Biomedical subjects

D Chevenne

Publications and source records attributed to D Chevenne.

13 recordsLinked to original sources

PubMed1996

Distribution of HLA-DQA1 and -DQB1 alleles and DQA1-DQB1 genotypes among Senegalese patients with insulin-dependent diabetes mellitus.

Transracial analysis is one method for distinguishing primary associations between insulin-dependent diabetes mellitus (IDDM) and HLA II alleles from those related to linkage disequilibrium. Black people have different DR-DQ relationships from other races and are a useful group to investigate HLA-D regions associated with IDDM. In this study, we compared the frequencies of HLA-DQA1 and DQB1 alleles in Senegalese IDDM and control subjects. DQA1*0301 was positively associated with insulin-dependent diabetes mellitus (p < 10(-9), OR 5.21), as were DQB1*0201 and *0302 (p < 10(-7) OR = 3.55, p < 10(-3) OR = 3.20, respectively). The positive associations with DQA1*0301, DQB1*0201 and DQB1*0302 are consistent with all racial groups investigated. However, taken together, the data in Senegalese population show that susceptibility and resistance to IDDM are associated both with particular haplotypes and DQA1-DQB1 heterodimers.

Adolescent↗

PubMed1995

HLA-DQ beta 1 typing and non-Asp57 alleles in the aborigine population of Senegal.

OBJECTIVE: To investigate, in Senegalese subjects, the frequency of human leukocyte antigen (HLA)-DQ beta 1 alleles and their role in susceptibility to insulin-dependent diabetes mellitus (IDDM). RESEARCH DESIGN AND METHODS: HLA-DQ beta 1 typing was done in 55 IDDM subjects and 118 nondiabetic control subjects by means of polymerase chain reaction restriction fragment length polymorphism. RESULTS: Alleles bearing a codon for an Asp residue at position 57 in the DQ beta-chain were associated with a significantly lower risk of IDDM. Alleles 0201 and 0302 (Ala57) were positively associated with diabetes, but allele 0501 (Val57) was less frequent in IDDM subjects than in control subjects. CONCLUSIONS: HLA-DQ beta 1 alleles may be genetic susceptibility markers for IDDM in the Senegalese population, as they are in Caucasian populations.

Adolescent↗

PubMed1995

[Determination of plasma proinsulins, insulin and C-peptide].

Insulin is synthesized from a precursor, proinsulin, then converted in the beta cell by sequential limited proteolysis into insulin and C-peptide, which are stored in secretory granules derived from the Golgi apparatus. Since this process is incomplete, some intact and partially processed proinsulins (split proinsulins) remain trapped in the granules and enter the circulation with insulin and C-peptide. As proinsulins are present in low concentration in serum and show structural homology with insulin and C-peptide, only two-site immunoassays using monoclonal antibodies can achieve sensitive and specific measurements of their intact and split forms. Insulin radioimmunoassays using polyclonal antibodies are not specific since such antibodies cross-react with proinsulins. Two-site immunoassays using monoclonal antibodies improve the specificity and the sensitivity of insulin determination. C-Peptide concentration is measured by radioimmunoassays using polyclonal antibodies which cross-react with proinsulins.

C-Peptide↗

PubMed1995

[Growth hormone (GH) and insulin-like growth factor 1 (IGF-1) in nutritional status].

Nutrition plays a pivotal role in the regulation of growth hormone (GH) and insulin-like growth factor 1 (IGF 1) secretions; GH and IGF 1 in turn significantly influence the use of nutrients in humans and animals. Fasting, and caloric or protein restriction increase circulating values of GH and decrease those of IGF 1. These findings strongly suggest peripheral growth hormone resistance. Mechanisms accounting for this GH refractoriness could be a marked reduction in GH receptors, a decrease in binding of GH to its receptor, or post-receptor phenomena. Peripheral refractoriness to IGF 1 has also been described during caloric intake restriction. Metabolic effects of GH and IGF 1 are strongly dependent on a protein anabolic mechanism, and modifications of circulating levels of these hormones could be explained as an adaptation to the nutritional microenvironment of the cells. Because of the potent anabolic effects of GH and IGF 1 on protein metabolism, several authors have proposed treating severe catabolic states with GH or IGF 1. In humans both hormones seem to enhance protein anabolism but only for short periods. Secondary effects are mainly hypoglycemia with IGF 1 and hyperglycemia with GH. The combination of GH + IGF 1 could be a suitable approach to obtain a synergistic effect on protein metabolism and achieve normal blood glucose concentrations.

