Author: "Roberto Miccoli" / Language: english - Searchworks@Jio Institute Digital Library Search Results

46 results on '"Roberto Miccoli"'

1. Efficacy of Dulaglutide in a Patient With Type 2 Diabetes, High Cardiovascular Risk, and HIV: A Case Report

Author: Angela Dardano, Michele Aragona, Giuseppe Daniele, Roberto Miccoli, and Stefano Del Prato
Subjects: case report, GLP-1 receptor agonist, dulaglutide, type 2 diabetes, ASCVD, HIV infection, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract: BackgroundType 2 diabetes (T2D) is a common comorbidity in people living with HIV (PLWH). Anti-hyperglycemic treatment in PLWH is still a challenge, and no randomized controlled studies using new glucose-lowering agents are currently available.Case DescriptionA 55-year-old-women was admitted to our Diabetes Unit because of hyperosmolar hyperglycemic state (HHS) and sepsis. The medical history included HIV infection and insulin-treated diabetes. On clinical examination, the lady appeared dehydrated with dry buccal mucosa, tachycardia, altered mental status, genital infection, and fever. On admission, plasma glucose was 54.5 mmol/L, HbA1c 155 mmol/mol, osmolarity 389.4 mOsm/kg, bicarbonate 24.6 mmol/L with no detectable serum ketones. The patient was treated with i.v. fluid and insulin, and antibiotic therapy commenced. Upon HHS and sepsis resolution, a basal-bolus insulin therapy was implemented that was followed by significant improvement of daily glucose profiles and progressive reduction of insulin requirement until complete discontinuation. A low dose of metformin plus linagliptin was started. Since a severe atherosclerotic disease was diagnosed, a GLP-1 receptor agonist, dulaglutide, was added to metformin upon linagliptin withdrawal with maintenance of good glycemic control, treatment adherence and amelioration of quality of life and no side effects.ConclusionThis case suggests that GLP-1 receptor agonist therapy may be effective and safe for treatment of T2D with high cardiovascular risk in PLWH, supporting the need of clinical trials directly assessing the safety and the efficacy of GLP-1 receptor agonist in these individuals.
Published: 2022
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2. Breaking Therapeutic Inertia With Alirocumab in an 80-Year-Old Patient With Severe Hypercholesterolemia: A Case Report

Author: Angela Dardano, Giuseppe Daniele, Giuseppe Penno, Roberto Miccoli, and Stefano Del Prato
Subjects: LDL cholesterol, PCSK9 inhibitors, alirocumab, elderly, case report, therapeutic inertia, Medicine (General), R5-920
Abstract: Background: Therapeutic inertia, defined as the failure to initiate or intensify therapy in a timely manner as per evidence-based clinical guidelines, is an important barrier limiting optimal care in the elderly. Therefore, overcoming therapeutic inertia is the core challenge when dealing with geriatric patients.Case Description: The patient was an 80-year-old man that attended our Outpatient Lipid Clinic (Pisa University Hospital) because of persistent high LDL cholesterol (LDLc) levels in a setting of a statin contraindication. He underwent five percutaneous coronary angioplasties with drug-eluting stents. In 2014, upon starting treatment with rosuvastatin for LDLc level of 7.59 mmol/L, the patient was admitted to the Emergency Room for a presumptive diagnosis of rhabdomyolysis (creatine kinase 6685 U/L) secondary to statin. Patient developed acute kidney injury treated with dialysis. After resolution, he was discharged with ezetimibe (10 mg daily). This treatment however failed to effectively reduce LDLc levels that ranged between 5.9 and 6.6 mmol/L for the ensuing 4-years. In 2018, at the time of our evaluation, in consideration of the age, we performed a comprehensive geriatric assessment that showed good functional and mental status supporting a reliable treatment with a proprotein convertase subtilisin–kexin type 9 inhibitor. Therefore, alirocumab was prescribed as add-on to ezetimibe. At 24-month follow-up, the geriatric assessment showed no significant changes, and alirocumab was well-tolerated. LDLc was 82% lower as compared to baseline values (from 6.6 to 1.2 mmol/L).Conclusions: This report describes a case of therapeutic inertia despite a very high-risk profile. It is also instrumental in highlightening that appropriate intensification of therapy in an elderly patient at high cardiovascular risk, by means of a patient-centered approach, may allow reaching therapeutic targets and overcoming the condition of therapeutic inertia.
Published: 2021
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3. Microvascular complications burden (nephropathy, retinopathy and peripheral polyneuropathy) affects risk of major vascular events and all-cause mortality in type 1 diabetes: a 10-year follow-up study

Author: Monia Garofolo, Elisa Gualdani, Rosa Giannarelli, Michele Aragona, Fabrizio Campi, Daniela Lucchesi, Giuseppe Daniele, Roberto Miccoli, Paolo Francesconi, Stefano Del Prato, and Giuseppe Penno
Subjects: Type 1 diabetes mellitus, Microvascular complications, Microvascular burden, Diabetic kidney disease, Diabetic retinopathy, Peripheral diabetic polyneuropathy, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Abstract Background Microvascular complications (MC) have been claimed to increase the risk for cardiovascular disease in diabetic subjects. However, the effect of MC burden on the risk of major vascular outcomes and all-cause mortality in type 1 diabetes is still poorly explored. We evaluated the relationship between microvascular complications burden and incidence of major cardiovascular events and all-cause mortality in subjects with type 1 diabetes. Methods We recruited 774 participants with type 1 diabetes in a single-center observational study over a follow-up of 10.8 ± 2.5 years. Hazard ratios (HR) for cardiovascular outcomes and all-cause death associated with microvascular complications were determined by unadjusted and adjusted Cox regression analysis. Results Out of 774 individuals, 54.9% had no-MC, 32.3% 1 MC, 9.7% 2 MC and 3.1% 3 MC. A total of 54 deaths (7.0%) occurred. Death rate increased from no-MC 2.1% (Ref) to 1 MC 7.2% (HR 3.54 [95% CI 1.59–7.87]), 2 MC 14.7% (HR 6.41 [95% CI 2.65–15.49]) and 3 MC 66.7% (HR 41.73 [95% CI 18.42–94.57], p
Published: 2019
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4. Clinical burden of diabetes in Italy in 2018: a look at a systemic disease from the ARNO Diabetes Observatory

Author: Gian Paolo Fadini, Enzo Bonora, Nello Martini, Salvatore Cataudella, Roberto Miccoli, Olga Vaccaro, and Elisa Rossi
Subjects: Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract: Introduction Diabetes is a highly prevalent disease worldwide and represents a challenge for patients and healthcare systems. This population-based study evaluated diabetes burden in Italy in 2018 by assessing all aspects of outpatient and hospital care.Research design and methods We investigated data of 11 300 750 residents in local health districts contributing to ARNO Diabetes Observatory (~20% of Italian inhabitants). All administrative healthcare claims were analyzed to gather information on access to medical resources. Subjects with diabetes, identified by antihyperglycemic drug prescriptions, disease-specific copayment exemption and hospital discharge codes, were compared with age, sex and residency-matched non-diabetic individuals.Results We identified 697 208 subjects with ascertained diabetes, yielding a prevalence of 6.2% (6.5% in men vs 5.9% in women, p2-fold higher in subjects with diabetes, mainly driven by hospitalizations and outpatient care related to chronic complications rather than to glucose-lowering drugs, diabetes-specific devices, or metabolic monitoring.Conclusions The burden of diabetes in Italy is particularly heavy and, as a systemic disease, it includes all aspects of clinical medicine, with consequent high expenses in all areas of healthcare.
Published: 2020
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5. Nesidioblastosis and Insulinoma: A Rare Coexistence and a Therapeutic Challenge

Author: Angela Dardano, Giuseppe Daniele, Roberto Lupi, Niccolò Napoli, Daniela Campani, Ugo Boggi, Stefano Del Prato, and Roberto Miccoli
Subjects: persistent hyperinsulinemic hypoglycemia, adult-onset β-cell nesidioblastosis, insulinoma, surgery, management, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract: Background: Nesidioblastosis and insulinoma are disorders of the endocrine pancreas causing endogenous hyperinsulinemic hypoglycemia. Their coexistence is very unusual and treatment represents a still unresolved dilemma.Case Description: The patient was a 43-year-old Caucasian woman, with a 2-year history of repeated severe hypoglycemic events. The diagnostic work-up was strongly suggestive of insulinoma and the patient was submitted to surgical treatment carried out laparoscopically under robotic assistance. However, surgical exploration and intraoperative ultrasonography failed to detect a pancreatic tumor. Resection was therefore carried out based on the results of selective intra-arterial calcium stimulation test, following a step-up approach, eventually leading to a pancreatoduodenectomy at the splenic artery. The histopathology examination and the immunohistochemical staining were consistent with adult-onset nesidioblastosis. After surgery, the patient continued to experience hypoglycemia with futile response to medical treatments (octreotide, calcium antagonists, diazoxide, and prednisone). Following multidisciplinary evaluation and critical review of a repeat abdominal computed tomography scan, a small nodular lesion was identified in the tail of the pancreas. The nodule was enucleated laparoscopically and the pathological examination revealed an insulinoma. In spite of the insulinoma resection, glycemic values were only partially restored, with residual nocturnal hypoglycemia. Administration of uncooked cornstarch (1.25 g/kg body weight) at bedtime was associated with significant improvement of interstitial glucose levels (p < 0.0001) and reduction of nocturnal hypoglycemia episodes (p = 0.0002).Conclusions: This report describes a rare coexistence of adult-onset nesidioblastosis and insulinoma, suggesting the existence of a wide and continuous spectrum of proliferative β-cell changes. Moreover, we propose that uncooked cornstarch may offer an additional approach to alleviate the hypoglycemic episodes when surgery is impracticable/unaccepted.
Published: 2020
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6. Influence of high density lipoprotein cholesterol levels on circulating monocytic angiogenic cells functions in individuals with type 2 diabetes mellitus

Author: Daniela Lucchesi, Simona Georgiana Popa, Veronica Sancho, Laura Giusti, Monia Garofolo, Giuseppe Daniele, Laura Pucci, Roberto Miccoli, Giuseppe Penno, and Stefano Del Prato
Subjects: Type 2 diabetes mellitus, Endothelial progenitor cells, Monocytic angiogenic cells, High-density lipoprotein cholesterol, Endothelial function, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Abstract Background High-density lipoproteins (HDLs) can exert anti-atherogenic effects. On top of removing excess cholesterol through reverse cholesterol transport, HDLs play beneficial actions on endothelial function and integrity. In particular, HDLs are strong determinant of endothelial progenitor cells (EPCs) number and function. To gain further insights into such an effect we characterized in vitro functionality of circulating “early” EPCs obtained from 60 type 2 diabetes individuals with low HDL-cholesterol (HDL-C) and 59 with high HDL-C levels. Methods After an overnight fast, venous blood was drawn in EDTA tubes and processed within 2-h from sampling. Peripheral blood mononuclear cells were isolated and plated on fibronectin coated culture dishes; after 3 days culture, adherent cells positive for Dil-ac-LDL/Lectin dual fluorescent staining were identified as monocytic angiogenic cells (MACs). After 5–7 days culture in EBM-2 medium, adherent cells were evaluated for viability/proliferation (MTT assay), senescence (beta-galactosidase activity detection), migration (modified Boyden chamber using VEGF as chemoattractant), adhesion capacity (on fibronectin-coated culture dishes) and ROS production (ROS-sensitive fluorescent probe CM-H2DCFDA). Results MACs obtained from diabetic individuals with high HDL-C had 23% higher viability compared to low HDL-C (111.6 ± 32.7% vs. 90.5 ± 28.6% optical density; p = 0.002). H2O2 exposure impaired MACs viability to a similar extent in both groups (109.2 ± 31.7% vs. 74.5 ± 40.8% in high HDL-C, p
Published: 2018
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7. Metabolic regulation of GLP-1 and PC1/3 in pancreatic α-cell line.

Author: Veronica Sancho, Giuseppe Daniele, Daniela Lucchesi, Roberto Lupi, Annamaria Ciccarone, Giuseppe Penno, Cristina Bianchi, Angela Dardano, Roberto Miccoli, and Stefano Del Prato
Subjects: Medicine, Science
Abstract: An intra-islet incretin system has been recently suggested to operate through modulation of the expression and activity of proconvertase 1/3 and 2 (PC1/3, PC2) in pancreatic alpha-cell accounting for local release of GLP-1. Little is known, whether this alpha-cell activity can be affected by the metabolic alterations occurring in type 2 diabetes, such as hyperglycemia, hyperlipidemia or hyperglucagonemia.AlphaTC1/6 cells from a mice pancreatic cell line were incubated in the presence of two glucose (G) concentration (5.5 and 16.7 mM) for 16 h with or without free fatty acid, IL6 or glucagon. GLP-1 secretion was measured by ELISA and expression of PC1/3 and PC2 by RT-PCR and western blot; cell viability was determined by MTT method, Reactive Oxygen Species generation (ROS) by H2DCFDA fluorescence and apoptosis by Annexin staining and Propidium Iodine (PI) fluorescence.Upon 16.7G incubation, GLP-1 secretion (total and active) was significantly increased in parallel with a significant increment in PC1/3 expression, a slight increase in cell viability and ROS generation and by a decrement in PC2 expression with no change in cell apoptosis. When cells were incubated at 5.5mM glucose with FFA, also an increment in GLP-1 secretion and PC1/3 expression was observed together an increment in ROS generation, a decrement in cell viability, and a modest increment in apoptosis. When incubated with 16.7mM glucose with FFA, the increment in GLP-1 secretion was reduced to basal, accompanied by an increment in apoptosis and ROS generation. This was also observed with IL-6, but in this case, no modification in ROS generation or apoptosis was observed when compared to 16.7mM glucose. The presence of glucagon did not modify any of the parameters studied.These data suggest that under hyperglycemic, hyperlipidemia or inflammatory conditions, alpha cells can increase expression PC1/3 and activate GLP-1 secretion, which may contribute protecting both alpha and beta-cells from glucose and lipotoxicity, while this effect seems to be lost in the presence of both pathophysiological conditions.
Published: 2017
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8. Plasma and fibroblasts of Tangier disease patients are disturbed in transferring phospholipids onto apolipoprotein A-I

Author: Arnold von Eckardstein, Ali Chirazi, Susanne Schuler-Lüttmann, Michael Walter, John J.P. Kastelein, Jürgen Geisel, José T. Real, Roberto Miccoli, Giorgio Noseda, Gunnar Höbbel, and Gerd Assmann
Subjects: prebeta-HDL, familial HDL deficiency, reverse cholesterol transport, cholesterol efflux, phospholipid transfer proteins, Biochemistry, QD415-436
Abstract: Plasmas of patients with Tangier disease (TD) lack lipid-rich α-HDL which, in normal plasma, constitutes the majority of high density lipoprotein (HDL). Residual amounts of apolipoprotein (apo)A-I in TD plasma occur as lipid-poor or even lipid-free preβ-HDL. By contrast to normal plasma, TD plasma does not convert preβ-HDL into α-HDL. Moreover, fibroblasts of TD patients were found to be defective in secreting cholesterol or phospholipids in the presence of lipid-free apoA-I. We have therefore hypothesized that both defective conversion of preβ-HDL into α-HDL and defective lipid efflux from TD cells onto lipid-free apoA-I result from a disturbance in phospholipid transfer occurring in both cellular and extracellular compartments. To test this hypothesis we established an assay that measures the activity of plasma, cells, and cell culture media to transfer radiolabeled phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylinositol (PI) from vesicles onto apoA-I, apoA-II, albumin, or reconstituted HDL. Plasmas, HDL, and lipoprotein-depleted plasma of normolipidemic probands as well as cell homogenates and culture media of normal fibroblasts were active at 37°C but not at 4°C in transferring radiolabeled PC, PI, and PE dose- and time-dependently onto either lipid-free apoA-I or reconstituted HDL. Transfer of glycerophospholipids onto apoA-II was much lower than onto apoA-I; transfer onto albumin was close to background. Compared to ten normolipidemic plasmas and four apoA-I-deficient plasmas, plasmas of six TD patients were significantly reduced by 40–50% in their glycerophospholipid transfer activities. Compared to eight normal fibroblast cell lines, homogenates and culture media of four TD fibroblast cell lines were reduced by 40–50% and 30–35%, respectively, in their activity to transfer PC, PI, or PE onto apoA-I. Our data suggest that in TD the same mechanism underlies both defective conversion of preβ-HDL into α-HDL and impaired efflux of cellular lipids, namely a defective phospholipid transfer.—von Eckardstein, A., A. Chirazi, S. Schuler-Lüttmann, M. Walter, J. J. P. Kastelein, J. Geisel, J. T. Real, R. Miccoli, G. Noseda, G. Höbbel, and G. Assmann. Plasma and fibroblasts of Tangier disease patients are disturbed in transferring phospholipids onto apolipoprotein A-I. J. Lipid Res. 1998. 39: 987–998.
Published: 1998
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9. Nesidioblastosis and Insulinoma: A Rare Coexistence and a Therapeutic Challenge

