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Biomedical subjects

M Marre

Publications and source records attributed to M Marre.

At least 19 recordsLinked to original sources
PubMed1999

Renal changes on hyperglycemia and angiotensin-converting enzyme in type 1 diabetes.

Hyperglycemia causes capillary vasodilation and high glomerular capillary hydraulic pressure, which lead to glomerulosclerosis and hypertension in type 1 diabetic subjects. The insertion/deletion (I/D) polymorphism of the angiotensin I-converting enzyme (ACE) gene can modulate risk of nephropathy due to hyperglycemia, and the II genotype (producing low plasma ACE concentrations and probably reduced renal angiotensin II generation and kinin inactivation) may protect against diabetic nephropathy. We tested the possible interaction between ACE I/D polymorphism and uncontrolled type 1 diabetes by measuring glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) during normoglycemia ( approximately 5 mmol/L) and hyperglycemia ( approximately 15 mmol/L) in 9 normoalbuminuric, normotensive type 1 diabetic subjects with the II genotype and 18 matched controls with the ID or DD genotype. Baseline GFR (145+/-22 mL/min per 1.73 m2) and ERPF (636+/-69 mL/min per 1.73 m2) of II subjects declined by 8+/-10% and 10+/-9%, respectively, during hyperglycemia; whereas baseline GFR (138+/-16 mL/min per 1.73 m2) and ERPF (607+/-93 mL/min per 1.73 m2) increased by 4+/-7% and 6+/-11%, respectively, in ID and DD subjects (II versus ID or DD subjects: P=0.0007 and P=0.0005, for GFR and ERPF, respectively). The changes in renal hemodynamics of subjects carrying 1 or 2 D alleles were compatible, with a mainly preglomerular vasodilation induced by hyperglycemia, proportional to plasma ACE concentration (P=0.024); this was not observed in subjects with the II genotype. Thus, type 1 diabetic individuals with the II genotype are resistant to glomerular changes induced by hyperglycemia, providing a basis for their reduced risk of nephropathy.

Adult↗
PubMed1999

Relationship between glomerular hyperfiltration and ACE insertion/deletion polymorphism in type 1 diabetic children and adolescents.

OBJECTIVE: Glomerular hyperfiltration may predict diabetic nephropathy in type 1 diabetes, and some studies suggest that the ACE D allele is associated with diabetic nephropathy. The aim of this study was to examine a possible relationship between glomerular hyperfiltration and ACE insertion/deletion (I/D) polymorphism in type 1 diabetic children and adolescents. RESEARCH DESIGN AND METHODS: A cross-sectional study was conducted to examine the relationship between glomerular hyperfiltration and ACE (I/D) polymorphism in 76 type 1 diabetic children and adolescents without diabetic nephropathy (mean +/- SD: age 16 +/- 3 years; diabetes duration 7 +/- 4 years; age at diabetes onset 9 +/- 4 years; HbA1c 9.5 +/- 1.9%). Glomerular hyperfiltration (defined as a glomerular filtration rate [GFR] > or = 135 ml.min-1. 1.73 m-2 and by 51Cr-labeled EDTA plasma disappearance technique) and ACE I/D genotypes and plasma levels (enzyme-linked immunosorbent assay [ELISA] method) were determined. RESULTS: Of the patients, 29 (38%) displayed glomerular hyperfiltration. An association between glomerular hyperfiltration and ACE (I/D) polymorphism was observed (chi 2 = 7.09, P = 0.029) because of a reduced proportion of DD genotypes among patients with glomerular hyperfiltration (4 vs. 19; chi 2 = 6.03, P = 0.014) and not because of an excess of the II genotype (5 vs. 9; chi 2 = 0.04, P = 0.83). Age, diabetes duration, age at diabetes onset, and HbA1c were not different according to genotype. Patients with glomerular hyperfiltration had low plasma ACE levels, compared with those with normal glomerular filtration (457 +/- 157 vs. 553 +/- 186 micrograms/l; P = 0.027). CONCLUSIONS: These results suggest an unexpected association between glomerular hyperfiltration and ACE (I/D) polymorphism, characterized by a defect of the DD genotype among type 1 diabetic children and adolescents with glomerular hyperfiltration.

