Evaluation of biomarkers for the prediction of pre-eclampsia in women with type 1 diabetes mellitus: A systematic review.

BACKGROUND: Pre-eclampsia is a leading cause of maternal and perinatal morbidity and mortality. Women with type 1 diabetes are considered a high-risk group for developing pre-eclampsia. Much research has focused on biomarkers as a means of screening for pre-eclampsia in the general maternal population; however, there is a lack of evidence for women with type 1 diabetes.
OBJECTIVES: To undertake a systematic review to identify potential biomarkers for the prediction of pre-eclampsia in women with type 1 diabetes.
SEARCH STRATEGY: We searched Medline, EMBASE, Maternity and Infant Care, Scopus, Web of Science and CINAHL SELECTION CRITERIA: Studies were included if they measured biomarkers in blood or urine of women who developed pre-eclampsia and had pre-gestational type 1 diabetes mellitus Data collection and analysis A narrative synthesis was adopted as a meta-analysis could not be performed, due to high study heterogeneity.
MAIN RESULTS: A total of 72 records were screened, with 21 eligible studies being included in the review. A wide range of biomarkers was investigated and study size varied from 34 to 1258 participants. No single biomarker appeared to be effective in predicting pre-eclampsia; however, glycaemic control was associated with an increased risk while a combination of angiogenic and anti-angiogenic factors seemed to be potentially useful.
CONCLUSIONS: Limited evidence suggests that combinations of biomarkers may be more effective in predicting pre-eclampsia than single biomarkers. Further research is needed to verify the predictive potential of biomarkers that have been measured in the general maternal population, as many studies exclude women with diabetes preceding pregnancy.

Salivary proteomics and peptidomics of type 1 diabetes Mellitus

A Diabetes Mellitus (DM) compreende um conjunto de desordens metabólicas comuns caracterizadas por hiperglicemia, que afeta diferentes órgãos do organismo. Ao longo do tempo, ocorrem danos microvasculares no glomérulo renal, retina e nervos periféricos, bem como doença macrovascular nas artérias. A composição da saliva também é afetada pela DM, com consequências na homeostasia oral. No entanto, o proteoma e o peptidoma salivar têm sido pouco explorados na DM tipo 1 e nas suas complicações crónicas. Tendo em conta o crescente interesse na saliva como fluido diagnóstico, o objetivo principal deste trabalho foi avaliar os eventos proteolíticos subjacentes à DM tipo 1 e às suas complicações microvasculares, bem como, caracterizar as alterações induzidas pela DM tipo 1 no proteoma e peptidoma salivar. A DM tipo 1 e particularmente as complicações microvasculares associadas modulam o perfil proteolítico dos fluidos biológicos, com diferenças significativas de atividade observadas na urina e saliva, atribuídas principalmente ao complexo Metaloproteinase da Matriz (MMP)-9/lipocalina associada à gelatinase de neutrófilos, aminopeptidase N, azurocidina e calicreína 1. O aumento da atividade proteolítica observado na saliva total dos diabéticos resultou no aumento da percentagem de péptidos, principalmente de um número acrescido de fragmentos de colagénio do tipo I, refletindo possivelmente um estado inflamatório crónico dos tecidos orais e periodontais. O peptidoma também corrobora uma maior suscetibilidade das proteínas salivares, especificamente, das proteínas ricas em prolina básicas (bPRP) 1, bPRP2 e proteínas ricas em prolina ácidas (aPRP) à proteólise, evidenciando a geração de fragmentos de proteínas associadas à ligação a bactérias. A análise do proteoma salivar baseada em iTRAQ mostrou uma sobre-expressão de L-plastina, fator do adenocarcinoma do pâncreas e das proteínas S100-A8 e S100-A9, enfatizando a importância do sistema imune inato na patogénese da DM tipo 1 e das complicações microvasculares associadas. A análise integrada de todas as proteínas expressas diferencialmente entre os pacientes diabéticos com ou sem complicações microvasculares e indivíduos saudáveis foi realizada com o STRING, onde se observam três conjuntos funcionalmente ligados, um compreende a interação entre o colagénio tipo I, colagénio tipo II e MMP-9, um segundo conjunto envolve a MMP-2 e o colagénio de tipo I e um terceiro conjunto composto por proteínas salivares e inflamatórias. Estes conjuntos estão associados com as vias Kegg de interação recetor-matriz extracelular, de adesão focal e migração transendotelial dos leucócitos. Por outro lado, a análise do proteoma e peptidoma salivar destacou potenciais biomarcadores para o diagnóstico e prognóstico da DM tipo 1 e das suas complicações.

Trabecular bone score in type 1 diabetes--a cross-sectional study.

