Physical activity patterns in type 1 diabetes in Spain: The SED1 study.

AIMS: To describe the physical activity (PA) frequency and intensity in the Spanish type 1 diabetes mellitus (T1D) population and its association with their glycemic control. METHODS: A cross-sectional observational study was carried out in 75 Spanish public hospitals (the SED1 study). T1D patients over 14years of age self-completed the International Physical Activity Questionnaire (IPAQ) to determine their level of exercise. The relationship between PA frequency and intensity in T1D patients and glycemic control and the diabetes therapeutic education received were analyzed. RESULTS: A total of 592 patients were evaluable. A 6.8% of the sample performed light PA, 20.9% moderate and 72.3% vigorous. Estimated PA presented a high inter-individual variability. Men consumed more energy (METS) than women, these differences being more noticeable in vigorous METS (2865.80 in men vs 1352.12 in women). Women invested more min/week in the domestic and garden area (639.03 vs 344.39, p = 0,022). A correlation between glycemic control and the METs was not observed. CONCLUSIONS: The Spanish T1D population performed PA in a higher frequency and intensity than the general population. A relationship between PA and glycemic control couldn´t be shown. However, limitations of the study should be kept in mind to discard a long-term positive influence.

Steno type 1 risk engine and preclinical atherosclerosis in Mediterranean individuals with type 1 diabetes.

BACKGROUND AND AIMS: Tools to detect type 1 diabetes (T1D) individuals at overt cardiovascular disease (CVD) risk are scarce. We aimed to assess the usefulness of the score 'Steno Type 1 Risk Engine' (Steno-Risk) to identify T1D patients with advanced carotid atherosclerosis. MATERIAL AND METHODS: T1D patients without CVD with at least one of the following were included: ≥40 years, diabetic nephropathy, or diabetes duration ≥10 years with ≥1 CVD risk factor. Intima-media thickness (IMT) and plaque presence (IMT ≥1.5 mm) were assessed by standardized B-mode ultrasonography. Steno-Risk was used to estimate 10-year risk (<10% low; 10%-20% moderate; ≥20% high risk). Associations between Steno-Risk and preclinical atherosclerosis were assessed after adjusting for other CVD risk factors. RESULTS: We evaluated 302 patients (55% men, age 47.8 ± 9.8 years, T1D duration 26.3 ± 9.3 years). The prevalence of carotid plaque and ≥2 plaques were 36.4% and 19.2%, respectively; without sex differences. Age (57.4 ± 7.4 vs 37.1 ± 6.2 years), T1D duration (31.3 ± 10.4 vs 21.5 ± 7.1 years), hypertension (52.3% vs 6.3%), nephropathy (25.6% vs 5.1%) and retinopathy (53.5% vs 32.9%) were higher in high-risk (n = 86) vs low-risk participants (n = 79; P < .001 for all). Preclinical atherosclerosis (IMT and plaque) increased in parallel with Steno-Risk (P < .001). In logistic regression analysis, both age ≥40 years and Steno-Risk ≥20% were associated with the presence of plaque (OR 4.22 [1.57-11.36] and 3.79 [1.61-6.80]; respectively), but only high Steno-Risk remained independently associated with ≥2 plaques (OR 3.31 [1.61-6.80]). CONCLUSION: Steno-Risk is independently associated with preclinical atherosclerosis. Further studies are needed to ascertain its usefulness in this high-risk population.

Long-term outcome of insulin pump therapy: reduction of hypoglycaemia and impact on glycaemic control.

