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1. Mechanisms of insulin resistance in obese pregnant women : potential therapeutic interventions

Author

Maitland, Rahat Ashraf, Poston, Lucilla, and academic, affiliated

Subjects
618.3
Abstract

Maternal obesity is associated with adverse pregnancy outcomes, especially the development of gestational diabetes mellitus (GDM), with associated risks for mother and infant. Improved understanding of glucose intolerance in obese women and better prediction and prevention of GDM is key to improving the health of mother and her child. This thesis reports two related projects. The first explored mechanisms of insulin resistance and prediction of GDM in obese pregnant women participating in the pilot study for the UK Pregnancies Better Eating and Activity Trial (UPBEAT), a lifestyle intervention RCT. The second investigated the potential of a dietary intervention to improve glycaemic profiles in this high-risk group. Following an 8 week dietary and physical activity intervention, a panel of biomarkers associated with obesity and insulin resistance were measured in 117 women in the pilot trial. At 27+0-28+6 weeks’ no difference was observed between the intervention and control arms but at 34+0-35+6 weeks’, significant reductions in plasma visfatin, cholesterol and LDL cholesterol were observed. Analysis by GDM status, confirmed greater concentrations of fructosamine, AST and insulin and lower plasma leptin and adiponectin in women who developed GDM. An algorithm based on clinical factors alone (age, parity, ethnicity and blood pressure at 15+0-18+6 weeks’ gestation) showed predictive potential which increased significantly with the addition of plasma adiponectin measured at 15+0-18+6 weeks. In obese pregnant women without GDM (n=16,) the effect of a slow-digesting low glycaemic index (SD-LGI) supplement drink was evaluated at 24+0-28+6 weeks’ gestation. Linear regression analysis with mixed modelling (LMM) showed a significant reduction in glycaemia over the 24 hour period following consumption of the test compared to the control supplement and habitual diet. Fasting and nocturnal glucose concentrations were also significantly improved. In summary biomarkers associated with insulin resistance were identified as potential targets for lifestyle interventions aimed at reducing GDM in obese women. A prediction model for GDM identified those at greatest risk and pending validation in the UPBEAT RCT may have the potential for translation into clinical care. Extending the role of interventions further, multiple improvements in parameters of glycaemic control were demonstrated using a SD-LGI nutritional supplement.

Published
2016

6. A Slow-Digesting, Low-Glycemic Load Nutritional Beverage Improves Glucose Tolerance in Obese Pregnant Women Without Gestational Diabetes

Author

Maitland, Rahat, primary, Patel, Nashita, additional, Barr, Suzanne, additional, Sherry, Christina, additional, Marriage, Barbara, additional, Seed, Paul, additional, Garcia Fernandez, Llenalia, additional, Lopez Pedrosa, Jose M., additional, Murphy, Helen, additional, Rueda, Ricardo, additional, and Poston, Lucilla, additional

Published
2018
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8. Early antenatal prediction of gestational diabetes in obese women:Development of prediction tools for targeted intervention

Author

White, Sara L., Lawlor, Debbie A., Briley, Annette L., Godfrey, Keith M., Nelson, Scott M., Oteng-Ntim, Eugene, Robson, Stephen C., Sattar, Naveed, Seed, Paul T., Vieira, Matias C., Welsh, Paul, Whitworth, Melissa, Poston, Lucilla, Pasupathy, Dharmintra, Shennan, Andrew, Singh, Claire, Sandall, Jane, Sanders, Thomas, Patel, Nashita, Flynn, Angela, Badger, Shirlene, Barr, Suzanne, Holmes, Bridget, Goff, Louise, Hunt, Clare, Filmer, Judy, Fetherstone, Jeni, Scholtz, Laura, Tarft, Hayley, Lucas, Anna, Tekletdadik, Tsigerada, Ricketts, Deborah, Gill, Carolyn, Ignatian, Alex Seroge, Boylen, Catherine, Adegoke, Funso, Lawley, Elodie, Butler, James, Maitland, Rahat, Khazaezadeh, Nina, Demilew, Jill, O'Connor, Sile, Evans, Yvonne, O'Donnell, Susan, De La Llera, Ari, Gutzwiller, Georgina, Hagg, Linda, Bell, Ruth, Hayes, Louise, and Ritson, Sarah

Subjects
endocrine system diseases, Physiology, Maternal Health, lcsh:Medicine, Type 2 diabetes, Biochemistry, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, Glucose Metabolism, Pregnancy, Medicine and Health Sciences, Diabetes diagnosis and management, 030212 general & internal medicine, Prospective Studies, lcsh:Science, Medicine(all), Multidisciplinary, Agricultural and Biological Sciences(all), Obstetrics, Obstetrics and Gynecology, 3. Good health, Gestational diabetes, Fructosamine, Physiological Parameters, Carbohydrate Metabolism, Female, Research Article, Adult, medicine.medical_specialty, HbA1c, Endocrine Disorders, General Science & Technology, 030209 endocrinology & metabolism, 03 medical and health sciences, Insulin resistance, Internal medicine, Diabetes mellitus, medicine, Diabetes Mellitus, Metabolomics, Humans, Hemoglobin, Obesity, Management of High-Risk Pregnancies, Adiponectin, business.industry, Biochemistry, Genetics and Molecular Biology(all), lcsh:R, Body Weight, Biology and Life Sciences, Proteins, nutritional and metabolic diseases, medicine.disease, Diagnostic medicine, Diabetes, Gestational, Metabolism, chemistry, Metabolic Disorders, Women's Health, lcsh:Q, business, Biomarkers
Abstract

