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J Timsit

Publications and source records attributed to J Timsit.

At least 19 recordsLinked to original sources
PubMed2006

Elevation of CKP induced by ezetimibe in monotherapy: report on two cases.

Few cases of myopathy have been reported in patients treated with ezetimibe as monotherapy or in association with a statin. We report on two cases of elevation of CKP that occurred upon monotherapy with ezetimibe, which were reversible after discontinuation of the drug. In both cases, patients previously experienced intolerance with other lipid-lowering agents. The pathogenesis of muscle toxicity associated with ezetimibe is not known yet. An interaction with statin or a toxicity mechanism common to several lipid-lowering drugs have been suggested. A potential role of induction of glucuronidation by numerous associated drugs can also be involved Although association of ezetimibe with myopathy seems to be uncommon, special attention should be given to patients treated with ezetimibe who had a previous intolerance to other lipid-lowering drugs and who received several drugs.

Anticholesteremic Agents↗
PubMed2006

Rectal lymphogranuloma venereum surveillance in France 2004-2005.

Lymphogranuloma venereum (LGV) is a sexually transmitted infection (STI) caused by Chlamydia trachomatis strains belonging to the L1, L2 or L3 genotype. An alert about an outbreak of LGV among MSM in the Netherlands was published in January 2004. The first cases of rectal LGV in France were retrospectively diagnosed in March 2004 and sentinel surveillance for LGV was implemented in April 2004. Most of the participating centres were located in the cities of Paris and Bordeaux. Only confirmed rectal LGV cases were included in the surveillance. Rectal specimens from men that were found to be positive for C trachomatis by PCR were sent to the National Reference Centre for Chlamydia infection for genotyping. Simple epidemiological data provided by clinicians and genotyping results were sent to the Institut de Veille Sanitaire (InVS) where data were anonymously recorded. A total of 328 C. trachomatis rectal strains isolated in men were genotyped by the end of December 2005. Of these, 244 (74%) were LGV strains belonging to the L2 genotype. No L1 or L3 C. trachomatis genotype was found. Diagnosis was made retrospectively for 46 cases. The median age of patients with LGV was 39 years. HIV status was known for 96 patients: 82/96 (85%) were HIV-infected. Most LGV cases were diagnosed in the Paris area (92%). Among the remaining 26% C. trachomatis strains, genotypes Da and G were the most frequent. As with syphilis in recent years, the emergence of LGV in Europe is mainly affecting HIV-infected MSM. The screening and treatment of STIs should be included in the clinical follow-up of all HIV-infected MSM.

Adult↗
PubMed2005

Stress myocardial scintigraphy and dobutamine echocardiography in the detection of coronary disease in asymptomatic patients with type 2 diabetes.

OBJECTIVE: The aims of this prospective study were: (1) to compare stress thallium-201 single photon emission computed tomography (SPECT) and dobutamine echocardiography (DE) in the detection of silent myocardial ischemia (SMI) in asymptomatic high risk diabetic patients; (2) to analyse long-term outcome after intensive care of SMI in these patients. METHODS: SPECT was performed in 100 high risk diabetic patients and DE in the first 75 patients. Coronary angiography was realized in patients with SMI, with revascularization for suitable lesions. Intensive treatment of atherosclerosis risk factors was performed in all patients. Patients were followed 2 +/- 0.5 years for the subsequent occurrence of cardiac death, myocardial infarction and revascularization. RESULTS: SMI was detected by SPECT in 62% and by DE in 10% of the patients (p < 0.0001), whereas significant coronary stenosis at angiography was detected by SPECT in 26% and by DE in 5% of the patients (p < 0.02). Independent predictive factors of significant coronary stenosis were male gender (p < 0.03) and peripheral arterial disease (p < 0.007). Nonfatal acute coronary syndrome occurred during follow-up in 2 patients (2%). Subsequent revascularization procedure was needed in 9 patients. Baseline patients' characteristics, as well as SMI, were not predictive of cardiac event during follow up. CONCLUSION: SPECT seems more accurate than DE to detect significant coronary stenosis in high risk asymptomatic diabetic patients. In this population, aggressive treatment of SMI with systematic revascularization combined with intensive care of risk factors is associated with a favorable long-term prognosis, similar in diabetic patients with and without initial SMI.

