PubMed Health⌕ Search

Biomedical subjects

S Manfrini

Publications and source records attributed to S Manfrini.

At least 19 recordsLinked to original sources
PubMed2007

Raised C-reactive protein levels in patients with recent onset type 1 diabetes.

BACKGROUND: To investigate serum concentrations of high-sensitive C-reactive protein (CRP) and alpha(1)-acid glycoprotein (AGP) in patients with T1DM, at diagnosis and after 12 months of intensive insulin therapy (T12). METHODS: CRP and AGP were measured in 44 recent onset T1DM patients (26M/18F, mean age 14.9 +/- 9.1 years), and 44 age- and sex-matched controls, using a highly sensitive immunonephelometric assay. RESULTS: There were no significant differences in the concentrations of high-sensitive C-reactive protein (hs-CRP) and AGP between patients and controls. hs-CRP levels significantly increased in patients at T12 compared to the levels at diagnosis [0.69 (0.14-15.5) versus 0.43 (0.14-7.47) mg/L, p < 0.05; for males: 0.77 (0.14-15.5) versus 0.35 (0.14-7.47) mg/L, p < 0.05; for females the increase was not significant]. AGP levels were not different at T12 compared to diagnosis. No significant correlations were found between hs-CRP and body mass index (BMI), C-peptide, glycosylated haemoglobin, or insulin dose. A strong correlation was found between hs-CRP values at diagnosis and those at T12 (rho = 0.73, p < 0.001); indeed, patients with hs-CRP levels above the 50th percentile at diagnosis showed significantly increased hs-CRP values at T12 compared to patients with baseline hs-CRP levels under the 50th percentile [1.61 (0.18-15.5) versus 0.16 (0.14-1.92) mg/L, p < 0.0001)], and to controls [0.55 (0.14-6.50), p = 0.001]. CONCLUSIONS: This is the first report showing that, despite good metabolic control, 1 year of overt T1DM is sufficient to increase hs-CRP levels, especially in males. hs-CRP levels at diagnosis is a predictor for the values observed at 12 months, suggesting the possibility to select a subgroup of patients requiring strict follow-up for cardiovascular complications.

Adolescent↗
PubMed2006

Metabolic factors affecting residual beta cell function assessed by C-peptide secretion in patients with newly diagnosed type 1 diabetes.

BACKGROUND: In recent onset of type 1 diabetes, the residual beta cell function, assessed by baseline and/or stimulated C-peptide secretion, can be a useful parameter to establish the extension of beta cell destruction. How metabolic parameters at diagnosis influence residual C-peptide secretion is not well established. PATIENTS AND METHODS: We analyzed 553 consecutive patients with recent onset (<4 weeks) of type 1 diabetes (250 females and 303 males, mean age 15+/-8 years). Baseline and stimulated C-peptide by i.v. glucagon were evaluated using a highly sensitive radio-immunoassay. Metabolic parameters including blood glucose, HbA1c, insulin dose, and BMI were also evaluated. RESULTS: Baseline and stimulated C-peptide were 0.26+/-0.22 and 0.47+/-0.38 nmol/l and correlated positively with age (p<0.001). There was no significant correlation between C-peptide and blood glucose at diagnosis. BMI was positively correlated with both baseline and stimulated C-peptide secretion (p<0.001). By contrast, HbA1c levels inversely correlated with both baseline and stimulated C-peptide secretion (p<0.001). CONCLUSION: In type 1 diabetes at diagnosis, baseline and stimulated C-peptide are higher in pubertal and young adult patients compared with pre-pubertal patients suggesting that such parameter can be used as an end point marker for studies aimed at protecting and/or restoring beta cells in patients with substantial beta cell function. High levels of HbA1c and lower BMI are dependent variables of C-peptide values.

Adolescent↗
PubMed2006

The effects of calcitriol and nicotinamide on residual pancreatic beta-cell function in patients with recent-onset Type 1 diabetes (IMDIAB XI).