UNLABELLED: Trabecular bone score (TBS) seems to provide additive value on BMD to identify individuals with prevalent fractures in T1D. TBS did not significantly differ between T1D patients and healthy controls, but TBS and HbA1c were independently associated with prevalent fractures in T1D. A TBS cutoff <1.42 reflected prevalent fractures with 91.7 % sensitivity and 43.2 % specificity. INTRODUCTION: Type 1 diabetes (T1D) increases the risk of osteoporotic fractures. TBS was recently proposed as an indirect measure of bone microarchitecture. This study aimed at investigating the TBS in T1D patients and healthy controls. Associations with prevalent fractures were tested. METHODS: One hundred nineteen T1D patients (59 males, 60 premenopausal females; mean age 43.4̴1;±̴1;8.9 years) and 68 healthy controls matched for gender, age, and body mass index (BMI) were analyzed. The TBS was calculated in the lumbar region, based on two-dimensional (2D) projections of DXA assessments. RESULTS: TBS was 1.357̴1;±̴1;0.129 in T1D patients and 1.389̴1;±̴1;0.085 in controls (p̴1;=̴1;0.075). T1D patients with prevalent fractures (n̴1;=̴1;24) had a significantly lower TBS than T1D patients without fractures (1.309̴1;±̴1;0.125 versus 1.370̴1;±̴1;0.127, p̴1;=̴1;0.04). The presence of fractures in T1D was associated with lower TBS (odds ratio̴1;=̴1;0.024, 95 % confidence interval (CI)̴1;=̴1;0.001-0.875; p̴1;=̴1;0.042) but not with age or BMI. TBS and HbA1c were independently associated with fractures. The area-under-the curve (AUC) of TBS was similar to that of total hip BMD in discriminating T1D patients with or without prevalent fractures. In this set-up, a TBS cutoff <1.42 discriminated the presence of fractures with a sensitivity of 91.7 % and a specificity of 43.2 %. CONCLUSIONS: TBS values are lower in T1D patients with prevalent fractures, suggesting an alteration of bone strength in this subgroup of patients. Reliable TBS cutoffs for the prediction of fracture risk in T1D need to be determined in larger prospective studies.

The effects of thermal stress on glucoregulation during exercise in participants with Type 1 Diabetes Mellitus

Type 1 Diabetes Mellitus (T1DM) is an autoimmune disease that destroys pancreatic beta cells, affecting glucose homeostasis. In T1DM, glucoregulation and carbohydrate oxidation may be altered in different ambient temperatures; however, current literature has yet to explore these mechanisms. This study examines the effects of 30 minutes of exercise at 65% VO2max in 5ºC, 20ºC and 35ºC in individuals with T1DM. No significant differences were observed for blood glucose across the 3 conditions (p = 0.442), but significance was found for core temperature, heat storage, and sweat rate (p < 0.01). Blood glucose was also shown to vary greatly between individuals among conditions. The mechanisms behind the differences in blood glucose may be due to the lack of significant glucagon production among conditions. These findings suggest that T1DM individuals may exercise submaximally for 30 minutes in different ambient temperatures without significant differences in glucoregulation.

An examination of outdoor experience in the development of character in young adults with Type 1 Diabetes

Connected in Motion is a not for profit organization serving young adults with Type 1 diabetes. The organization hosted outdoor and experiential Type 1 diabetes education programs in January of2009 and 2010. The weekends provided non-clinical alternative Type 1 diabetes education to the underserved population of young adults within Canada. Six women living with Type I diabetes and between the ages of 22 and 30 participated in the Winter Slipstream weekends participated in this phenomenological research study. Through semi-structured interviews and artifact-elicitation interviews, ,{ the lived experiences of the participants were examined. Data analysis indicated that the sense of community created through outdoor programming and experiential education for young adults with Type I diabetes stimulated the development of self-efficacy and participant-perceived improvement in Type 1 diabetes self-management. There was no indication that outdoor and experiential Type I diabetes education had any impact on the development of autonomy among participants. Recommendations are made to encourage the successful implementation of further alternative (non-clinical) Type 1 diabetes education programs for young adults living with Type 1 diabetes.

