Search PubMed⌕ Search

Biomedical subjects

D Maugendre

Publications and source records attributed to D Maugendre.

49 records · Page 3Linked to original sources
PubMed1991

Acute insulin response to intravenous glucose, glucagon and arginine in some subjects at risk for type 1 (insulin-dependent) diabetes mellitus.

The relationships between first-phase insulin secretion to i.v. glucagon and i.v. arginine were studied in 19 healthy adult volunteers (Group I) and in 21 subjects at risk for Type 1 (insulin-dependent) diabetes mellitus with either a "normal" (n = 11; Group IIa) or a "low" insulin response to i.v. glucose (n = 10; Group IIb). Groups I and IIa displayed similar insulin responses to the three secretagogues. In contrast, Group IIb demonstrated lower insulin responses to both glucagon and arginine than control subjects (p less than 0.007 and p less than 0.04 respectively) or than "normo-responders" to glucose (p less than 0.007 and p less than 0.04 respectively). In Group IIb however, arginine-stimulated insulin release was increased compared to the response to glucose (p less than 0.006), while glucagon and glucose led to non-statistically different responses. Five "low-responders" developed Type 1 diabetes. As a group, they displayed lower responses to glucagon and to arginine than subjects who up to now have not developed the disease (p less than 0.05 and p less than 0.0003 respectively). In the subjects who progressed to diabetes, the responses to glucose and glucagon were similarly blunted. In the "low-responders" who have not developed the disease, no statistical difference could be detected between mean responses to glucagon and glucose, but four out of these five subjects had a glucagon-stimulated response within the control range and higher than their corresponding response to glucose. Arginine led to a higher stimulation than glucose, in subgroups that either progressed to diabetes (p less than 0.006) or did not (p less than 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Beta-cell cytoadherent lymphocytes in some subjects at risk for type 1 (insulin-dependent) diabetes: progression to diabetes within 2 years.

The increased binding in vitro of CD3 CD4 T-lymphocytes from type 1 (insulin-dependent) diabetic patients to beta-cell membrane antigens compared to lymphocytes from control subjects was previously shown to be a marker of cell-mediated immunity, called diabetic rosettes. In the present study diabetic rosettes were detected in some subjects at risk for type 1 diabetes (first degree relatives of type 1 diabetic patients or nondiabetic subjects with previous transient hyperglycaemia). The mean number of lymphocytes adherent to beta-cells (beta-CL) was significantly higher in subjects at risk for type 1 diabetes than in age- and sex-matched control blood bank donors (P less than 10(-6]. This number of beta-CL was higher in type 1 diabetic patients than in subjects at risk (P less than 10(-6], and one-way analysis of variance by rank (Kruskal-Wallis) revealed that the three populations (controls, diabetics, and risk subjects) were different in terms of beta-CL values (P less than 0.001). The percentage of subjects at risk that had a positive test (arbitrarily defined as a beta-CL value higher than the 95th percentile of 228 controls) was 20%. No difference was observed between the two subgroups of subjects at risk in terms of either mean +/- SEM of beta-CL or percentages of individuals with a positive test. These diabetic rosettes were slightly associated with acute insulin response to iv glucose lower than the 5th percentile of controls (immunoreactive insulin at 1 +/- 3 min, 250 pmol/L; by chi 2, P = 0.04) and with HLA DR 3/4 heterozygosity (by chi 2, P = 0.04). They were not associated with islet cell antibodies (regardless of the threshold for positivity, expressed in Juvenile Diabetes Foundation units), insulin autoantibodies, activated (HLA DR+) T-lymphocytes, or sex. A statistical association was detected between HLA DR 3/4 heterozygosity and a low acute insulin response to iv glucose (by chi 2, P less than 0.003). The preliminary (2-yr) longitudinal follow-up revealed that out of five islet cell antibody-positive subjects who progressed to type 1 diabetes, three displayed beta-CL values higher than the 90th percentile of controls. Diabetic rosettes could, thus, be detected in some individuals at risk for type 1 diabetes as a marker of cell-mediated immunity.