BACKGROUND: A number of recent studies underline the importance of vitamin D in the pathogenesis of Type 1 diabetes (T1D). AIMS: The aim of this study was to investigate whether supplementation with the active form of vitamin D (calcitriol) in subjects with recent-onset T1D protects residual pancreatic beta-cell function and improves glycaemic control (HbA(1c) and insulin requirement). METHODS: In this open-label randomized trial, 70 subjects with recent-onset T1D, mean age 13.6 years +/- 7.6 sd were randomized to calcitriol (0.25 microg on alternate days) or nicotinamide (25 mg/kg daily) and followed up for 1 year. Intensive insulin therapy was implemented with three daily injections of regular insulin + NPH insulin at bedtime. RESULTS: No significant differences were observed between calcitriol and nicotinamide groups in respect of baseline/stimulated C-peptide or HbA1c 1 year after diagnosis, but the insulin dose at 3 and 6 months was significantly reduced in the calcitriol group. CONCLUSIONS: At the dosage used, calcitriol has a modest effect on residual pancreatic beta-cell function and only temporarily reduces the insulin dose.

Adolescent↗
PubMed2005

Low levels of 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 in patients with newly diagnosed type 1 diabetes.

BACKGROUND AND AIMS: An epidemiological retrospective study and a recent prospective study from Finland have both concluded that vitamin D3 supplementation at birth protects individuals from type 1 diabetes later in life. Moreover, it is thought that vitamin D3 supplementation, in particular its activated form, 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3], may act as an immunomodulator, facilitating the shift from a Th1 to a Th2 immune response. The aim of this surveillance study was to measure levels of both 25-hydroxyvitamin D3 (25OHD3) and 1,25-dihydroxyvitamin D3 in patients with newly diagnosed type 1 diabetes as compared to normal subjects. METHODS: We measured plasma levels of 25-hydroxyvitamin D3 [25OHD3] and 1,25-dihydroxyvitamin D3 by radioimmunoassay in 88 consecutive patients with newly diagnosed type 1 diabetes (mean age 14.6 years; diagnosis within the last week), and in 57 healthy age and sex-matched subjects (mean age 16.5 years) born and residing in the Lazio region of continental Italy. RESULTS: Mean levels of both 25OHD3 and 1,25-(OH)2D3 were significantly lower in patients compared to controls (p < 0.01 and p < 0.03, respectively). There was no correlation between 1,25-(OH)2D3 plasma level and metabolic control status at disease diagnosis, age, gender, or most importantly, seasonality of disease diagnosis. This new observation endorses the findings of the Finnish study, even though Italy is a geographic area with more hours of sunlight than Finland. CONCLUSIONS: These findings suggest that vitamin D3 may be an important pathogenic factor in type 1 diabetes independent of geographical latitude, and that its supplementation should be considered not only at birth, but also at diagnosis of type 1 diabetes with the aim of favouring a Th2 immune response and protecting residual beta cells from further destruction.

Adolescent↗
PubMed2005

A two year observational study of nicotinamide and intensive insulin therapy in patients with recent onset type 1 diabetes mellitus.

BACKGROUND AND AIMS: A number of trials have evaluated residual beta-cell function in patients with recent onset type 1 diabetes mellitus (DM1) treated with nicotinamide in addition to intensive insulin therapy (IIT). In most studies, only a slight decline of C-peptide secretion was observed 12 months after diagnosis; however, no data is available on C-peptide secretion and metabolic control in patients continuing nicotinamide and IIT for up to 2 years after diagnosis. PATIENTS AND METHODS: We retrospectively analysed data from 25 patients (mean age 14.7 years +/- 5 SD) with DM1 in whom nicotinamide at a dose of 25 mg/kg b. wt. was added from diagnosis (< 4 weeks) to IIT (three injections of regular insulin at meals + one NPH at bed time) and continued for up to 2 years after diagnosis. Data were also analysed from patients (n = 27) in whom IIT was introduced at diagnosis and who were similarly followed for 2 years. Baseline C-peptide as well as insulin dose and HbA1c levels were evaluated at 12 and 24 months after diagnosis. RESULTS: In the course of the follow-up, patients on nicotinamide + IIT or IIT alone did not significantly differ in terms of C-peptide secretion (values at 24 months in the two groups were 0.19 +/- 0.24 nM vs 0.19 +/- 0.13 nM, respectively). Insulin requirement (0.6 +/- 0.3 U/kg/day vs 0.7 +/- 0.2 U/kg/day at 24 months, respectively) did not differ between the two groups. However, HbA1c was significantly lower 2 years after diagnosis in patients treated with nicotinamide + IIT (6.09 +/- 0.9% vs 6.98 +/- 0.9%, respectively, p < 0.01). No adverse effects were observed in patients receiving nicotinamide for 2 years. CONCLUSION: Implementation of IIT with the addition of nicotinamide at diagnosis continued for 2 years improves metabolic control as assessed by HbA1c. In both nicotinamide and control patients, no decline in C-peptide was detected 2 years after diagnosis, indicating that IIT preserves C-peptide secretion. We conclude that nicotinamide + IIT at diagnosis of DM1 prolonged for up to 2 years can be recommended, but longer follow-up is required to determine whether nicotinamide should be continued beyond this period.