Author: Roberto Miccoli, Ugo Boggi, Niccolò Napoli, Giuseppe Daniele, Roberto Lupi, Daniela Campani, Stefano Del Prato, and Angela Dardano
Subjects: 0301 basic medicine, Adult, Blood Glucose, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Octreotide, Nesidioblastosis, 030209 endocrinology & metabolism, Case Report, Splenic artery, Hypoglycemia, insulinoma, medicine.disease_cause, Gastroenterology, lcsh:Diseases of the endocrine glands. Clinical endocrinology, Diagnosis, Differential, surgery, 03 medical and health sciences, 0302 clinical medicine, Pancreatectomy, Endocrinology, Pancreatic tumor, Internal medicine, medicine.artery, medicine, persistent hyperinsulinemic hypoglycemia, adult-onset β-cell nesidioblastosis, insulinoma, surgery, management, Humans, Hyperinsulinemic hypoglycemia, Insulinoma, lcsh:RC648-665, business.industry, Starch, adult-onset β-cell nesidioblastosis, medicine.disease, Circadian Rhythm, Pancreatic Neoplasms, 030104 developmental biology, medicine.anatomical_structure, persistent hyperinsulinemic hypoglycemia, Congenital Hyperinsulinism, Female, Pancreas, business, management, medicine.drug
Abstract: Background: Nesidioblastosis and insulinoma are disorders of the endocrine pancreas causing endogenous hyperinsulinemic hypoglycemia. Their coexistence is very unusual and treatment represents a still unresolved dilemma.Case Description: The patient was a 43-year-old Caucasian woman, with a 2-year history of repeated severe hypoglycemic events. The diagnostic work-up was strongly suggestive of insulinoma and the patient was submitted to surgical treatment carried out laparoscopically under robotic assistance. However, surgical exploration and intraoperative ultrasonography failed to detect a pancreatic tumor. Resection was therefore carried out based on the results of selective intra-arterial calcium stimulation test, following a step-up approach, eventually leading to a pancreatoduodenectomy at the splenic artery. The histopathology examination and the immunohistochemical staining were consistent with adult-onset nesidioblastosis. After surgery, the patient continued to experience hypoglycemia with futile response to medical treatments (octreotide, calcium antagonists, diazoxide, and prednisone). Following multidisciplinary evaluation and critical review of a repeat abdominal computed tomography scan, a small nodular lesion was identified in the tail of the pancreas. The nodule was enucleated laparoscopically and the pathological examination revealed an insulinoma. In spite of the insulinoma resection, glycemic values were only partially restored, with residual nocturnal hypoglycemia. Administration of uncooked cornstarch (1.25 g/kg body weight) at bedtime was associated with significant improvement of interstitial glucose levels (p < 0.0001) and reduction of nocturnal hypoglycemia episodes (p = 0.0002).Conclusions: This report describes a rare coexistence of adult-onset nesidioblastosis and insulinoma, suggesting the existence of a wide and continuous spectrum of proliferative β-cell changes. Moreover, we propose that uncooked cornstarch may offer an additional approach to alleviate the hypoglycemic episodes when surgery is impracticable/unaccepted.
Published: 2020
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10. A view on the quality of diabetes care in Italy and the role of Diabetes Clinics from the 2018 ARNO Diabetes Observatory

Author: Roberto Miccoli, Gian Paolo Fadini, Salvatore Cataudella, Olga Vaccaro, Nello Martini, Elisa Rossi, Giulio Marchesini, Enzo Bonora, Bonora, E., Cataudella, S., Marchesini, G., Miccoli, R., Vaccaro, O., Fadini, G. P., Martini, N., Rossi, E., Bonora E., Cataudella S., Marchesini G., Miccoli R., Vaccaro O., Fadini G.P., Martini N., and Rossi E.
Subjects: Blood Glucose, Male, Glycated Hemoglobin A, Time Factors, Endocrinology, Diabetes and Metabolism, Medicine (miscellaneous), Practice Patterns, Disease, 030204 cardiovascular system & hematology, Ambulatory Care Facilities, 0302 clinical medicine, Adherence, Anti-hyperglycemic agents, Diabetes mellitus, Monitoring, Quality of care, Aged, Aged, 80 and over, Biomarkers, Diabetes Mellitus, Female, Glycemic Control, Guideline Adherence, Humans, Hypoglycemic Agents, Italy, Middle Aged, Practice Guidelines as Topic, Practice Patterns, Physicians', Prevalence, Quality Indicators, Health Care, Treatment Outcome, Health care, 80 and over, Nutrition and Dietetics, medicine.diagnostic_test, Carotid ultrasonography, Eye examination, Cardiology and Cardiovascular Medicine, Human, medicine.medical_specialty, Diabetes mellitu, Time Factor, 030209 endocrinology & metabolism, Anti-hyperglycemic agent, 03 medical and health sciences, medicine, Medical prescription, Glycated Hemoglobin, Physicians', Hypoglycemic Agent, business.industry, Biomarker, medicine.disease, Health Care, Ambulatory Care Facilitie, Emergency medicine, Quality Indicators, Microalbuminuria, business, Lipid profile
Abstract: Backgrounds and aims To investigate relevant indicators of quality of care in a large population-based sample of people with diabetes representative of clinical practice in Italy in 2018. Methods and results We analyzed data from 11,300,750 subjects. All administrative healthcare claims collected in 2018 were scrutinized to identify subjects with diabetes and investigate several indicators of quality of care. Subjects with diabetes were identified by anti-hyperglycemic drug prescriptions, disease-specific co-payment exemption and hospital discharge codes. Indicators of quality of care pertained to monitoring (HbA1c, creatinine, lipid profile, microalbuminuria, eye examination, ECG, ultrasonography of carotid and lower limb arteries) and diabetes treatment (anti-hyperglycemic agents in subjects with cardiovascular disease, CVD). Subjects attending and nonattending Diabetes Clinics were compared. We identified 697,208 individuals with diabetes. HbA1c was assessed at least once in the year in 62.7%, creatinine in 62.3%, total cholesterol in 59.6%, microalbuminuria in 34.3%. Frequency of eye examination was 8.2%, ECG 23.5%, carotid ultrasonography 14.3%, lower limb ultrasonography 7.6%. Among anti-hyperglycemic drugs, SGLT-2 inhibitors were prescribed to ~5% and GLP-1 receptor agonists to ~5% although the proportion of subjects with CVD was ~45%. Subjects attending Diabetes Clinics had higher figures for all these monitoring and treatment indicators. Conclusions The implementation of national and international guidelines regarding disease monitoring and treatment is far from being satisfactory, especially among subjects nonattending Diabetes Clinics. Further efforts and investments are needed for better disseminating guidelines, more efficaciously engaging healthcare professionals and more strongly empowering the healthcare system to improve diabetes care.
Published: 2020

11. Invited review. Series: Implications of the recent CVOTs in type 2 diabetes: Which patients for GLP-1RA or SGLT-2 inhibitor?

Author: Angela, Dardano, Roberto, Miccoli, Cristina, Bianchi, Giuseppe, Daniele, and Stefano, Del Prato
Subjects: Heart Failure, CVOTs, Diabetic kidney disease, GLP1 receptor agonist, MACE, SGLT2 inhibitor, Type 2 diabetes, Myocardial Infarction, Atherosclerosis, Glucagon-Like Peptide-1 Receptor, Diabetes Mellitus, Type 2, Cardiovascular Diseases, Humans, Hypoglycemic Agents, Diabetic Nephropathies, Risk Reduction Behavior, Sodium-Glucose Transporter 2 Inhibitors
Abstract: Large cardiovascular outcome trials (CVOTs) have lent support to a cardiovascular protection with the use of SGLT2-inhibitors (SGLT2is) and GLP1-Receptor Agonists (GLP1-RAs) in subjects with type 2 diabetes. These two classes of novel glucose lowering agents have been shown to have a similar effect on the risk reduction of Major Adverse Cardiovascular Events (MACE: nonfatal myocardial infarction, nonfatal stroke, cardiovascular mortality). Nonetheless, they may not be simply interchangeable. Rather, careful evaluation of all the results of CVOTs leads identification of different effects that may allow profiling of the ideal individuals with T2DM who may benefit most from the use of one or the other class of agents. These differences include effect on heart failure, stroke and diabetic kidney disease that have prompt recent guidelines and recommendation for the treatment of type 2 diabetes to suggest the preferential use of SGLT2is in those with evidence of heart failure and impaired kidney function, while both SGLT2i and GLP1-RAs with proven effect could be use in those with prevalent atherosclerotic cardiovascular disease. This review discusses all these elements of differentiation along with others that in the future may help establishing the best cardiorenal benefit for individuals with T2DM.
Published: 2020

12. Clinical burden of diabetes in Italy in 2018: A look at a systemic disease from the ARNO Diabetes Observatory

Author: Salvatore Cataudella, Nello Martini, Olga Vaccaro, Giulio Marchesini, Enzo Bonora, Elisa Rossi, Roberto Miccoli, Gian Paolo Fadini, Bonora, E., Cataudella, S., Marchesini, G., Miccoli, R., Vaccaro, O., Fadini, G. P., Martini, N., Rossi, E., Bonora E., Cataudella S., Marchesini G., Miccoli R., Vaccaro O., Fadini G.P., Martini N., and Rossi E.
Subjects: Research design, Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Population, Disease, health care and epidemiology, Diseases of the endocrine glands. Clinical endocrinology, Ambulatory care, administrative data, Diabetes mellitus, Health care, medicine, Diabetes Mellitus, Humans, Hypoglycemic Agents, Medical prescription, Epidemiology/Health Services Research, education, Copayment, education.field_of_study, business.industry, Health Care Costs, hospitalization, resource use, medicine.disease, RC648-665, Italy, Family medicine, Female, business
Abstract: IntroductionDiabetes is a highly prevalent disease worldwide and represents a challenge for patients and healthcare systems. This population-based study evaluated diabetes burden in Italy in 2018 by assessing all aspects of outpatient and hospital care.Research design and methodsWe investigated data of 11 300 750 residents in local health districts contributing to ARNO Diabetes Observatory (~20% of Italian inhabitants). All administrative healthcare claims were analyzed to gather information on access to medical resources. Subjects with diabetes, identified by antihyperglycemic drug prescriptions, disease-specific copayment exemption and hospital discharge codes, were compared with age, sex and residency-matched non-diabetic individuals.ResultsWe identified 697 208 subjects with ascertained diabetes, yielding a prevalence of 6.2% (6.5% in men vs 5.9% in women, p2-fold higher in subjects with diabetes, mainly driven by hospitalizations and outpatient care related to chronic complications rather than to glucose-lowering drugs, diabetes-specific devices, or metabolic monitoring.ConclusionsThe burden of diabetes in Italy is particularly heavy and, as a systemic disease, it includes all aspects of clinical medicine, with consequent high expenses in all areas of healthcare.
Published: 2020

13. Microvascular complications burden (nephropathy, retinopathy and peripheral polyneuropathy) affects risk of major vascular events and all-cause mortality in type 1 diabetes: A 10-year follow-up study

Author: Daniela Lucchesi, Elisa Gualdani, Fabrizio Campi, Giuseppe Daniele, Monia Garofolo, Stefano Del Prato, Michele Aragona, Roberto Miccoli, Giuseppe Penno, Paolo Francesconi, and Rosa Giannarelli
Subjects: Adult, Male, medicine.medical_specialty, lcsh:Diseases of the circulatory (Cardiovascular) system, Time Factors, Microvascular complications, All-cause mortality, Cardiovascular disease, Diabetic kidney disease, Diabetic retinopathy, Microvascular burden, Peripheral diabetic polyneuropathy, Type 1 diabetes mellitus, Endocrinology, Diabetes and Metabolism, Risk Assessment, Nephropathy, Diabetic Neuropathies, Risk Factors, Diabetes mellitus, Internal medicine, Cause of Death, medicine, Humans, Cumulative incidence, Diabetic Nephropathies, Original Investigation, Aged, Type 1 diabetes, Proportional hazards model, business.industry, Mortality rate, Incidence (epidemiology), Incidence, Hazard ratio, Middle Aged, medicine.disease, Prognosis, Cross-Sectional Studies, Diabetes Mellitus, Type 1, Italy, lcsh:RC666-701, Female, Cardiology and Cardiovascular Medicine, business, Follow-Up Studies
Abstract: BackgroundMicrovascular complications (MC) have been claimed to increase the risk for cardiovascular disease in diabetic subjects. However, the effect of MC burden on the risk of major vascular outcomes and all-cause mortality in type 1 diabetes is still poorly explored. We evaluated the relationship between microvascular complications burden and incidence of major cardiovascular events and all-cause mortality in subjects with type 1 diabetes.MethodsWe recruited 774 participants with type 1 diabetes in a single-center observational study over a follow-up of 10.8 ± 2.5 years. Hazard ratios (HR) for cardiovascular outcomes and all-cause death associated with microvascular complications were determined by unadjusted and adjusted Cox regression analysis.ResultsOut of 774 individuals, 54.9% had no-MC, 32.3% 1 MC, 9.7% 2 MC and 3.1% 3 MC. A total of 54 deaths (7.0%) occurred. Death rate increased from no-MC 2.1% (Ref) to 1 MC 7.2% (HR 3.54 [95% CI 1.59–7.87]), 2 MC 14.7% (HR 6.41 [95% CI 2.65–15.49]) and 3 MC 66.7% (HR 41.73 [95% CI 18.42–94.57], p ConclusionsIn type 1 diabetes, microvascular complications burden increases in an independent dose-dependent manner the risk of major cardiovascular outcomes and all-cause mortality. The presence and number of microvascular complications should be considered in stratifying overall cardiovascular risk in type 1 diabetes.
Published: 2019

14. Influence of high density lipoprotein cholesterol levels on circulating monocytic angiogenic cells functions in individuals with type 2 diabetes mellitus

Author: Laura Pucci, Veronica Sancho, Stefano Del Prato, Laura Giusti, Roberto Miccoli, Monia Garofolo, Giuseppe Daniele, Giuseppe Penno, Daniela Lucchesi, and Simona Georgiana Popa
Subjects: Male, 0301 basic medicine, lcsh:Diseases of the circulatory (Cardiovascular) system, Endocrinology, Diabetes and Metabolism, Type 2 diabetes, 030204 cardiovascular system & hematology, Endothelial function, Endothelial progenitor cells, High-density lipoprotein cholesterol, Monocytic angiogenic cells, Type 2 diabetes mellitus, Monocytes, chemistry.chemical_compound, 0302 clinical medicine, High-density lipoprotein, Endocrinology, Cell Movement, Cells, Cultured, Neovascularization, Pathologic, Reverse cholesterol transport, Middle Aged, Internal Medicine, Cardiology and Cardiovascular Medicine, Diabetes and Metabolism, Phenotype, Female, medicine.medical_specialty, Cell Survival, Peripheral blood mononuclear cell, Andrology, 03 medical and health sciences, Internal medicine, Diabetes mellitus, Cell Adhesion, medicine, Humans, Progenitor cell, Aged, Cell Proliferation, Cholesterol, business.industry, Cholesterol, HDL, medicine.disease, In vitro, 030104 developmental biology, Diabetes Mellitus, Type 2, chemistry, lcsh:RC666-701, Reactive Oxygen Species, business, Biomarkers
Abstract: Background High-density lipoproteins (HDLs) can exert anti-atherogenic effects. On top of removing excess cholesterol through reverse cholesterol transport, HDLs play beneficial actions on endothelial function and integrity. In particular, HDLs are strong determinant of endothelial progenitor cells (EPCs) number and function. To gain further insights into such an effect we characterized in vitro functionality of circulating “early” EPCs obtained from 60 type 2 diabetes individuals with low HDL-cholesterol (HDL-C) and 59 with high HDL-C levels. Methods After an overnight fast, venous blood was drawn in EDTA tubes and processed within 2-h from sampling. Peripheral blood mononuclear cells were isolated and plated on fibronectin coated culture dishes; after 3 days culture, adherent cells positive for Dil-ac-LDL/Lectin dual fluorescent staining were identified as monocytic angiogenic cells (MACs). After 5–7 days culture in EBM-2 medium, adherent cells were evaluated for viability/proliferation (MTT assay), senescence (beta-galactosidase activity detection), migration (modified Boyden chamber using VEGF as chemoattractant), adhesion capacity (on fibronectin-coated culture dishes) and ROS production (ROS-sensitive fluorescent probe CM-H2DCFDA). Results MACs obtained from diabetic individuals with high HDL-C had 23% higher viability compared to low HDL-C (111.6 ± 32.7% vs. 90.5 ± 28.6% optical density; p = 0.002). H2O2 exposure impaired MACs viability to a similar extent in both groups (109.2 ± 31.7% vs. 74.5 ± 40.8% in high HDL-C, p
Published: 2018
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15. Diabetic ketoacidosis and acute pancreatitis associated with antipsychotic drugs: report of a case

Author: Maria Cristina Campopiano, Stefano Del Prato, Cosimo Rodia, Alessandra Bertolotto, Cristina Bianchi, Angela Dardano, Roberto Miccoli, and Annamaria Ciccarone
Subjects: medicine.medical_specialty, Diabetic ketoacidosis, business.industry, medicine.medical_treatment, Internal medicine, medicine, Acute pancreatitis, Antipsychotic, medicine.disease, business
Published: 2018

16. The relative burden of diabetes complications on healthcare costs: The population-based ARNO Diabetes Observatory, Italy

Author: Eva Pagano, Marisa De Rosa, Elisa Rossi, E. Cinconze, Roberto Miccoli, Olga Vaccaro, Enzo Bonora, Graziella Bruno, MARCHESINI REGGIANI, GIULIO, Eva, Pagano, Marisa De Rosa, Elisa, Rossi, Cinconze, E., MARCHESINI REGGIANI, Giulio, Roberto, Miccoli, Olga, Vaccaro, Enzo, Bonora, and Graziella, Bruno
Subjects: Cost, Health care delivery, Endocrinology, Diabetes and Metabolism, Nutrition and Dietetic, Medicine (miscellaneous), Cardiology and Cardiovascular Medicine, health care economics and organizations, Diabetes complication
Abstract: 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.
Published: 2016

