Management of metabolic alterations in adult kidney transplant recipients: A joint position statement of the Italian Society of Nephrology (SIN), the Italian Society for Organ Transplantation (SITO) and the Italian Diabetes Society (SID)

Chronic metabolic alterations such as post-transplant diabetes mellitus (PTDM), dyslipidaemias and overweight/obesity significantly impact on kidney transplant (KT) outcomes. This joint position statement is based on the evidence on the management of metabolic alterations in KT recipients (KTRs) published after the release of the 2009 KDIGO clinical practice guideline for the care of KTRs. Members of the Italian Society of Nephrology (SIN), the Italian Society for Organ Transplantation (SITO) and the Italian Diabetes Society (SID) selected to represent professionals involved in the management of KTRs undertook a systematic review of the published evidence for the management of PTDM, dyslipidaemias and obesity in this setting. The aim of this work is to provide an updated review of the evidence on the prevention, diagnosis and treatment of metabolic alterations in KTRs, in order to support physicians, patients and the Healthcare System in the decision-making process when choosing among the various available options.     

Cardiovascular risk profile and blood pressure control in Italian hypertensive patients under specialist care

BACKGROUND: Information on the association between high hypertension and metabolic risk factors in Italy is limited. Furthermore, data on the rate of blood pressure control in the Italian hypertensive population are restricted to some Italian regions only, and refer usually to surveys performed, in most instances, several years ago. METHODS: In the present study, a total of 4059 essential hypertensive patients were examined consecutively from March to June 2000 by 450 cardiovascular specialists (cardiologists, internists and diabetologists) operating throughout the Italian territory. Analysable data were obtained in 3812 patients. RESULTS: Blood pressure control by treatment (< 140/90 mmHg) was infrequent (11.9%), this being particularly the case for systolic as compared to diastolic blood pressure (15.1 versus 33.7%). Hypertension was the only risk factor in only 13.7% of the patients, the association with diabetes, hypercholesterolaemia or obesity characterizing the remaining cases. About 60% of the patients fell into the high or very high cardiovascular risk category of the World Health Organization/International Society of Hypertension (WHO/ISH) Guidelines. Compared to low or moderate cardiovascular risk, multiple antihypertensive drug treatment was more frequently used in individuals at high or very high risk. These conditions were frequently underdiagnosed by physicians. CONCLUSIONS: Thus, in Italy, hypertension continues to be a poorly controlled condition. Despite being a Mediterranean country, the occurrence of hypertension is commonly associated with metabolic risk factors and often with a high or very high cardiovascular risk profile. This is not properly identified by specialist physicians.     

Indications for renal biopsy in patients with diabetes. Joint position statement of the Italian Society of Nephrology and the Italian Diabetes Society

AimsThis joint document of the Italian Society of Nephrology and the Italian Diabetes Society reviews the main indications to perform a renal biopsy in diabetic patients, according to the recommendations of a panel of experts based on all available scientific evidence.Data synthesisRenal biopsy has a pivotal role in assessing the nature and severity of renal injury in patients with diabetic kidney disease (DKD). The procedure is mandatory in the presence of one of more of the following features: rapid onset or progression of albuminuria or sudden onset of nephrotic syndrome, rapid GFR decline with or without albuminuria, hematuria, active urine sediment, clinical and/or laboratory suspicion of other systemic diseases, and, in patients with type 1 diabetes, short diabetes duration and absence of retinopathy. Indeed, ~40% of diabetic individuals with kidney injury undergoing renal biopsy are affected by a non-diabetic renal disease (NDRD). Furthermore, the histological evaluation of patients with suspected classical diabetic nephropathy allows to define the extent of glomerular, tubulo-interstitial and vascular lesions, thus providing important prognostic (and potentially therapeutic) data. In the future, the indications for renal biopsy might be extended to the definition of the histological lesions underlying the “nonalbuminuric” DKD phenotypes, as well as to the evaluation of the response to treatment with the new anti-hyperglycemic drugs that provide cardiorenal protection.ConclusionsIn view of the heterogeneous clinical presentation and course of DKD and of the related heterogeneous histopathological patterns, a more extensive use of renal biopsy may be crucial to provide valuable information with important pathogenic, diagnostic, prognostic, and therapeutic implications.     

