Inquadramento fisiopatologico della trasduzione del segnale insulinico

Rosario Amato*, Miranda Menniti, Giorgia Bulotta, Nicola Perrotti *Dipartimento di Medicina Sperimentale e Clinica “G.Salvatore”, Università Magna Graecia di Catanzaro

Biochimica Clinica: 2006; 30(5-6): 444-448 [Article in italian]

ABSTRACT. Pathophysiology of the insulin receptor signal transduction. Diabetes mellitus is a major public health problem. The chronic complications of diabetes are a leading cause of blindness, kidney failure, amputations, increased risk of vascular disease and stroke. In the aim to develop better therapies, many researchers have investigated areas related to insulin and diabetes. In the last decade the insulin signalling pathway has been dissected, offering to the scientific community the possibility to improve the therapeutic approach and the understanding of the molecular pathophysiology of insulin signalling. This work is mainly focused on the revision of the knowledge gathered in the last few years in the field of Insulin signal transduction, in the effort to develop an integrated review between clinical and experimental diabetologists.

Il “Maturity Onset Diabetes of the Young” (MODY)

Fabrizio Barbetti Dipartimento di Medicina Interna, Univ. Tor Vergata e Ospedale Pediatrico Bambino Gesù IRCCS, e Fondazione Parco Biomedico S Raffaele, Roma

Biochimica Clinica: 2006; 30(5-6): 449-456 [Article in italian]

ABSTRACT. The Maturity Onset Diabetes of the Young (MODY). The Maturity Onset Diabetes of the Young (MODY) is a monogenic, autosomal dominant form of diabetes mellitus which is readily distinguishable, on a clinical ground, from the common, polygenic forms currently designated as type 1 (T1D) and type 2 (T2D) diabetes. MODY can be caused by mutations in 6 different genes, but a percentage varying from 15 up to 45% of patients clinically defined as MODY do not bear a mutation in any of the known MODY genes. In most MODY patients a mutation in the enzyme glucokinase (GCK/MODY2) or in the transcription factor hepatocyte nuclear factor-1 (HNF-1/MODY3) is detected, the relative frequency depending on the population studied and on the clinical setting (pediatric versus adult diabetes clinic) where the index case is referred. Several studies have demonstrated that the clinical features and the metabolic profile of patients bearing a MODY 2 mutation allow the clinician to diffentiate them from patients with a defect of the TCF1 (MODY3) gene. Moreover, MODY3 has been one of the first examples of pharmacogenomics in the area of diabetes.Recently, it has been also demonstrated that homozygous or compound heterozygous mutations of the GCK lead to a very rare form of monogenic diabetes called Permanent Neonatal Diabetes Mellitus. MODY is a useful model of diabetes caused by an array of defects of the pancreatic beta cell.

Aterosclerosi e diabete: due facce della stessa medaglia

Massimo Federici* Stefano Rizza, Renato Lauro *Centro per l’Aterosclerosi Policlinico Tor Vergata e Dipartimento di Medicina Interna, Università di Roma Tor Vergata

Biochimica Clinica: 2006; 30(5-6): 457-461 [Article in italian]

ABSTRACT. Atherosclerosis and diabetes: two faces of the same coin. Type 2 diabetes mellitus and atherosclerosis, the two major health problems from western countries in the next decades, are often associated in patients. While we were used to thinking atherosclerosis as a complication of diabetes, we have now learned that the tho diseases arise from common mechanisms. In this article we review this new scenario which is changing our diagnostic and therapeutic approach. The new approach to control the burden of diabetes and atherosclerosis is to search for simultaneous prevention and treatment of the two diseases.

Diabete e coagulazione

Roberto Testa*, Sophie Testa INRCA IRCCS, Università Politecnica delle Marche

Biochimica Clinica: 2006; 30(5-6): 462-467 [Article in italian]

ABSTRACT. Diabetes and coagulation. Diabetes mellitus is a metabolic disorder principally characterized by hyperglicemia and complications related to micro and macroangiopathy. Type 2 diabetes is the principal risk factor for coronary artery disease and patients with diabetes are two to four times more likely to develop cardiovascular disease. The metabolic disorder in diabetic patients causes endothelial damage, platelet activation and imbalance of the coagulation cascade, with a relative prothrombotic state due to increased levels of von Willebrand factor, fibrinogen, D-dimer, thrombin and factor VII. Impaired fibrinolysis is strongly involved in the genesis of vascular complications in type 2 diabetes. The fibrinolytic system regulates the conversion of plasminogen to plasmin, allowing the degradation of fibrin deposits in the blood vessels. Type 2 diabetes mellitus coagulation abnormalities and the role of plasminogen activator inhibitor type 1 (PAI-1), its deletion/insertion polymorphism (4G/5G), thombin activatable fibrinolysis inhibitor (TAFI) and lipoprotein(a) (Lp(a)) and the effects of activated innate immunity on fibrinolysis are discussed in this review.

