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Objective This study compares the patterns of visceral (VIS) and subcutaneous (SC) adipose tissue (AT)-derived metabolites from non-obese (BMI 24-26 kg/m2) and obese subjects (BMI > 40 kg/m2) with no major metabolic risk factors other than BMI. Methods SC- and VIS- AT obtained from obese (Ob) and non-obese (NOb) subjects during surgery were incubated to obtain their metabolites. Differences related to obesity or anatomical provenances of AT were assessed using an untargeted metabolomics approach based on gas chromatography-mass spectrometry. Results The overall effect of obesity on the metabolite profile resulted more remarkable than the effect of regional AT. Only the depletion of 2-ketoisocaproic (2-KIC) acid reached statistical significance for the SC-AT alone, although it was observed in both depots. Obesity induced more significant changes in several amino acids levels of the VIS-AT metabolites. On the one hand, higher released levels of glutamine and alanine were detected in the VIS- obese AT, whereas on the other, the VIS- obese AT presented a diminished uptake of essential amino acids (methionine, threonine, lysine), BCAAs, leucine, and serine. Conclusion This study shows that obesity markedly affects the amino acid metabolic signature of the AT before the clinical onset of other significant metabolic alterations aside from BMI. [ABSTRACT FROM AUTHOR]

To compare the efficacy, safety and tolerability of linagliptin or placebo administered for 24 weeks in combination with pioglitazone in patients with type 2 diabetes mellitus (T2DM) exhibiting insufficient glycaemic control (HbA1c 7.5-11.0%). Patients were randomized to receive the initial combination of 30 mg pioglitazone plus 5 mg linagliptin (n = 259) or pioglitazone plus placebo (n = 130), all once daily. The primary endpoint was change from baseline in HbA1c after 24 weeks of treatment, adjusted for baseline HbA1c and prior antidiabetes medication. After 24 weeks of treatment, the adjusted mean change (±s.e.) in HbA1c with the initial combination of linagliptin plus pioglitazone was −1.06% (±0.06), compared with −0.56% (±0.09) for placebo plus pioglitazone. The difference in adjusted mean HbA1c in the linagliptin group compared with placebo was −0.51% (95% confidence interval [CI] −0.71, −0.30; p < 0.0001). Reductions in fasting plasma glucose (FPG) were significantly greater for linagliptin plus pioglitazone than with placebo plus pioglitazone; −1.8 and −1.0 mmol/l, respectively, equating to a treatment difference of −0.8 mmol/l (95% CI −1.2, −0.4; p < 0.0001). Patients taking linagliptin plus pioglitazone, compared with those receiving placebo plus pioglitazone, were more likely to achieve HbA1c of <7.0% (42.9 vs. 30.5%, respectively; p = 0.0051) and reduction in HbA1c of ≥0.5% (75.0 vs. 50.8%, respectively; p < 0.0001). β-cell function, exemplified by the ratio of relative change in adjusted mean HOMA-IR and disposition index, improved. The proportion of patients that experienced at least one adverse event was similar for both groups. Hypoglycaemic episodes (all mild) occurred in 1.2% of the linagliptin plus pioglitazone patients and none in the placebo plus pioglitazone group. Initial combination therapy with linagliptin plus pioglitazone was well tolerated and produced significant and clinically meaningful improvements in glycaemic control. This combination may offer a valuable additive initial treatment option for T2DM, particularly where metformin either is not well tolerated or is contraindicated, such as in patients with renal impairment. [ABSTRACT FROM AUTHOR]

