C Mathieu

University of Leuven, Louvain, Flanders, Belgium

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Publications (210)732.97 Total impact

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    ABSTRACT: Aims: To assess the efficacy and safety of canagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, in patients with type 2 diabetes enrolled in the CANagliflozin cardioVascular Assessment Study (CANVAS) who were on an incretin mimetic (i.e. dipeptidyl peptidase-4 [DPP-4] inhibitor or glucagon-like peptide-1 [GLP-1] receptor agonist). Materials and methods: CANVAS is a double-blind, placebo-controlled study that randomized participants to placebo or canagliflozin 100 or 300 mg added to routine therapy. This post hoc analysis assessed efficacy and safety of canagliflozin 100 and 300 mg compared with placebo in subsets of patients from CANVAS who were taking background DPP-4 inhibitors or GLP-1 receptor agonists with or without other antihyperglycaemic agents at week 18. Results: Of the 4,330 CANVAS patients, 316 were taking DPP-4 inhibitors and 95 were taking GLP-1 receptor agonists. At 18 weeks, canagliflozin 100 and 300 mg provided larger placebo-subtracted reductions (95% confidence interval) in HbA1c in patients taking DPP-4 inhibitors (-0.56% [-0.77, -0.35] and -0.75% [-0.95, -0.54], respectively) and GLP-1 receptor agonists (-1.00% [-1.35, -0.65] and -1.06% [-1.43, -0.69], respectively). Body weight and blood pressure (BP) reductions were seen with canagliflozin versus placebo in both subsets. Greater incidences of genital mycotic infections and osmotic diuresis-related adverse events (AEs) were seen with canagliflozin compared with placebo. Incidence of hypoglycaemia was numerically higher with canagliflozin versus placebo; nearly all occurred in patients on background insulin or insulin secretagogues. Conclusions: In patients on background incretin mimetics, canagliflozin improved HbA1c, body weight and BP, with an increased incidence of AEs related to SGLT2 inhibition.
    Diabetes Obesity and Metabolism 10/2015; DOI:10.1111/dom.12589 · 6.36 Impact Factor
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    ABSTRACT: Objective: To evaluate attainment of diabetes-related treatment goals with canagliflozin, a sodium glucose co-transporter 2 inhibitor, versus placebo in patients with type 2 diabetes mellitus (T2DM). Research design and methods: Data were pooled from four 26-week, placebo-controlled, Phase 3 studies of patients with T2DM (N = 2,313). Goal attainment with canagliflozin 100 and 300 mg versus placebo was evaluated in the overall population, and in subgroups based on age and sex, at baseline and Week 26. Clinical trial registration: ClinicalTrials.gov, NCT01081834, NCT01106677, NCT01106625, NCT01106690 Main Outcome Measures: Proportion of patients achieving hemoglobin A1C (A1C) <7.0% and ≤6.5%, systolic blood pressure (SBP) <140 and <130 mmHg, diastolic blood pressure (DBP) <90 and <80 mmHg, low-density lipoprotein cholesterol (LDL-C) <100 mg/dL (2.6 mmol/L), high-density lipoprotein cholesterol (HDL-C) ≥40 mg/dL (1.0 mmol/L), and the composite endpoint of A1C <7.0%, BP <130/80 mmHg, and LDL-C <100 mg/dL (2.6 mmol/L) at baseline and Week 26, and proportion with body weight reduction ≥5% at Week 26. Results: At baseline, similar proportions of patients met diabetes-related treatment goals across groups. At Week 26, a greater proportion of patients achieved A1C, SBP, DBP, and HDL-C goals with canagliflozin 100 and 300 mg compared with placebo. More patients achieved body weight reduction of ≥5% with canagliflozin 100 and 300 mg versus placebo at Week 26. Fewer patients had LDL-C <100 mg/dL (2.6 mmol/L) at Week 26 with canagliflozin 100 and 300 mg versus placebo. Canagliflozin 100 and 300 mg also provided better attainment of the composite endpoint of A1C <7.0%, BP <130/80 mmHg, and LDL-C <100 mg/dL (2.6 mmol/L) compared with placebo. Attainment of diabetes-related treatment goals was generally similar regardless of age and sex. Key limitations of this analysis include the selection of specific treatment targets that may not be reflective of all patient experiences, the non-prespecified, post hoc nature of the analysis, as well as the short duration of studies included in the pooled population. Conclusion: Canagliflozin was associated with better attainment of diabetes-related treatment goals compared with placebo, and was generally well tolerated at 26 weeks.