Adolescent↗
PubMed2004

Glucose evaluation trial for remission (GETREM) in type 1 diabetes: a European multicentre study.

OBJECTIVE: Strict metabolic control during the 1st year of type 1 diabetes is thought to be a key factor for achieving clinical remission. The aims of this study were two-fold: (i) to evaluate the frequency and duration of spontaneous remission (defined according to the parameters issued by the International Diabetic Immunotherapy Group (IDIG)) in a European population of consecutive recent onset type 1 diabetes patients (aged 5-35 years), followed-up for a period of 36 months with a common protocol of intensive insulin therapy and without adjunct immune-intervention; and (ii) to identify the predictive factors for clinical remission. RESEARCH DESIGN AND METHOD: A total of 189 consecutive patients with newly diagnosed type 1 diabetes according to ADA criteria were recruited in participating centres (Belgium, Czech Republic, Estonia, France, Germany, Hungary, Italy, Poland, Romania, Sweden and Turkey) and followed-up for a period of up to 36 months. In all patients, intensive insulin therapy was implemented consisting of three or four injections of regular insulin daily with NPH insulin at bedtime. Adjustment of insulin dose was made according to a common protocol. Various clinical characteristics (age, gender, severity of presentation, etc.), history (presence of diabetic siblings in the family, etc.) and integrated parameters of metabolic control (HbA(1c), blood glucose, the total insulin dose at hospital discharge adjusted for body weight) were collected. RESULTS: Twenty-two patients (11.6%) experienced remission. The median duration of remission was 9.6 months and the range was 31 months. There was a wide variation among centres. Logistic regression analysis focused on the centre as the main variable in achieving remission. CONCLUSION: Remission was shown to be very heterogeneous between centres depending on 'other factors' such as patient care and family awareness of the disease rather than on 'measurable factors' such as sex, age, HbA(1c) and severity of presentation at diagnosis. Using intensive insulin therapy and optimisation of metabolic control, remission occurred in nearly one out of eight patients.

Adolescent↗
PubMed2004

A randomized trial of nicotinamide and vitamin E in children with recent onset type 1 diabetes (IMDIAB IX).

OBJECTIVE: Various adjuvant therapies have been introduced along with intensive insulin therapy in patients with recent onset type 1 diabetes. Nicotinamide (NA), administered at diagnosis of the disease, can have beneficial effects on the clinical remission rate, improve metabolic control and preserve or slightly increase beta-cell function, probably by reducing toxicity due to free oxygen radicals. Vitamin E, a known antioxidant, inhibits lipid peroxidation; this can lead to protection of islet beta cells from the combined effects of interleukin 1, tumor necrosis factor and gamma interferon. The aim of the present study was to investigate whether the addition of vitamin E to NA could improve metabolic control and the residual beta-cell function, as measured by C-peptide secretion, in children and adolescents with recent onset type 1 diabetes; patients were followed-up for 2 years after diagnosis. PATIENTS AND STUDY DESIGN: Recent onset type 1 diabetes patients (n=64, mean age 8.8 years) were recruited by participating centres of the IMDIAB group. Thirty-two patients were randomized to NA (25 mg/kg body weight) plus vitamin E (15 mg/kg body weight); 32 patients acted as controls and received NA only at the same dose as above. Intensive insulin therapy was applied to both treatment groups. RESULTS: There were three drop outs during the 2-year follow-up period. Overall, patients assigned to the NA+vitamin E group or the NA group did not significantly differ in terms of glycated hemoglobin (HbA1c) levels, insulin requirement or baseline C-peptide secretion. Patients diagnosed at an age of less than 9 years showed significantly reduced C-peptide levels compared with those aged over 9 years at diagnosis and at the 2-year follow-up but there were no differences between the NA and NA+vitamin E treated groups. However at 6 months, patients over 9 years of age treated with NA+vitamin E showed significantly higher C-peptide compared with the NA group (P<0.003). In both age groups and in the different treatment groups, C-peptide levels found at diagnosis were preserved 2 years later. CONCLUSIONS: The use of NA alone, or in combination with vitamin E, along with intensive insulin therapy is able to preserve baseline C-peptide secretion for up to 2 years after diagnosis. This finding is of particular interest for pre-pubertal children with type 1 diabetes and has never been reported before.

