Uremia and HbA1c measured by high-performance liquid chromatography.
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Chromatography, High Pressure Liquid↗
Biomedical subjects
D Chevenne
Publications and source records attributed to D Chevenne.
Proinsulin and specific insulin responses to an oral glucose tolerance test in a healthy population.
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Administration, Oral↗
[HLA-markers and diabetic retinopathy in the Senegalese population].
Patients with IDDM often develop severe forms of retinopathy, supposed to be associated to risk factors such as hypertension, poor glycemic control and nephropathy. A controversial intervention of a genetic marker was evoked so as some diabetic patients have retinopathy in the absence of known risk factors. HLA-DR and DQ markers were compared in two groups of patients with IDDM respectively constituted of patients with and without severe retinopathy. HLA typing was carried out by polymerase chain reaction (PCR) and restriction fragments of length polymorphism (RFLP). DR9 (p < 10(-4); O.R. = 8.36) and DQA1*0301 (p < 0.05; O.R = 2.92) alleles were positively associated to diabetic retinopathy, at the opposite of DR3 (p < 10(-3); O.R: 0.01) and DQA1* (p < 10(-9); O.R = 0.15). Furthermore, among the genotypes previously considered as risk markers of IDDM in senegalese people, only DR4: DQA1*0301:DQB1*0302/DR9: DQA1*0301: DQB1*0201 was often observed in retinopathy.
Adolescent↗
[Insulin-dependent diabetes in Senegal: HLA-DR combinations according to age of onset and sex].
In insulin-dependent diabetes mellitus, HLA-DR markers are involved, namely DR3, DR4 and DR9 alleles, among black senegalese populations. Studying the different associations of these alleles showed a strong predisposition to insulin-dependent diabetes mellitus with DR3/4 (p > 10(-2); OR = 13.6); DR4/9 (p < 10(-2); OR = 8.32) and DR9/9 (p < 0.05; OR = 7.78). And then it was observed a tendency to an inverse relationship of DR3/4 frequency with age of onset in male patients.
Adolescent↗
Reduced final height and indications for insulin resistance in 20 year olds born small for gestational age: regional cohort study.
OBJECTIVE: To investigate whether the association between low birth weight and increased risk of developing impaired glucose tolerance, insulin resistance, hypertriglyceridaemia, and hypertension in middle age is apparent by the age of 20 in people born small for gestational age. DESIGN: Regional cohort study. SETTING: Maternity registry, Haguenau, France. SUBJECTS: 236 full term singleton babies born small for gestational age (birth weight or length, or both, below third centile) during 1971-8 and 281 with normal birth weight (between 25th and 75th centile). All subjects were contacted and evaluated at a mean (SD) age of 20.6 (2.1) years. MAIN OUTCOME MEASURES: Adult height; concentrations of glucose, insulin, and proinsulin during an oral glucose tolerance test; lipid and fibrinogen concentrations; and blood pressure. RESULTS: After sex and target height were adjusted for, subjects who had been born small for gestational age were significantly shorter at age 20 than those with a normal birth weight (men 4.5 cm shorter (95% confidence interval 6.0 to 3.0 cm); women 3.94 cm shorter (5.2 to 2.7 cm)). After sex and body mass index were adjusted for, mean plasma glucose concentration 30 minutes after a glucose load, fasting insulin concentration (in women), and insulin and proinsulin concentrations 30 and 120 minutes after a glucose load were significantly higher in subjects who had been born small for gestational age than in those with a normal birth weight. Mean lipid and fibrinogen concentrations and blood pressure were not different between the two groups. CONCLUSIONS: Intrauterine growth retardation has long term consequences such as reduced final height Raised insulin and proinsulin concentrations are present in young adults born small for gestational age and could be markers of early changes in insulin sensitivity.
Adolescent↗
DNA polymorphisms of apolipoprotein B in the population of Senegal.
Three apolipoprotein B (apoB) genetic polymorphisms, the XbaI, MspI and EcoRI restriction fragment length polymorphisms (RFLPs), were analysed for 221 individuals in Senegal by polymerase chain reaction. Allelic frequency determination revealed that this population has 0.79 XbaI- (X-), 0.96 MspI+ (M+), and 0.89 EcoRI+ (E+). Major genotypes were X-/X- (0.62), M+/M+ (0.92) and E+/E+ (0.80). The XbaI allele frequency is different (p < 10(-9)) from that in Caucasians (0.47) and from that in Mongoloids (0.98). Significant differences between Senegalese and Caucasians, and between Senegalese and Mongoloids were also observed for the EcoRI and MspI alleles of the apoB genes.
Apolipoproteins B↗
Susceptibility to type 1 diabetes in the Senegalese population is linked to HLA-DQ and not TAP and LMP genes.
OBJECTIVE: To investigate the frequency of the transporter associated with antigen processing (TAP) and large multifunctional protease (LMP) alleles and their role in the susceptibility to type 1 diabetes, in comparison with the well-known HLA-DQ alleles susceptibility, in Senegalese subjects. RESEARCH DESIGN AND METHODS: Three loci in the TAP/LMP region were analyzed in 92 type 1 diabetic subjects and 117 nondiabetic control subjects by means of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: No association was found between the studied polymorphisms of TAP1, TAP2, and LMP2 and type 1 diabetes in the Senegalese population, in contrast to the HLA-DQA1 and DQB1 genes, which were associated with type 1 diabetes. CONCLUSIONS: Diabetogenic genes in the class II HLA region are located near the DQA1 and DQB1 loci rather than the TAP and LMP loci.
ATP-Binding Cassette Transporters↗
[Contribution of plasma C-peptide to the classification of sugar diabetes in Dakar, Senegal].
When diabetes has been diagnosed, its classification into different types is traditionally carried out according to clinical criteria. But with arising of new parameters, one of which is C-peptide, and various subtypes of diabetes, it became more difficult. So, in order to improve the accuracy of the classification, 270 diabetic patients and 269 controls, all black senegalese subjects, were submitted to a two-step oral glucose tolerance test (0 and 120 min.) with determination of plasma glucose and C-peptide concentrations. The majority of NIDDM were confirmed at the opposite of IDDM; furthermore, it has been pointed out a group corresponding with impaired glucose tolerance (IGT) among the initial controls. When comparing the two classification modes, before and after plasma C-peptide determination, it appeared statistically significant differences with p values of 10(-4) for both IDDM and NIDDM.
Adult↗
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↗
[HLA-DR:DQ genotypes and insulin-dependent diabetes in Senegal].
At the opposite of HLA-DR, HLA-DQ was not well documented in homogeneous negroïd populations. So, 93 IDDM and 115 control patients, all black senegalese people, were studied. The results showed three HLA-DQ IDDM-related susceptibility genotypes and also a high risk conferred by HLA-DR4/DR9 usually described in Mongoloïd people. Furthermore, DR:DQ associations allowed the identification of three IDDM predisposition genotypes, each of them with a characteristic mean age for disease diagnosis.
Adult↗
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↗
[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↗
[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↗
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↗
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↗
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↗
[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↗
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↗