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Biomedical subjects

M Marre

Publications and source records attributed to M Marre.

At least 19 recordsLinked to original sources

Increased plasma adiponectin concentrations are associated with microangiopathy in type 1 diabetic subjects.

AIMS/HYPOTHESIS: Insulin resistance is related to an increased risk of diabetic retinopathy and nephropathy in type 1 diabetes. Patients with insulin resistance and/or macrovascular disease have abnormally low levels of adiponectin. The aim of this study was to investigate the relationships between adiponectin and renal and retinal diabetic complications in type 1 diabetic patients. METHODS: In this 6-year prospective follow-up observational study, we evaluated the severity of retinopathy at baseline and determined the incident risk of microalbuminuria in 126 normoalbuminuric patients with type 1 diabetes. Each patient was age- and sex-matched to two non-diabetic control subjects. RESULTS: Plasma adiponectin concentrations were significantly higher in diabetic subjects than in control subjects (p < 0.0001). The adiponectin concentration was significantly higher in patients with severe diabetic retinopathy than in those without (39.1+/-14.0 vs 29.0+/-13.0 microg/ml, p = 0.0005). The 18 patients who developed persistent microalbuminuria had higher adiponectin concentrations than the other patients (35.8+/-14.5 vs 30.6+/-13.7 microg/ml). Increased adiponectin concentrations were independently associated with the occurrence of microalbuminuria (p = 0.0158) after adjustment for baseline urinary albumin concentration (p = 0.004), sex (p = 0.0054), blood pressure (NS) and metabolic control (NS). CONCLUSIONS/INTERPRETATION: The elevated adiponectin concentrations observed in subjects with microvascular disease may indicate an altered regulation of this adipocytokine in patients with complications associated with type 1 diabetes.

Adiponectin↗

Polymorphisms of the receptor of advanced glycation endproducts (RAGE) and the development of nephropathy in type 1 diabetic patients.

OBJECTIVES: We investigated the association of the RAGE (Receptor for Advanced Glycation End products) exon3 gene polymorphisms with stages of nephropathy in type 1 diabetes. METHODS: The RAGE exon 3 genotype was assessed by Denaturing Gradient Gel Electrophoresis (DGGE) procedure in 487 type 1 diabetic patients with proliferative retinopathy subdivided into four groups according to their level of renal involvement and in 351 control subjects (GENEDIAB study). RESULTS: We reported here three main low frequency dimorphisms, previously submitted to data banks, Gly82Ser, Val89 CTC/CTG, and Arg77Cys. The genotype distribution of these polymorphisms was not statistically different in type 1 diabetic patients compared to healthy controls (p=0.37). Among the three described polymorphisms, only the RAGE Gly82Ser genotype frequency was significantly increased in the group with advanced nephropathy (11%) defined by a chronic renal failure compared to the three others groups: no nephropathy, 5%; incipient (microalbuminuria) 5%; established (macroalbuminuria), 2%) (P=0.04). The 82 Ser allele was identified as an independent risk marker for the stage of advanced nephropathy: adjusted odds ratio 3.17(95% CI 1,32-7,85, p=0.008). CONCLUSION: These data suggest that the 82 Ser allele of the RAGE gene is a risk allele for developing advanced nephropathy. This suggests that some RAGE gene polymorphisms may be associated with progression to diabetic advanced nephropathy in Caucasian type 1 diabetic patients.

Amino Acid Substitution↗

Cross-sectional study of care, socio-economic status and complications in young French patients with type 1 diabetes mellitus.