    Current Medical Research and Opinion 09/2015; 31(11):1-30. DOI:10.1185/03007995.2015.1082991 · 2.65 Impact Factor
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    ABSTRACT: Sodium-glucose transporter-2 (SGLT-2) inhibitors have emerged as novel oral glucose-lowering agents for type 2 diabetes. SGLT-2 inhibitors improve glycemic control by blocking sodium-glucose cotransport in the renal proximal tubules, thereby promoting glycosuria. In this review, it is discussed mechanistically how SGLT-2 inhibitors might be particularly relevant to use in patients with or at high risk for heart failure. On a daily base, SGLT-2 inhibitors block ~330–495 mEq sodium reabsorbed in the proximal tubules, although substantial amounts can be reabsorbed more distally in the nephron. Increased sodium offering to the distal nephron is sensed at the macula densa and may attenuate neurohumoral activation, thereby improving salt sensitivity, augmenting diuretic efficacy of loop and thiazide diuretics, and potentiating the native natriuretic peptide system. Whether the favorable profile offered by SGLT-2 inhibitors is renoprotective and whether SGLT-2 inhibition can relieve and/or prevent congestion beyond traditional diuretic drugs warrants further investigation.
    Current Cardiovascular Risk Reports 08/2015; 9(8). DOI:10.1007/s12170-015-0467-0
  • M Grundner · S Heller · C Mathieu · R Kapur · ML Wolden · B Zinman ·

    Diabetologie und Stoffwechsel 04/2015; 10(S 01). DOI:10.1055/s-0035-1549620 · 0.33 Impact Factor
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    ABSTRACT: Cytochrome oxidase (COX) dysfunction is associated with mitochondrial oxidative stress. We determined the association between COX expression, obesity and type 2 diabetes. COX4I1 and COX10 genes were measured in monocytes of 24 lean controls, 31 glucose-tolerant and 67 diabetic obese patients, and 17 morbidly obese patients before and after bariatric surgery. We investigated the effect of caloric restriction and PPAR agonist treatment on Cox in obese diabetic mice, and that of diet-induced insulin resistance in Streptozotocin-treated mice. Low COX4I1 was associated with type 2 diabetes in obese patients, adjusting for age, gender, smoking, and IL-6, and hs-CRP, all related to metabolic syndrome (Odds Ratio: 6.1, 95%CI: 2.3-16). In contrast, COX10 was low in glucose-tolerant and diabetic obese patients. In morbidly obese patients, COX4I1 was lower in visceral adipose tissue collected at bariatric surgery. In their monocytes, COX4I1 decreased after bariatric surgery, and low COX4I1 at 4 months was associated with metabolic syndrome at 7 years. In leptin-deficient obese diabetic mice, Cox4i1 was low in white visceral adipose tissue (n=13; P<0.001) compared to age-matched lean mice (n=10). PPARγ-agonist treatment (n=13) but not caloric restriction (n=11) increased Cox4i1 (P<0.001). Increase in Cox4i1 depended on increase in Glut4 expression and insulin sensitivity, independent of increase in blood adiponectin. In streptozotocin-treated mice (three groups of 7 mice, diet-induced insulin resistance decreased Cox4i1 and Glut4 (P<0.001 for both). COX4I1 depression is related to insulin resistance and type 2 diabetes in obesity. In peripheral blood monocytes it may be a diagnostically useful biomarker.International Journal of Obesity accepted article preview online, 14 April 2015. doi:10.1038/ijo.2015.58.
