SUGAR-DIP trial: Oral medication strategy versus insulin for diabetes in pregnancy, study protocol for a multicentre, open-label, non-inferiority, randomised controlled trial

Introduction In women with gestational diabetes mellitus (GDM) requiring pharmacotherapy, insulin was the established first-line treatment. More recently, oral glucose lowering drugs (OGLDs) have gained popularity as a patient-friendly, less expensive and safe alternative. Monotherapy with metformin or glibenclamide (glyburide) is incorporated in several international guidelines. In women who do not reach sufficient glucose control with OGLD monotherapy, usually insulin is added, either with or without continuation of OGLDs. No reliable data from clinical trials, however, are available on the effectiveness of a treatment strategy using all three agents, metformin, glibenclamide and insulin, in a stepwise approach, compared with insulin-only therapy for improving pregnancy outcomes. In this trial, we aim to assess the clinical effectiveness, cost-effectiveness and patient experience of a stepwise combined OGLD treatment protocol, compared with conventional insulin-based therapy for GDM. Methods The SUGAR-DIP trial is an open-label, multicentre randomised controlled non-inferiority trial. Participants are women with GDM who do not reach target glycaemic control with modification of diet, between 16 and 34 weeks of gestation. Participants will be randomised to either treatment with OGLDs, starting with metformin and supplemented as needed with glibenclamide, or randomised to treatment with insulin. In women who do not reach target glycaemic control with combined metformin and glibenclamide, glibenclamide will be substituted with insulin, while continuing metformin. The primary outcome will be the incidence of large-for-gestational-age infants (birth weight >90th percentile). Secondary outcome measures are maternal diabetes-related endpoints, obstetric complications, neonatal complications and cost-effectiveness analysis. Outcomes will be analysed according to the intention-to-treat principle. Ethics and dissemination The study protocol was approved by the Ethics Committee of the Utrecht University Medical Centre. Approval by the boards of management for all participating hospitals will be obtained. Trial results will be submitted for publication in peer-reviewed journals

Variabilidade espacial da agregação do solo avaliada pela geometria fractal e geoestatística Spatial variability of soil aggregation evaluated by fractal geometry and geostatistics

Este trabalho teve por objetivo explorar a aplicabilidade da teoria de fractais no estudo da variabilidade espacial em agregação de solo. A geometria de fractais tem sido proposta como um modelo para a distribuição de tamanho de partículas. A distribuição do tamanho de agregados do solo, expressos em termos de massa, é apresentada. Os parâmetros do modelo, tais como: a dimensão fractal D, medida representativa da fragmentação do solo (quanto maior seu valor, maior a fragmentação), e o tamanho do maior agregado R L foram definidos como ferramentas descritivas para a agregação do solo. Os agregados foram coletados em uma profundidade de 0-10 cm de um Latossolo Vermelho distrófico típico álico textura argilosa, em Angatuba, São Paulo. Uma grade regular de 100 x 100 m foi usada e a amostragem realizada em 76 pontos nos quais se determinou a distribuição de agregados por via úmida, usando água, álcool e benzeno como pré-tratamentos. Pelo exame de semivariogramas, constatou-se a ocorrência de dependência espacial. A krigagem ordinária foi usada como interpolador e mapas de contorno mostraram-se de grande utilidade na descrição da variabilidade espacial de agregação do solo.<br>This work explored the applicability of the fractal theory for studies into space variability of soil aggregation. Fractal geometry has become a model for soil size particle distribution. The distribution of soil aggregates in terms of its mass was obtained, and model parameters such as the fractal dimension D, which is a representative measure of the soil fragmentation (the larger its value, the larger the fragmentation), and the largest aggregate size R L were defined as descriptive tools for soil aggregation. The aggregates were collected at a depth of 0-10 cm of a Clayey Ferrasol in Angatuba, São Paulo. A regular grid of 100 x 100 m was used and samples collected from 76 points, where the aggregate distribution was determined by humid way (water, alcohol and benzene). Spatial dependence was verified by semivariogram exams. Simple kriging was used as interpolator, and contour maps were elaborated, proving to be useful tools to describe the spatial variability of soil aggregation

SUGAR-DIP trial: oral medication strategy versus insulin for diabetes in pregnancy, study protocol for a multicentre, open-label, non-inferiority, randomised controlled trial

Contains fulltext : 208558.pdf (publisher's version ) (Open Access)INTRODUCTION: In women with gestational diabetes mellitus (GDM) requiring pharmacotherapy, insulin was the established first-line treatment. More recently, oral glucose lowering drugs (OGLDs) have gained popularity as a patient-friendly, less expensive and safe alternative. Monotherapy with metformin or glibenclamide (glyburide) is incorporated in several international guidelines. In women who do not reach sufficient glucose control with OGLD monotherapy, usually insulin is added, either with or without continuation of OGLDs. No reliable data from clinical trials, however, are available on the effectiveness of a treatment strategy using all three agents, metformin, glibenclamide and insulin, in a stepwise approach, compared with insulin-only therapy for improving pregnancy outcomes. In this trial, we aim to assess the clinical effectiveness, cost-effectiveness and patient experience of a stepwise combined OGLD treatment protocol, compared with conventional insulin-based therapy for GDM. METHODS: The SUGAR-DIP trial is an open-label, multicentre randomised controlled non-inferiority trial. Participants are women with GDM who do not reach target glycaemic control with modification of diet, between 16 and 34 weeks of gestation. Participants will be randomised to either treatment with OGLDs, starting with metformin and supplemented as needed with glibenclamide, or randomised to treatment with insulin. In women who do not reach target glycaemic control with combined metformin and glibenclamide, glibenclamide will be substituted with insulin, while continuing metformin. The primary outcome will be the incidence of large-for-gestational-age infants (birth weight >90th percentile). Secondary outcome measures are maternal diabetes-related endpoints, obstetric complications, neonatal complications and cost-effectiveness analysis. Outcomes will be analysed according to the intention-to-treat principle. ETHICS AND DISSEMINATION: The study protocol was approved by the Ethics Committee of the Utrecht University Medical Centre. Approval by the boards of management for all participating hospitals will be obtained. Trial results will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NTR6134; Pre-results