OBJECTIVES: To describe the present status of type 1 diabetes care in France and study the relations between clinical and socio-economic variables on one hand and disease management and prevalence of complications on the other hand. METHODS: A random sample of 365 French specialists in diabetes care performed a cross-sectional study and included consecutively 562 children aged 10-16 and 1691 adults aged 16-45, with more than 2 years of type 1 diabetes. The main outcome measures were the prevalence of complications (retinal, renal, lower-limb, cardiovascular, ketoacidosis); disease management parameters (blood pressure, HbA1c, daily number of insulin injections, frequency of visits to a specialist in diabetes, membership of a patient association); socio-economic status as a score, and treatments received. RESULTS: Retinal complications were rare in children (0.7%) and common in adults (28.3%). 10.2% children and 15.2% adults had micro- or macro-albuminuria, 4.7% adults had plasma creatinine >or=150 micromol/L. Only 15% children and 26% adults had HbA1c<7%, 86.2% children and 62.7% adults had blood pressure<130/85 mmHg; 58% children and 80% adults had at least 3 daily insulin injections. In adults, the risk of experiencing at least one complication was linked significantly with diabetes duration, HbA1c, and socio-economic status. Age, sex, type of insulin therapy, tobacco consumption, and blood pressure control were not significant parameters. Ketoacidosis in the preceding year was only linked with HbA1C and socio-economic status. CONCLUSION: Although this sample of patients had overall a fair socio-economic status and were followed-up by specialists of diabetes care, metabolic and blood pressure control were not optimal. The care of French type 1 diabetics could probably be improved by a stricter control of glycaemia and blood pressure, and an earlier use of intensive insulin treatment, with a particular focus on adolescents and patients with the lowest socio-economic status.

Adolescent↗

Evaluation of a screening program for diabetic retinopathy in a primary care setting Dodia (Dépistage ophtalmologique du diabète) study.

OBJECTIVES: The aim of this observational study was to evaluate the screening for diabetic retinopathy (DR) using eye fundus photography taken by a nonmydriatic camera and transmitted trough the Internet to an ophthalmological reading centre, as compared to a dilated eye examination performed by an ophthalmologist. METHODS: A total of 456 and 426 diabetic patients were included by two different groups of primary care physicians (PCPs), 358 being screened with the non-mydriatic camera (experimental group) and 320 with dilated eye fundus exam (control group). RESULTS: The proportion of screened patients for whom PCPs received a screening report within the 6-month follow-up period was 74,1% for the experimental group and 71,5% for the control group. Screening for DR was negative in 77,6% of patients with eye fundus photographs vs 89,6% with dilated eye examination. DR was diagnosed in 62 patients (17,3%) with eye fundus photographs versus 31 with dilated eye examination (10,4%). Referral to an ophthalmologist was required in 59 reports of patients with photographs (16.5%), 23 of them due to high grade DR. Finally, the non-mydriatic camera was found of little inconvenience by patients. CONCLUSION: The telemedical approach to DR screening proved to be effective in providing primary care practitioners with information about their patient's eye status. This screening method allowed to identify patients requiring prompt referral to the ophthalmologist for further complete eye examination. In conclusion, this study provided successful results of DR screening using fundus photography in primary care patients, and strongly supports the need to further extend this screening program in a larger number of French sites.

Diabetes Mellitus, Type 1↗

Serum triglycerides are a predictive factor for the development and the progression of renal and retinal complications in patients with type 1 diabetes.

OBJECTIVES: It is controversial that serum lipIds affect the development and progression of microvascular complications in patients with type 1 diabetes. METHODS: We prospectively followed 297 patients with type 1 diabetes without end-stage renal disease for 7 Years (range: 2-10). Serum lipIds were measured at baseline (total and HDL-cholesterol, triglycerIdes and calculated LDL-cholesterol, Lipoprotein (a)). The primary end-point was the occurrence of a renal event and the secondary end-point was the occurrence of a retinal event, defined as the progression to a higher stage of diabetic nephropathy or retinopathy, respectively. RESULTS: Serum triglycerIde (TG) levels were higher in patients who progressed in nephropathy than in those who dId not [median 1.21 (range 0.41-2.96) vs 0.91 (0.31-11.07) mmol/l; p=0.0037] and in those who developed retinal events than in those who dId not [1.05 (0.46-8.27) vs 0.87 mmol/l (0.31-11.07); p=0.0302], both in the whole cohort and in patients with normoalbuminuria at baseline. After adjustment for systolic blood pressure (SBP), diabetes duration, gender, stage of complications at baseline and glycohemoglobin (HbA1c), the relative risk for progression was 2.01 (95% CI: 1.07-3.77) for nephropathy and 2.30 (95% CI: 1.03-5.12) for retinopathy for patients having serum TG in the highest tertile, compared to the others. This result persisted when only patients with normoalbuminuria were consIdered. CONCLUSION: High triglycerIde levels are an independent predictive factor of both renal and retinal complications in patients with type 1 diabetes.