A Gain Scheduling Model Predictive Controller for Blood Glucose Control in Type 1 Diabetes

This paper presents a control strategy for blood glucose(BG) level regulation in type 1 diabetic patients. To design the controller, model-based predictive control scheme has been applied to a newly developed diabetic patient model. The controller is provided with a feedforward loop to improve meal compensation, a gain-scheduling scheme to account for different BG levels, and an asymmetric cost function to reduce hypoglycemic risk. A simulation environment that has been approved for testing of artificial pancreas control algorithms has been used to test the controller. The simulation results show a good controller performance in fasting conditions and meal disturbance rejection, and robustness against model–patient mismatch and errors in meal estimation

Prediction of glucose excursions under uncertain parameters and food intake in intensive insulin therapy for type 1 diabetes mellitus

Considering the difficulty in the insulin dosage selection and the problem of hyper- and hypoglycaemia episodes in type 1 diabetes, dosage-aid systems appear as tremendously helpful for these patients. A model-based approach to this problem must unavoidably consider uncertainty sources such as the large intra-patient variability and food intake. This work addresses the prediction of glycaemia for a given insulin therapy face to parametric and input uncertainty, by means of modal interval analysis. As result, a band containing all possible glucose excursions suffered by the patient for the given uncertainty is obtained. From it, a safer prediction of possible hyper- and hypoglycaemia episodes can be calculated

Biodritin microencapsulated human islets of langerhans and their potential for type 1 diabetes mellitus therapy

Background. Microencapsulation of pancreatic islets with polymeric compounds constitutes an attractive alternative therapy for type 1 diabetes mellitus. The major limiting factor is the availability of a biocompatible and mechanically stable polymer. We investigated the potential of Biodritin, a novel polymer constituted of alginate and chondroitin sulfate, for islet microencapsulation. Methods. Biodritin microcapsules were obtained using an air jet droplet generator and gelated with barium or calcium chloride. Microencapsulated rat insulinoma RINm5F cells were tested for viability using the [3-(4,5-dimetyl-thiazol-2-yl)-2,5-diphenyl-tetrazoliumbromide] [MTT] colorimetric assay. Microencapsulated rat pancreatic islets were coincubated with macrophages derived from mouse peritoneal liquid to assess the immunomodulatory potential of the microcapsules, using quantitative real time-PCR (qPCR). Biodritin biocompatibility was demonstrated by subcutaneous injection of empty microcapsules into immunocompetent Wistar rats. Insulin secretion by microencapsulated human pancreatic islets was evaluated using an electrochemoluminescent assay. Microencapsulated human islets transplanted into chemically induced diabetic mice were monitored for reversal of hyperglycemia. Results. The metabolic activity of microencapsulated RINm5F cells persisted for at least 15 days. Interleukin-1 beta expression by macrophages was observed during coculture with islets microencapsulated with Biodritin-CaCl2, but not with Biodritin-BaCl2. No statistical difference in glucose-stimulated insulin secretion was observed between nonencapsulated and microencapsulated islets. Upon microencapsulated islet transplantation, the blood glucose level of diabetic mice normalized; they remained euglycemic for at least 60 days, displaying normal oral glucose tolerance tests. Conclusion. This study demonstrated that Biodritin can be used for islet microencapsulation and reversal of diabetes; however, further investigations are required to assess its potential for long-term transplantation.

Health-related quality of life and metabolic control in children with type 1 diabetes : a prospective cohort study

OBJECTIVE—To assess change in health-related quality of life (HRQOL) in children with diabetes over 2 years and determine its relationship to change in metabolic control.

RESEARCH DESIGN AND METHODS—In 1998, parents of children aged 5–18 years attending a tertiary diabetes clinic reported their child’s HRQOL using the Child Health Questionnaire PF-50. Those aged 12–18 years also self-reported their HRQOL using the analogous Child Health Questionnaire CF-80. HbA_1c levels were recorded. In 2000, identical measures were collected for those who were aged ≤18 years and still attending the clinic.

RESULTS—Of 117 eligible subjects, 83 (71%) participated. Parents reported no significant difference in children’s HRQOL at baseline and follow-up. However, adolescents reported significant improvements on the Family Activities (P < 0.001), Bodily Pain (P = 0.04), and General Health Perceptions (P = 0.001) scales and worsening on the Behavior (P = 0.04) scale. HbA1c at baseline and follow-up were strongly correlated (r = 0.57). HbA_1c increased significantly (mean 7.8% in 1998 vs. 8.5% in 2000; P < 0.001), with lower baseline HbA_1c strongly predicting an increase in HbA_1c over the 2 years (r² = 0.25, P < 0.001). Lower parent-reported Physical Summary and adolescent-reported Physical Functioning scores at baseline also predicted increasing HbA_1c. Poorer parent-reported Psychosocial Summary scores were related to higher HbA_1c at both times but did not predict change in HbA_1c.

CONCLUSIONS—Changes in parent and adolescent reports of HRQOL differ. Better physical functioning may protect against deteriorating HbA_1c, at least in the medium term. While the HRQOL of children with diabetes does not appear to deteriorate over time, we should not be complacent, as it is consistently poorer than that of their healthy peers.