Sodium tungstate is an anti-obesity drug targeting peripheral tissues. In vivo, sodium tungstate reduces body weight gain and food intake through increasing energy expenditure and lipid oxidation, but it also modulates hypothalamic gene expression when orally administered, raising the possibility of a direct effect of sodium tungstate on the central nervous system. Sodium tungstate was administered intraperitoneally (ip) to Wistar rats, and its levels were measured in cerebrospinal fluid through mass spectrometry. Body weight gain and food intake were monitored for 24 h after its administration in the third ventricle. Hypothalamic protein was obtained and subjected to western blot. In vitro, hypothalamic N29/4 cells were treated with 100 µM sodium tungstate or 1 nM leptin, and protein and neural gene expression were analysed. Sodium tungstate crossed the blood-brain barrier, reaching a concentration of 1.31 ± 0.07 mg/l in cerebrospinal fluid 30 min after ip injection. When centrally administered, sodium tungstate decreased body weight gain and food intake and increased the phosphorylation state of the main kinases and proteins involved in leptin signalling. In vitro, sodium tungstate increased the phosphorylation of janus kinase-2 (JAK2) and extracellular signal-regulated kinase-1/2 (ERK1/2), but the activation of each kinase did not depend on each other. It regulated c-myc gene expression through the JAK2/STAT system and c-fos and AgRP (agouti-related peptide) gene expression through the ERK1/2 pathway simultaneously and independently. Sodium tungstate increased the activity of several kinases involved in the leptin signalling system in an independent way, making it a suitable and promising candidate as a leptin-mimetic compound in order to manage obesity. [ABSTRACT FROM AUTHOR]

Considering the poor long-term success of current dietary and pharmacological interventions, we aimed to evaluate the potential effect of sodium tungstate in the treatment of grade I and II obesity ( identifier: NCT00555074). Prospective, randomized, placebo-controlled, double-blind, proof-of-concept study was carried out. Following a 2-week lead-in period, 30 obese (body mass index, BMI 30.0-39.9 kg/m), non-diabetic subjects were randomized to receive either sodium tungstate (100 mg bid) or placebo for 6 weeks. The primary study endpoint was the absolute change in body weight relative to the time of randomization. Treatment with sodium tungstate [−0.135 ± 0.268 kg (95% CI −0.686 to +0.416 kg)] was not associated with a significant weight loss compared to placebo [−0.063 ± 0.277 kg (95% CI −0.632 to +0.507 kg)] (p = 0.854). Likewise, treatment with sodium tungstate was not associated with significant changes in fat mass (DEXA), resting energy expenditure (indirect calorimetry) or caloric consumption (3-day food records). Our data do not support sodium tungstate as a pharmacological agent in the treatment of human obesity. [ABSTRACT FROM AUTHOR]

Objective: For many patients with type 2 diabetes, oral antidiabetic agents (OADs) do not provide optimal glycaemic control, necessitating insulin therapy. Fear of hypoglycaemia is a major barrier to initiating insulin therapy. The AT.LANTUS study investigated optimal methods to initiate and maintain insulin glargine (LANTUS®, glargine, Sanofi-aventis, Paris, France) therapy using two treatment algorithms. This subgroup analysis investigated the initiation of once-daily glargine therapy in patients suboptimally controlled on multiple OADs. Research Design and Methods: This study was a 24-week, multinational (59 countries), multicenter (611), randomized study. Algorithm 1 was a clinic-driven titration and algorithm 2 was a patient-driven titration. Titration was based on target fasting blood glucose ≤100 mg/dl (≤5.5 mmol/l). Algorithms were compared for incidence of severe hypoglycaemia [requiring assistance and blood glucose <50 mg/dl (<2.8 mmol/l)] and baseline to end-point change in haemoglobin A1c (HbA1c). Results: Of the 4961 patients enrolled in the study, 865 were included in this subgroup analysis: 340 received glargine plus 1 OAD and 525 received glargine plus >1 OAD. Incidence of severe hypoglycaemia was <1%. HbA1c decreased significantly between baseline and end-point for patients receiving glargine plus 1 OAD (−1.4%, p < 0.001; algorithm 1 −1.3% vs. algorithm 2 −1.5%; p = 0.03) and glargine plus >1 OAD (−1.7%, p < 0.001; algorithm 1 −1.5% vs. algorithm 2 −1.8%; p = 0.001). Conclusions: This study shows that initiation of once-daily glargine with OADs results in significant reduction of HbA1c with a low risk of hypoglycaemia. The greater reduction in HbA1c was seen in patients randomized to the patient-driven algorithm (algorithm 2) on 1 or >1 OAD. [ABSTRACT FROM AUTHOR]