Adult↗
PubMed1990

["Diabetic rosettes": a cellular immunity marker in subjects at risk for type I diabetes].

The authors have previously described a marker of cell-mediated, called "diabetic rosettes", revealed by the increased binding of CD3 CD4 lymphocytes from type I diabetic patients to beta-cell membrane antigens, as compared to lymphocytes from control subjects. In the present study, they have detected such "diabetic rosettes" in some subjects at risk for type I diabetes. The mean value of lymphocytes adhering to beta (RINm5F)-cells (beta-CL) was statistically higher in those subjects at risk than in control blood bank donors (p = 0.003). When a positive test was arbitrarily defined as a value of beta-CL higher than the 95th percentile of controls, 20 p. cent of the subjects at risk were classified as beta-CL+. No difference was observed between two subgroups of subjects at risk: first degree relatives of type I diabetic patients, and non-diabetic subjects with transient hyperglycaemia. "Diabetic rosettes" were associated with HLA DR 3/4 heterozygosity (p less than 0.04) and with a "low" acute insulin release to IV glucose (p = 0.05). They were not associated with islet-cell antibodies, insulin autoantibodies, or "activated" (HLA DR+) T-lymphocytes. The authors suggest that "diabetic rosettes" represent a marker of cellular immunity in some subjects at risk for type I diabetes.

Adolescent↗
PubMed1989

Class II MHC antigen induction on rat insulinoma (RINm5F) and colon carcinoma (TS) cells by co-culture with diabetic and normal xenogenic lymphocytes.

Two MHC Class II-negative rat epithelial cell lines (RINm5F beta-cells and TS colic cells) were co-cultured with xenogenic lymphocytes from Type I diabetic patients or from low-dose streptozotocin (SZ) diabetic mice. MHC Class II antigens (Ag) were easily induced on both cell lines in such co-culture conditions, representing an experimental approach to insulitis. Our data indicate that: (1) lymphocytes from diabetic patients or from SZ mice were more efficient than lymphocytes from healthy controls in inducing Class II Ag on RIN cells. Lymphocytes from patients with autoimmune thyroid diseases were also more efficient than control lymphocytes, indicating that the ability to induce Class II may be related to the activation of lymphocytes rather than being diabetes-specific. (2) Rat colon carcinoma cells (TS) were also induced to express high levels of Class II Ag upon co-culture with SZ or control mouse lymphocytes. (3) Class II+ RIN cells were observed after 24 h of co-culture; their number increased after 48 and 72 h. The number of class II+ RIN increased proportionally to the number of lymphocytes in the culture. (4) Induction of Class II Ag was obtained by cell-free supernatants of mouse lymphocytes/RIN co-cultures and was inhibited by cyclosporine A, suggesting that Class II induction in this model is mediated by lymphokines. (5) Depletion experiments indicate that both monocytes and lymphocytes play a role in this Class II induction.

Animals↗
PubMed1988

Inhibition of insulin release in vitro mediated by mononuclear cells from diabetic patients treated with cyclosporin A or placebo.

Anti-beta-cell-specific cell-mediated immunity was studied over a 12-mo period in 65 recently diagnosed diabetic patients randomly receiving either cyclosporin or placebo. Anti-beta-cell cellular immunity was assessed by an in vitro test based on the inhibition of insulin release from cultured rat islet cells by patients' mononuclear cells. This beta-cell-suppressive effect disappeared in cyclosporin A-treated patients within 1 mo and did not reappear during 12 mo of follow-up. Conversely, the suppressive effect persisted unchanged in placebo-treated patients during 12 mo of follow-up. These changes were predictive neither of cyclosporin A-induced remission nor of relapses. Results of the insulin-release inhibition test were not correlated to islet cell autoantibodies or HLA phenotype.