Adult↗

Screening for diabetic retinopathy: the first telemedical approach in a primary care setting in France.

OBJECTIVES: Diabetic retinopathy (DR) remains a major cause of visual impairment in France, due to insufficient regular annual screening. Fundus photography is a sensitive alternative to ophthalmoscopy for DR screening. The aim of our study was to report the first telemedical approach to this screening in a primary care setting in France. METHODS: A DR screening centre equipped with a nonmydriatic camera was opened in the 18th district of northern Paris and placed at the disposal of general practitioners (GPs) of the Réseau de Santé Paris Nord (North Paris Health Network). These GPs were invited to send their diabetic patients who had no known DR and had had no fundus examination for more than one year to this screening center. Retinal photographs were taken by an orthoptist without pupillary dilation and sent for grading through the Internet to the Lariboisière Hopital Ophthalmology Department. RESULTS: During an 18-month period, 912 DR screening examinations were performed in 868 diabetic patients referred to the DR screening center by 240 GPs. Patients' mean +/- SD age was 59.9 +/- 11.1 years. Of these 868 patients, 260 (30%) said they never have had an ophthalmological examination. Diabetic retinopathy was detected in 197 patients (22.7%). The proportion of patients for whom fundus photographs of one or both eyes could not be assessed was 10.1%. 159 patients (18.3%) required referral to an ophthalmologist. CONCLUSION: Nonmydriatic photography, combined with teletransmission to a reading centre, proved to be a feasible valid method for the detection of DR. This screening method allowed the identification of patients requiring prompt referral to an ophthalmologist for further complete eye examination.

Adolescent↗

[A common mutation C677T in the 5,10-methyltetrahydrofolate reductase gene is associated to idiopathic deep venous thrombosis].

PURPOSE: Moderate hyperhomocysteinemia is a risk factor for deep venous thrombosis. The homozygous C677T methylenetetrahydrofolate reductase (MTHFR) mutation is associated with increased level of total plasma homocysteine. The association between homozygous C677T mutation and deep venous thrombosis is still controversial. METHOD: In order to evaluate this association, we studied the prevalence of C677T mutation in 168 patients with confirmed deep venous thrombosis; 31 with an idiopathic deep venous thrombosis (group A) and 137 with thromboembolic event explained by one or more clinical and/or biological risk factors (group B). RESULTS: The distribution of genotypes was different between group A and B [++/+ -/- -(n(%))] : 9(29)/10(32)/12(39) vs 16(12)/57(42)/64(46) (chi(2) : 6.03; P: 0.049). The comparison between homozygotes and the two other genotypes showed significant statistical relationship between homozygous genotype and idiopathic character of deep venous thrombosis (chi(2) : 6.01; P : 0.014; OR : 3.09 [IC 95% : 1.06-8.53]). CONCLUSION: These results suggest that homozygous C677T methylenetetrahydrofolate reductase mutation could be considered as a genetic risk factor for venous thrombosis.

Adult↗

Influence of initial hyperglycaemia, weight and age on the blood glucose lowering efficacy and incidence of hypoglycaemic symptoms with a single-tablet metformin-glibenclamide therapy (Glucovance) in type 2 diabetes.

AIM: To evaluate the efficacy and incidence of hypoglycaemic symptoms associated with fixed combinations of metformin and glibenclamide (glyburide in the USA) formulated within a single tablet (tablet strengths 250 mg/1.25 mg, 500 mg/2.5 mg and 500 mg/5 mg), in comparison with metformin 500 mg and glibenclamide 2.5-5 mg monotherapy, in clinically important patient subgroups within the type 2 diabetic population. METHODS: A total of 1856 patients from three randomized, double-blind, multicentre, parallel-group clinical trials were stratified at baseline according to HbA1C (< 8% or > or = 8%), age (< 65 years or > or = 65 years) and body mass index (BMI; < 28 kg/m2 or > or = 28 kg/m2). The effects of study treatments on HbA1C and the incidence of hypoglycaemic symptoms were determined in each subgroup. RESULTS: The combination treatments were more effective than either monotherapy irrespective of baseline HbA1C, age or BMI in each trial. Antihyperglycaemic effects were greater in patients with HbA1C > or = 8% at baseline, especially with the combinations. The majority of hypoglycaemic symptoms with glibenclamide-containing treatments occurred in patients with HbA1C < 8% at baseline. Neither age nor BMI had a marked effect on the efficacy of the combination treatments, and there was no increase in hypoglycaemic symptoms in older patients. CONCLUSIONS: Single-tablet metformin-glibenclamide combination treatment is more effective than metformin or glibenclamide monotherapy, and is well tolerated in patients with hyperglycaemia inadequately controlled by diet and exercise or antidiabetic monotherapy, irrespective of their severity of hyperglycaemia at baseline, age or weight.

