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Aroon Hingorani

Publications and source records attributed to Aroon Hingorani.

2 recordsLinked to original sources

Large-scale multiethnic electronic health record resource for diabetes complications research: the North West London Diabetes Cohort (NWLDC) - cohort profile.

PURPOSE: The North West London Diabetes Cohort is established to provide systematic characterisation of a large diabetes population as a foundation for complications research and prognostic modelling. Many predictive modelling studies neglect the essential descriptive characterisation of underlying cohorts, focusing narrowly on model accuracy. This cohort profile addresses this gap by comprehensively describing the demographic composition, clinical characteristics and complication incidence patterns. The notably diverse, multiethnic population enables examination of ethnic disparities and supports future development of reliable prognostic models and evidence-based prevention strategies for diabetes complications. PARTICIPANTS: At baseline, 337 271 patients with diabetes were identified. It includes 279 067 patients with type 2 diabetes, 17 638 with type 1 diabetes, 33 590 with gestational diabetes and 6916 with unspecified diabetes. The earliest diabetes diagnosis dates to January 1932, with data updated to 27 May 2025. FINDINGS TO DATE: This cohort profile describes baseline characteristics of patients with comprehensive data collected on demographics (age, sex, Deprivation Index, ethnicity), clinical measures (glycated haemoglobin, body mass index, blood pressure, lipids and estimated glomerular filtration rate) and 14 major diabetes complications tracked longitudinally. Key findings for patients with type 2 diabetes reveal diabetic retinopathy as the most common complication (74.6 per 1000 person-years), followed by hypertension (51.0) and kidney disease (31.4). Cumulative incidence analyses using the Aalen-Johansen estimator, which accounts for mortality as a competing risk, demonstrated significant ethnic disparities, with black, Asian, mixed and other ethnic groups showing elevated risk compared with white patients. Time-varying Cox models identified strong clustering between cardiovascular and renal complications, confirming a cardiometabolic-renal syndrome. Mental health conditions (depression and anxiety) were prevalent throughout the disease timeline, occurring both before and after diabetes diagnosis. FUTURE PLANS: This cohort will be used as a platform for developing and validating prognostic models for diabetes complications, enabling risk stratification and targeted interventions. Future work will incorporate medication data to refine diabetes type classification, examine the effectiveness of antidiabetic medications in preventing different complications and address demographic differences in prognostic model performance and prediction accuracy. To better characterise lifestyle, further interrogation of electronic health record data will examine recording of advice given, including dietary advice, referral to weight management schemes and presence of alcohol consumption codes.

Humans

Genome-wide gene-sleep interaction study identifies novel lipid loci in 732,564 participants.

BACKGROUND AND AIMS: Deviations from the population mean in sleep duration have been associated with increased risk for developing dyslipidemia and atherosclerotic cardiovascular disease, but the mechanism of effect is poorly characterized. We performed large-scale genome-wide gene-sleep interaction analyses of lipid levels to identify genetic variants underpinning the biomolecular pathways of sleep-associated lipid disturbances and to suggest possible druggable targets. METHODS: We collected data from 55 cohorts with a combined sample size of 732,564 participants (87&#xa0;% European ancestry) with data on lipid traits (high-density lipoprotein [HDL-c] and low-density lipoprotein [LDL-c] cholesterol and triglycerides [TG]). Short (STST) and long (LTST) total sleep time were defined by the extreme 20&#xa0;% of the age- and sex-standardized values within each cohort. Based on cohort-level summary statistics data, we performed meta-analyses for one-degree of freedom tests of interaction and two-degree of freedom joint tests of the SNP-main and -interaction effect on lipid levels. RESULTS: The one-degree of freedom variant-sleep interaction test identified 10 novel loci (Pint<5.0e-9), and we additionally identify 7 loci within the two-degree of freedom analyses (Pjoint<5.0e-9 in combination with Pint<6.6e-6). Multiple loci, including those mapped to APSH (target for aspartic and succinic acid) and SLC8A1 showed biological plausibility and druggability potential based on literature. CONCLUSIONS: Collectively, the 17 (9 with short and 8 with long sleep) loci provided evidence into the biomolecular mechanisms underlying sleep-associated lipid changes, including potential involvement of the vitamin D receptor pathway. Collectively, these findings may contribute developing novel interventions for treating dyslipidemia in people with sleep disturbances.

Humans