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Biomedical subjects

B Vialettes

Publications and source records attributed to B Vialettes.

At least 55 records · Page 3Linked to original sources
PubMed1998

Diverging evolution of anti-GAD and anti-IA-2 antibodies in long-standing diabetes mellitus as a function of age at onset: no association with complications.

Glutamic acid decarboxylase autoantibodies (GAD-A) and tyrosine phosphatase IA-2 autoantibodies (IA2-A) were measured in sera of 50 recently diagnosed (<6 wk, 33% younger than 15 yr), 19 short-term (1 to 9 yr, 35% with onset age below 15 yr) and 89 long-standing diabetic patients (>10 yr, 57% with onset age below 15 yr). Complications were assessed by clinical examination, retinal angiographs and microalbuminuria measurement. Both prevalences and levels of GAD-A and IA2-A decreased with increasing duration of diabetes. However even in those with long duration diabetes, 15 to 63% of the sera were still positive for one or two antibodies. In the group with onset after the age of 15 yr, significantly higher prevalences and levels of GAD-A (but not IA2-A) was observed in comparison with the group with earlier onset. No association was found with any microvascular complications in any group. We conclude that GAD-A and IA2-A persist in some diabetic patients, despite a long duration. Persistence of GAD-A was greatest in those with postpubertal disease onset. We speculate that persistence of some beta-cells or specific environmental factors can sustain one autoimmune reaction especially in some postpubertal-onset diabetic patients.

Adolescent↗
PubMed1998

Study of serum big-insulin-like growth factor (IGF)-II and IGF binding proteins in two patients with extrapancreatic tumor hypoglycemia, using a combination of Western blotting methods.

Extrapancreatic tumor hypoglycemia (EPTH) is associated with increased amounts of high-molecular-weight precursor forms of insulin-like growth factor (IGF)-II ('big-IGF-II') that have a primary role in the pathophysiology of hypoglycemia. In the present study, using Western ligand and immunoblotting methods, we investigated IGF-binding proteins (IGFBPs), IGFBP-3 proteolysis and big-IGF-II in pre- and postoperative serum from two patients with EPTH due to benign pleural fibroma. In the preoperative serum, IGFBP-3 was reduced and IGFBP-2 was increased compared with that from an age-matched healthy control. IGFBP-3 proteolysis was dramatically reduced in one patient, whereas no major alteration was observed in the other (9% and 120% of control serum, respectively). IGFBPs progressively returned to a subnormal pattern in postoperative serum, whereas IGFBP- 3 proteolysis remained greater than in preoperative serum in both patients at days 14 and 90 after surgery. High-molecular-weight forms of IGF-II predominate in EPTH serum (65% and 57% of total IGF-II immunoreactivity in patients 1 and 2, respectively, compared with 2 5% in control serum). Two forms, of molecular mass 10 and 12 kDa ('standard big-IGF-II') were present in both EPTH and control sera, whereas two additional forms, of molecular mass 15 and 18 kDa ('big big-IGF-II') were observed in EPTH sera only. Big big-IGF-II represented 72% and 55% of total high-molecular-weight forms of IGF-II in the two EPTH sera, respectively. All big forms of IGF-II disappeared from the serum as early as 6 h after surgery. This study shows that combination of simple Western blotting methods, available routinely in most laboratories, should prove useful in providing reliable physiopathological information in EPTH.

Blotting, Western↗
PubMed1998

[Food preferences in anorectic girls at the beginning of therapy].

