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Biomedical subjects

R Gomis

Publications and source records attributed to R Gomis.

At least 19 recordsLinked to original sources
PubMed2006

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.

Adult↗
PubMed2006

Comparison of the effects of continuous subcutaneous insulin infusion (CSII) and NPH-based multiple daily insulin injections (MDI) on glycaemic control and quality of life: results of the 5-nations trial.

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 HbA(1c), 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 HbA(1c) (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.

Adult↗
PubMed2005

Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycaemia in Diabetes (RECORD): study design and protocol.

AIMS/HYPOTHESIS: Studies suggest that in addition to blood glucose concentrations, thiazolidinediones such as rosiglitazone improve some cardiovascular (CV) risk factors and surrogate markers, that are abnormal in type 2 diabetes. However, fluid retention might lead to cardiac failure in a minority of people. The aim of the Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycaemia in Diabetes (RECORD) study is to evaluate the long-term impact of these effects on CV outcomes, as well as on long-term glycaemic control, in people with type 2 diabetes. MATERIALS AND METHODS: RECORD is a 6-year, randomised, open-label study in type 2 diabetic patients with inadequate blood glucose control (HbA1c 7.1-9.0%) on metformin or sulphonylurea alone. The study is being performed in 327 centres in Europe and Australasia. After a 4-week run-in, participants were randomised by current treatment stratum to add-on rosiglitazone, metformin or sulphonylurea, with dose titration to a target HbA1c of < or = 7.0%. If confirmed HbA1c rises to > or = 8.5%, either a third glucose-lowering drug is added (rosiglitazone-treated group) or insulin is started (non-rosiglitazone group). The same criterion for failure of triple oral drug therapy in the rosiglitazone-treated group is used for starting insulin in this group. The primary endpoint is the time to first CV hospitalisation or death, blindly adjudicated by a central endpoints committee. The study aim is to evaluate non-inferiority of the rosiglitazone group vs the non-rosiglitazone group with respect to CV outcomes. Safety, tolerability and study conduct are monitored by an independent board. All CV endpoint and safety data are held and analysed by a clinical trials organisation, and are not available to the study investigators while data collection is open. RESULTS: Over a 2-year period a total of 7,428 people were screened in 25 countries. Of these, 4,458 were randomised; 2,228 on background metformin, 2,230 on background sulphonylurea. Approximately half of the participants are male (52%) and almost all are Caucasian (99%). CONCLUSIONS/INTERPRETATION: The RECORD study should provide robust data on the extent to which rosiglitazone, in combination with metformin or sulphonylurea therapy, affects CV outcomes and progression of diabetes in the long term.

Blood Glucose↗
PubMed2005

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.

Adult↗
PubMed2005

The importance of diagnostic criteria in the association between the metabolic syndrome and cardiovascular disease in obese subjects.

OBJECTIVE: To investigate whether the association between the metabolic syndrome (MS) and cardiovascular disease (CVD) in obese adults is influenced by the criteria used to diagnose the MS. DESIGN AND SUBJECTS: Cross-sectional study in 389 obese adults (male/female: 26%/74%; body mass index (BMI): 30.1-63.2 kg/m2; age: 18-79 y). MEASUREMENTS: To diagnose the MS by the WHO or the ATPIII criteria, body mass index, waist circumference, fasting and 2-h oral Glucose tolerance test plasma glucose, fasting plasma triglycerides and HDL cholesterol, systolic and diastolic blood pressure, 24-h albumin excretion, and fasting insulin were measured. The association between the MS diagnosed with either definition and self-referred CVD was investigated. RESULTS: The prevalence of the MS by the WHO was higher than by the ATPIII criteria (WHO 69.1%, ATPIII 49.4%; P<0.001). The MS diagnosed by the WHO criteria was significantly associated with self-referred CVD (odds ratio (OR) 5.80, 95% CI 1.35-24.95, P<0.05), whereas the ATPIIII MS was not (OR 1.34, 95% CI 0.59-3.03). An elevated blood pressure (OR 5.04, 95% CI 1.41-18.01, P<0.05) and microalbuminuria (OR 2.61, 95% CI 1.06-6.40, P<0.05) were independently associated with CVD. Consideration of the OGTT data as part of the ATPIII MS definition improved its associations with CVD (OR 4.39, 95% CI 1.29-14.94, P<0.05). CONCLUSION: The WHO criteria appear to identify a greater number of obese adults at risk for CVD. Nevertheless, the addition of an OGTT at least in nondiabetic patients with two ATPIII-defined metabolic risk factors may help to improve the association between the MS and CVD in obese adults.

