The Type and the Position of HNF1A Mutation Modulate Age at Diagnosis of Diabetes in Patients with Maturity-Onset Diabetes of the Young (MODY)-3

OBJECTIVE—The clinical expression of maturity-onset diabetes of the young (MODY)-3 is highly variable. This may be due to environmental and/or genetic factors, including molecular characteristics of the hepatocyte nuclear factor 1-α (HNF1A) gene mutation. RESEARCH DESIGN AND METHODS—We analyzed the mutations identified in 356 unrelated MODY3 patients, including 118 novel mutations, and searched for correlations between the genotype and age at diagnosis of diabetes. RESULTS—Missense mutations prevailed in the dimerization and DNA-binding domains (74%), while truncating mutations were predominant in the transactivation domain (62%). The majority (83%) of the mutations were located in exons 1- 6, thus affecting the three HNF1A isoforms. Age at diagnosis of diabetes was lower in patients with truncating mutations than in those with missense mutations (18 vs. 22 years, P = 0.005). Missense mutations affecting the dimerization/DNA-binding domains were associated with a lower age at diagnosis than those affecting the transactivation domain (20 vs. 30 years, P = 10−4). Patients with missense mutations affecting the three isoforms were younger at diagnosis than those with missense mutations involving one or two isoforms (P = 0.03). CONCLUSIONS—These data show that part of the variability of the clinical expression in MODY3 patients may be explained by the type and the location of HNF1A mutations. These findings should be considered in studies for the search of additional modifier genetic factors

Extensive study of human insulin immunoassays: promises and pitfalls for insulin analogue detection and quantification:

BACKGROUND: Over the last few decades, new synthetic insulin analogues have been developed. Their measurement is of prime importance in the investigation of hypoglycaemia, but their quantification is hampered by variable cross-reactivity with many insulin assays. For clinical analysis, it has now become essential to know the potential cross-reactivity of analogues of interest. METHODS: In this work, we performed an extensive study of insulin analogue cross-reactivity using numerous human insulin immunoassays. We investigated the cross-reactivity of five analogues (lispro, aspart, glulisine, glargine, detemir) and two glargine metabolites (M1 and M2) with 16 commercial human insulin immunoassays as a function of concentration. RESULTS: The cross-reactivity values for insulin analogues or glargine metabolites ranged from 0% to 264%. Four assays were more specific to human insulin, resulting in negligible cross-reactivity with the analogues. However, none of the 16 assays was completely free of cross-reactivity with analogues or metabolites. The results show that analogue cross-reactivity, which varies to a large degree, is far from negligible, and should not be overlooked in clinical investigations. CONCLUSIONS: This study has established the cross-reactivity of five insulin analogues and two glargine metabolites using 16 immunoassays to facilitate the choice of the immunoassay(s) and to provide sensitive and specific analyses in clinical routine or investigation

Efficacy and Safety of Flexible Versus Fixed Dosing Intervals of Insulin Glargine 300 U/mL in People with Type 2 Diabetes

Background: Insulin glargine 300 U/mL (Gla-300) has a more constant and prolonged action profile than insulin glargine 100 U/mL and in clinical studies is associated with similar glycemic control but less hypoglycemia. Whether its effects are altered by variability of injection time was examined in two 3-month substudies. Materials and Methods: Eligible participants completing 6 months of optimized treatment with Gla-300 in EDITION 1 (n = 109) and EDITION 2 (n = 89), having a mean hemoglobin A1c (HbA(1c)) level of 7.3 % (SD 1.0 %), were randomized (1:1) to groups advised to increase variability of between-injection intervals to 24 +/- up to 3 h or to maintain fixed 24-h intervals for 3 months. Changes of HbA(1c) level and other efficacy and safety measures were assessed. Results: In the fixed-dosing group, 64% of participants reported all intervals within the 23-25-h range, compared with 15% of those advised flexible dosing. In the fixed- and flexible-dosing groups, 12% and 41%, respectively, of between-injection intervals were outside the 23-25-h range, and 2% and 16%, respectively, were outside the 21-27-h range. Least squares mean between-group difference in HbA(1c) change from baseline was 0.05 % (95% confidence interval [CI], -0.13 to 0.23); for fasting plasma glucose, 2.7 mg/dL (95% CI, -9.0 to 14.4); and for daily basal insulin dose, 0.00 U/kg (95% CI, -0.02 to 0.03). Frequencies of hypoglycemia and adverse events did not differ between groups. Conclusions: The efficacy and safety of Gla-300 demonstrated in EDITION 1 and EDITION 2 are maintained in substudies when the insulin was injected up to 3 h before or after the usual time of administration.Peer reviewe

L’autisme au quotidien : témoignage d’un pédiatre en Seine-Saint-Denis

International audienceA paediatrician who has been practicing for over 30 years in Seine-Saint Denis tells of the difficulties encountered by parents of autistic children living in this Paris suburb. He describes the serious shortfalls in the integration of these children in full-time schooling, the interweaving of social, cultural, educational and medical factors, the focus on diagnosis and research at the expense of follow-up and assistance to families, the shortage of professionals with an interest in these issues, and the “accounting” logic of hospital medicine. As he nears retirement, he worries about the drastic reduction in general practitioners and paediatricians in this suburban area, where the children from underprivileged families are dually penalised, on account of their illness and on account of their social situation.Un pédiatre qui exerce depuis plus de 30ans en Seine-Saint-Denis témoigne des difficultés particulières rencontrées par les parents d’enfants autistes qui vivent dans cette banlieue parisienne. Il raconte les profondes carences d’accueil en milieu éducatif à temps plein, l’intrication de facteurs sociaux, culturels, éducatifs et médicaux, la focalisation sur le diagnostic et la recherche au détriment du suivi et de l’aide aux familles, la mise à l’écart des enfants qui présentent le plus de difficultés, le manque de professionnels qui s’y intéressent et la logique comptable de la médecine à l’hôpital. À l’approche de la retraite, il s’inquiète de la diminution drastique des généralistes et pédiatres dans cette banlieue où les enfants de familles défavorisées sont doublement exclus, du fait de leur pathologie et de leur situation sociale

Measuring standards of living at the income group level A Lorraine-Luxembourg comparative analysis

Paper presented at the Final Int. Conf of the ESF Scientific Network on Household Panel Studies, CEPS/INSTEAD held Walferdange (LU), 1-2 Jun 1993Available from British Library Document Supply Centre- DSC:9349.2264(ESF-ESNHPS-WP--74) / BLDSC - British Library Document Supply CentreSIGLEGBUnited Kingdo

Analysing standards of living with panel data At income group or houshold level?

SIGLEAvailable from British Library Document Supply Centre- DSC:9349.2264(ESF-ESNHPS-WP--56) / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Premiers enseignements de l’étude DESCENDANCE : prévalence des dysglycémies méconnues chez des apparentés de diabétiques de type 2 sur deux générations

peer reviewe

Diabeloop Closed-Loop Achieves Better Blood-Glucose Control than Sensor-Augmented Pump over Three Days Involving Intensive Physical Exercise: A Randomized, Crossover Trial

International audienc