Changes in markers of hepatic steatosis and fibrosis in patients with type 2 diabetes during treatment with glucagon-like peptide-1 receptor agonists. A multicenter retrospective longitudinal study.

AIMS: Metabolic dysfunction-associated fatty liver disease (MAFLD) is common in people with type 2 diabetes (T2D) and can progress to advanced fibrosis and cirrhosis. In this retrospective study, we explored the longitudinal changes in markers of hepatic steatosis and fibrosis during T2D treatment with glucagon-like peptide-1 receptor agonists (GLP-1RAs). METHODS: We analysed observational data from six diabetes outpatient clinics. In the whole T2D population, we calculated the hepatic steatosis index (HSI), which we previously validated against liver ultrasonography, and the Fibrosis (Fib)-4 index. We then identified patients who initiated a GLP-1RA from 2010 to 2018 and for whom data were available to evaluate changes in both HSI and Fib-4 scores over 24 months. RESULTS: From 83,116 outpatients with T2D, 41,302 (49.7%) had complete data for calculating HSI and Fib-4. Most of these T2D patients (∼70%) had MAFLD (defined as HSI>36), 9.7% of whom had advanced fibrosis based on Fib-4 thresholds. Patients with low compared to high risk of advanced fibrosis were 5-times more likely to be treated with GLP-1RA. In 535 patients who initiated a GLP-1RA, the prevalence of MAFLD based on HSI declined significantly at 6 and 24 months, but Fib-4 categories did not. HSI improved significantly only in patients receiving human-based but not exendin-based GLP-1RA, while patients concomitantly receiving metformin had less worsening in Fib-4 categories. CONCLUSIONS: MAFLD is very common among outpatients with T2D (∼70%) and the estimated prevalence of advanced fibrosis was ∼10%. Treatment with GLP-1RAs significantly improved MAFLD, but not MAFLD-associated advanced fibrosis.

Deintensification of basal-bolus insulin after initiation of GLP-1RA in patients with type 2 diabetes under routine care.

AIMS: We evaluated de-intensification of basal-bolus insulin (BBI) after initiation of a GLP-1 receptor agonist (GLP-1RA) under routine care. RESEARCH DESIGN AND METHODS: This retrospective, multicenter study conducted at outpatient clinics in North-East Italy collected data on patients with T2D on BBI who initiated a GLP-1RA. Patients were divided according to whether they de-intensified BBI at the end of observation by stopping prandial insulin. RESULTS: We included 425 patients with mean age of 61.3 years and 13 years of diabetes duration. Baseline HbA1c was 8.6% and BMI was 35.5 kg/m2. After 14 months. 58.6% of patients de-intensified BBI after initiating GLP-1RA: they were younger, had a shorter disease duration, lower HbA1c and insulin dose, and less frequent microangiopathy than those who continued BBI. A probability estimation based on these variables was validated in an independent cohort of 40 patients. Body weight improved in both groups, but HbA1c and fasting plasma glucose significantly declined only among patients who de-intensified BBI. Patients who de-intensified BBI and persisted on GLP-1RA at the last observation (80.7%) had greater HbA1c reductions. CONCLUSION: Under routine care, GLP-1RA initiation frequently allowed discontinuing BBI, especially among patients with shorter disease duration, lower insulin requirement, and better glucose control.

A structured therapeutic education program for children and adolescents with type 1 diabetes: an analysis of the efficacy of the "Pediatric Education for Diabetes" project.