    International journal of obesity (2005) 04/2015; 39(8). DOI:10.1038/ijo.2015.58 · 5.00 Impact Factor
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    ABSTRACT: STAT-1 plays a crucial role in cytokine-induced beta-cell destruction. However, its precise downstream pathways have not been completely clarified. We performed a proteome analysis of cytokine-exposed C57Bl/6 and STAT-1(-/-) mouse islets and prioritized proteins for their potential in relation to type 1 diabetes (T1D). Differential proteins were identified using a combination of 2D-DIGE and MALDI-TOF/TOF analysis and were subjected to Ingenuity Pathway analysis (IPA). Protein-protein interaction networks were created and a phenome-interactome ranking of the differential proteins based on their assignment to T1D was performed. Numerous STAT-1-regulated proteins were identified and divided in different groups according to their biological function. The largest group of proteins was the one involved in protein synthesis and processing. Network analysis revealed a complex interaction between proteins from different functional groups and IPA analysis confirmed the protective effect of STAT-1 deletion on cytokine-induced beta-cell death. Finally, a central role in this STAT-1 regulated mechanism was assigned to small ubiquitin-related modifier 4 (SUMO4). These findings confirm a central role for STAT-1 in pancreatic islet inflammation-induced destruction and most importantly elucidate the underlying proteomic pathways involved. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    PROTEOMICS - CLINICAL APPLICATIONS 02/2015; 9(9). DOI:10.1002/prca.201400124 · 2.96 Impact Factor
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    ABSTRACT: Type 1 diabetes (T1D) is a chronic autoimmune disease characterised by excessive immune reactions against auto-antigens of pancreatic β-cells. Restoring auto-antigen tolerance remains the superior therapeutic strategy. Oral auto-antigen administration uses the tolerogenic nature of the gut-associated immune system to induce antigen-specific tolerance. However, due to gastric degradation, proper mucosal product delivery often imposes a challenge. Recombinant Lactococcus lactis have proven to be effective and safe carriers for gastrointestinal delivery of therapeutic products: L. lactis secreting diabetes-associated auto-antigens in combination with interleukin (IL)-10 have demonstrated therapeutic efficacy in a well-defined mouse model for T1D. Here, we describe the construction of recombinant L. lactis secreting the 65 kDa isoform of glutamic acid decarboxylase (GAD65) and tyrosine phosphatase-like protein ICA512 (IA-2), two major T1D-related auto-antigens. Attempts to secrete full size human GAD65 and IA-2 protein by L. lactis were unsuccessful. Trimming of GAD65 and IA-2 was investigated to optimise antigen secretion while maintaining sufficient bacterial growth. GAD65370-575 and IA-2635-979 showed to be efficiently secreted by recombinant L. lactis. Antigen secretion was verified by immunoblotting. Plasmid-derived GAD65 and IA-2 expression was combined in single strains with human IL-10 expression, a desired combination to allow tolerance induction. This study reports the generation of recombinant L. lactis secreting two major diabetes-related auto-antigens: human GAD65 and IA-2, by themselves or combined with the anti-inflammatory cytokine human IL-10. Prohibitive sequence obstacles hampering antigen secretion were resolved by trimming the full size proteins.