Adolescent↗
PubMed2004

Effect of 4G/5G PAI-1 polymorphism on the response of PAI-1 activity to vitamin E supplementation in Type 2 diabetic patients.

Plasminogen activator inhibitor type 1 (PAI-1) is an independent cardiovascular risk factor and increases in patients with Type 2 diabetes mellitus. The 4G/5G polymorphism of PAI-1 has been reported to be involved in the incidence of cardiovascular disease by regulation of PAI-1 levels, but this relation is still under debate. The aim of the study was to test the effect of 4G/5G polymorphism on the lowering of PAI-1 levels in Type 2 diabetic patients during vitamin E supplementation. Ninety-three Type 2 diabetic subjects (age +/- SD, 62.1 +/- 6.1 yr) were enrolled and treated with vitamin E (500 IU/die) for 10 weeks. We determined the 4G/5G polymorphism and PAI-1 activity at baseline, during (5th and 10th week) and after (30th week) vitamin E supplementation. No significant differences were found in PAI-1 and its determinants among the three genotypic groups at baseline. Decrements were detected in the whole group in PAI-1 at the 5th and the 10th week from baseline followed by an increase at the 30th week (p<0.001). Patients with 4G/4G and 4G/5G genotypes showed a different trend with respect to those with 5G/5G in PAI-1. In particular, there was a decrease in 4G/4G and 4G/5G PAI-1 levels from the 10th week, while a decrease in 5G/5G PAI-1 was observed from the 5th week (p<0.01). The delayed decrease, found in patients with at least one 4G allele with respect to those with 5G/5G genotype, demonstrates that 4G/5G polymorphism mainly influences the rate of decrease of PAI-1 after supplementation with vitamin E in Type 2 diabetic subjects.

Antioxidants↗
PubMed2003

Environmental risk factors for type 1 diabetes in Rome and province.

BACKGROUND: In subjects genetically susceptible to type 1 diabetes, exposure to environmental factors during the gestational period, the neonatal period, and the first years of life is thought to play an important role in triggering the immune process leading to beta cell destruction. AIMS: To investigate risk factors for inhabitants of continental Italy. METHODS: A case-control study of 150 type 1 diabetes cases and 750 control subjects (age range 6-18 years) was carried out in Rome and its province, measuring the exposure to environmental risk factors. RESULTS: Three environmental factors were found to occur significantly more in the diabetic group than in the controls. During the mothers' pregnancies, the one risk factor which proved to be higher in diabetics than in controls was maternal infectious disease. During the neonatal period, no risk factors associated with the disease were detected. During early life, eczema and a short duration of breast feeding (less than three months), occurred significantly more in diabetic cases than controls. CONCLUSION: Eczema and breast feeding for less than three months are risk factors for type 1 diabetes in a southern European population. The type, duration, and mode of treatment for infectious diseases during pregnancy need additional investigation as risk factors for type 1 diabetes.

Adolescent↗
PubMed2003

A hospital survey of the clinical features of diabetes in Congo.