Adolescent↗
PubMed2005

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.

Adolescent↗
PubMed2004

Mutation at position -132 in the islet amyloid polypeptide ( IAPP) gene promoter enhances basal transcriptional activity through a new CRE-like binding site.

AIMS/HYPOTHESIS: Mutations in the islet amyloid polypeptide ( IAPP) gene may play a potential role in the abnormal regulation or expression of the peptide. The aim of this study was to determine the functional role of the -132 G/A mutation reported in the promoter region of the IAPP gene in a population of Spanish Type 2 diabetic patients. METHODS: We investigated the transcriptional activity using MIN6 cells and luciferase reporter plasmids in several culture conditions. Key regulatory elements of the IAPP promoter region were also analysed by electrophoretic mobility shift assays (EMSA). RESULTS: The mutant construct doubled IAPP transcriptional activity ( p<0.001). Both constructs showed severely reduced promoter activity (four-fold decrease) in the presence of verapamil and diazoxide. In contrast, IAPP promoter activity was doubled after incubation with forskolin or dexamethasone, regardless of the glucose concentrations in the culture media. EMSA revealed that the -132 G/A mutation increased the binding affinity through two DNA-protein complexes. In addition, a cAMP-responsive element binding protein (CREB) was identified by super-shift EMSA. CONCLUSIONS/INTERPRETATION: Our studies show that the wild-type and the mutant constructs are regulated in a similar pattern under all conditions, strongly indicating that the -132 G/A mutation increases basal but not inducible transcription. These results may be explained by new binding to the mutant region through CREB and other transcription factors not yet identified.

Amino Acid Substitution↗
PubMed2004

Acarbose for the prevention of Type 2 diabetes, hypertension and cardiovascular disease in subjects with impaired glucose tolerance: facts and interpretations concerning the critical analysis of the STOP-NIDDM Trial data.

The STOP-NIDDM Trial has shown that acarbose treatment in subjects with impaired glucose tolerance is associated with a significant risk reduction in the development of diabetes, hypertension and cardiovascular complications. Kaiser and Sawicki have accused the investigators of the STOP-NIDDM Trial of major biases in the conduct of the study, of manipulating the data and of conflict of interest. The aim of this paper is to present data and explanations refuting these allegations. In the STOP-NIDDM Trial, 61 subjects were excluded from the efficacy analysis before unblinding for legitimate reasons: failure to satisfy major entry criteria (n=17) and lack of post-randomisation data (n=44). Blinding and randomisation were carried out by an independent biostatistician. Titration of placebo/acarbose is well described in the protocol and in the study design paper. Of the study population, 9.3% had a fasting plasma glucose of > or =7.0 mmol/l at screening and could have been diabetic according to the new diagnostic criteria. However, even if these subjects are excluded, patients having acarbose treatment still saw a significant risk reduction in the development of diabetes (p=0.0027). The changes in weight are consistent in different publications and are related to different times of follow-up and assessment. Weight change does have an effect on the development of diabetes, but acarbose treatment is still effective even after adjusting for this (p=0.0063). The cardiovascular endpoints were a clearly designated assessment in the original protocol, and only those defined in the protocol and ascertained by the independent Cardiovascular Event Adjudication Committee were used in the analysis. Hypertension was defined according to the most recent diagnostic criteria. The STOP-NIDDM Trial results are scientifically sound and credible. The investigators stand strongly behind these results demonstrating that acarbose treatment is associated with a delay in the development of diabetes, hypertension and cardiovascular complications in a high-risk population with IGT.