Adolescent↗
PubMed1987

Cytoadherence of lymphocytes from type I diabetic subjects to insulin-secreting cells. Marker of anti-beta-cell cellular immunity.

We studied the ability of lymphocytes from type I (insulin-dependent) diabetic patients to adhere to murine beta-cells. Lymphocytes from 17 recent-onset type I diabetic subjects (less than 6 mo) displayed enhanced ability to form rosettes with RINm5F cells (P less than .001) compared with lymphocytes from 27 healthy subjects forming background rosettes, whereas the number of RIN cytoadherent lymphocytes was unimpaired in 12 type II (non-insulin-dependent) diabetic subjects. This phenomenon tended to decline in 21 subjects with long-standing diabetes (greater than 1 yr) who taken as a group presented a normal number of RIN rosetting lymphocytes. The islet specificity of these diabetic rosettes was confirmed because, compared with controls, lymphocytes from recent-onset type I diabetic subjects also displayed a greater intensity of adherence to normal mouse islets but not to unrelated K562 and TS cell lines. As demonstrated by indirect immunofluorescence studies, these diabetic rosettes contained 54% of T-lymphocytes (OKT3+, OKT4+, or OKT8+), whereas only 20% of T-lymphocytes were found in background rosettes. The high percentage (66%) of la+ cells found in diabetic rosettes suggests that at least some of the cytoadherent T-lymphocytes from recent-onset type I diabetic subjects are activated. Natural killer (NK) cells do not seem to be the major cell type implicated in this phenomenon, because Leu 11+ cells were less represented in diabetic rosettes (25%) than in background rosettes (53%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMedDate not supplied

Inter and intra individual variability of acute insulin response during intravenous glucose tolerance tests.

To analyze the inter- and intra-individual variability of acute insulin response to intravenous glucose (AIRG), 41 healthy volunteers underwent an intravenous glucose tolerance test (IVGTT) and 29 of them a second IVGTT 1 to 9 months later. Basal glycemic, insulin (IRI), and C-peptide values were similar for both IVGTTs. Different indices were used to estimate AIRG. A great inter-individual variability of AIRG (CV around 60%) was detected. AIRGs were not statistically different between the two IVGTTs, and the within-subject variation was fair at the group level (CVs approximately 30%). However, individual coefficients of variation ranged from 2 to 60% between the two tests. Moreover, subjects considered as "low" responders during test 1, returned to "normal" values during test 2. Conversely, other subjects dropped to a "low" response in IVGTT 2. Insulin peak (IRI max) occurred between 1 and 3 minutes after glucose infusion in 85% of the control population, but time points of IRI max were different for 45% of the population between the two IVGTTs. These results suggest that AIRG during IVGTTs are reproducible at the group level, but that AIRG has to be interpreted with caution in individual early detection of pre-insulin-dependent diabetes mellitus because inter- and intra-individual variability could be high even for some normal subjects.

Adult↗
PubMedDate not supplied

Effects of cyclosporin on autoimmune diabetes induced in mice by streptozotocin: beta cell-toxicity and rebound of insulitis after cessation of treatment.