Adrenergic beta-Agonists↗
PubMed2005

Factors associated with virological response in HIV-infected patients failing antiretroviral therapy: a prospective cohort study.

OBJECTIVES: To assess the antiviral response to optimized therapy following genotypic resistance testing and to identify factors associated with virological response in HIV-1-infected patients failing antiretroviral therapy. METHODS: A prospective cohort study was conducted in 344 HIV-1-infected patients who underwent genotypic resistance testing because of virological failure. Virological response was defined as a plasma HIV RNA level below 200 HIV-1 RNA copies/mL or a drop of plasma viral load from baseline of more than 1 log10. A multivariate logistic regression analysis was performed to identify factors associated with virological response. RESULTS: The median age of the patients was 40 years, with a male to female ratio of 4:1. Fifty-one per cent of patients had received the three major classes of antiretrovirals and the median duration of previous antiretroviral therapy was 4.6 years. At baseline, the median plasma HIV RNA level was 4.4 log10 copies/mL and the median CD4 cell count was 274 cells/microL. At 3 months, 55% of patients (188 of 344) had a virological response, which was sustained at 6 months (53%). Predictors of virological response were exposure to two or fewer protease inhibitors [odds ratio (OR) 1.8; P=0.046], and use in optimized therapy of a new class of antiretrovirals (OR 2.9; P=0.006), of more than two new drugs (OR 3.0; P<0.0001), of abacavir (OR 1.9; P=0.03), or of lopinavir/ritonavir (OR 3.7; P=0.0002). CONCLUSIONS: A high proportion of patients achieved a short-term virological response in this cohort study. Patients with the least experience of protease inhibitor treatment and in whom a new class of antiretroviral, more than two new drugs, abacavir or lopinavir/ritonavir was used in optimized therapy had the best virological outcome.

Adult↗
PubMed2004

The Gly482Ser polymorphism in the peroxisome proliferator-activated receptor-gamma coactivator-1 gene is associated with hypertension in type 2 diabetic men.

AIMS/HYPOTHESIS: Peroxisome proliferator-activated receptor-gamma coactivator-1 (PPARGC1) acts as a cofactor for several nuclear hormone receptors in many tissues and organs implicated in blood pressure regulation. Here, we assessed the association between the Gly482Ser variant of PPARGC1 and the arterial hypertension frequently found in subjects with type 2 diabetes. METHODS: We studied a group of 479 men and 253 women with type 2 diabetes. Arterial hypertension was present in 70% of the men and in 73% of the women. Genotypes were examined by PCR restriction fragment length polymorphism. A logistic regression analysis was performed to assess the covariables associated with arterial hypertension. RESULTS: There was an association between Ser allele homozygosis and arterial hypertension in type 2 diabetic men (odds ratio of 2.52 vs Gly allele homozygosis; 95% CI: 1.32-5.00; p=0.0064), but not in women. The prevalence of arterial hypertension in type 2 diabetic men was 77% vs 73% vs 67% for Ser-Ser, Gly-Ser and Gly-Gly carriers respectively (p=0.021). Age, BMI, the use of insulin, and triglyceride and creatinine levels were also independently associated with arterial hypertension in this cohort. CONCLUSIONS/INTERPRETATION: We have observed a sex-specific association between the PPARGC-1 gene Gly482Ser polymorphism and arterial hypertension in type 2 diabetic men. Further studies are needed to investigate the genetic, biochemical and pathophysiological basis of this allelic association.

Amino Acid Substitution↗
PubMed2004

Heterogeneity of diabetes phenotype in patients with 3243 bp mutation of mitochondrial DNA (Maternally Inherited Diabetes and Deafness or MIDD).