17. Metabolic regulation of GLP-1 and PC1/3 in pancreatic α-cell line

Author: Angela Dardano, Annamaria Ciccarone, Veronica Sancho, Roberto Miccoli, Roberto Lupi, Daniela Lucchesi, Stefano Del Prato, Giuseppe Daniele, Cristina Bianchi, and Giuseppe Penno
Subjects: 0301 basic medicine, Genetics and Molecular Biology (all), Physiology, Peptide Hormones, lcsh:Medicine, Apoptosis, Artificial Gene Amplification and Extension, Polymerase Chain Reaction, Biochemistry, Endocrinology, 0302 clinical medicine, Glucose Metabolism, Glucagon-Like Peptide 1, Annexin, Biochemistry, Genetics and Molecular Biology (all), Agricultural and Biological Sciences (all), Medicine and Health Sciences, lcsh:Science, Multidisciplinary, Cell Death, Organic Compounds, Monosaccharides, Type 2 Diabetes, Chemistry, Proprotein Convertase 2, Proprotein Convertase 1, Lipotoxicity, Cell Processes, Physical Sciences, Carbohydrate Metabolism, Research Article, medicine.medical_specialty, endocrine system, Cell Survival, Endocrine Disorders, Carbohydrates, Incretin, 030209 endocrinology & metabolism, Carbohydrate metabolism, Biology, Research and Analysis Methods, Models, Biological, Glucagon, Cell Line, 03 medical and health sciences, Internal medicine, Diabetes Mellitus, medicine, Humans, Secretion, Viability assay, Molecular Biology Techniques, Molecular Biology, Interleukin-6, Organic Chemistry, lcsh:R, Chemical Compounds, Biology and Life Sciences, Cell Biology, Hormones, Glucose, Metabolism, 030104 developmental biology, Gene Expression Regulation, Glucagon-Secreting Cells, Metabolic Disorders, lcsh:Q, Reactive Oxygen Species, Physiological Processes
Abstract: Background and aims An intra-islet incretin system has been recently suggested to operate through modulation of the expression and activity of proconvertase 1/3 and 2 (PC1/3, PC2) in pancreatic alpha-cell accounting for local release of GLP-1. Little is known, whether this alpha-cell activity can be affected by the metabolic alterations occurring in type 2 diabetes, such as hyperglycemia, hyperlipidemia or hyperglucagonemia. Materials and methods AlphaTC1/6 cells from a mice pancreatic cell line were incubated in the presence of two glucose (G) concentration (5.5 and 16.7 mM) for 16 h with or without free fatty acid, IL6 or glucagon. GLP-1 secretion was measured by ELISA and expression of PC1/3 and PC2 by RT-PCR and western blot; cell viability was determined by MTT method, Reactive Oxygen Species generation (ROS) by H2DCFDA fluorescence and apoptosis by Annexin staining and Propidium Iodine (PI) fluorescence. Results Upon 16.7G incubation, GLP-1 secretion (total and active) was significantly increased in parallel with a significant increment in PC1/3 expression, a slight increase in cell viability and ROS generation and by a decrement in PC2 expression with no change in cell apoptosis. When cells were incubated at 5.5mM glucose with FFA, also an increment in GLP-1 secretion and PC1/3 expression was observed together an increment in ROS generation, a decrement in cell viability, and a modest increment in apoptosis. When incubated with 16.7mM glucose with FFA, the increment in GLP-1 secretion was reduced to basal, accompanied by an increment in apoptosis and ROS generation. This was also observed with IL-6, but in this case, no modification in ROS generation or apoptosis was observed when compared to 16.7mM glucose. The presence of glucagon did not modify any of the parameters studied. Conclusion These data suggest that under hyperglycemic, hyperlipidemia or inflammatory conditions, alpha cells can increase expression PC1/3 and activate GLP-1 secretion, which may contribute protecting both alpha and beta-cells from glucose and lipotoxicity, while this effect seems to be lost in the presence of both pathophysiological conditions.
Published: 2017

18. Feasibility and Effectiveness in Clinical Practice of a Multifactorial Intervention for the Reduction of Cardiovascular Risk in Patients With Type 2 Diabetes

Author: Roberto Miccoli, Gianpaolo Reboldi, Ivana Zavaroni, Diego Ardigò, Mariella Trovati, Olga Vaccaro, Massimo Boemi, Franco Cavalot, L. Franzini, Pierpaolo De Feo, and Angela A. Rivellese
Subjects: Research design, Male, medicine.medical_specialty, Randomization, Endocrinology, Diabetes and Metabolism, Type 2 diabetes, law.invention, Randomized controlled trial, law, Internal medicine, Diabetes mellitus, Internal Medicine, Medicine, Humans, Cluster randomised controlled trial, Original Research, Advanced and Specialized Nursing, Glycated Hemoglobin, Intention-to-treat analysis, business.industry, Clinical Care/Education/Nutrition/Psychosocial Research, Middle Aged, medicine.disease, Interim analysis, Diabetes Mellitus, Type 2, Cardiovascular Diseases, Physical therapy, Female, business, Algorithms
Abstract: OBJECTIVE To evaluate the feasibility and effectiveness of an intensive, multifactorial cardiovascular risk reduction intervention in a clinic-based setting. RESEARCH DESIGN AND METHODS The study was a pragmatic, cluster randomized trial, with the diabetes clinic as the unit of randomization. Clinics were randomly assigned to either continue their usual care (n = 5) or to apply an intensive intervention aimed at the optimal control of cardiovascular disease (CVD) risk factors and hyperglycemia (n = 4). To account for clustering, mixed model regression techniques were used to compare differences in CVD risk factors and HbA1c. Analyses were performed both by intent to treat and as treated per protocol. RESULTS Nine clinics completed the study; 1,461 patients with type 2 diabetes and no previous cardiovascular events were enrolled. After 2 years, participants in the interventional group had significantly lower BMI, HbA1c, LDL cholesterol, and triglyceride levels and significantly higher HDL cholesterol level than did the usual care group. The proportion of patients reaching the treatment goals was systematically higher in the interventional clinics (35% vs. 24% for LDL cholesterol, P = 0.1299; 93% vs. 82% for HDL cholesterol, P = 0.0005; 80% vs. 64% for triglycerides, P = 0.0002; 39% vs. 22% for HbA1c, P = 0.0259; 13% vs. 5% for blood pressure, P = 0.1638). The analysis as treated per protocol confirmed these findings, showing larger and always significant differences between the study arms for all targets. CONCLUSIONS A multifactorial intensive intervention in type 2 diabetes is feasible and effective in clinical practice and it is associated with significant and durable improvement in HbA1c and CVD risk profile.
Published: 2013

19. 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

Author: Salvatore Cataudella, Roberto Miccoli, Graziella Bruno, Enzo Bonora, M. De Rosa, Eugenio Rossi, Eva Pagano, Olga Vaccaro, Giulio Marchesini, and Vaccaro, Olga
Subjects: Blood Glucose, Male, Pediatrics, Glycated Hemoglobin A, Time Factors, National Health Programs, Cost-Benefit Analysis, Endocrinology, Diabetes and Metabolism, Medicine (miscellaneous), 030204 cardiovascular system & hematology, Indirect costs, Endocrinology, 0302 clinical medicine, Direct costs, Health care, Prevalence, Insulin, Hospital Costs, Child, Survey, education.field_of_study, Nutrition and Dietetics, Incidence (epidemiology), Incidence, Diabetes and Metabolism, Treatment Outcome, Type 1 diabetes, Italy, Child, Preschool, Cohort, Female, Cardiology and Cardiovascular Medicine, Type 1, Adult, medicine.medical_specialty, Adolescent, Diabetic ketoacidosis, Population, 030209 endocrinology & metabolism, Type 1 diabetes, Direct cost, Drug Costs, Diabetic Ketoacidosis, Biomarkers, Diabetes Mellitus, Type 1, Humans, Hypoglycemic Agents, Infant, Infant, Newborn, Quality Indicators, Health Care, Young Adult, 03 medical and health sciences, Diabetes mellitus, Diabetes Mellitus, medicine, Preschool, education, Glycated Hemoglobin, business.industry, Newborn, medicine.disease, Health Care, Quality Indicators, business, Demography
Abstract: To assess temporal trend in incidence (2003-12) and prevalence (2002-12) of type 1 diabetes in children and young adults, direct costs and selected indicators of quality of care under the coverage of the universalistic Italian National Health System (NHS).The ARNO Observatory, a healthcare monitoring system based on administrative data, identified a population-based multiregional cohort of subjects aged 0-29 years. Type 1 diabetes was defined by at least two prescriptions of insulin over 12 months and continuous insulin-treatment in the following year. Indicators of quality of care and directs costs were assessed in persons with diabetes and in people without diabetes, individually matched for age, gender and health unit (1:4 ratio). We identified 2357 incident cases of type 1 diabetes aged 0-29 years (completeness of ascertainment, 99%). Incidence rates were similar in ages 0-14 (15.8, 95% CI 14.9-16.8) and 15-29 years (16.3, 15.4-17.2), with no significant trend. Prevalence increased from 137 to 166.9/100,000, particularly in the age 15-29 years. Direct costs accounted for € 2117 in persons with diabetes and € 292 in control individuals. A statistically significant decreasing trend in hospitalization for acute complications was evident (p 0.001), which was almost completely due to ketoacidosis. People with at least one HbA1c measurement over the year were 48.5%.We showed high incidence and increasing prevalence of type 1 diabetes in young adults in Italy, which impact on direct costs under the universalistic coverage of the NHS.
Published: 2016

20. Pathogenetic Mechanisms and Cardiovascular Risk

Author: Simona Frontoni, Roberto Miccoli, M. A. Dolci, Riccardo C. Bonadonna, Giulio Marchesini, Francesco Giorgino, Franco Cavalot, Emanuela Faloia, Gisella M. Cavallo, Cristina Bianchi, Frida Leonetti, and Stefano Del Prato
Subjects: Adult, Male, medicine.medical_specialty, Cardiovascular and Metabolic Risk, endocrine system diseases, Endocrinology, Diabetes and Metabolism, Prediabetic State, chemistry.chemical_compound, Insulin resistance, Internal medicine, Diabetes mellitus, Internal Medicine, medicine, Humans, Prediabetes, Risk factor, Original Research, Advanced and Specialized Nursing, Glycated Hemoglobin, Glucose tolerance test, medicine.diagnostic_test, C-Peptide, C-peptide, business.industry, Type 2 Diabetes Mellitus, nutritional and metabolic diseases, Glucose Tolerance Test, Middle Aged, medicine.disease, Endocrinology, chemistry, Diabetes Mellitus, Type 2, Cardiovascular Diseases, Female, Glycated hemoglobin, Insulin Resistance, business
Abstract: OBJECTIVE To ascertain to which extent the use of HbA1c and oral glucose tolerance test (OGTT) for diagnosis of glucose tolerance could identify individuals with different pathogenetic mechanisms and cardiovascular risk profile. RESEARCH DESIGN AND METHODS A total of 844 subjects (44% men; age 49.5 ± 11 years; BMI 29 ± 5 kg/m2) participated in this study. Parameters of β-cell function were derived from deconvolution of the plasma C-peptide concentration after a 75-g OGTT and insulin sensitivity assessed by homeostasis model assessment of insulin resistance (IR). Cardiovascular risk profile was based on determination of plasma lipids and measurements of body weight, waist circumference, and blood pressure. Glucose regulation categories by OGTT and HbA1c were compared with respect to insulin action, insulin secretion, and cardiovascular risk profile. RESULTS OGTT results showed 42% of the subjects had prediabetes and 15% had type 2 diabetes mellitus (T2DM), whereas the corresponding figures based on HbA1c were 38 and 11%, with a respective concordance rate of 54 and 44%. Subjects meeting both diagnostic criteria for prediabetes presented greater IR and impairment of insulin secretion and had a worse cardiovascular risk profile than those with normal glucose tolerance at both diagnostic methods. In a logistic regression analyses adjusted for age, sex, and BMI, prediabetic subjects, and even more T2DM subjects by OGTT, had greater chance to have IR and impaired insulin secretion. CONCLUSIONS HbA1c identifies a smaller proportion of prediabetic individuals and even a smaller proportion of T2DM individuals than OGTT, with no difference in IR, insulin secretion, and cardiovascular risk profile. Subjects fulfilling both diagnostic methods for prediabetes or T2DM are characterized by a worse metabolic profile.
Published: 2012

21. New forms of insulin and insulin therapies for the treatment of type 2 diabetes

Author: Angela Dardano, Roberto Miccoli, Avivit Cahn, and Stefano Del Prato
Subjects: medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Glucagon-Like Peptides, Type 2 diabetes, Disease, Bioinformatics, Internal Medicine, Endocrinology, Pharmacotherapy, Pharmacokinetics, Internal medicine, Diabetes mellitus, medicine, Humans, Hypoglycemic Agents, Insulin, Sodium-Glucose Transporter 2 Inhibitors, Dipeptidyl-Peptidase IV Inhibitors, business.industry, Delivery mode, medicine.disease, Diabetes and Metabolism, Treatment Outcome, Diabetes Mellitus, Type 2, Pharmacodynamics, Drug Therapy, Combination, business
Abstract: Insulin is a common treatment option for many patients with type 2 diabetes, and is generally used late in the natural history of the disease. Its injectable delivery mode, propensity for weight gain and hypoglycaemia, and the paucity of trials assessing the risk-to-safety ratio of early insulin use are major shortcomings associated with its use in patients with type 2 diabetes. Development of new insulins-such as insulin analogues, including long-acting and short-acting insulins-now provide alternative treatment options to human insulin. These novel insulin formulations and innovative insulin delivery methods, such as oral or inhaled insulin, have been developed with the aim to reduce insulin-associated hypoglycaemia, lower intraindividual pharmacokinetic and pharmacodynamic variability, and improve imitation of physiological insulin release. Availability of newer glucose-lowering drugs (such as glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, and sodium-glucose co-transporter-2 inhibitors) also offers the opportunity for combination treatment; the results of the first trials in this area of research suggest that such treatment might lead to use of reduced insulin doses, less weight gain, and fewer hypoglycaemic episodes than insulin treatment alone. These and future developments will hopefully offer better opportunities for individualisation of insulin treatment for patients with type 2 diabetes.
Published: 2015

22. Access to emergency room for hypoglycaemia in people with diabetes

Author: Elisabetta, Salutini, Cristina, Bianchi, Massimo, Santini, Angela, Dardano, Giuseppe, Daniele, Giuseppe, Penno, Roberto, Miccoli, and Stefano, Del Prato
Subjects: Adult, Aged, 80 and over, Male, emergency room, Ambulances, Length of Stay, Middle Aged, sulphonylurea, Health Services Accessibility, Hypoglycemia, Diabetes Mellitus, Type 1, Logistic Models, Sulfonylurea Compounds, Diabetes Mellitus, Type 2, Italy, Humans, Hypoglycemic Agents, Insulin, Female, Hospital Mortality, hypoglycaemia, type 2 diabetes, Emergency Service, Hospital, Aged
Abstract: Hypoglycaemia is a major burden of the pharmacological therapy of diabetes and is associated with increased morbidity, mortality and treatment costs.We screened all admissions to the emergency room of the Pisa University Hospital from 1 January 2009 to 31 December 2013, selecting individuals with a discharge diagnosis of hypoglycaemia. We retrieved 500 admissions involving adult diabetic patients: age 71 ± 16 years; M/F 50.2/49.8%; 70.2% type 2 diabetes (T2DM).Among T2DM, 42.2% were on insulin, 10.8% on insulin plus oral anti-diabetes drugs and 38.2% on oral anti-diabetes drugs alone (92% sulphonylureas/glinides ± insulin-sensitizers). Glibenclamide was the most frequently used sulphonylurea (69%). Individuals treated with oral anti-diabetes drugs were older than those on insulin (79 ± 11 versus 74 ± 12 years; p 0.0001). Among patients taking sulphonylurea, 47% had estimated glomerular filtration rate60 mL/min/1.73 m(2) and 13.5% had30 mL/min/1.73 m(2) . In-hospital admission occurred in 20% of cases. Hospitalized patients with T2DM were older than those discharged (80 ± 10 versus 76 ± 12 years, p 0.01) and were on oral antidiabetic drugs in 54.8% of the cases, whereas 35.7% were on insulin (χ(2) , p 0.0001) and 8.3% on combined therapy. Notably, 93.5% of those on oral anti-diabetic drugs were taking a secretagogue. Insulin-treated subjects were younger than those treated with oral anti-diabetic drugs alone (77 ± 12 versus 82 ± 7 years; p 0.02). The mean in-hospital annual mortality rate was 85 deaths per 1000 patients-year.Our results support the recommendation that the risk associated with insulin and insulin-secretagogues should be carefully assessed, particularly when prescribed in vulnerable patients with T2DM.
Published: 2015