We have investigated the effects of an oral cyclosporin (CsA) treatment on "autoimmune" diabetes induced in CD1 male mice by 5 low doses (40 mg/kg/day) of streptozotocin (SZ). CsA (50, 25, or 12.5 mg/kg/day) induced significant hyperglycaemia and insulinopenia by the 3rd day after the last SZ injection, whereas mice receiving SZ only remained non diabetic at that time. Enhancement of SZ-induced diabetes by CsA was thus noted. Mice receiving CsA and SZ displayed a significantly higher number of degranulated and necrotic beta cells. Similarly, CsA enhanced "toxic" diabetes produced by a single high dose of SZ. Furthermore, mice treated with CsA alone displayed glucose intolerance, insulinopenia, and high pancreatic CsA content. These abnormalities were reversed by 2 weeks after CsA withdrawal. Islets isolated from CsA treated mice displayed in vitro decreased stimulated insulin secretion. During the period of administration, CsA led to a decrease of Lyt 1 +/Lyt 2 + ratio in spleen cells and prevented the insulitis in low dose SZ-treated mice. However, at CsA withdrawal, a rebound of insulitis occurred with a higher intensity. Immunohistochemical phenotyping on frozen pancreatic sections revealed that Lyt 1 + lymphocytes predominated on Lyt 2 + cells in the rebound insulitis. In this model: (1) CsA impairs glucose stimulated insulin release and alters beta cells. This reversible toxic effect accounts for enhancement of SZ-induced diabetes; (2) insulitis was slackened by CsA but developed, as a rebound, with CsA withdrawal associated with a prominence of Lyt 1 + lymphocytes.

Animals↗
PubMedDate not supplied

Increase in thiobarbituric acid-reactive substances and vascular complications in type 2 diabetes mellitus.

Lipid peroxidation was assessed by measuring the concentrations of thiobarbituric acid-reactive substances in plasma from 204 Type 2 diabetic patients, relative to 107 controls. The concentrations obtained in diabetic patients (3.08 +/- 0.37 mumol/l) were significantly higher than in controls (2.80 +/- 0.34 mumol/l) (p < 0.0001). Values were also significantly increased in patients with macroangiopathy and/or microangiopathy (3.17 +/- 0.41 mumol/l), relative to patients void of vascular complications (2.92 +/- 0.34 mumol/l) (p < 0.001). Elevated concentrations were independent of the type of vascular complication and their possible associations. In patients without vascular affection, thiobarbituric acid-reactive substances were in significantly higher concentrations in hypertensive (3.07 +/- 0.36 mumol/l) than in normotensive (2.87 +/- 0.29 mumol/l) (p < 0.01) patients. There was a correlation between these values and those of total cholesterol (r = 0.46, p < 0.0001) and triglyceride (r = 0.45, p < 0.0001). Statistical analysis by multivariate logistical regression revealed that among the independent factors (TBARS, APO A1, hypertension, age), thiobarbituric acid-reactive substances constituted the parameter most strongly linked to the existence of vascular complications. This study has evidenced a lipid peroxidation disorder in non insulin- dependent diabetes mellitus, more marked in patients with vascular affection. Thiobarbituric acid-reactive substances appear to be an independent marker of vascular complications in Type 2 diabetes.

Adult↗
PubMedDate not supplied

Predictive value of age-related acute insulin response to glucose in subjects at risk for type 1 diabetes: results of a 6-year follow-up study from west-France.

The acute insulin response to i.v. glucose (AIRG) was evaluated in 344 first-degree relatives of patients with Type 1 diabetes. In 318 relatives aged 3 to 48 years without islet cell antibody and insulin autoantibody, correlations (p < 0.0006) were found between age and fasting insulinaemia, fasting glycaemia, or AIRG, with a peak during puberty. Assuming that these relatives without islet cells and insulin auto-antibodies have a low risk of developing Type 1 diabetes, we provided a "standard age-related chart" for AIRG with a "low" AIRG defined as a value below the 1st percentile for each pubertal stage. Using these cut-off points, predictive characteristics of a low AIRG for progression towards diabetes within 6 years were analysed. Four relatives developed diabetes and one displayed impaired oral glucose tolerance. Four out of these 5 subjects had islet cell and insulin auto-antibodies, but the other one was negative for these markers. Three of these 5 subjects had low AIRG at entry (30, 24 and 1 months before diabetes, respectively). The two others displayed a steady progressive decline (p < 0.02) of age-related during the follow-up before impaired oral glucose tolerance and diabetes appeared (rate of decline: 15 microU/ml/year). Thus, independently of the presence of islet cell antibodies, the predictive value of a low age-related AIRG during the follow-up is greater than the single low AIRG at entry.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