OBJECTIVE: In patients with maternally inherited diabetes and deafness (MIDD), due to 3 243 A > G mutation of mitochondrial DNA (mtDNA), diabetes may present with variable phenotypes. OBJECTIVE: To ascertain the existence of two distinct phenotypes, MIDD1 and MIDD2, in a series of patients with MIDD. DESIGN: Multicenter prospective study. PATIENTS: 77 patients with diabetes and the mtDNA 3243 mutation and 139 control patients with type 1 (T1D) or type 2 (T2D) diabetes, matched according to initial presentation of diabetes, age at onset, sex, and duration of diabetes (24 T1D and 115 T2D, including 55 treated with insulin). MEASUREMENTS: Anthropometric characteristics (height, body weight, body mass index [BMI], sex), family history of diabetes, and characteristics of diabetes (age at onset, treatment, hemoglobin A1c [HbA1c]), extrapancreatic manifestations. RESULTS: In 13 cases (17%, MIDD1), diabetes presented as insulin-dependent from the onset, with ketoacidosis in 6 cases. In 64 cases (83%, MIDD2), diabetes resembled T2D, and was treated with diet in 12 cases, oral hypoglycemic agents in 21 cases, or insulin in 31 cases. Compared with patients with MIDD2, patients with MIDD1 were characterized by lower age at onset of first manifestation of MIDD (25.4 +/- 9.6 vs 33.7 +/- 13.2 Years, P<0.0005), lower body weight (49.1 +/- 7.4 vs 56.3 +/- 10.9 kg, P<0.0025), lower BMI (18.2 +/- 2.3 vs 20.9 +/- 3.6 kg/m2, P<0.0005), and higher HbA1c levels (9.5 +/- 2.0 vs 7.5 +/- 1.6%, P<0.0005). Frequency of family history of diabetes and of extrapancreatic manifestations was the same in both MIDD subtypes. No difference was found within the MIDD2 subtype when comparing patients treated with or without insulin. Compared with matched controls, patients with MIDD had a lower BMI (MIDD1/T1D 18.2 +/- 2.3 vs 24.0 +/- 3.6 kg/m2 and MIDD2/T2D 20.9 +/- 3.6 vs 30.2 +/- 5.9 kg/m2, P<0.0025). Lastly, male patients with MIDD had a shorter height than controls (MIDD1/T1D: 166.1 +/- 3.2 vs 177.3 +/- 6.6 cm and MIDD2/T2D: 168.4 +/- 7.2 vs 173.6 +/- 6.6 cm P<0.025). CONCLUSIONS: These results confirm the existence of two different phenotypes in MIDD, MIDD1 and MIDD2, which may be related to the severity of the mitochondrial disease. The role of other genetic and/or environmental factors in the variable phenotype of MIDD remains to be elucidated.

Adult↗
PubMed2004

Cumulative adverse effects of diabetes mellitus and hypertension on coronary flow velocity reserve.

BACKGROUND: this study aimed to assess the hypothesis that essential hypertension (EH) may increase coronary microcirculation dysfunction in patients with type 2 diabetes mellitus (DM). Microvascular dysfunction has been reported in patients with DM or EH. Discordant results have been reported on cumulative adverse effects of the simultaneous presence of DM and EH on coronary flow velocity reserve (CFR). METHODS: CFR were compared in 13 hypertensive diabetics (group 1), 12 normotensive diabetics (group 2), 11 hypertensive non diabetics (group 3) and 29 normotensive non diabetic patients (group 4). CFR was calculated using an intracoronary Doppler-tipped flow wire. RESULTS: CFR was significantly lower in patients with both DM and EH (2.2 +/- 0.4 in group 1 vs 2.8 +/- 0.5, 2.8 +/- 0.6 and 2.9 +/- 0.7 in groups 2, 3 and 4 respectively, p<0.01). The presence of hypertension reduced CFR in diabetic patients with angiographically abnormal but unobstructed coronary arteries (2.1 +/- 0.3 in hypertensive vs 3.1 +/- 0.2 in normotensive diabetic patients, p<0.02). No cumulative adverse effect was observed in diabetics with angiographically normal coronary arteries (2.3 +/- 0.6 in hypertensive vs 2.6 +/- 0.5 in normotensive diabetic patients, NS). Multivariate analysis revealed that combination of DM and EH (p<0.007) was independently related to CFR. CONCLUSIONS: the presence of hypertension appears to worsen coronary microangiopathy in diabetic patients with unobstructed coronary artery disease. The cumulative effect of EH and DM on CFR impairment has consequences for decision-making during coronary angioplasty and could identify patients at risk for cardiomyopathy.

