Young people with Type 1 diabetes of non-white ethnicity and lower socio-economic status have poorer glycaemic control in England and Wales

Background The impact of ethnicity and socio-economic status (SES) on glycaemic control during childhood Type 1 diabetes is poorly understood in England and Wales. Methods We studied 18 478 children with Type 1 diabetes

Early Response to Preventive Strategies in the Diabetes Prevention Program

BACKGROUND Recommendations for diabetes prevention in patients with prediabetes include lifestyle modification and metformin. However, the significance of early weight loss and glucose measurements when monitoring response to these proven interventions is unknown. OBJECTIVE To quantify the relationship between early measures of weight and glucose and subsequent diabetes in patients undergoing diabetes prevention interventions. DESIGN Analysis of results from a randomized controlled trial in 27 academic medical centers in the United States. PARTICIPANTS/INTERVENTIONS 3,041 adults with hyperglycemia randomized to lifestyle (n = 1,018), metformin (n = 1,036), or placebo (n = 987) with complete follow-up in The Diabetes Prevention Program. MAIN MEASURES Independent variables were weight loss at 6 and 12 months; fasting glucose (FG) at 6 months; hemoglobin A1c (HbA1c) at 6 months; and post-load glucose at 12 months. The main outcome was time to diabetes diagnosis. KEY RESULTS After 6 months, 604 participants developed diabetes in the lifestyle (n = 140), metformin (n = 206), and placebo (n = 258) arms over 2.7 years. In the lifestyle arm, 6-month weight loss predicted decreased diabetes risk in a graded fashion: adjusted HR (95 % CI) 0.65 (0.35–1.22), 0.62 (0.33–1.18), 0.46 (0.24–0.87), 0.34 (0.18–0.64), and 0.15 (0.07–0.30) for 0–60 % lower diabetes risk across arms. We found a significant interaction between 6-month weight loss and FG in the lifestyle arm (P = 0.038). CONCLUSION Weight and glucose at 6 and 12 months strongly predict lower subsequent diabetes risk with a lifestyle intervention; lower FG predicts lower risk even with substantial weight loss. Early reduction in glycemia is a stronger predictor of future diabetes risk than weight loss for metformin. We offer the first evidence to guide clinicians in making interval management decisions for high-risk patients undertaking measures to prevent diabetes

From metabonomics to pharmacometabonomics: The role of metabolic profiling in personalized medicine

Variable patient responses to drugs are a key issue for medicine and for drug discovery and development. Personalised medicine, that is the selection of medicines for subgroups of patients so as to maximise drug efficacy and minimise toxicity, is a key goal of 21st century healthcare. Currently, most personalised medicine paradigms rely on clinical judgement based on the patient’s history, and on the analysis of the patients’ genome to predict drug effects i.e. pharmacogenomics. However, variability in patient responses to drugs is dependent upon many environmental factors to which human genomics is essentially blind. A new paradigm for predicting drug responses based on individual pre-dose metabolite profiles has emerged in the past decade: pharmacometabonomics, which is defined as ‘the prediction of the outcome (for example, efficacy or toxicity) of a drug or xenobiotic intervention in an individual based on a mathematical model of pre-intervention metabolite signatures’. The new pharmacometabonomics paradigm is complementary to pharmacogenomics but has the advantage of being sensitive to environmental as well as genomic factors. This review will chart the discovery and development of pharmacometabonomics, and provide examples of its current utility and possible future developments

Sexual Figures of Kerala: Cultural Practices, Regionality and the Politics of Sexuality.

