Precision Medicine In Diabetes Research Articles

A second step towards precision medicine in diabetes.

A second step towards precision medicine in diabetes.

Polygenic Risk Score and Precision Medicine in Diabetes

Precision medicine involves tailoring medical treatment to the individual characteristics, needs, and preferences of each patient. In the realm of diabetes, genetic, environmental, and lifestyle factors must all be considered when developing personalized management strategies. Polygenic risk refers to the cumulative risk of developing a disease based on the presence of multiple genetic variants across the genome. Understanding the polygenic nature of diabetes assists in identifying various genetic factors that contribute to its onset, progression, and the development of complications. Recent studies indicate that polygenic risk scores are instrumental in distinguishing between type 1 diabetes, monogenic diabetes, and type 2 diabetes. Moreover, these scores can predict incident type 2 diabetes in women with a history of gestational diabetes and can be used to forecast diabetic complications. When polygenic risk scores are combined with other risk factors such as age, body mass index, and family history, risk stratification is enhanced, pinpointing individuals who may benefit most from early intervention strategies. Challenges related to practical use of polygenic scores include ethnicity specificity, data privacy, and generating evidence in the clinical setting. We aim to explore opportunities as well as challenges related to utilizing polygenic risk in precision medicine.

Tailoring medical treatment in Pakistan: The promise of precision medicine

Madam, I am writing to discuss the rapidly evolving field of precision medicine (PM), an exciting and highly relevant topic that has garnered increasing attention in Pakistan in recent years. PM is an approach that considers individual differences in genetics, environment, and lifestyle to tailor medical treatment for each patient, rather than relying on a one-size-fits-all approach1. There are several potential benefits of PM for patients in Pakistan. By tailoring treatments to individual needs, PM can lead to more effective treatments and improved patient outcomes. For instance, a recent study found that PM approaches resulted in better outcomes for patients with head and neck cancer2. We can also see big applications of PM in diabetes, which is quite a common disease in Pakistan. PM can revolutionize diabetes care by utilizing genetics to inform diagnosis, therapy, drug dosage, monitoring, and treatment of complications, while it may not yet be widely used, it is expected to become a routine aspect of diabetes care in the near future3. In addition, PM can reduce healthcare costs in the long run by avoiding unnecessary treatments and hospitalizations4. Despite these benefits, the adoption of PM in Pakistan is still in its early stages. There is progress to be made in implementing PM in the country, and several challenges must be overcome such as investment in the infrastructure, training, research, and development required to make PM more widely available and affordable. One big issue regarding PM is its role in the public health domain, as public health experts have expressed doubts about prioritizing individualized approaches for treating sick individuals instead of population-based prevention programs that consider broader factors affecting health like behavior, environment, and society5. But populations managed by PM contribute to a vast amount of data with their unique genetic and socioeconomic traits. Through the analysis of this data using more modern technology, such as machine learning, high risk people may be predicted, which is a game-changer for public health6. To achieve this reality of PM, there is a need to invest in infrastructure, training, and research in this field. In conclusion, PM has the potential to revolutionize healthcare by providing personalized treatment options based on individual factors such as genetics and lifestyle. While there are challenges to implementing PM in LMICs, the field is advancing rapidly, and ongoing research is providing hope for the bright future of personalized medicine in Pakistan.

Precision medicine in diabetes: from discovery to implementation

Precision medicine in diabetes: from discovery to implementation

Human pluripotent stem cells as a platform for precision medicine in diabetes

Human pluripotent stem cells as a platform for precision medicine in diabetes

Differential Spectrum of Albumin Glycation, Oxidation, and Truncation in Type 2 and Type 1 Diabetes: Clinical and Biological Implications.