Age Factors↗

Evaluation of a new non-mydriatic digital camera for detection of diabetic retinopathy.

AIMS: To compare the results of fundus photography using a new non-mydriatic digital camera with the results of reference standard of Early Treatment Diabetic Retinopathy Study (ETDRS) retinal photographs, for the detection of diabetic retinopathy (DR). METHODS: Fundus colour photographs were taken with a Topcon non-mydriatic camera of 147 eyes of 74 diabetic patients, without pupillary dilation (five overlapping fields of 45 degrees; posterior pole, nasal, temporal, superior and inferior). Three retinal specialists classified the photographs in a masked fashion, as showing no DR or mild non-proliferative DR (NPDR) not requiring referral, moderate or more severe NPDR and/or macular oedema, or as non-gradable image requiring referral. ETDRS 35-mm colour slides served as reference images for DR detection. RESULTS: For moderately severe to severe DR, the sensitivities of detection reported by the three observers were 92, 100 and 92%, respectively, and the specificities, 87, 85, and 88%. For four levels of DR severity (none or mild NPDR, moderate NPDR, severe NPDR and proliferative DR), the percentages of exact agreement between the three observers on the retinopathy grades assigned to the non-mydriatic photographs and to the ETDRS reference slides were 94.6, 93 and 87.6%, respectively (kappa 0.60-0.80). Sixteen eyes of nine patients (11%) were judged ungradable by at least one observer. In a second series of 110 patients, evaluated in the setting of a screening procedure, fewer photographs were ungradable (< 6%). CONCLUSION: These results suggest that fundus photographs taken by the Topcon TRC-NW6S non-mydriatic camera, without pupillary dilation, are suitable for DR screening.

Adult↗

Angiotensin-I-converting enzyme insertion/deletion polymorphism and high urinary albumin concentration in French Type 2 diabetes patients.

AIMS: Family-based studies suggest a genetic basis for nephropathy in Type 2 diabetes. The angiotensin-I-converting enzyme (ACE) gene is a candidate gene for Type 1 diabetes nephropathy. We assessed the association between high urinary albumin concentration and ACE insertion/deletion (I/D) polymorphism, in French Type 2 diabetes patients. METHODS: We studied 3139 micro/macroalbuminuric French patients recruited in the DIABHYCAR Study, an ACE inhibition trial in Type 2 diabetes patients with renal and cardiovascular outcomes. The main inclusion criteria were age >/= 50 years, urinary albumin concentration >/= 20 mg/l assessed centrally during two consecutive screening visits, and plasma creatinine concentration </= 150 micro mol/l. These patients were compared with 605 normoalbuminuric (NA; urinary albumin concentration < 10 mg/l at first screening for the DIABHYCAR Study) French patients. ACE I/D genotype was determined by nested polymerase chain reaction. RESULTS: The ACE I/D polymorphism was in Hardy-Weinberg equilibrium. The distribution of genotypes did not differ significantly between micro/macroalbuminuric and NA patients: 552 and 115 II, 1468 and 282 ID, 1119 and 208 DD (P = 0.67). However, the ACE D allele was more frequent among normotensive micro/macroalbuminuric patients than among NA patients (P = 0.039). CONCLUSIONS: The ACE I/D polymorphism was not associated with high urinary albumin concentration in French Type 2 diabetes patients.

Aged↗

Effect of indapamide SR on microalbuminuria--the NESTOR study (Natrilix SR versus Enalapril Study in Type 2 diabetic hypertensives with micrOalbuminuRia)--rationale and protocol for the main trial.

