Mimbacas A.,Clemente Estable Biologic Research Institute IIBCE |
Vitarella G.,Diabetology Unit |
Souto J.,Clemente Estable Biologic Research Institute IIBCE |
Reyes A.L.,Clemente Estable Biologic Research Institute IIBCE |
And 4 more authors.
Journal of Pediatric Genetics | Year: 2012
The concept of a new form of diabetes, with signs of both types 1 and 2, has not been often considered, until recently. It is of immense interest to explore the role of the admixture that characterizes the Uruguayan population (higher and different from other Latin America countries) for the presence of such expression of that particular disease. We describe here a child who possibly presents with this expression. He had typical signs of both diabetic conditions: type 1 (young age, positive immunologic and genetic markers, ketoacidosis) and type 2 (obesity [body mass index = 36 kg/m2] and acanthosis nigricans). In spite of complying with the established guidelines, therapeutic and nutritional control, quality of life and good metabolic control, the patient’s obesity had been continually increasing. Looking for a genetic explanation, we studied three single nucleotide polymorphisms involved in three different metabolic pathways (peroxisome proliferator-activated receptor gamma 2, insulin receptor substrate-1 and uncoupling protein-2) associated with insulin resistance. Our patient showed three mutations, GG, GA, GG, associated with insulin resistance that explains obesity associated with limited response to the commonly used drugs. According to the clinical presentation and the genetic and immunological background, we considered that this patient presents with a new form of diabetes. We have termed this particular disease "hybrid diabetes" because of the involvement of genes associated with both the classical type of diabetes. However, at least in an admixed population such as in Uruguay, clinical classification would not strictly dictate the choice of treatment. © 2012 - IOS Press and the authors.
Salvi F.,Italian National Research Centres On Aging Inrca |
Marchetti A.,Italian National Research Centres On Aging Inrca |
D'Angelo F.,Diabetology Unit |
Boemi M.,Diabetology Unit |
And 3 more authors.
Drug Safety | Year: 2012
Older adults are about four to seven times more likely than younger persons to experience adverse drug events (ADEs) that cause hospitalization, especially if they are women and take multiple medications. The prevalence of drug-related hospitalizations has been reported to be as high as 31%, with large heterogeneity between different studies, depending on study setting (all hospital admissions or only acute hospital admissions), study population (entire hospital, specific wards, selected population and/or age groups), type of drug-related problem measured (adverse drug reaction or ADE), method of data collection (chart review, spontaneous reporting or database research) and method and definition used to detect ADEs. The higher risk of drug-related hospitalizations in older adults is mainly caused by age-related pharmacokinetic and pharmacodynamic changes, a higher number of chronic conditions and polypharmacy, which is often associated with the use of potentially inappropriate drugs. Other factors that have been involved are errors related to prescription or administration of drugs, medication non-adherence and inadequate monitoring of pharmacological therapies.Afew commonly used drugs are responsible for the majority of emergency hospitalizations in older subjects, i.e. warfarin, oral antiplatelet agents, insulin and oral hypoglycaemic agents, central nervous system agents. The aims of the present review are to summarize recent evidence concerning drug-related hospitalization in older adults, to assess the contribution of specific medications, and to identify potential interventions able to reduce the occurrence of these drug-related events, as they are, at least partly, potentially preventable. Adis © 2012 Springer International Publishing AG. All rights reserved.
Vaccaro O.,University of Naples Federico II |
Franzini L.,University of Parma |
Miccoli R.,University of Pisa |
Cavalot F.,University of Turin |
And 7 more authors.
Diabetes Care | Year: 2013
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. © 2013 by the American Diabetes Association.
Monesi L.,Irccs Instituto Of Ricerche Farmacologiche Mario Negri |
Tettamanti M.,Irccs Instituto Of Ricerche Farmacologiche Mario Negri |
Cortesi L.,Irccs Instituto Of Ricerche Farmacologiche Mario Negri |
Baviera M.,Irccs Instituto Of Ricerche Farmacologiche Mario Negri |
And 11 more authors.