This dissertation examines discourses of sexuality in Kerala, a “model state” known for successful development, gender equity and literacy rates in India. Kerala’s restructuring in the 1990s era of liberalization has shifted the governmental and political discourses of sexuality. I examine the post-1990s public sphere of Kerala as it changes and yet retains its connection to earlier periods. Through the examination of formative networks of visual and literary cultural practices of the region, I offer a critical understanding of the politics of sexuality. The domestic woman is foundational to the making of Kerala as a model state. My analysis focuses on how non-normative sexual figures of the prostitute and the lesbian claim subject positions in the post-1990s within the context of complex cultural practices in the region. I move away from a politics of empowerment and progress in order to locate forms of resistance that are tenuous, tactical and marked by affective excess. My focus on the long, ruptured history of sexuality in Kerala troubles the liberatory movement from silence to speech. I focus on vernacular, mass cultural materials produced by the state and activist organizations. I also examine the disorderly circuits of popular texts and public events. The first chapter analyzes the cult representation of the prostitute in pre-1990s popular media and its afterlife in the post-1990s period in my analyses of the Malayalam film Avalude Ravukal (Her Nights 1978) and the Kunjibi murder case (1987). The second chapter focuses on the dual autobiographical project of Nalini Jameela, a sex worker (2005), and its critique of public health and rights paradigms. The third chapter demonstrates that a film from the 1980s can be more disruptive than a recent transnational production Sancharram (The Journey 2004), labeled the first lesbian film set in Kerala. A study of the narratives of lesbian suicides recorded by the activist group Sahayatrika (Co-traveller), the fourth chapter locates tentative acts and practices that render vulnerable the regulatory norms of heterosexuality. This dissertation thus analyzes the region not as a space of exception but rather as a set of cultural practices that unsettle sexual politics.Ph.D.English and Women's StudiesUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/78876/1/navnee_2.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/78876/2/navnee_1.pd

NMR-based pharmacometabonomics: A new paradigm for personalised or precision medicine

Metabolic profiling by NMR spectroscopy or hyphenated mass spectrometry, known as metabonomics or metabolomics, is an important tool for systems-based approaches in biology and medicine. The experiments are typically done in a diagnostic fashion where changes in metabolite profiles are interpreted as a consequence of an intervention or event; be that a change in diet, the administration of a drug, physical exertion or the onset of a disease. By contrast, pharmacometabonomics takes a prognostic approach to metabolic profiling, in order to predict the effects of drug dosing before it occurs. Differences in pre-dose metabolite profiles between groups of subjects are used to predict post-dose differences in response to drug administration. Thus the paradigm is inverted and pharmacometabonomics is the metabolic equivalent of pharmacogenomics. Although the field is still in its infancy, it is expected that pharmacometabonomics, alongside pharmacogenomics, will assist with the delivery of personalised or precision medicine to patients, which is a critical goal of 21st century healthcare

Trans-ethnic Meta-analysis and Functional Annotation Illuminates the Genetic Architecture of Fasting Glucose and Insulin

Knowledge of the genetic basis of the type 2 diabetes (T2D)-related quantitative traits fasting glucose (FG) and insulin (FI) in African ancestry (AA) individuals has been limited. In non-diabetic subjects of AA (n = 20,209) and European ancestry (EA; n = 57,292), we performed trans-ethnic (AA+EA) fine-mapping of 54 established EA FG or FI loci with detailed functional annotation, assessed their relevance in AA individuals, and sought previously undescribed loci through trans-ethnic (AA+EA) meta-analysis. We narrowed credible sets of variants driving association signals for 22/54 EA-associated loci; 18/22 credible sets overlapped with active islet-specific enhancers or transcription factor (TF) binding sites, and 21/22 contained at least one TF motif. Of the 54 EA-associated loci, 23 were shared between EA and AA. Replication with an additional 10,096 AA individuals identified two previously undescribed FI loci, chrX FAM133A (rs213676) and chr5 PELO (rs6450057). Trans-ethnic analyses with regulatory annotation illuminate the genetic architecture of glycemic traits and suggest gene regulation as a target to advance precision medicine for T2D. Our approach to utilize state-of-the-art functional annotation and implement trans-ethnic association analysis for discovery and fine-mapping offers a framework for further follow-up and characterization of GWAS signals of complex trait loc

Measurement of Weight in Clinical Trials: Is One Day Enough?