AIMS: To determine the long-term outcome of continuous subcutaneous insulin infusion (CSII) in Type 1 diabetes according to Catalan National Health Service indications. METHODS: Retrospective observational study including 178 patients with Type 1 diabetes who started CSII treatment in our centre (2003-2008). All patients were followed in our CSII programme for outpatients for at least 5 years. Data on annual HbA1c levels were collected, and the main indication for starting CSII was analysed. RESULTS: Twenty-seven of 178 patients were excluded because of loss to follow-up or withdrawal from CSII, thus 151 patients (aged 37.4 ± 10.5 years, 64% women) were analysed. The main indications for starting CSII were suboptimal metabolic control (60.9%), severe hypoglycaemia/hypoglycaemia unawareness (25.5%) and others (13.6%). HbA1c was 64 ± 13 mmol/mol (8.0 ± 1.2%) at the start of CSII and 62 ± 13 mmol/mol (7.8 ± 1.2%) after 5 years in the total cohort (P = 0.1). The severe hypoglycaemia rates were 0.66 ± 1.61 and 0.17 ± 0.42 episodes/patient/year (P < 0.001). In patients with suboptimal metabolic control, HbA1c decreased from 68 ± 12 mmol/mol (8.4 ± 1.1%) to 64 ± 14 mmol/mol (8.0 ± 1.3%) (P = 0.016), with 37.4% of those in this group having an HbA1c ≤ 58 mmol/mol (7.5%) after 5 years. In patients starting CSII due to severe hypoglycaemia the problem was considered resolved in 93%, and in 64% of those starting CSII because of suboptimal glycaemic control, HbA1c improved significantly. CONCLUSIONS: CSII therapy achieves and maintains its efficacy mainly in terms of reducing severe hypoglycaemia. In the whole group of patients, the reduction in HbA1c is transient and disappears after 5 years.

Sustained efficacy of insulin pump therapy compared with multiple daily injections in type 2 diabetes: 12-month data from the OpT2mise randomized trial.

AIMS: To compare insulin pump therapy and multiple daily injections (MDI) in patients with type 2 diabetes receiving basal and prandial insulin analogues. METHODS: After a 2-month dose-optimization period, 331 patients with glycated haemoglobin (HbA1c) levels ≥8.0% and ≤12% were randomized to pump therapy or continued MDI for 6 months [randomization phase (RP)]. The MDI group was subsequently switched to pump therapy during a 6-month continuation phase (CP). The primary endpoint was the between-group difference in change in mean HbA1c from baseline to the end of the RP. RESULTS: The mean HbA1c at baseline was 9% in both groups. At the end of the RP, the reduction in HbA1c was significantly greater with pump therapy than with MDI (-1.1 ± 1.2% vs -0.4 ± 1.1%; p < 0.001). The pump therapy group maintained this improvement to 12 months while the MDI group, which was switched to pump therapy, showed a 0.8% reduction: the final HbA1c level was identical in both arms. In the RP, total daily insulin dose (TDD) was 20.4% lower with pump therapy than with MDI and remained stable in the CP. The MDI-pump group showed a 19% decline in TDD, such that by 12 months TDD was equivalent in both groups. There were no differences in weight gain or ketoacidosis between groups. In the CP, one patient in each group experienced severe hypoglycaemia. CONCLUSIONS: Pump therapy has a sustained durable effect on glycaemic control in uncontrolled type 2 diabetes.

Successful Pancreas Transplantation From a Deceased Donor Intoxicated With Oral Antidiabetic Agent: A Case Report.

Simultaneous kidney pancreas transplantation (SKP) is a common procedure for the patient with long-term type 1 diabetes mellitus (DM) with terminal renal failure. It is unusual to consider the pancreas from a deceased donor who died after an acute intoxication with oral antidiabetic agent (OAA), which would suggest an abnormal functionality of the organ and preclude the potential use of the graft. We present a case of a successful pancreatic transplantation from a donor who died of acute cerebral edema secondary to severe hypoglycemia induced by OAA acute intoxication.

Impact of continuous glucose monitoring on quality of life, treatment satisfaction, and use of medical care resources: analyses from the SWITCH study.

To investigate the impact of continuous glucose monitoring (CGM) on health-related quality of life (HRQOL), treatment satisfaction (TS) medical resource use, and indirect costs in the SWITCH study. SWITCH was a multicentre, randomized, crossover study. Patients with type 1 diabetes (n = 153) using continuous subcutaneous insulin infusion (CSII) were randomized to a 12 month sensor-On/Off or sensor-Off/On sequence (6 months each treatment), with a 4-month washout between periods. HRQOL in children and TS in adults were measured using validated questionnaires. Medical resource utilization data were collected. In adults, TS was significantly higher in the sensor-On arm, and there were significant improvements in ratings for treatment convenience and flexibility. There were no clinically significant differences in children's HRQOL or parents' proxy ratings. The incidence of severe hypoglycaemia, unscheduled visits, or diabetes-related hospitalizations did not differ significantly between the two arms. Adult patients made fewer telephone consultations during the sensor-On arm; children's caregivers made similar numbers of telephone consultations during both arms, and calls were on average only 3 min longer during the sensor-On arm. Regarding indirect costs, children with >70 % sensor usage missed fewer school days, compared with the sensor-Off arm (P = 0.0046) but there was no significant difference in the adults days of work off. The addition of CGM to CSII resulted in better metabolic control without imposing an additional burden on the patient or increased medical resource use, and offered the potential for cost offsets.