    Beneficial Microbes 01/2015; 6(4):1-11. DOI:10.3920/BM2014.0083 · 2.61 Impact Factor

  • C. Mathieu · Heller SR · R. Kapur · M. Lyng Wolden · B. Zinman ·
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    ABSTRACT: Aims: A prospective meta-analysis of phase 3 trials showed lower rates of nocturnal hypoglycaemia with insulin degludec vs. insulin glargine. We investigated the consistency of the results across different definitions of hypoglycaemia. Methods: This post-hoc, patient-level meta-analysis included six randomized, controlled, 26- or 52-week phase 3a trials in insulin-naïve participants with Type 2 diabetes mellitus (Type 2 diabetesinsulin naïve ), participants with Type 2 diabetes mellitus using basal-bolus therapy (Type 2 diabetesBB ) and those with Type 1 diabetes mellitus. We used three definitions of hypoglycaemia and different timescales for the nocturnal period. Rates were analysed for the entire core trial period, the 'maintenance period' only, and the extension trial set population. Analyses utilized a negative binomial regression model. Results: In Type 2 diabetesinsulin naïve participants, risk of nocturnal hypoglycaemia was significantly lower with insulin degludec vs. insulin glargine for all hypoglycaemia definitions and trial periods. Risk was also lower for the timescale 21.59-05.59, but not 00.01-07.59. For Type 2 diabetesBB , nocturnal hypoglycaemia rates were lower with insulin degludec vs. insulin glargine across all definitions, timescales and trial periods, with one exception. For individuals with Type 1 diabetes mellitus, nocturnal hypoglycaemia risk was significantly lower with insulin degludec during the maintenance period for the original definition (plasma glucose < 3.1 mmol/l, timescale 00.01-05.59) and in the extension trial set population for all hypoglycaemia definitions except for the nocturnal timescale 00.01-07.59. Conclusions: Compared with insulin glargine, insulin degludec is associated with lower rates of nocturnal hypoglycaemia in people with Type 2 diabetes mellitus, and similar or lower rates in Type 1 diabetes mellitus, across different definitions. This article is protected by copyright. All rights reserved.
    Diabetes 11/2014; 106:S109. DOI:10.1016/S0168-8227(14)70415-2 · 8.10 Impact Factor

  • Canadian Journal of Diabetes 10/2014; 38(5):S58-S59. DOI:10.1016/j.jcjd.2014.07.161 · 2.00 Impact Factor
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    ABSTRACT: Insulin degludec (IDeg) is a new basal insulin with an ultra‐long and stable glucose‐lowering effect. We compared once‐daily IDeg and insulin glargine (IGlar), both in combination with metformin ± dipeptidyl peptidase‐4 inhibitors, in a 52‐week, open‐label, treat‐to‐target trial in patients with type 2 diabetes followed by a 52‐week extension trial in which subjects [n = 725/1030 (70.4%)] maintained their initial randomised treatment. Health status was assessed at baseline and 105 weeks using the Short Form‐36 (SF‐36 v2) questionnaire. SF‐36 scores were analysed (ITT population) using anova, with adjustments for covariates. At 105 weeks, the overall physical component score was significantly better with IDeg versus IGlar [treatment contrast (TC): 1.1 (0.1; 2.1)95%CI, p 95% CI, p 95% CI, p Keywords: SF‐36; hypoglycaemia; insulin degludec; patient‐reported outcomes; quality of life; type 2 diabetes Document Type: Research Article DOI: http://dx.doi.org/10.1111/dom.12271 Publication date: September 1, 2014 $(document).ready(function() { var shortdescription = $(".originaldescription").text().replace(/\\&/g, '&').replace(/\\, '<').replace(/\\>/g, '>').replace(/\\t/g, ' ').replace(/\\n/g, ''); if (shortdescription.length > 350){ shortdescription = "" + shortdescription.substring(0,250) + "... more"; } $(".descriptionitem").prepend(shortdescription); $(".shortdescription a").click(function() { $(".shortdescription").hide(); $(".originaldescription").slideDown(); return false; }); }); Related content In this: publication By this: publisher In this Subject: Internal Medicine By this author: Rodbard, H. W. ; Cariou, B. ; Zinman, B. ; Handelsman, Y. ; Wolden, M. L. ; Rana, A. ; Mathieu, C. GA_googleFillSlot("Horizontal_banner_bottom");