Acarbose↗
PubMed2004

Identification of iduronate-2-sulfatase in mouse pancreatic islets.

The lysosomal enzyme iduronate-2-sulfatase (IDS) is expressed in pancreatic islets and is responsible for degradation of proteoglycans, such as perlecan and dermatan sulfate. To determine the role of IDS in islets, expression and regulation of the gene and localization of the enzyme were investigated in mouse pancreatic islets and clonal cells. The Ids gene was expressed in mouse islets and beta- and alpha-clonal cells, in which it was localized intracellularly in lysosomes. The transcriptional expression of Ids in mouse islets increased with glucose in a dose-dependent manner (11.5, 40.2, 88, and 179% at 5.5, 11.1, 16.7, and 24.4 mM, respectively, P < 0.01 for 16.7 and 24.4 mM glucose vs. 3 mM glucose). This increase was not produced by glyceraldehyde (1 mM) or 6-deoxyglucose (21.4 mM) and was blocked by the addition of mannoheptulose (21.4 mM). Neither insulin content nor secretory response to glucose (16.7 mM) was altered in mouse islets infected with lentiviral constructs carrying the IDS gene in sense orientation. Furthermore, no decrease in islet cell viability was observed in mouse islets carrying lentiviral contracts compared with controls. However, insulin content was reduced (35% vs. controls, P < 0.001) in islets infected with IDS antisense construct, while the secretory response of those islets to glucose was maintained. Inhibition of IDS by antisense infection led to an increase in lysosomal size and a high rate of insulin granule degradation via the crinophagic route in pancreatic beta-cells. We conclude that IDS is localized in lysosomes in pancreatic islet cells and expression is regulated by glucose. IDS has a potential role in the normal pathway of lysosomal degradation of secretory peptides and is likely to be essential to maintain pancreatic beta-cell function.

Animals↗
PubMed2004

Stable and functional regeneration of pancreatic beta-cell population in nSTZ-rats treated with tungstate.

AIMS/HYPOTHESIS: Sodium tungstate has recently emerged as an effective oral treatment for diabetes. We examined the effects of tungstate administration in the beta-cell mass of the pancreas as well as its therapeutic potential. METHODS: Sodium tungstate was administered via drinking water to healthy and neonatal streptozotocin (nSTZ)-diabetic rats for one month. The pancreas from each rat was removed and morphometric and immunocytochemical studies were carried out. The molecular mechanism of tungstate's action was also studied. RESULTS: In nSTZ rats administration of this compound normalised glycaemia, and increased insulinaemia and islet insulin content. Blood glucose concentrations were normalised as early as on day 4 of treatment, and tungstate treatment produced a partial recovery of beta-cell mass. The rats remained normoglycaemic after tungstate withdrawal. Morphometric studies showed that the increase in beta-cell mass was not due to beta-cell hypertrophy but to hyperplasia, with an increase in islet density in treated diabetic rats. Tungstate treatment increased extra-islet beta-cell replication without modifying intra-islet beta-cell replication rates. Moreover, the treatment induced increases in insulin-positive cells located close to ducts; and in PDX-1 positive cells scattered in the exocrine tissue, suggesting active neogenesis. In islets from treated diabetic rats, tungstate is able to increase the phosphorylation state of PDX-1 through the activation of p38. CONCLUSION/INTERPRETATION: These observations indicate that tungstate treatment is able to regenerate a stable, functional pancreatic beta-cell population which leads to and maintains normoglycaemia.

Animals↗
PubMed2004

Pancreatic islets from cyclin-dependent kinase 4/R24C (Cdk4) knockin mice have significantly increased beta cell mass and are physiologically functional, indicating that Cdk4 is a potential target for pancreatic beta cell mass regeneration in Type 1 diabetes.