Diabetes mellitus and periodontitis. Bidirectional relationship and clinical implications. A consensus document

Diabetes and periodontitis are chronic diseases with an increasing prevalence in the German population. There is a bi-directional relationship between both diseases. Diabetes promotes the occurrence, the progression and the severity of periodontitis. Periodontitis complicates the glycemic control of diabetes, increases the risk of diabetes-associated complications and possibly even of its onset. In view of the existing evidence, that is still not sufficiently communicated within the medical community, an expert panel consisting of four diabetologists and four periodontists has addressed the following questions: What is the effect of diabetes mellitus on periodontitis and on periodontal therapy? What is the effect of periodontitis on diabetes mellitus? What are the practical consequences, that result for interdisciplinary treatment strategies? The treatment of periodontal infections should become an integral part of the management of diabetes, whereas glycemic control is a prerequisite for successful periodontal therapy.     

The implementation of a strategy for the primary prevention of diabetes mellitus

A pyruvate test for glucose tolerance was used during prophylactic medical examination of 47 students and 27 children without risk factors, 54 students with risk factors, 31 patients with type I diabetes mellitus and 220 construction workers in order to test a new methodological basis for the strategy of primary prevention of diabetes mellitus. The investigations showed the presence in a general population of 3-modal distribution of a variant of the capillary blood pyruvate level on the 120th min. of a GTT according to physiological glucose tolerance, potential (prediabetic) and actual (diabetic) carbohydrate metabolic derangements. A high informative value of the pyruvate test for glucose tolerance makes this method appropriate for identification of persons, genetically predisposed to the development of diabetes mellitus, for implementation of a population strategy of prevention of this disease as well as strategy of prevention of diabetes among persons with risk factors.     

Diabetes mellitus and periodontitis: a tale of two common interrelated diseases

Diabetes mellitus (a group of metabolic disorders characterized by hyperglycemia) and periodontitis (a microbially induced inflammatory disorder that affects the supporting structures of teeth) are both common, chronic conditions. Multiple studies have demonstrated that diabetes mellitus (type 1 and type 2) is an established risk factor for periodontitis. Findings from mechanistic studies indicate that diabetes mellitus leads to a hyperinflammatory response to the periodontal microbiota and also impairs resolution of inflammation and repair, which leads to accelerated periodontal destruction. The cell surface receptor for advanced glycation end products and its ligands are expressed in the periodontium of individuals with diabetes mellitus and seem to mediate these processes. The association between the two diseases is bidirectional, as periodontitis has been reported to adversely affect glycemic control in patients with diabetes mellitus and to contribute to the development of diabetic complications. In addition, meta-analyses conclude that periodontal therapy in individuals with diabetes mellitus can result in a modest improvement of glycemic control. The effect of periodontal infections on diabetes mellitus is potentially explained by the resulting increase in levels of systemic proinflammatory mediators, which exacerbates insulin resistance. As our understanding of the relationship between diabetes mellitus and periodontitis deepens, increased patient awareness of the link between diabetes mellitus and oral health and collaboration among medical and dental professionals for the management of affected individuals become increasingly important.     

Management of nodal diffuse large B-cell lymphomas: practice guidelines from the Italian Society of Hematology, the Italian Society of Experimental Hematology and the Italian Group for Bone Marrow Transplantation

The Italian Society of Hematology (SIE) and two affiliate societies (SIES and GITMO) commissioned a project to develop clinical practice guidelines for the treatment of nodal diffuse large B-cell non Hodgkin lymphomas (DLBCL). Key questions clinically relevant to the management of patients with nodal DLBCL were formulated by an Advisory Committee (AC) and approved by an Expert Panel (EP) composed of eight senior hematologists. After a comprehensive and systematic literature review, the EP formulated therapy recommendations and graded them according to the supporting evidence. An explicit approach to consensus methodologies was used for evidence interpretation and for producing recommendations in the absence of strong evidence. The EP formulated recommendations on which first-line therapy to choose in patients with nodal DLBCL. Patients of all ages, with stage I-II disease and no adverse prognostic factors should receive abbreviated chemotherapy with an anthracycline-containing regimen plus involved field radiotherapy (35-40 Gy). Patients with stage I-II disease and at least one adverse prognostic factor, or with stage III-IV disease, should receive frontline chemoimmunotherapy with CHOP, CHOP-like or third-generation chemotherapy plus rituximab. Recommendations on stem cell transplantation and on which therapy to adopt for refractory or relapsed patients were also formulated.     

Hyperglycaemia and cardiovascular risk

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.     

Periodontitis and risk of diabetes mellitus

Diabetes mellitus (DM) is a complex disease with varying degrees of systemic and oral complications. The periodontium is also a target for diabetic damage. Diabetes is a pandemic in both developed and developing countries. In recent years, a link between periodontitis and diabetes mellitus has been postulated. The oral cavity serves as a continuous source of infectious agents that could further worsen the diabetic status of the patient and serve as an important risk factor deterioration of diabetes mellitus. The present review highlights the relationship between diabetes mellitus and periodontitis. The potential mechanisms involved in the deterioration of diabetic status and periodontal disease are also discussed.     