Screening e diagnosi del diabete gestazionale

Annunziata Lapolla*, Maria Grazia Dalfrà *Dipartimento di Scienze Mediche e Chirurgiche, Cattedra di Malattie del Metabolismo, Università degli Studi di Padova

Biochimica Clinica: 2006; 30(5-6): 468-474 [Article in italian]

ABSTRACT. Screening and diagnosis of gestational diabetes mellitus. Gestational diabetes is a pathology which has shown an increasing frequency during the last years and, if not treated, may still have adverse fetal and maternal outcomes. This condition has therefore to be diagnosed in time and properly treated, although actually the screening and diagnosis procedures of the disease are not univocal. Waiting for the results of the current studies, that will give definite answers to the still open questions, the Study Group on Diabetes and Pregnancy of the SID chooses not to modify the screening and diagnosis criteria of gestational diabetes, which are reported in this paper.

Dimetilarginina asimmetrica e diabete

Maurizio Marra Dipartimento Ricerche Gerontologiche e Geriatriche, Unità Operativa Diabetologia, I.N.R.C.A, Ancona

Biochimica Clinica: 2006; 30(5-62): 475-481 [Article in italian]

ABSTRACT. Asymmetric dimethylarginine and diabetes. The endothelial dysfunction is a common aspect in the diabetic patients and play a role in diabetic vascular complications. This early event in the atherosclerotic process is due to a reduction of nitric oxide and of the activity of Nitric Oxide Synthase (NOS). An elevated concentration of Asymmetric Dimethylarginine (ADMA), an endogenous NOS inhibitor, is per se considered a risk factor for endothelial dysfunction. Increased ADMA levels has been found in diabetic subjects (type 1 and type 2) and in subjects with insulin resistance syndrome. In all these conditions, elevated levels of ADMA are linked to the reduction of the activity of Dimethylarginine Dimethylaminohydrolase (DDAH), the enzyme that degrade ADMA, and to the increase of oxidative stress. Moreover the relationships between ADMA levels and some of the main metabolic parameters involved in diabetic pathology and its complications are well clarified. However the role of DDAH polymorphisms in the modulation of ADMA levels must be clarified and deepen in the develop of diabetic vascular complications. New and more affordable analytical methods will be able to obtain these data.

Aggiornamenti in tema di auto-monitoraggio glicemico nei pazienti diabetici

Giuseppe Lippi*, Martina Montagnana *Università Cattolica del Sacro Cuore - Istituto di Medicina Legale - Roma

Biochimica Clinica: 2006; 30(5-6): 482-486 [Article in italian]

ABSTRACT. Updates on the self monitoring of blood glucose in diabetic patients. Diabetes mellitus is one of the most popular pathologies worldwide, especially among children and adolescents. A bulk of clinical evidences highlights that the self-monitoring of blood glucose is a pivotal aspect in the clinical management of diabetic patients, to prevent a wide set of complications. The self-monitoring of blood glucose is actually based on sophisticated electronic instruments, which are however small, easy to handle and require a minimal amount of capillary blood to perform the analysis. Despite remarkable technological advances have allowed high productive standards, there are still some perplexities on both the analytic quality of the data and results comparability among different analyzers and between analyzers and the second reference method based on the measurement of plasma glucose by esokinase. The imminent introduction of innovative disposals, based on subcutaneous electrodes for the continuous glucose monitoring will hopefully permit to overcome most of the analytic problems, improving contextually the patient’s care and containing expenditures.

Avanzamenti nella misura e nell'utilizzo clinico dell'emoglobina glicata

Andrea Mosca Dipartimento di Scienze e Tecnologie Biomediche, Università degli Studi di Milano

Biochimica Clinica: 2006; 30(5-6): 487-492 [Article in italian]

ABSTRACT. Advances in the measurement and clinical utility of glycated hemoglobin. Aim of the present work is to give an update about the clinical utility of the measurement of glycated hemoglobin, as well to summarize the state-of-the-art of the process of standardization of HbA1c worldwide. Recent data collected from various EQAS studies are presented, with some more details about the quality of HbA1c measurement in Italy. A brief discussion about the problems related to the transition to the IFCC standardized assays is presented, together with the most recent proposals related to the studies on the relationship between HbA1c and mean blood glucose.