Aim: The AT.LANTUS study compared insulin glargine initiation and titration using one of two algorithms in suboptimally controlled subjects with type 2 diabetes mellitus (T2DM) based on a primary outcome of severe hypoglycaemia. Secondary outcomes included other categories of hypoglycaemia, glycaemic control, weight changes and insulin dose. Here, we report the results of a subanalysis of the trial, which investigated whether insulin glargine can be initiated and titrated as effectively in primary [general practitioner (GP)] as secondary (hospital) care in patients with T2DM in the UK. Methods: The main study was a multicentre (n = 611), multinational (n = 59), open-label, 24-week randomized trial in 4588 suboptimally controlled subjects with T2DM. Insulin glargine was titrated to target fasting blood glucose (FBG) levels of ≤5.5 mmol/l according to algorithm 1 (clinic-driven titration) or algorithm 2 (patient-managed titration). In this substudy, 819 subjects (GP, n = 215; hospital, n = 604) from 57 primary and 130 secondary care centres were included in the subanalysis; subjects were switched to once-daily insulin glargine from baseline treatments that consisted primarily of oral antidiabetic agents (OADs) (38%) only or premixed insulin +/− OAD (23%). Results: Both the GP and the hospital groups of subjects experienced a low incidence of severe hypoglycaemia (<1%), with significant decreases in HbA1c levels (−0.51 and −0.95% respectively; p < 0.001), large reductions in FBG levels (−2.72 and 3.0 mmol/l respectively; p < 0.001) and modest weight gain of 1 and 1.2 kg respectively (p < 0.05). With the exception of absolute reductions in HbA1c and reductions in basal and prandial insulin made on switching to insulin glargine, there were few significant differences in subjects managed in primary compared with secondary care. Conclusions: This study shows that despite differences in diabetes duration and baseline glycaemic control, an insulin glargine–based therapy can be safely and effectively initiated in a diverse range of suboptimally controlled subjects with T2DM in both primary and secondary care settings in the UK. Rates of hypoglycaemia were low and consistent with the results of the main study. Absolute reductions in HbA1c were greatest in the secondary care setting, but similar levels of glycaemic control were achieved in both groups due to differences in baseline HbA1c. In the patients managed in primary care, there was an overall reduction in prandial and basal insulin used when switching to a basal insulin regimen and a lack of titration of prandial insulin. Therefore, the role of prandial insulin, its initiation and titration, appears to be an area that requires more focus in primary care. [ABSTRACT FROM AUTHOR]

Aims To compare glucose control over 18 months between rosiglitazone oral combination therapy and combination metformin and sulphonylurea in people with Type 2 diabetes. Methods RECORD, a multicentre, parallel-group study of cardiovascular outcomes, enrolled people with an HbA1c of 7.1–9.0% on maximum doses of metformin or sulphonylurea. If on metformin they were randomized to add-on rosiglitazone or sulphonylurea (open label) and if on sulphonylurea to rosiglitazone or metformin. HbA1c was managed to ≤ 7.0% by dose titration. A prospectively defined analysis of glycaemic control on the first 1122 participants is reported here, with a primary outcome assessed against a non-inferiority margin for HbA1c of 0.4%. Results At 18 months, HbA1c reduction on background metformin was similar with rosiglitazone and sulphonylurea [difference 0.07 (95% CI −0.09, 0.23)%], as was the change when rosiglitazone or metformin was added to sulphonylurea [0.06 (−0.09, 0.20)%]. At 6 months, the effect on HbA1c was greater with add-on sulphonylurea, but was similar whether sulphonylurea was added to rosiglitazone or metformin. Differences in fasting plasma glucose were not statistically significant at 18 months [rosiglitazone vs. sulphonylurea −0.36 (−0.74, 0.02) mmol/l, rosiglitazone vs. metformin −0.34 (−0.73, 0.05) mmol/l]. Increased homeostasis model assessment insulin sensitivity and reduced C-reactive protein were greater with rosiglitazone than metformin or sulphonylurea (all P ≤ 0.001). Body weight was significantly increased with rosiglitazone compared with sulphonylurea [difference 1.2 (0.4, 2.0) kg, P = 0.003] and metformin [difference 4.3 (3.6, 5.1) kg, P < 0.001]. Conclusions In people with diabetes, rosiglitazone in combination with metformin or sulphonylurea was demonstrated to be non-inferior to the standard combination of metformin + sulphonylurea in lowering HbA1c over 18 months, and produces greater improvements in C-reactive protein and basal insulin sensitivity but is also associated with greater weight gain. [ABSTRACT FROM AUTHOR]