BACKGROUND: Therapeutic education for Type 1 Diabetes involves the process of transmitting knowledge and developing the skills and behavior required to treat the disease. guidelines agree on stressing the importance of therapeutic educational intervention in teaching self-management skills to children and adolescents with Type 1 Diabetes (T1D). This study presents the results of the "Pediatric Education for Type 1 Diabetes (T1D)" (PED) project, specifically designed for children and adolescents aged 6 to 16, and structured on guidelines indications, as part of a broader clinical-educational intervention for Type 1 diabetes. METHODS: Twenty-four patients with Type 1 diabetes (mean age: 12,13 y; SD=1.48 y; range 9-14) were studied in a 12-month PED structured project followed by an educational summer camp. All the activities were designed and organized by a multidisciplinary team (dietitian, pediatric diabetologist, nurse, psychologist and adult diabetologist). Glycated hemoglobin (HbA1C), knowledge about Type 1 Diabetes (T1D) (self-monitoring and nutrition), self-management (self-monitoring, nutrition and flexibility of medical treatment), and wellbeing were used as outcome measures. RESULTS: Data suggest that the PED had a positive impact on all the targeted levels indicated for recommended care. CONCLUSIONS: The results of this study seem to confirm the effectiveness in altering the three levels of "knowing," "know-how" and "wellbeing" required to optimize the quality of life of young patients with Type 1 diabetes. In addition, the proposed model, where a pediatric diabetologist always cooperates with an adult diabetologist, seems to be a permanent solution to the transitional gap widely discussed in the literature.

MicroRNA-21/PDCD4 Proapoptotic Signaling From Circulating CD34+ Cells to Vascular Endothelial Cells: A Potential Contributor to Adverse Cardiovascular Outcomes in Patients With Critical Limb Ischemia.

OBJECTIVE: In patients with type 2 diabetes (T2D) and critical limb ischemia (CLI), migration of circulating CD34+ cells predicted cardiovascular mortality at 18 months after revascularization. This study aimed to provide long-term validation and mechanistic understanding of the biomarker. RESEARCH DESIGN AND METHODS: The association between CD34+ cell migration and cardiovascular mortality was reassessed at 6 years after revascularization. In a new series of T2D-CLI and control subjects, immuno-sorted bone marrow CD34+ cells were profiled for miRNA expression and assessed for apoptosis and angiogenesis activity. The differentially regulated miRNA-21 and its proapoptotic target, PDCD4, were titrated to verify their contribution in transferring damaging signals from CD34+ cells to endothelial cells. RESULTS: Multivariable regression analysis confirmed that CD34+ cell migration forecasts long-term cardiovascular mortality. CD34+ cells from T2D-CLI patients were more apoptotic and less proangiogenic than those from control subjects and featured miRNA-21 downregulation, modulation of several long noncoding RNAs acting as miRNA-21 sponges, and upregulation of the miRNA-21 proapoptotic target PDCD4. Silencing miR-21 in control CD34+ cells phenocopied the T2D-CLI cell behavior. In coculture, T2D-CLI CD34+ cells imprinted naive endothelial cells, increasing apoptosis, reducing network formation, and modulating the TUG1 sponge/miRNA-21/PDCD4 axis. Silencing PDCD4 or scavenging reactive oxygen species protected endothelial cells from the negative influence of T2D-CLI CD34+ cells. CONCLUSIONS: Migration of CD34+ cells predicts long-term cardiovascular mortality in T2D-CLI patients. An altered paracrine signaling conveys antiangiogenic and proapoptotic features from CD34+ cells to the endothelium. This damaging interaction may increase the risk for life-threatening complications.

Effectiveness of Dulaglutide in the Real World and in Special Populations of Type 2 Diabetic Patients.

CONTEXT: In randomized controlled trials (RCTs) on type 2 diabetes (T2D) patients, the glucagon-like peptide-1 (GLP-1) receptor agonist (GLP-RA) dulaglutide reduced HbA1c and body weight, but generalizability of such findings to real-world T2D patients is challenging. OBJECTIVE: We evaluated effectiveness of dulaglutide in routine clinical practice, especially in subgroups of patient that are underrepresented in RCTs. DESIGN: Retrospective multicenter study. SETTING: Diabetes outpatient clinics. PATIENTS AND INTERVENTION: All consecutive patients who initiated dulaglutide between 2015 and 2018. MAIN OUTCOME MEASURES: Changes in HbA1c and body weight were assessed up to 30 months after baseline. Effectiveness was analyzed in patient subgroups according to: prior use of GLP-1RA, persistence on treatment and dose, age, sex, disease duration, renal function, obesity, cardiovascular disease, or concomitant use of insulin or sulphonylurea. RESULTS: From a background population of 83,116 patients, 2084 initiated dulaglutide (15.3% switching from another GLP-1RA), 1307 of whom had at least 1 follow-up visit. Overall, dulaglutide reduced HbA1c by 1.0% and body weight by 2.9 kg at the end of observation. These effects were more pronounced in GLP-1RA-naïve patients and in those with shorter disease duration. Improvement in HbA1c was highly significant and consistent across all subgroups, including those aged ≥ 75 years, nonobese, or with chronic kidney disease. Body weight declined in all subgroups and significantly more with the 1.5-mg versus 0.75-mg dose. CONCLUSIONS: In real-world T2D patients, effectiveness of dulaglutide on HbA1c and body weight reduction was highly consistent and significant even in subgroups of patients poorly represented in RCTs.