Adolescent↗
PubMed1999

Genetics and the prediction of complications in type 1 diabetes.

OBJECTIVE: Epidemiological evidence suggests that genetic factors can affect the course of type 1 diabetes complications produced by long-lasting hyperglycemia. In this review, the current strategies applicable to identifying these genetic factors are examined, as are recent findings on the genetics of diabetic nephropathy and whether these are applicable to type 1 diabetes patient care. RESEARCH DESIGN AND METHODS: Whole-genome screening and candidate gene strategies can be applied to the genetics of type 1 diabetes complications. The search for candidate genes can focus on enzymes involved in glucose metabolism or on those affecting non-glycemic-dependent vascular risk. For each candidate, the level of evidence may vary from case-control to intervention studies. Literature on diabetic complications and a possible role for genetics was examined systematically. RESULTS: The most significant results were obtained regarding a role for polymorphisms of the renin-angiotensin system in diabetic nephropathy. Several studies suggest a role for angiotensin I converting enzyme insertion/deletion polymorphism in the development of renal complications. However, the level of evidence is currently not sufficient to recommend treatment strategy based on this or any other polymorphism. CONCLUSIONS: The search for a genetic basis of type 1 diabetes complications is an important avenue to examine their pathophysiologies. However, it is still premature to apply the current findings in this domain to type 1 diabetes patient care.

Case-Control Studies↗
PubMed1999

[Metabolic mechanisms of renal fibrosis: diabetes].

Diabetic nephropathy, a cause for renal fibrosis, results from glomerular haemodynamic abnormalities: intra-glomerular hypertension is provoked by pre-glomerular vasodilatation (a consequence of hyperglycaemia) facing to constitutive, post-glomerular, vascular resistances. Pre-glomerular vasodilatation is due to abnormal glucose metabolism during hyperglycaemia. Studies on pathophysiology, genetics, and treatment of diabetic nephropathy are oriented by these latter two components of risk for renal fibrosis.

Diabetic Nephropathies↗
PubMed1998

[Type 2 diabetes: new therapeutic perspectives].

UKPDS: The results of the United Kingdom Prospective Diabetes Study (UKPDS) were reported in 1998. This multi-center, prospective, randomized, intervention trial of 5102 newly-diagnosed patients with type 2 diabetes mellitus was aimed at determining whether improved blood glucose control can prevent complications and reduce associated morbidity and mortality. THE RESULTS: Improved blood glucose control was shown to reduce the number of complications, mainly by reducing the effect of microangiopathy. There was however no reduction in the number of diabetes-related deaths nor in the risk of myocardial infarction or sudden death. CONTROVERSY OVER CALCIUM ANTAGONISTS: Calcium antagonists are suspected of increasing the risk of cardiovascular disease. On the basis of published reports, the JNC VI guidelines are recommended: calcium antagonists should not be used as first line treatment in diabetics. RECENT DRUGS: Acarbose, an alpha-glucosidase inhibitor, lowers post-prandial blood glucose level. It has marketing approval for single-drug regimens in France. Miglitol, another alpha-glucosidase inhibitor, would have the same therapeutic effect. Orliatort, an gastro-intestinal lipase inhibitor, is indicated in obese patients but long-term results are lacking to evaluate effects in diabetics.

Acarbose↗
PubMed1998

Microalbuminuria and prevention of renal insufficiency and cardiovascular diseases.

Microalbuminuria, a slightly elevated urinary albumin excretion, predicts renal failure in insulin-dependent diabetic patients and premature cardiovascular mortality in non-insulin-dependent diabetic patients and in the general population. It can be related to all currently established cardiovascular risk factors. Regarding the relationship between urinary albumin and blood pressure, microalbuminuria seems to be an early indicator of renal disease, causing high blood pressure in some instances, whereas it looks like the consequences of renal damage produced by severe hypertension in other instances. To establish whether microalbuminuria is an integrated risk marker for renal and cardiovascular events, or truly a risk factor, and to validate the usefulness of some peculiar treatment strategies, clinical trials are required, taking microalbuminuria as a selection criteria, and renal and cardiovascular events as endpoints.