Animals↗

PubMed1994

Immunoradiometric assay of human intact proinsulin applied to patients with type 2 diabetes, impaired glucose tolerance, and hyperandrogenism.

We describe an immunoradiometric assay for human intact proinsulin in serum. In this method, one monoclonal antibody, coated onto polyacrylamide beads, cross-reacts with proinsulins and insulin. A sandwich is formed with intact proinsulin, split (65-66) proinsulin, and des (64-65) proinsulin binding with an 125I-labeled monoclonal antibody specific for an epitope at the intact B-C junction of proinsulin. Because split (65-66) and des (64-65) proinsulin concentrations are very low in serum, this assay essentially measures intact proinsulin. When we used 1-mL serum samples, the mean detection limit was 0.4 pmol/L. Mean proinsulin concentrations (pmol/L) were 3.4 (range 1-9.1) in healthy fasting subjects, 28.5 (9.7-101) in patients with type 2 diabetes (treated with metformin and sulfonylureas), 5.0 (1.6-9.3) in women with hyperandrogenism and normal insulinemia, 10.3 (2.6-36) in women with hyperandrogenism and hyperinsulinemia, and 8.5 (4.8-21.3) in patients with impaired glucose tolerance.

Adult↗

PubMed1993

The development of hyperglycaemia in patients with insulin-resistant generalized lipoatrophic syndromes.

Insulin resistance is present in patients suffering from lipoatrophic syndromes long before the onset of diabetes mellitus. Thus, the decreased peripheral glucose disposal may not be the only mechanism of hyperglycaemia. The kinetic parameters of glucose homeostasis were evaluated in six young females aged 15, 16, 18, 19 and 24 years with generalized lipoatrophy; one patient was studied both at 12 and 15 years. Insulin resistance was evaluated in vivo by the hyperinsulinaemic euglycaemic clamp (3-4 insulin infusion rates from 1 to 100 mU/kg.min). All patients showed a rightward shift of the dose-response curve, indicating decreased insulin sensitivity. In two patients, maximal glucose disposal was moderately decreased, while in five patients it was dramatically reduced (3.6-6.9 mg/kg.min). Fasting plasma glucose was variable (4.3-18.3 mmol/l) and did not correlate with peripheral glucose disposal rates. Hepatic glucose production, measured by infusion of [6,6-2H] glucose, varied from 1.7 to 8.3 mg/kg.min and was significantly correlated with fasting plasma glucose. The overproduction of glucose despite basal hyperinsulinism suggested hepatic insulin resistance, which was confirmed by the abnormal response to constant unlabelled glucose infusion (2 mg/kg.min) in five patients. In conclusion, impaired glucose tolerance seems to develop in generalized lipoatrophy with aggravated peripheral insulin resistance. The present data show that fasting hyperglycaemia is mainly the consequence of increased hepatic glucose production.

Adolescent↗

PubMed1993

Variability of serum human growth hormone levels in different commercial assays: specificity of growth hormone-releasing hormone stimulation.

Serum human growth hormone (hGH) levels were measured with three different commercial kits, comprising a radioimmunoassay (RIA) (bioMérieux, Marcy-l'Etoile, France, 'bmpoly') and two immunoradiometric assays (IRMA) (bioMérieux, 'bmmono', and CIS bioInternational, Gif-sur-Yvette, France, 'cismono'). Samples were collected after various stimulation tests [arginine-insulin, growth hormone-releasing hormone (GHRH), L-dopa and glucagon-beta-axolol] from children who were undergoing evaluation for short stature. Values obtained with the IRMAs were consistently lower than those obtained with the RIA. Furthermore, the cismono/bmmono and cismono/bmpoly values ratios were always significantly higher when samples were collected during GHRH stimulation than during the other stimulation tests. These data indicate that GHRH could induce a particular form of hGH molecule (in nature or in amount), recognized by the monoclonal antibodies in the cismono kit and that a specific form of hGH may be released by GHRH stimulation.

Child↗

PubMed1992

[Research of factors for glucose intolerance in mucoviscidosis].