Bone fragility in patients with diabetes mellitus: A consensus statement from the working group of the Italian Diabetes Society (SID), Italian Society of Endocrinology (SIE), Italian Society of Gerontology and Geriatrics (SIGG), Italian Society of Orthopaedics and Traumatology (SIOT)

Bone fragility is one of the possible complications of diabetes, either type 1 (T1D) or type 2 (T2D). Bone fragility can affect patients of different age and with different disease severity depending on type of diabetes, disease duration and the presence of other complications. Fracture risk assessment should be started at different stages in the natural history of the disease depending on the type of diabetes and other risk factors. The risk of fracture in T1D is higher than in T2D, imposing a much earlier screening and therapeutic intervention that should also take into account a patient's life expectancy, diabetes complications etc. The therapeutic armamentarium for T2D has been enriched with drugs that may influence bone metabolism, and clinicians should be aware of these effects.Considering the complexity of diabetes and osteoporosis and the range of variables that influence treatment choices in a given individual, the Working Group on bone fragility in patients with diabetes mellitus has identified and issued recommendations based on the variables that should guide screening of bone fragility and management of diabetes and bone fragility: (A)ge, (B)MD, (C)omplications, (D)uration of disease, & (F)ractures (ABCD&F). Consideration of these parameters may help clinicians identify the best time for screening, the appropriate glycaemic target and anti-osteoporosis drug for patients with diabetes at risk of or with bone fragility.     

First Italian Consensus Statement on Diagnosis, Prevention and Treatment of Cardiovascular Complications in HIV-infected Patients in the HAART Era (2006)

Abstract The present document contains recommendations for assessment, prevention and treatment of cardiovascular risk for HIV-infected patients. All recommendations were graded according to the strength and quality of the evidence and were voted on by 73 members of the Italian Cardiovascular Risk Guidelines Working Group which includes both experts in HIV/AIDS care and in cardiovascular and metabolic medicine. Since antiretroviral drug exposure represents only one risk factor, continued emphasis on an integrated management is given. This should include prevention and treatment of known cardiovascular risk factors (such as dyslipidaemia, diabetes, insulin resistance, healthy diet, physical activity, avoidance of smoking), but also rational switch of antiretroviral drugs. A rational switch strategy should consider both metabolic and anthropometric disturbances and effectiveness of antiretroviral regimens. Members of the Italian Cardiovascular Risk Guidelines Working Group are listed in acknowledgments.     

The prevalence of polycystic ovaries in women with type 2 diabetes mellitus

OBJECTIVE: Polycystic ovary syndrome (PCOS) and type 2 diabetes mellitus are both common conditions associated with insulin resistance and compensatory hyperinsulinaemia. Previous reports have noted that impaired glucose tolerance and diabetes are common in women with PCOS. In this report we present the results of the converse study: the prevalence of polycystic ovaries in premenopausal women presenting with type 2 diabetes mellitus. SUBJECTS: Subjects were recruited from a hospital Diabetes Clinic. A search of computerized records identified 49 premenopausal women with type 2 diabetes mellitus being treated with diet alone or oral hypoglycaemic agents of whom 38 (76%) patients agreed to be studied. DESIGN: A cross-sectional study recording clinical, demographic and anthropometric data. Measurements of fasting metabolic parameters, reproductive endocrine profiles and ovarian dimensions were taken. RESULTS: Eighty-two percent of women with type 2 diabetes mellitus had polycystic ovaries on ultrasound. Of these women, 52% had clinical evidence of cutaneous hyperandrogenism and/or menstrual disturbance. Correlations between metabolic and reproductive parameters were consistent with a stimulatory action of insulin on the ovary. There was no significant difference between the PCO and non-PCO groups with respect to metabolic profiles. CONCLUSIONS: Women with type 2 diabetes mellitus have a higher prevalence of polycystic ovaries than that reported in the general population. Not all women with hyperinsulinaemia due to type 2 diabetes mellitus, however, develop PCO suggesting that hyperinsulinaemia alone is not sufficient for the expression of this ovarian morphology.     

