33 research outputs found
Advanced glycation end-products in microvascular complications of type 2 diabetes: Are they “major actors” in metabolic memory?
No full textAn excess of advanced glycation end-products (AGE) is one of the most important mechanisms in the pathophysiology of chronic diabetic complications. This review summarizes the role of these compounds in microvascular pathogenesis, particularly in the light of recently proposed biochemical mechanisms for diabetic retinopathy, nephropathy and neuropathy. Then we focus on the relationship between AGE and “metabolic memory”, to clarify AGE’s role in the link between micro- and macrovascular complications. Recent studies indicate AGE not so much as “actors”, and more as “directors” of processes leading to these complications. They have several intra- and extracellular targets, so they can be seen as a “bridge” between intra- and extracellular damage. This may partly explain the clinical link between micro- and macrovascular disease in diabetes, and help clarify the mechanisms behind metabolic memory. The pathophysiological cascades triggered by AGE have a dominant, hyperglycemia-independent role in the microvascular complications of diabetes so prevention and treatment must focus not only on early glycemic control, but also on reducing the factors related to glycooxidative stress
Gestational Diabetes Mellitus and Future Cardiovascular Risk: An Update
No full textThe prevalence of gestational diabetes mellitus is increasing in parallel with the rising prevalence of type 2 diabetes and obesity around the world. Current evidence strongly suggests that women who have had gestational diabetes mellitus are at greater risk of cardiovascular disease later in life. Given the growing prevalence of gestational diabetes mellitus, it is important to identify appropriate reliable markers of cardiovascular disease and specific treatment strategies capable of containing obesity, diabetes, and metabolic syndrome in order to reduce the burden of cardiovascular disease in the women affected
Long-term effect of pioglitazone vs glimepiride on lipoprotein oxidation in patients with type 2 diabetes: a prospective randomized study
No full textAims: Type 2 diabetes (DM2) is associated to oxidative modifications of high-density lipoproteins (HDL), which can interfere with their function. Pioglitazone has proved effective in raising HDL cholesterol (HDL-C) and lowering small dense low-density lipoprotein (LDL), but no clinical studies have examined its effect on lipoprotein oxidation in patients with DM2. Methods: We assessed the effect of pioglitazone vs glimepiride after 1 year on HDL oxidation, expressed as relative abundance of peptides containing Met 112 O in ApoA-I (oxApoA-I) estimated by mass spectrometry (MALDI/TOF/TOF), in 95 patients with DM2. The oxLDL and AGE were quantified by ELISA. Results: Patients receiving pioglitazone showed a significant increase in the concentration of ApoA-I (Δ = 7.2 ± 14.8 mg/dL, p < 0.02) and a reduction in oxApoA-I (Δ = − 1.0 ± 2.6%, p < 0.02); this reduction was not significantly different from glimepiride. oxLDL showed a slight, but not significant increase in both treatment groups. Regression analysis showed a correlation between ΔoxApoA-I and ΔAGE (r = 0.30; p = 0.007) in all patients, while both of these parameters were unrelated to changes in HbA1c, HDL-C, duration of illness, or use of statins. Conclusions: Long-term treatment with pioglitazone was effective in reducing the oxidation of HDL, but not LDL in patients with DM2, while glimepiride didn’t. This finding seems to be associated to the change of glyco-oxidation status, not to any improvement in glycemic control or lipid profile. Trial registration: NCT00700856, ClinicalTrials.gov Registered June 18, 2008
Telemedicina: etica, informazione e responsabilità professionale.