23. Optimal therapy of type 2 diabetes: a controversial challenge

Author: Angela Dardano, Giuseppe Penno, Stefano Del Prato, and Roberto Miccoli
Subjects: Blood Glucose, Male, medicine.medical_specialty, Aging, type 2 diabetes mellitus, Type 2 diabetes, Disease, elderly, Quality of life (healthcare), Risk Factors, Diabetes mellitus, medicine, Humans, Hypoglycemic Agents, polypharmacy, Intensive care medicine, Aged, Polypharmacy, Clinical Trials as Topic, treatment, business.industry, Type 2 Diabetes Mellitus, Cell Biology, medicine.disease, Malnutrition, Diabetes Mellitus, Type 2, Practice Guidelines as Topic, Physical therapy, Life expectancy, glycemic control, Female, business, Research Paper
Abstract: Type 2 diabetes mellitus (T2DM) is one of the most common chronic disorders in older adults and the number of elderly diabetic subjects is growing worldwide. Nonetheless, the diagnosis of T2DM in elderly population is often missed or delayed until an acute metabolic emergency occurs. Accumulating evidence suggests that both aging and environmental factors contribute to the high prevalence of diabetes in the elderly. Clinical management of T2DM in elderly subjects presents unique challenges because of the multifaceted geriatric scenario. Diabetes significantly lowers the chances of “successful” aging, notably it increases functional limitations and impairs quality of life. In this regard, older diabetic patients have a high burden of comorbidities, diabetes-related complications, physical disability, cognitive impairment and malnutrition, and they are more susceptible to the complications of dysglycemia and polypharmacy. Several national and international organizations have delivered guidelines to implement optimal therapy in older diabetic patients based on individualized treatment goals. This means appreciation of the heterogeneity of the disease as generated by life expectancy, functional reserve, social support, as well as personal preference. This paper will review current treatments for achieving glycemic targets in elderly diabetic patients, and discuss the potential role of emerging treatments in this patient population.
Published: 2014

24. Lipoprotein Glomerulopathy: molecular chatacterization of three Italian patients and literature survey

Author: Mariarita Puntoni, T Sampietro, Giovanna Pasquariello, Sebastiano Cal, Pellegrino Masiello, Roberto Miccoli, Livia Pisciotta, Matilde Masini, Francesco Sbrana, Stefano Bertolini, and A. Pasquariello
Subjects: Apolipoprotein E, medicine.medical_specialty, business.industry, Lipoprotein Glomerulopathy, Glomerular lipoprotein thrombi, Dominant inheritance with incomplete penetrance, medicine.disease, APOE gene mutation, Lipoprotein glomerulopathy (LPG), Hyperlipidemia, Endocrinology, Internal medicine, Medicine, lipids (amino acids, peptides, and proteins), Literature survey, business, Kidney disease, Lipoprotein
Abstract: Lipoprotein Glomerulopathy: Molecular Characterization of Three Italian Patients and Literature Survey Lipoprotein glomerulopathy (LPG) is a rare kidney disease, mainly reported in Asian subjects, linked with rare APOE gene mutations resulting in a structurally abnormal Apolipoprotein E (ApoE), the plasma accumulation of lipoprotein remnants and the formation of lipid thrombi in glomerular capillaries. This study reports the molecular characterization of three unrelated Italian patients with long standing LPG.
Published: 2014

25. Lipid-free apolipoprotein (apo) A-I is converted into alpha-migrating high density lipoproteins by lipoprotein-depleted plasma of normolipidemic donors and apo A-I-deficient patients but not of Tangier disease patients

Author: Roberto Miccoli, Gerd Assmann, Arnold von Eckardstein, John J.P. Kastelein, Jürgen Geisel, José T. Real, J. A. Kuivenhoven, Yadong Huang, G. Noseda, and Other departments
Subjects: Adult, Male, medicine.medical_specialty, Apolipoprotein B, Lipoproteins, Blood Donors, chemistry.chemical_compound, Tangier disease, High-density lipoprotein, Reference Values, Phospholipid transfer protein, Internal medicine, medicine, Humans, Phospholipids, Tangier Disease, Aged, Apolipoprotein A-I, biology, Chemistry, Cholesterol, Vesicle, Albumin, Middle Aged, medicine.disease, Endocrinology, biology.protein, Female, lipids (amino acids, peptides, and proteins), Lipoproteins, HDL, Cardiology and Cardiovascular Medicine, Lipoprotein
Abstract: Plasma of patients with Tangier disease (TD) is devoid of alpha-LpA-I (apolipoprotein A-I-containing lipoprotein), which in normolipidemic plasma constitutes the majority of high density lipoprotein (HDL). The residual amounts of apolipoprotein A-I (apo A-I) in TD plasma have electrophoretic prebeta1-LpA-I mobility. We have previously demonstrated that TD plasma does not convert prebeta1-LpA-I into alpha-LpA-I. In this study we found that plasmas of normolipidemic controls, apo A-I-deficient patients and patients with fish-eye disease, but not plasmas of six TD patients, convert biotinylated lipid-free apo A-I into alpha-LpA-I. Supplementation of plasma with free oleic acid or fatty acid free albumin neither inhibited conversion activity in normal plasmas nor reconstituted it in TD plasma. In normal plasma the conversion activity was assessed in HDL and in the lipoprotein-free fraction. The latter fraction, however, generated larger particles only in the presence of exogenous phospholipid vesicles. To obtain particles with alpha-mobility, these vesicles had to contain phosphatidylinositol and/or cholesterol. Lipoprotein-depleted TD plasma did not convert lipid-free apo A-I into alpha-LpA-I even in the presence of exogenous vesicles with phospholipids or cholesterol. Taken together we conclude that disturbed transfer of glycerophospholipds onto apo A-I or prebeta1-LpA-I prevents maturation of HDL and thereby possibly causes deficiency of HDL cholesterol in patients with TD. Moreover, the lack of alpha-LpA-I in TD plasma together with its failure to convert exogenous apo A-I into an alpha-migrating particle provide specific tests for the diagnosis of TD.
Published: 1998
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26. The Global Cardiovascular Risk Transition: Associations of Four Metabolic Risk Factors with Macroeconomic Variables in 1980 and 2008

Author: Goodarz, Danaei, Gitanjali, M Singh, Christopher, J Paciorek, John, K Lin, Melanie, J Cowan, Mariel, M Finucane, Farshad, Farzadfar, Gretchen, A Stevens, Leanne, M Riley, Yuan, Lu, Mayuree, Rao, Majid, Ezzati, Global Burden of Metabolic Risk Factors of Chronic Diseases Collaborating Group: Writing and Global Analysis Group: Goodarz Danaei, Paciorek, Christopher J., Lin, John K., Cowan, Melanie J., Finucane, Mariel M., Stevens, Gretchen A., Riley, Leanne M., Peres, Cynthia Pérez, Román Pérez-Fernández, Rafael Pichardo, Hwee Pin Phua, Majid Ezzati. Contributed equally to the research and manuscript and listed in alphabetic order. Country Data Group: Geir Aamodt, Ziad Abdeen, Nabila A. Abdella, Hanan F. Abdul Rahim, Juliet Addo, Wichai Aekplakorn, Mustafa M. Afifi, Enrico Agabiti-Rosei, Carlos A. Aguilar Salinas, Charles Agyemang, Mohamed M. Ali, Mohannad Al-Nsour, Abdul R. Al-Nuaim, Ramachandran Ambady, Pertti Aro, Fereidoun Azizi, Carlo M. Barbagallo, Marco Antonio M. Barbieri, Alberto Barceló, Sandhi M. Barreto, Henrique Barros, Leonelo E. Bautista, Athanase Benetos, Peter Bjerregaard, Cecilia Björkelund, Simona Bo, Martin Bobak, Enzo Bonora, Babu V. Bontha, Manuel A. Botana, Pascal Bovet, Juergen Breckenkamp, Monique M. Breteler, Grazyna Broda, Ian J. Brown, Michael Bursztyn, Antonio Cabrera de León, Hannia Campos, Francesco P. Cappuccio, Vincenzo Capuano, Edoardo Casiglia, Maurizio Castellano, Katia Castetbon, Luis Cea, ChihJen Chang, Noureddine Chaouki, Somnath Chatterji, Chien-Jen Chen, Zhengming Chen, Jin-Su Choi, Lily Chua, Renata Cífková, Linda J. Cobiac, Richard S. Cooper, Anna Maria Corsi, Michael C. Costanza, Cora L. Craig, Rachel S. Dankner, Saeed Dastgiri, Elias Delgado, Gonul Dinc, Yasufumi Doi, Guang-Hui Dong, Eleonora Dorsi, Nico Dragano, Adam Drewnowski, Robert W. Eggertsen, Paul Elliott, Anders Engeland, Cihangir Erem, Alireza Esteghamati, Caroline H. D. Fall, Jian-Gao Fan, Catterina Ferreccio, Leopold Fezeu, Josélia O. Firmo, Hermes J. Florez, Nélida S. Fornés, F. Gerry R. Fowkes, Guido Franceschini, Fredrik Frisk, Flávio D. Fuchs, Eva L. Fuller, Linn Getz, Simona Giampaoli, Luis F. Gómez, Juan M. Gomez-Zumaquero, Sidsel Graff-Iversen, Janet F. Grant, Ramiro Guerrero Carvajal, Martin C. Gulliford, Rajeev Gupta, Prakash C. Gupta, Oye Gureje, Tine W. Hansen, Jun Hata, Jiang He, Noor Heim, Joachim Heinrich, Tomas Hemmingsson, Anselm Hennis, William H. Herman, Victor M. Herrera, Suzanne Ho, Michelle Holdsworth, Gunilla Hollman Frisman, Wilma M. Hopman, Akhtar Hussain, Abdullatif Husseini, M. Mohsen Ibrahim, Nayu Ikeda, Bjarne K. Jacobsen, Hashem Y. Jaddou, Tazeen H. Jafar, Mohsen Janghorbani, Grazyna Jasienska, Michel R. Joffres, Jost B. Jonas, Othman A. Kadiki, Ofra Kalter-Leibovici, Raoul M. Kamadjeu, Ioannis Karalis, Mika J. Kastarinen, Joanne Katz, Lital Keinan-Boker, Paul Kelly, Omid Khalilzadeh, Young-Ho Khang, Stefan Kiechl, Ki Woong Kim, Yutaka Kiyohara, Junji Kobayashi, Maressa P. Krause, Růžena Kubínová, Pawel Kurjata, Yadlapalli S. Kusuma, Tai Hing Lam, Arnulf Langhammer, Carlene M. M. Lawes, Cai Le, Jeannette Lee, Claire Lévy-Marchal, Yanping Li, Yuqiu Li, Stephen Lim, T. O. Lim, Xu Lin, Cheng-Chieh Lin, Hsien-Ho Lin, Lars Lind, Lauren Lissner, Xiaoqing Liu, Patricio Lopez-Jaramillo, Roberto Lorbeer, Guansheng Ma, Stefan Ma, Francesc Macià, David R. MacLean, Stefania Maggi, Dianna J. Magliano, Marcia Makdisse, Giuseppe Mancia, Toshifumi Mannami, Pedro Marques-Vidal, Jean Claude N. Mbanya, Norma McFarlane-Anderson, Roberto Miccoli, Juhani Miettola, Hoang V. Minh, Juan F. Miquel, J. Jaime Miranda, Mostafa K. Mohamed, V. Mohan, Salim Mohanna, Ali Mokdad, Willem F. Mollentze, Dante D. Morales, Karen Morgan, Lorenza M. Muiesan, Sergio Muntoni, Iraj Nabipour, Tomoko Nakagami, Vinay Nangia, Barbara Nemesure, Martin Neovius, Kjersti A. Nerhus, Flavio Nervi, Hannelore Neuhauser, Minh Nguyen, Toshiharu Ninomiya, Marianna Noale, Sang W. Oh, Takayoshi Ohkubo, Oliviero Olivieri, Ayse Emel Önal, Altan Onat, Myriam Oróstegui, Hermann Ouedraogo, Wen-Harn Pan, Demosthenes B. Panagiotakos, Francesco Panza, Yongsoo Park, Valeria M. A. Passos, Mangesh S. Pednekar, Marco A., Pistelli, Francesco, Pedro Plans, Maria Polakowska, Neil Poulter, Dorairaj Prabhakaran, Qing Qiao, Masoud Rafiei, Olli, T. Raitakari, Luiz R. Ramos, Sanjay Rampal, Lekhraj Rampal, Finn Rasmussen, Kanala K. R. Reddy, Josep Redon, Luis Revilla, Victoria Reyes-García, Ragab B. Roaeid, Fernando Rodriguez-Artalejo, Rosalba Rojas-Martinez, Kimmo Ronkainen, Luis Rosero-Bixby, Gregory A. Roth, Harshpal S. Sachdev, José R. Sánchez, Selim Y. Sanisoglu, Susana Sans, Nizal Sarraf-Zadegan, Marcia Scazufca, Beatriz D. Schaan, Norberto Schapochnik, Hedi Schelleman, Ione J. C. Schneider, C. Mary Schooling, Bernhard Schwarz, Cevad Sekuri, Martha S. Sereday, Lluís Serra-Majem, Jonathan Shaw, Abdul S. Shera, Zumin Shi, Rahman Shiri, Xiao Ou Shu, Diego Augusto Santos Silva, Eglé Silva, Leon A. Simons, Margaret Smith, Stefan Söderberg, Suharko Soebardi, Vincenzo Solfrizzi, Emily Sonestedt, Ahmet Soysal, Pär Stattin, Aryeh D. Stein, George S. Stergiou, Jochanan Stessman, Akihiro Sudo, Machi Suka, Valter Sundh, Kristina Sundquist, Johan Sundström, Andrew B. Swai, E. Shyong Tai, Kristian Tambs, Fikru Tesfaye, George N. Thomas, Margaret Thorogood, Reijo S. Tilvis, Martin Tobias, Liv E. Torheim, Peter Trenkwalder, Jaakko O. Tuomilehto, Josep A. Tur, Christophe Tzourio, Ana I. Uhernik, Flora A. Ukoli, Nigel Unwin, Stephen Vander Hoorn, Mark P. Vanderpump, Jose Javier Varo, Marit B. Veierød, Gustavo Velásquez-Meléndez, Monique Verschuren, Lucie Viet, Salvador Villalpando, Jesus Vioque, Peter Vollenweider, Stefano Volpato, Ningli Wang, Ya X. Wang, Mark Ward, Sarwono Waspadji, Lennart X. Welin, Lars Wilhelmsen, Johann Willeit, Mark Woodward, André J. Xavier, Fei Xu, Liang Xu, Akira Yamamoto, Gonghuan Yang, Xiaoguang Yang, Li-Chia Yeh, Jin-Sang Yoon, Qisheng You, Zhijie Yu, Jian Zhang, Lei Zhang, Wei Zheng, and Maigeng Zhou.
Subjects: obesity, diabetes mellitus, blood pressure, cholesterol, epidemiology
Published: 2013

27. Insulin as an early treatment for type 2 diabetes

Author: Cristina Bianchi, Angela Dardano, Roberto Miccoli, and Stefano Del Prato
Subjects: Advanced and Specialized Nursing, medicine.medical_specialty, business.industry, Vascular disease, Endocrinology, Diabetes and Metabolism, Insulin, medicine.medical_treatment, Hazard ratio, Type 2 diabetes, medicine.disease, Endocrinology, Years of potential life lost, Internal medicine, Diabetes mellitus, Internal Medicine, Cardiology, medicine, Myocardial infarction, business, Glycemic
Abstract: The Emerging Risk Factors Collaboration (1) has recently confirmed that type 2 diabetes remains associated with substantial premature mortality. Compared with nondiabetic individuals, those with diabetes have a hazard ratio (HR) of 1.80 (95% CI 1.71–1.90) for death from any cause, 1.25 (1.19–1.31) for death from cancer, 2.32 (2.11–2.56) for death from vascular causes, and 1.73 (1.62–1.85) for death from other causes. As is apparent, the greater risk is owing to cardiovascular (CV) disease, which accounts for >60% of the years of life lost because of diabetes. Although this increase in CV risk is largely attributable to the coexistence of multiple metabolic and hemodynamic disorders, elevation of plasma glucose levels remains strongly associated with increased CV morbidity and mortality (2–4). In support of a potential direct effect of plasma glucose elevation is the association between fasting plasma glucose levels >100 mg/dL (5.6 mmol/L) and vascular death (1). Since this a near-linear association (1,5) it has been postulated that reduction of plasma glucose levels should exert a positive impact on CV morbidity and mortality. In the UK Prospective Diabetes Study (UKPDS), improvement of glycemic control was associated with a 16% reduction in the risk of myocardial infarction without achieving statistical significance ( P < 0.052) (6). Glycemic control in that seminal trial was, however, relatively unsuccessful. Though intensively treated patients achieved an average A1C of 7%, a progressive worsening in glycemic control occurred after the initial improvement. A more aggressive and successful approach was adopted in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) (7) and Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) (8) trials and Veterans Affairs Diabetes Trial (VADT) (9). In all these three large studies, glycemic control was achieved (A1C 6.5–7.0%) and maintained over a substantial period of …
Published: 2013

28. PPARG2 Pro12Ala and ADAMTS9 rs4607103 as 'insulin resistance loci' and 'insulin secretion loci' in Italian individuals. The GENFIEV study and the Verona Newly Diagnosed Type 2 Diabetes Study (VNDS) 4

