DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Hyperglycemia — screening already-approved drugs against its 34-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleHyperglycemia maps to a 34-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
No approved-drug candidate for hyperglycemia is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
Molecular view
glucagon like peptide 1 receptor (GLP1R) — GLP1R is one of the genes genetically linked to this disease in Open Targets — shown as context, not as a drug target we're pursuing: no approved-drug candidate for this disease is yet corroborated in the literature we found.
Loading structure…
helix sheet 1sdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6X19 · 2.1 Å · ligand 3-{(1S)-1-[5-(2,2-dimethylmorpholin-4-yl)-2-{(4S)-2-(4-fluoro-3,5-dimethylphenyl)-3-[3-(4-fluoro-1-methyl-1H-indazol-5-yl)-2-oxo-2,3-dihydro-1H-imidazol-1-yl]-4-methyl-2,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridine-5-carbonyl}-1H-indol-1-yl]butyl}-1,2,4-oxadiazol-5(4H)-one (UK1). Experimental structure, not a prediction.
What the evidence adds up to
A 2007 review of hyperglycaemia in hospitalised patients states that hyperglycaemia increases mortality rate, risk of postoperative nosocomial infection, need for intensive care unit admission, length of hospital stay, and hospital charges. The same review notes that intensive therapy to correct hyperglycaemia in hospitalised patients reduces mortality and the risk of infections and other adverse outcomes. A 2018 review describes hyperglycaemia-induced pathology in the cardiovascular system and mentions molecular targeting of cardiovascular and diabetes mellitus therapies to treat hyperglycaemia, inflammation, thrombosis, dyslipidaemia, atherosclerosis, and hypertension.
A 2015 review identifies hyperglycaemia as a major risk factor for accelerating the development of multiple cardiovascular complications of diabetes, stating that even minor deviations from normal glucose levels can increase cardiovascular risk and that the proportion of patients affected increases substantially with worsening severity of dysglycaemia. The same review notes that most animal models require simultaneous exposure to hyperlipidemia and hyperglycaemia for lesion progression, but that severity is clearly accelerated during chronic hyperglycaemia. A 2019 review states that more than 140 million people worldwide suffer from diabetes, that hyperglycaemia in diabetes results from defects in insulin secretion, insulin action, or both, and that the pathophysiology of diabetes is not fully elucidated. It adds that the interrelationships between molecular and metabolic mechanisms contributing to the disease remain a mystery.
A 2016 review on risk reduction recommends that medications of proven efficacy on the primary condition that exhibit a low risk for dysglycaemia should be given preference, particularly in high-risk individuals, and that the first step is a thoughtful evaluation of indications for any prescription based on compelling evidence. No drug is named in any of these abstracts as a repurposed candidate for hyperglycaemia. The 2007 review documents benefits of intensive therapy but does not specify which agents or protocols were used.
What is missing is any clinical trial data testing a specific repurposed drug against hyperglycaemia in a controlled setting. The abstracts provide no patient stratification strategy, no sample sizes for any intervention, and no survival or response rates for any drug. Funding for such trials, a defined repurposing candidate, and a trial design that accounts for the complex interplay of insulin secretion, insulin resistance, and cardiovascular risk remain absent.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Pathophysiology of cardiovascular disease in diabetes mellitus
AbstractDiabetes mellitus elicits cellular, epigenetic, and post-translational changes that directly or indirectly affect the biology of the vasculature and other metabolic systems resulting in the apparition of cardiovascular disease. In this review, we provide a current perspective on the most recent discoveries in this field, with particular focus on hyperglycemia- induced pathology in the cardiovascular system. We also provide perspective on the clinical importance of molecular targeting of cardiovascular and diabetes mellitus therapies to treat hyperglycemia, inflammation, thrombosis, dyslipidemia, atherosclerosis, and hypertension.
ISRN Cardiology · 2012 · 36 citations · open access
Glycemic Control during Coronary Artery Bypass Graft Surgery
AbstractHyperglycemia, which occurs in the perioperative period during cardiac surgery, has been shown to be associated with increased morbidity and mortality. The management of perioperative hyperglycemia during coronary artery bypass graft surgery and all cardiac surgical procedures has been the focus of intensive study in recent years. This report will paper the pathophysiology responsible for the detrimental effects of perioperative hyperglycemia during cardiac surgery, show how continuous insulin infusions in the perioperative period have improved outcomes, and discuss the results of trials designed to determine what level of a glycemic control is necessary to achieve optimal clinical outcomes.