Nutrition, Metabolism and Cardiovascular Diseases | Year: 2014
Aims: To investigate the incidence of major cardiovascular complications and mortality in the first years of follow-up in patients with newly diagnosed diabetes. Methods and results: We examined incidence rates of hospitalization for cardiovascular reasons and death among new patients with diabetes using the administrative health database of the nine million inhabitants of Lombardy followed from 2002 to 2007. Age and sex-adjusted rates were calculated and hazard ratios (HR) were estimated with a matched population without diabetes of the same sex, age (±1 year) and general practitioner.There were 158,426 patients with newly diagnosed diabetes and 314,115 subjects without diabetes. Mean follow-up was 33.0 months (SD ± 17.5). 9.7% of patients with diabetes were hospitalized for cardiovascular events vs. 5.4% of subjects without diabetes; mortality rate was higher in patients with diabetes (7.7% vs. 4.4%). The estimated probability of hospitalization during the follow up was higher in patients with diabetes than in subjects without for coronary heart disease (HR 1.4, 95% CI 1.3-1.4), cerebrovascular disease (HR 1.3.95% CI 1.2-1.3), heart failure (HR 1.4, 95% CI 1.3-1.4) as was mortality (HR 1.4, 95% CI 1.4-1.4).Younger patients with diabetes had a risk of death or hospital admission for cardio-cerebrovascular events similar to subjects without diabetes ten years older. Conclusions: The elevated morbidity and mortality risks were clear since the onset of diabetes and rose over time. These data highlight the importance of prompt and comprehensive patients care in addition to anti-diabetic therapy in patients with newly diagnosed diabetes. © 2013 Elsevier B.V.
Lapolla A.,University of Padua |
Frison V.,Diabetology Service |
Bettio M.,Diabetology Service |
Pos M.D.,Diabetology Service |
And 26 more authors.
Clinical Therapeutics | Year: 2015
Purpose Treatment with liraglutide in randomized controlled trials is associated with significant reductions in glycated hemoglobin (HbA1c) and weight loss in type 2 diabetes patients. The aim of this retrospective observational study was to investigate correlations of glycemic control and weight outcomes with baseline characteristics of patients starting liraglutide in outpatient clinics in Italy. Methods Type 2 diabetes patients were followed from baseline to 4, 8, and 12 months. Changes in glycemic parameters, weight, blood pressure, and lipids were assessed. Subanalyses were performed according to baseline characteristics. Multivariate linear and logistic regressions were used to assess correlations between glycemic efficacy, weight reduction, and liraglutide discontinuation after 12 months and baseline characteristics. Findings Four hundred and eighty-one patients were included. Mean (SD) age at baseline was 57.3 (9.2) years, diabetes duration was 9.5 (6.8) years, weight was 106.7 (20.8) kg, body mass index (BMI; calculated as kg/m2) was 37.1 (6.6), HbA1c was 8.7% (1.3%), fasting plasma glucose was 168.5 (45.3) mg/dL; 38.2% were treated previously with insulin and 52.2% were treated with metformin alone. After 12 months, mean (SD) changes were HbA1c -1.2% (1.4%), fasting plasma glucose -28.3 (41.1) mg/dL, weight -3.5 (5.8) kg, BMI -1.3 (2.1), waist circumference -2.6 (6.7) cm (all, P < 0.001). Drop in weight and HbA1c did not differ between baseline BMI classes ≤30 or >30. Weight loss was unchanged among diabetes duration quartiles, and HbA;bsubesub& reduction was significantly greater in patients with ≤4 years of diabetes duration (P = 0.01). Non-insulin-treated patients reached HbA1c ≤7% significantly more often than treated patients (44.2% vs 21.2%; odds ratio = 2.94; P < 0.001) and had significantly greater weight loss (-4.5 [8.2] kg vs -2.6 [5.4] kg; P = 0.03). Patients on metformin reached HbA;bsubesub& target more frequently than others (43.1% vs 29.7%; odds ratio = 1.80; 95% CI, 1.05-3.07). Significant positive determinants for HbA;bsubesub& reduction after 12 months were baseline HbA;bsubesub& age, and prior metformin monotherapy, and weight loss at 12 months was positively correlated with baseline weight, and negatively correlated with prior insulin treatment. Overall, 5.0% of patients interrupted liraglutide before the 12th month due to lack of glycemic control; they were less frequently treated with metformin only before liraglutide (29.2% vs 50.2%; P = 0.04). Implications Treatment with liraglutide in a real-world setting is associated with low therapy failure, good glycemic response, weight loss, and improvement in systolic blood pressure and lipid profile. The HbA;bsubesub& drop did not differ among baseline BMI classes, indicating that efficacy is maintained in patients with lower BMI. The probability of reaching HbA1c ≤7% was significantly higher in patients previously treated with metformin alone and without any previous insulin. This could reinforce the hypothesis that better results with liraglutide could be achieved in patients after early metformin failure. © 2015 Elsevier HS Journals, Inc.