No full textTelemedicine — as defined in the European Economic and Social Committee document published on December 23, 2009
in relation with the Communication COM (2008) 689 European Commission (Telemedicine for the benefit of patients,
healthcare systems and society) — is the performance of health care services, through the use of ICT, in circumstances
in which the physician and the patient (or two physicians) are not in the same location. It involves secure transmission of
medical data and information, through text, sound, images or other forms needed for the prevention, diagnosis, treatment
and follow-up of patients. Telemedicine is an unexpected “cultural revolution”, can help improve the lives of European
citizens, both patients and health professionals, while tackling the challenges to healthcare systems. The development of
tools for telemedicine offers the opportunity to find new ideas to the traditional problems of medicine and improve the use
of the National Health Service. It was created to health following purposes: secondary prevention, diagnosis, treatment,
rehabilitation, monitoring. Now, it was widely recognized that the Telemedicine does not replace the traditional health
services in personal patient-physician relationship, but complements it potentially improve effectiveness, efficiency and
appropriateness of complying, however, to all their rights and obligations of any medical act with special care of training
and information
Role of fructosamine-3-kinase in protecting against the onset of microvascular and macrovascular complications in patients with T2DM
No full textIntroduction Microangiopathic and macroangiopathic complications are the main cause of morbidity and mortality in the diabetic population. Numerous publications have highlighted the role of glycation in the onset of complications of diabetes. In this context, the detection of fructosamine-3-kinase (FN3K) -an enzyme capable of counteracting the effect of hyperglycemia by intervening in protein glycation -has attracted great interest. Several studies have linked FN3K genetic variability to its enzymatic activity and glycated hemoglobin (HbA1c) levels. Here, we investigated the role of FN3K polymorphisms in the development of microvascular and macrovascular complications of diabetes. Research design and methods The anthropometric and biochemical parameters, and any medical history of microangiopathic and macroangiopathic complications, were documented in a sample of 80 subjects with type 2 diabetes. All subjects were screened for FN3K gene and analyzed for the combination of three polymorphisms known to be associated with its enzymatic activity (rs3859206 and rs2256339 in the promoter region and rs1056534 in exon 6). Results The combination of allelic variants of FN3K polymorphisms resulted in 13 distinct genotypic variants within the cohort. Comparison between genotypes showed no significant differences in terms of demographic, anthropometric and biochemical parameters, risk markers and long-term complications, except for a higher age and vitamin E levels associated with the genotype presenting GG at position -385, TT at position -232, and CC at c.900 A. Evaluating the microangiopathic and macroangiopathic complications as a whole, we found that they appeared significantly less present in this genotype compared with all other genotypes (p=0.0306). Conclusions The group of patients carrying the favorable allele for the three polymorphisms of the FN3K gene revealed less severe microangiopathy and macroangiopathy, suggesting a protective role of this genotype against the onset of the complications of diabetes
Genetic variability of the fructosamine 3-kinase gene in diabetic patients
No full textBACKGROUND:
Nonenzymatic glycation appears to be an important factor in the pathogenesis of diabetic complications. Fructosamine 3-kinase (FN3K), initially identified in erythrocytes, appears to be responsible for the removal of fructosamine from proteins, suggesting a protective role in nonenzymatic glycation. Recently, genetic variants in the FN3K gene have been studied in diabetic patients. The aim of our study was the molecular characterization of the FN3K gene in a representative group of Italian patients with type 1 (T1DM) and 2 (T2DM) diabetes mellitus and in a cohort of healthy controls.
METHODS:
Seventy diabetic subjects (35 type 1 and 35 type 2) with stable glycemic control and 33 healthy control subjects were evaluated using PCR and direct sequencing of the FN3K gene. Denaturing high performance liquid chromatography (DHPLC) was used in controls for screening for the presence of the genetic variants previously found in diabetic patients.
RESULTS:
Seven different genetic variants were identified, five of them already reported and two new: the p.R187X and p.Y239C mutations identified in two females affected by T2DM. No significant association was found between certain polymorphisms and diabetes conditions. Preliminary haplotype studies are also reported. With respect to genotypes, we noted that some were not present in all the investigated cohort, and some were found related to higher glycated hemoglobin compared to others, although not at a significant level, probably because of the small number of subjects investigated.
CONCLUSIONS:
In conclusion, this study identified two new mutations and additional variants within the FN3K gene. This is the first study on FN3K in Italy. Future work is needed to achieve a better understanding of the FN3K enzyme and its possible clinical utility in the management of diabetic patients
The importance of HbA1c and glucose variability in patients with type 1 and type 2 diabetes: outcome of continuous glucose monitoring (CGM).