American Journal of Health-System Pharmacy · 2007 · 34 citations
Etiology and effect on outcomes of hyperglycemia in hospitalized patients
AbstractPURPOSE: The prevalence of diabetes in U.S. hospitals, etiology and pathophysiology of hyperglycemia in hospitalized patients, impact of hyperglycemia on patient outcomes, and benefits of hyperglycemia correction are described. SUMMARY: Diabetes mellitus is a common and costly condition with an increasing prevalence in the U.S. Hyperglycemia is common among hospital patients with and without diabetes. Possible causes of hyperglycemia include illness-related metabolic stress, parenteral nutrition, and pharmacotherapy. The deposition of advanced glycosylation end products, capillary basement membrane thickening, impaired immune function, oxidative stress, impaired lipid metabolism, prothrombotic changes, activation of protein kinase C-beta, vascular leakage, capillary non perfusion, and induction of vascular endothelial growth factor are among the harmful effects of hyperglycemia. In various types of patients and hospital settings, hyperglycemia increases the mortality rate, risk of postoperative nosocomial infection, need for intensive care unit admission, length of hospital stay, and hospital charges. The benefits of using intensive therapy to correct hyperglycemia in hospitalized patients in reducing mortality and the risk of infections and other adverse outcomes are well documented. CONCLUSION: Efforts are needed to manage hyperglycemia in hospitalized patients with and without diabetes to minimize the morbidity, mortality, and costs associated with hyperglycemia.
Journal of Current and Advance Medical Research · 2019 · 2 citations · open access
Genetics of Type 2 Diabetes: A Review
AbstractDiabetes Mellitus (DM), one of the most non-communicable diseases, is increasing day by day in an alarming way. More than 140 million people are suffering from diabetes throughout the world. It is not a single disease entity, but rather a group of metabolic disorders sharing the common underlying feature of hyperglycemia. Hyperglycemia in diabetes results from defects in insulin secretion, insulin action, or, most commonly, both. The chronic hyperglycemia and attendant metabolic deregulation may be associated with secondary damage in multiple organ systems, especially the kidneys, eyes, nerves, and blood vessels. The pathophysiology of diabetes is not fully elucidated. Insulin secretory dysfunction and insulin resistance or both is main candidate for this metabolic disorder, moreover various genetic and environmental factors may also involve in this process. Racial variations play also an important role as evidenced by various studies. However, the interrelationships between the molecular and metabolic mechanisms in these parameters contributing this life threatening disease still remain a mystery to the scientists. Journal of Current and Advance Medical Research 2019;6(1):59-63
AbstractHyperglycemia is a major risk factor for accelerating the rate of development of multiple cardiovascular complications of diabetes. The effect of hyperglycemia is strong enough that even minor deviations from normal glucose levels can lead to increased cardiovascular risk; however, the proportion of patients who are affected increases substantially with worsening severity of dysglycemia. The molecular mechanisms by which hyperglycemia leads to accelerated progression of atherosclerosis are complex. Vascular smooth muscle cells (VSMCs) also undergo several biochemical changes in response to hyperglycemia. Multiple molecular mechanisms converge to enhance lesion progression in the presence of hyperglycemia. While most animal models require simultaneous exposure to hyperlipidemia and hyperglycemia, the severity of lesion progression is clearly accelerated during exposure to chronic hyperglycemia. Further, the role of non-HDL cholesterol that is bound to lipoprotein particles other than LDL in accelerating atherosclerosis may be important.
American Diabetes Association eBooks · 2016 · 0 citations
12: General Approach to Risk Reduction
AbstractThe first step toward reduction of the risk of iatrogenic hyperglycemia is a thoughtful evaluation of the indications for any prescription, which should be based on compelling evidence. Whenever feasible, medications of proven efficacy on the primary condition that exhibit a low risk for dysglycemia should be given preference, particularly in high-risk individuals.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
DeCure is a research and publication project, not medical advice and not a treatment. "DeCure for X" describes a research goal, not a claim that a cure exists. Backing a cure is a contribution to fund the research — it is not an investment, and confers no yield, royalty, equity or IP ownership. Papers are published open-access by the DeCure.ai DAO.