Aims The goal of the study was to determine whether continuous subcutaneous insulin infusion (CSII) differs from a multiple daily injection (MDI) regimen based on neutral protamine hagedorn (NPH) as basal insulin with respect to glycaemic control and quality of life in people with Type 1 diabetes. Methods The 5-Nations trial was a randomized, controlled, crossover trial conducted in 11 European centres. Two hundred and seventy-two patients were treated with CSII or MDI during a 2-month run-in period followed by a 6-month treatment period, respectively. The quality of glycaemic control was assessed by HbA1c, blood glucose values, and the frequency of hypoglycaemic events. For the evaluation of the quality of life, three different self-report questionnaires have been assessed. Results CSII treatment resulted in lower HbA1c (7.45 vs. 7.67%, P < 0.001), mean blood glucose level (8.6 vs. 9.4 mmol/l, P < 0.001) and less fluctuation in blood glucose levels than MDI ( ± 3.9 vs. ± 4.3 mmol/l, P < 0.001). There was a marked reduction in the frequency of hypoglycaemic events using CSII compared with MDI, with an incidence ratio of 1.12 [95% confidence interval (CI): 1.08–1.17] and 2.61 (95% CI: 1.59–4.29) for mild and severe hypoglycaemia, respectively. The overall score of the diabetes quality of life questionnaire was higher for CSII ( P < 0.001), and an improvement in pump users’ perception of mental health was detected when using the SF-12 questionnaire ( P < 0.05). Conclusion CSII usage offers significant benefits over NPH-based MDI for individuals with Type 1 diabetes, with improvement in all significant metabolic parameters as well as in patients’ quality of life. Additional studies are needed to compare CSII with glargine- and detemir-based MDI. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

To study clinical characteristics,β-cell function, HLA typing and mutations in the hepatocyte nuclear factor (HNF)-1α andHNF-4α genes in Type 1 diabetes mellitus (T1D) patients without pancreatic autoantibodies.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 theHNF-1α andHNF-4α genes were performed.No differences were found in clinical presentation, metabolic control andβ-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 Aspβ57 in the Ab neg group, but in all the cases in combination with susceptible T1D haplotypes. We found two previously reported polymorphisms (HNF-1α, Ala98Val;HNF-4α, Thr130Ile) in Ab neg and a new variant (Ser165Gly) in theHNF-4α gene in an Ab pos subject.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-1α and HNF-4α are unlikely to be major contributors to the pathogenesis of diabetes in antibody-negative T1D.Diabet. Med. (2004) [ABSTRACT FROM AUTHOR]

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. Copyright 2004 Diabetes UK [ABSTRACT FROM AUTHOR]

The aims of the study were to determine whether transforming growth factor β1 TGF-β1 levels are raised at diagnosis of Type 1 diabetes mellitus and are related to blood glucose. 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, HbA1c, lipid profile and TGF-β1 levels and TGF-β1 levels in 24-h urine were determined. The control group included 14 non-diabetic subjects with similar characteristics to those of the diabetic group. Plasma and urinary TGF-β1 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, HbA1c 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-β1 levels. A statistically significant correlation was observed between plasma TGF-β1 and insulin dosage (U/kg/day) ( r = 0.52, P = 0.037). The increased TGF-β1 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. Diabet. Med. (2004) [ABSTRACT FROM AUTHOR]

SummaryAims This study was designed to test the efficacy and safety of low-dose rosiglitazone, a potent, insulin-sensitizing thiazolidinedione, in combination with sulphonylurea in Type 2 diabetic patients. Methods For the intention-to-treat analysis, 574 patients (59% male, mean age 61 years) were available, randomized to receive 26 weeks of twice-daily placebo (n = 192), rosiglitazone 1 mg (n = 199) or rosiglitazone 2 mg (n = 183) in addition to existing sulphonylurea treatment with gliclazide (47.6% of patients), glibenclamide (41.8%) or glipizide (9.4%) (two patients were taking carbutamide or glimepiride). Change in haemoglobin A1c (HbA1c), fasting plasma glucose (FPG), fructosamine, insulin, C-peptide, albumin, and lipids were measured, and safety was evaluated. Results Mean baseline HbA1c was 9.2% and FPG was 11.4 mmol/l. Rosiglitazone at doses of 1 and 2 mg b.d. plus sulphonylurea produced significant decreases, compared with sulphonylurea plus placebo, in HbA1c (-0.59% and -1.03%, respectively; both P < 0.0001) and FPG (1.35 mmol/l and 2.44 mmol/l, respectively; both P < 0.0001). Both HDL-cholesterol and LDL-cholesterol increased and potentially beneficial decreases in non-esterified fatty acids and gamma glutamyl transpeptidase levels were seen in both rosiglitazone groups. The overall incidence of adverse experiences was similar in all three treatment groups, with no significant cardiac events, hypoglycaemia or hepatotoxicity. Conclusions Overall, the combination of rosiglitazone and a sulphonylurea was safe, well tolerated and effective in patients with Type 2 diabetes. [ABSTRACT FROM AUTHOR]