The occurrence of diabetes mellitus is increasing throughout the world, both in industrialised nations and in developing countries. While this disease is not a leading cause of death in developing country populations, it must nevertheless be considered for its social and economic impact. This study examines the clinical and epidemiological situation of diabetes mellitus in the city of Kinshasa, Democratic Republic of Congo, as based on data from two city hospitals: Saint Joseph's Hospital (SJH) and the Centre Hospitalier Monkole (CHM), two urban health facilities typical of those developing countries. The results show that diabetes is a real public health problem in Congo. Average blood glucose levels were above 300 mg/dl in 44.4% of patients at SJH and 41.5% at CHM, and hypertension (> or = 140/90 mmHg) was reported in 35.8% of patients at SJH and 20% at CHM. The management of diabetes and, in particular, its complications is suffering because of some cultural influences but mainly economic ones. In fact, incidence of disease complications is closely linked to the financial status of patients and facilities. SJH, which serves mainly the low-income community, has a greater incidence of severe diabetes-associated complications than CHM, which treats patients with a higher mean income level. SJH hospitalised patients had a 24.7% incidence of diabetic foot with 3 amputations as compared to only a 10% incidence and no amputations for CHM hospitalised patients. At SJH, 17.3% of patients died during the study, while at CHM none died. Overall, differences in the prevalence of complications between SJH and CHM patients were found not to be significant. For the large majority of Congo population, education on diabetes is not available, and due to the failure of the national health system, access to treatment is impossible. Furthermore, because most diabetic people in Congo go untreated, the mortality rate for the disease is high. Congo would greatly benefit from a national diabetes program in order to give all diabetic patients in Congo access to good and consistent medical care.

Adult↗
PubMed2002

Antibodies to bovine beta-casein in diabetes and other autoimmune diseases.

Cow's milk is thought to be an environmental trigger for autoimmune response in Type 1 diabetes. In the present study, our aim was to investigate the antibody response to bovine beta-casein in different immune- and non-immune-mediated diseases and to establish whether such an antibody response is specific to Type 1 diabetes. We measured antibodies to bovine beta-casein using an enzyme-linked immunosorbent assay in a total of 519 sera from subjects as follows: 71 patients with Type 1 diabetes, 33 patients with coeliac disease, 100 patients with latent autoimmune diabetes in adults (LADA), 50 patients with autoimmune thyroid disease (ATD), 50 patients with Type 2 diabetes, 24 patients with multiple sclerosis (MS), and 3 different groups of controls (n = 191). Significantly increased levels of antibodies to beta-casein were found in patients with Type 1 diabetes, coeliac disease and in LADA compared to age-matched controls (p = 0.01, p = 0.02 and p = 0.01, respectively). No differences were observed in beta-casein antibody titres between patients with other disease conditions (MS, and ATD) and age-matched controls. The highest antibody response to beta-casein in Type 1 diabetic patients and in patients with coeliac disease could reflect the gut mucosal immune disorders common to Type 1 diabetes and coeliac disease. Furthermore, the elevated beta-casein antibody levels found in LADA patients suggest that the antibody response to this protein may be relevant in autoimmune diabetes.

Adolescent↗
PubMed2001

Biochemical markers of type 1 diabetes: clinical use.

In type 1 diabetes, a number of specific and non-specific antigens have been identified. The major autoantigens involved in the destructive process of beta-cells leading to the development of type 1 diabetes are proinsulin/insulin, glutamic acid decarboxylase (GAD) and the transmembrane protein tyrosine phosphatase (IA-2). These are the only autoantigens that partially satisfy the criteria by which an autoantigen or cross-reactive nonself antigen could be evaluated for a pathogenic role in autoimmune diseases. Antigens by definition induce antibody production and in type 1 diabetes, such (auto) antibodies are accepted as biochemical markers for the disease. Here we describe the main features and usefulness of these markers for disease prediction.

Animals↗
PubMed2001

Vitamin E intake reduces plasminogen activator inhibitor type 1 in T2DM patients.

Previous studies hypothesised that vitamin E could protect against coronary heart disease and vascular complications in diabetes, but no studies have been performed regarding its eventual effects on fibrinolysis. Nevertheless, in Type 2 diabetes mellitus (T2DM) a profound reduction in the fibrinolytic activity has been demonstrated to be involved in vascular complications, probably due to plasminogen activator inhibitor type 1 (PAI-1) overproduction. On this basis we aimed to verify whether an antioxidant treatment with vitamin E is able to lower PAI-1 plasma levels in T2DM. Thirteen T2DM patients (9 males and 4 females; mean age+/-SD, 64.4+/-3.3 yr) were selected through strict admission criteria. These patients were treated with vitamin E (500 IU/die) for 10 weeks. Glyco-lipometabolic, oxidative and haemocoagulative parameters were evaluated at baseline and after 5, 10, 30 and 60 weeks. Vitamin E levels at different times were [median (interquartile range)] 6.1 (5.3-7.7), 8.5 (7.3-9.9), 9.7 (8.9-12.9), 5.6 (4.4-6.8), 5.7 (4.5-7.1) microg/ml, respectively. Significant differences were found for PAI-1 antigen (p=0.006), PAI-1 activity (p=0.028), apolipoprotein B (p=0.015) and antioxidant defence, evaluated as ferric reducing ability of plasma (FRAP) values (p=0.005). Particularly, decrements were detected for PAI-1 antigen between baseline and the 10th week (p<0.05), followed by an increase back to basal at the 30th week. Similar behaviour was found for PAI-1 activity. Regarding the antioxidant defence, FRAP values increased until the 30th week (p<0.05) with a decrease at the 60th week. These results demonstrate that vitamin E is able to lower PAI-1 levels in diabetic patients but this effect does not seem related to improvements of glycometabolic data or to the increase in FRAP values, suggesting that PAI-1 overproduction can be decreased by other effects of vitamin E on endothelial cells.