Le linee guida della International Diabetes Federation (idf) per il trattamento del diabete mellito di tipo 2

Marco Orsini Federici*, Massimo Massi Benedetti *Dipartimento di Medicina Interna, Università di Perugia

Biochimica Clinica: 2006; 30(5-6): 493-498 [Article in italian]

ABSTRACT. International Diabetes Federation Guidelines for the Managemnt of Type 2 Diabetes. Several national and international evidences demonstrate a wide variability of diabetes care. As a consequence in recent years a growing number of protocols and guidelines have been proposed in order to rationalise and standardise the delivery of care. Nevertheless frequently recommendations remain unapplied and targets are not reached due to the fact that guidelines usually reflect high level of care impossible to be implemented in most local environments. To overcome such difficulty the International Diabetes Federation (IDF) launched in 2005 the Global Guidelines for Type 2 Diabetes. The novel approach of IDF consists of tailoring indications derived from “evidence based medicine” to local specific conditions thus allowing the best diabetes care to be delivered according to each specific condition. Three different levels of care have been proposed, standard, minimal and comprehensive, in order to guarantee that each person with diabetes has the possibility to benefit of a proved effective diabetes care irrespective of the level of available resources den of diabetes and atherosclerosis is to search for simultaneous prevention and treatment of the two diseases.

Linee Guida e Raccomandazioni per le Analisi di Laboratorio nella Diagnosi e nella Gestione del Diabete Mellito

David B. Sacks*, David E. Bruns, David E. Goldstein, Noel K. Maclaren, Jay M. Mcdonald, and Marian Parrott *Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston;

Biochimica Clinica: 2006; 30(5-6): 499-536 [Article in italian]

ABSTRACT. Guidelines and Recommendations for Laboratory Analysis in the Diagnosis and Management of Diabetes Mellitus. Background: Multiple laboratory tests are used in the diagnosis and management of patients with diabetes mellitus. The quality of the scientific evidence supporting the use of these assays varies substantially. Approach: An expert committee drafted evidence-based recommendations for the use of laboratory analysis in patients with diabetes. An external panel of experts reviewed a draft of the guidelines, which were modified in response to the reviewers’ suggestions. A revised draft was posted on the Internet and was presented at the AACC Annual Meeting in July, 2000. The recommendations were modified again in response to oral and written comments. The guidelines were reviewed by the Professional Practice Committee of the American Diabetes Association. Content: Measurement of plasma glucose remains the sole diagnostic criterion for diabetes. Monitoring of glycemic control is performed by the patients, who measure their own plasma or blood glucose with meters, and by laboratory analysis of glycated hemoglobin. The potential roles of noninvasive glucose monitoring, genetic testing, autoantibodies, microalbumin, proinsulin, C-peptide, and other analytes are addressed. Summary: The guidelines provide specific recommendations based on published data or derived from expert consensus. Several analytes are of minimal clinical value at the present time, and measurement of them isnot recommended. © 2002 American Association for Clinical Chemistry

Raccomandazioni per l’esecuzione della curva standard da carico orale di glucosio (OGTT) per la diagnosi di diabete mellito

Paolo Andreani*, Anna Caldini, Mariarosa Carta, Ferruccio Ceriotti, Alberto Falorni,Grazia Ferrai, Franco Ghiara, Elvino Giordani, Maristella Graziani, Annunziata Lapolla, Giuseppe Lippi, Claudia Lo Cascio, Italiano Maccaroni, Lucia Malloggi, Maurizio Marra, Massimo Massi Benedetti, Ettore Migali, Martina Montagnana, Maura Musso, Renata Paleari, Gabriele Pegoretti, Maria Letizia Tomassoni, Roberto Testa, Andrea Mosca, per il Gruppo di Studio Intersocietario Diabete Mellito *Az. Ospedaliera, Terni

Biochimica Clinica: 2006; 30(5-6): 537-540 [Article in italian]

ABSTRACT. Recommendation for the execution of the oral glucose tolerance test for the diagnosis of diabetes mellitus. The present document report the recommendations concerning the Oral Glucose Tolearance Test (OGTT) performed for the classification of diabetes. These recommendations have been elaborated by the Italian joint Study Group on Diabetes Mellitus.

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