Glucose tolerance has been assessed in cystic fibrosis (CF) children using HbA1C and plasma glucose and insulin determinations during an oral glucose tolerance test (OGTT), along with the determination of HLA-DR and islet-cell (ICA) and anti-insulin (IAA) antibodies. Of 49 patients (25 males, 24 females), aged 2 to 21 years (mean = 10.9 years), 29 had normal glucose tolerance (WHO criteria) during OGTT, 14 had impaired glucose tolerance (IGT) and 6 had an isolated hyperglycemia at 120 min. Fasting plasma glucose and HbA1C were significantly higher in IGT than in normoglycemic patients. However, these two parameters showed poor individual predictive value of disturbance in glucose tolerance. Of 14 patients with abnormal OGTT, 7 were aged below 10 years, with 2 as young as 5 years; 8 patients were females. HLA antigens characteristic of type I diabetes tended to be found less frequently in CF patients than in the general population: 9% were DR3, 7% were DR4 and none was DR3/DR4. There were no HLA differences according to glucose tolerance. ICA and IAA were respectively detected in only one patient. Stimulated plasma insulin was low but did not correlate with glucose tolerance. In conclusion, impaired glucose tolerance is common in cystic fibrosis and can be found early in life. Although insulin secretion is decreased in this population, it does not seem to be the only factor responsible for impaired glucose intolerance. The absence of the genetical and immunological characteristics of type I diabetes confirms that glucose intolerance in cystic fibrosis is due to other pathogenetic mechanisms.

Adolescent↗

PubMed1991

Relationship between first-phase insulin secretion and age, HLA, islet cell antibody status, and development of type I diabetes in 220 juvenile first-degree relatives of diabetic patients.

OBJECTIVE: To assess the adequacy of the first-phase insulin response for predicting development of insulin-dependent diabetes. RESEARCH DESIGN AND METHODS: Determinations were made of 1- and 3-min insulin responses to glucose (0.5 g/kg i.v.), islet cell antibodies (ICAs), insulin autoantibodies (IAAs), and HLA. We studied 220 first-degree relatives (aged 3-29 yr) of diabetic patients; 75 underwent two or more tests. RESULTS: At the first test, insulin responses correlated with age in ICA- children less than or equal to 11 yr old (r = 0.46, p less than 0.001). Individual responses varied widely in all ages, and low values were common (5th percentile: 108 pM in children less than 5 yr old, 180 pM thereafter). No correlation was found between insulin responses and IAAs or HLA. The responses of 15 ICA+ subjects were not significantly different from those of ICA- subjects after excluding the influence of age. At subsequent tests, ICA+ and ICA- subjects displayed distinct changes; the mean +/- SE insulin response increased in ICA- subjects from 619.2 +/- 40.8 to 716.4 +/- 50.4 pM (P less than 0.001) but declined in ICA+ subjects from 403.2 +/- 91.8 to 313.8 +/- 67.2 pM (P less than 0.02). During follow-up, 5 of 9 (56%) consistently ICA+ siblings developed diabetes or impaired glucose tolerance compared with 1 of 54 (2%) consistently ICA- subjects. The sensitivity and specificity of two or more low insulin responses (300 pM) for predicting progression to diabetes were 60 and 96%, respectively; the predictive value was 43%. The highest predictive value (75%) was achieved by the combination consistently ICA+, consistently low insulin response, and HLA-DR3/4. However, in no subject could the time of onset of diabetes be deduced from the decline of the insulin response. CONCLUSIONS: Consecutive intravenous glucose tolerance tests are a useful complement for predicting progression to diabetes but not its onset.

Age Factors↗

PubMed1991

[Somatomedins].