Effectiveness of dulaglutide vs liraglutide and exenatide once-weekly. A real-world study and meta-analysis of observational studies.

INTRODUCTION AND AIM: Real-word data on the head-to-head comparisons among glucagon-like peptide-1 receptor agonists (GLP-1RA) are scant. Therefore, we aimed to compare the effectiveness of dulaglutide versus liraglutide and exenatide once weekly (exeOW) in type 2 diabetic (T2D) patients under routine care. METHODS: This was a retrospective, multicenter, real-world study on patients with T2D (aged 18-80) initiating a GLP-1RA between 2010 and 2018 at specialist outpatient clinics. We compared the effectiveness of dulaglutide versus liraglutide and exeOW on the changes in HbA1c (primary outcome), body weight, blood pressure and fasting glucose (secondary outcomes). Average follow-up was 5.9 months. Channelling biases were addressed with propensity score matching or multivariable adjustment. Meta-analyses of observational studies, covering the same comparisons, are also presented. RESULTS: 849, 1371 and 198 patients were included in the dulaglutide, liraglutide and exeOW groups, respectively. The reduction of HbA1c was greater with dulaglutide than with liraglutide (-0.24 ±â€¯0.08%; p = 0.003), and was confirmed in the meta-analysis of observational studies. In our study, dulaglutide showed similar effectiveness compared to exeOW. When these results were pooled with other observational studies, dulaglutide showed a greater reduction of HbA1c (-0.19%; p = 0.003) and body weight (-0.8 kg; p = 0.007). CONCLUSIONS: In a real-world scenario, dulaglutide reduced HbA1c more than liraglutide. Conversely, we found similar effect of dulaglutide and exeOW, with statistical differences arising solely when results were meta-analysed with those from other observational studies. Lack of up-titration for liraglutide and higher discontinuation rate for exeOW likely influenced the estimated treatment difference.

Trend 2010-2018 in the clinical use of GLP-1 receptor agonists for the treatment of type 2 diabetes in routine clinical practice: an observational study from Northeast Italy.

AIMS: Several GLP-1 receptor agonists (GLP-1RA) have become available for the treatment of type 2 diabetes (T2D), and evidence on their beneficial effects has evolved. We evaluated how the clinical phenotype of patients initiating GLP-1RA changed from 2010 to 2018. METHODS: This was a retrospective study conducted at six diabetes outpatient clinics in Northeast Italy. We collected data of T2D patients who initiated new GLP-1RA between 2010 and 2018. We recorded baseline characteristics, including demographics, anthropometrics, cardiovascular risk factors, glucose control, lipid profile, liver enzymes, renal function and concomitant medications. We recorded updated HbA1c and body weight at follow-up. RESULTS: There were 83,116 T2D patients from a general population of ~ 1,380,000 inhabitants. Among 6167 cases of GLP-1RA initiation, 5408 were analyzed after excluding intra-class switchers. Prescription of GLP-1RA increased exponentially, and the change in the type of GLP-1RA reflected waves of their entering the market. From 2010 to 2018, there were significant increases in baseline age, diabetes duration and prevalence of male sex, of cardiovascular disease and of insulin users. Blood pressure and cholesterol levels decreased concomitantly with increasing use of medications for the control of cardiovascular risk. Baseline average HbA1c (8.3% [67 mmol/mol]) and BMI (34 kg/m2) and their improvement after GLP-1RA initiation did not change over time. CONCLUSIONS: Despite the early positioning of GLP-1RA in T2D treatment algorithms, GLP-1RA have been prescribed in patients with progressively more advanced disease stage and especially in the presence of cardiovascular disease. Optimization of GLP-1RA use in routine clinical practice is still needed.