    Diabetes Obesity and Metabolism 09/2014; 16(9). DOI:10.1111/dom.12271 · 6.36 Impact Factor
  • L Merker · B Zinman · J Vora · M Niemeyer · MA Gall · C Mathieu ·

    Diabetologie und Stoffwechsel 05/2014; 9(S 01). DOI:10.1055/s-0034-1375071 · 0.33 Impact Factor
  • Jo Hoste · Evis Daci · Chantal Mathieu ·
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    ABSTRACT: Aim: To assess the efficacy and safety of vildagliptin versus other oral glucose-lowering drugs added to antidiabetic monotherapy in Belgian patients with type 2 diabetes mellitus, in comparison to the global EDGE study results. Methods: This is a pre-specified post-hoc subanalysis of the Belgian patient cohort from a worldwide 1-year observational study that compared the effectiveness and tolerability of vildagliptin to other oral antidiabetic agents in type 2 diabetes patients failing monotherapy with oral glucose-lowering agents (EDGE). A total of 1793 Belgian patients were enrolled. Physicians could add any oral antidiabetic drug and patients entered either into the vildagliptin or the comparator cohort. The primary effectiveness and tolerability endpoint was defined as the proportion of patients having a treatment response (HbA1c reduction from baseline to month 12 endpoint >0·3%) without hypoglycemia, weight gain, peripheral oedema, or gastrointestinal side-effects. Results: In the Belgian population, 37·8% of patients in the vildagliptin group and 32·8% in the comparator group had a decrease in HbA1c of >0·3% without the predefined tolerability issues of hypoglycemia, weight gain, oedema or, gastrointestinal complaints (primary endpoint), resulting in an unadjusted odds ratio of 1·24 (95% CI: 0·96-1·61). Mean HbA1c change from baseline was -0·81% in the vildagliptin cohort and -0·75% in the comparator cohort. Overall, vildagliptin was well tolerated with similarly low incidences of total adverse events (14·9% versus 14·5% in the compactor group) and serious adverse events (2·7% versus 2·5% in the comparator group). Conclusion: In this EDGE subgroup of Belgian patients with type 2 diabetes who do not achieve the glycemic targets with monotherapy, a similar trend as in the global EDGE study was observed. Adding vildagliptin as a second oral glucose-lowering agent resulted in lowering HbA1c to <7% without weight gain, hypoglycemia or peripheral oedema in a higher proportion of patients than comparator oral antidiabetic drugs, with no differences in the reported number of adverse events.
    03/2014; 69(3):2295333714Y0000000018. DOI:10.1179/2295333714Y.0000000018
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    ABSTRACT: Apoptosis of pancreatic beta cells is a feature of type 2 diabetes and its prevention may have therapeutic benefit. High glucose concentrations induce apoptosis of islet cells, and this requires the proapoptotic Bcl-2 homology domain 3 (BH3)-only proteins Bim and Puma. We studied the stress pathways induced by glucotoxicity in beta cells that result in apoptosis. High concentrations of glucose or ribose increased expression of the transcription factor CHOP (C/EBP homologous protein) but not endoplasmic reticulum (ER) chaperones, indicating activation of proapoptotic ER stress signaling. Inhibition of ER stress prevented ribose-induced upregulation of Chop and Puma mRNA, and partially protected islets from glucotoxicity. Loss of Bim or Puma partially protected islets from the canonical ER stressor thapsigargin. The antioxidant N-acetyl-cysteine also partially protected islets from glucotoxicity. Islets deficient in both Bim and Puma, but not Bim or Puma alone, were significantly protected from killing induced by the mitochondrial reactive oxygen species donor rotenone. Our data demonstrate that high concentrations of glucose induce ER and oxidative stress, which causes cell death mediated by Bim and Puma. We observed significantly higher Bim and Puma mRNA in islets of human donors with type 2 diabetes. This indicates that inhibition of Bim and Puma, or their inducers, may prevent beta-cell destruction in type 2 diabetes.