AIMS/HYPOTHESIS: Cyclin-dependent kinase 4 (Cdk4) is crucial for beta cell development. A mutation in the gene encoding for Cdk4, Cdk4R24C, causes this kinase to be insensitive to INK4 cell cycle inhibitors and induces beta cell hyperplasia in Cdk4R24C knockin mice. We aimed to determine whether this Cdk4R24C mutation also affects proper islet function, and whether it promotes proliferation in human islets lentivirally transduced with Cdk4R24C cDNA. METHODS: Our study was conducted on wild-type and Cdk4R24C knockin mice. Pancreases were morphometrically analysed. Intraperitoneal glucose tolerance tests and intravenous insulin tolerance tests were performed on wild-type and Cdk4R24C mice. We also did in vitro islet perifusion studies and islet metabolic labelling analysis. Human islets were transduced with Cdk4R24C cDNA. RESULTS: Pancreatic islets from Cdk4R24C knockin mice exhibit a larger insulin-producing beta cell area and a higher insulin content than islets from wild-type littermates. Insulin secretion in response to glucose is faster and reaches a higher peak in Cdk4R24C mice without leading to hypoglycaemia. Conversion of pro-insulin into insulin and its intermediates is similar in Cdk4R24C and wild-type mice. Glucose utilisation and oxidation measured per islet were similar in both experimental groups. Insulin secretion was faster and enhanced in Cdk4R24C islets perifused with 16.7 mmol/l glucose, with slower decay kinetics when glucose returned to 2.8 mmol/l. Moreover, human islets expressing Cdk4R24C cDNA exhibited higher beta cell proliferation. CONCLUSIONS/INTERPRETATION: Despite their hyperplastic growth, Cdk4R24C insulin-producing islet cells behave like differentiated beta cells with regard to insulin production, insulin secretion in response to glucose, and islet glucose metabolism. Therefore Cdk4 could possibly be used to engineer a source of beta cell mass for islet transplantation.

Animals↗
PubMed2004

Initiating oral glucose-lowering therapy with metformin in type 2 diabetic patients: an evidence-based strategy to reduce the burden of late-developing diabetes complications.

A major aim of glucose-lowering therapy in people with diabetes is to delay or prevent the late-developing complications of diabetes that threaten the quality and duration of life. While intensive interventions to control hyperglycaemia may impair well-being to some extent, the balance of quality of life is usually highly positive. Diet and exercise therapy remains the cornerstone of management, and should usually be given a trial alone first. However, the magnitude and duration of benefit from this intervention is insufficient for most people. More frequent, early, use of metformin is an evidence-based strategy for reducing the risk of adverse outcomes of diabetes in people with type 2 diabetes with sub-optimal glucose control on lifestyle measures alone. This has been recognised in recent evidenced-based guidelines from the UK National Institute for Clinical Excellence and from Diabetes UK, which now support the use of metformin as initial pharmacological therapy for all people without contraindications to the drug. Other national and local guideline committees should consider updating their recommendations on diabetes management in line with these findings.

Body Mass Index↗
PubMed2004

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.

Adult↗
PubMed2003

A high carbohydrate diet does not induce hyperglycaemia in a mitochondrial glycerol-3-phosphate dehydrogenase-deficient mouse.

AIMS/HYPOTHESIS: The electrons of the glycolysis-derived reduced form of NADH are transferred to mitochondria through the NADH shuttle system. There are two NADH shuttles: the glycerol phosphate and malate-aspartate shuttle. Mice with a targeted disruption of mitochondrial glycerol-3-phosphate dehydrogenase, a rate-limiting enzyme of the glycerol phosphate shuttle, are not diabetic and have normal islet glucose-induced secretion. In this study, we analyzed if environmental factors, such as a high carbohydrate diet could contribute to the development of Type 2 diabetes mellitus in mice with a specific defective genetic background. METHODS: The mice were fed with a high carbohydrate diet for 1 and 6 months, and several biochemical parameters were analysed. The mitochondrial respiratory activity was assayed by polarography; and the islet function was studied by islet perifusion and pancreas perfusion. RESULTS: The high carbohydrate diet induced hyperglycaemia, hyperinsulinaemia, and islet hyperplasia in the wild-type and heterozygote mice. Activity of the respiratory chain complex I also increased in these mice. In contrast, these effects were not observed in the null mice fed with the diet; in addition, these null mice had an increased insulin sensitivity compared to wild-type mice. CONCLUSION/INTERPRETATION: The phenotype of the mice with an impairment of NADH shuttles does not worsen when fed a high carbohydrate diet; moreover, the diet does not compromise islet function.