Spazzafumo L.,Biostatistical Center |
Olivieri F.,Marche Polytechnic University |
Olivieri F.,Inrca National Institute |
Abbatecola A.M.,Scientific Direction |
And 15 more authors.
Age | Year: 2013
Factor structure analyses have revealed the presence of specific biological system markers in healthy humans and diseases. However, this type of approach in very old persons and in type 2 diabetes (T2DM) is lacking. A total sample of 2,137 Italians consisted of two groups: 1,604 healthy and 533 with T2DM. Age (years) was categorized as adults (≤65), old (66-85), oldest old (>85-98) and centenarians (≥99). Specific biomarkers of routine haematological and biochemical testing were tested across each age group. Exploratory factorial analysis (EFA) by principal component method with Varimax rotation was used to identify factors including related variables. Structural equation modelling (SEM) was applied to confirm factor solutions for each age group. EFA and SEM identified specific factor structures according to age in both groups. An age-associated reduction of factor structure was observed from adults to oldest old in the healthy group (explained variance 60.4% vs 50.3%) and from adults to old in the T2DM group (explained variance 57.4% vs 44.2%). Centenarians showed three-factor structure similar to those of adults (explained variance 58.4%). The inflammatory component became the major factor in old group and was the first one in T2DM. SEM analysis in healthy subjects suggested that the glucose levels had an important role in the oldest old. Factorial structure change during healthy ageing was associated with a decrease in complexity but showed an increase in variability and inflammation. Structural relationship changes observed in healthy subjects appeared earlier in diabetic patients and later in centenarians. © 2011 American Aging Association.
PubMed | Diabetology Unit and Clemente Estable Biologic Research Institute IIBCE
Type: Journal Article | Journal: Journal of pediatric genetics | Year: 2016
The concept of a new form of diabetes, with signs of both types 1 and 2, has not been often considered, until recently. It is of immense interest to explore the role of the admixture that characterizes the Uruguayan population (higher and different from other Latin America countries) for the presence of such expression of that particular disease. We describe here a child who possibly presents with this expression. He had typical signs of both diabetic conditions: type 1 (young age, positive immunologic and genetic markers, ketoacidosis) and type 2 (obesity [body mass index = 36 kg/m(2)] and acanthosis nigricans). In spite of complying with the established guidelines, therapeutic and nutritional control, quality of life and good metabolic control, the patients obesity had been continually increasing. Looking for a genetic explanation, we studied three single nucleotide polymorphisms involved in three different metabolic pathways (peroxisome proliferator-activated receptor gamma 2, insulin receptor substrate-1 and uncoupling protein-2) associated with insulin resistance. Our patient showed three mutations, GG, GA, GG, associated with insulin resistance that explains obesity associated with limited response to the commonly used drugs. According to the clinical presentation and the genetic and immunological background, we considered that this patient presents with a new form of diabetes. We have termed this particular disease hybrid diabetes because of the involvement of genes associated with both the classical type of diabetes. However, at least in an admixed population such as in Uruguay, clinical classification would not strictly dictate the choice of treatment.