Fixed versus flexible combination of GLP-1 receptor agonists with basal insulin in type 2 diabetes: A retrospective multicentre comparative effectiveness study.

BACKGROUND AND AIMS: The combination of basal insulin (BI) and GLP-1 receptor agonists (GLP-1RAs) is a rational and effective therapy for patients with uncontrolled type 2 diabetes (T2D). We compared the effectiveness of fixed and flexible BI/GLP-1RA combinations using routinely accumulated clinical data. METHODS: This was a retrospective, multicentre, real-world study concerning T2D patients initiating a fixed or flexible BI/GLP-1RA combination (NCT03959865). The primary endpoint was change in HbA1c. Secondary endpoints were changes in body weight, fasting plasma glucose (FPG) and systolic blood pressure (SBP). Confounding was addressed by propensity score matching (PSM) or multivariable adjustment (MVA). RESULTS: A total of 609 patients were included in the study, 131 in the fixed group and 478 in the flexible group. The two groups differed in terms of diabetes duration, body weight and concomitant medications. After 5.7 months, observed HbA1c reductions were 0.6% and 0.8%, and body weight reductions were 2.8 kg and 1.2 kg in the flexible and fixed groups, respectively. Following PSM, HbA1c declined similarly in the two groups, whereas reduction in body weight was significantly in favour of the flexible combination. Findings were robust in sensitivity analyses, with the exception that, with MVA, a significantly higher reduction in HbA1c was detected in the fixed group. Final doses of BI were higher in the fixed group, whereas those of GLP-1RA were higher in the flexible group. CONCLUSIONS: In routine specialist care, initiation of the fixed or flexible BI/GLP-1RA combination allowed similar improvement in glycaemic control, but greater weight loss was observed with the flexible combination. This difference reflected dosages of BI and GLP-1RAs.

Can Nurse-Based Management Screening Ensure Adequate Outcomes in Patients With Gestational Diabetes? A Comparison of 2 Organizational Models.

BACKGROUND: Gestational diabetes mellitus (GDM) is an impaired glucose tolerance with onset or first recognition during pregnancy. The purpose of this study is to evaluate the clinical outcomes of a blood glucose monitoring protocol implemented by nurses and dietitians in a diabetes team to the previously established protocol of direct monitoring of GDM patients by a diabetologist. METHODS: Two groups of patients were formed: The first group was based on a traditional protocol (P1: 230 patients) with patients' blood glucose constantly checked by a diabetologist. In the second structured group (P2: 220 patients) patients were referred to a diabetologist only if they required insulin therapy. RESULTS: The number of medical visits (P2: 1.28 ± 0.70 vs P1: 3.27 ± 1.44; P < .001) and the percentage of patients with hypoglycemia (P2: 6.8% vs P1: 15.2%; P < .006) were found to be lower in group P2 than in group P1. In both groups, a direct relationship was found between a parental history of diabetes and the risk of GDM (odds ratio [OR]: P1 = 2.2 [1.17-4.12]; P2 = 2.5 [1.26-5.12]). In group P1, it was observed that hyperweight gain in patients who were already overweight before becoming pregnant significantly increased the risk of macrosomia (OR: 3.11 [1.39-25.7]), whereas this was not detected in patients in group P2. In group P2, a correlation was found between macrosomia and insulin therapy (OR: 0.066 vs 0.34). In group P1 and group P2, a correlation was observed between insulin therapy and a family history of diabetes (OR: 2.20 vs 2.27), and a body mass index of greater than 30 kg/m in group P2 (OR: 3.0 vs 1.47). CONCLUSIONS: The data we collected show that creating a structured protocol for GDM management reduces the number of medical visits required by patients without increasing the risk of hypoglycemia, macrosomia, or hyperweight gain during pregnancy.

Proinsulin-expressing dendritic cells in type 2 neuropathic diabetic patients with and without foot lesions.

