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Biomedical subjects

A Grimaldi

Publications and source records attributed to A Grimaldi.

At least 73 records · Page 4Linked to original sources
PubMed2000

Lack of relationship in long-term type 1 diabetic patients between diabetic nephropathy and polymorphisms in apolipoprotein epsilon, lipoprotein lipase and cholesteryl ester transfer protein. Genétique de la Nephropathie Diabétique Study Group. Données Epidémiologiques sur le Syndrome d'Insulino-Résistance Study Group.

BACKGROUND: Genetic susceptibility contributes to the risk of diabetic nephropathy. Lipid disorders may favour diabetic nephropathy. Thus polymorphisms in lipid metabolism are candidates for the genetic component of risk for diabetic nephropathy. METHODS: We searched for a contribution of the genetic polymorphisms of lipoprotein lipase (LPL), cholesteryl ester transfer protein (CETP) and apolipoprotein epsilon (Apo E) to the development of diabetic nephropathy by studying 494 type 1 diabetic patients with proliferative retinopathy and various stages of diabetic nephropathy (GENEDIAB Study). The selection process ensured that all patients had expressed their risk of chronic complications due to uncontrolled diabetes. Thus the nephropathy stages were largely influenced by genetic background. The lipid profile included fasting plasma total cholesterol (TC), triglycerides (TG), apolipoprotein A1 (Apo A1) and B (Apo B), and lipoprotein (a) (Lp(a)). Genetic polymorphisms were determined by PCR-based detection of Apo epsilon (e2/e3/e4), LPL (mutation Asn 291 Ser) and CETP (TAQ:IB B1/B2). RESULTS: One hundred and fifty-seven patients (32%) had no nephropathy, 104 (21%) incipient nephropathy, 126 (25%) established nephropathy and 107 (22%) advanced nephropathy. There was a significant relationship between the stages of diabetic nephropathy and TC (P=0.002), TG (P<0.0001), Apo B (P=0.0007) or Lp(a) (P=0. 038), but not Apo A1. However the genetic polymorphism distributions of LPL, CETP and Apo epsilon did not differ in terms of renal complications. The study power to reject the null hypothesis was 58% for the Apo epsilon genotypes. CONCLUSION: These results support no or only marginal effects of a genetic basis for lipid disturbances encountered in diabetic nephropathy.

Adult↗
PubMed2000

Lamin A/C gene: sex-determined expression of mutations in Dunnigan-type familial partial lipodystrophy and absence of coding mutations in congenital and acquired generalized lipoatrophy.

Missense mutations of the lamin A/C gene, LMNA, have been recently identified in Dunnigan-type familial partial lipodystrophy (FPLD), which belongs to a heterogeneous group of rare disorders affecting adipose tissue distribution and metabolism. In this study, we sequenced the LMNA coding region from patients presenting with FPLD or other forms of lipodystrophy. We identified two heterozygous mutations in exon 8, R482W and R482Q, in FPLD patients (six families and one individual) with various clinical presentations. In addition, we found a novel heterozygous mutation (R584H) in exon 11, encoding specifically the lamin A isoform, in a patient with typical FPLD. Clinical and biochemical investigations in FPLD patients revealed that the expression and the severity of the phenotype were markedly dependent on sex, with female patients being more markedly affected. In subjects with generalized lipoatrophy, either congenital (13 case subjects) or acquired (14 case subjects), or Barraquer-Simon syndrome (2 case subjects), the entire LMNA coding sequence was normal. Although FPLD mutations are predominantly localized in exon 8 of LMNA, the finding of a novel mutation at codon 584, together with the R582H heterozygous substitution recently described, confirms that the C-terminal region specific to the lamin A isoform is a second susceptibility region for mutations in FPLD.

Adipose Tissue↗
PubMed2000

[Role of antibiotic therapy in diabetic foot management].

Antibiotic therapy is not the most important component in diabetic foot ulcer management which should be based on weight bearing avoidance and arterial revascularization. However antibiotic therapy is necessary in presence of extensive deep involvement or systemic signs of infection. Initial antimicrobial treatment depends on bacteria supposed origin. For patients not coming from hospital, the initial choice antibiotic is an amoxicillin/clavulanate agent because it offers optimal coverage for most pathogens involved in those diabetic foot lesions (gram positive cocci, gram negative and anaerobic organisms). For patients at high risk to be infected with nosocomially acquired pathogens, the initial antibiotic therapy must cover methicillin-resistant staphylococci, resistant pseudomonas aeruginosa or enterobacteriae. In all cases, when definitive reliable cultures are reported, initial antibiotic regimens should be revised to narrow the coverage to specific pathogens. In presence of osteomyelitis, a temporary combination of two agents which are known to reach high bone concentrations is necessary, and antibiotic therapy should be continued for at least two months. In other cases, antibiotic treatment duration depends on clinical out come.

