left ventricle outflow tract dimension vs Triglycerides*0.290.01719HbA1c** vs. ApoC-III0.230.03021* Parameter log-transformed**Subjects with HbA1c&lt;6.4% excluded

Disclosure
R. Meral: None. A. Digenio: Employee; Self; Akcea Therapeutics. A.H. Neidert: None. J. Tami: Employee; Self; Ionis Pharmaceuticals, Inc.. Stock/Shareholder; Self; Ionis Pharmaceuticals, Inc. E.A. Oral: Advisory Panel; Self; Aegerion Pharmaceuticals. Research Support; Self; Aegerion Pharmaceuticals, Akcea Therapeutics. Advisory Panel; Self; Akcea Therapeutics. Research Support; Self; Ionis Pharmaceuticals, Inc., AstraZeneca. Other Relationship; Self; Aegerion Pharmaceuticals.
Analysis of the Association between PCSK9 Levels and Plasma Lipid Levels in Cameroonians with Type 2 Diabetes
Authors: CAMILLE B.M. , MBACHAM WILFRED F. , SOBNGWI EUGÈNE , MBANYA JEAN CLAUDE 
Published: June 2018

Studies have shown that intensive LDL-lowering therapy results in a significant reduction in cardiovascular disease (CVD) risk and improved outcomes. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key regulator of LDL cholesterol (LDL-C) and an independent CVD risk marker. PCSK9 has additionally been related to CRP which is also a CVD risk marker. The emerging importance of the inhibition of PCSK9 for the treatment of hypercholesterolemia warrants investigations in different populations. This is the first study evaluating the association between PCSK9 and plasma lipid levels in Sub-Saharan Africa.
A Cross sectional analysis was conducted at a major hospital in Yaound9, Cameroon in a cohort of 82 participants (53% females) with median age of 51[42-58] years. There were 28 non-obese type 2 diabetes (T2D) patients with median known duration of diabetes of 3.08[1.06-6.50] years, matched for age and sex to 28 obese nondiabetic and 26 lean nondiabetic subjects. Serum PCSK9 levels were measured using sandwich ELISA method. PCSK9 and hs-CRP levels were significantly higher in obese and T2D subjects relative to the lean controls (p&lt;0.001 and p =0.0respectively). BMI was an independent predictor for PCSK9 and hs-CRP levels and this association remained after adjustment for potential confounders. Lean female subjects had significantly higher PCSK9 levels than males (p=0.004) and positive correlation of PCSK9 with LDL-C and total cholesterol (r=0.4, p=0.048 and r=0.5, p=0.039 respectively). An association was not found between PCSK9 and plasma lipid levels in obese and type 2 diabetes subjects nor was it found between PCSK9 and hs-CRP.
Obese and type 2 diabetes subjects have higher PCSK9 and hs-CRP levels when compared to lean controls, suggesting that these metabolic states potentially impact PCSK9 levels in Cameroonian patients.

Disclosure
C.B.M. Mba: None. W.F. Mbacham: None. E. Sobngwi: None. J. Mbanya: Advisory Panel; Self; GlaxoSmithKline plc.. Speaker's Bureau; Self; Novo Nordisk A/S, Sanofi, Servier.
Gender and Risk of Cardiovascular Events in Patients with Diabetic Foot
Authors: ANICHINI ROBERTO , POLICARDO LAURA , FRANCESCONI PAOLO , FRANCIA PIERGIORGIO , DE BELLIS ALESSANDRA , GULISANO MASSIMO , SEGHIERI GIUSEPPE 
Published: June 2018

In patients with diabetic foot (DF) the risk of developing cardiovascular events or renal failure is strongly increased. While DF is more frequent in males, it is yet unknown if there is a gender difference about cardiovascular events or renal failure incidence in patients with diabetic foot. The aim of this study was to evaluate the risk of hospitalization for cardiovascular events (ASCVD: heart attack, ischemic stroke or heart failure) or chronic renal failure (CKD), stratified by gender, in a population of diabetic patients living in Tuscany from 2012 to 2016. On the basis of administrative data bases, patients living in Tuscany at the 1st of January 2012 were divided into 2 subgroups: patients previously hospitalized for diabetic foot (ulcers, infections, major or minor amputations, gangrene or Charcot foot) and patients without history of hospitalization for diabetic foot. Data were collected from the regional hospitalization registry, and in the two groups the risk of developing ASCVD or CKD by the Cox regression corrected by age and comorbidities (Charlson Index of previous hospitalizations) separately in males and females was evaluated. 240238 patients with diabetes (121442 males, 118796 females) were identified. After the corrections made by age, sex and Charlson index, males showed a major risk of developing diabetic foot (DF): Odds Ratio (OR):2.018 (95% CI:1.901-2.141); p&lt;0.0001.The corrected risk of hospitalization for ASCVD and CKD in patients with previous diagnosis of DF was higher in females [Hazard Ratio (HR):1.647 (1.470-1838)] than in males (HR:1.458 (1.348-1.574); p=0,04. In the population investigated, the risk of hospitalization for DF was two time higher in males, while, the risk of hospitalization for ASCVD corrected by confounding factors, in patients previously hospitalized for DF, was significantly higher in females.

Disclosure
R. Anichini: Advisory Panel; Self; Abbott. Speaker's Bureau; Self; Novartis Pharmaceuticals Corporation, Boehringer Ingelheim GmbH. Advisory Panel; Self; Eli Lilly and Company, AstraZeneca. Speaker's Bureau; Self; Merck & Co., Inc., Takeda Development Centre Europe Ltd.. Advisory Panel; Self; Sanofi, Janssen Pharmaceuticals, Inc.. Research Support; Self; Grünenthal Group. L. Policardo: None. P. Francesconi: None. P. Francia: None. A. de Bellis: Speaker's Bureau; Self; Eli Lilly and Company, AstraZeneca, Novo Nordisk A/S. Research Support; Self; Grünenthal Group. M. Gulisano: None. G. Seghieri: None.