Les glycogénoses sont des maladies touchant la synthèse ou la dégradation du glycogène. Un diagnostic précoce et une diète optimale, incluant la prévention des hypoglycémies, sont d’une importante cruciale pour le devenir des patients. Les présents travaux visaient la confirmation génétique de glycogénose chez des patients inuits du Nunavik ainsi que l’évaluation de l’impact sur le sommeil et la qualité de vie d’une nouvelle thérapie nutritionnelle, GlycosadeTM, dans une cohorte de patients montréalaise. Par séquençage d’exome, nous avons identifié la mutation causale de glycogénose au Nunavik, permettant un diagnostic précoce et un dépistage des membres de la famille. Nous avons aussi introduit une fécule de maïs à action prolongée et évalué prospectivement le sommeil et la qualité de vie des patients avec glycogénose avant et après ce traitement. Nous avons mis en évidence des troubles de sommeil chez les patients et avons discuté du GlycosadeTM comme d’une option thérapeutique prometteuse. / Glycogen storage diseases are diseases affecting glycogen synthesis or degradation. Early diagnosis and optimal diet, including hypoglycemia prevention, are essential for better patient outcomes. The present work aimed to genetically confirm glycogen storage disease in Inuit from Nunavik and to evaluate the impact of a new nutritional therapy, GlycosadeTM, on sleep and quality of life in a cohort of patients from Montreal. We identified the causative mutation of glycogen storage disease in Nunavik by means of exome sequencing allowing early diagnosis and screening of family members. We also introduced a long acting form of cornstarch and prospectively assessed sleep and quality of life before and after this treatment in patients with glycogen storage disease. We highlighted sleep disturbances in patients and discussed GlycosadeTM as a promising therapeutic option.

Objectif : Déterminer la fiabilité et la précision d’un prototype d’appareil non invasif de mesure de glucose dans le tissu interstitiel, le PGS (Photonic Glucose Sensor), en utilisant des clamps glycémiques multi-étagés. Méthodes : Le PGS a été évalué chez 13 sujets avec diabète de type 1. Deux PGS étaient testés par sujet, un sur chacun des triceps, pour évaluer la sensibilité, la spécificité, la reproductibilité et la précision comparativement à la technique de référence (le Beckman®). Chaque sujet était soumis à un clamp de glucose multi-étagé de 8 heures aux concentrations de 3, 5, 8 et 12 mmol/L, de 2 heures chacun. Résultats : La corrélation entre le PGS et le Beckman® était de 0,70. Pour la détection des hypoglycémies, la sensibilité était de 63,4%, la spécificité de 91,6%, la valeur prédictive positive (VPP) 71,8% et la valeur prédictive négative (VPN) 88,2%. Pour la détection de l’hyperglycémie, la sensibilité était de 64,7% et la spécificité de 92%, la VPP 70,8% et la VPN : 89,7%. La courbe ROC (Receiver Operating Characteristics) démontrait une précision de 0,86 pour l’hypoglycémie et de 0,87 pour l’hyperglycémie. La reproductibilité selon la « Clark Error Grid » était de 88% (A+B). Conclusion : La performance du PGS était comparable, sinon meilleure que les autres appareils sur le marché(Freestyle® Navigator, Medtronic Guardian® RT, Dexcom® STS-7) avec l’avantage qu’il n’y a pas d’aiguille. Il s’agit donc d’un appareil avec beaucoup de potentiel comme outil pour faciliter le monitoring au cours du traitement intensif du diabète. Mot clés : Diabète, diabète de type 1, PGS (Photonic Glucose Sensor), mesure continue de glucose, courbe ROC, « Clark Error Grid». / Objective: To determine the reliability and precision of a prototype of a non-invasive device for continuous measurement of interstitial glucose, the PGS (Photonic Glucose Sensor), using multi-level glycaemic clamp. Methods: The PGS was evaluated in 13 subjects with type 1 diabetes. Two PGS were tested with each subject, one on each triceps, to evaluate the sensitivity, specificity, reproducibility and accuracy compared to the reference technique, the glucose analyzer Beckman®. Each subject was submitted to a multi-level 8 hour glucose clamp at 3, 5, 8 and 12 mmol / L, 2 hours each. Results: The correlation between the PGS and the Beckman® was 0.70. For the detection of hypoglycaemia, the sensitivity was 63.4%, the specificity 91.6%, the positive predictive value (PPV) 71.8% and the negative predictive value (NPV) 88.2%. For the detection of hyperglycaemia, the sensitivity was 64.7% the specificity 92%, the PPV 70.8% and the NPV: 89.7%. The ROC (Receiver Operating Characteristics) curve showed an accuracy of 0.86 and 0.87 for hypoglycaemia and hyperglycaemia respectively. Reproducibility according to the Clark Error Grid was 88% in the A and B zone. Conclusion: The performance of the PGS was comparable or better than other continuous glucose monitoring devices on the market (Freestyle® Navigator, Medtronic Guardian® RT, Dexcom® STS-7) with the advantage that it has no needle. It is therefore an interesting device and hopefully, which could facilitate the monitoring in the intensive treatment of diabetes. Key words: Diabetes, type 1 diabetes, PGS (Photonic Glucose Sensor), ROC curve, Clark Error Grid, continuous glucose monitoring, CGMS.

