A5082891416- Diabetes Treatment and Management
- Genetic Associations and Epidemiology
- Diabetes Management and Research
- Metabolism, Diabetes, and Cancer
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Liver Disease Diagnosis and Treatment
- Diabetes and associated disorders
- Bioinformatics and Genomic Networks
- Pharmacology and Obesity Treatment
- Nutrition, Genetics, and Disease
- Cardiovascular Function and Risk Factors
- Blood Pressure and Hypertension Studies
- Pancreatic function and diabetes
- Nuclear Receptors and Signaling
- Diabetes Management and Education
- Neurological and metabolic disorders
- Lipoproteins and Cardiovascular Health
- Erythropoietin and Anemia Treatment
- Gastric Cancer Management and Outcomes
- Machine Learning in Healthcare
- Pharmacogenetics and Drug Metabolism
- Macrophage Migration Inhibitory Factor
- GDF15 and Related Biomarkers
- Drug Transport and Resistance Mechanisms
- RNA modifications and cancer
Genomics (United Kingdom)
2020-2024
University of Dundee
2014-2024
Ninewells Hospital
2007-2024
PharmacoGenetics (China)
2017
Abstract Aims To ascertain the frequency and identify predictors of self‐reported hypoglycaemia in Type 1 insulin‐treated 2 diabetes. Methods A random sample 267 people with diabetes were recruited from a population‐based register Tayside, Scotland. Each subject prospectively recorded number mild severe hypoglycaemic episodes experienced over 1‐month period. Ordinal logistic regression was performed to potential hypoglycaemia. Results Five hundred seventy‐two events reported by 155 patients....
A scavenger that protects the heart Coronary disease is a tale of two forms plasma cholesterol. In contrast to well-established effects “bad” cholesterol (LDL-C), role “good” (HDL-C) mysterious. Elevated HDL-C correlates with lower risk disease, yet drugs raise levels do not reduce risk. Zanoni et al. found some people exceptionally high carry rare sequence variant in gene encoding major receptor, receptor BI. This destroys receptor's ability take up HDL-C. Interestingly, this have higher...
Metformin is the most widely prescribed medication for treatment of type 2 diabetes (T2D). However, gastrointestinal (GI) side effects develop in ~25% patients treated with metformin, leading to discontinuation therapy ~5% cases. We hypothesized that reduced transport metformin via organic cation transporter 1 (OCT1) could increase concentration intestine, increased risk severe GI and drug discontinuation. compared phenotype, carriage reduced-function OCT1 variants, concomitant prescribing...
Background: Good glycaemic control improves outcomes in patients with type 2 diabetes, but the extent to which this depends on adherence insulin treatment is uncertain. Aim: To investigate association between and insulin-treated diabetes. Design: Observational records-based study. Methods: We studied all diabetes who were resident Tayside, Scotland from 1 January 1995 30 September 2001, treated insulin. Adherence was measured as annual number of days coverage recommended dose, calculated...
In this study, Prokopenko and colleagues provide novel evidence for causal relationship between adiposity heart failure increased liver enzymes using a Mendelian randomization study design. Please see later in the article Editors' Summary
Metformin is a first-line oral agent used in the treatment of type 2 diabetes, but glycaemic response to this drug highly variable. Understanding genetic contribution metformin might increase possibility personalising treatment. We aimed establish heritability using genome-wide complex trait analysis (GCTA) method.
To investigate the association between visit-to-visit HbA1c variability and cardiovascular events microvascular complications in patients with newly diagnosed type 2 diabetes.This retrospective cohort study analyzed from Tayside Fife Scottish Care Information-Diabetes Collaboration (SCI-DC) who were observable diagnosis of diabetes had at least five measurements before outcomes evaluated. We used previously reported score (HVS), calculated as percentage number changes >0.5% (5.5 mmol/mol)...
Abstract Aims/hypothesis Five clusters based on clinical characteristics have been suggested as diabetes subtypes: one autoimmune and four subtypes of type 2 diabetes. In the current study we replicate cross-validate these in three large cohorts using variables readily measured clinic. Methods independent cohorts, total 15,940 individuals were clustered age, BMI, HbA 1c , random or fasting C-peptide, HDL-cholesterol. Clusters cross-validated against original HOMA measures. addition, between...
A precision medicine approach in type 2 diabetes could enhance targeting specific glucose-lowering therapies to individual patients most likely benefit. We aimed use the recently developed Bayesian causal forest (BCF) method develop and validate an individualised treatment selection algorithm for two major drug classes, sodium-glucose cotransporter inhibitors (SGLT2i) glucagon-like peptide-1 receptor agonists (GLP1-RA).
Aims Controversy exists regarding the importance of glycaemic control in patients with type 2 diabetes mellitus ( T2DM ) and chronic heart failure CHF based on conflicting reports using single baseline glycosyated haemoglobin HbA 1c ). Using time‐weighted mean serial measurements has been found to be a better predictor diabetic complications as it reflects burden for that individual over time. We therefore sought confirm this large cohort incident . Methods results A was calculated all...
To look at adverse outcomes for patients on liothyronine compared to l-thyroxine. Some trials have examined the relative merits of but none looked in large numbers.An observational study all prescribed thyroid hormone replacement Tayside Scotland (population 400 000) from 1997 2014.A group having ever used (n = 400) was those who had only l-thyroxine 33 955). All were followed up until end-point, death or leaving Tayside.Mortality rates and admissions with cardiovascular disease, atrial...