Blood Flow Velocity↗
PubMed2003

Alexithymia in insulin-dependent diabetes mellitus is related to depression and not to somatic variables or compliance.

OBJECTIVES: To assess the prevalence of alexithymia in insulin-dependent diabetic mellitus (IDDM) outpatients. To examine whether alexithymia is associated with diabetic somatic variables, depression, and compliance. METHOD: Our sample comprised 69 diabetic outpatients followed in a university hospital. We assessed the prevalence of alexithymia (26-item Toronto Alexithymia Scale, TAS-26) and the relationships among alexithymia, depression (13-item Beck Depression Inventory, BDI-13), somatic diabetic variables (glycosylated hemoglobin, number of mild or severe hypoglycemia, somatic complications), and compliance (observer-rater scale completed by diabetologist). RESULTS: The prevalence of alexithymia in IDDM patients was low (14.4%). Alexithymia and depression, as measured by TAS-26 and BDI-13 scores, respectively, correlated with each other. Alexithymia was not correlated with glycemic control, somatic complications, or compliance. CONCLUSION: In our sample, alexithymia was related to depression and not to somatic factors or compliance.

Adult↗
PubMed2002

Fetal macrosomia and maternal weight gain during pregnancy.

BACKGROUND: To calculate an adjusted maternal weight gain during pregnancy including infant and placental weights to the actual weight gain and secondarily examine its influence on the occurrence of fetal macrosomia. METHODS: The corrected weight gain was calculated as follows: maternal body weight at the last prenatal visit - (pregravid body weight + birth weight + placental weight) in 259 women (65 with type 1 diabetes, 69 with gestational diabetes mellitus, and 125 controls). RESULTS: Although weight gain was greater in non obese normal glucose tolerant and type 1 diabetic mothers of macrosomic infants, the difference was no longer significant when using corrected maternal weight gain. The correlation between birth weight and maternal weight gain decreased when using this index. CONCLUSION: The corrected weight gain is a better estimate of true accretion of maternal weight. Our results suggest that recommendations for weight gain during pregnancy should take this index into account.

Adult↗
PubMed2001

Maternally inherited diabetes and deafness: a multicenter study.

BACKGROUND: Maternally inherited diabetes and deafness (MIDD), which is seen in 0.5% to 2.8% of patients with type 2 diabetes mellitus, is related to a point mutation at position 3243 of mitochondrial (mt) DNA. Its clinical description is incomplete. OBJECTIVE: To study the clinical presentation and complications of diabetes in patients with MIDD and to identify clinical characteristics that may help select diabetic patients for mtDNA mutation screening. DESIGN: Multicenter prospective descriptive study. SETTING: 16 French departments of internal medicine, diabetes and metabolic diseases, or both. PATIENTS: 54 patients with type 2 diabetes mellitus and the mtDNA 3243 mutation. MEASUREMENTS: Characteristics of diabetes, metabolic control (glycosylated hemoglobin level), complications of diabetes, and involvement of other organs. RESULTS: On average, patients with MIDD were young at diabetes onset and presented with a normal or low body mass index. None were obese. Seventy-three percent of probands had a maternal family history of diabetes. Diabetes was non-insulin-dependent at onset in 87% of patients; however, 46% of patients had non-insulin-dependent disease at onset but progressed to insulin therapy after a mean duration of approximately 10 years. Neurosensory hearing loss was present in almost all patients. Eighty-six percent of patients who received an ophthalmologic examination had macular pattern dystrophy (a specific retinal lesion). Forty-three percent of patients had myopathy, 15% had cardiomyopathy, and 18% (9 of 51) had neuropsychiatric symptoms. Although the prevalence of diabetic retinopathy was 8% among patients who received an ophthalmologic examination, lower than expected after a mean 12-year duration of diabetes, prevalence of kidney disease was 28%. This suggests that a specific renal involvement was the result of mitochondrial disease. CONCLUSIONS: Maternally inherited diabetes and deafness has a specific clinical profile that may help identify diabetic patients for mtDNA testing.