To determine the eating habits of patients with anorexia nervosa, we compared a group of 21 anorectic girls satisfying DSM-III-R criteria (A: 19 +/- 6.6 years; 14.2 +/- 2 kg/m2) with 30 control girls (C: 19.8 +/- 3.3 years; 20.9 +/- 4.4 kg/m2). A standardised form listing 226 food items was used to assess their food preferences. For each food category except vegetables and fish, the medium rate of positive appreciation was lower in group A than in group C. However, a positive correlation was found between the two groups (except for dairy and diet products), showing no major distortion of taste in group A. Anorectic girls generally discarded the sweetest fruit and the fattest meats, but sometimes chose to eat high-calorie food, possibly because of its supposed nutritional value. Their dislike for so-called "light" products was also apparent. Moreover, no regressive tendency to childish choices was found in their eating habits. It is concluded that group A displayed a narrowed food field, but without distortions of taste.

Adolescent↗
PubMed1997

Specific reg II gene overexpression in the non-obese diabetic mouse pancreas during active diabetogenesis.

The reg gene, previously described in islets of 90% pancreatectomized and nicotinamide-treated rats, has been shown to be expressed in many pharmacological or surgical animal models of beta cell regeneration. We have studied the non-obese diabetic (NOD) mouse, which represents a good model of spontaneous autoimmune diabetes in which regenerative processes have recently been demonstrated. Two reg genes have been described in the mouse genome, both recognized by the human reg cDNA. In a previous work, using the human probe, we have demonstrated a strong correlation between pancreatic reg gene expression and the likelihood of developing diabetes. In the present study, we have examined the respective levels of both mouse reg I and reg II mRNA in the NOD mouse pancreas using their specific cDNA probes. We found that reg II expression was specifically prevalent compared to reg I, irrespective of sex or state of the disease. Reg II mRNA was particularly increased in overtly diabetic female mice and in cyclophosphamide-treated male mice. These data underline the need to study separately the reg genes using specific probes and show that both reg genes are subjected to various regulations, strongly suggesting that their physiological functions may be different.

Animals↗
PubMed1997

Multilocus linkage of familial hyperkalaemia and hypertension, pseudohypoaldosteronism type II, to chromosomes 1q31-42 and 17p11-q21.

Essential hypertension is a common multifactorial trait. The molecular basis of a number of rare diseases that after blood pressure in humans has been established, identifying pathways that may be involved in more common forms of hypertension. Pseudohypoaldosteronism type II (PHAII, also known as familial hyperkalaemia and hypertension or Gordon's syndrome; OMIM #145260), is characterized by hyperkalaemia despite normal renal glomerular filtration, hypertension and correction of physiologic abnormalities by thiazide diuretics. Mild hyperchloremia, metabolic acidosis and suppressed plasma renin activity are variable associated findings. The pathogenesis of PHAII is unknown, although clinical studies indicate an abnormality in renal ion transport. As thiazide diuretics are among the most efficacious agents in the treatment of essential hypertension, understanding the pathogenesis of PHAII may be of relevance to more common forms of hypertension. Analysis of linkage in eight PHAII families showing autosomal dominant transmission demonstrates locus heterogeneity of this trait, with a multilocus lod score of 8.1 for linkage of PHAII to chromosomes 1q31-q42 and 17p11-q21. Interestingly, the chromosome-17 locus overlaps a syntenic interval in rat that contains a blood pressure quantitative trait locus (QTL). Our findings provide a first step toward identification of the molecular basis of PHAII.

Animals↗
PubMed1997

Clinical aspects of mitochondrial diabetes.

Mitochondrial diabetes is a new nosological entity, the most common form of which is maternally inherited diabetes and deafness (MIDD) syndrome. In this syndrome, delayed insulin dependency is frequently observed, although any form of glucose intolerance is possible. The mechanism of diabetes is localised at the beta-cell level. The participation of an autoimmune process in beta-cell loss is still controversial. An association with macular pattern dystrophy and infraclinical myopathy is common and can facilitate diagnosis. Muscle 31-P MR spectroscopy is a non-invasive tool to detect oxidative and phosphorylative alterations and monitor the reversion of these anomalies through specific treatments. Numerous other mutations, deletions or duplications of mtDNA have been associated with diabetes. The description of mitochondrial diabetes is still in progress. In future, an understanding of the mechanism of glucose intolerance in these diseases should open the way to specific preventive treatments in subjects carrying diabetogeneic mutations of mtDNA.