L’hypoglycémie est une barrière au traitement du diabète de type 1 (DbT1). La collation au coucher est recommandée pour prévenir l’hypoglycémie nocturne (HN), mais son efficacité n’est pas démontrée. Objectif : Déterminer si une prise alimentaire en soirée est associée à la survenue d’HN. Étude observationnelle : 100 DbT1 ont porté un lecteur de glucose en continu et complété un journal alimentaire pendant 72 heures. L’HN est survenue durant 28 % des nuits. Une prise alimentaire en soirée n’était pas associée à l’HN. Toutefois, dans un modèle ajusté, l’apport en glucides en soirée était positivement associé aux HN (avec injection d’insuline rapide) et l’apport en protéines inversement associé aux HN (sans injection d’insuline rapide). Manger en soirée ne semble pas associé à moins d’HN. Des études contrôlées sont nécessaires pour comprendre l’effet de la collation au coucher sur le contrôle glycémique et le rôle de l’insuline rapide injectée en soirée. / Hypoglycemia remains a limiting factor of type 1 diabetes (T1D) treatment. Bedtime snack is often suggested to reduce nocturnal hypoglycemia (NH), but its effectiveness is not supported by evidence-based data. Objective: To determine the association between post-dinner dietary intake and NH occurrence. This is an observational study during which 100 T1D wore a blinded continuous glucose monitoring system and completed a food diary for 72 hours. NH occurred on 28 % of the 282 nights studied. Post-dinner dietary intake was not associated with NH. However, in multivariate models, carbohydrate intake was positively associated with NH (when rapid insulin was injected) and protein intake was inversely associated with NH (without rapid insulin injected). Post-dinner dietary intake does not seem to be associated with a reduce occurrence of NH. Further studies are needed to better understand the impact of bedtime snack on glycemic control and the role of the injection of rapid insulin in the evening.

Der Gestationsdiabetes betrifft etwa 5 von 100 Schwangeren. In unserer prospektiven, randomisierten Studie mit Crossover-Design untersuchten wir den Einfluß der Kohlenhydrataufnahme auf den Glukosestoffwechsel Schwangerer. 18 Gestationsdiabetikerinnen, 9 Frauen mit eingeschränkter Glukosetoleranz und 25 Kontrollen haben jeweils eine Woche eine kohlenhydratarme (35 Energieprozent) und eine kohlenhydratreiche (55 Energieprozent) Diät durchgeführt. Auswirkungen wurden anhand des konventionellen BZTPs und des kontinuierlich messenden Glukosesensors CGMS® untersucht. Die KH-Aufnahme wurde mittels einer Ernährungsberatung deutlich beeinflußt, und lag bei 39 % in der KH-reduzierten, und bei 49 % in der KH-reichen Woche. Nach DDG-Kriterien hatte der KH-Anteil bei keiner Gruppe einen signifikanten Einfluß bezüglich der Insulinpflicht. Dagegen waren der BZTP-Mittelwert und die AUC (area under the curve des CGMS®) der GDMs und der Kontrollen signifikant niedriger in der KH-armen Woche. In dieser Woche nahmen die Probandinnen auch eine niedrigere Energiemenge zu sich. Bei einer selektierten Untergruppe konnten wir diesen Einfluß ausgrenzen, und für die Kontrollgruppe eine signifikante Erniedrigung bezüglich der BZTP-Mediane und der AUCs nachweisen. Diese Beobachtungen belegen, daß ein höherer Kohlenhydratanteil mit erhöhten Blutzuckerwerten assoziiert ist. Außerdem wurde ein größerer Einfluß einer kohlenhydratarmen Ernährung auf die postprandialen als auf die Nüchternwerte festgestellt. Wegen der Auswirkungen auf das fetale Wachstum soll man bei Gestationsdiabetikerinnen eine kohlenhydratarme Ernährung empfehlen. / Gestational diabetes affects about 5 % of pregnancies. In our randomized prospective study with crossover design we examined the influence of carbohydrate intake on the glucose metabolism of pregnant women. 18 women with gestational diabetes, 9 with impaired glucose tolerance and 25 controls were put on a low (35 energy %) carbohydrate diet for one week and a high (55 energy %) carbohydrate diet for another. Blood glucose levels were recorded by self-monitoring and with a continuous glucose monitoring sensor (CGMS ®). Carbohydrate intake was strongly influenced by dietary advice, amounting to 39% into the low carbohydrate and 49% in the high carbohydrate week. According to DDG criteria, carbohydrate intake had no significant influence on insulin requirements. In contrast, mean blood glucose levels and the AUC (area under of the curve of the CGMS ®) were significantly lower for both gestational diabetics and controls in the low carbohydrate week. During this week, the average caloric intake was also reduced. We could exclude this influence for a selected subgroup, in which the controls displayed a significant reduction in median glucose levels and the AUCs. We could thus show that a higher carbohydrate content is associated with raised blood glucose levels. Furthermore, the influence of a low carbohydrate diet was greater on postprandial than on fasting levels. Because of the effects on fetal growth, one should recommend a low carbohydrate diet for gestational diabetics.