Aged↗
PubMed2000

Endovenous management of saphenous vein reflux. Endovenous Reflux Management Study Group.

PURPOSE: This study assessed clinical outcomes of two catheter-based endovenous procedures to eliminate or greatly mitigate saphenous vein reflux. MATERIALS AND METHODS: A computer-controlled, dedicated generator and two catheter designs were used to treat 210 patients at 16 private clinic and university centers in Europe. The Closure catheter applied resistive heating over long vein lengths to cause maximum wall contraction for permanent obliteration; the Restore catheter induced a short subvalvular constriction to improve the competence of mobile but nonmeeting leaflets. RESULTS: Closure treatment caused acute obliteration in 141 (93%) of 151 limbs; Restore treatment, shrinking one or more valves, acutely reduced reflux to less than 1 second in 41 (60%) of 68 limbs. Closure treatments were associated with early recanalization (6%), paresthesias (thigh, 9%; leg, 51%; P <.001), 3 skin burns, and 3 deep-vein thrombus extensions, with 1 embolism. Restore treatments were thrombogenic (16%) despite prophylactic anticoagulation, and treated valves enlarged over 6 weeks, becoming less competent. Clinical Efficacy Assessment Project clinical class was significantly improved after both treatments, up to 1 year. At 6 months, 87% of 53 Closure patients were class 0 or 1, 75% were symptom-free, and 96% of 55 treated limbs were completely free of reflux. Fourteen of 31 Restore patients (45%) had no symptoms, but 55% were class 2 or lower and only 19% had less than 1-second reflux. CONCLUSION: Closure treatment is clinically effective, albeit with offsetting complications and early failures; these are being addressed through four procedural modifications. Restore valve shrinking, although conceptually attractive, is too problematic to be competitive with Closure treatment or saphenectomy.

Catheterization, Peripheral↗
PubMed2000

Fibronectin and lipoprotein(a) are inversely related to plasminogen activator inhibitor type-1 levels in Type 2 diabetic patients without complications.

Plasminogen activator inhibitor type-1 (PAI-1), the most important physiological fibrinolysis inhibitor, is considered an independent factor of cardiovascular risk in Type 2 diabetes mellitus (T2DM). In previous papers we demonstrated that a T2DM population without complications presents: 1) PAI-1 not increased with respect to a control group; and 2) a negative correlation between PAI-1 and lipoprotein(a) [Lp(a)], suggesting that in these subjects PAI-1 levels could be modulated by the "endothelial stress" induced by Lp(a) and diabetes. This work has been performed in order to better verify this intriguing hypothesis, and the endothelial stress has been evaluated through a marker of endothelial damage, fibronectin (FNC). For this purpose we chose a T2DM population without complications (n=73) and a control group (n=46). Plasma concentrations of FNC, Lp(a), PAI-1 antigen and activity, and the main parameters of lipo- and glycometabolic balance were determined. Fibronectin was significantly higher in diabetics with respect to controls (p<0.01). As expected, significant correlation between PAI-1 antigen, PAI-1 activity and Lp(a) (r=-0.54,p<0.01 and r=-0.39,p<0.01, respectively) was found only in diabetic patients. In the same group FNC showed a significant correlation with PAI-1 antigen and activity (r=-0.49,p<0.01 and r=-0.47; p<0.01, respectively), while no relationship was found between Lp(a) and FNC. Multiple regression analysis showed statistically significant correlation between PAI-1 antigen and PAI-1 activity with FNC and Lp(a) in diabetic patients without complications (p<0.05). These data suggest that in absence of complications, the endothelium is able to modulate PAI-1 levels, favouring in that way the fibrinolytic pathway and, subsequently, the recovery of the endothelial integrity. This modulation seems to be related to parameters such as Lp(a) and FNC, although the mechanisms of the endothelial stress of these two molecules seem to be different.