Somatomedins or insulin-like growth factors (IGFs) are two polypeptides (IGF I and IGF II) whose structure shows great homology with proinsulin. Mostly synthetized by the liver but also by many tissues, they circulate in blood bound to specific binding proteins (IGFBPs). IGFBP3, a 120 to 150 kDa complex, carries over 95% of blood IGFs and its production is stimulated by growth hormone (hGH). On the contrary, IGFBP1, a 40 to 50 kDa protein, increases in case of hGH-deficiency. An IGFBP of 34 kDa, which is the major BP in cerebrospinal fluid but also present in blood, shows a great affinity for IGF II whereas the others BPs show similar affinities for both IGFs. Little is known about the other BP, IGFBP2. Two receptors can be found in most tissues: type 1, which binds IGFs and insulin, type 2, which binds IGF II preferentially to IGF I but not insulin. Type 1 IGF receptor has structural and enzymatic (phosphorylation of one of its own sub-units) similarities with the insulin receptor and mediates the action of IGF I. Type 2 receptor has an homology with the bovine cation-dependent mannose-6-phosphate receptor and has no known function. Liver production of IGF I is mainly under the control of hGH and other factors such as diet; other tissues are less or not at all under the control of hGH. The blood levels of IGF I raise from birth to the end of puberty, then decrease and remain almost stable during adulthood. The activity of IGF I on skeletal growth is well established and the determination of its plasma levels by radioimmunoassay is of great clinical utility in the diagnosis of growth disorders. IGF I levels in blood are high in case of acromegaly, low in hGH-deficiency, undernutrition, hypothyroidy and renal failure. IGF I acts in an autocrine/paracrine way and probably endocrine sometimes. How IGF II synthesis is regulated is not well known, in any case, IGF II has no effect on growth and the regulation of its secretion is hardly influenced by hGH, its blood levels remain unchanged in acromegaly and are irregularly diminished in hGH-deficiency. Moreover, IGF I and II promote cellular growth and differentiation. This activity could be of great importance during fetal life.

Animals↗

PubMed1991

Protein A-sepharose used to measure free insulin in plasma.

Diabetic patients receiving insulin therapy generally develop anti-insulin antibodies that must be eliminated, usually by extraction with polyethylene glycol (PEG), before determining the concentration of free (active) insulin in plasma. We describe a new method for removing such antibodies, with the use of Protein A coupled to Sepharose microspheres. The results correlate well with those by the PEG method, although values are systematically higher or lower for given samples, according to the initial titer of the antibody measured in terms of binding capacity. Further studies are required to clarify this observation.

Adult↗

PubMed1991

[Decrease of early insulin secretion, risk factor of insulin-dependent diabetes. Prospective study in families with diabetic children].

In order to study the capacity of the first phase insulin response (FPIR) for predicting insulin-dependent diabetes (IDDM), we have performed one or more intravenous glucose tolerance tests (IVGTT) and determined islet-cell antibodies (ICA) and HLA-types in 220 first degree relatives of IDDM patients (194 siblings, 26 offsprings) aged 2 to 29 years. They were prospectively followed for periods ranging from 18 months to 8 years. The immunological and metabolic changes in 9 subjects who have developed IDDM or impaired glucose tolerance during the study and in 3 ICA-positive non-diabetic subjects were compared to those in ICA-negative subjects. Although the mean FPIR (1 + 3 min. plasma insulin) was significantly lower in ICA-positive compared with ICA-negative subjects, a unique low FPIR had no predictive value at the individual level. At repeated tests, the two groups followed distinctive evolutive patterns: ICA-negative subjects usually had higher FPIRs at a 2nd test, while FPIRs remained low or still decreased in ICA-positive subjects. Follow-up of subjects at high risk showed good concordance between the different predictive factors: among the 9 subjects who have developed IDDM, 7 had persisting ICA, 8 were HLA-DR3, DR4; the FPIR was consistently low in 3 and low at least once in 4. Progressive loss of the FPIR allowing to predict the time of onset of IDDM, was not observed.

Adolescent↗

PubMed1989

The contribution of intermediate-acting insulin preparations to daytime insulin treatment.

Hyperglycaemia in the afternoon is often not prevented by increasing the intermediate insulin dose in C-peptide deficient Type 1 diabetic patients, particularly children, treated with two injections of mixtures of short- and intermediate-acting insulins. To provide a better understanding of this, 19 Type 1 diabetic patients were studied using the euglycaemic clamp technique, after SC injection of either soluble, isophane (NPH) or lente insulin, or mixtures of these preparations. SC injection of 0.6 U kg-1 insulin, as either intermediate-acting (isophane (NPH) or lente) insulin alone or as a mixture of 50% soluble + 50% intermediate-acting insulins, indicates that, for the same total dose of SC insulin, a shift from soluble to intermediate-acting insulin results in a major loss of activity during the first 6 h after injection, with no compensatory increase over the next 6 h. The morning hypoglycaemic activity depends on different mechanisms with isophane (NPH) or lente insulin; the effects of soluble and isophane (NHP) insulin are superimposed, while with lente insulin, the peak of soluble insulin is blunted. For the afternoon, even large doses of isophane (NPH) or lente insulin do not meet the peak of insulin requirements following lunch.

Adult↗