Background: Albumin, the most abundant and physiologically vital serum protein, accumulates a range of chemical modifications, as consequence of encounters with large number of reactive molecules whose concentrations increase in serum under pathological conditions. Methods: In a "proof of concept" study, mass spectrometric analysis was utilized to quantitate albumin post-translational modifications (glycation, oxidation, and truncation; individual isoforms and total) in four informative subject groups [type 1 diabetes (T1DM), type 2 diabetes (T2DM), prediabetes-obesity and healthy; all with estimated glomerular filtration rate ≥60 mL/(min·m2)]. Besides glycated albumin (GA/mass spectrometry), glycated serum protein (GSP/nitro blue tetrazolium colorimetry), and glycated hemoglobin (HbA1c/high-performance liquid chromatography) were also measured. Results: A wide spectrum of albumin molecular modifications was identified in diabetes, with significant differences between T2DM and T1DM. Albumin glycation: GA correlated more strongly with HbA1c in T1DM, compared to T2DM. Higher albumin glycation isoforms (human serum albumin +3G/2G) were more stable and discriminative markers of mean glycemia. Albumin oxidation: T2DM, in comparison with T1DM, showed enhanced oxidative and dual (glycation plus oxidation) modifications, representing extreme molecular pathology. Albumin truncation: There was dramatic reduction ("deficiency") of truncated albumin isoforms in T2DM, and significant reduction in T1DM. Albumin truncation negatively correlated with severity of albumin glycation (mean glycemia) and albumin oxidation (cysteinylation). Possible mechanisms of insulin resistance, with associated increased free fatty acids binding to albumin, in stimulating albumin oxidation and inhibiting albumin glycation ("metabolic cross talks") are reviewed. Conclusions: Albumin molecular modifications in diabetes, together with significant differences between T2DM and T1DM, suggest possible role for insulin resistance in their genesis and consequent cell, tissue, and vascular dysfunction/damage. Albumin molecular fingerprinting can provide valuable insights into pathogenesis, diagnosis, monitoring, and future therapies for diabetes. Identification of biomarker battery ("albuminomics," "diabetomics") driven diverse "healthy," prediabetes, obesity, and T2DM phenotypes represents additional novel step toward precision medicine in diabetes and related disorders.

Exploring Metabolomic Patterns in Type 2 Diabetes Mellitus and Response to Glucose-Lowering Medications-Review.

The spectrum of information related to precision medicine in diabetes generally includes clinical data, genetics, and omics-based biomarkers that can guide personalized decisions on diabetes care. Given the remarkable progress in patient risk characterization, there is particular interest in using molecular biomarkers to guide diabetes management. Metabolomics is an emerging molecular approach that helps better understand the etiology and promises the identification of novel biomarkers for complex diseases. Both targeted or untargeted metabolites extracted from cells, biofluids, or tissues can be investigated by established high-throughput platforms, like nuclear magnetic resonance (NMR) and mass spectrometry (MS) techniques. Metabolomics is proposed as a valuable tool in precision diabetes medicine to discover biomarkers for diagnosis, prognosis, and management of the progress of diabetes through personalized phenotyping and individualized drug-response monitoring. This review offers an overview of metabolomics knowledge as potential biomarkers in type 2 diabetes mellitus (T2D) diagnosis and the response to glucose-lowering medications.

222-LB: Global Equity in Precision Medicine in Diabetes Research—A Scientometric Review

Objective: While non-Europid populations contribute to nearly 80% of the global diabetes burdens, they are grossly underrepresented in research. Given the growing interest in precision diabetes research, we investigated the proportion of such research in these populations. Methods: We undertook an electronic search of literature in PubMed from 2010 to 2023 to identify studies in precision medicine in diabetes in populations from East Asia (EA), Latin America & Caribbean (LAC), Middle East & North Africa (MENA), South Asia (SA) and South East Asia & Pacific Islands (SEAP). We did not include Central Asia, Eastern Europe, and Sub-Saharan Africa in the current analysis. Two reviewers independently screened titles and abstracts selected by region-stratified sampling to identify articles relevant to precision diabetes. A third reviewer resolved any differences. We estimated the proportion of relevant research using probability sampling weights, and key themes using computational text abstraction. Results: Of the 197,570 studies identified from PubMed, only 15,756 (8.0%) were in populations from EA (4.8%), LAC (1.0%), MENA (0.8%), SA (1.4%) and SEAP (<0.1%) regions. After screening titles and abstracts of 1,686 studies, we estimate only 39.1% [95%CI: 36.1, 42.1] were research relevant to precision medicine in diabetes. Among research relevant to precision diabetes, only 5.9% [5.0, 6.9] of studies are from non-Europid populations (EA: 3.5% [2.7, 4.3], LAC: 0.9% [0.7, 1.2], MENA: <0.1%, SA: 1.5% [1.2, 1.8], SEAP: <0.1%). Nearly 48.9% [46.8, 51.2] of the relevant research used genomics technologies for precision medicine in diabetes. Conclusions: While the vast majority of the global diabetes burden stem from non-Europid populations, only 6% of precision diabetes research are from these populations. This knowledge asymmetry should be addressed to maximize scientific advances and health equity. Disclosure A. Soniwala: None. S. Kim: None. K. Narayan: None. J. Varghese: None. Funding National Institutes of Health (1P30DK111024-01, 1P01HL154996-01A1 to K.M.V.N.)