    Cell Death & Disease 03/2014; 5(3):e1124. DOI:10.1038/cddis.2014.88 · 5.01 Impact Factor
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    ABSTRACT: Two treatment strategies were compared in patients with type 2 diabetes (T2DM) on basal insulin requiring intensification: addition of once-daily (OD) liraglutide (Lira) or OD insulin aspart (IAsp) with largest meal. Subjects completing 104 weeks (52-week main trial BEGIN ONCE LONG + 52-week extension) on insulin degludec (IDeg) OD + metformin with HbA1c ≥7.0% [≥53 mmol/mol] were randomized to IDeg+Lira (n = 88, mean HbA1c: 7.7% [61 mmol/mol]) or IDeg+IAsp (n = 89, mean HbA1c: 7.7%) for 26 weeks, continuing metformin. Subjects completing 104 weeks with HbA1c <7.0% continued IDeg + metformin in a third, non-randomized arm (n = 236). IDeg+Lira reduced HbA1c (-0.74%-points) significantly more than IDeg+IAsp (-0.39%-points); estimated treatment difference (IDeg+Lira-IDeg+IAsp) -0.32%-points [-0.53; -0.12]95% CI ; p = 0.0024. More IDeg+Lira (49.4%) than IDeg+IAsp (7.2%) subjects achieved HbA1c <7.0% without confirmed hypoglycaemia (plasma glucose <3.1 mmol/l [<56 mg/dl] or severe hypoglycaemia) and without weight gain; estimated odds ratio (IDeg+Lira/IDeg+IAsp) 13.79 [5.24; 36.28]95% CI ; p < 0.0001. IDeg+Lira subjects had significantly less confirmed and nocturnal confirmed hypoglycaemia, and significantly greater weight loss (-2.8 kg) versus IDeg+IAsp (+0.9 kg); ETD (IDeg+Lira-IDeg+IAsp) -3.75 kg [-4.70; -2.79]95% CI ; p < 0.0001. Other than more gastrointestinal side effects with IDeg+Lira, no safety differences occurred. Durability of IDeg was established in the non-randomized arm, as mean HbA1c remained <7.0% (mean 6.5% [48 mmol/mol] at end-of-trial). IDeg+Lira improved long-term glycaemic control, with weight loss and less hypoglycaemia versus adding a single daily dose of IAsp in patients with T2DM inadequately controlled with IDeg + metformin.
    Diabetes Obesity and Metabolism 01/2014; 16(7). DOI:10.1111/dom.12262 · 6.36 Impact Factor
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    ABSTRACT: Type 1 diabetes is due to destruction of pancreatic β-cells. Lysine deacetylase inhibitors (KDACi) protect β-cells from inflammatory destruction in vitro and are promising immunomodulators. Here we demonstrate that the clinically well-tolerated KDACi vorinostat and givinostat revert diabetes in the nonobese diabetic (NOD) mouse model of type 1 diabetes and counteract inflammatory target cell damage by a mechanism of action consistent with transcription factor-rather than global chromatin-hyperacetylation. Weaning NOD mice received low doses of vorinostat and givinostat in their drinking water until 100-120 d of age. Diabetes incidence was reduced by 38% and 45%, respectively, there was a 15% increase in the percentage of islets without infiltration, and pancreatic insulin content increased by 200%. Vorinostat treatment increased the frequency of functional regulatory T-cell subsets and their transcription factors Gata3 and FoxP3 in parallel to a decrease in inflammatory dendritic cell subsets and their cytokines IL-6, IL-12, and TNF-α. KDACi also inhibited LPS-induced Cox-2 expression in peritoneal macrophages from C57BL/6 and NOD mice. In insulin-producing β-cells, givinostat did not upregulate expression of the anti-inflammatory genes Socs1-3 or sirtuin-1 but reduced levels of IL-1β + IFN-γ-induced proinflammatory Il1a, Il1b, Tnfα, Fas, Cxcl2, and reduced cytokine-induced ERK phosphorylation. Further, NF-κB genomic iNos promoter binding was reduced by 50%, and NF-κB-dependent mRNA expression was blocked. These effects were associated with NF-κB subunit p65 hyperacetylation. Taken together, these data provide a rationale for clinical trials of safety and efficacy of KDACi in patients with autoimmune disease such as type 1 diabetes.