Young women with type 1 diabetes' management of turning points and transitions

The authors used grounded theory to explore and develop a substantive theory to explain how 20 young women with type 1 diabetes managed their lives when facing turning points and undergoing transitions. The women experienced a basic social problem: being in the grip of blood glucose levels (BGLs), which consisted of three categories: (a) the impact of being susceptible to fluctuating BGLs, (b) the responses of other people to the individual woman’s diabetes, and (c) the impact of the individual women’s diabetes on other people’s lives. The women used a basic social process to overcome the basic social problem by creating stability, which involved using three interconnected subprocesses: forming meaningful
relationships, enhancing attentiveness to blood glucose levels, and putting things in perspective. Insights into the processes and strategies used by the women have important implications for provision of care and service delivery.

The mother-daughter guilt dynamic : effects of type 1 diabetes during life transitions

Aim. The aim of the study was to explore and describe the strategies young women with type 1 diabetes used to manage life transitions. The paper describes one aspect of how guilt dynamic often operates between mothers and daughters and how the women managed the guilt dynamic to create stability in their lives.
Background. When a child is diagnosed with diabetes, major transitional changes occur in the relationships between the mother and her child. The changes affect the psychological and social aspects of their lives and have a major impact on how young women manage their diabetes. A guilt dynamic between mothers and young women with diabetes emerged as a major theme in a larger study that investigated how young women with diabetes managed life transitions. Although the literature indicates that mothers of chronically ill children experience guilt feelings towards their children, little research was identified that addressed the emotional dynamics between mothers and daughters with diabetes.
Design. Using grounded theory method, interviews were conducted with 20 women with type 1 diabetes and five mothers during 2002 and 2003. Constant comparative analysis was used to analyse the data and develop an in-depth understanding of the experience of living with diabetes during life transitions.
Findings. The findings revealed that guilt feelings created a two-way dependency between mothers and their daughters with diabetes. The two-way dependency involved feelings of being a burden to each other, difficulty balancing responsibilities for diabetes management, difficulty relinquishing emotional and social dependency especially during life transitions. In addition, these issues were rarely discussed openly with each other or with health professionals. The findings provide additional information about the human experience of the mother–daughter relationship and the effect on coping with diabetes in the context of life transitions.
Conclusions. Understanding the impact diabetes has on the emotional and social well being of both women with type 1 diabetes and their mothers is critical in planning appropriate support for both groups. Most importantly, it is critical to understand the guilt dynamic that operates during young women with diabetes' life transitions when the daughters' dependency on their mother's control and responsibility for diabetes management undergo changes resulting in emotional responses, especially guilt feelings.
Relevance to clinical practice. Health professionals need to understand the emotional and social impact of the guilt dynamics between young women with type 1 diabetes and their mothers. Adequate and appropriate support can minimize the guilt feelings and enhance stability and quality of life for both mothers and their daughters, especially during major life transitions, such as motherhood.

Transitions : experiences of women with type 1 diabetes : Turning points and transitions as experienced by young women with type 1 diabetes in Australia

The relationship among psychosocial stress, coping and metabolic control has a key effect on diabetes clinical outcomes and mental health. Life transitions are peak times of major change within personal and social contexts, which add stress affecting on peoples? problem solving. The thesis describes young women with Type 1 diabetes? perspectives of the problems encountered and how they managed them when they faced turning points and made life transitions. The study identified the women?s health concerns and factors that enhanced or hindered their ability to manage turning points and transitions. A substantive theory that comprised a problem of ?being in the grip of blood glucose levels? (BGLs) and a process termed ?creating stability? to manage life transitions was developed. The state of being in the grip of BGLs was associated with the impact of fluctuating BGLs; responses of other people to the womens? diabetes and the impact of diabetes on other people?s lives. The women managed these problems by engaging in social and psychological strategies helping them to stabilised their lives and feel more in control during life transitions.

Psychological impact of DAFNE training in adults with Type 1 diabetes

This thesis investigated the psychological impact of an education intervention, Dose Adjustment for Normal Eating (DAFNE), in adults with type 1 diabetes. The results demonstrated that the education programme improved participants' subjective wellbeing, self-efficacy and reduced diabetes-related distress compared to a comparison group that engaged in usual care. The portfolio examined the use of mindfulness-based strategies, in particular Acceptance and Commitment Therapy (ACT) in four case studies which illustrated that the impact of the therapy is directly related to the the willingness of the client to engage in the practices.

Turning points and transitions : experiences of young women with Type 1 diabetes

This research explores young women with Type 1 diabetes' perspectives of the problems and how they manage them when facing turning points and making life transitions. The study presents a substantive theory of how the women tried to minimise the grip of blood glucose levels felt during transitions by creating stability in their lives.