Adolescent↗
PubMed2001

A dinucleotide repeat polymorphism at the poly(ADP-ribose) polymerase gene is not associated with predisposition to type 1 diabetes in French Caucasians.

The poly (ADP-ribose) polymerase (PARP) is a nuclear enzyme that detects and binds DNA strand breaks. Excessive PARP activation leads to the death of mice islet beta-cells by depleting cellular energy reserves. On the other hand, PARP-mutant mice are resistant to streptozotocine-induced diabetes, and in the non-obese diabetic (NOD) mouse model, treatment with nicotinamide, a PARP inhibitor, protects islet cells against cytotoxic actions in vitro and results in a decreased incidence of type 1 diabetes. PARP gene in human is located within a recently identified type 1 diabetes-susceptibility region on chromosome 1q41-42, and contains a polymorphic CA dinucleotide repeat in the promoter region. To consider the putative involvement of PARP polymorphism in predisposition to type 1 diabetes, we performed genotyping for the various alleles of the CA dinucleotide repeat in 158 unrelated French Caucasian patients with type 1 diabetes and 193 ethnically-matched healthy controls. We found no significant difference of PARP alleles distribution between patients and controls, even after stratification of the patients according to HLA class II genotype or to age at disease onset. Our results suggest that this PARP polymorphism does not influence susceptibility to type 1 diabetes in French Caucasians.

Adolescent↗
PubMed2001

Variations in the vitamin D-binding protein (Gc locus) and risk of type 2 diabetes mellitus in French Caucasians.

Electrophoretic variants of the vitamin D-binding protein (DBP) have been reported to be associated with type 2 diabetes mellitus (DM) or with prediabetic phenotypes in several non-Caucasian populations. Two frequent missense polymorphisms at codons 416 (Asp --> Glu) and 420 (Thr --> Lys) are the genetic basis for the 3 common electrophoretic variants of DBP (Gc1F, Gc1S, and Gc2) and the resulting circulating phenotypes (Gc1F/Gc1F, Gc1F/Gc1S, Gc1S/Gc1S, Gc1F/Gc2, Gc1S/Gc2, and Gc2/Gc2). In this study, we investigated the association of these polymorphisms with type 2 DM in French Caucasian subjects. Variations at codons 416 and 420 were examined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Allele frequencies at both codons did not differ in type 2 DM patients and in control subjects (Asp416: 42.4% v 46.2%, respectively, P =.33; Lys420: 25.5% v 29.0%, respectively, P =.31). Distribution of genotypes at both codons, of the haplotypes defined by the 2 codons, and of the DBP phenotypes defined by the haplotypes were also similar in diabetic and control subjects. In conclusion, our study suggests that genetic variants of the DBP gene are not associated with the susceptibility to type 2 DM in French Caucasians.

Adult↗
PubMed2001

Vitamin D receptor gene polymorphisms are associated with obesity in type 2 diabetic subjects with early age of onset.