Animals↗
PubMed2003

Evidence of expression of endotoxin receptors CD14, toll-like receptors TLR4 and TLR2 and associated molecule MD-2 and of sensitivity to endotoxin (LPS) in islet beta cells.

CD14, a GPI-linked membrane protein, is a component of the lipopolysaccharide (LPS) receptor complex, one of the pattern-recognizing receptors (PRR) expressed by myeloid lineage cells. Here we report that CD14, the functionally linked toll-like receptor molecules, TLR2 and TLR4, and the associated molecule MD-2 are expressed in endocrine cells of the human pancreatic islets. CD14 expression in human pancreatic islets was determined by immunofluorescence staining of tissue sections and primary cultures, and confirmed by flow cytometry of dispersed normal islets and SV40-transformed islet cells (HP62). The latter cells synthesized and secreted CD14 in response to lipopolysaccharide (LPS) in a time- and dose-dependent manner. Reverse transcription polymerase chain reaction (RT-PCR)-Southern was positive for CD14, TLR2, TLR4 and MD-2 in human pancreas, purified islets and HP62 cells. In vitro experiments using rat islets (also positive for CD14 by RT-PCR) and HP62 cells showed that LPS regulates glucose-dependent insulin secretion and induces inflammatory cytokines [interleukin (IL)-1alpha, IL-6 and tumour necrosis factor (TNF)-alpha]. The functional expression of CD14 and associated molecules in islet beta cells adds a new pathway that islet cells may follow to adjust their function to endotoxaemia situations and become vulnerable to the inflammatory events that occur during diabetogenic insulitis.

Adolescent↗
PubMed2003

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.

Adult↗
PubMed2002

Serum concentrations of the interferon-gamma-inducible chemokine IP-10/CXCL10 are augmented in both newly diagnosed Type I diabetes mellitus patients and subjects at risk of developing the disease.

AIMS/HYPOTHESIS: Chemokines are chemotactic cytokines controlling the recruitment of leukocytes from the blood by regulating integrin adhesiveness. It has been shown that the migration of CD4+Th1 and CD4+Th2 cells is governed by specific chemokines. Increasing evidence suggests that the CD4+Th1 cheomoattractant chemokine CXCL10, also termed Interferon (IFN)-gamma -inducible protein (IP)-10 is pathogenetically involved in several immunoinflammatory and autoimmune diseases. METHODS: IFN-gamma and IP-10 were quantified by solid-phase ELISA in sera of patients with either newly diagnosed or long-term Type I (insulin-dependent) diabetes mellitus, and in sera of their healthy first degree relatives. The latter were subdivided into "low" and "high" risk prediabetic subjects depending on whether they were negative or positive for the anti-beta-cell autoantibodies ICA and GAD. RESULTS: Compared with healthy control subjects (18%, 9/50), those with a low risk of disease (21%, 5/24) and the group of patients with long-term Type I diabetes (24%, 12/50), IP-10 was found more frequently and at increased concentrations in both newly diagnosed Type I diabetic patients (84%, 42/50) and in those with a high risk of disease (73%, 16/22); in the latter, the IP-10 concentrations correlated with those of IFN-gamma. CONCLUSION/INTERPRETATION: Circulating IP-10 concentrations is increased in patients with Type I diabetes, but only during the early and subclinical stage of the disease.

Adult↗