Diabetic neuropathy is the most common complication of diabetes and is frequently associated with foot ischemia and infection, but its pathogenesis is controversial. We hypothesized that proinsulin expression in peripheral blood mononuclear cells is a process relevant to this condition and could represent a link among hyperglycemia, nerve susceptibility, and diabetic foot lesions. We assessed proinsulin expression by using flow cytometry in dendritic cells from control participants and patients with type 2 diabetes with or without peripheral neuropathy or accompanied by diabetic foot. Among 32 non-neuropathic and 120 neuropathic patients with type 2 diabetes, we performed leg electromyography and found average sensory sural nerve conduction velocities of 48 ± 4 and 30 ± 4 m/s, respectively ( P < 0.03). Of those with neuropathy, 42 were without lesions, 39 had foot lesions, and 39 had neuroischemic foot lesions (allux oximetry <30 mmHg). In this well-defined diabetic population, but not in nondiabetic participants, a progressively increasing level of peripheral blood dendritic cell proinsulin expression was detected, which directly correlated with circulating TNF-α levels ( P < 0.002) and multiple conduction velocities of leg nerves ( P < 0.05). These results are consistent with the hypothesis that, in type 2 diabetes, proinsulin-expressing blood cells, possibly via their involvement in innate immunity, may play a role in diabetic peripheral neuropathy and foot lesions.-Sambataro, M., Sambado, L., Trevisiol, E., Cacciatore, M., Furlan, A., Stefani, P. M., Seganfreddo, E., Durante, E., Conte, S., Della Bella, S., Paccagnella, A., dei Tos, A. P. Proinsulin-expressing dendritic cells in type 2 neuropathic diabetic patients with and without foot lesions.

Enteral nutrition at home and in nursing homes: an 11-year (2002-2012) epidemiological analysis.

BACKGROUND: Home enteral nutrition (HEN) is a well-established extra-hospital therapy that can reduce the risk of malnutrition, ensure the rapid discharge of patients from hospital and significantly reduce health care expenditure. The data reported in this study allow us to understand the relationships between mortality, the place of treatment either at patients' homes (PH) or in nursing homes (NHR) and nutritional status. METHODS: Patients were analyzed according to age, gender, underlying disease, the Karnofsky Index, type of enteral access device (nasogastric tube or percutaneous endoscopic gastrostomy), weight and Body Mass Index (BMI). The duration of HEN therapy was then calculated and the outcome was established on patient mortality or survival. RESULTS: Over an 11-year period, 3246 subjects were administered HEN therapy. The mean duration of HEN therapy was equal to 312±487 days at PH and 398±573 in NHR. The mean incidence is 406±58 patients/million inhabitants/year at PH and 319±44 in NHR (mean prevalence rate: 464±129 cases/million inhabitants at PH compared to 478±164 in NHR). Analysis of variance was used for continuous variables. The study reveals that >8% (8.6% at PH; 8.5% in NHR) of patients die within 10 days of starting HEN therapy. CONCLUSIONS: The study shows a progressive increase in HEN therapy and highlights clinical, organizational and ethical issues, which also need to be analyzed in relation to the progressively aging population.

Nutritional Support in Cancer Patients: A Position Paper from the Italian Society of Medical Oncology (AIOM) and the Italian Society of Artificial Nutrition and Metabolism (SINPE).

Malnutrition is a frequent problem in cancer patients, which leads to prolonged hospitalization, a higher degree of treatment-related toxicity, reduced response to cancer treatment, impaired quality of life and a worse overall prognosis. The attitude towards this issue varies considerably and many malnourished patients receive inadequate nutritional support. We reviewed available data present in the literature, together with the guidelines issued by scientific societies and health authorities, on the nutritional management of patients with cancer, in order to make suitable and concise practical recommendations for appropriate nutritional support in this patient population. Evidence from the literature suggests that nutritional screening should be performed using validated tools (the Nutritional Risk Screening 2002 [NRS 2002], the Malnutrition Universal Screening Tool [MUST], the Malnutrition Screening Tool [MST] and the Mini Nutritional Assessment [MNA]), both at diagnosis and at regular time points during the course of disease according to tumor type, stage and treatment. Patients at nutritional risk should be promptly referred for comprehensive nutritional assessment and support to clinical nutrition services or medical personnel with documented skills in clinical nutrition, specifically for cancer patients. Nutritional intervention should be actively managed and targeted for each patient; it should comprise personalized dietary counseling and/or artificial nutrition according to spontaneous food intake, tolerance and effectiveness. Nutritional support may be integrated into palliative care programs. "Alternative hypocaloric anti-cancer diets" (e.g. macrobiotic or vegan diets) should not be recommended as they may worsen nutritional status. Well-designed clinical trials are needed to further our knowledge of the nutritional support required in different care settings for cancer patients.