Author: Roberto Miccoli, Maddalena Trombetta, Pier Franco Pignatti, Elisabetta Trabetti, Sara Bonetti, Enzo Bonora, Maria Linda Boselli, Riccardo C. Bonadonna, Giovanni Malerba, and S. Del Prato
Subjects: Adult, Male, medicine.medical_specialty, Peroxisome proliferator-activated receptor gamma, Genotype, endocrine system diseases, Endocrinology, Diabetes and Metabolism, ADAMTS9 Protein, Single-nucleotide polymorphism, Type 2 diabetes, Biology, Endocrinology, Insulin resistance, Risk Factors, Internal medicine, Diabetes mellitus, Insulin Secretion, Mendelian randomization, Internal Medicine, medicine, Humans, Insulin, Point Mutation, Genetic Predisposition to Disease, nutritional and metabolic diseases, General Medicine, VNDS, Middle Aged, medicine.disease, Pathophysiology, PPAR gamma, ADAM Proteins, Cross-Sectional Studies, Phenotype, Diabetes Mellitus, Type 2, Italy, Female, Insulin Resistance
Abstract: We investigated cross-sectionally whether the type 2 diabetes (T2DM) risk alleles of rs1801282 (PPARG2) and rs4607103 (ADAMTS9) were associated with T2DM and/or insulin sensitivity (IS) and beta cell function (βF) in Italians without and with newly diagnosed T2DM. In 676 nondiabetic subjects (336 NGR and 340 IGR) from the GENFIEV study and in 597 patients from the Verona Newly Diagnosed Type 2 Diabetes Study (VNDS), we (1) genotyped rs1801282 and rs4607103, (2) assessed βF by C-peptide/glucose modeling after OGTT, and (3) assessed IS by HOMA-IR in both studies and by euglycemic insulin clamp in VNDS only. Logistic, linear, and two-stage least squares regression analyses were used to test (a) genetic associations with T2DM and with pathophysiological phenotypes, (b) causal relationships of the latter ones with T2DM by a Mendelian randomization design. Both SNPs were associated with T2DM. The rs4607103 risk allele was associated to impaired βF (p
Published: 2013

29. Pleiotropic Effects of GIP on Islet Function Involves Osteopontin

Author: Marco Bugliani, Emma Ahlqvist, Piero Marchetti, Ola Hansson, Timothy J. Kieffer, Emily Sonestedt, Yang De Marinis, Alena Stančáková, Kasper Pilgaard, Nils Wierup, Stefano DelPrato, Sara Bonetti, Markku Laakso, Olga Kotova, Charlotte Brøns, Roberto Miccoli, Valeriya Lyssenko, Peter M. Nilsson, Pontus Dunér, Peter Osmark, Tiinamaija Tuomi, Albert Salehi, Pernille Poulsen, Sten Madsbad, Allan Vaag, Lisa Berglund, Alexander Balhuizen, Richa Saxena, Olle Melander, Johanna Kuusisto, Anna Wendt, Leif Groop, Marju Orho-Melander, Anna Jonsson, Maria F. Gomez, Jalal Taneera, Bo Isomaa, Riccardo C. Bonadonna, and Lena Eliasson
Subjects: Male, endocrine system, medicine.medical_specialty, osteopontin, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, islet function, 030209 endocrinology & metabolism, Gastric Inhibitory Polypeptide, Type 2 diabetes, Biology, beta cell function, Islets of Langerhans, 03 medical and health sciences, 0302 clinical medicine, Gastric inhibitory polypeptide, Glucagon-Like Peptide 1, Insulin-Secreting Cells, Internal medicine, Insulin Secretion, Genetics, Internal Medicine, medicine, Humans, Insulin, Osteopontin, Alleles, GIPR, 030304 developmental biology, 0303 health sciences, geography, GIP, geography.geographical_feature_category, medicine.disease, Islet, Glucagon-like peptide-1, pleiotropic effect of GIP, Endocrinology, Postprandial, Diabetes Mellitus, Type 2, Apoptosis, biology.protein, hormones, hormone substitutes, and hormone antagonists, Genome-Wide Association Study
Abstract: OBJECTIVE The incretin hormone GIP (glucose-dependent insulinotropic polypeptide) promotes pancreatic β-cell function by potentiating insulin secretion and β-cell proliferation. Recently, a combined analysis of several genome-wide association studies (Meta-analysis of Glucose and Insulin-Related Traits Consortium [MAGIC]) showed association to postprandial insulin at the GIP receptor (GIPR) locus. Here we explored mechanisms that could explain the protective effects of GIP on islet function. RESEARCH DESIGN AND METHODS Associations of GIPR rs10423928 with metabolic and anthropometric phenotypes in both nondiabetic (N = 53,730) and type 2 diabetic individuals (N = 2,731) were explored by combining data from 11 studies. Insulin secretion was measured both in vivo in nondiabetic subjects and in vitro in islets from cadaver donors. Insulin secretion was also measured in response to exogenous GIP. The in vitro measurements included protein and gene expression as well as measurements of β-cell viability and proliferation. RESULTS The A allele of GIPR rs10423928 was associated with impaired glucose- and GIP-stimulated insulin secretion and a decrease in BMI, lean body mass, and waist circumference. The decrease in BMI almost completely neutralized the effect of impaired insulin secretion on risk of type 2 diabetes. Expression of GIPR mRNA was decreased in human islets from carriers of the A allele or patients with type 2 diabetes. GIP stimulated osteopontin (OPN) mRNA and protein expression. OPN expression was lower in carriers of the A allele. Both GIP and OPN prevented cytokine-induced reduction in cell viability (apoptosis). In addition, OPN stimulated cell proliferation in insulin-secreting cells. CONCLUSIONS These findings support β-cell proliferative and antiapoptotic roles for GIP in addition to its action as an incretin hormone. Identification of a link between GIP and OPN may shed new light on the role of GIP in preservation of functional β-cell mass in humans.
Published: 2011

30. 2009 SIPREC consensus document executive summary: Cardiovascular prevention in subjects with impaired fasting glucose or impaired glucose tolerance

Author: Maria Grazia Modena, Bruno Trimarco, Diego Vanuzzo, Paolo Cavallo Perin, Paolo Verdecchia, Claudio Borghi, Stefano Del Prato, Massimo Chiariello, Enzo Manzato, Roberto Miccoli, Gabriele Riccardi, Augusto Zaninelli, Massimo Volpe, Giorgio Sesti, Antonio Tiengo, Volpe, Massimo, Borghi, Claudio, Cavallo Perin, Paolo, Chiariello, Massimo, Manzato, Enzo, Miccoli, Roberto, Modena, Maria G., Riccardi, Gabriele, Sesti, Giorgio, Tiengo, Antonio, Trimarco, Bruno, Vanuzzo, Diego, Verdecchia, Paolo, Zaninelli, Augusto, and Del Prato, Stefano
Subjects: medicine.medical_specialty, hypertension, Population, metabolic syndrome, Impaired glucose tolerance, Diabetes mellitus, insulin resistance, Epidemiology, medicine, Internal Medicine, Intensive care medicine, education, Socioeconomic status, education.field_of_study, Executive summary, business.industry, diabetes mellitu, cardiovascular prevention, medicine.disease, Impaired fasting glucose, impaired glucose tolerance, abnormal glucose regulation, diabetes mellitus, Medical emergency, Metabolic syndrome, business, Cardiology and Cardiovascular Medicine
Abstract: Cardiovascular diseases still represent the leading cause of mortality and hospitalization, worldwide. As a consequence of the marked demographic changes observed in the general population, the improved survival rate after an acute cardiovascular event and the progressive rise of costs (mostly due to technological and pharmacological innovations), the estimated burden of cardiovascular diseases will be soon become insurmountable for national healthcare systems. In this view, an integrated approach aimed at improving strategies for cardiovascular disease prevention and, thus, limiting the negative outcomes, would probably be successful. Such an approach may not only achieve long-term benefits, but even significant advantages in the short to medium term, mostly in asymptomatic high-risk individuals. Indeed, this latter population of asymptomatic high-risk individuals would mostly benefit from extensive application and improvement of strategies for cardiovascular disease prevention with a favourable cost-benefit ratio. The Italian Society for Cardiovascular Disease Prevention — Societa Italiana per la Prevenzione Cardiovascolare (SIPREC) — has recognized this strategic aim, focusing a significant part of its institutional actions on the effort for providing educational supports and consensus documents, which represent an overview of the scientific knowledge and personal clinical expertise by national and international key opinion leaders. Expert committees periodically generate ‘state-of-the-art’ documents on specific scientific topics with relevant socioeconomic implications and large clinical impact. The present article is dedicated to healthcare professionals, is based on the available evidence, and provides information on diagnostic algorithms and therapeutic options on abnormal glucose regulation (or dysglycaemia). The relationship between abnormalities in glucose metabolism and cardiovascular complications represents an important and relatively early target for cardiovascular disease prevention. SIPREC identified, even in this clinical setting, a group of scientific experts in order to form a multidisciplinary ‘task force’. This group has been asked to explain in a short, simple and effective fashion the epidemiological impact and the pathophysiological nature of the problem, its clinical features, potential diagnostic algorithms and therapeutic options, and its influence on the clinical practice of both specialist physicians and general practitioners. This work provides the background for discussing novel future strategies for cardiovascular prevention. It is also aimed at highlighting the importance of an emerging marker of cardiovascular risk, which is often not recognized and underestimated.
Published: 2010

31. POSTPRANDIAL HYPERGLYCEMIA IS A DETERMINANT OF PLATELET ACTIVATION IN EARLY 2 DIABETES MELLITUS

Author: Roberto Miccoli, Carlo Patrono, Giovanni Ciabattoni, Maurizio Averna, R Lauro, Antonino Consoli, Stefano Lattanzio, N Pulizzi, P. Di Fulvio, P Sbraccia, A. Ganci, F. Santilli, Gloria Formoso, Giovanni Davì, Santilli, F, Formoso, G, Sbraccia, P, Averna, M, Miccoli, R, Di Fulvio, P, Ganci, A, Pulizzi, N, Lattanzio, S, Ciabattoni, G, Consoli, A, Lauro, R, Patrono, C, Davì, G, Patrono, C, and Davì, G
Subjects: Blood Glucose, Male, Time Factors, Settore MED/09 - Medicina Interna, Dinoprost, postprandial hyperglycemia, platelet activation, Medicine, Enzyme Inhibitors, Settore MED/49 - Scienze Tecniche Dietetiche Applicate, Acarbose, platelet, Hemoglobin A, Hematology, Middle Aged, Postprandial Period, P-Selectin, Postprandial, Treatment Outcome, C-Reactive Protein, Italy, Female, Biological Markers, Type 2, medicine.drug, acarbose, platelet activation, postprandial hyperglycemia, type 2 diabetes mellitus, medicine.medical_specialty, Settore BIO/14 - FARMACOLOGIA, Urinary system, CD40 Ligand, Glycosylated, Arginine, Excretion, Lipid Peroxidation, Hemoglobin A, Glycosylated, Diabetes Mellitus, Type 2, Hypoglycemic Agents, Platelet Activation, Aged, Thromboxane B2, Double-Blind Method, Humans, Hyperglycemia, alpha-Glucosidases, Internal medicine, Diabetes mellitus, Diabetes Mellitus, Glycoside Hydrolase Inhibitors, Platelet activation, Glycemic, Glycated Hemoglobin, business.industry, Type 2 Diabetes Mellitus, medicine.disease, Endocrinology, business, Biomarkers
Abstract: BACKGROUND: Chronic hyperglycemia is a major contributor to in vivo platelet activation in diabetes mellitus. OBJECTIVES: To evaluate the effects of acarbose, an alpha-glucosidase inhibitor, on platelet activation and its determinants in newly diagnosed type 2 diabetic patients. METHODS: Forty-eight subjects (26 males, aged 61 +/- 8 years) with early type 2 diabetes (baseline hemoglobin A(1c) < or = 7% and no previous hypoglycemic treatment) were randomly assigned to acarbose up to 100 mg three times a day or placebo, and evaluated every 4 weeks for 20 weeks. The main outcome measures were urinary 11-dehydro-thromboxane (TX)B(2) (marker of in vivo platelet activation) and 8-iso-prostaglandin (PG)F(2alpha) (marker of in vivo lipid peroxidation) excretion rate, 2-h postprandial plasma glucose (PPG) after a test meal, and assessment of glucose fluctuations by mean amplitude of glycemic excursions (MAGE). RESULTS: Baseline measurements revealed biochemical evidence of enhanced lipid peroxidation and platelet activation. As compared with the placebo group, patients treated with acarbose had statistically significant reductions in urinary 11-dehydro-TXB(2) and 8-iso-PGF(2alpha) excretion rate as early as after 8 weeks and at each subsequent time point (between-group P < 0.0001 at 12, 16 and 20 weeks), following earlier decreases in PPG and MAGE. Multiple regression analyses in the acarbose group revealed that PPG was the only significant predictor of 11-dehydro-TXB(2) urinary excretion rate (beta = 0.39, P = 0.002) and MAGE the only predictor of 8-iso-PGF(2alpha) urinary excretion rate (beta = 0.42, P = 0.001). CONCLUSIONS: Postprandial hyperglycemia is associated with enhanced lipid peroxidation and platelet activation in early type 2 diabetes. A moderate decrease in PPG achieved with acarbose causes time-dependent downregulation of these phenomena, suggesting a causal link between early metabolic abnormalities and platelet activation in this setting.
Published: 2010

32. Prognostic implications of diabetes phenotyping: new concepts for an old disease

Author: Roberto Miccoli, Giuseppe Daniele, Stefano Del Prato, Graziano Di Cianni, and Cristina Bianchi
Subjects: Adult, Pediatrics, medicine.medical_specialty, medicine.medical_treatment, Bioinformatics, Diagnosis, Differential, Polyuria, Weight loss, Diabetes mellitus, Internal Medicine, medicine, Humans, business.industry, Insulin, Diabetic retinopathy, medicine.disease, Prognosis, Obesity, Diabetes Mellitus, Type 1, Phenotype, Diabetes Mellitus, Type 2, Emergency Medicine, Microalbuminuria, Female, medicine.symptom, business, Polydipsia
Abstract: Dr. Daniele: The case record presented here is that of D.S., a woman who is now 35 years. Her case report begins when she was 14 years (1987) at which time she underwent screening for diabetes because of her obesity (weight 95 kg, BMI 36 kg/m) and her family history of diabetes (mother and maternal grandmother). Based on her fasting glucose level (160 mg/dl), she was diagnosed with diabetes mellitus. At that time, her level of HbA1c was 7.8%. D.S. began treatment with a low calorie diet with which she obtained a moderate weight reduction (about 10–15 kg). During the following years, she has had several weight fluctuations until she reached 67 kg in 1995. Throughout that period, she had several medical visits, but there is no available information regarding her glucose levels. At 22 years of age (1996), she was admitted into the hospital following a hyperglycemic crisis, accompanied by polyuria and polydipsia. This hospitalization resulted in the diagnosis of insulin-dependent diabetes mellitus and subsequently, she began insulin treatment. On that occasion, diabetic retinopathy was found. The following years she saw an improvement in her glucose levels (HbA1c 6.5%) but a worsening of the retinopathy (diffuse microaneurysms, microhemorthages, and hard exudates) that required bilateral laser therapy. Concurrently, she developed a peripheral motor and sensory neuropathy, and then microalbuminuria but with preserved renal function. She continued insulin with four daily injections and maintained good metabolic control (HbA1c \ 6.5–7%), although her body weight rose continuously until she again reached 95 kg in 2000. In 2003, her HbA1c levels increased (7.8%) and she gained an additional 5 kg.
Published: 2009

33. Changing the treatment paradigm for type 2 diabetes

Author: Giuseppe Penno, Stefano Del Prato, and Roberto Miccoli
Subjects: Blood Glucose, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Type 2 diabetes, law.invention, Randomized controlled trial, Patient Education as Topic, law, Diabetes mellitus, Internal medicine, Internal Medicine, Medicine, Humans, Hypoglycemic Agents, Diabetes Progression, Prevention, and Treatment, Exercise, Life Style, Glycemic, Macrovascular disease, Advanced and Specialized Nursing, business.industry, Standard treatment, Hazard ratio, medicine.disease, Metformin, Surgery, Treatment, Diabetes Mellitus, Type 2, Hyperglycemia, business, Delivery of Health Care, Risk Reduction Behavior, Algorithms, Diabetic Angiopathies, medicine.drug
Abstract: Based on the results of the U.K. Prospective Diabetes Study (UKPDS), “… treatment of type 2 diabetes [should] include aggressive efforts to lower blood glucose levels as close to normal as possible. …” This was the recommendation the American Diabetes Association promulgated based on the results of the UKPDS when published (1). The suggestion was soon adopted by official guidelines in every region of the world (2). They are generally consistent in recommending an A1C goal of 10,000 subjects with type 2 diabetes and vascular disease, or multiple CV risk factors, to an intensive treatment program targeting normal blood glucose values and A1C
Published: 2009

34. 'The potential of PDZ domains in the expression of modified saporin variants'

Author: Giansanti, Francesco, LUANA DI LEANDRO, Roberto, Miccoli, Ilias, Koutris, Pitari, Giuseppina, Alessio, Lombardi, MARIA SERENA FABBRINI, Flavell, DAVID J., Flavell, SOPSAMORN U., Stefano, Gianni, and Ippoliti, Rodolfo
Published: 2008

35. Insulin Resistance and Lipid Disorders

Author: Roberto Miccoli, Stefano Del Prato, Cristina Bianchi, and Giuseppe Penno
Subjects: medicine.medical_specialty, Very low-density lipoprotein, Reverse cholesterol transport, nutritional and metabolic diseases, Biology, medicine.disease, Biochemistry, Endocrinology, Insulin resistance, Lipotoxicity, insulin resistance, lipid disorders, Internal medicine, medicine, Lipolysis, lipids (amino acids, peptides, and proteins), Hepatic lipase, Dyslipidemia, Chylomicron
Abstract: The dyslipidemia of insulin resistance is characterized by elevated levels of triglycerides (TGs), low HDL-cholesterol and small dense LDL particles. Many of these features are affected by the reduction in insulin sensitivity, with a central role played by abnormalities in assembly and secretion of VLDL. Postprandial hyperlipidemia is common in insulin-resistant individuals, probably owing to reduced lipolysis of nascent chylomicrons. Increased exchange of HDL cholesteryl esters for TGs is associated with lipolysis of HDL-TG by hepatic lipase and this produces dysfuntional particles that are less stable than normal particles and contribute to decreased reverse cholesterol transport. On the other hand, TG accumulation has been described as dangerous for several tissues, the so-called lipotoxicity, particularly for pancreatic β-cells where it results in impairment of glucose-stimulated insulin secretion and accelerated apoptosis. Recently, islet dysfunction and loss of insulin secretion have also been assoc...
Published: 2008