In type 2 diabetic hypertensive patients, microalbuminuria can be due to hypertension and/or diabetic nephropathy. Angiotensin-converting enzyme (ACE) inhibitors act preferentially on microalbuminuria due to diabetic nephropathy. The objective is to demonstrate the efficacy of a thiazide-like diuretic, indapamide sustained release (SR), at reducing microalbuminuria in hypertensive type 2 diabetic patients in comparison with an ACE inhibitor, enalapril. The study is an international multicentre, 12-month, randomized, double-blind, controlled, two parallel group study of type 2 diabetic patients with hypertension (140 mmHg < or = systolic blood pressure <180 mmHg and diastolic blood pressure <110 mmHg) and microalbuminuria. Intervention is after a 4-week placebo period, patients with microalbuminuria > or = 20 and < or = 200 microg/min are randomized to indapamide SR 1.5 mg or to enalapril 10 mg once a day for a one-year treatment period. An additional label treatment by amlodipine 5-10 mg (1st step) and atenolol 50-100 mg (2nd step) a day is permitted after 6 weeks of treatment based upon blood pressure response. The main outcome measures are microalbuminuria expressed as urinary albumin to creatinine ratio, albumin fractional clearance, and albumin excretion rate evaluated on overnight urine collections. Secondary criteria are supine and standing systolic, diastolic and mean blood pressure; and biological and clinical safety. This study will complete the knowledge of the efficacy of indapamide SR in hypertension and target organ damage and will provide valuable information on the management of type 2 diabetic hypertensives with microalbuminuria.

Adult↗

Before oral agents fail: the case for starting insulin early.

The progressive nature of Type 2 diabetes presents a challenge over the choice and course of treatment. Strict metabolic control is recommended to reduce the risk of diabetic morbidity and premature mortality. Treatment usually occurs in a step-wise manner as the insulin secretory capacity of the beta-cells diminishes. There are a variety of oral hypoglycaemic agents (OHAs) to choose from but the efficacy of all is influenced by beta-cell function. Eventual progression to insulin therapy is inevitable after beta-cell failure and it is important that this is not delayed. Insulin in combination with OHAs can significantly improve glycaemic control and provide a 'bridge' from oral-only to insulin-only therapy. Combination therapy requires few injections and there is a reduced tendency for weight gain compared with multiple insulin injection regimens. After starting insulin, metabolic control may significantly improve in OHA-treated patients. It is therefore prudent to initiate insulin at an early stage in the course of Type 2 diabetes. In this context, the use of premixed insulin analogues in combination with OHAs allows effective postprandial glucose control, a twice-daily injection regimen and a short meal-injection interval.

Blood Glucose↗

Nateglinide improves glycaemic control when added to metformin monotherapy: results of a randomized trial with type 2 diabetes patients.

AIMS/HYPOTHESIS: This study evaluated the addition of nateglinide, a d-phenylalanine derivative that restores early phase insulin release, to metformin in type 2 diabetes patients stabilized on high-dose metformin. METHODS: This multicentre, double-blind, parallel group trial included 467 metformin-treated patients with glycosylated haemoglobin (HbA1c) between 6.8% and 11%. Patients were randomized to add nateglinide 60 mg, 120 mg or placebo before three meals to metformin 1000 mg b.i.d. for 24 weeks. RESULTS: HbA1c was significantly reduced with nateglinide 60 mg and 120 mg plus metformin compared with metformin control (-0.36%, p = 0.003; -0.59%, p < 0.001 respectively). Greater benefits occurred if patients had elevated HbA1c at baseline (-1.38% with nateglinide 120 mg in patients with HbA1c > 9.5%). A modest fasting plasma glucose reduction was observed. Most symptoms suggestive of hypoglycaemia occurred in patients with low HbA1c levels (<or= 8%) at baseline, although no confirmed cases of hypoglycaemia occurred with nateglinide 60 mg in this patient group. Events suggestive of hypoglycaemia were confirmed in 1.1% of cases (plasma glucose <or= 3.3 mmol/l). Weight gain over 24 weeks was 0.9 kg with nateglinide 120 mg vs. metformin alone, and plasma lipids remained unchanged. CONCLUSIONS/INTERPRETATION: In patients stabilized on high-dose metformin, the addition of nateglinide improved glycaemic control. The combination of these agents was well tolerated and both doses of nateglinide proved effective. The efficacy of nateglinide 60 mg and the low rate of hypoglycaemia observed at this dose make it suitable for patients close to their therapeutic target on metformin monotherapy.