Effectiveness and tolerability of second-line therapy with vildagliptin vs. other oral agents in type 2 diabetes: a real-life worldwide observational study (EDGE).

AIM: Real-life studies are needed to confirm the clinical relevance of findings from randomised controlled trials (RCTs). This study aimed to assess the effectiveness and tolerability of vildagliptin add-on vs. other oral antihyperglycaemic drugs (OADs) added to OAD monotherapy in a real-life setting, and to explore the advantages and limitations of large-scale 'pragmatic' trials. METHODS: EDGE was a prospective, 1-year, worldwide, real-life observational study in which 2957 physicians reported on the effects of second-line OADs in 45,868 patients with T2DM not reaching glycaemic targets with monotherapy. Physicians could add any OAD, and patients entered either vildagliptin or (pooled) comparator cohort. The primary effectiveness and tolerability end-point (PEP) evaluated proportions of patients decreasing HbA(1c) > 0.3%, without hypoglycaemia, weight gain, peripheral oedema or gastrointestinal side effects. The most clinically relevant secondary end-point (SEP 3) was attainment of end-point HbA(1c) < 7% without hypoglycaemia or ≥ 3% increase in body weight. RESULTS: In this large group of T2DM patients, a second OAD was added at mean HbA(1c) of 8.2 ± 1.3%, with no baseline HbA(1c) difference between cohorts. Second-line OAD therapy attained the PEP in the majority of patients, with higher attainment in those prescribed a vildagliptin-based regimen. The adjusted odds ratio was 1.49 (95% CI: 1.42, 1.55; p < 0.001). In patients with baseline HbA(1c) ≥ 7%, SEP 3 was achieved by 35% of patients on a vildagliptin-based combination and by 23% of those receiving comparator combinations. The adjusted odds ratio was 1.96 (95% CI: 1.85, 2.07; p < 0.001). Safety events were reported infrequently and safety profiles of vildagliptin and other OADs were consistent with previous data. CONCLUSION: EDGE demonstrates that in a 'real-life' setting, vildagliptin as second OAD can lower HbA(1c) to target without well-recognised OAD side effects, more frequently than comparator OADs. In addition, EDGE illustrates that conducting large-scale, prospective, real-life studies poses challenges but yields valuable clinical information complementary to RCTs.

The use and efficacy of continuous glucose monitoring in type 1 diabetes treated with insulin pump therapy: a randomised controlled trial.

AIMS/HYPOTHESIS: The aim of this multicentre, randomised, controlled crossover study was to determine the efficacy of adding continuous glucose monitoring (CGM) to insulin pump therapy (CSII) in type 1 diabetes. METHODS: Children and adults (n = 153) on CSII with HbA(1c) 7.5-9.5% (58.5-80.3 mmol/mol) were randomised to (CGM) a Sensor On or Sensor Off arm for 6 months. After 4 months' washout, participants crossed over to the other arm for 6 months. Paediatric and adult participants were separately electronically randomised through the case report form according to a predefined randomisation sequence in eight secondary and tertiary centres. The primary outcome was the difference in HbA(1c) levels between arms after 6 months. RESULTS: Seventy-seven participants were randomised to the On/Off sequence and 76 to the Off/On sequence; all were included in the primary analysis. The mean difference in HbA(1c) was -0.43% (-4.74 mmol/mol) in favour of the Sensor On arm (8.04% [64.34 mmol/mol] vs 8.47% [69.08 mmol/mol]; 95% CI -0.32%, -0.55% [-3.50, -6.01 mmol/mol]; p < 0.001). Following cessation of glucose sensing, HbA(1c) reverted to baseline levels. Less time was spent with sensor glucose <3.9 mmol/l during the Sensor On arm than in the Sensor Off arm (19 vs 31 min/day; p = 0.009). The mean number of daily boluses increased in the Sensor On arm (6.8 ± 2.5 vs 5.8 ± 1.9, p < 0.0001), together with the frequency of use of the temporary basal rate (0.75 ± 1.11 vs 0.26 ± 0.47, p < 0.0001) and manual insulin suspend (0.91 ± 1.25 vs 0.70 ± 0.75, p < 0.018) functions. Four vs two events of severe hypoglycaemia occurred in the Sensor On and Sensor Off arm, respectively (p = 0.40). CONCLUSIONS/INTERPRETATION: Continuous glucose monitoring was associated with decreased HbA(1c) levels and time spent in hypoglycaemia in individuals with type 1 diabetes using CSII. More frequent self-adjustments of insulin therapy may have contributed to these effects.