Getting it right first time – precision medicine in diabetes

Abstract Precision medicine – ‘The right therapy for the right patient at the right time – every time’ – has been a hot topic over the past few years. The definition refers not just to treatment but also to diagnosis, prevention and prognosis. The evidence base for precision medicine is drawn from three categories: (i) assessment of the genetic and metabolic state; (ii) interrogation of big data to inform disease categories; (iii) science‐guided preventative and treatment decisions.The American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) launched the Precision Medicine in Diabetes Initiative (PMDI) in 2018. Their first consensus report was published in 2020, with a four‐phase plan in place to produce guidelines and commence education of clinicians and patients by 2025.The best example of precision medicine in diabetes is monogenic diabetes, for which a genetic test in an individual identifies a specific diabetes type with implications for treatment. At the other extreme, ADA/EASD guidelines for type 2 diabetes identify four broad groups (cardiovascular disease risk; risk of hypoglycaemia; weight; cost) to guide treatment choice. Data analysis has led to identification of clusters within type 2 diabetes, with different clinical and genetic characteristics, but simple clinical factors such as age, weight, and eGFR may be sufficient to predict therapeutic response.For precision medicine to benefit the millions of people with diabetes globally, characteristics used to identify the best treatment for subgroups of populations must be easily measured and inexpensive. Precision medicine is a tool to aid treatment selection but the final choice must lie with the person who will be taking the treatment. Copyright © 2022 John Wiley & Sons.

On the Verge of Precision Medicine in Diabetes.

The epidemic of type 2 diabetes (T2D) is a significant global public health challenge and a major cause of morbidity and mortality. Despite the recent proliferation of pharmacological agents for the treatment of T2D, current therapies simply treat the symptom, i.e. hyperglycemia, and do not directly address the underlying disease process or modify the disease course. This article summarizes how genomic discovery has contributed to unraveling the heterogeneity in T2D, reviews relevant discoveries in the pharmacogenetics of five commonly prescribed glucose-lowering agents, presents evidence supporting how pharmacogenetics can be leveraged to advance precision medicine, and calls attention to important research gaps to its implementation to guide treatment choices.

Precision Medicine in Type 2 Diabetes

Precision medicine is an innovative approach to tailoring disease prevention and treatment that takes into account differences in people’s genes, environments, and lifestyle patterns. The aim of such an approach is to lead a shift in the clinical treatment paradigm from a trial-and-error or perceptive approach to the right drug, for the right patient, at the right time. The characterization of human biology and behaviors is now possible at scale owing to advances in biomarkers, bioimaging, and wearable technologies. In addition, big data from electronic medical records, health insurance databases, and other platforms have become available. These have enabled the generation of new insights into the phenotype known as diabetes. Precision medicine in diabetes (PMD) refers to an approach to optimize the diagnosis, prediction, and prevention or treatment of diabetes by integrating multi-dimensional data accounting for individual differences. The potential for precision treatment in diabetes is vast and should be considered cost-effective. Compared to precision medicine of monogenic diabetes, precision medicine of type 2 diabetes is difficult due to the polygenic condition in which environment as well as thousands of etiological genetic variants play an important role. Although there are the great concerns about PMD, which is complex and difficult to do, is required much time, we look forward to clinical utility in the treatment of patients based on their effects on different classes of markers, including race, metabolic status, other phenotypic markers, and omics data for each class of antihyperglycemic medication in the near future.