36. Optimizing management of metabolic syndrome to reduce the risk: focus on life-style

Author: Giuseppe Penno, Giuseppe Daniele, Roberto Miccoli, Cristina Bianchi, Luca Benzi, and Stefano Del Prato
Subjects: medicine.medical_specialty, Nutritional Status, Disease, Type 2 diabetes, Motor Activity, Therapeutic approach, Pharmacotherapy, Insulin resistance, Risk Factors, Environmental health, Internal Medicine, medicine, Genetic predisposition, Humans, Exercise, Life Style, Metabolic Syndrome, business.industry, Smoking, Feeding Behavior, medicine.disease, Obesity, Cardiovascular Diseases, Emergency Medicine, Physical therapy, Insulin Resistance, Metabolic syndrome, business, Risk Reduction Behavior
Abstract: The prevalence of metabolic syndrome (MS) is increasing all over the world and its incidence is expected to rise in the next years. Although genetic predisposition appears to play an important role in the regulation of metabolic parameters and in particular of body weight, the rapid increase in the prevalence of obesity and MS suggests that ecological factors (social, economic, cultural and physical environment) are promoting those conditions in susceptible individuals. People with MS are at increased risk of type 2 diabetes and cardiovascular disease and therefore they represent a priority target for preventive strategies. Life-style modifications based on healthy diet and increased physical activity are an effective preventing and therapeutic approach. Unfortunately, implementation of life-style modification and maintenance of effects is a difficult task both at personal and social level, thus drug therapy can be taken into account.
Published: 2008

37. Non-traditional markers of atherosclerosis potentiate the risk of coronary heart disease in patients with type 2 diabetes and metabolic syndrome

Author: Lucia Malloggi, M. Corfini, Giuseppe Penno, Stefano Del Prato, Graziano Di Cianni, Roberto Miccoli, M. G. Giovannitti, Rossana Barontini, and Cristina Bianchi
Subjects: Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Population, Medicine (miscellaneous), Coronary Disease, Type 2 diabetes, Risk Assessment, Gastroenterology, Risk Factors, Diabetes mellitus, Internal medicine, Odds Ratio, Prevalence, Humans, Medicine, education, National Cholesterol Education Program, Serum Albumin, Aged, Glycated Hemoglobin, Metabolic Syndrome, education.field_of_study, Nutrition and Dietetics, business.industry, Cholesterol, HDL, Fibrinogen, nutritional and metabolic diseases, Type 2 Diabetes Mellitus, Cholesterol, LDL, Odds ratio, Middle Aged, Atherosclerosis, medicine.disease, Uric Acid, Cholesterol, Cross-Sectional Studies, Endocrinology, Diabetes Mellitus, Type 2, Italy, Creatinine, Female, lipids (amino acids, peptides, and proteins), Microalbuminuria, Metabolic syndrome, Cardiology and Cardiovascular Medicine, business, Biomarkers
Abstract: Background and aims The aims of this study were to establish the prevalence of metabolic syndrome (MS), in type 2 diabetes mellitus (DM), according to National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria, and to assess the association of MS with other cardiovascular (CV) risk factors in these patients. Methods and results A cross-sectional study was conducted in 1610 patients with type 2 DM. Glycated hemoglobin A1c (HbA1c), total cholesterol, low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C), uric acid, fibrinogen, creatinine, and albumin/creatinine ratios were measured. The risk of coronary heart disease (CHD) was calculated using the UKPDS Risk Engine. Seventy percent of the diabetic population met the criteria for MS; central obesity and hypertension were the most common criteria. Subjects with MS had higher levels of HbA1c, LDL-C, non-HDL-C, uric acid, and fibrinogen compared to patients without MS. Similarly, microalbuminuria and a high triglyceride (Tg)/HDL-C ratio (a marker of small LDL-C) occurred more frequently in patients with MS. When patients with no history of CHD events were considered, mean CHD risk was greater in those with, than those without, MS. Conclusions MS is highly prevalent in type 2 DM and is commonly associated with non-traditional CV risk factors. The diagnosis of MS seems to confer additional CHD risk in patients with type 2 diabetes.
Published: 2008

38. Pharmacological intervention in prediabetes: considering the risks and benefits

Author: S. Del Prato, Cristina Bianchi, Giuseppe Penno, and Roberto Miccoli
Subjects: medicine.medical_specialty, business.industry, Endocrinology, Diabetes and Metabolism, Psychological intervention, Type 2 Diabetes Mellitus, Context (language use), Type 2 diabetes, medicine.disease, Prediabetic State, Endocrinology, Diabetes Mellitus, Type 2, Risk Factors, Intervention (counseling), Diabetes mellitus, Internal Medicine, Physical therapy, Humans, Medicine, Obesity, Prediabetes, business, Intensive care medicine, Adverse effect, Life Style
Abstract: The impact of the diabetes epidemic will be staggering in terms of costs to individuals and society. Social educational initiatives are imperative to altering the lifestyle trends that drive the growth of the epidemic. Targeted lifestyle or drug interventions aimed at preventing progression from prediabetes to type 2 diabetes mellitus carry costs and risks that need to be considered in the context of expected benefits, which also need to be carefully defined. In terms of pharmacological intervention as part of a primary prevention programme, the risk/benefit assessment must include the potential for adverse effects in a large population of asymptomatic individuals, a significant proportion of whom would not progress to diabetes in the absence of treatment and in whom impaired glucose regulation may reflect different underlying pathogenetic mechanisms. Improving the balance of risks and benefits in drug interventions will require a greater ability to determine which treatments are likely to safely improve glucose regulation and prevent diabetes and its adverse cardiovascular outcomes in individual patients.
Published: 2007

39. Early impairment of beta-cell function and insulin sensitivity characterizes normotolerant Caucasian women with previous gestational diabetes

Author: Alessandra Ghio, Roberto Miccoli, Stefano Del Prato, Riccardo C. Bonadonna, Cristina Lencioni, L Volpe, Luca Benzi, Ilaria Cuccuru, Graziano Di Cianni, and Kyriazoula Chatzianagnostou
Subjects: Adult, Blood Glucose, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Medicine (miscellaneous), beta cell function, White People, Impaired glucose tolerance, Insulin resistance, Pregnancy, Insulin-Secreting Cells, Internal medicine, insulin resistance, medicine, Humans, Insulin, Glucose tolerance test, Nutrition and Dietetics, medicine.diagnostic_test, business.industry, nutritional and metabolic diseases, Type 2 Diabetes Mellitus, Glucose Tolerance Test, medicine.disease, Impaired fasting glucose, Gestational diabetes, Diabetes, Gestational, Endocrinology, gestational diabetes, Female, Blood sugar regulation, Cardiology and Cardiovascular Medicine, business
Abstract: Women with previous gestational diabetes (pGDM) are at high risk of developing type 2 diabetes mellitus. The aim of this study was to evaluate insulin action and insulin secretion in women with pGDM.One hundred and fifty-three pGDM women and 45 with normal glucose tolerance during pregnancy (controls) were studied 1-3years after delivery. Insulin sensitivity (ISI) and beta-cell secretory capacity (beta-index) were derived from 75-g OGTT. Disposition Index was calculated as the product of beta-index and ISI. One hundred and twenty-two pGDM were normotolerant (NGT) and 31 had impaired glucose regulation (IGR) i.e. impaired glucose tolerance and/or impaired fasting glucose. NGT-pGDM, as compared to controls, had significant impairment in insulin action (ISI: 5.46+/-2.81 vs. 7.38+/-3.68, P0.01) and insulin secretion (beta-index: 4.68+/-1.01 vs. 5.24+/-0.82 pmol/min/m(2); P0.01). A further impairment was apparent in IGR-pGDM for beta-index (4.16+/-1.09; P0.05). The disposition index was reduced in NGT-pGDM as compared to controls (33.9%) and further reduced in IGR-pGDM (28.6%, vs. NGT-pGDM; ANOVA P0.001). In women of normal weight, ISI and beta-index were significantly (P0.01) impaired in NGT-pGDM compared to controls and further reduced in IGR-pGDM, although a more pronounced defect in insulin secretion was apparent in these women (beta-index: 4.02+/-0.9; P0.05).Normotolerant women with pGDM show both impairment in insulin secretion and action irrespective of body weight. A more pronounced defect in insulin secretion seems to characterize normal weight women while a more prominent defect in insulin action is found in overweight women.
Published: 2006

40. 40(th) EASD Annual Meeting of the European Association for the Study of Diabetes : Munich, Germany, 5-9 September 2004