PubMed | Diabetology Unit, Irccs Instituto Of Ricerche Farmacologiche Mario Negri and Regional Health Ministry
Type: | Journal: Nutrition, metabolism, and cardiovascular diseases : NMCD | Year: 2016
In contrast to the well-documented global prevalence of diabetes, much less is known about the epidemiology of cardiovascular (CV) complications in recent years. We describe the incidence of major CV events, deaths and drug prescribing patterns from 2002 to 2012 in subjects with (DM) or without diabetes mellitus (No DM).Subjects and outcomes were identified using linkable health administrative databases of Lombardy, a region in Northern Italy. A logistic regression model was used to compare myocardial infarction (MI), stroke, major amputation and death between DM and No DM in 2002 and 2012 and between the two index years in each population. The interaction between years and diabetes was introduced in the model. From 2002 to 2012 the incidence of major CV complications and death fell in both groups with a larger reduction among DM only for CV events: OR (95% CI) for the interaction 0.86 (0.79-0.93) for MI, 0.89 (0.82-0.96) for stroke, 0.78 (0.57-1.06) for major amputations. CV prevention drugs rose considerably from 2002 to 2012 particularly in DM and a switch towards safer antihyperglycemic drugs was also observed.Major CV complications and death declined from 2002 to 2012 in both DM and No DM. This might be due to a larger increase in prescriptions of CV drugs in DM and a relevant change toward recommended antihyperglycemic drugs.
Culeddu N.,CNR Institute of Biomolecular Chemistry |
Chessa M.,Sardinian Mediterranean Imaging Research Group |
Porcu M.C.,CNR Institute of Biomolecular Chemistry |
Fresu P.,University of Sassari |
And 3 more authors.
Metabolomics | Year: 2012
The genetic homogeneity of the people of Sardinia makes it an ideal place to study genetic related diseases such as type 1 diabetes, which in this island has one of the highest incidence worldwide. The principal objective of this study was to use 1H high-resolution NMR spectroscopy and supervised methods of multivariate data analysis to highlight the importance of the variation of low concentration metabolites between healthy and diabetic Sardinian children. To achieve this goal, statistical analyses were performed after removal of the prevailing signals of sugars and citrate (related to carbohydrate metabolism) and of hippurate (a metabolite of bacterial origins) whose presence overwhelmed all the other compounds effects on classification. The variable influence in the statistical model showed that other metabolites deriving from gut microbial metabolism (p-cresol sulphate and phenylacetylglycine) were heavily involved in classification. This suggests the importance of changes in gut microbiota composition associated with type 1 diabetes in children. © 2012 Springer Science+Business Media, LLC.
PubMed | University of Verona, Diabetology Unit, Azienda Ospedaliera Spedali Civili di Brescia and University of Brescia
Type: | Journal: Scientific reports | Year: 2015
To evaluate the effects of supervised exercise training (SET) on cardiometabolic risk, cardiorespiratory fitness and oxidative stress status in 2 diabetes mellitus (T2DM), twenty male subjects with T2DM were randomly assigned to an intervention group, which performed SET in a hospital-based setting, and to a control group. SET consisted of a 12-month supervised aerobic, resistance and flexibility training. A reference group of ten healthy male subjects was also recruited for baseline evaluation only. Participants underwent medical examination, biochemical analyses and cardiopulmonary exercise testing. Oxidative stress markers (1-palmitoyl-2-[5-oxovaleroyl]-sn-glycero-3-phosphorylcholine [POVPC]; 1-palmitoyl-2-glutaroyl-sn-glycero-3-phosphorylcholine [PGPC]) were measured in plasma and in peripheral blood mononuclear cells. All investigations were carried out at baseline and after 12 months. SET yielded a significant modification (p < 0.05) in the following parameters: VOmax (+14.4%), gas exchange threshold (+23.4%), waist circumference (-1.4%), total cholesterol (-14.6%), LDL cholesterol (-20.2%), fasting insulinemia (-48.5%), HOMA-IR (-52.5%), plasma POVPC (-27.9%) and PGPC (-31.6%). After 12 months, the control group presented a VOmax and a gas exchange threshold significantly lower than the intervention group. Plasma POVC and PGPC were significantly different from healthy subjects before the intervention, but not after. In conclusion, SET was effective in improving cardiorespiratory fitness, cardiometabolic risk and oxidative stress status in T2DM.