Background. Weight is typically measured on a single day in research studies. This practice assumes negligible day-to-day weight variability, although little evidence exists to support this assumption. We compared the precision of measuring weight on one versus two days among control participants in the Weight Loss Maintenance trial. Methods. Trained staff measured weight on two separate days at baseline, 12 months, and 30 months (2004–2007). We calculated the standard deviation (SD) of mean weight change from baseline to the 12- and 30-month visits using (a) the first and (b) both daily weights from each visit and conducted a variance components analysis (2009). Results. Of the 316 participants with follow-up measurements, mean (SD) age was 55.8 (8.5) years, BMI was 30.8 (4.5) kg/m2, 64% were women, 36% were black, and 50% were obese. At 12 months, the SD of mean weight change was 5.1 versus 5.0 kg using one versus two days of weight measurements (P = .76), while at 30 months the corresponding SDs were 6.3 and 6.3 kg (P = .98). We observed similar findings within subgroups of BMI, sex, and race. Day-to-day variability within individuals accounted for <1% of variability in weight. Conclusions. Measurement of weight on two separate days has no advantage over measurement on a single day in studies with well-standardized weight measurement protocols

Transition between Pediatric and Adult Diabetes Healthcare Services:An Online Global Survey of Experiences and Perceptions of Young People with Diabetes and Their Carers

INTRODUCTION: Young adults with diabetes face many challenges during emerging adulthood. Our study aimed to identify experiences and perceptions of people with diabetes (PwD) (aged 14-25 years) and their carers, around transition planning, and the actual transfer from pediatric to adult diabetes healthcare services.METHODS: Data were collected via an online global survey (seven language options), broadly advertised by the scientific societies ISPAD, EASD, patient advocates, team members and partners, via newsletters, websites, e-mails, and social media.RESULTS: There were 146 respondents from 29 countries. Of these, 90 (61.6%) were PwD age 18.5 (±3.6 years), diagnosed at 9.0 (±4.4 years), and 56 (38.3%) carers. Respondents receiving care in pediatric units (vs. adult) (58.2%) had higher care satisfaction and more frequent appointments (p &lt; 0.05); 65.1% of respondents reported a fixed transfer age (≥18 years). Overall, 45.2% detailed transfer-related concerns; 44.3% felt their psychosocial needs were adequately addressed, 24.7% felt unprepared for areas of self-management. Combined pediatric and adult diabetes clinics (56.2%), and psychologist support (50.7%) were most desired.CONCLUSION: Findings highlight the urgent need to improve the transition process. A joint ISPAD, EASD, and ADA consensus report is in preparation.</p

Using Genetic Technologies To Reduce, Rather Than Widen, Health Disparities

Evidence shows that both biological and nonbiological factors contribute to health disparities. Genetics, in particular, plays a part in how common diseases manifest themselves. Today, unprecedented advances in genetically based diagnoses and treatments provide opportunities for personalized medicine. However, disadvantaged groups may lack access to these advances, and treatments based on research on non-Hispanic whites might not be generalizable to members of minority groups. Unless genetic technologies become universally accessible, existing disparities could be widened. Addressing this issue will require integrated strategies, including expanding genetic research, improving genetic literacy, and enhancing access to genetic technologies among minority populations in a way that avoids harms such as stigmatization

A Systematic Review of Factors Associated With Transition Readiness and the Transfer to Adult Health Care for Young People With Diabetes

This systematic review describes factors associated with transition readiness and the transfer of care from pediatric to adult health care services among adolescents and young adults with diabetes. Overall, thirty-three international nonintervention, nonqualitative studies were identified between 2018 and 2023. Collectively, this review’s findings identify targets for intervention and may inform policies and care practices related to transition, such as transition readiness, family and peer support, mental health support, and engagement in pediatric care