Phenotype changes at the onset of type 1 diabetes in young adults from a mediterranean area throughout the last decade.

The Accelerator hypothesis postulates that Type 1 Diabetes (T1D) and Type 2 Diabetes are mostly the same disorder. Till now, the data testing the hypothesis and the importance of BMI and insulin resistance in the development of T1D comes almost exclusively from childhood. Our study aimed to investigate changes in clinical and metabolic characteristics of young adults at diagnosis of T1D during the last decade in a Mediterranean area. Ninety-three adults (> or =18 years) with newly diagnosed T1D were evaluated from our database. Thirty-one of them were diagnosed in the period 07/1994-1995 (G95), 39 between 07/1998 and 1999 (G99) and 23 in 2003 (G03). Plasma C-peptide measurements were performed before and 6 min after intravenous injection of 1 mg of glucagon. In those subjects with a basal C-peptide > 0.2 nmol/l, insulin resistance was evaluated using the HOMA-2 model. HbAc, GAD, IA2 and insulin autoantibodies were measured. There was not a significant rise in BMI at diagnosis of T1D in young adults admitted to our Hospital. This was also the case when BMI after 4 weeks of diagnosis was considered (23.7 +/- 3.6, 23,6 +/- 2.4 and 23.4 +/- 3.3 kg/m2, G95 G99 and G03, respectively). In the entire group of subjects, we could not observed any relationship between the patients BMI and age at diagnosis. Likewise, we could not observed differences in any of the clinical, immunological or metabolic characteristics. IR was not different between groups (G95 n=18, 0.73 +/- 0.21; G99 n=29, 0.86 +/- 0.33; G3 n=13, 0.66 +/- 0.34) and was not related to the age at diagnosis. In summary, our data collected from young adults with newly diagnosed T1D from a Mediterranean area indicates that the phenotype, including BMI, at the onset of the disease has not substantially varied during the last decade. In spite of our data do not fit with the accelerator hypothesis the postulate could be of interest in a different age group.

Efficacy of continuous subcutaneous insulin infusion in Type 1 diabetes: a 2-year perspective using the established criteria for funding from a National Health Service.

AIM: To determine the 2-year efficacy of continuous subcutaneous insulin infusion (CSII) following the current established criteria for funding of a National Health Service. METHODS: Longitudinal, prospective, observational unicentre study. Included in the study were 153 Type 1 diabetes (T1D) subjects, previously treated with multiple daily injections (MDI) of insulin, in whom CSII was started in accordance with the criteria for reimbursement of the Catalan National Health Service. At baseline, we recorded data on age, gender, duration of the disease, body mass index (BMI), insulin dose and indications for CSII. Glycated haemoglobin (HbA(1c)) and the frequency of hypoglycaemic events were used to assess glycaemic control. Quality of life was assessed using three different self-report questionnaires. After 24 months, these same items were remeasured in all subjects. Serious adverse events and injection-site complications were also recorded. RESULTS: In 96% of subjects, CSII indication included less than optimal glycaemic control using MDI. HbA(1c) fell from 7.9 +/- 1.3 to 7.3 +/- 1.1% (P < or = 0.001) after 24 months of CSII. Insulin requirements were significantly lower at the end of follow-up (0.55 +/- 0.21 U/kg body weight) in comparison with before use of CSII (0.70 +/- 0.20, P < or = 0.001). BMI increased from 24.0 +/- 3.1 to 24.4 +/- 3.2 kg/m(2) after 24 months (P < or = 0.025). The rate of episodes of diabetic ketoacidosis per year remained unchanged. Mild and severe hypoglycaemic episodes were significantly reduced. The scores in all subsets of the Diabetes Quality-of-Life (DQoL) questionnaire significantly improved after 24 months of CSII. CONCLUSIONS: CSII, commenced according to the criteria for a nationally funded clinical programme, improves glycaemic control and quality-of-life outcomes with fewer hypoglycaemic episodes in T1D subjects previously conventionally treated with MDI.