No full textGlucose variability has recently been investigated in diabetic patients in several studies, but most of them considered only a few variability indicators and did not systematically correlate them with patients' HbA1c levels and other important characteristics. In thus study, the correlations between HbA1c levels and metabolic control (average glucose, AG), glucose variability (SD, CONGA, MAGE, MODD, BG ROC), hyperglycemia (HBGI), hypoglycemia (LBGI) and postprandial (AUC PP) indices were investigated in patients with type 1 and type 2 diabetes. The study involved 68 patients divided into 3 groups as follows: 35 patients had type 1 diabetes (group 1); 17 had type 2 diabetes and were taking multiple daily injections (MDI) of insulin (group 2); and 16 patients had type 2 diabetes treated with OHA and/or basal insulin (group 3). The indicators were obtained over at least 48 h using a continuous glucose monitoring (CGM) system. HbA1c levels were measured at the baseline and after CGM. HbA1c correlated significantly with AG (r = 0.74), AUC PP (r = 0.69) and HBGI (r = 0.74), but only in type 1 diabetic patients. Patients with longstanding disease and type 1 diabetes had a greater glucose variability, irrespective of their HbA1c levels. Insulin therapy with MDI correlated strongly with HbA1c, but not with glucose variability. HbA1c levels identify states of sustained hyperglycemia and seem to be unaffected by hypoglycemic episodes or short-lived glucose spikes, consequently revealing shortcomings as a "gold standard" indicator of metabolic control. Glucose variability indicators describe the glucose profile of type 1 diabetic patients and identify any worsening glycemic control (typical of longstanding diabetes) more accurately than HbA1c tests
Possible role of fructosamine 3-kinase genotyping for the management of diabetic patients
No full textDiabetes mellitus is a global pandemic and continues to increase in numbers and significance. Several pathogenic processes are involved in the development of such disease and these mechanisms could be influenced by genetic, epigenetic and environmental factors. Non-enzymatic glycation reactions of proteins have been strongly related to pathogenesis of chronic diabetic complications. The identification of fructosamine 3-kinase (FN3K), an enzyme involved in protein deglycation, a new form of protein repair, is of great interest. FN3K phosphorylates fructosamines on the third carbon of their sugar moiety, making them unstable and causing them to detach from proteins, suggesting a protective role of this enzyme. Moreover, the variability in FN3K activity has been associated with some polymorphisms in the FN3K gene. Here we argue about genetic studies and evidence of FN3K involvement in diabetes, together with results of our analysis of the FN3K gene on a Caucasian cohort of diabetic patients. Present knowledge suggests that FN3K could act in concert with other molecular mechanisms and may impact on gene expression and activity of other enzymes involved in deglycation process
Alta prevalencia de anticuerpos antitiroideos positivos, baja concentración de hormonas tiroideas y alta concentración de tirotrofina (TSH) asociado a una baja concentración de vitamina D (VitD) en pacientes pediátricos
No full textIntroducción. La VitD está asociada tradicionalmente a la homeostasis del calcio y la mineralización ósea. Diversos estudios han demostrado la asociación entre los niveles de VitD y algunas alteraciones no óseas, que fueron descriptas como efectos no clásicos. Objetivo del estudio. Estudiar la asociación entre el status de VitD, la presencia de anticuerpos, antitiroperoxidasa (ATPO) y antitiroglobulina (UATG), hormonas tiroideas (triiodotironina (T3), tiroxina (T4), tiroxina libre (FT4)) y TSH sérico en un grupo de pacientes pediátricos con metabolismo óseo balanceado. Metodología empleada: 153 pacientes, 57 niños y 96 niñas con edades entre 1 y 18 años, con calcio (Ca), fósforo (P), hormona paratiroidea (PTH), y fosfatasa alcalina (FAL) dentro de parámetros normales. La función tiroidea fue