Sensory neuropathy hampers nociception-mediated bone marrow stem cell release in mice and patients with diabetes.

AIMS/HYPOTHESIS: Upon tissue injury, peripheral sensory neurons release nociceptive factors (e.g. substance P [SP]), which exert local and systemic actions including the recruitment of bone marrow (BM)-derived haematopoietic stem and progenitor cells (HSPCs) endowed with paracrine pro-angiogenic properties. We herein explore whether diabetic neuropathy interferes with these phenomena. METHODS: We first investigated the presence of sensory neuropathy in the BM of patients with type 2 diabetes by immunohistochemistry and morphometry analyses of nerve size and density and assessment of SP release by ELISA. We next analysed the association of sensory neuropathy with altered HSPC release under ischaemia or following direct stimulation with granulocyte colony-stimulating factor (G-CSF). BM and circulating HSPCs expressing the neurokinin 1 receptor (NK1R), which is the main SP receptor, were measured by flow cytometry. We finally assessed whether an altered modulation of SP secretion interferes with the mobilisation and homing of NK1R-HSPCs in a mouse model of type 2 diabetes after limb ischaemia (LI). RESULTS: Nociceptive fibres were reduced in the BM of patients and mice with type 2 diabetes. Patients with neuropathy showed a remarkable reduction in NK1R-HSPC mobilisation under ischaemia or upon G-CSF stimulation. Following LI, diabetic mice manifested an altered SP gradient between BM, peripheral blood and limb muscles, accompanied by a depressed recruitment of NK1R-HSPCs to the ischaemic site. CONCLUSIONS/INTERPRETATION: Sensory neuropathy translates into defective liberation and homing of reparative HSPCs. Nociceptors may represent a new target for treatment of diabetic complications.

Prognostic significance of circulating and endothelial progenitor cell markers in type 2 diabetic foot.

Objective. We studied circulating precursor cells (CPC) in type 2 diabetes mellitus (T2DM) with neuropathic foot lesions with or without critical limb ischemia and relationships between endothelial precursor cells (EPC) and peripheral neuropathy. Methods and Subjects. We measured peripheral blood CD34, CD133, and CD45 markers for CPC and KDR, CD31 markers for EPC by citofluorimetry and systemic neural nociceptor CGRP (calcitonin gene related protein) by ELISA in 8 healthy controls (C) and 62 T2DM patients: 14 with neuropathy (N), 20 with neuropathic foot lesions (N1), and 28 with neuroischemic recent revascularized (N2) foot lesions. Timing of lesions was: acute (until 6 weeks), healed, and not healed. Results. CD34+ and CD133+ were reduced in N, N1, and N2 versus C, and CD34+ were lower in N2 versus N1 (P = 0.03). In N2 CD34+KDR+ remain elevated in healed versus chronic lesions and, in N1 CD133+31+ were elevated in acute lesions. CGRP was reduced in N2 and N1 versus C (P < 0.04 versus C 26 ± 2 pg/mL). CD34+KDR+ correlated in N2 with oximetry and negatively in N1 with CGRP. Conclusions. CD34+ CPC are reduced in diabetes with advanced complications and diabetic foot. CD34+KDR+ and CD31+133+ EPC differentiation could have a prognostic and therapeutic significance in the healing process of neuropathic and neuroischemic lesions.

Home enteral feeding: analysis and improvement of organizational models.

AIM: The purpose of this study was to analyze the organizational models of home enteral feeding used in 5 local health authorities (LHAs) in the Veneto region (Italy). By comparing these models with the main guidelines, the authors have attempted to determine the "minimum standards" to be adopted at an organizational level. MATERIALS AND METHODS: This 3-stage study analyzes procedures, precoded actions, and recordable processes. Stage 1: objectives were defined, work methods selected, and reference guidelines chosen. Stage 2: flowcharts were drafted to show the actions and work paths taken for the 5 LHAs. Stage 3: flowcharts were compared with data from the literature. RESULTS: The study shows that very different organizational models exist. For instance, by comparing organizational processes with the procedures prescribed by the guidelines, it can be seen that the mean percentages of actions taken by the 5 LHAs, for patients in both rest homes and nursing homes, rarely exceeds the threshold of 50% (on a scale from 0% to 100%). CONCLUSION: This study shows that home enteral feeding is neither optimized nor uniform in the 5 LHAs and that standardized methods are not used for clinical monitoring.