OBJECTIVE: Allelic variations in the vitamin D receptor (VDR) gene were reported to modulate insulin secretion in response to glucose. VDR was investigated as a candidate gene for type 2 diabetes mellitus (T2DM). METHOD: Four single nucleotide polymorphisms (SNPs) in intron 8 (BsmI, Tru9I, ApaI) and exon 9 (TaqI) of the VDR gene were examined in 309 unrelated French subjects with T2DM and 143 controls. RESULTS: The distribution of alleles and genotypes of the four SNPs was similar in patients and controls. However, in patients whose age at diagnosis of diabetes was < or =45 years, homozygous subjects for the T-allele of the TaqI SNP had a higher body mass index (BMI) (31.7+/-6.7 kg/m2, P=0.0058) and an increased prevalence of obesity (81%, P=0.005) with respect to heterozygous subjects (27.9+/-5.0 kg/m2; 46%) or homozygous subjects for the t-allele (27.7+/-5.0 kg/m2; 52%). Similar results were observed for homozygous subjects for the b-allele of the BsmI SNP. Logistic regression analysis demonstrated that TT homozygosity was independently associated with obesity in these subjects (odds ratio, 4.64; 95% confidence interval (CI), 1.64-14.76; P=0.0056). CONCLUSION: VDR is not a major gene for T2DM in French Caucasians. However, polymorphisms in the VDR gene are associated with the susceptibility to obesity in subjects with early-onset T2DM. The pathophysiological mechanisms of these associations remain unexplained, but they could be related to a direct effect of vitamin D in adypocyte differentiation and metabolism, or to an indirect effect by modulation of insulin secretion.

Age of Onset↗
PubMed2001

A common stromal cell-derived factor-1 chemokine gene variant is associated with the early onset of type 1 diabetes.

Type 1 diabetes results from the autoimmune destruction of pancreatic beta-cells. Although the disease shows a strong association with HLA class II alleles, other genes may influence the initiation or the rate of progression of the autoimmune process. The recruitment of mononuclear cells within the islets of Langerhans is a critical step in the pathogenesis of the disease. Because chemokines are cytokines that promote migration of mononuclear cells, we hypothesized that polymorphisms in chemokine receptor or chemokine genes, CCR5 and SDF1, may be involved in susceptibility to or clinical expression of type 1 diabetes. The frequencies of the CCR5-delta32 and SDF1-3'A (801G-->A in the 3' untranslated region) variants were similar in 208 unrelated Caucasian patients with type 1 diabetes and in 120 Caucasian control subjects. They were not modified after stratification for the predisposing HLA-DR3 and -DR4 haplotypes. However, the SDF1-3'A variant was strongly associated with early onset (< 15 years) of the disease (odds ratio 2.6, P = 0.0019). On average, the presence of the SDF1-3'A allele was associated with a 5-year reduction in the age at onset of diabetes (P = 0.0067). Our results suggest that stromal cell-derived factor-1 may be implicated in the aggressiveness of the autoimmune process leading to type 1 diabetes. These preliminary data require replication in other populations.

3' Untranslated Regions↗
PubMed2001

Heterogeneity of fetal growth in type 1 diabetic pregnancy.

OBJECTIVE: To investigate the frequency of macrosomia in an homogeneous cohort of type 1 diabetic mothers and to analyze the influence of maternal factors and glycemic control on the incidence of fetal macrosomia. MATERIAL AND METHODS: Fifty-five consecutive type 1 diabetic first-pregnancies were prospectively studied. Macrosomia was defined by a ponderal index above the 90(th) percentile. Venous cord blood levels of insulin, C peptide and leptin were measured at delivery. The influence of HbA1c levels and other maternal variables on the occurrence of macrosomia and on the ponderal index was assessed using a stepwise regression logistic model. RESULTS: The mean (+/- SD) birth weight was 3482 (+/- 497) g at 37.4 +/- 1.0 weeks gestation. Macrosomia occurred in 29 cases (53.7%). Fetal insulin, C peptide and leptin levels were significantly higher in macrosomic than in non macrosomic infants. Maternal age, duration of diabetes, pregravid body mass index, parity, weight gain during pregnancy, presence of a microangiopathy, nephropathy, smoking habits, gestational hypertension or preeclampsia, and HbA1c levels throughout pregnancy did not differed between mothers of macrosomic and non macrosomic infants. In the stepwise analysis none of these covariates was explanatory of the ponderal index. CONCLUSIONS: The frequency of macrosomia remains very high in infants of type 1 diabetic mothers despite a reasonable degree of glycemic control. The variability of the fetal growth response to mild hyperglycemia prompts for the identification of other factors involved in the modulation of fetal growth.

Adult↗