DNA, Mitochondrial↗
PubMed1997

Pseudohypertriglyceridaemia.

A mistake can be made in interpreting plasma triglyceride levels since in some cases pseudohypertriglyceridaemia may result from increased plasma glycerol due to a glycerol kinase deficit. Most automated triglyceride assays used in laboratories do not contain a negative control, i.e. a glycerol assay. We report two cases with pseudohypertriglyceridaemia due to hyperglycerolaemia and describe the clinical and biological features which suggested the diagnosis.

Adult↗
PubMed1997

Different TH2-TH1 balance in V beta 8 and V beta 6 subsets of splenocytes in NOD females in the early phase of diabetogenesis.

Non-obese diabetic (NOD) mice spontaneously develop T-cell-mediated autoimmune diabetes. Initial work on the diabetogenic T-cell repertoire indicated that autoreactive T lymphocytes were polyclonal but that the presence of specific subsets (V beta 8 or V beta 6) might be required for induction of the disease. Further functional analysis of NOD mice T lymphocytes was limited because of the relative anergic state of these cells due to abnormal patterns of cytokine secretion. The purpose of the present study was to establish experimental conditions allowing the exploration of the functional features of minor T-lymphocyte subsets in vitro using low doses of cofactors. The ability of splenocytes to proliferate, respond to, or secrete interleukin-2 and interleukin-4 was explored in young, pre-diabetic or old non-diabetic female NOD mice. No significant bias in T-cell receptor usage was noted in the spleen of these animals, whereas V beta 6 + lymphocytes could be very efficiently stimulated by interleukin-4 and also produce low but detectable amounts of interleukin-4 during the pre-diabetic period in female NOD mice. These results suggest that diabetes induction is preceded by V beta + subset-specific functional changes in the ability of various T cells to respond to or secrete interleukin-2 and interleukin-4, indicating a functional imbalance of the T-cell repertoire expanded by the autoimmune process.

Animals↗
PubMed1996

Insulin kinetics in type I diabetic patients treated by continuous intraperitoneal insulin infusion: influence of anti-insulin antibodies.

Continuous intraperitoneal insulin infusion (CIPII) is a promising therapy of patients with Type 1 (insulin-dependent) diabetes mellitus (IDDM), since it improves metabolic control and decreases frequency of severe hypoglycaemia. This could be due to more appropriate insulin kinetics. Our aim, therefore, was to compare plasma free insulin levels achieved in patients with Type 1 diabetes chronically treated with CSII or CIPII. Furthermore, as anti-insulin antibodies increase with this treatment, we wanted to assess their influence upon insulin kinetics. Plasma free insulin profiles were obtained during the night and then after the bolus for breakfast and the bolus for lunch in 11 patients with Type 1 diabetes treated successively by CSII and CIPII. In another group of 16 patients with long-term Type 1 diabetes, treated by CIPII, we examined the influence of anti-insulin antibody level on insulin kinetics after a bolus. During the night, plasma free insulin levels were lower with CIPII than with CSII (12:00 am: 10.1 +/- 1.7 vs 18.5 +/- 2.6 mU l-1; 4:00 am: 9.1 +/- 2 vs 15 +/- 3 mU l-1), p < 0.01. After the bolus, CIPII lead to an earlier (1h vs 3h) and higher (25.8 +/- 3.3 vs 18 +/- 2.7, p < 0.05) plasma free insulin peak than CSII. With CIPII, the return to baseline level was observed within 3 h. Conversely, during CSII, insulin levels did not return to baseline until the next meal. After the bolus, high insulin-antibody levels were associated with a reduced maximal value of plasma free insulin peak. Taken together, these findings suggest that CIPII provides plasma free insulin profiles which are much closer to physiology than CSII. This could explain the lower rate of severe hypoglycaemia observed with this type of treatment. But in long-term CIPII treated patients with high anti-insulin antibody level, insulin profile could be moderately modified. This emphasizes the need for a less immunogenic insulin preparation.