All obese women are categorised as being of equally high risk of gestational diabetes (GDM) whereas the majority do not develop the disorder. Lifestyle and pharmacological interventions in unselected obese pregnant women have been unsuccessful in preventing GDM. Our aim was to develop a prediction tool for early identification of obese women at high risk of GDM to facilitate targeted interventions in those most likely to benefit. Clinical and anthropometric data and non-fasting blood samples were obtained at 1518 weeks' gestation in 1303 obese pregnant women from UPBEAT, a randomised controlled trial of a behavioural intervention. Twenty one candidate biomarkers associated with insulin resistance, and a targeted nuclear magnetic resonance (NMR) metabolome were measured. Prediction models were constructed using stepwise logistic regression. Twenty six percent of women (n = 337) developed GDM (International Association of Diabetes and Pregnancy Study Groups criteria). A model based on clinical and anthropometric variables (age, previous GDM, family history of type 2 diabetes, systolic blood pressure, sum of skinfold thicknesses, waist:height and neck:thigh ratios) provided an area under the curve of 0.71 (95% CI 0.68-0.74). This increased to 0.77 (95%CI 0.73-0.80) with addition of candidate biomarkers (random glucose, haemoglobin A1c (HbA1c), fructosamine, adiponectin, sex hormone binding globulin, triglycerides), but was not improved by addition of NMR metabolites (0.77; 95%CI 0.74-0.81). Clinically translatable models for GDM prediction including readily measurable variables e.g. mid-arm circumference, age, systolic blood pressure, HbA1c and adiponectin are described. Using a ≥35% risk threshold, all models identified a group of high risk obese women of whom approximately 50% (positive predictive value) later developed GDM, with a negative predictive value of 80%. Tools for early pregnancy identification of obese women at risk of GDM are described which could enable targeted interventions for GDM prevention in women who will benefit the most.

Published
2016
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9. YDEF training survey 2014

Author

Grant, Paul, primary, Chakera, Ali, additional, Cheer, Kelly, additional, Herring, Roselle, additional, Maitland, Rahat, additional, George, Jyothis, additional, Piya, Milan, additional, and Little, Stuart, additional

Published
2014
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10. Admission Glucose Number (AGN): A Point of Admission Score Associated With Inpatient Glucose Variability, Hypoglycemia, and Mortality.

Author

McKechnie J, Maitland R, Sainsbury CAR, and Jones GC

Subjects
Aged, Biomarkers blood, Diabetes Mellitus, Type 2 diagnosis, Diabetes Mellitus, Type 2 mortality, Female, Glycated Hemoglobin metabolism, Humans, Hypoglycemia diagnosis, Hypoglycemia mortality, Male, Middle Aged, Risk Assessment, Risk Factors, Time Factors, Blood Glucose metabolism, Diabetes Mellitus, Type 2 blood, Hospital Mortality, Hypoglycemia blood, Patient Admission
Abstract

Aims: We investigated a point of admission metric of glycemia, the Admission Glucose Number (AGN), and its relationship with both high risk inpatient glucose patterns and mortality in hospital inpatients with type 2 diabetes (T2DM)., Methods: Inpatient capillary blood glucose (CBG) data for patients with T2DM in our health board were identified for a 5-year period and associated with most recent preadmission HbA1c. AGN was calculated as first CBG measured during admission (mmol/L), subtracted from most recent preadmission HbA1c (converted to estimated median glucose mmol/l) within 15 months preadmission. The association between AGN and CBG variability (interquartile range), hypoglycemia free survival (HR) and both inpatient and 100-day mortality (HR) were investigated., Results: A total of 21 045 first admissions with available HbA1c data were identified. A positive correlation between AGN and glycemic variability was described (partial correlation coefficient 0.25, P < .001), which was stronger than the correlation of either of AGNs' individual components: adjusted CBG1 = 0.07 ( P < .001), eAG = 0.08 ( P < .001). The hazard ratio for time to first recorded CBG < 3 mmol/L for high AGN versus low AGN was 1.74 (95% CI 1.55-1.96), P < .001. A high AGN was associated with increased 100-day mortality (HR 1.26, P = .005), however not with in-hospital mortality (HR = 1.31, P = .08)., Conclusion: AGN is a simple metric that combines 2 readily available measures associated with adverse outcome in T2DM. AGN may be a useful tool to stratify patients for risk of hypoglycemia and postdischarge death.

Published
2019
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