Precision Medicine in Diabetes: state of the art based on recent Consensus

There has long been strong emphasis on personalization in the treatment of diabetes; evidence of individual differences in symptomatology, presentation, behavior, preferences, social status, response to treatment, comorbidity or clinical course have led clinicians to seek greater focus on the individual. However, this approach cannot yet be called Precision Medicine in diabetes. In this article we want to describe the state of the art of Precision Medicine starting from the two Consensus documents published by the Precision Medicine in Diabetes Initiative (PMDI) born in 2018 within American Diabetes Association (ADA) and European Association for the Study of Diabetes (EASD) with the aim of understanding the state of the art, the possibilities of application and future lines of research in the construction of a precision medicine applied to diabetes. The five pillars of precision medicine applied to diabetes will be examined: precision diagnosis, precision prevention, precision treatment, precision prognostics and precision monitoring. Following will be described the fields of applications and the possible developments and insights, also within italian diabetological reality. KEY WORDS precision medicine; diabetes; personalization; diagnosis; prevention.

ADA/EASD Precision Medicine in Diabetes Initiative: An International Perspective and Future Vision for Precision Medicine in Diabetes.

ADA/EASD Precision Medicine in Diabetes Initiative: An International Perspective and Future Vision for Precision Medicine in Diabetes.

Roles of plasma leptin and resistin in novel subgroups of type 2 diabetes driven by cluster analysis

BackgroundA novel classification has been introduced to promote precision medicine in diabetes. The current study aimed to investigate the relationship between leptin and resistin levels with novel refined subgroups in patients with type 2 diabetes mellitus (T2DM).MethodsThe k-means analysis was conducted to cluster 541 T2DM patients into the following four subgroups: mild obesity-related diabetes (MOD), severe insulin-deficient diabetes (SIDD), severe insulin-resistant diabetes (SIRD) and mild age-related diabetes (MARD). Individuals meeting the exclusion criteria were eliminated, the data for 285 patients were analyzed. Characteristics were determined using various clinical parameters. Both the leptin and resistin levels were determined using enzyme-linked immunosorbent assay.ResultsThe highest levels of plasma leptin were in the MOD group with relatively lower levels in the SIDD and SIRD groups (P < 0.001). The SIRD group had a higher resistin concentration than the MARD group (P = 0.024) while no statistical significance in resistin levels was found between the SIDD and MOD groups. Logistic regression demonstrated that plasma resistin was associated with a higher risk of diabetic nephropathy (odds ratios (OR) = 2.255, P = 0.001). According to receiver operating characteristic (ROC) curves, the area under the curve (AUC) of resistin (0.748, 95% CI 0.610–0.887) was significantly greater than that of HOMA2-IR (0.447, 95% CI 0.280–0.614) (P < 0.05) for diabetic nephropathy in the SIRD group.ConclusionsLeptin levels were different in four subgroups of T2DM and were highest in the MOD group. Resistin was elevated in the SIRD group and was closely related to diabetic nephropathy.

Heterogeneity of Diabetes: β-Cells, Phenotypes, and Precision Medicine: Proceedings of an International Symposium of the Canadian Institutes of Health Research's Institute of Nutrition, Metabolism and Diabetes and the U.S. National Institutes of Health's National Institute of Diabetes and Digestive and Kidney Diseases.

One hundred years have passed since the discovery of insulin-an achievement that transformed diabetes from a fatal illness into a manageable chronic condition. The decades since that momentous achievement have brought ever more rapid innovation and advancement in diabetes research and clinical care. To celebrate the important work of the past century and help to chart a course for its continuation into the next, the Canadian Institutes of Health Research's Institute of Nutrition, Metabolism and Diabetes and the U.S. National Institutes of Health's National Institute of Diabetes and Digestive and Kidney Diseases recently held a joint international symposium, bringing together a cohort of researchers with diverse interests and backgrounds from both countries and beyond to discuss their collective quest to better understand the heterogeneity of diabetes and thus gain insights to inform new directions in diabetes treatment and prevention. This article summarizes the proceedings of that symposium, which spanned cutting-edge research into various aspects of islet biology, the heterogeneity of diabetic phenotypes, and the current state of and future prospects for precision medicine in diabetes.

Heterogeneity of Diabetes: β-Cells, Phenotypes, and Precision Medicine: Proceedings of an International Symposium of the Canadian Institutes of Health Research's Institute of Nutrition, Metabolism and Diabetes and the U.S. National Institutes of Health's National Institute of Diabetes and Digestive and Kidney Diseases.