Blood Glucose↗
PubMed1999

Poorly controlled elderly Type 2 diabetic patients: the effects of increasing sulphonylurea dosages or adding metformin.

AIMS: To assess the effects and safety of increasing sulphonylurea dosages or adding metformin in poorly controlled elderly Type 2 diabetic patients. METHODS: A 18-month multicentre clinical study was performed on sulphonylurea-treated diabetic patients over 70 years of age with well-preserved renal function, steady fasting blood glucose > or = 200 mg/dl and HbA1c > or = 9%. Patients were randomly assigned to sulphonylurea increased up to its maximum dosage (1st group) or to addition of metformin (2nd group). Glycaemic control, lipid pattern, haemostatic status and safety were monitored during run-in, at baseline and at scheduled intervals for 18 months. Results refer to 85 patients in the 1st group and 89 patients in the 2nd with complete data. RESULTS: Similar improvements in glycaemic levels were observed with both treatments within the first month and a similar decrease in HbA1c within the third month. No further changes occurred in glycaemic control. In the 1st group, fasting glucose (mmol/l, mean +/- SE) decreased from 14.21 +/- 0.49 to 9.88 +/- 0.21, average day-long glucose from 14.87 +/- 0.27 to 10.69 +/- 0.19 and HbAt1c(%) from 10.32 +/- 0.13 to 8.66 +/- 0.13. In the 2nd treatment group fasting glucose decreased from 14.59 +/- 0.61 to 9.05 +/- 37.28, average day-long glucose from 15.09 +/- 0.29 to 10.32 +/- 0.21 and HbA1c from 10.33 +/- 0.13 to 8.77+/-0.12 (for all P<0.0005). In this 2nd group, a decrease in LDL-cholesterol (P < 0.05) and an increase in HDL-cholesterol levels (P < 0.02) were also observed. In the 1st group, anthrombin III activity increased significantly (P<0.01). In the 2nd group, significant reductions in markers of platelet function (FP4 and betaTG, P < 0.01), thrombin generation (FPA, F1 + 2 and D-D, P<0.01), and fibrinolysis inhibition (PAI-1 activity, PAI-1 antigen, P< 0.001) were observed. Increases in some fibrinolytic activation markers (t-PA activity, and AT-III activity, P<0.01) occurred. Fasting lactate concentrations were unchanged in the metformin-treated group. No serious adverse effects were observed in either group. CONCLUSIONS: These results suggest that either high sulphonylurea dosages or a therapy combining lower sulphonylurea dosages with metformin are effective and safe in an aged but healthy population. Metformin provides additional benefits counteracting several cardiovascular risk factors but must be administered with caution, bearing in mind the general contra-indications for the drug but not age alone.

Aged↗
PubMed1999

Determination of plasma metformin by a new cation-exchange HPLC technique.

Metformin is an oral antihyperglycemic agent used in the therapy of noninsulin-dependent diabetic patients. This biguanide can induce dangerous complications such as lactic acidosis when its plasma concentration is too high. For this reason, the determination of plasma metformin should always be done during treatment. We developed a new HPLC method, for the routine determination of plasma metformin, with good reliability, rapid execution, and low costs. Sample preparation involved precipitation of the plasma proteins containing the internal standard buformin with a mixture of methanol, zinc sulfate, and ethylene glycol; the diluted supernatant was injected into a cation-exchange column. The mobile phase was potassium dihydrogenphosphate buffer-containing acetonitrile. The eluent was monitored at 236 nm. The calibration curve is linear within the range of 20-4000 ng/mL; the within-day coefficients of variation were less than 2.2% for metformin and 1.5% for buformin; the day-to-day coefficients of variation were less than 2.5% for metformin and 1.9% for buformin. The mean recoveries obtained from supplemented samples were included between 99.4 and 104.2% for metformin. Many characteristics make this method useful and easily accessible to all clinical laboratories equipped with HPLC instrumentation.

Administration, Oral↗