The Association of Cardiometabolic, Diet and Lifestyle Parameters With Plasma Glucagon-like Peptide-1: An IMI DIRECT Study.

Context: The role of glucagon-like peptide-1 (GLP-1) in type 2 diabetes (T2D) and obesity is not fully understood.

Objective: We investigate the association of cardiometabolic, diet, and lifestyle parameters on fasting and postprandial GLP-1 in people at risk of, or living with, T2D.

Methods: We analyzed cross-sectional data from the two Innovative Medicines Initiative (IMI) Diabetes Research on Patient Stratification (DIRECT) cohorts, cohort 1 (n = 2127) individuals at risk of diabetes; cohort 2 (n = 789) individuals with new-onset T2D.

Precision medicine for cardiometabolic disease: a framework for clinical translation.

Cardiometabolic disease is a major threat to global health. Precision medicine has great potential to help to reduce the burden of this common and complex disease cluster, and to enhance contemporary evidence-based medicine. Its key pillars are diagnostics; prediction (of the primary disease); prevention (of the primary disease); prognosis (prediction of complications of the primary disease); treatment (of the primary disease or its complications); and monitoring (of risk exposure, treatment response, and disease progression or remission).

Discovery of drug-omics associations in type 2 diabetes with generative deep-learning models.

The application of multiple omics technologies in biomedical cohorts has the potential to reveal patient-level disease characteristics and individualized response to treatment. However, the scale and heterogeneous nature of multi-modal data makes integration and inference a non-trivial task. We developed a deep-learning-based framework, multi-omics variational autoencoders (MOVE), to integrate such data and applied it to a cohort of 789 people with newly diagnosed type 2 diabetes with deep multi-omics phenotyping from the DIRECT consortium.

Four groups of type 2 diabetes contribute to the etiological and clinical heterogeneity in newly diagnosed individuals: An IMI DIRECT study.

The presentation and underlying pathophysiology of type 2 diabetes (T2D) is complex and heterogeneous. Recent studies attempted to stratify T2D into distinct subgroups using data-driven approaches, but their clinical utility may be limited if categorical representations of complex phenotypes are suboptimal. We apply a soft-clustering (archetype) method to characterize newly diagnosed T2D based on 32 clinical variables.

Profiles of Glucose Metabolism in Different Prediabetes Phenotypes, Classified by Fasting Glycemia, 2-Hour OGTT, Glycated Hemoglobin, and 1-Hour OGTT: An IMI DIRECT Study.

Differences in glucose metabolism among categories of prediabetes have not been systematically investigated. In this longitudinal study, participants ( = 2,111) underwent a 2-h 75-g oral glucose tolerance test (OGTT) at baseline and 48 months. HbA was also measured.

Processes Underlying Glycemic Deterioration in Type 2 Diabetes: An IMI DIRECT Study.

Objective: We investigated the processes underlying glycemic deterioration in type 2 diabetes (T2D).

Research Design And Methods: A total of 732 recently diagnosed patients with T2D from the Innovative Medicines Initiative Diabetes Research on Patient Stratification (IMI DIRECT) study were extensively phenotyped over 3 years, including measures of insulin sensitivity (OGIS), β-cell glucose sensitivity (GS), and insulin clearance (CLIm) from mixed meal tests, liver enzymes, lipid profiles, and baseline regional fat from MRI. The associations between the longitudinal metabolic patterns and HbA deterioration, adjusted for changes in BMI and in diabetes medications, were assessed via stepwise multivariable linear and logistic regression.

Post-load glucose subgroups and associated metabolic traits in individuals with type 2 diabetes: An IMI-DIRECT study.

Aim: Subclasses of different glycaemic disturbances could explain the variation in characteristics of individuals with type 2 diabetes (T2D). We aimed to examine the association between subgroups based on their glucose curves during a five-point mixed-meal tolerance test (MMT) and metabolic traits at baseline and glycaemic deterioration in individuals with T2D.

Methods: The study included 787 individuals with newly diagnosed T2D from the Diabetes Research on Patient Stratification (IMI-DIRECT) Study.

Genome-Wide Association Analysis of Pancreatic Beta-Cell Glucose Sensitivity.

Context: Pancreatic beta-cell glucose sensitivity is the slope of the plasma glucose-insulin secretion relationship and is a key predictor of deteriorating glucose tolerance and development of type 2 diabetes. However, there are no large-scale studies looking at the genetic determinants of beta-cell glucose sensitivity.

Objective: To understand the genetic determinants of pancreatic beta-cell glucose sensitivity using genome-wide meta-analysis and candidate gene studies.

Predicting and elucidating the etiology of fatty liver disease: A machine learning modeling and validation study in the IMI DIRECT cohorts.

Background: Non-alcoholic fatty liver disease (NAFLD) is highly prevalent and causes serious health complications in individuals with and without type 2 diabetes (T2D). Early diagnosis of NAFLD is important, as this can help prevent irreversible damage to the liver and, ultimately, hepatocellular carcinomas. We sought to expand etiological understanding and develop a diagnostic tool for NAFLD using machine learning.