Anti-Bacterial Agents↗
PubMed2000

Managing type 2 diabetes in France: the ECODIA survey.

In order to describe the profile and medical management of type 2 diabetes patients in France, a descriptive cross-sectional survey was conducted in 1999 among a national random sample of 311 general practitioners and 51 specialists. A practitioner questionnaire was designed to collect information on a representative sample of 4,119 patients presenting with type 2 diabetes. Data collected included demographic and clinical information and a full description of diabetes management over a 6-month retrospective period. Over 50% of the patients were more than 67 years old; 54% were male. Diabetes had been diagnosed 8.9 years earlier on average, most frequently (73%) during a visit not related to diabetes' symptoms or complications. 42% of patients had a BMI > or =30 kg/m(2), 46% were hypertensive (BP > 140-80 mmHg), 53% had a LDL-Cholesterol over 1.3 g/l. Overall, 33% of patients had at least one diabetic complication. 60% of patients had had at least one HbA1c dosage in the last 6 months. Among them, 31% had a HbA1c level over 8% and 35% between 6. 5% and 8%. 85% of patients were treated with oral anti-diabetic drugs, 9.5% with diet and exercise only and 5% with insulin. Sulfonylureas were the most commonly prescribed anti-diabetic agent, either alone or in combination. This survey confirms that the management of patients with type 2 diabetes is still often inappropriate in France despite recent progress. Improved disease management and monitoring is required in France as in other developed countries.

Aged↗
PubMed1999

[Diagnostic criteria for type 2 diabetes].

A new definition of diabetes is just about to be adopted by WHO. The main change concerns the glycemic threshold for diagnosis of diabetes. Its value will decrease from 7.7 mmol/L to 7 mmol/L. This drop is neither the consequence of a methodological change (diabetes remains defined by glycemic values at risk of retinopathy) nor a revision of the gold standard (glycemic value > or = 11 mmol/L at 2 h. post glucose load remains the most accurate criterion for diagnosis). The only purpose of the new definition is to better correlate fasting glycemia with the 2 h. post load value during OGTT. So, the new definition of diabetes with a glycemic value > or = 7 mmol/L will allow to do diagnosis without OGTT. The WHO experts hope that this simplification will improve the earliness of diagnosis and treatment. WHO will propose to categorize 3 groups according to glycemic values: normal values < 6.05 mmol/L, diabetic values > 7 mmol/L, and impaired fasting glucose encompassing values above normal but below the diagnosis cut-off for diabetes (plasma glucose > or = 6.05 mmol/L to < 7.0 mmol/L). This impaired fasting glucose should be considered as a risk factor for diabetes and cardiovascular disease.

Blood Glucose↗
PubMed1999

Histopathological changes after induced injury in leeches.

Cells involved in leech inflammatory responses have been characterized by morphological, histochemical, and immunohistochemical methods. Macrophage-like cells, NK-like cells, and granulocytes migrated shortly after injury by pricking with bacterial lipopolysaccharide. Inflammatory responses increased progressively and provoked cell migration to the body wall and then to wound surfaces. Macrophages, NK cells, and granulocytes display similar features and behavior traits in invertebrates and vertebrates.

Animals↗
PubMed1999

[Combined renal and pancreas transplantation as treatment for chronic renal insufficiency of diabetic origin: a series of 50 consecutive transplantations].