SummaryAims To elucidate the effect of prophylactic insulin, in a treatment schedule previously demonstrated to achieve β-cell rest, in a group of high-risk, non-diabetic first-degree relatives of Type 1 diabetic patients. Methods Ten high risk subjects for Type 1 diabetes mellitus (DM) (seven male/three female, aged 19.8 ± 9.6 years) defined as: first-degree relatives of Type 1 DM patients, islet cell autoantibodies (ICA) ≥20 Juvenile Diabetes Foundation (JDF) units twice, first phase insulin response (FPIR) to glucose in an intravenous glucose tolerance test ≤10th percentile of a control group were included in an open pilot trial. Five were treated with subcutaneous insulin: 0.1 IU/kg body weight/day of neutral protamine hagedorn (NPH) insulin once a day. Five declined treatment and were used as controls. Control and treatment groups did not differ in terms of age, ICA, insulin autoantibodies (IAA), glutamic acid dehydrogenase (GAD) and FPIR. Results Three out of five subjects in both groups developed Type 1 DM during follow-up: after 21, and 32–57 months in the insulin-treated group and after 4, and 18–60 months in the untreated group. Three out of six subjects who developed overt diabetes had a FPIR below the 2nd percentile of the control value at the onset of the study. All subjects who developed diabetes were positive for antibodies to GAD and expressed the HLA-DR3 or DR4 alleles, whereas only one of the nono-progessors had these parameters (P < 0.05). During follow-up, a decrease in ICA titres was observed in the group which received prophylactic insulin in contrast with the untreated group. GAD, as well as insulin secretory capacity, remained unchanged in both groups. Conclusion The subcutaneous administration of insulin (0.1 IU/kg body weight/day of NPH insulin once a day) in our group of high-risk subjects for Type 1 DM produced only a minor effect in some immunological markers (ICA), without preventing the... [ABSTRACT FROM AUTHOR]

This article describes a course for reinforcing the knowledge of biochemistry in secondary school science teachers. The Department of Biochemistry and Molecular Biology of the University of Barcelona designed a course to bring these teachers up to date with this discipline. In addition to updating their knowledge of biochemistry and molecular biology, this course aims to provide teachers with a set of relevant laboratory practices that can be applied in their practical lessons. [ABSTRACT FROM AUTHOR]

Sodium tungstate is an effective antidiabetic agent. Oral administration of sodium tungstate normalised glycaemia and increased insulinaemia in neonatal streptozotocin rats that displayed symptoms mimicking symptoms associated with diabetes. Tungstate treatment increases extra-islet beta-cell replication without modifying intraislet beta-cell replication rates. Moreover, the treatment induces an increase in insulin-positive cells located close to ducts, as well as PDX-1 positive cells scattered in the exocrine tissue, suggesting active neogenesis. Remarkably, after tungstate withdrawal, animals remained normoglycaemic. [ABSTRACT FROM AUTHOR]

Sodium tungstate is an effective antidiabetic agent. Oral administration of sodium tungstate normalised glycaemia and increased insulinaemia in neonatal streptozotocin rats that displayed symptoms mimicking symptoms associated with diabetes. Tungstate treatment increases extra-isletβ-cell replication without modifying intraisletβ-cell replication rates. Moreover, the treatment induces an increase in insulin-positive cells located close to ducts, as well as PDX-1 positive cells scattered in the exocrine tissue, suggesting active neogenesis. Remarkably, after tungstate withdrawal, animals remained normoglycaemic. [ABSTRACT FROM AUTHOR]

Abstract 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. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "The effect of linagliptin on glycemic control and tolerability in patients with type 2 diabetes mellitus: a systematic review and meta-analysis," by D. Singh-Franco and colleagues in the 2012 issue.