Adult↗
PubMed1996

A new mutation of the gene encoding the transcription factor Pit-1 is responsible for combined pituitary hormone deficiency.

The pituitary-specific transcription factor Pit-1/GHF1 regulates the expression of PRL, GH, and TSH beta genes through binding to specific regions of the promoters of these genes. Mutations of the Pit-1 gene have been shown to be responsible for a syndrome of combined pituitary hormone deficiency (CPHD), including complete GH and PRL deficiencies and central hypothyroidism. We studied four siblings presenting with CPHD born to healthy consanguinous parents. All four affected children had complete GH deficiency diagnosed in early childhood. They later developed hypothyroidism and were found to have undetectable PRL levels. The pituitary gland was hypoplastic at magnetic resonance examination in one of the patients. Amplification of genomic DNA and subsequent sequencing of the six exons of the Pit-1 gene allowed identification in the four patients with CPHD of an as yet undescribed mutation in exon 3. A substitution of T go G induced a change from a Phe to a Cys residue at position 135 within the hydrophobic core of the POU-specific DNA-binding domain of the Pit-1 protein. All affected children were homozygous for the mutation, whereas the mother was heterozygous, suggesting a recessive mode of inheritance. Molecular studies in other affected families will allow instructive genotype-phenotype correlations concerning the Pit-1 gene.

Adolescent↗
PubMed1996

Insulin-induced lipoatrophy in type I diabetes. A possible tumor necrosis factor-alpha-mediated dedifferentiation of adipocytes.

OBJECTIVE: To test the hypothesis that tumor necrosis factor (TNF)-alpha may mediate the loss and the dedifferentiation of subcutaneous fat tissue in the insulin-induced lipoatrophies of a diabetic patient who presented extensive lesions. RESEARCH DESIGN AND METHODS: An in vitro exploration of cytokine production by peripheral blood mononuclear cells (PBMC) from the reported case was performed and compared with the same explorations of PBMC from three nondiabetic subjects and three diabetic patients without lipoatrophic lesions. A proliferation test and an evaluation of TNF-alpha and interleukin (IL)-6 production from PBMC in presence of insulin were studied. RESULTS: The production of TNF-alpha and IL-6 by the macrophages of the patient in presence of insulin were dramatically increased in comparison with control subjects. This process needed cooperation with other lymphoid cells and was abrogated by dexamethasone. CONCLUSIONS: In our reported case, a local hyperproduction of TNF-alpha from macrophages that was induced by the injected insulin could explain the dedifferentiation of the adipocytes of the subcutaneous tissue and the reversion that was induced by the local injection of dexamethasone.

Adipocytes↗
PubMed1996

Reg protein: a potential beta-cell-specific growth factor?

Beta-cell regeneration in adult pancreas is usually considered to be limited. However, various animal models suggest that this tissue is still capable of regeneration under certain conditions. Reg protein could be responsible for this replicative process. The reg gene codes for a 166 amino-acid protein usually synthesized and secreted by pancreatic acinar cells but expressed in islet beta cells during experimental regenerative processes in animals (90% pancreatectomy + nicotinamide, or insulinoma tumor removal in rats, or the "wrapping pancreas model" in the hamster). In addition, recombinant rat reg protein can stimulate beta-cell replication in vivo and in vitro. In animal models of Type 1 diabetes mellitus, reg gene overexpression occurs during active phases of diabetogenesis and could be a defence mechanism. During human pancreatic development, reg gene is expressed at an early stage but is not associated with the expression of other pancreatic genes. Conversely, gene expression for reg and insulin are correlated in adult pancreas. Accordingly, reg protein could be a beta-cell-specific growth factor implicated in the maintenance of beta-cell mass, especially in adult pancreas.

Animals↗