evaluada midiendo T3, T4, FT4, TSH, ATPO y UATG. Ensayos: Ca, P y FAL fueron realizados en COBAS 501, Roche. PTH, UATG y ATPO en Immulite 2000, Siemens; los anticuerpos fueron considerados positivos cuando los resultados dieron por sobre el límite de sensibilidad analítica para cada ensayo. VitD, T3, T4, FT4 y TSH en Architect i2000, Abbott. Resultados obtenidos. Encontramos una correlación positiva entre los niveles de VitD(ng/ml) y T3(ng/ml) (T3=1.2843+0.0062xVitD, r:0.71, p<0.019;); T4(µg/dl) (T4= 6.9663+0.0267xVitD, r:0.62, p<0.049) y FT4(ng/dl) (FT4=1.0702+0.0042xVitD, r:0.80, p<0.006) y una correlación negativa entre VitD y TSH (µIU/ml) (TSH=4.1721-0.0488xVitD, r: 0.75, p<0.018). La presencia de anticuerpos fue significativa en el grupo en pacientes deficientes (VitD entre 10 – 20) comparada con el grupo suficientes (VitD 30 – 80) p<0.015, pero no con el grupo de insuficientes (VitD 20 – 30) y tampoco se halló diferencias entre el grupo insuficientes y suficientes. Conclusiones. Los resultados muestran un posible efecto inmunomodulador de la VitD sobre la función tiroidea de pacientes pediátricos, también se observó una correlación entre los niveles de VitD, hormonas tiroideas y TSH.Introduction. VitD has traditionally been associated with systemic calcium homeostasis and bone mineralization. Observational studies have demonstrated the association of VitD status with a number of common disorders that have been described as non-classic effects of VitD. Aim. The purpose of the present study is to investigate the association between VitD status and anti-thyroid antibodies, serum thyroid hormones and serum TSH in a pediatric cohort with balanced bone metabolism. Methods. One hundred fifty-three patients, fifty-seven boys, and ninety-six girls with ages ranging from 1 to 18 years, with calcium, phosphorus, parathyroid hormone, and alkaline phosphatase levels within the normal range. Thyroid function was assessed with thyroid hormones triiodothyronine (T3), thyroxine (T4) and Free thyroxine (FT4), TSH and anti-thyroid antibodies. Calcium, phosphorus and akaline phosphatase were assessed by Cobas 501, Roche Laboratories. Paratohormone, Anti-thyroglobuline Antibody and Anti-thyroperoxidase Antibody by Immulite 2000, Siemens. Antithyroid Antibodies were considered positive when the result was over the analytical sensitive limit for each assay. VitD, T3, T4, FT4 and TSH were evaluated by Architect i2000, Abbott. Results. We have found a positive correlation between levels of VitD (ng/ml) and T3(ng/ml) (T3= 1.2843+0.0062xVitD, r:0.71, p<0.019); T4(µg/dl) (T4= 6.9663+0.0267xVitD, r: 0.62, p<0.049) and FT4(ng/dl) (FT4 = 1.0702+0.0042xVitD, r: 0.80, p<0.006) and a statistically significant negative correlation between VitD and TSH (µIU/ml) levels (TSH= 4.1721-0.0488xVitD, r: 0.75, p<0.018). Thyroid antibodies were significantly higher in the group of deficient (VitD between 10 – 20) than in the sufficient (VitD 30 – 80) but not compared with the insufficient group (VitD 20 – 30), while between the insufficient and sufficient, there were not significant differences. Conclusions. These results suggest that VitD might also have al immunomodulator effect on thyroid function in a pediatric cohort, as well as thyroid hormones and TSH vary according to VitD levels in patients with bone metabolism balanced.Fil: Zaidman, V. E.. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Maceiras, M.. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Lazzati, J. M.. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Kutasz, E. P.. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: D'Isa, P.. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Chilelli, C.. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Tau, C.. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Viterbo, G.. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Rivarola, Marco Aurelio. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Belgorosky, Alicia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Chaler, E. A.. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentin
