La Néphronophtise (NPH) est une maladie autosomique récessive, qui se caractérise par des lésions tubulo-interstitielles conduisant à une insuffisance rénale terminale avant l'âge adulte. A ce jour des mutations dans 20 gènes (NPHP1-20) ont été identifiées comme responsables de la maladie. Les produits de ces gènes, les néphrocystines ou NPHP, se localisent et ont un rôle au cil primaire, définissant ainsi la NPH comme une ciliopathie. Nous avons identifié des mutations dans un nouveau gène candidat. Ces mutations ont été détectées dans six familles indépendantes, présentant une NPH tardive avec une fibrose rénale importante. Ce gène code MAPKBP1, une protéine très peu étudiée, ayant été décrite comme une protéine d'échafaudage de la voie JNK. MAPKBP1 interagit également avec WDR62, le produit d'un paralogue qui est le second gène le plus fréquemment muté dans les microcéphalies primaire récessives. La protéine WDR62 localise aux pôles du fuseau mitotiques (MSP) d'où elle régule l'orientation de l'axe des mitoses via la voie JNK dans le système nerveux central. Au cours de mon travail de thèse au sein du laboratoire des Maladies Rénales Héréditaires de l'Institut Imagine, j'ai étudié les fonctions cellulaires de la protéine MAPKBP1. J'ai ainsi pu mettre en évidence dans les lignées cellulaires ainsi que dans les tissus, que la protéine MAPKBP1 n'est pas présente au cil primaire et que les fibroblastes de patients ne présentent pas de défauts de ciliogenèse, indiquant que MAPKBP1 pourrait être le représentant d'une nouvelle famille de NPHP ne possédant pas de fonctions ciliaires. De manière intéressante, j'ai pu observer que MAPKBP1 est recruté aux MSP au cours des phases précoces de la mitose. Ainsi, en démontrant que certaines des mutations retrouvées chez les patients affectent le recrutement de MAPKBP1 aux MSP et perturbent également l'interaction de MAPKBP1 avec JNK et/ou WDR62, j'ai pu valider l'effet pathogène de ces mutations. De plus, j'ai montré des défauts dans la voie de réponse aux dommages à l'ADN dans les différents fibroblastes de patients comme récemment observé dans de nombreux modèles NPHP. / Nephronophthisis (NPH) is an autosomal recessive disease, characterised by tubulointerstitial lesions leading to an end-stage renal disease before adulthood. Causative mutations in 20 genes (NPHP1-20) have been identified so far. The products of those genes, the nephrocystins or NPHP, localise and function at the primary cilium, defining NPH as a ciliopathy. We identified mutations in a new candidate gene. Those mutations have been detected in six independent families, displaying late onset NPH with massive fibrosis. This gene encode MAPKBP1, a poorly studied protein that has been described as JNK pathway scaffold protein. MAPKBP1 also interacts with WDR62, the product of a paralogue which is the second most frequently mutated gene in recessive primary microcephalies. The protein WDR62 localises at the mitotic spindle poles (MSP) from where it regulates the orientation of the axis of division, through activation of JNK pathway in the central nervous system. During my work in the laboratory of Hereditary Kidney Diseases in the Imagine Institute, I studied MAPKBP1 cellular functions. I could show that in the various cell lines that have been tested, as well as in human kidney tissues, MAPKBP1 is not present at the primary cilia. And I also could show in patient fibroblasts that there is no ciliary defects, indicating that MAPKBP1 could be a novel NPHP protein that do not display ciliary functions. Interestingly, I could observe that MAPKBP1 is recruited at the MSPs during mitosis. Demonstrating that some patient mutations affect the recruitment of MAPKBP1 at the MSPs and also disturb interaction with JNK and/or WDR62, I could validate the pathogenic effect of those mutations. In addition, I could show defects in the DNA damage response in patient fibroblasts, as observed recently in various NPHP models.

Submitted by Fabio Sobreira Campos da Costa (fabio.sobreira@ufpe.br) on 2017-07-17T15:08:05Z No. of bitstreams: 2 license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5) CUSTO UTILIDADE DA INSULINA GLARGINA E NPH REV 4.pdf: 871032 bytes, checksum: 61243dd09cce2d9260cb9239a873d2ca (MD5) / Made available in DSpace on 2017-07-17T15:08:06Z (GMT). No. of bitstreams: 2 license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5) CUSTO UTILIDADE DA INSULINA GLARGINA E NPH REV 4.pdf: 871032 bytes, checksum: 61243dd09cce2d9260cb9239a873d2ca (MD5) Previous issue date: 2014-10-31 / INTRODUÇÃO: O Diabetes Mellitus é um transtorno metabólico, caracterizado por hiperglicemia. É considerada condição sensível à Atenção Primária, tendo impacto por reduzir ou retardar as complicações da doença. A reposição de insulina para o diabete mellitus tipo 2 é indicada quando somente mudanças no estilo de vida associados a hipoglicemiante oral forem insuficientes para obter controle glicêmico. OBJETIVOS: Determinar o custo-utilidade da insulina glargina e insulina NPH para o tratamento de pacientes com diabetes mellitus tipo 2 atendidos no Sistema Único de Saúde do Município de Recife – PE. MÉTODOS: Foi realizada comparação da categoria custos médicos diretos de duas intervenções terapêuticas indicadas para o tratamento do diabete mellitus tipo 2. A avaliação de custo-utilidade foi realizada a partir da perspectiva do Sistema Único de Saúde. Foi considerado um horizonte analítico de 10 anos. Os dados coletados foram de fontes secundárias, de sistema de informação em saúde, dados dos relatórios emitidos nos sistemas de informatização das Farmácias do Recife e da Farmácia do Estado de Pernambuco e fontes da literatura. Para a análise de decisão, foram consideradas as hipoglicemias noturnas e não noturnas graves e não graves. RESULTADOS: O indivíduo médio, representante de Pernambuco, apresenta 8,7 anos de diagnóstico do DM2, recebem aproximadamente 14,4 frascos de insulina NPH ou Glargina ao ano, dados estes, utilizados na probabilidade de transição. Para o cenário das complicações agudas, o custo do usuário foi calculado para 2013: sem complicação em uso da insulina NPH foi de R$ 1.237,95 e para insulina Glargina R$ 4.935,42. Foi considerado 12 episódios de hipoglicemia noturna grave ao ano. A redução de risco de hipoglicemia para pacientes em uso da insulina Glargina é de 50,9% apresentando cinco episódios ao ano. A razão de custo incremental (RCEI) do presente estudo, indica um valor agregado adicionado de R$ 12.987,4892 por AVAQ ganho a cada ano de tratamento com a insulina glargina em relação a NPH. CONCLUSÕES: Houve redução de episódio de hipoglicemia noturna grave da insulina glargina comparado com a insulina NPH. Os dados apresentados não permite afirmar qual da intervenção é mais efetiva, apenas mostra que a insulina glargina tem um maior custo-utilidade e um custo médico direto maior. Os custos incrementais e os benefícios alcançados em anos de vidas ganhos produziu uma Razão de R$ 12.987,4892 ao ano para a insulina glargina. Diante das incertezas acerca da efetividade das insulinas analisadas, faz-se necessário a realização de estudos aprofundados entre estas intervenções terapêuticas. / INTRODUCTION: Diabetes mellitus is a metabolic disorder characterized by hyperglycemia. It is considered sensitive to Primary Health Care, considering its impacting to reduce or delay complications of the disease. Replacement of insulin for diabetes mellitus type 2 is indicated only when changes in lifestyle associated with oral hypoglycemic agents are insufficient to obtain glycemic control. OBJECTIVES: To determine the cost-utility of insulin glargine and NPH insulin for the treatment of patients with type 2 diabetes mellitus treated at the Unified Health System of the Municipality of Recife - Pernambuco. METHODS: We compared the direct medical costs of category two therapeutic interventions indicated for the treatment of diabetes mellitus type 2 was performed Assessment of cost-utility analysis was performed from the perspective of the Health System was considered an analytic horizon of 10 years.. The data were collected from secondary sources of health information system data reports issued in the computerization of Pharmacies and Pharmacy Recife Pernambuco State and literature sources systems. For decision analysis, were considered nocturnal hypoglycemia and nocturnal not serious and not serious. RESULTS AND DISCUSSION: The average individual, representative of Pernambuco, has 8.7 years of diagnosis of T2DM, receive approximately 14.4 vials of NPH or glargine per year, these data are used in the transition probability. For the setting of acute complications, the user cost was calculated for 2013: Uncomplicated in use NPH insulin was R$ 1,237.95 and R$ 4,935.42 insulin glargine. Was considered 12 episodes of severe nocturnal hypoglycemia per year. The reduced risk of hypoglycemia for patients on insulin glargine is 50.9% with five episodes per year. The ratio of incremental cost (ICER) of this study, indicates a value added of R$ 12,987.4892 per QALY gained every year of treatment with insulin glargine compared to NPH. CONCLUSION: There was a reduction of severe nocturnal hypoglycemia episode of insulin glargine compared with NPH insulin. The data presented allows not say which intervention is most effective, just shows that insulin glargine has a higher utility cost and a direct medical cost higher. Incremental costs and benefits achieved gains in years of life produced a ratio of R$ 12.987,4892 year to insulin glargine. Given the uncertainties about the effectiveness of insulin analyzed, it is necessary to conduct in-depth studies of these therapeutic interventions.

This work deals with development and optimization of a method for separation and detection of pro- tamines using capillary zone electrophoresis. The developed method uses a fused silica capillary with inner diameter of 50 µm and effective length of 41,5 cm. Driving voltage is 30 kV. Background electrolyte is aque- ous solution of 45 mmol dm−3 phosphoric acid. Analyte is detected spectrophotometrically at wavelength of 200 nm. Sample is injected hydrodynamically. The method allows for determination of protamines in the concentration range between 11 µg ml−1 to 1000 µg ml−1 , limit of detection is 4 µg ml−1 . Viablity of the method has been verified with a real sample of NPH insulin injection. For sufficiently sensitive detection of protamines in NPH insuline it is necessary to prepare the sample in acidic environment. For the pur- poses of this work the sample was acidified by addition of background electrolyte into the sample so that the background electrolyte concentration in the resulting solution of the sample was 18 mmol dm−3 . The main advantage of the method is the rapid analysis, migration time of the analyte is about 2 min. Disadvantage of the method in comparison to alternate methods using CZE or RP-HPLC is the inability to separate individ- ual protamine peptides. This disadvantage...

Impairments in walking and balance are symptoms of normal pressure hydrocephalus. Measuring walking speed is therefore important for diagnosing and following the rehabilitation of patients with the diagnosis. However, performing the measurement at the hospital is costly and requires a lot of resources. Therefore, this study aims to propose a design concept enabling patients to measure their walking speed at home. When designing for the elderly and people with cognitive impairments there are various aspects that need to be considered. For instance, one needs to consider that these individuals may have reduced vision, attention, and memory. Through a literature review, guidelines on how to design both generally and specifically for the target group have been gathered. These guidelines were used to develop a prototype which has been evaluated in usability tests and interviews. In total, eleven people participated in the study. The study included a low-fidelity evaluation and a high-fidelity evaluation of the prototype. While the prototype was generally considered intuitive and user-friendly, participants suggested improvements such as reducing unnecessary instructions. Further, it was evident that some elements were hard to see. Overall, participants had a positive attitude to the application and to perform measurements outside of the hospital. The evaluations resulted in a set of final design requirements that concluded simplicity, clarity, and visibility to be vital when designing for the elderly and people with cognitive impairments. / Nedsättningar i gång och balans är symtom på normaltryckshydrocefalus. Att mäta gånghastighet är därför viktigt för att diagnostisera och följa rehabiliteringen av patienter med diagnosen. Att utföra mätningen på sjukhuset är dock kostsamt och kräver mycket resurser. Därför syftar denna studie till att föreslå ett designkoncept som gör det möjligt för patienter att mäta sin gånghastighet hemma. När man designar för äldre och personer med kognitiva funktionsnedsättningar finns det olika aspekter som måste beaktas. Till exempel måste man tänka på att dessa individer kan ha nedsatt syn, uppmärksamhet och minne. Genom en litteraturgenomgång har riktlinjer för hur man designar både generellt och specifikt för målgruppen samlats in. Dessa riktlinjer användes för att utveckla en prototyp som har utvärderats i användarberhetstester och intervjuer. Totalt deltog elva personer i studien. Studien inkluderade en utvärdering av prototypen tidigt i designprocessen och en i slutet av designprocessen. Medan prototypen i allmänhet ansågs logisk och användarvänlig, föreslog deltagarna att minska onödiga instruktioner. Vidare var det uppenbart att vissa element i prototypen var svåra att se. Sammantaget hade deltagarna en positiv inställning till applikationen och att utföra mätningar utanför sjukhuset. Utvärderingarna resulterade i en uppsättning slutliga designkrav som beskriver enkelhet, tydlighet och synlighet som avgörande vid design för äldre och personer med kognitiva funktionsnedsättningar.

Idiopathic normal pressure hydrocephalus (iNPH) is a condition with dilated cerebral ventricles but intracranial pressure within normal limits. The symptoms of gait impairment, cognitive decline and urinary incontinence develop gradually. Treatment with shunt insertion results in improvement in eight out of ten patients. The cerebrospinal fluid tap test (CSF TT) and preoperative magnetic resonance imaging (MRI) are methods used to select patients who may benefit from shunt surgery, but they are performed and interpreted differently in different centers throughout the world. The aim of this thesis was to evaluate the performance of the CSF TT and the underlying mechanisms of improvement in gait function after CSF removal, and to investigate the prognostic value of preoperative MRI scans. Improvement in gait and changes in cerebral blood flow (CBF) after a CSF TT were investigated in two prospective studies that included 39 and 20 patients, respectively. Gait assessment and perfusion MRI were done before and several times during the first 24 hours after a CSF TT. Perfusion was investigated with pseudo-continuous arterial spin labeling. At the group level, gait function was significantly improved at all investigation times, but only one-third of individual CSF TT responders were improved at all investigation times. In patients with increased CBF in lateral and frontal white matter after the CSF TT, gait function improved more than it did in patients with decreased CBF in these regions. However, in the whole sample, there was no significant increase in CBF after CSF removal. Preoperative MRI scans were retrospectively evaluated in 109 patients with iNPH who had undergone shunt surgery. The callosal angle was smaller in shunt responders compared with non-responders. The following findings showed the highest association with a positive outcome after shunting: a small callosal angle, wide temporal horns, and occurrence of disproportionally enlarged subarachnoid space hydrocephalus. In conclusion, CBF in white matter close to the lateral ventricles may play a role in the reversibility of symptoms after CSF removal in patients with iNPH. The CSF TT should be reevaluated if the patient does not initially improve, and preoperative MRI investigations can add prognostic information regarding the selection of shunt candidates.

Ziel der Studie: Ziel waren die Analyse und der Vergleich der diagnostischen und prädiktiven Wertigkeit verschiedener klinischer Testmethoden, invasiver Hirndruckmessung und Liquordynamiktestung. Diese sollten gegenüber der probatorischen externen Liquordrainage (ELD) hinsichtlich ihrer Verwendbarkeit bei der Vorhersage eines Therapieansprechens und ihrer diagnostischen Aussagekraft bei der Diagnostik des idiopathischen Normaldruckhydrocephalus (iNPH) verglichen werden. Patienten und Methoden 68 konsekutive Patienten mit V. a. iNPH wurden prospektiv evaluiert. Die präoperative Diagnostik beinhaltete klinische Testbatterien, Übernachtmessungen des intrakraniellen Druckes (OVM), lumbalen Liquorinfusionstest (LIFT) sowie 24 - 72 stündige externe Lumbaldrainage. Univariate, multivariate und logistische Regressionsanalysen wurden durchgeführt, um prädiktive Werte für einzelne Parameter oder Parameterkombinationen in Hinblick auf das Ansprechen auf eine Shunttherapie zu evaluieren. Resultate: Die positive Testung mittels externer Lumbaldrainage konnte in 87,9 % der Patienten korrekt ein Ansprechen auf VP-Shuntimplantation vorhersagen. Mini Mental State Tests (MMST) mit Werten unter 21 / 30 Punkten (mittelschwere kognitive Störung) waren mit einem hohen Risiko für ein Versagen der Shunttherapie assoziiert (Spezifität 93 % und Sensititvität 67 %). Der LIFT-Parameter ROut war mit dem in der Literatur empfohlenen Grenzwert von >12 mmHg / ml / min in 21 % der Patienten falsch positiv. Die Parameter RAP, ICP und SW-Aktivität des OVM lieferten unterschiedliche Ergebnisse in den einzelnen Patientengruppen, waren aber nicht mit dem Outcome assoziiert. In einer multivariaten Regressionsanalyse ließ sich ein signifikanter Zusammenhang zwischen der Parameterkombination MMST, ROut und Änderung der Amplitude des intrakraniellen Druckes im LIFT (AMP Q) und dem Behandlungsergebnis 12 Monate nach Shuntimplantation darstellen (p = 0,04). Trotz der Vielzahl verfügbarer Tests und Diagnostikpfade besitzt die prächirurgische klinische Testung und einfache probatorische ELD die beste Vorhersagekraft für eine Symptombesserung nach Shunttherapie. Die Komplikationsrate invasiver Tests war in unserer Studie 5,4 %. Die multivariaten und univariaten Regressionsanalysen zeigten, dass das Outcome wahrscheinlich lediglich in Parameterkombinationen verschiedener Tests vorhergesagt werden kann. Dies entspricht der noch heute ungeklärten, am ehesten multifaktoriellen Pathogenese des iNPH. Ein aktualisierter Diagnostikpfad auf Grundlage der Studienergebnisse wurde vorgeschlagen. Zur Therapieentscheidung bei NPH sollte eine bereits bestehende kognitive Störung als prognostisch ungünstiger Faktor (MMST < 21) berücksichtigt werden. Da ∆- MMST einen prognostischen Wert für das Outcome darstellt, kann eine Verbesserung der kognitiven Fähigkeiten als positive Reaktion gewertet werden. Bei einer Verschlechterung wird eher ein ungünstiger Verlauf angenommen. Die hohe Streuvarianz lässt mathematisch keine Aussage für den Vorhersagewert der einzelnen Parameter zu. Für den individuellen Patienten ist bei der prospektiven Beratung kein Einzelparameter in der Lage, mit herausragender prognostischer Sicherheit ein Therapieansprechen vorherzusagen, sodass die detaillierte Untersuchung mit Bewertung aller erhobenen Daten sowie der geschilderten Symptome vor und nach Liquordrainage weiterhin zuverlässigste Vorgehensweise bleibt. Da kein signifikanter Zusammenhang zwischen Kiefer-präOP und ROut (p = 0,31) belegt werden konnte, korreliert das Ausmaß der Erkrankung folglich nicht mit ROut. Vorhergehend Publizierende verwiesen dahingegen auf eine Reduktion von ROut im Verlauf der Erkrankung vor Therapiebeginn/ parallel zum Erkrankungszeitraum vor Einsetzen einer Therapie [5]. Die Annahme, der iNPH gehe im Krankheitsverlauf von einer primär reinen Pulsationsstörung in eine neurochirurgisch nicht therapierbare metabolisch-neurodegenerative Erkrankung über, ist daher naheliegend. Das untersuchte Patientenkollektiv ließ allerdings keinen Beleg eines Zusammenhangs zwischen letztendlichem Outcome und Erkrankungsdauer vor Therapiebeginn zu (R2 = 0,009).:Inhaltsverzeichnis 4 Abkürzungsverzeichnis 6 1. Einleitung und Zielsetzung der Studie 9 1.1. Einleitung 9 1.2. Zielsetzung der Studie 9 1.3. Hypothesen 11 2. Originalpublikation 12 3. Methodik 18 3.1. Klinische Testung und Scores 19 3.2. Invasive Diagnostik 19 3.3. Evaluation des Behandlungsergebnisses 20 3.4. Datenanalyse 21 4. Ergebnisse 22 4.1. Demographische Daten 22 4.2. Ergebnisse und prädiktiver Wert der klinischen Parameter 23 4.3. Ergebnisse der invasiven Testungen und prädiktiver Wert der einzelnen Testverfahren 25 4.3.1. Overnight-Monitoring 25 4.3.2. Lumbaler Infusionstest 26 4.3.3. Probatorische Lumbaldrainage 29 4.4. Prädiktive Faktoren für das Ansprechen auf Shunttherapie 30 4.5. Uni- und multivariate Regressionsanalysen 30 4.5.1. Univariate Regressionsanalyse 31 4.5.2. Multivariate Regressionsanalyse 31 4.5.3. „Die Kadenz“ – Multiple logistische Regressionsmodelle 35 4.6. Diagnostische Komplikationen 37 5. Diskussion 38 6. Schlussfolgerung 42 7. Zusammenfassung 43 8. Anhang 46 9. Literaturnachweis 50 10. Danksagung 54 11. Erklärung über die eigenständige Abfassung der Arbeit 56 12. Erklärung zum Eigenanteil der Dissertationsschrift 57

Submitted by Cláudia Bueno (claudiamoura18@gmail.com) on 2015-10-15T19:58:50Z No. of bitstreams: 2 Tese - NELSON RASSI - 2014.pdf: 2531801 bytes, checksum: 4a281a91c2ca563e8fead55207f00d61 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Approved for entry into archive by Cláudia Bueno (claudiamoura18@gmail.com) on 2015-10-15T20:31:04Z (GMT) No. of bitstreams: 2 Tese - NELSON RASSI - 2014.pdf: 2531801 bytes, checksum: 4a281a91c2ca563e8fead55207f00d61 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Made available in DSpace on 2015-10-15T20:31:04Z (GMT). No. of bitstreams: 2 Tese - NELSON RASSI - 2014.pdf: 2531801 bytes, checksum: 4a281a91c2ca563e8fead55207f00d61 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Previous issue date: 2014-09-13 / Background: The number of patients with Type 2 Diabetes Mellitus (T2DM) in Brazil has, in recent decades, increased substantially and insulin therapy is often necessary in a large portion of this population in order to achieve appropriate glycemic control. Objective: To evaluate glycemic control achieved with recombinant human insulin NPH - Gansulin and compares it with human NPH insulin - Humulin N® in patients with Type 2 Diabetes Mellitus. Subjects and methods: A prospective, double-blind, randomized, parallel, single center with 37 individuals with type 2 diabetes using insulin NPH insulin. For statistical analyzes were used: the multiple comparison test of Tukey-Kramer test, Wilcoxon paired comparison test and Chi- Square. It was regarded level of significance value lower than 5% (p<0.05). Results: Insulins NPH and Humulin Gansulin showed similar reductions in HbA1c at the end of the study compared to baseline. Initial HbA1c 7.91% in the Humulin group was reduced to 6.56% (p<0.001) at the end of the study whereas in the Gansulin the glycated hemoglobin was reduced from 8.18% to 6.65% (p<0.001). At the end of the study there was no significant difference between the glycated hemoglobin levels (p=0.2410), fasting blood glucose (p=0.9257) and glucose at bedtime (p=0.3906) between the two types of insulin. Regarding the number of hypoglycemic events, there was no significant difference between the two insulins and no severe hypoglycemic episodes were recorded. Conclusion: The NPH Gansulin (Insuneo N®) presented glycemic control similar to that presented by human insulin Humulin N® in patients with DM2. It was considered level of significance value less than 5%. / Fundamento: O número de pacientes com Diabetes Mellitus Tipo 2 (DM2) no Brasil tem, nas últimas décadas, aumentado substancialmente e a terapia insulínica é necessária em uma grande parcela desta população com a finalidade de adquirir controle glicêmico adequado. Objetivo: Avaliar o controle glicêmico obtido com a insulina humana recombinante NPH – Gansulin e compará-la com o da insulina humana NPH – Humulin N® em pacientes com Diabetes Mellitus Tipo 2 (DM2). Sujeitos e métodos: Estudo prospectivo, duplo cego, randomizado, paralelo e monocêntrico com 37 indivíduos portadores de diabetes tipo 2, em uso de insulina NPH. Para as análises estatísticas foram utilizados: o teste de comparações múltiplas de Tukey-Kramer, o teste de comparação pareada de Wilcoxon e o teste Chi-Square. Foi considerado como nível de significância o valor inferior a 5% (p<0,05). Resultados: As insulinas NPH Humulin e Gansulin apresentaram reduções semelhantes da HbA1c ao final do estudo, quando comparadas aos valores iniciais. A HbA1c inicial de 7,91% do grupo Humulin foi reduzida para 6,56% (p<0,001), enquanto que na do Gansulin, a redução foi de 8,18% para 6,65% (p<0,001). Ao final do estudo não houve diferença significativa entre os valores de hemoglobina glicada (p=0,2410), glicemia jejum (p=0,9257) e glicemia ao deitar (p=0,3906) entre os dois tipos de insulina. Em relação ao número de eventos hipoglicêmicos, não se observou diferença significativa entre as duas insulinas e não foram registrados episódios hipoglicêmicos graves. Conclusão: A insulina NPH Gansulin apresentou controle glicêmico semelhante ao apresentado pela insulina humana Humulin N® em pacientes com DM2.

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