Abstract Type 1 diabetes is considered to be a T cell-mediated autoimmune disease characterized by destruction of the pancreatic beta cells. Its prediction is currently based on diabetes-associated autoantibodies, giving a cumulative risk of 84% during 15 years of follow-up since seroconversion. Prediction of the timing of clinical onset has remained challenging, however. This thesis examines glucose metabolism in autoantibody-positive children with a high risk of developing type 1 diabetes. Out of a total of 14,876 children with an increased genetic risk followed up from birth in the Finnish DIPP study, 567 developed ≥2 autoantibodies during the follow-up and 255 of these (45%) were diagnosed with type 1 diabetes until the end of December 2011. The glucose parameters measured were HbA1c, OGTT and random plasma glucose with 3 to 12 months interval. Seven-day continuous glucose monitoring (CGM) was performed on an age and sex-matched cohort. We showed that rising HbA1c, impaired glucose tolerance in OGTT, random plasma glucose values of ≥7.8mmol/l and potentially CGM can predict type 1 diabetes with a median time to diagnosis of approximately one year. Our results suggest that especially HbA1c and random plasma glucose are cost-effective and improve the prediction of diabetes. These markers may be useful for monitoring the response to treatment in prevention studies. / Tiivistelmä Tyypin 1 diabetesta pidetään T-soluvälitteisenä autoimmuunitautina, joka johtaa haiman beetasolujen tuhoutumiseen. Tyypin 1 diabeteksen ennustaminen perustuu tällä hetkellä diabetekseen assosioituviin vasta-aineisiin, jotka antavat 84% kumulatiivisen riskin 15 vuoden seurannassa. Taudin puhkeamisen ajankohdan ennustaminen on kuitenkin edelleen vaikeaa. Tämä väitöskirja käsittelee glukoosiaineenvaihduntaa vasta-ainepositiivisilla lapsilla, joilla on suurentunut riski sairastua tyypin 1 diabetekseen. Suomalaisessa DIPP-tutkimuksessa vasta-aineiden kehittymistä on seurattu yhteensä 14876 lapselta. Seurannan aikana 567 lasta kehitti ≥2 autovasta-ainetta ja näistä 255 (45%) sairastui tyypin 1 diabetekseen joulukuun loppuun 2011 mennessä. Glukoosiaineenvaihduntaa seurattiin tutkimalla HbA1c, OGTT ja satunnaisia verensokeriarvoja 3-12 kuukauden välein. Ikä ja sukupuolivakioidussa kohortissa tehtiin jatkuvan sokeripitoisuuden seuranta (CGM). Tutkimuksessamme nouseva HbA1c, heikentynyt sokerin sieto OGTT-kokeessa, satunnainen verensokeri ≥7.8 mmol/l ja mahdollisesti CGM ennustavat tyypin 1 diabeteksen puhkeamista. Tulostemme perusteella erityisesti kustannustehokkaat HbA1c ja satunnainen verensokeri parantavat diabeteksen ennustamista. Nämä parametrit saattavat olla hyödyllisiä myös preventiotutkimuksissa hoitovasteen seurannassa.

<p>Since the late 1970s, biomedical researchers have heavily invested in the development of portable insulin pumps that allow people with Type 1 Diabetes (T1D) to carry several days-worth of insulin to be injected on an as-needed basis. That means fewer needles and syringes, making regular insulin injections less time consuming and troublesome. As insulin pump use has become more widespread over the past twenty years among people with T1D, the social and cultural effects of using these medical devices on their everyday experiences have become both increasingly apparent for individuals yet consistently absent from social and cultural studies of the disease.</p><p><br></p><p>In this dissertation, I explore the technological, medical, and cultural networks of insulin pump treatment to identify the role(s) these biomedicalized treatment acts play in the structuring of people, their bodies, and the cultural values constructed around various medical technologies. As I will show, insulin pump treatment alters people’s bodies and identities as devices become integrated as co-productive actors within patient-users’ biological and social systems. By analyzing personal interviews and digital media produced by people with T1D alongside archival materials, this study identifies compulsory patterns in the practices, structures, and narratives related to insulin pump use to center chapters around the productive (and sometimes stifling) relationship between people, bodies, technologies, and American culture.</p><p><br></p><p>By analyzing the layered and intersecting sites of insulin pump treatment together, this project reveals how medical technologies, health identities, bodies, and cultures are co-constructed and co-defined in ways that bind them together—mutually constitutive, medically compelled, cultural and social. New bodies and new systems, I argue, come with new (in)visibilities, and while this new technologically-produced legibility of the body provides unprecedented management of the symptoms and side-effects of the disease, it also brings with it unforeseen social consequences that require changes to people’s everyday lives and practices. </p>