Discovery of biomarkers for glycaemic deterioration before and after the onset of type 2 diabetes: descriptive characteristics of the epidemiological studies within the IMI DIRECT Consortium.

Aims/hypothesis: Here, we describe the characteristics of the Innovative Medicines Initiative (IMI) Diabetes Research on Patient Stratification (DIRECT) epidemiological cohorts at baseline and follow-up examinations (18, 36 and 48 months of follow-up).

Methods: From a sampling frame of 24,682 adults of European ancestry enrolled in population-based cohorts across Europe, participants at varying risk of glycaemic deterioration were identified using a risk prediction algorithm (based on age, BMI, waist circumference, use of antihypertensive medication, smoking status and parental history of type 2 diabetes) and enrolled into a prospective cohort study (n = 2127) (cohort 1, prediabetes risk). We also recruited people from clinical registries with type 2 diabetes diagnosed 6-24 months previously (n = 789) into a second cohort study (cohort 2, diabetes).

Adult-onset type 1 diabetes: Predictors of glycaemic control.

Aims: Knowledge about adult-onset (AO) type 1 diabetes remains insufficient. We sought to characterize the initial 5 years of AO type 1 diabetes and hypothesized that initial factors predictive of subsequent glycaemic control might exist.

Materials And Methods: A retrospective cohort study based on electronic medical records of 280 subjects with newly diagnosed AO type 1 diabetes (>18 years of age, excluding secondary and latent autoimmune diabetes) with available data for the initial 5-year treatment.

Empagliflozin compared with glimepiride in metformin-treated patients with type 2 diabetes: 208-week data from a masked randomized controlled trial.

Aim: To report results at week 208, including a 104-week masked extension, of the EMPA-REG H2H-SU trial in patients with type 2 diabetes with inadequate glycaemic control on metformin, in which empagliflozin 25 mg given for 104 weeks provided a sustained reduction in glycated haemoglobin (HbA1c) with a small but statistically significant benefit vs glimepiride, sustained reductions in weight and blood pressure, and low risk of hypoglycaemia.

Research Design And Methods: Patients with type 2 diabetes and HbA1c 53-86 mmol/mol (7% to 10%) were randomized to empagliflozin 25 mg or glimepiride 1 to 4 mg for 104 weeks as add-on to metformin. Patients who completed the randomized treatment period could participate in a 104-week extension in which they continued the double-blind treatment allocated at randomization.

Correction to: Comparison of Adipose Distribution Indices with Gold Standard Body Composition Assessments in the EMPA-REG H2H SU Trial: A Body Composition Sub-Study.

In the original publication, disclosure statement for the author Ian J. Neeland was published incorrectly. The correct statement should read as "Ian J.

Stratification of type 2 diabetes based on routine clinical markers.

Aims: We hypothesized that patients with dysregulated type 2 diabetes may be stratified based on routine clinical markers.

Methods: In this retrospective cohort study, diabetes related clinical measures including age at onset, diabetes duration, HbA, BMI, HOMA2-β, HOMA2-IR and GAD65 autoantibodies, were used for sub-grouping patients by K-means clustering and for adjusting. Probability of diabetes complications (95% confidence interval), were calculated using logistic regression.

Impact of a multifactorial treatment programme on clinical outcomes and cardiovascular risk estimates: a retrospective cohort study from a specialised diabetes centre in Denmark.

Objectives: To investigate the impact of a multifactorial treatment programme in a real-life setting on clinical outcomes and estimated cardiovascular disease (CVD) risk.

Design: A retrospective observational cohort study, using data from the electronic medical records and national registers.

Setting: Tertiary diabetes centre in Denmark.

Treatment Modality-Dependent Risk of Diabetic Ketoacidosis in Patients with Type 1 Diabetes: Danish Adult Diabetes Database Study.

Background And Aims: The aim of this study was to evaluate the incidence rates of diabetic ketoacidosis (DKA) according to treatment modality in patients with type 1 diabetes (T1D) in Denmark, either multiple daily injections (MDI) or continuous subcutaneous insulin infusion (CSII).

Materials And Methods: A total of 20,902 T1D registered in the Danish Adult Diabetes Database were followed for an average of 5.4 years.

Longitudinal Assessment of PTH in Community-Dwelling Older Women-Elevations Are Not Associated With Mortality.

Context: In older women, the magnitude of elevated parathyroid hormone (PTH) and its consequence is unclear.

Objective: To describe normal PTH profiles over time and the association with mortality.

Design And Participants: There were 1044 community-dwelling women in the Malmö Osteoporosis Prospective Risk Assessment cohort (OPRA) who attended baseline (age 75 years).

Higher health literacy is associated with better glycemic control in adults with type 1 diabetes: a cohort study among 1399 Danes.

Aim: Self-management of diabetes is influenced by a range of factors including the ability to access, understand, appraise, and use of health information in everyday life, which can collectively be called health literacy. We investigated associations between nine domains of health literacy and HbA1c level in people with type 1 diabetes.

Methods: A cross-sectional study was conducted with 1399 people with type 1 diabetes attending a Danish specialist diabetes clinic.