Managing Multiple Cardiovascular Risk Factors: State of the Science

Cardiovascular risk comprises genetic, lifestyle, and metabolic factors. Risk factors frequently occur simultaneously, compounding the risk for a cardiovascular event. The most commonly occurring metabolic clustering includes elevated blood pressure, dyslipidemia (high triglyceride levels and low levels of high-density lipoprotein cholesterol), and impaired glucose tolerance or type 2 diabetes mellitus. Together with visceral obesity, this clustering of risk factors is known as the metabolic syndrome. Although the definition of the metabolic syndrome and its relevance in clinical practice are the subject of discussion, there is emerging consensus about the importance of treating all risk factors early and aggressively. Recent evidence suggests that new-onset diabetes mellitus and microalbuminuria are independent risk factors that should be considered when assessing composite cardiovascular risk. Treatment should be tailored to a patient's risk profile, with consideration of the varying effects that agents of different therapeutic classes have on cardiovascular and metabolic parameters.     

Metabolic syndrome X: a review

Metabolic syndrome X is a multifaceted syndrome, which occurs frequently in the general population. It is more common in men than in women. A large segment of the adult population of industrialized countries develops the metabolic syndrome, produced by genetic, hormonal and lifestyle factors such as obesity, physical inactivity and certain nutrient excesses. This disease is characterized by the clustering of insulin resistance and hyperinsulinemia, and is often associated with dyslipidemia (atherogenic plasma lipid profile), essential hypertension, abdominal (visceral) obesity, glucose intolerance or noninsulin-dependent diabetes mellitus and an increased risk of cardiovascular events. Abnormalities of blood coagulation (higher plasminogen activator inhibitor type 1 and fibrinogen levels), hyperuricemia and microalbuminuria have also been found in metabolic syndrome X. This review summarizes the present knowledge of abnormalities in this syndrome. Each risk factor is reviewed, and potential criteria for diagnosis and therapeutic targets are discussed. Because patients with metabolic syndrome X accumulate cardiac risk factors, they should be given special attention in terms of diagnosis and treatment.     

Management of nodal indolent (non marginal-zone) non-Hodgkin's lymphomas: practice guidelines from the Italian Society of Hematology, Italian Society of Experimental Hematology and Italian Group for Bone Marrow Transplantation

The Italian Society of Hematology (SIE) and the two affiliated societies (SIES and GITMO) commissioned a project to develop clinical practice guidelines for the treatment of nodal indolent non-Hodgkin's lymphomas (NHL). Key questions clinically relevant to the management of patients with nodal indolent NHL were formulated by an Advisory Committee and approved by an Expert Panel composed of eight senior hematologists. After a comprehensive, systematic review of the literature, the Expert Panel formulated therapy recommendations and graded them according to the supporting evidence. An explicit approach to consensus methodologies was used for evidence interpretation and for providing recommendations based on poor evidence. The Expert Panel formulated recommendations on when to start a lymphoma-specific therapy, which first-line therapy to choose and which therapy to adopt for patients with relapsed, refractory and transformed disease. Treatment deferral was recommended for patients with stage III-IV disease without systemic symptoms, high tumor burden, extranodal disease, cytopenia due to marrow involvement, leukemic phase, serous effusion and high lactate dehydrogenase levels. Patients with stage I-II disease and a low tumor burden should receive frontline external involved-field radiotherapy, while patients with a high tumor burden or a severe prognostic score should receive front-line chemotherapy plus involved-field radiotherapy. Younger patients with stage III-IV disease should receive front-line therapy with anthracycline- or fludarabine-based regimens combined with rituximab, while older patients who are candidates for treatment should receive single-agent alkylating therapy. By using a systematic literature review and an explicit approach to consensus among experts, recommendations for the key therapeutic decisions in patients with nodal indolent NHL are provided.     

Coronary heart disease, type 2 diabetes mellitus and cardiovascular disease risk factors: a study on a middle-aged and elderly population

The risk for all the manifestations of atherosclerotic disease is increased in patients affected by type 2 diabetes mellitus. The aim of the present work was to evaluate the prevalence of coronary heart disease (CHD) in a well-characterized middle-aged and elderly Italian diabetic population. The population studied included 3862 subjects, i.e. all the patients affected by type 2 diabetes of age >or=50 years attending the outpatient diabetes care unit of INRCA in Ancona (Italy) from 1 August 1997 to 31 July 1998. We collected and analysed both clinical and laboratory data by means of a computerized data base for the outpatient clinic management. The prevalence rate of CHD was 20.25% in this population. The groups with CHD and without CHD did not differ significantly with respect to age at onset of diabetes, body mass index and HbA1c levels, while patients with CHD were significantly older than patients without CHD and had a longer duration of diabetes. The prevalence of patients with hypertension (52.9 vs 63.0%, P<0.001), hypercholesterolemia (11.6 vs 14.1%, P<0.05) and hyperlipidemia (17.8 vs 23.3%, P<0.001) was significantly higher in the group of diabetic subjects affected by CHD than in patients not affected by heart ischemic disease. It might be hypothesized that the improvement of metabolic profile and the currently feasible control of non-diabetic risk factors could reduce cardiovascular disease rates in type 2 diabetic patients.     