Albuminuria↗
PubMed1998

Ambulatory blood pressure and urinary albumin excretion in diabetic (non-insulin-dependent and insulin-dependent) hypertensive patients: relationships at baseline and after treatment by the angiotensin converting enzyme inhibitor trandolapril.

The aim of the present study was to examine the relationships between ambulatory blood pressure (ABPM) and urinary albumin excretion (UAE) in diabetic (non-insulin dependent [NIDDM] and insulin-dependent [IDDM]) hypertensives at baseline and after treatment by an angiotensin converting enzyme (ACE) inhibitor. After a 3-week placebo period, patients were treated for 16 weeks with trandolapril, 2 to 4 mg/day. The UAE and blood pressure (mercury sphygmomanometer and 24-h ABPM) were measured at baseline and repeated on trandolapril. Predictive factors of abnormal UAE (24-h UAE > or = 30 mg) were determined using univariate and multivariate analysis (logistic regression). Predictors of UAE decrease were also searched. One hundred seventy-one patients entered the analysis. Baseline office BP was 164+/-14 / 97+/-6 mm Hg and 24-h BP was 142+/-17 / 83+/-10 mm Hg. Seventy-four patients (43%) had UAE > or = 30 mg. Independent risk factors for abnormal UAE were nighttime diastolic BP (odds ratio [OR] = 4.1, confidence interval [CI] = 2.0 to 8.6, P = .0001), diabetes duration (OR = 2.4, CI = 1.1 to 5.0, P = .025), and presence of retinopathy (OR = 3.2, CI = 1.0 to 10.0, P = .047). Conversely, office BP level was not significantly related to UAE. On treatment, office BP levels decreased to 143+/-13 / 82+/-8 mm Hg (P < .0001) and 24-h BP levels to 134+/-17 / 78+/-9 mm Hg (P < .0001). In the abnormal UAE group, UAE significantly decreased from 76 to 50 mg/day (P = .006). After treatment, independent predictive factors of abnormal UAE were: on-drug fasting plasma glucose (OR = 3.5, CI = 1.7 to 7.4, P = .0009) and on-drug nighttime diastolic BP (OR = 3.5, CI = 1.7 to 7.4, P = .001). The only predictor of UAE decrease was a 24-h systolic BP decrease (OR = 2.3, CI = 1.3 to 4.3, P = .007). We conclude that in diabetic hypertensives with abnormal UAE, trandolapril exhibited a sustained 24-h antihypertensive effect and provided a consistent reduction of microalbuminuria. This study confirmed the superiority of ABPM over clinical BP to predict target organ damage.

Albuminuria↗
PubMed1998

Necrobiosis lipoidica: treatment by hyperbaric oxygen and local corticosteroids.

Necrobiosis lipoidica (NL) is closely associated with diabetes mellitus. Two-thirds to three-fourths of patients with NL have diabetes, although NL occurs in only 0.3% of diabetic patients. Typical lesions are found on pretibial skin, usually in young female diabetic patients whose disease is inadequately controlled. The cause of this dermopathy remains unknown. Multiple treatments have been described but have not led to consistent results. We report the case of a 28-year-old insulin-dependent diabetic woman with a disease duration of 23 years who spontaneously developed ulcerated NL on pretibial skin. NL progressively improved during 113 sessions of hyperbaric oxygen therapy and local corticosteroids.

Administration, Topical↗
PubMed1998

[Choice of first line treatment for arterial hypertension: should one avoid dihydropyridines in diabetic patients?].