STUDY AIM: The aim of this study was to report the results of 50 transplantations of kidney and pancreas performed in the same surgical centre for chronic renal insufficiency of patients with insulino-dependent diabetes. PATIENTS AND METHOD: From 1989 to 1999, 50 pancreatic transplantations were consecutively performed, 48 combined with a kidney transplantation and two in patients having a functioning kidney graft. The whole pancreas was transplanted in the right iliac fossa through an extraperitoneal approach with duodeno-vesical bypass of exocrine secretion. The kidney was transplanted in the left iliac fossa through a different extraperitoneal approach. Immunosuppression protocol included Azathioprine replaced by Mycophenolate Mofetil since 1996, associated with corticotherapy and Ciclosporine replaced by FK 506 since 1997. Recipients were 32 women and 18 men (mean age: 37 +/- 5 years) treated by insulinotherapy since 23 +/- 6 years and receiving 35 +/- 10 insulin units per day. Peptide C was 0.33 +/- 0.35 mg/mL and serum creatinin 726 +/- 260 mumol/L. RESULTS: One patient died on d10 from pulmonary artery thrombosis due to unknown drepanocytosis. The most frequent postoperative complications were leakage of duodeno-vesical anastomosis (n = 9) decreasing in frequency with experience, reoperated with preservation of the pancreatic graft in all cases and venous thrombosis of the pancreatic graft (n = 5) with a definitive loss of function. Secondary deaths occurred at 24, 36, 48, 50, 72 months with functioning grafts in two patients. With a mean 5-year follow-up, 44 patients were alive (88% of the whole series), 34 of them with two functional grafts (68% of the whole series) Sixteen pancreas grafts were lost: three by death of the patients, eight from surgical complications, four by rejection and one by transplantectomy of a functional graft. CONCLUSION: Combined kidney and pancreas transplantation is now very efficient in the treatment of diabetic renal insufficiency. Total pancreas transplantation through an extraperitoneal approach seems to be the safest method. A very strict selection of both donors and recipients is necessary.

Adult↗
PubMed1999

Possible roles of extracellular matrix and cytoskeleton in leech body wall muscles.

Round circomyarian fibres of leeches are peculiar helical muscles. The fibres are characterized by a lack of junctions, being separated by a thick extracellular matrix, and by scarce end-plates. Even so, the fibres grouped in units show the same degree of contraction. Biochemical, immunocytochemical and ultrastructural studies were performed in order: (a) to demonstrate the presence in the extracellular matrix of fibronectin, collagen type IV and laminin and in the cytoskeleton of desmin and alpha-actinin; (b) to show the possible link of extracellular matrix with the scaffold of intermediate filaments; (c) to evaluate how the extracellular matrix can play a role in the transduction of a signal during contraction-relaxation-superelongation phases.

Journal Article↗
PubMed1999

Propranolol in hypoglycaemia unawareness.

The effect of propranolol on the occurrence of hypoglycaemic symptoms was assessed in insulin-dependent diabetic patients with hypoglycaemia unawareness. A double-blind, randomised parallel group study (2:1 fashion) was conducted over 4-week period. The propranolol group (n = 9) received 20 mg (week 1 and 2) and 30 mg (week 3 and 4) twice daily, and the other group (n = 5) a matched placebo for 4 weeks. Patients included had experienced at least two severe hypoglycaemic episodes (coma or seizures) during the previous year, which were characterised by a lack of adrenergic symptoms and required the assistance of another person. The mean number of hypoglycaemias during the study period was similar in both groups (placebo: 13 +/- 2 propranolol: 11 +/- 1), whereas the number of totally asymptomatic hypoglycaemias (< 0.6 g/l) was lower on propranolol than on placebo (3 +/- 1 vs 8 +/- 3, NS) and the number of symptomatic hypoglycaemias was higher (7.2 +/- 2 vs 4.6 +/- 1, NS). Subjective evaluation of treatment by the investigators showed 0/5 successes in the placebo group and 5/9 in the propranolol group (chi2 = 4.32, p = 0.038). The main advantage of propranolol over placebo was an increased incidence of sweating. The ratio [number of hypoglycaemias with sweating/total number of hypoglycaemias] being higher with propranolol (0.28 +/- 0.08 vs 0.06 +/- 0.02, p = 0.06). This pilot study suggests that beta-blockers may be useful in restoring adrenergic symptoms during hypoglycaemia in insulin-dependent diabetic patients without warning symptoms of hypoglycaemia. This beneficial effect seems to be predominantly related to an increase in hypoglycaemia-induced sweating. A larger study is needed to confirm or invalidate these preliminary results.

Adrenergic beta-Antagonists↗
PubMed1999

[Epidemiology of cardio-vascular complications of diabetes].