Aged↗

[Fundus photography for the screening for diabetic retinopathy].

Despite the efficacy of laser photocoagulation to prevent complications of diabetic retinopathy, diabetic retinopathy remains a major cause of visual impairment and blindness in France. This is mainly due to a too late diagnosis of diabetic retinopathy. In an effort to detect diabetic retinopathy at an early stage before visual loss, international and national guidelines for the screening for diabetic retinopathy have been developed, which recommend annual fundus examination for all diabetic patients. In France, a recent survey showed that less than 50% of diabetic patients had had an eye examination during the previous year. With the increasing number of diabetic patients and the decreasing number of ophthalmologists, this situation should not improve by the next 15 years. Fundus photography is a method at least as sensitive as ophthalmoscopy in the screening for diabetic retinopathy. New nonmydriatic cameras and digital photography may allow a network organization of several screening centers around a central ophthalmological reading center where digital images could be transmitted. This organization should improve the screening for diabetic retinopathy, while saving medical time.

Blindness↗

[Treatment of hypertensive type 2 diabetes patients with microalbuminuria].

PRIMARY OBJECTIVE: The first fundamental study devoted to the reduction of microalbuminuria with a antihypertensive diuretic (indapamide SR) in type 2 diabetes with hypertension, the Marre study (NESTOR) was designed to demonstrate that this antihypertension agent could be an interesting therapeutic alternative by comparing its efficacy on microalbuminuria with that of enalapril 10 mg during a treatment period of 52 weeks. RESULTS: It was demonstrated that indapamide SR is the only diuretic providing a significant reduction (35%) in the microalbuminuria observed in hypertensive patients with type 2 diabetes. At the endpoint, comparison with the group of patients treated with enalapril, showed no significant difference in fractionated albumin clearance or in the percentage of patients with normoalbuminuria, microalbuminuria or gross proteinuria. Safety and tolerance were comparable for the two treatments.

Albuminuria↗

[Reflexion of French experts on the key points of the symposium].

The French experts present at the Eutherapy Symposium held in Prague confirmed the importance of left ventricular hypertrophy (LVH) and microalbuminuria as major independent risk factors for cardiovascular disease. Factors that must be considered for the treatment of hypertension in patients, particularly with type 2 diabetes. Professor J.M. Mallion stressed the contribution of thiazide and thiazide-like diruetics as indapamid, especially the 1.5 mg SR formulation. Professor F. Forette and Doctor O. Hanon recalled that the HYVET study is expected to confirm the beneficial effect of this same treatment on morbidity and mortality in very elderly patients. Professor O. Dubourg recalled the beneficial effect of indapamid SR on LVH demonstrated in the LIVE study. Likewise, Professor M. Marre emphasized its important impact on microalbuminuria as shown in the NESTOR study.

Adult↗

[What allows a type 1 diabetic to be well controlled].

Long-term studies carried out in type 1 insulin-dependent diabetic population have clearly demonstrated a tight glycaemic control to be a key factor in type 1 diabetes mellitus survival. A better HbA1c is associated with lesser retina and kidney complications. The DCCT study has clearly shown intensive insulin treatment (3 or more insulin injections per day) to be superior to conventional regimen (one or 2 insulin injections per day) to reduce the risk for development (primary prevention) of late diabetic complications. However, such intensive insulin regimen should be started early, maintained on the long-term, and should be based on a regular and adequate blood glucose self-monitoring. The beneficial effects of a tight glycaemic control to reduce the risk for progression (secondary prevention) of late diabetic complications has not been proved yet. Consequently, at this stage, non-glycaemic interventions (antihypertensive treatment with angiotensin-converting-enzyme inhibitors, laser photocoagulation surgery) are the most useful treatment modalities. The global prognosis of type 1 insulin-dependent diabetics is strongly linked to the patient attitude, to his understanding of the disease and to his motivation to participate in the disease management. This requests permanent, long-term, intensive patient's information and education. Information tools (from oral information to website) and strategies (from usual educational courses by the diabetes care team to general public information) remain to be fully evaluated.

Biomarkers↗