    Proceedings of the National Academy of Sciences 01/2014; 111(3). DOI:10.1073/pnas.1320850111 · 9.67 Impact Factor
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    ABSTRACT: Improvements in the clinical condition of patients with type 2 diabetes are often accompanied by improvements in health-related quality of life and other patient-reported outcomes (PROs), but data assessing injectable treatment initiation from the patient's perspective in routine clinical practice are lacking. We examined PROs in patients initiating injectable treatment in the CHOICE (CHanges to treatment and Outcomes in patients with type 2 diabetes initiating InjeCtablE therapy) study. CHOICE was a 24-month, prospective observational study conducted in six European countries. Patients initiated exenatide twice daily (BID) or insulin based on a physician's clinical judgement. Clinical and PRO data were collected at baseline (injectable therapy initiation) and after approximately 3, 6, 12, 18 and 24 months. The two treatment cohorts had different baseline characteristics; therefore, no statistical comparisons of endpoints between main cohorts were conducted. There were 2388 patients eligible for analysis (exenatide BID cohort, n = 1114; insulin cohort, n = 1274). Mean positive changes in Impact of Weight on Quality of Life-Lite (IWQOL-Lite) total score and EuroQoL5-Dimension (EQ-5D) index and visual analogue scale (VAS) scores were observed in both cohorts with most changes observed during the first 6 months after injectable therapy initiation. Patients who experienced weight loss (>=1 kg) at 24 months appeared to have higher mean improvements in IWQOL-Lite total score than did patients with weight gain or no weight change. Patients who met the composite clinical endpoint of glycated haemoglobin (HbA1c) <7.0%, no weight gain (<=1 kg) and no hypoglycaemia generally experienced higher mean improvements in EQ-5D index and VAS scores (compared with patients who did not meet this endpoint) and Diabetes Health Profile-18 scores (versus the main cohorts). High levels of missing data were observed for all PRO measures in both cohorts compared with those for clinical outcomes. These data from a clinical practice study support those from clinical trials, suggesting that PROs are not adversely affected, and may be improved, by injectable therapy initiation. PRO data may aid appropriate treatment selection for individual patients.Trial registration: ClinicalTrials.gov, NCT00635492.
    Health and Quality of Life Outcomes 12/2013; 11(1):217. DOI:10.1186/1477-7525-11-217 · 2.12 Impact Factor
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    ABSTRACT: There is lack of consensus concerning the best screening strategy for gestational diabetes (GDM). The aim of our survey was therefore to investigate attitudes and practices of all obstetrical centers in the northern part of Belgium regarding screening for pregestational diabetes in early pregnancy and screening for GDM. We also aimed to identify the penetrance of the 'International Association of Diabetes in Pregnancy Study Groups' (IADPSG) screening strategy for GDM. The survey was conducted from May 2012 till January 2013. The survey was distributed to every obstetrical center in the northern part of Belgium by email and/or mail with reminders by phone and personal contact. From the 65 obstetrical centers, 69% responded. Of all centers, 27% had a structured database on the number of women with GDM. Of all centers, 82% screened for pregestational diabetes in early pregnancy and 56% of centers screened for GDM before 24 weeks. Screening before 24 weeks was mostly based on risk factors. Screening for GDM after 24 weeks, was done universally in 87% of centers. The mean estimated prevalence of GDM was 7 ± 5%. The most commonly used screening strategy was a two-step approach with a glucose challenge test (GCT) and 100 g oral glucose tolerance test (OGTT), used by 56% of centers, with 23 centers using the Carpenter & Coustan criteria. The 75 g OGTT with the IADPSG criteria was used by 33% of centers but 4 of these centers still used a GCT before proceeding to the full OGTT. This survey demonstrates that in the northern part of Belgium, there still is a large variation in screening strategy for pregestational diabetes in early pregnancy and GDM. Only 25% of centers have already implemented the one-step IADPSG screening strategy.