Focuses on a study which assessed the impact of the 1997 American Diabetes Association criteria for the diagnosis of diabetes mellitus among employees. Methodology used in the study; Discussion on the results of the study; Conclusion.

Background: Secreted frizzled-related protein 5 (SFRP5) has been linked to obesity. Results are conflicting regarding its association with type 2 diabetes (T2D) in humans. We aimed to investigate circulating SFRP5 in prediabetes and T2D and its potential association with parameters of insulin resistance and beta-cell function., Methods: We studied 70 drug-naïve T2D patients, 70 prediabetic subjects and 70 controls. All subjects were body mass index matched to the T2D patients and overweight or obese. SFRP5, hormones and cytokines levels were measured by ELISA., Results: Serum SFRP5 levels were elevated in T2D patients as compared with prediabetic subjects (median 15.6, interquartile range [9-24.5] ng/mL vs 9.8 [5-14.2] ng/mL, p < 0.001, respectively) and controls (15.6 [9-24.5] ng/mL vs 10.4 [6.7-16.6] ng/mL, P < 0.001, respectively). No differences were found in serum SFRP5 levels between prediabetic subjects and controls (9.8 [5-14.2] ng/mL vs 10.4 [6.7-16.6] ng/mL, p = 0.472, respectively). After adjusting for potential confounders (age, gender, body mass index, triglycerides, high-density lipoprotein cholesterol and blood pressure), T2D was still associated with higher values of SFRP5 as compared with prediabetes in multinomial logistic regression analysis (fully adjusted odds ratio 3.50, 95% confidence interval 1.40-8.79, p = 0.008). The association was more subtle when comparing T2D with normal glucose tolerance state (fully adjusted odds ratio 2.18, 95% confidence interval 0.91-5.21, p = 0.078)., Conclusions: Circulating SFRP5 levels were independently associated with T2D as compared with prediabetes and normal glucose tolerance state., (Copyright © 2014 John Wiley & Sons, Ltd.)

The Diabetes Control and Complications Trial (DCCT) demonstrated that intensive management in people with type 1 diabetes delays the onset and the progression of microvascular complications associated with the disease. However, it is also known that intensive regimens can increase the number of hypoglycaemias and that the perception of symptoms decreases in relation to the statutes of metabolic control 1. Impairment of hypoglycaemic awareness is reported by up to 50% of patients with type 1 diabetes and it is associated with an increase of severe episodes of hypoglycaemia 2. Self-monitoring of blood glucose (SMBG) has become a major tool in the management of diabetes. Current recommendations suggest frequent SMBG. The major inconvenience of SMBG is due to the limitations of the glycaemic profile obtained from intermittent finger-sticks. This is an incomplete picture of blood glucose excursions; moreover, the frequent SMBG is not readily accepted by patients suffering from diabetes because it is invasive and painful., (Copyright 2004 John Wiley & Sons, Ltd.)

True (cofactor-independent) anticardiolipin antibodies (aCL) are thought to lack lupus anticoagulant (LA) activity and pathogenic potential. A serum monoclonal immunoglobulin Mlambda (mIgMlambda) with aCL and LA activities found in a man with a splenicIgMlambda+ B-cell lymphoplasmacytic lymphoma (LPL) without thrombotic events has been characterized. LPL-derived hybridoma clones (designated HY-FRO) producing the serum mIgMlambda were obtained. mIgMlambda secreted by HY-FRO grown in protein-free culture medium, like that purified from serum, (i) showed binding, in a cofactor-free system, to solid-phase CL and phosphatidylserine (PS) and to the membrane of PS-expressing cells (apoptotic cells and activated platelets); (ii) failed to bind neutral phospholipids (PL), beta2Glycoprotein, histone, ssDNA, dsDNA, human IgG and umbilical vein endothelial cells. Absorption with apoptotic cells abolished its binding to anionic plate-bound CL and PS. IgMlambda-FRO used poorly mutated VH and Vlambda region genes, with a pattern that was inconsistent with an antigen-driven selection. Basic amino acids were present in the IgH complementarity determining region 3 (CDR3), which can be important for binding to anionic PL. These findings demonstrate unequivocally that true anti-anionic PL IgM antibodies can exert LA and indicate this anti-PL type does not involve thrombophilia.