Outcome of pregnancy in women with type 1 diabetes intensively treated with continuous subcutaneous insulin infusion or conventional therapy. A case-control study.

The aim was to evaluate and compare the outcome of pregnancies of women with type 1 diabetes (T1D) intensively treated with continuous subcutaneous insulin infusion (CSII) or multiple daily injections (MDI). Twenty-nine women with T1D receiving CSII during pregnancy as intensive insulin therapy (27 started CSII during pregnancy planning while 2 started CSII during the 1st month of gestation) were matched for age, duration of T1D, White's classification, BMI before gestation, parity and HbA1c before pregnancy with 29 women treated with MDI. Metabolic control and acute complications were registered including ketoacidosis and severe hypoglycaemic episodes, and the development of hypertension induced by pregnancy and pre-eclampsia. Perinatal mortality, stillbirth, minor and major congenital malformations, macrosomia, weeks at delivery, caesarean section and perinatal complications were also recorded. As expected, there were no differences between the two groups in terms of age, duration of the disease, White's classification, BMI before gestation, parity and HbA1c before pregnancy. The proportion of subjects who received preconceptional guidance and planned pregnancy did not differ between groups. No differences were observed in HbA1c, insulin dose and BMI throughout gestation in either group of patients. Maternal, foetal and perinatal outcome were similar in women treated with CSII or MDI. The use of CSII in pregestational T1D women is associated with similar results in metabolic control, maternal, foetal and perinatal outcome during pregnancy to those obtained using MDI.

Telecare in a structured therapeutic education programme addressed to patients with type 1 diabetes and poor metabolic control.

OBJECTIVE: To assess the effects of telecare on the results of intensive follow-up in T1D patients with poor metabolic control. METHODS: After initial evaluation, 40 T1D were randomised to either a Telecare (TG) or Conventional Group (CG). Patients had an intensive 6-month follow-up and helped to make decisions concerning treatment self-management. The TG had 12 appointments: 9 telematic with the GlucoBeep system+3 ambulatory. The CG had 12 outpatient appointments. At 0, 6 (end of study) and 12 months, metabolic control, self-management and quality of life were evaluated. Cost analysis was made at study end. RESULTS: Thirty patients completed the study (16 TG, 14 CG). Intention to treat analysis included 19 TG and 16 CG. Improvement in HbA(1c) was similar in both groups TG: 8.4+/-1.2%; 7.5+/-1.4%; 7.6+/-0.9%, p=0.008; CG: 8.9+/-1.3%; 7.7+/-0.9%; 7.6+/-0.7%, p=0.001; with a decrease in hypoglycaemic events and improvement in self-management and quality of life. Patient costs were lower in the TG versus CG in appointment length (0.25h versus 0.5h). However, 30% of the diabetes team and patient appointments were longer than expected due to technical difficulties: (0.25h versus 1h). CONCLUSIONS: Intensive telematic follow-up achieves similar results to those of intensive face-to-face follow-up with lower patient costs. However, communication technology must be improved.

Lack of effect of intermittently administered sodium fusidate in patients with newly diagnosed type 1 diabetes mellitus: the FUSIDM trial.