    Diabetology and Metabolic Syndrome 11/2013; 5(1):66. DOI:10.1186/1758-5996-5-66 · 2.17 Impact Factor
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    ABSTRACT: 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3), and its analogs (i.e. 14,20-bis-epi-19-nor-23-yne-1α,25(OH)2D3 - TX527) have been shown to prevent autoimmunity and prolong islet graft survival in the non-obese diabetic (NOD) mouse. Their effects are mediated by their action on various immune cell types, such as dendritic cells (DC) and T cells. We have previously reported important direct effects of TX527 on human T cells, on their cytokine/chemokine profiles, T regulatory cell markers, homing characteristics and chemotaxis. In order to fully understand the molecular mechanisms underlying the beneficial properties of TX527 on human T cells, we applied here 2-dimensional difference gel electrophoresis (2-D DIGE) to analyze the global protein alterations induced by TX527 on human synchronized T cells. We detected differential expression of 64 protein spots upon TX527 treatment, of which 65.6% could be successfully identified using tandem mass spectrometry (MALDI-TOF/TOF). The identified proteins function in various processes, such as metabolism and energy pathways, cytoskeleton and protein metabolism. When comparing the proteomics data to our previously performed microarray data on the same set of cells, we found an overlap of 17 different mRNAs/proteins. For some of these (e.g. PSME2, HSPA8), the direction of regulation was not similar, hereby reinforcing the important role of post-transcriptional/translational processes in the functionality of proteins. In addition, although 2-D DIGE offers the possibility of picking up post-translational processes, it lacks the ability to detect molecules with extreme molecular weight (MW) and isoelectrical point (pI) values, or very low abundant/hydrophobic proteins. This study highlights therefore the importance of combining different experimental approaches to obtain a complete picture of the underlying mechanisms and general processes being affected in T cells upon TX527 treatment. These processes lead altogether to the generation of T cells with interesting immunomodulatory features for clinical applications in the treatment of autoimmune diseases or in the prevention of graft rejection.
    The Journal of steroid biochemistry and molecular biology 10/2013; 144. DOI:10.1016/j.jsbmb.2013.10.013 · 3.63 Impact Factor
  • Katrien Benhalima · Chantal Mathieu ·
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    ABSTRACT: To review recently published studies examining new data on screening strategies and diagnostic criteria for gestational diabetes (GDM). Professional organizations continue to have differing recommendations concerning the best screening strategy for GDM. An independent expert panel appointed by the National Institutes of Health has recently recommended to continue with the two-step approach for screening. Recent evidence shows that the glucose challenge test seems acceptable to screen for GDM but that an Hba1c measurement is not a good alternative. The International Association of Diabetes and Pregnancy Study Groups (IADPSG) screening strategy remains controversial with studies showing a high inconsistency in associations with adverse pregnancy outcome and cost-effectiveness analyses show conflicting results. To reduce the number of oral glucose tolerance tests needed, clinical prediction models may be implemented. It is now generally accepted that, especially in high-risk women, overt diabetes should be excluded at first prenatal visit. However, internationally the debate on the best screening strategy for GDM continues. In most populations the implementation of the IADPSG screening strategy will lead to an important increase in the prevalence of GDM and associated costs and workload. Risk stratification in IADPSG-positive women may reduce over-treatment. Using clinical prediction models may be a more cost-effective alternative.
    Current opinion in obstetrics & gynecology 10/2013; 25(6). DOI:10.1097/GCO.0000000000000028 · 2.07 Impact Factor

Publication Stats

6k Citations
732.97 Total Impact Points


  • 1993-2014
    • University of Leuven
      • Laboratory for Experimental Medicine and Endocrinology (LEGENDO)
      Louvain, Flanders, Belgium
  • 2013
    • Leuven University College
      Louvain, Flemish, Belgium
  • 1995-2013
    • Universitair Ziekenhuis Leuven
      • • Department of Endocrinology
      • • Department of Psychiatry
      Louvain, Flanders, Belgium
  • 1998-2012
    • Catholic University of Louvain
      • Department of Surgery - CHIR
      Лувен-ла-Нев, Walloon, Belgium
  • 1997-2008
    • The Catholic University of America
      Washington, Washington, D.C., United States
  • 2001
    • Vrije Universiteit Brussel
      Bruxelles, Brussels Capital Region, Belgium