Epidemiologic studies indicate that hyperglycaemia is responsible for microangiopathy, but that its role in macroangiopathy is more controversial. The relative risk of coronary heart disease (CHD) is 2- to 3-fold greater for diabetic men and 3- to 5-fold greater for diabetic women. It is greater for lower limb arteriopathy (4- to 6-fold) and amputations (10- to 20-fold). Although relative risk is rather constant for different populations, absolute CHD risk depends on other risk factors and the rate of risk in the non-diabetic population. Yet hyperglycaemia is also a causal factor for CHD risk, as demonstrated in cohort studies of Type 1 diabetic patients without diabetic glomerulopathy or any associated CHD risk factors, and especially in diabetic Pima Indians who are genetically protected against hypercholesterolaemia and hypertension. Finally, according to WESDR and UKPDS data, the 10-year risk of cardiovascular mortality increases by 10% for every 1% increase in HbA1c value. Hyperglycaemia can be linked to atherogenesis through several pathways: gluco-oxidation of the extracellular matrix inducing accelerated atherosclerosis, endothelial dysfunction, with a decreased production or inactivation of NO, a thrombogenic tendency, with increase in PAI1, Willebrandt factor and platelet aggregation, and last (but not least) dyslipidaemia subsequent to lipoprotein glycooxidation and increased production of VLDL. Hyperglycaemia was associated with hyperlipoproteinaemia and high plasma triglyceride levels, low plasma HDL levels and high plasma levels of small and dense LDL in three high risk populations: diabetic women, Asian migrants, and the Finnish population of Kupsio. Moreover, impaired glucose tolerance appears to be a CHD risk marker indicative of insulin resistance apparently responsible for atherosclerosis related to an association of CHD risk factors rather than to hyperinsulinaemia. The precedence of insulin resistance over onset of Type 2 diabetes is consistent with the existence, at diagnosis, of clinical complications of atherosclerosis in 20% of cases, as confirmed in the UKPDS study. Finally, though blood glucose control by sulphonylureas and insulin does not appear to be deleterious, these drugs have not shown their efficacy in reducing macrovascular adverse events in Type 2 diabetes, either because the cumulative incidence of events is inadequate (DCCT) or the efficacy of long-term hypoglycaemic effects is not apparent (UKPDS). Moreover, these studies have shown that exogenous as well as endogenous hyperinsulinaemia can lead to increase in weight, with potentially atherogenic android fat distribution. In conclusion, though the correlation between hyperglycaemia and microangiopathy is linear and well-established worldwide (with every 1% increase or decrease in HbA1c resulting in a 30% increase or decrease in microangiopathic events), the same is not true for macroangiopathy, whose prevalence is variable among populations. Thus, CHD mortality due to diabetes is 5-fold lower in France than in Finland, though the Monica study indicates a disparity within the French community.

Cardiac Output, Low↗
PubMed1997

Phobic symptoms, particularly the fear of blood and injury, are associated with poor glycemic control in type I diabetic adults.

OBJECTIVE: To investigate the presence of psychiatric disorders and symptoms in type I diabetic patients and to identify those that may influence metabolic control as assessed by GHb levels. RESEARCH DESIGN AND METHODS: This was a cross-sectional study. One hundred and two consecutive patients with type I diabetes who were regular outpatient visitors of a diabetology department were evaluated. The psychiatric assessments included self-rating questionnaires (General Health Questionnaire and Fear Questionnaire) and observer-rating questionnaires (Montgomery-Asberg Depression Rating Scale [MADRS] and Mini International Interview). Diabetic characteristics were assessed by a structured interview. The observer was blind to the diabetic characteristics of the patients. RESULTS: Type I diabetic patients with GHb levels > or = 8% had higher psychological distress, scored significantly higher for symptoms of agoraphobia and for fear of blood and injury, had substantially higher levels of anxiety-depression, and performed significantly fewer blood glucose measurements per day. They did not differ in MADRS score from patients with GHb levels < 8%. Multivariate analysis showed that GHb was positively associated with the total score of phobic symptoms and the level of anxiety-depression and inversely associated with the number of daily blood glucose measurements. These factors explained 41% of the variance of GHb. The inverse relationship between GHb and the number of blood glucose measurements per day was mainly influenced by the fear of blood and injury. Patients with high scores for the fear of blood and injury performed fewer blood glucose measurements and had poorer glycemic control; conversely, subjects without fear of blood and injury performed more daily blood glucose measurements and had better glycemic control. CONCLUSIONS: Phobic symptoms are frequent in patients with type I diabetes. The intensity of phobic symptoms and anxiety-depression negatively influences metabolic control. Increased fear of blood and injury may lead some patients to perform few home blood glucose measurements and may result in poorer glycemic control. This suggests that, by decreasing the fear of blood, injury, and injection, metabolic control may be improved.

Adolescent↗