Inflammatory mediators involved in the progression of the metabolic syndrome

The metabolic syndrome is often associated with type 2 diabetes mellitus, dyslipidemia, atherosclerosis, hypertension, steatosis of the liver and other organs, as well as hypertension, type 2 diabetes mellitus, and atherosclerosis. Recent studies have implicated a number of inflammatory mediators including cytokines, adipokines and eicosanoids in the inflammatory responses that accompany the metabolic syndrome. Measurements of the circulating levels of the inflammatory molecules that accompany this syndrome might provide leads to therapeutic approaches to modulate the inflammatory responses and thereby alter disease progression. In this review, we summarize recent studies on classical and newer inflammatory mediators in the pathogenesis of the metabolic syndrome in humans and experimental models.     

Effects of Periodontal Therapy on Metabolic Control in Patients With Type 2 Diabetes Mellitus and Periodontal Disease: A Meta-Analysis

Epidemiologic studies have reported increased incidence, prevalence and acuity of periodontitis in adults with diabetes and some have also suggested that treating periodontal disease may improve glycemic control in diabetic patients.This meta-analysis was conducted to evaluate the effects of different periodontal therapies on metabolic control in patients with type 2 diabetes mellitus (T2DM) and periodontal disease.We searched the Medline, EMBASE and Cochrane Library (Central) databases up to January 2014 for relevant studies pertaining to periodontal treatments and glycemic control in adults with T2DM. The search terms were periodontal treatment/periodontal therapy, diabetes/diabetes mellitus, periodontitis/periodontal and glycemic control. The primary outcome measure taken from the included studies was glycated hemoglobin (HbA1c).We compared differences in patients’ pre- and post-intervention HbA1c results between a treatment group receiving scaling and root planing (SRP) combined with administration of oral doxycycline (n = 71) and controls receiving SRP alone or SRP plus placebo (n = 72). Meta-analysis was performed using Comprehensive Meta Analysis software.Nineteen randomized controlled trials (RCTs) were identified. Four trials involving a total of 143 patients with T2DM and periodontal disease were determined to be eligible for analysis. Data of 1 study were not retained for meta-analysis because HbA1c results were recorded as median with IQR. Meta-analysis of the included 3 studies revealed no significant differences in HbA1c results between the periodontal treatment group (n = 71) and control group (n = 72) (HbA1c SMD = −0.238, 95% CI = −0.616 to 0.140; P = 0.217).Systemic doxycycline added to SRP does not significantly improve metabolic control in patients with T2DM and chronic periodontitis. Current evidence is insufficient to support a significant association between periodontal therapy and metabolic control in this patient population. However, evidence suggests that periodontal therapy itself improves metabolic control and reinforces that T2DM is a risk factor for periodontitis.     

HBV and HCV infection in type 2 diabetes mellitus: a survey in three diabetes units in different Italian areas

Viral infections and the metabolic syndrome may coexist in several individuals, due to the large prevalence of obesity and type 2 diabetes mellitus (T2DM). Antiviral therapy has changed the natural history of chronic viral hepatitis, but viral infection may remain undiagnosed in the absence of systematic screening. We determined the prevalence of HBV and/or HCV infection in an Italian cohort with T2DM (859 consecutive patients, 413 females) in three Italian centers: Turin, Bologna, and Naples. Screening for viral disease was coupled with the determination of parameters of metabolic syndrome. Fourteen patients were HBsAg-positive, 51 anti-HCV with a prevalence of genotype-1 infection in 58% of cases. Thirty cases had newly diagnosed viral markers, only one-third had already-diagnosed liver disease, 16 were being followed-up by a Liver Unit, and 9 cases had received antiviral treatment. Patients with viral markers had higher liver enzyme levels in comparison with virus-negative patients (P < 0.0001), whereas the prevalence of the metabolic syndrome was similar in the 2 groups. A positive correlation between BMI and alanine aminostransferase levels was only present in virus-negative cases, where the probability of enzyme levels above the upper limit of normal increased by 5% for unit of increase in BMI (OR: 1.05; 95% CI: 1.003–1.100, P = 0.037). In conclusion, the prevalence of HBV and HCV is non-negligible in patients with T2DM, but these cases may long remain undiagnosed. Elevated liver enzymes might be frequently disregarded in diabetes Units and ascribed to metabolic syndrome, thus excluding T2DM patients from specific disease-modifying antiviral treatment for hepatitis.