Quality improvement for integrated management of patients with type 2 diabetes (PRIHTA project stage 1).

PURPOSE: The purpose of the study was to show how a different collaborative relationship with family doctors and increasingly specialized diabetologists could lead to a 50% reduction in recurrent appointments due to procedural errors and a 50% reduction in the average waiting times for a specialist medical visit. METHODS: A qualitative and quantitative definition of the problem was made using the Lean Six Sigma method: (Define); process indicators were observed that might interfere with the objectives of this study (Measure); descriptive statistics were used to confirm the validity and significance of the results (Analyze); and finally strategies were established to intervene on these variables (Improve). RESULTS: Four groups of action led to optimization of the objectives: (1) establishing clinical protocols for primary care physicians for treating hospitalized patients with type 2 diabetes and hyperglycemia; (2) increasing the autonomy of nursing care staff; (3) reorganizing the appointments booking office; and (4) making diabetes clinics more specialized. CONCLUSIONS: Thanks to this project, primary care physicians have rediscovered their role and defined their diagnostic-therapeutic function under a shared scientific protocol. The model presented in this study provides scope for reflection on the role of the diabetologist, proposing an "alternative" that concerns only the care of patients with metabolic decompensation.

Nutritional intervention for improving treatment tolerance in cancer patients.

PURPOSE OF REVIEW: This study aims to assess various types of nutritional intervention for improving treatment tolerance in patients with malnutrition related to the cancer anorexia-cachexia syndrome. RECENT FINDINGS: Malnutrition in cancer patients is associated with a poor prognosis, whereas weight loss is an important predictor of mortality. Disease and treatments have a major impact on nutritional status. By improving the latter, we can change the prognosis, quality of life and functional status, facilitating improved tolerance to treatment. Dietary counselling, recommended for patients at risk of malnutrition, should be introduced early in close collaboration with the patient. Administering oral nutritional supplements to malnourished patients has been shown to lead to a reduction in mortality, in complications and in the length of hospital stay. Supplementation with enteral nutrition has demonstrated an increase in appetite, energy intake, nutritional status and, above all, reduced gastrointestinal toxicity from cancer treatments due to a better response to them. Supplementation with home parenteral nutrition in aphagic and terminal patients has shown improved quality of life, energy balance, body composition and prolonged survival. SUMMARY: Supplementation with ω3 fatty acids appears to offer benefits that are verifiable at a biochemical, clinical and functional level. Related literature, however, provides conflicting results; therefore further studies will be required to confirm their efficacy. Supplementation with glutamine appears to support the efficacy of chemoradiotherapy treatment while reducing toxicity of the tissues and improving outcomes. Oral supplementation with branched amino acid appears to reduce the length of hospital stay, decrease morbidity and improve the quality of life, without any changes in mortality. Perioperative supplementation with arginine has shown a reduced incidence of complications and a significant increase in long-term survival.

Early nutritional intervention improves treatment tolerance and outcomes in head and neck cancer patients undergoing concurrent chemoradiotherapy.