AIMS/HYPOTHESIS: We evaluated in a double-blind study the effect of early treatment with the immunomodulatory drug fusidin in patients with newly diagnosed type 1 diabetes mellitus. METHODS: Twenty-eight adults with newly diagnosed type 1 diabetes were included in the study. The patients were randomly assigned (computer-generated random number sequence) to two experimental groups. Patients allocated to the fusidin (FUS) group (n=15) received sodium fusidate (fusidin; 500 mg orally three times daily for 4 weeks). Subsequently the drug was given at the same dose and scheduled for two consecutive weeks a month followed by 2 weeks a month without the drug for 20 weeks. Subjects allocated to the placebo (PCB) group (n=13) received placebo according to the same schedule and conditions described for sodium fusidate in the FUS group. All patients received a diet adjusted to their age and BMI, and intensive insulin therapy. RESULTS: There were no statistically significant differences between the FUS and PCB groups in beta cell function, evaluated by basal and glucagon-stimulated C-peptide values during the follow-up (24 and 48 weeks). There was also no difference between the two groups in insulin requirement after 48 weeks (0.4+/-0.2 and 0.4+/-0.2 U/kg body weight for the FUS and PCB groups, respectively). Antibody titres, including insulin autoantibodies, were similar in the two groups during the follow-up. CONCLUSIONS/INTERPRETATION: Early treatment of newly diagnosed type 1 diabetes patients with intermittently administered fusidin failed to influence the natural course of the disease.

Clinical characteristics, beta-cell function, HLA class II and mutations in MODY genes in non-paediatric subjects with Type 1 diabetes without pancreatic autoantibodies.

OBJECTIVE: To study clinical characteristics, beta-cell function, HLA typing and mutations in the hepatocyte nuclear factor (HNF)-1alpha and HNF-4alpha genes in Type 1 diabetes mellitus (T1D) patients without pancreatic autoantibodies. DESIGN AND METHODS: Twenty patients without pancreatic autoantibodies (Ab neg) and 20 with autoantibodies (Ab pos), age/gender matched, were included (age 17-34 years). Islet cell, glutamic acid decarboxylase, tyrosine phosphatase and insulin autoantibodies, basal and stimulated C-peptide were measured. HLA-DRB1-DQA1-DQB1 typing and screening for mutations in the HNF-1alpha and HNF-4alpha genes were performed. RESULTS: No differences were found in clinical presentation, metabolic control and beta-cell function in the two groups (onset or after 12 months). DRB1*0301-DQA1*0501-DQB1*0201 was the most frequent haplotype in both groups but we found a higher proportion of protective T1D haplotypes and Asp(beta57) in the Ab neg group, but in all the cases in combination with susceptible T1D haplotypes. We found two previously reported polymorphisms (HNF-1alpha, Ala98Val; HNF-4alpha, Thr130Ile) in Ab neg and a new variant (Ser165Gly) in the HNF-4alpha gene in an Ab pos subject. Conclusions In a non-paediatric population with newly diagnosed T1D, the absence of islet antibodies does not imply clinical or metabolic differences when compared with those cases with islet antibodies. Despite a similar HLA-DR/DQ typing, the presence of protective alleles and molecular properties in a higher proportion in the Ab neg group suggests that these factors could modulate the presence or absence of islet antibodies. Variants in HNF-1alpha and HNF-4alpha are unlikely to be major contributors to the pathogenesis of diabetes in antibody-negative T1D.

Transforming growth factor beta at clinical onset of Type 1 diabetes mellitus. A pilot study.

AIMS: The aims of the study were to determine whether transforming growth factor beta1 TGF-beta1 levels are raised at diagnosis of Type 1 diabetes mellitus and are related to blood glucose. SUBJECTS AND METHODS: Fourteen patients (mean age 24.3 +/- 4.9 years) admitted to hospital for onset of Type 1 diabetes were studied. On the first day of hospitalization, before insulin therapy, and at 1, 4 and 16 weeks, fasting blood glucose, HbA(1c), lipid profile and TGF-beta1 levels and TGF-beta1 levels in 24-h urine were determined. The control group included 14 non-diabetic subjects with similar characteristics to those of the diabetic group. RESULTS: Plasma and urinary TGF-beta1 levels were significantly lower in controls (4.7 (1.6-6.8) ng/ml P < 0.001; 5.7 (1.5-8.5) ng/mg urinary creatinine, P < 0.01) than in patients with Type 1 diabetes mellitus [10.5 (1.8-24.9) ng/ml; 10.1 (4.2-29.8) ng/mg urinary creatinine]. On study completion, HbA(1c) fell from 11.6 +/- 2.0 to 5.4 +/- 0.6% (P < 0.001). Improved metabolic control was not associated with changes in plasma (9.4 (2.6-19.5)/5.9 (1.6-21.5)/7.0 (2.3-30.2)/10.5 (1.8-24.9) ng/ml at baseline, 1, 4 and 16 weeks, respectively) or urinary (12.0 (4.7-29.5)/10.9 (1.5-20.5)/8.7 (4.3-16.9)/10.1 (4.2-29.8) ng/mg urinary creatinine) TGF-beta1 levels. A statistically significant correlation was observed between plasma TGF-beta1 and insulin dosage (U/kg/day) (r = 0.52, P = 0.037). CONCLUSIONS: The increased TGF-beta1 production observed herein was not modulated by glycaemic reduction and could be a response to immuno-inflammatory activation present at the onset of Type 1 diabetes.