Choice of first-line treatment for arterial hypertension: should dihydropiridines be avoided in diabetic patients? The use of dihydropyridines as first-line antihypertensive drugs in Type 2 (non-insulin-dependent) diabetic subjects has recently been challenged by several clinical trials that found increased risk of cardiovascular events (sudden death and myocardial infarction). This report provides a critical appraisal of available data. The main shortcomings of these trials are that clinical events were secondary outcomes in studies designed for other purposes (effects of antihypertensive drugs on blood pressure control or metabolic tolerance); that control groups on placebo or reference treatment were lacking in both trials; and that one trial was stopped at the request of the safety committee. Therefore, estimates of potentially adverse effects are imprecise and may be biased. Until data from large-scale ongoing trials are available, dihydropyridines should continue to be used as second-step antihypertensive drugs in Type 2 patients.

Antihypertensive Agents↗
PubMed1997

Contribution of genetic polymorphism in the renin-angiotensin system to the development of renal complications in insulin-dependent diabetes: Genetique de la Nephropathie Diabetique (GENEDIAB) study group.

Diabetic nephropathy is a glomerular disease due to uncontrolled diabetes and genetic factors. It can be caused by glomerular hypertension produced by capillary vasodilation, due to diabetes, against constitutional glomerular resistance. As angiotensin II increases glomerular pressure, we studied the relationship between genetic polymorphisms in the renin-angiotensin system-angiotensin I converting enzyme (ACE), angiotensinogen (AGT), and angiotensin II, subtype 1, receptor-and the renal involvement of insulin-dependent diabetic subjects with proliferative retinopathy: those exposed to the risk of nephropathy due to diabetes. Of 494 subjects recruited in 17 centers in France and Belgium (GENEDIAB Study), 157 (32%) had no nephropathy, 104 (21%) incipient (microalbuminuria), 126 (25 %) established (proteinuria), and 107 (22%) advanced (plasma creatinine > or = 150 micromol/liter or renal replacement therapy) nephropathy. The severity of renal involvement was associated with ACE insertion/deletion (I/D) polymorphism: chi2 for trend 5.135, P = 0.023; adjusted odds ratio attributable to the D allele 1.889 (95% CI 1.209-2.952, P = 0.0052). Renal involvement was not directly linked to other polymorphisms. However, ACE I-D and AGT M235T polymorphisms interacted significantly (P = 0.0166): in subjects with ACE ID and DD genotypes, renal involvement increased from the AGT MM to TT genotypes. Thus, genetic determinants that affect renal angiotensin II and kinin productions are risk factors for the progression of glomerular disease in uncontrolled insulin-dependent diabetic patients.

Adult↗
PubMed1997

Microalbuminuria as a predictor of a drop in glomerular filtration rate in subjects with non-insulin-dependent diabetes mellitus and hypertension.

UNLABELLED: Hypertension and non-insulin-dependent diabetes mellitus (NIDDM) are two major risk factors for end-stage renal failure. The value of microalbuminuria (urinary albumin excretion [UAE]: 30-300 mg/24 h) as an indicator of the glomerular filtration rate (GFR) is not known in these patients. METHODS: The relationships between microalbuminuria and GFR in subjects with NIDDM and hypertension were studied cross-sectionally (Study I) and longitudinally (Study II). RESULTS: In study I, 205 NIDDM subjects with hypertension (151 with normoalbuminuria [UAE < 30 mg/24 h] and 54 with microalbuminuria) were studied. The GFR of subjects with normoalbuminuria (97 +/- 30 ml/min) (mean +/- SD), and microalbuminuria (97 +/- 27 ml/min; NS) were similar. Study II examined 51 of the subjects with normoalbuminuria and 21 with microalbuminuria 22 months (range 13-57) later. The GFR of subjects with microalbuminuria (-10 +/- 19 ml/min) declined more than in those with normoalbuminuria (+4 +/- 17 ml/min; Student's t-test: p = 0.0022). The predictive value of microalbuminuria for a drop in GFR was independent of the antihypertensive treatment used, the follow-up time, or changes in UAE. The only variable linked to GFR loss in subjects with microalbuminuria was an increase in diastolic blood pressure (p = 0.0298). CONCLUSION: Microalbuminuria is a risk factor for a drop in GRF in NIDDM subjects with hypertension, and a reduction in blood pressure is the only effective way to prevent a loss of GFR in subjects with microalbuminuria.