OBJECTIVE To evaluate the association between metformin use and anemia risk in type 2 diabetes, time-course for this, a randomized controlled trial (RCT) real-world population data. RESEARCH DESIGN AND METHODS Anemia was defined as hemoglobin measure of <11 g/dL. In RCTs A Diabetes Outcome Progression Trial (ADOPT; n = 3,967) UK Prospective Study (UKPDS; 1,473), logistic regression used to model nonlinear mixed models change hematological parameters. observational Genetics Audit...
Type 2 diabetes is a multifactorial disease with multiple underlying aetiologies. To address this heterogeneity, investigators of previous study clustered people according to five subtypes. The aim the current investigate etiology these clusters by comparing their molecular signatures. In three independent cohorts, in total 15,940 individuals were based on clinical characteristics. subset, genetic (N = 12,828), metabolomic 2,945), lipidomic 2,593), and proteomic 1,170) data obtained plasma....
We identify biomarkers for disease progression in three type 2 diabetes cohorts encompassing 2,973 individuals across molecular classes, metabolites, lipids and proteins. Homocitrulline, isoleucine 2-aminoadipic acid, eight triacylglycerol species, lowered sphingomyelin 42:2;2 levels are predictive of faster towards insulin requirement. Of ~1,300 proteins examined two cohorts, GDF15/MIC-1, IL-18Ra, CRELD1, NogoR, FAS, ENPP7 associated with progression, whilst SMAC/DIABLO, SPOCK1 HEMK2...
To assess the real-world cardiovascular (CV) safety for sulfonylureas (SU), in comparison with dipeptidyl peptidase 4 inhibitors (DPP4i) and thiazolidinediones (TZD), through development of robust methodology causal inference a whole nation study.A cohort study was performed including people type 2 diabetes diagnosed Scotland before 31 December 2017, who failed to reach HbA1c 48 mmol/mol despite metformin monotherapy initiated second-line pharmacotherapy (SU/DPP4i/TZD) on or after 1 January...
Abstract Aims In treating Type 2 diabetes (T2DM), UK guidelines recommend metformin in obese and overweight patients, either sulphonylureas or normal weight patients. Although other factors influence prescribing choice, a key objective T2DM is to lower plasma glucose. There little data on how glycaemic response oral agents varies with body mass index (BMI). Therefore, we assessed current practice effect of BMI large population cohort. Methods was determined 3856 patients sulphonylurea...
Metformin is renally excreted and has been associated with the development of lactic acidosis. Although current advice to omit metformin during illnesses that may increase risk acute kidney injury (AKI), evidence supporting this lacking. We investigated relationship between AKI, lactate concentrations acidosis in those exposed metformin.
Abstract Aims/hypothesis People with type 2 diabetes are heterogeneous in their disease trajectory, some progressing more quickly to insulin initiation than others. Although classical biomarkers such as age, HbA 1c and duration associated glycaemic progression, it is unclear how well variables predict or requirement whether newly identified markers have added predictive value. Methods In two prospective cohort studies part of IMI-RHAPSODY, we investigated clinical three types molecular...
OBJECTIVE—To derive and validate an absolute risk algorithm for major coronary heart disease (CHD) events in the U.K. population with type 2 diabetes. RESEARCH DESIGN AND METHODS—A cohort diabetes was constructed Tayside, Scotland, U.K., longitudinally followed-up to June 2004. Participants were all people registered general practices Diabetes Audit Research database (97% sensitive) no previous CHD event complete measurements (n = 4,569). The main outcome measure of defined as fatal or...
Metformin is the most commonly prescribed oral agent used in treatment of type 2 diabetes. It effective at reducing glycosylated Haemoglobin (HbA1c) and decreasing microvascular macrovascular disease. However, up to 25% patients develop gastrointestinal side effects leading cessation 5-10% users. XL (glucophage SR) a once day preparation that delays absorption, decreased peak metformin concentrations. We hypothesised would be better tolerated than standard immediate release (IR) improved...
Common variation in the fat mass and obesity (FTO)-related gene is associated with increased body susceptibility to type 2 diabetes. We hypothesized that this would also associate metabolic phenotypes of insulin resistance risk cardiovascular morbidity mortality.FTO rs9939609 genotype was determined 4897 patients diabetes prospective Genetics Diabetes Audit Research Study Tayside Scotland study. The A allele lower plasma high-density lipoprotein cholesterol (mean difference, 0.03 mmol/L;...
As genetic association studies increase in size to 100 000s of individuals, subtle biases may influence conclusions. One possible bias is ‘index event bias’ (IEB) that appears due the stratification by, or enrichment for, disease status when testing associations between variants and a disease-associated trait. We aimed test extent which IEB influences some known trait range study designs provide statistical framework for assessing future associations. Analyzing data from 113 203 non-diabetic...
Abstract Aims Increased visit‐to‐visit glycaemic variability is independently associated with adverse outcomes in Type 2 diabetes. Our aim was to identify the patient characteristics raised people Methods A case–control study conducted establish associations between HbA 1c and clinical covariates 10 130 Variability calculated by two metrics [ sd coefficient of variation ( CV )] from a minimum four readings obtained over 4‐year period. High low groups were defined as top bottom tertile or ,...