One hundred years have passed since the discovery of insulin-an achievement that transformed diabetes from a fatal illness into a manageable chronic condition. The decades since that momentous achievement have brought ever more rapid innovation and advancement in diabetes research and clinical care. To celebrate the important work of the past century and help to chart a course for its continuation into the next, the Canadian Institutes of Health Research's Institute of Nutrition, Metabolism and Diabetes and the U.S. National Institutes of Health's National Institute of Diabetes and Digestive and Kidney Diseases recently held a joint international symposium, bringing together a cohort of researchers with diverse interests and backgrounds from both countries and beyond to discuss their collective quest to better understand the heterogeneity of diabetes and thus gain insights to inform new directions in diabetes treatment and prevention. This article summarizes the proceedings of that symposium, which spanned cutting-edge research into various aspects of islet biology, the heterogeneity of diabetic phenotypes, and the current state of and future prospects for precision medicine in diabetes.

Heterogeneity of Diabetes: β-Cells, Phenotypes, and Precision Medicine: Proceedings of an International Symposium of the Canadian Institutes of Health Research’s Institute of Nutrition, Metabolism and Diabetes and the U.S. National Institutes of Health’s National Institute of Diabetes and Digestive and Kidney Diseases

One hundred years have passed since the discovery of insulin—an achievement that transformed diabetes from a fatal illness into a manageable chronic condition. The decades since that momentous achievement have brought ever more rapid innovation and advancement in diabetes research and clinical care. To celebrate the important work of the past century and help to chart a course for its continuation into the next, the Canadian Institutes of Health Research’s Institute of Nutrition, Metabolism and Diabetes and the U.S. National Institutes of Health’s National Institute of Diabetes and Digestive and Kidney Diseases recently held a joint international symposium, bringing together a cohort of researchers with diverse interests and backgrounds from both countries and beyond to discuss their collective quest to better understand the heterogeneity of diabetes and thus gain insights to inform new directions in diabetes treatment and prevention. This article summarizes the proceedings of that symposium, which spanned cutting-edge research into various aspects of islet biology, the heterogeneity of diabetic phenotypes, and the current state of and future prospects for precision medicine in diabetes.

Predicting diabetes risk in diverse populations: what next?

Diabetes is a major health problem of the 21st century, affecting 463 million individuals globally. 1 International Diabetes FederationIDF Diabetes Atlas. 9th edition. https://www.diabetesatlas.org/en/resources/Date: 2019 Date accessed: September 12, 2021 Google Scholar Early identification of diabetes and therapy targeted to the individual can alter disease progression and reduce the risk of costly complications. The accuracy and utility of current prediction models that use clinical risk factors varies with age, race or ethnicity, and natural history of disease, including the characteristics and appearance of risk factors before disease onset. Incorporation of genetic risks, not affected by temporal changes, with clinical risk factors might improve outcomes and reveal the promise of precision medicine in diabetes.

Prediction, diagnosis, prevention and treatment: genetic-led care of patients with diabetes

Introduction Diabetes mellitus is a serious metabolic disorder that is associated with high morbidity and mortality, and that affects people worldwide – especially in Asia. Genetics plays an important role in disease development, prevention, and therapeutic approach. Precision medicine in diabetes requires a profound understanding of both genetics and the plethora of mechanisms of diabetes. Areas covered This review comprehensively describes and discusses the recent advances in genetics-based prediction, diagnosis, prevention, and treatment of diabetes, and the potential impact of these advances on precision medicine, especially in the Asian population. We analyzed the available literature from the PubMed Central® (PMC) archive. Expert opinion Advanced genetic knowledge can lead to the precise diagnosis, improved risk prediction, diabetes prevention, and genetics-based diabetes treatment. Increased understanding, availability, and affordability of genetics-based strategies will improve the quality of life of those with and those at risk for developing diabetes.

Towards precision medicine in diabetes? A critical review of glucotypes.

In response to a study previously published in PLOS Biology, this Formal Comment thoroughly examines the concept of 'glucotypes' with regard to its generalisability, interpretability and relationship to more traditional measures used to describe data from continuous glucose monitoring.