Lower rate of tumor necrosis factor-alpha -863A allele and higher concentration of tumor necrosis factor-alpha receptor 2 in first-degree relatives of subjects with type 2 diabetes.

Allelic variants of the tumor necrosis factor-alpha (TNF-alpha) gene seem to contribute to insulin resistance increasing the transcription rate of TNF-alpha. The TNF-alpha -863A allele is associated with a lower expression of TNF-alpha gene and less secretion of the cytokine. To investigate whether an abnormal TNF-alpha system regulation may contribute to early impairment of insulin action in first-degree relatives of patients with type 2 diabetes mellitus (DM), we studied the TNF-alpha -863C/A polymorphism and the soluble fraction of TNF-alpha receptor-2 (sTNFR2) concentration in these subjects in comparison to a control group. A total of 52% of subjects in the relatives' group showed an abnormal oral glucose tolerance (either as impaired glucose tolerance [IGT] or diabetes) and had more features of the insulin resistance syndrome, despite showing similar body composition as controls. The plasma concentration of the sTNFR2 was higher and insulin sensitivity (%S) was lower in the relatives' group than in the controls. Likewise, the TNF-alpha -863A allele was more commonly detected in the control group (10 of 41) than in the relative's group (2 of 36, P =.029). In a multivariate linear regression analysis, neither TNF-alpha -863A allele nor sTNFR2 independently determined %S. Only body mass index (BMI) and the presence of a positive family history of DM were independent determinants of insulin resistance. In summary, our study showed a lower rate of TNF-alpha -863A allele and higher concentrations of sTNFR2 in first-degree relatives of DM subjects. These findings could be included among the genetic, metabolic, and clinical heterogeneity that characterizes the pathophysiology of DM. The presence of abnormalities in the TNF-alpha pathway could predispose to the development of DM in subjects at risk for the disease.

Effects of atorvastatin on glucose homeostasis, postprandial triglyceride response and C-reactive protein in subjects with impaired fasting glucose.

AIMS: To investigate the effects of atorvastatin on glucose homeostasis, the basal and postprandial lipid profiles and the CRP levels (C reactive protein) in subjects with impaired fasting glucose (IFG). METHODS: Thirty-three subjects (22 men and 11 women) were included in our study. All displayed an IFG (fasting plasma glucose between 6.1 and 7.0 mmol/l) on at least two occasions during the last 6 months prior the study. They were randomly assigned to receive either 40 mg atorvastatin/day (n=16) or placebo (n=17) over 16 weeks, in a double-blind design. Before and after the end of the study all participants underwent on three consecutive days: a 75-g oral glucose tolerance test, a frequent sampling intravenous glucose tolerance test with Minimal Model analysis and a meal tolerance test (glucose, insulin and triglycerides). CRP was measured before and after the treatment period. RESULTS: CRP decreased significantly in the atorvastatin-treated group compared with the placebo group (percent change respect initial values; -42.3 %[-21.5 to - 63.1] and -9.6%[15.0 to -34.0], respectively, p<0.01). Atorvastatin treatment did not produce any change in oral glucose tolerance categories or induce any change in glucose and insulin response in OGTT. The statin produced a trend towards a significant improvement in insulin sensitivity as expressed by a change in Si from baseline to the end of treatment. Atorvastatin reduced the postprandial response of triglycerides to the meal test compared with placebo (19-26 % across the meal test, p<0.05) correlating with the amelioration observed in Si (-0.34, p<0.05; percentage changes). CONCLUSION: Our results suggest that the use of statins in subjects with IFG seems to include other potentially beneficial actions in addition to their cholesterol-lowering effects.