Author: S. Artigas, A V Dreval, Mark I. McCarthy, C Watson, Peter H. Bennett, M Quint, Y Ikeda, E Alpert, F Schiele, H Sekihara, Erik Gylfe, P Lowe, J Kuhlmann, Alain Golay, V Longo, Shahidul Alam Khan Akm., L G Mantovani, M Zawodniak-Szalapska, G Winkler, T Harrity, L Virág, U Johne, Kuo S-W., Linda C Tapsell, J Rodriguez, Michel Komajda, K Kankova, Carole A. Cull, M Sporna, E Estilles, U Ribel, M C Spruce, E Buzzigoli, T Prazak, J K McLaughlin, M K Lingohr, M Lim, F Calara, A Siebenhofer, G Meregalli, Roberto Anichini, A D Baron, R Kurashvili, P C Butler, G I Fantus, T. E. De Gooyer, Park Y-M., R. Walther, S Heinrich, Agnieszka Zawiejska, S Mukherjee, Nikolaos Papanas, G Wong, Ian D. Caterson, David M. Maahs, Shuichi Kaneko, Alexandra E. Butler, Francisco Javier Ampudia-Blasco, O N Kong, Attali J-R., C A Hedman, K Oshinyemi, Nicolle Müller, I C Cranston, N Okumus, M V Vlaiculescu, Balasubramanian Ravikumar, W W Cheatham, K Mukasa, K B Biswas, Annunziata Lapolla, Phil McEwan, G Mader, Gilles Chassot, Dragi Anevski, Werner A. Scherbaum, M Donath, C Hesselmann, R A Gandhi, David E. Moller, Ezio Bonifacio, C Garcia, V Ifandi, P Hornnes, Nieuwenhoven Fav., C Puech, S Pérez-Del-Pulgar, Kim S-R., G Hines, C Rubio Terrés, Michael Gaster, N. Hosszufalusi, A Scholze, Andrew A. Young, Stavros Liatis, F Hariri, S Tan, Paul Valensi, Allan E. Karlsen, J Kim, E. Moberg, J Kaiser, L Berman, G Nelson, A Altkrüger, P Kothare, D B Cook, S Doran, G. van Dijk, Shahnaz Shahinfar, Kim C-S., P Stahl, M Manousaki, S Sigrist, S K Lim, M. P. Stern, A Guberti, C Rezzani, J McKenney, Karl Thomaseth, Sofia Carlsson, M Julia, R Brillante, I Rubesova, T Darkow, E Matsumoto, Wendy M. Macfarlane, M Di Martino, G Bardini, Rossella Menghini, D Duhot, E Farcasiu, Annalisa Natalicchio, I Lindner, J Buvat, Christian L. Brand, Harry Dorchy, Iwona Pietrzak, Z T Luo, P Home, M Ekelund, Jesper Gromada, Kristine Færch, F Piarulli, H Kim, R Mentel, Zsuzsanna K. Zsengellér, Dullaart Rpf., Anton Luger, Thomas A. Pearson, V Manicardi, P Rösen, Feng Y-M., R Morganti, Lars Hansen, Demuth H-U., Haruo Kasai, A Shostak, Rudi Steffensen, G Taylor, Markolf Hanefeld, C Santini, E Hamaguchi, Roberto Miccoli, F Storms, M Cooper, Y Lee, Allison E. Aiello, P Smith, T Suehiro, K Treece, M Waluś, Timothy A Welborn, Simone Baltrusch, E Kontela, S Chai, J Crean, H Yokoyama, Johan G. Eriksson, Rafael Hernández Hernández, J Rodríguez-Saldaña, M P Tornero, G Formoso, D. Lovell, E Bingham, A Mylonakis, M Manteghetti, D Fedele, Antonio Martín-Duce, Ralph A. DeFronzo, D Salcedo, Kurt Højlund, Antonio Petrone, Sheu Whh., C Gutierrez, Flavia Pricci, S Kurita, Z G Abbas, M M Benedetti, Philippe A. Halban, Daniel J. Cox, O Ljungkvist, Justine Davies, J Palsgaard, Lars Sjöström, E Bosi, L Janin-Manificat, W. F. Kelly, M. Fernandez, E Colak, O V Mulyarchik, B Kronshage, F Lang, M Erfurth, Takashi Kadowaki, N Jendrike, U Walter, J Wishart, Y. Neye, D Kim, N Furuhashi, M Barsotti, D Florow, L Ke, L Borgquist, N C Jackson, Ffolliott M. Fisher, V Baskar, K Yoshioka, Bryan A. Wolf, G Chabrier, R Skoumal, Livio Luzi, H Kose, I Pharisien, B. Klein, H Winiarska, M C Johnson, L Griffiths, Nonna Kravchun, C Combe, Baptist Gallwitz, J Zdychova, L Skorda, Jorma Ilonen, W Gao, I N Steen, A Terrinoni, P D Ambery, W Kern, C M Kusminski, Cho M-H., Paolo Pozzilli, Louise G. Grunnet, E Schönle, David R Matthews, Robert W. Taylor, Y Cohen, Kim H-S., M P Eccles, N B Tutuncu, D McDowell, Richard M. Bergenstal, K Takamatsu, T Steiner, Jaan Palgi, Valdemar Grill, N Niculescu, G Federici, S Lehto, P. M. McKeigue, M Barone, Michael E. Trautmann, S Smirnov, J Mannion, M Eto, C Rousseau, M Conti, C S Ernest, Antonio Ceriello, D H Schweitzer, Jung E-D., Andreas Festa, Avijit Lahiri, A Shepelkevich, A Murro, A Kollmann, Jonathan R.S. Arch, R Landgraf, Son H-Y., I Engelsberger, E Agardh, S Rodríguez-Mulero, P J Kraml, K Lee, D. F. Du Toit, E Kim, G Fadini, Williams Ajk., Philip Home, M B Antcieferov, C Perlemoine, D Perrea, Song X-L., D Ruggieri, Krister Bokvist, Heidi Sørensen, Bilbao, G Yoshino, J P Taylor, Shen H-M., S M Furier, R Urquhart, J Wohlgelernter, Jianping Weng, T. Baba, Q Hong, C Silva, Castaigne J-P., M Felaco, X X Zhang, M Jaroň, Milla Rosengård-Bärlund, J G Papp, Toshio Miyata, Lervang H-H., Park M-K., I Kinalska, A Long, Oomen Phn., N Kogawa, Ippolita Patrizia Patera, S. Karadeniz, Dinesh Selvarajah, D S Chung, A Wensaas, Richard Imrich, M Recasens, J Ruxer, O Buchea, E Wilpart, S P Stepanenko, Le Ttd., H Ohgawara, Mariaconsuelo Valentini, A Mondok, M Peltonen, Marianne O. Larsen, K Chatzianagnostou, Agneta Ståhle, A L Ferrari, L Bordier, F Maingrette, A Matsuda, G Vukomanovic, Jakob D. Wikstrom, T Yamakita, E Gorostiaga, J Jin, B Gopalan, Heinz Drexel, S Hewitt, Rury R. Holman, C Dieterle, T L Ruchti, N Asatiani, M Sidira, A Iezzi, A J Sommerfield, D Châtenet, M L Olsen, R Bergemann, C Koehler, T L Kuraeva, B Balas, Christian Berne, E Santos-Mazo, G Smith, A Siejka, R Kožnarová, A Mattina, S Sheikh, A Adomeit, M Rasmussen, J. Fagerudd, N Busciantella Ricci, Nuria Vilarrasa, E Hammar, T L Thoms, L Aydın, Ron G. Rosenfeld, A Nikolajuk, R Gos, C L Morgan, H L Yu, D Dheelchand, S Ramrath, N Boudriga, Jerome I. Rotter, C Jahannault, W M Weston, Folke Lindgärde, M Hertlova, D Knight, A Monroy-Mayorga, E Pardini, A Chamson-Reig, B Franke, Janie McCluskey, Joseph Bryan, C Nikolopoulou, Christie M. Ballantyne, Fausto Santeusanio, L Pegoraro, M Lee, A Klimenko, S Jaiveer, K. Pettersson-Fernholm, Michael A. Nauck, A Ekbom-Schnell, G Deferrari, Riccardo Schiaffini, S. Pampanelli, Khan Aka., David Hopkins, Maija Wessman, M Kamarinos, Noh J-H., O Ebisui, K McCarroll, Jeppe Sturis, Peter Nowotny, N Gorbenko, Åke Sjöholm, David G. Maggs, A E Halseth, B Cresci, A A Ortiz-Gress, A Korakovouni, O Matejkova, C E Mogensen, C J Lin, Ramon Gomis, H Seaman, C Granier, Yang C-H., F Assah, O Sanchez, Fausto Machicao, Peter G. Morris, Alberto Ortiz, A Giardinelli, D Bracaglia, A Gonzalo, S Pavlatos, Andreas Lechner, F Canovic, L Sjolind, Allan Vaag, Birgitte Bruun Nielsen, David A. Ziegler, Vito Lampasona, R Gershoni-Baruch, A. Dei Cas, H Renz, E Mena, Matthew Waltham, Kim D-M., H Levanen, D D Mick, Valentina Alexandrovna Peterkova, E Meskhishvili, Sarah Nutland, R Bustani, John R. Lindsay, M Christoforidou, A Abicht, E Harno, K Cyganek, A Fitchet, S Neelotpol, P Nikishin, P Serradas, J Hinrichsen, M Halvorson, M Chovatia, B Voet, Jinny Willis, E Parretti, M Haslbeck, M Wellard, L Teng, Julio Wainstein, J S Fischer, K. Lalic, D Roggenland, I Gich, R Anwar, Maurizio Cassader, D Serota, X J Li, R J Schotzinger, Vilmundur Gudnason, Björn Zethelius, S A Wootton, W Andrzejewski, R Rezsohazy, R Gao, T Klimentova, T Mazurek, I Bruckner, C Dohrmann, R E James, G daSilva Xavier, Kim S-Y., A Dorca, Stuart J. Pocock, Terri J. Allen, I Giovos, P B Parab, N H Andersen, P Fotinakis, Miriam Cnop, H Lee, Norbert Tennagels, Omorodola I. Abatan, F Ailett, I. Lager, D Manzella, H Hut, Larry A. Distiller, G Lip, Lim S-K., Rong Zhang, T Tsuno, Steen Knudsen, M. Bajardi, Manuel Benito, Dai Sugimoto, Melvin J. Prince, D W Dunstan, D Rankins, K A Majali, G Ozansoy, Isabella Russo, S Uçak, G Annuzzi, R Talar-Wojnarowska, K Lange, S Neugebauer-Baba, Campbell H. Thompson, Eric Renard, P. D. Mountjoy, Z Morrison, Elizabeth A. Davis, Franco Cavallo, C Corvaja, R Antuña, Craig John Currie, H Linnebjerg, He Y-L., A J Palmer, Mariola R. Chacón, H Malinska, M. Jones, R Lichnovská, K Mandes, Paolo Tessari, T Mokhort, A Laina, H. L. Y. Chan, I Schmidt, R Banks, Richard G. IJzerman, L Ksinantova, G Setti, H Vaudry, A Gallo, V Spallone, Chen J-W., Thomas Danne, A Chong, M Hallschmid, S Aczel, S Hulme, N Islam, M Hosoi, P M Ternan, P Di Bartolo, N Bishara, T Shibasaki, Martin A. Osterhoff, Im S-S., M Jecht, T Hamaguchi, S Mattera, K Ways, Elizabeth Northam, U Rajala, Reinhard W. Holl, L Yang, S Panaiotopoulos, K Horvath, R Kluge, Thora B. Bodvarsdottir, Y Dong, Irene Alemanno, C McDougall, Reimar W. Thomsen, M Campbell, W Rabl, John Öhrvik, Yuichiro Yamada, Paola Ungaro, W Benzer, Mike Sampson, Roberto Trevisan, R G Radu, Aas A-M., P E Lobo, Ricardo Scott, S M Son, Josephine M. Forbes, T A Hillier, K L Wyne, Louis L. Nguyen, J Farmer, M H Tan, Kwon H-S., J Yang, L Sandvik, Franco Folli, A K Jenum, M Nguyen, W Pratipanawatr, A L Frederiksen, Rebecca Smith, Lee H-J., A Schäfer, C Manuelli, G S Denver, T Vukovich, B Maceira, K Matsumoto, K. Chokkalingam, Nurcan Üçeyler, P Modi, Timothy M. Morgan, S Mertens, B M Singh, Michaela Riedl, K Iso, C Cucurullo, G. F. Bottazzo, M Calvani, K Hur, J Wetzels, Kazuhiro Takahashi, Y Aso, H Stammer, M G Masding, Fitsum Guebre-Egziabher, J L González-Sánchez, L Armstrong, Alberto Maran, Peter G.F. Swift, S S Popovic, J Starczynski, E Vitacolonna, Luigi Laviola, R W Gelling, Marina Cardellini, D Barilla, Rosa de Diego Martínez, W H Landschulz, Anne Mette Rosenfalck, R K Wong, Kevin E. Schneider, K Peros, Giuseppe Nanni, F Zhang, I Rákóczi, T Iburi, M Nakhjavani, X Q Zhang, S Tournis, Per Lav Madsen, Graham A. Hitman, A. Tura, K Laubner, N D Kostic, Lawrence M. Dolan, R. Sinha Roy, J A Wagner, J. Tuomilehto, J Hauptman, M Abdel-Ghany, D Lacombe, Toralph Ruge, Johannes A Maassen, Triantafyllos Didangelos, K Sasaki, I Argüelles, Klaus Levin, C Popow, Emanuel Christ, R Chetty, L Baillet-Blanco, Jo-Ann Salmon, T Mine, James L. Trevaskis, I Franke, J Gorski, E A Andrianova, A Dayan, A Caballero, Aleksandra Gilis-Januszewska, M Yasujima, Z Kasalová, C.D.A. Stehouwer, F. K. Gorus, G A Nichols, A Glowania, David P. Strachan, P Fredlund, N. F. da Silva, P Reboldi, M Sausbier, K H Groenier, G Stuccio, N Guttman, K R Ahmed, A D Ristic, T Kapellen, J Coutcher, Aldo V. Greco, Oswald Wagner, A Zagayko, Maria Alevizaki, B B Zhang, W F Ferris, Jenny Fredriksson, Lois Jovanovic, J Hänninen, R De Giglio, Kazuo Yagui, O Potterat, P Hamliton, R E Scranton, B Mankovsky, A Stylianou, B Fellström, Abdel-Wahab Yha., M Kitagawa, Katherine L. Baldock, F R Johnson, F Baigts, S D'Addato, F J Sanz, A Mistry, S D Wise, T Pratipanawatr, U R Fölsch, James R.C. Parkinson, Claudia Sommer, C Park, F E Griffiths, M L Martí, R Demirtunc, S Taniguchi, J Lundkvist, T Siegmund, Juan Sztajzel, C Dienesch, F Baumgartner, L Scalone, T M Mckolanis, K Otake, Ullrik Pedersen-Bjergaard, T M Vriesendorp, Michael B. Wheeler, Henry Schmitt, Peter Hovind, S Lange, Stephane Roze, L. Van Gaal, B Klaproth, Anthony E. Civitarese, D Eckland, A Dagar, D F Hopkins, Kari Stefansson, C Gonzalez-Yanes, B Meyboom-de Jong, D. J. Betteridge, K Buhling, M Crepaldi, Ana M. Wägner, L Renna, L Volpe, R McBride, V Corbo, E O Brennesvik, R P Hayes, R Abdollahnia, G Viviani, C F Liew, Francisco Pérez-Bravo, Jeffrey Baron, Brian M. Frier, H H Samira, D Szentendrei, K. J. Schjoedt, W K Waldhäusl, D Gniuli, D Zou, G Tschank, V Urbančič, A L Nolan, Albertini J-P., J Malcomson, M Larbig, C Cheyssac, K Aurich, C M Kesson, S Heller, Maija E. Miettinen, R F Luco, Adrian J. Cameron, Luigi Mattiello, Z. Metelko, X E Zhang, M Parramón, I. G. Obrosova, J Fruchart, M Ilic, Björn Eliasson, Gilles Chatellier, M A Martín, D M Kendall, Holger Luthman, V F Varillas, D Maccubbin, Jang S-A., Amalia Gastaldelli, E Salzsieder, P. de Mol, A Yoshida, H D Lindner, D Gostiljac, M Just, Pan C-Y., J M Fujitaki, G Eiermann, K Bergenheim, A D Frick, A Agacdiken, K Varytimiadis, K Cseh, D A Jackson, S Calderari, Dena G. Hernandez, H M Liebich, K Min, F. de Zegher, Bernd Kulzer, K Han, Ulrich A. Müller, D Marrero, H Hatakeyama, René Koopman, Doo H-K., Petr Wohl, P. Sharp, P Forder, Thor Aspelund, N Meneveau, R M Schmülling, R Aubert, Thom Sam., H Youshikawa, M Ankelo, D Bowden, I Kelly, Frédéric Fumeron, M Sartini, Robert S. Sherwin, L Varadhan, A Criscimanna, John Betteridge, V Jelic, M Bartnik, N Lemke, B Ursø, A Bertoldo, A M Owona, H Okochi, L Pérez-Tamajó, S L Monfre, Daniel Brandhorst, K T Legg, Andries J. Smit, Veronica Sancho, Masashi Hirai, C Klein, Paul J. Thornalley, A Chaidaroglou, K Miura, B Zinman, O M Dvoynishnikova, J Plank, Jan Bolinder, C Lush, B Rubi, R Pozzilli, M Bashir, S A Shtandel, F Mosca, A Naskalska, Josef Vcelak, U Sausbier, P Cavaiani, T U Baehring, Michele Solimena, P Formisano, M Rastaldi, Bernard Thorens, J Ruzzin, E Arbit, M. Hori, Torkel B. Brismar, E Soltes Rak, A Filo, P Heinke, Matthew P. Coghlan, M Masotti, I Perevozskaya, K Ahn, I Moules, K Van Dyck, I Goldstein, Z Mathe, G Z Zhao, S Fajardo, J Taylor, S Chrul, J C Pareja, D Hadjidakis, A J Scheen, N Siddiqua, D C Cavan, R Grella, Krabbe S, H J Rochlitz, A E Hinkkanen, W Wilpshaar, Richard Stevens, M Dreyer, S Hara, X Wang, Melania Manco, D Gillen, Magalie A. Ravier, Olli Simell, John C. Lawrence, Kohnert K-D., Agardh C-D., A Berghold, L Kristensen, Grant Sfa., N Gursoy, Leif Groop, N Freemantle, Anja Schweizer, L Pala, Legros J-J., C. Di Pietro, N. Yamamoto, J Magyar, B Nikolovski, H Ikeda, D Lee, Bruce A. Buckingham, A O Wollitzer, I Kennedy, C Ernest, Neville H. McClenaghan, S Tanaka, Asimina Mitrakou, T Heinze, W Kerner, Moeenaldeen Al-Sayed, Charles Thivolet, L Klaff, A Miconi, Cristina Valeri, J. O. Christensen, K. Ekberg, A Jardine, T Endo, X Zhang, D F Child, A Kienitz, D K Seidel, H. Tada, Sylvie Abouna, Cyrus Cooper, Catherine R Chittleborough, Roberta Assaloni, S Corbi, A K Bose, K Ozawa, C Ahn, K A Deans, G Jackowski, Martin Gibson, Patrick McElduff, O A Mojiminiyi, Manuel Serrano-Ríos, O Dupuy, A L Davydov, Iwar Klimes, Sten-Anders Ivarsson, N Ichino, R Matsutomo, E R Smith, A Stefanovska, B Dehmel, K Koniavitou, E Agascioglu, M Hatazaki, J. M. Gibson, T Yada, P Ribaux, M Rupnik, K Fridell, G Scutaru, L Chugunova, Henrietta Mulnier, A Kendereski, H Lehnert, C Billi, M Sobczak, Francisco M-Mj., L K Archibald, S Sukumvanich, David B. Dunger, I. Benke, G Yillar, N Stingemore, J. M. Boavida, Y Shi, Jimmy D. Bell, L Bozzetto, Andrew J. Ahmann, E Jebens, J Keiding, Elena Henkel, Mark Fineman, J F McRae, Carol Forsblom, S Martemucci, Lourdes Ibáñez, P G Prieto, L Ringholm Nielsen, S Pratas, B von Stritzky, Julio Rosenstock, Lee K-W., J Stocks, L J Strow, I Samarguliani, L Wennekes, R Cheung, Abhishek Nag, Roberto Gambino, Y Suleymanoglu, E Murphy, T T Durck, M F Peyrot, Y Unno, Alexander Mayorov, Eleuterio Ferrannini, D. C. Rao, D Neely, H Karunajeewa, J Palmisano, Julia B. Lewis, M Ravid, G Pons, E Junca, P Vexiau, S Sailesh, D K Miloslavskiy, O N Bondarenko, U Smith, S Torri, Constantine Tsigos, Cesario Bianchi, Mattia Locatelli, D Jaquet, Virpi Lindi, M Moroi, M E Tushuizen, P Pelicci, R Scognamiglio, Pal Pacher, S M Thyssen, A Péterfalvi, Y Ho, S Guntram, L Romics, T Nakagami, Clive S. Cockram, Irina Kowalska, K Brodbeck, Gojka Roglic, J. Dörig, Lise Tarnow, Therese Tillin, A López-Alba, Martin Krššák, Moses Elisaf, S Hata, D P Snoeck, D Schmoll, O V Udovichenko, A Scaramuzza, J Paul, John H. Fuller, Nicholas Katsilambros, Michele Muggeo, Pia Ekbom, Piero Marchetti, V Melki, C Bailleau, H Stavrianos, A D'Errico, Geremia B. Bolli, Amabile Maier, Kelter A-R., Anders Green, Q J Morélis, Steffen Thiel, C Watkins, R C Cheung, A Clark, Elvira Fioriti, N Ari, Nam J-Y., Y Cottin, L G Krinelke, H Al Mohammedi, Simon C. Fleming, C Jones, Z Kerényi, Ahn Y-H., Meile M-J., P Nánási, M Graner, V Canonico, Gangnerau M-N., Hugh R. Taylor, Giovanni Sartore, A. Dejgaard, Carol Kelley, S. Ali, Stéphane Dalle, Jeffrey S. Gonzalez, Elena Šeböková, Alexander Beck, Ingo B. Leibiger, M Rosu, C Pencea, Werner Waldhäusl, Kaltenbacher M-C., R Butzer, S Thore, Adam G. Tabak, Angelo Avogaro, E Standi, Boris Kovatchev, O Bradescu, Patrizia Dentelli, A Fujita, C Verri, R Chlup, Prasad Ydm., S V Hörsten, van der Merwe M-T., D Hilliard, W Klein, D Worthley, M Udvardy, Berit R. Jensen, A D'Avanzo, J Monaghan, K P Yeo, Guivarch P-H., B Bauduceau, D Weghuber, P Tatti, J Ybarra, S Gwozdziewiczová, E Gasparini, B Saltin, Charlotte Granhall, Howard Leventhal, R Marin, M Tumiati, Cicero Afg., L Csémy, B Berger, S Mikros, D Dall'Asta, M Shahmanesh, Y G Vasiljev, F Potthoff, H S Randeva, G De Berardis, J O Logan, K Warncke, P Uitterlinden, E Rehring, K Gilmore, K Shankhdhar, V V Bojko, M Vahatalo, E A Korolyova, D Wiemann, P G Lankisch, D Hendrie, F Galtier, M Rybarczyk, Gisela Dahlquist, N N Rudovich, G Stein, A Liebl, F Tan, A Westerlund, S Gronemann, I Franklin, Jonathan A. Prince, Peter Arner, E Skliros, T. Sparre, M Vigas, Maddalena Trombetta, L. Bjerre Knudsen, A C Sima, I Dubroca, Alastair Gray, I Weets, R Ferraresi, Schauer Ujw., E. Leinonen, S Corazza, Jonathan Levy, P K Prakash, R Guzder, S. Barnhill, John Blangero, J Herreros, G. de Vries, Cheng Ptw., A Macías-Batista, K. Capito, R Thomas, G Thomas, G Boemi, Lotte Pietraszek, Pierre Fontaine, I Holme, J Smedegaard, C A Harrop, U Helwig, B Levy, A P Gribben, Hiroto Furuta, P Beckett, S Giannini, Ruth L. Coleman, Eva Fernqvist-Forbes, N Cugnardey, A Dumas, Jane Pinaire, S E Hofer, D Shimono, Erik H. Serné, Alain D. Baron, C Battista, M Tanen, M Klementova, V Adams, J Komorowski, Antonio Nicolucci, E. C. Burns, H Sydall, M G Fanara, M G Giovannitti, N Okabayashi, Magdalena Szurkowska, I A Eroshkin, M. I. J. Uusitupa, D Ma, C C Dieguez, J Sutcliffe-Goulden, A V Gaddi, Michał Arabski, Serge Halimi, Wendy C. Burns, S Seclén, H Sugano, A Vinterby, K Backx, L F Diaconu, Fernando Gomez-Peralta, O'Harte Fpm., G Lepeniotis, D Laune, H Kvasničková, N H Wallén, G Boner, G Cieślik, Robert Hermann, Paul Q. Thomas, Y Kumon, Maria Maiello, M Atkins, Kenneth A. Earle, Guowang Xu, H Y Bae, I Reynisdottir, D Perez, D E Cannon, P Fabietti, I Geronooz, J Østergaard, K J Jeitler, S Skourtis, A Zambanini, A Saemann, K Kuboki, Helen L. Lutgers, A C Thai, Arne Melander, D Pinkowski, S G Straub, S A Wolfe-Coote, A Totora, Hayley Dickinson, A Lindenmair, A Ginis, I Faturos, F Van Eylen, C Huard, F Fu, N Wang, B M Rasmussen, Angela Napoli, L Granato, Markus M. Lerch, M. Frandsen, A Lyras, Lawrence S. Phillips, J Mabley, R Goldschmeding, B K Kilhovd, W Liu, Greg Poffenberger, P Cipriano, Anna Maria Charlotte K Lindqvist, A Matsuzawa, J Wang, T Yu, M S Pepper, Lena M. Thorn, Y Sakamoto, Blanche Schwappach, Anna L. Gloyn, P Dupraz, A. M. Schmidt, M Psallas, V Tsirimbis, Carl D. Langefeld, D Sass, H E Scholtz, M. Cailleau, Lauren Julia Brown, K Phillips, M. Iezzi, C Jayawarna, Eleni Anastasiou, R Lobmann, R Lundershausen, H Fujiwara, H R Nan, I C Smith, I A Karpova, A Navazio, S Kang, T. Hansen, T Watanabe, Gang Hu, Malik Rja., T Kennedy-Martin, Ulla M Smidt, J.M. Dekker, A A Fisher, H Liu, R E Pratley, B Sun, C Fledelius, J F Raposo, R Langham, Ahn S-Y., B R Waterhouse, Shaoping Deng, W Ricart, S V Melnichenko, Henrike Sell, M. Tomalino, N Takeda, Paola Massucco, A Harlan, W Henrich, C D Byrne, R Junik, Khalid Hussain, D Pop Gorceva, Torben Hansen, C Ritterath, K Ogawa, D V Phan, Bradley S Metcalf, Robb E. Moses, Juan P. Frias, Hitoshi Ishii, C Brisard, P Wolkow, H H Maurer, Ingo Rustenbeck, Juris J. Meier, Octavian Savu, S D Lin, V B Bregovski, A Fox, S Cicala, M. Koenen, L Vignati, O de Divitiis, Constantin Ionescu-Tirgoviste, Kilian Rittig, J Song, Riccardo Candido, F Cohen-Boulakia, U Shankhdhar, P Jahan, Antonio Tiengo, E Liepinsh, C Álvarez, Sigurd Lenzen, James E. Foley, A. del Arco, M A Maitan, U Mollenhauer, M A Na, A Beha, B Aicher, Gabriele Meyer, E Sommariva, J Åman, B Gmeinhart, Theede A-M., Bjorn Bolinder, Giulio Ceolotto, S Sbrana, F Biarnes, Damini Dey, Barbara Thorand, H H Klein, Juliana C.N. Chan, L Piconi, S Gudbjornsdottir, E Bobbioni-Harsch, Joanna Polanska, Cristian Serafinceanu, S Gambardella, Olivier Huber, J D Brunzell, T Nagasawa, Loretta Vileikyte, A Szocs, H Löwel, Z Lin, Anders Juul, H Tsuneki, L Sauriol, G Siebert, Marit E. Jørgensen, K Matthies, Brian D. Green, P Jurowski, Z Gao, M Furuya, Silvia Manfrini, Efthymios Motakis, E Souvatzoglou, Qian Y-Z., Byun S-H., T Nguyen, M R Anwar, Geltrude Mingrone, B. Idzior-Walus, Mamas A. Mamas, G Scholl-Schilling, C Bittner, A E Raptis, L Laghi, Murray Stewart, M Orel, Janet M. 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D, Torjesen, P, Kilhovd, B, Berg, T, Sandvik, L, Hanssen, K, Mentink, C, Donchenko, G, Stepanenko, S, Maingrette, F, Deng, H, Lindenmair, A, Freudenthaler, A, Baumgartner parzer, S, Nizheradze, K, Khoruzhenko, A, Tronko, N, Sheu, W, Ou, H, Shen, H, Lin, T, Wu, H, Yang, C, Mogylnytska, L, Schmoelzer, I, Davies, J, Band, M, Struthers, A, Prázný, M, Škrha, J, Kasalová, Z, Neelotpol, S, Jahan, P, Kauschke, S, Harrop, C, Schäfer, A, Widder, J, Eigenthaler, M, Walter, U, Uchimura, I, Ikebukuro, M, Kaibara, M, Hirata, M, Helal, R, Pervin, F, Yang, X, Jansson, P, Nagaev, I, Jack, M, Carvalho, E, Sunnerhagen, K, Cam, M, Cushman, S, Smith, U, Creely, S, Farmer, J, Gustafson, B, Kusminski, C, Krusinova, E, Wohl, P, Klementova, M, Lanska, V, Mcdougall, C, Kelly, I, Abbas, Z, Lutale, J, Archibald, L, Karunajeewa, H, Stingemore, N, Stuccio, G, Mcgechie, D, Muller, L, Hak, E, Goudzwaard, W, Montorsi, F, Homering, M, Sprenger, K, Goldstein, I, Asnaghi, V, Ferrari, G, Rastaldi, M, Gabellini, D, Dell'Antonio, G, Maestroni, A, Ruggieri, D, Luzi, L, Piemonti, L, Zerbini, G, Anafaroglu, I, Tutuncu, N, Sultana, M, Siddiqua, N, Iwasaki, T, Nakajima, A, Yoneda, M, Mukasa, K, Tanaka, S, and Sekihara, H
Subjects: 0303 health sciences, medicine.medical_specialty, business.industry, EASD, Endocrinology, Diabetes and Metabolism, Human physiology, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, Diabetes mellitus, Family medicine, Internal Medicine, Medicine, business, 030217 neurology & neurosurgery, 030304 developmental biology
Published: 2004