GOALS OF WORK: Patients with head and neck cancer (HNC) undergoing chemoradiotherapy are at high risk of malnutrition, which is related to complication rate. The aim of this study was to investigate the impact of an early intensive nutritional intervention on nutritional status and outcomes in patients undergoing chemoradiotherapy for HNC. MATERIALS AND METHODS: We analysed retrospectively the clinical documentation of 33 HNC patients who were referred for early nutritional intervention (nutrition intervention group, NG) before they were submitted to chemoradiotherapy. The outcome of these patients was compared to that of 33 patients who received chemoradiotherapy without receiving a specifically designed early nutrition support programme (control group, CG). MAIN RESULTS: NG patients lost less weight during chemoradiotherapy compared to CG patients (-4.6 +/- 4.1% vs -8.1 +/- 4.8% of pre-treatment weight, p < 0.01, at the completion of treatment). Patients in the NG experienced fewer radiotherapy breaks (>5 days) for toxicity (30.3% vs 63.6%, p < 0.01); the mean number of days of radiation delayed for toxicity was 4.4 +/- 5.2 in NG vs 7.6 +/- 6.5 in CG (p < 0.05); a linear correlation was found between percentage of weight lost from baseline to chemoradiotherapy completion and days of radiation delays (p < 0.01). There were less patients who had an unplanned hospitalisation in the NG relative to the CG (16.1% vs 41.4%, p = 0.03). In the NG, symptoms having an effect on the nutritional status developed early and were present in the nearly totality of patients at chemotherapy completion; 60.6% of NG patients needed tube feeding. CONCLUSIONS: Early nutrition intervention in patients with HNC receiving chemoradiotherapy resulted in an improved treatment tolerance and fewer admissions to hospital. This result suggests that nutritional intervention must be initiated before chemoradiotherapy, and it needs to be continued after treatment completion.

Enteral nutrition in nursing home residents: a 5-year (2001-2005) epidemiological analysis.

BACKGROUND: Despite controversy and increasing use of enteral nutrition (EN) among elderly people, descriptive population-based data are scarce. The aim of this study was to evaluate the epidemiological data of nursing home residents (NHRs) who received EN in a northeast area of Italy. METHODS: All NHRs referred to our Nutrition Service for EN between 2001 and 2005 were enrolled. Data collected at EN initiation included age, gender, underlying disease, Karnofsky index, type of enteral access device, presence of pressure ulcers, weight, body mass index, and daily enteral intake. The outcomes considered were patient survival and duration of therapy. RESULTS: The 482 NHRs (130 males; 352 females) received EN. The mean incidence (cases/million population/year) and prevalence (cases/million population) were 223.4 and 279.4, respectively. An average of 6.6% of all NHRs were tube fed. EN was prescribed for the following conditions: 27.7% cerebrovascular accident, 54.6% neurodegenerative disease, 2.7% head and neck cancer, 1.2% abdominal cancer, 1.3% head trauma, 4.8% congenital disease, 7.7% other. Almost all patients had a Karnofsky index

Home enteral nutrition in adults: a five-year (2001-2005) epidemiological analysis.

BACKGROUND: In the last twenty years Home Enteral Nutrition (HEN) has undergone considerable development and has determined economic and organisational changes. The aim of this study is to evaluate the epidemiological data of 655 patients treated in the five-year period (2001-2005) in an area in the North-East of Italy. METHODS: The following data were analysed at the initiation of HEN: age, sex, pathology, Karnofsky index, type of enteral access device, presence of pressure ulcers, weight, body mass index, haematochemical tests, daily enteral intake. Length of therapy and patient survival were then considered. The outcome was based on patient mortality and the patient's ability to resume oral nutrition. RESULTS: HEN was prescribed for the following pathologies: 26.7% neurovascular, 40.9% neurodegenerative, 11.5% head-neck cancer, 9.8% abdominal cancer, 1.5% head injury, 2.6% congenital anomaly, 7.0% other pathologies. Before commencement of enteral feeding an average of 22.9% weight loss from past weight was observed across all indications for HEN. Mean incidence (cases/10(6) inhabitants/year) and prevalence (cases/10(6) inhabitants) were respectively 308.7 (range 80.7-355.6) and 379.8 (range 138.7-534.6). The median length of HEN was 196 days; only 7.9% of patients resumed oral nutrition. The median survival rate was 9.1 months and resulted influenced by age (Odds ratio: 1.80; 95% Confidence Interval: 1.19-2.72), sex (0.22; 0.08-0.59), and Karnofsky index (0.65; 0.43-0.97). Resumption of oral nutrition was influenced by age (0.50; 0.36-0.68), sex (2.50; 1.23-5.06), Karnofsky index (1.55; 1.15-2.10) and type of enteral access device (0.44; 0.26-0.76). CONCLUSIONS: Efficient organisation means being able to look after a greater number of patients undergoing HEN, raising awareness regarding the nutritional treatment.