Albuminuria↗
PubMed1997

Multiple antibody status in type 1 diabetic patients and subjects at various risk with islet-cell antibodies.

The frequency of 37/40 kD antibodies and their association with other pancreatic humoral markers were studied in 109 recently diagnosed Type 1 diabetic patients and 116 subjects with islet-cell antibodies (ICA) at various risk for this disease (64 relatives of Type 1 diabetic patients, 23 schoolchildren with no family history of diabetes, and 29 patients with Graves' disease). At the time of diagnosis, 37/40 kD antibodies were detected in 45% of Type 1a and 77% of Type 1b diabetic patients (p = 0.03). Antibodies to glutamic acid decarboxylase (GAD) and/or 37/40 kD were present with the same frequency as ICA (86%). The frequency of 37/40 kD antibodies was not significantly different between the 3 groups at risk, in contrast with GAD antibodies which were found at a lower frequency in schoolchildren (p < 0.02). Frequencies of other pancreatic markers (ICA cross-reactive with mouse pancreas and insulin autoantibodies) and the combination of ICA with at least two other markers were significantly higher in relatives than in the other groups at risk (p < 0.02). Out of 116 ICA-positive non-diabetic subjects, 10 developed diabetes. All 10 displayed 37/40kD and/or GAD antibodies during the prediabetic phase. In 8 of these 10 patients, ICA was combined with at least two other markers, whereas this association was detected in only 17 of the remaining 106 subjects who did not progress to diabetes (p < 10(-4). Thus, 37/40 kD antibodies were found in about half of Type 1 diabetic patients, and with a higher-frequency in Type 1b than 1a. In ICA-positive non-diabetic subjects, our date confirm that a combination of multiple antibodies, including GAD antibodies and 37/40 kD antibodies, can enhance the predictive value for diabetes. Comparison of ICA-positive relatives of diabetic patients, schoolchildren and patients with Graves' disease revealed distinct frequencies and combinations of markers of diabetes. This might reflect different patterns of progression among these 3 groups.

Animals↗
PubMed1997

Proposed criteria for the diagnosis of diabetes: evidence from a French epidemiological study (D.E.S.I.R.).

The American Diabetes Association and a working group of the International Diabetes Federation and the World Health Organisation are considering the possibility of lowering the level of fasting glucose for diagnosis of diabetes from 7.8 mM to 7.0 mM (126 mg/dl) and adding a "hyperglycaemia" category (6.1-6.9 mM). This report studied the resulting change in the frequency of diabetes in the French D.E.S.I.R. cohort and evaluated cardiovascular risk factors according to the proposed limits. The frequency of treated diabetes was 1.0% in this cohort of more than 5,000 French men and women 30 to 64 years of age, 0.7% had a fasting glucose > or = 7.8 mM versus 1.6% for the proposed > or = 7.0 mM. Using the new criteria, 3.8% of men and 1.6% of women would be diabetic. For many cardiovascular risk factors, men with fasting glucose > or = 7.8 mM had a significantly higher risk than those in the (7.0-7.7 mM) range, whereas no significant differences were found for women. There were few differences between the (7.0-7.7 mM) and (6.1-6.9 mM) ranges, but highly significant differences were apparent for both sexes between the normoglycaemic (< 6.1 mM) and hyperglycaemic (6.1-6.9 mM) categories. The percentage of men with two or more of ten risk factors increased with fasting glucose: 36% in the normoglycaemic (< 6.1 mM) and 49% in the hyperglycaemic (6.1-6.9 mM) categories; 73% with fasting glucose in (7.0-7.7 mM) versus 90% with fasting glucose > or = 7.8 mM. In women, the corresponding percentages were lower: 26% and 60%, 32% versus 64% respectively. The major increase in cardiovascular risk factors would appear to occur at 6.1 mM, for men, whereas the increase in the combination of risk factors was at the more conservative cut-off of 7.0 mM.

Adult↗