41. Hyperglycaemia and cardiovascular risk

Author: Roberto Miccoli, S Del Prato, Cristina Bianchi, and Francesca Palumbo
Subjects: Blood Glucose, Risk, cardiovascular risk, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Population, Endocrinology, Risk Factors, Internal medicine, Diabetes mellitus, Internal Medicine, Medicine, Effective treatment, Humans, Myocardial infarction, education, Glycemic, Cardiovascular mortality, Glycated Hemoglobin, education.field_of_study, business.industry, Type 2 Diabetes Mellitus, General Medicine, medicine.disease, Survival Analysis, Cardiovascular Diseases, hyperglycemia, Metabolic syndrome, Morbidity, business, Biomarkers
Abstract: Cardiovascular diseases represent, today, the principal cause of mortality in the general population, especially in subjects with type 2 diabetes mellitus. In these patients the risk of death from cardiovascular diseases is equal to that of non-diabetic subjects with a previous episode of myocardial infarction. Many factors concur to determine such high risk. Hyperglycaemia contributes to the increase in morbidity and cardiovascular mortality associated with diabetes mellitus. Hyperglycaemia acts as a multiplier of cardiovascular risk due to frequent association of multiple risk factors in diabetic patients. Therefore, effective treatment requires a more complete assessment of quantitative and qualitative aspects of glycemic control as well as all components of the diabetic syndrome or, more commonly, metabolic syndrome.
Published: 2003

42. Recurrent mutations of the apolipoprotein A-I gene in three kindreds with severe HDL deficiency

Author: Roberto Miccoli, Stefano Bertolini, Patrizia Tarugi, Paola Alessandrini, Sebastiano Calandra, Guido Franceschini, Livia Pisciotta, Gabriele Bittolo Bon, Alfredo Cantafora, Laura Calabresi, and Claudio Cortese
Subjects: Adult, Male, medicine.medical_specialty, Heterozygote, Apolipoprotein B, Adolescent, Molecular Sequence Data, Biology, medicine.disease_cause, Compound heterozygosity, Polymerase Chain Reaction, Severity of Illness Index, Coronary artery disease, Frameshift mutation, Loss of heterozygosity, Exon, chemistry.chemical_compound, High-density lipoprotein, Recurrence, Internal medicine, Haplotype analysis, medicine, Humans, Genetic Predisposition to Disease, Alleles, Genetics, Mutation, Polymorphism, Genetic, Apolipoprotein A-I, Base Sequence, Apolipoprotein A-I gene mutations, Haplotype, apolipoprotein A-I gene, HDL deficiency, Pedigree, Endocrinology, chemistry, Italy, biology.protein, lipids (amino acids, peptides, and proteins), Female, Cardiology and Cardiovascular Medicine, Deficiency Diseases, Lipoproteins, HDL
Abstract: Two siblings with high density lipoprotein (HDL) deficiency and no plasma apolipoprotein A-I (Apo A-I) were found to be homozygous for a cytosine deletion in exon 3 of Apo A-I gene (c.85 del C, Q5FsX11). This mutation causes a frameshift leading to a premature stop codon and abolishes the synthesis of Apo A-I. Although both siblings had corneal opacifications and planar xanthomas, only one of them had premature coronary artery disease, probably as the result of mildly elevated LDL levels. In two other unrelated subjects HDL deficiency was due to heterozygosity for a nucleotide substitution in exon 4 of Apo A-I gene (c.494 T>G, L141R). Both Apo A-I mutations were reported previously in an Italian kindred which included compound heterozygotes and simple heterozygotes. We investigated all carriers of these mutations in the three kindreds and in the one previously reported. Plasma Apo A-I and HDL-C levels were lower in the mutation carriers than in non-carrier family members. These levels, however, were lower in L141R carriers than in carriers of c.85 del C. Haplotype analysis performed using several polymorphisms suggested that both the c.85 del C and L141R are likely to be recurrent mutations.
Published: 2003

43. Prevalence and risk factors for gestational diabetes assessed by universal screening

Author: Roberto Miccoli, G Teti, Cristina Lencioni, Kyriazoula Chatzianagnostou, L Volpe, S. Del Prato, Graziano Di Cianni, Luca Benzi, Pietro Bottone, Ilaria Cuccuru, and Alessandra Ghio
Subjects: Adult, medicine.medical_specialty, endocrine system diseases, Endocrinology, Diabetes and Metabolism, Population, Overweight, Endocrinology, Pregnancy, Risk Factors, Diabetes mellitus, Prevalence, Internal Medicine, medicine, Humans, Mass Screening, Family history, Risk factor, education, Societies, Medical, Gynecology, education.field_of_study, Obstetrics, business.industry, Body Weight, nutritional and metabolic diseases, Retrospective cohort study, General Medicine, Glucose Tolerance Test, medicine.disease, Body Height, female genital diseases and pregnancy complications, Gestational diabetes, Diabetes, Gestational, Parity, Italy, Cohort, Female, medicine.symptom, gestational diabetes, business
Abstract: In order to evaluate the prevalence of gestational diabetes mellitus (GDM) and the presence of risk factors for GDM, we conducted a retrospective study of a cohort of Italian women. In addition, we compared universal versus selective screening to validate the ADA's recommendations in our population. From June 1st, 1995 to December 31st, 2001, universal screening for GDM was performed in 3950 women. The glucose challenge test (GCT) was positive (GCT+) in 1389 cases (35.2%). The 1-h glucose level after GCT enabled us to diagnose GDM directly in 24 pregnant women. Oral glucose tolerance test (OGTT) was performed in 1221 GCT+ women (144 cases with GCT+ dropped out) and GDM was diagnosed in 284 (23.2%) of them. OGTT was also performed in 391 randomly chosen, women from the GCT negative (GCT-) group. In this last group 25 (6.3%) women had GDM. Thus, the total number of subjects with GDM was 333 out of 3806 with a prevalence of 8.74% in the entire cohort. Assuming that the rate of GDM observed in the random sample of GCT- women is applicable to the whole group of 2561 GCT- women, then 161 GCT- patients could also have GDM. This will further increase the estimated prevalence for the whole cohort up to 12.3% (i.e. 469 out of 3806 pregnant women). There were 236 (5.6%) women with a low risk for GDM (normal weight, age less than 25 years and without a family history of diabetes). In this group we found 34 cases and five cases with positive screening test and GDM, respectively. Thus, if we excluded low risk women from the screening test, as suggested by ADA recommendations, only five women with GDM would have been missed. However, about 95% of our population were at medium or high risk for GDM and, therefore, would have been screened. The rate of GDM was significantly higher in women with a positive history of diabetes, increasing age, previous pregnancies, pre-pregnancy overweight and short stature. After logistic regression analysis, GDM diagnosis was significantly correlated with age (P
Published: 2003

44. Effects of pravastatin treatment on lipoprotein levels and composition in patients with type 2 diabetes mellitus and hypercholesterolemia

Author: Riccardo Trifirò, Renzo Navalesi, M. G. Giovannitti, Roberto Anichini, Anna Ceraudo, Adelaide Dolci, and Roberto Miccoli
Subjects: medicine.medical_specialty, pravastatin treatment, medicine.medical_treatment, Type 2 diabetes, Diabetes mellitus, Internal medicine, polycyclic compounds, lipoprotein levels, type 2 diabetes, hypercolesterolemia, Medicine, Pharmacology (medical), Pharmacology, Chemotherapy, medicine.diagnostic_test, business.industry, nutritional and metabolic diseases, Type 2 Diabetes Mellitus, medicine.disease, Hydroxymethylglutaryl-CoA reductase, Endocrinology, lipids (amino acids, peptides, and proteins), business, Lipid profile, Pravastatin, medicine.drug, Lipoprotein
Abstract: Objective To assess the effects of pravastatin on lipoprotein levels and composition in patients with type 2 diabetes mellitus and hypercholesterolemia. The role of pravastatin in glucose control also was assessed. Background Several factors, including abnormalities of lipoprotein composition, may contribute to the increased risk of coronary heart disease in diabetes mellitus. Methods Patients with type 2 diabetes mellitus of at least 3 years' duration entered the study at the 4-week run-in period, during which they received a standard diet. For the remaining 18 weeks of the study, they received pravastatin 20 mg/d. Results In 51 patients, pravastatin decreased total cholesterol concentrations (289 ± 40 to 227 ± 37) ( P P P P Conclusions In patients with type 2 diabetes mellitus and hypercholesterolemia, pravastatin improved the lipid profile and the atherogenic potential associated with abnormal lipoprotein composition.
Published: 2000

45. Plasma and fibroblasts of Tangier disease patients are disturbed in transferring phospholipids onto apolipoprotein A-I

Author: Michael Walter, A. von Eckardstein, Roberto Miccoli, Susanne Schuler-Lüttmann, A. Chirazi, Gerd Assmann, José T. Real, G. Hobbel, G. Noseda, John J.P. Kastelein, Jürgen Geisel, and Other departments
Subjects: Adult, Male, transferring phospholipids, Phospholipid, Tangier disease, Phosphatidic Acids, QD415-436, Phosphatidylinositols, Biochemistry, chemistry.chemical_compound, Endocrinology, Phosphatidylcholine, Phospholipid transfer protein, Extracellular, medicine, Humans, Cells, Cultured, Phosphatidylethanolamine, Apolipoprotein A-I, Cholesterol, Phosphatidylethanolamines, Reverse cholesterol transport, nutritional and metabolic diseases, Biological Transport, Cell Biology, Fibroblasts, medicine.disease, Molecular biology, familial HDL deficiency, reverse cholesterol transport, Lipoproteins, LDL, phospholipid transfer proteins, prebeta-HDL, chemistry, Phosphatidylcholines, Female, lipids (amino acids, peptides, and proteins), cholesterol efflux
Abstract: Plasmas of patients with Tangier disease (TD) lack lipid-rich α-HDL which, in normal plasma, constitutes the majority of high density lipoprotein (HDL). Residual amounts of apolipoprotein (apo)A-I in TD plasma occur as lipid-poor or even lipid-free preβ-HDL. By contrast to normal plasma, TD plasma does not convert preβ-HDL into α-HDL. Moreover, fibroblasts of TD patients were found to be defective in secreting cholesterol or phospholipids in the presence of lipid-free apoA-I. We have therefore hypothesized that both defective conversion of preβ-HDL into α-HDL and defective lipid efflux from TD cells onto lipid-free apoA-I result from a disturbance in phospholipid transfer occurring in both cellular and extracellular compartments. To test this hypothesis we established an assay that measures the activity of plasma, cells, and cell culture media to transfer radiolabeled phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylinositol (PI) from vesicles onto apoA-I, apoA-II, albumin, or reconstituted HDL. Plasmas, HDL, and lipoprotein-depleted plasma of normolipidemic probands as well as cell homogenates and culture media of normal fibroblasts were active at 37°C but not at 4°C in transferring radiolabeled PC, PI, and PE dose- and time-dependently onto either lipid-free apoA-I or reconstituted HDL. Transfer of glycerophospholipids onto apoA-II was much lower than onto apoA-I; transfer onto albumin was close to background. Compared to ten normolipidemic plasmas and four apoA-I-deficient plasmas, plasmas of six TD patients were significantly reduced by 40–50% in their glycerophospholipid transfer activities. Compared to eight normal fibroblast cell lines, homogenates and culture media of four TD fibroblast cell lines were reduced by 40–50% and 30–35%, respectively, in their activity to transfer PC, PI, or PE onto apoA-I. Our data suggest that in TD the same mechanism underlies both defective conversion of preβ-HDL into α-HDL and impaired efflux of cellular lipids, namely a defective phospholipid transfer.—von Eckardstein, A., A. Chirazi, S. Schuler-Lüttmann, M. Walter, J. J. P. Kastelein, J. Geisel, J. T. Real, R. Miccoli, G. Noseda, G. Höbbel, and G. Assmann. Plasma and fibroblasts of Tangier disease patients are disturbed in transferring phospholipids onto apolipoprotein A-I. J. Lipid Res. 1998. 39: 987–998.
Published: 1998

46. Genetically determined absence of HDL-cholesterol and coronary atherosclerosis

Author: Arnold von Eckardstein, Leonardo Odoguardi, Roberto Miccoli, Gerd Assmann, H. Wiebusch, Harald Funke, and Renzo Navalesi
Subjects: medicine.medical_specialty, HDL-cholesterol, coronary atherosclerosis, business.industry, Cholesterol, Point mutation, General Medicine, chemistry.chemical_compound, Endocrinology, chemistry, Internal medicine, Medicine, Allele, business, Hdl deficiency, Coronary atherosclerosis
Published: 1995

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