DeCure's autonomous Metabolic AI scientist is researching a drug-repurposing hypothesis for prediabetes syndrome — screening already-approved drugs against its 32-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease modulePrediabetes syndrome maps to a 32-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
approvedMetforminApproved drug
Structures already discussed alongside prediabetes syndrome in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
Crystal structure of human CYP3A4 — Metformin has a real, experimentally solved structure in complex with this target (PDB 5G5J, 2.6 Å). This is the drug's own deposited structure, not a prediction, and confirms it is a structurally characterised molecule rather than an untested guess.
Loading structure…
helix sheet mf8drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 5G5J · 2.6 Å · ligand Metformin (MF8). Experimental structure, not a prediction.
What the evidence adds up to
The earliest abstracts frame prediabetes as a poorly defined inherited state of impaired insulin response, with one 1977 paper explicitly arguing the term should be abandoned because it carries a risk probability no different from labels like prehypertension. A 1963 editorial on pregnancy and diabetes reviews the then-current concept of a prediabetic state as a dynamic resistance to a genetic diabetogenic influence, but offers no data on intervention. A 2024 review of youth-onset type 2 diabetes states that prediabetes is a phase where defects in β-cell function relative to insulin sensitivity emerge, and that youth-onset disease progresses more rapidly than adult-onset, with early vascular complications; it lists genetic, epigenetic, social, and environmental determinants but provides no trial results.
A 2013 cross-sectional study of 110 prediabetic patients and 76 controls found serum hs-CRP levels and carotid intima media thickness were statistically higher in the prediabetic group, with positive correlations between CIMT and fasting blood glucose, HbA1c, hs-CRP, and BMI. The authors conclude that early intervention in the prediabetic state is important for primary prevention of diabetes and cardiovascular disease, but this is an observational association, not a treatment outcome. A 2015 questionnaire study of 122 Indian doctors found that 100% of general practitioners, 97.9% of postgraduates, 91.3% of physicians, and 64.2% of specialists preferred diet and exercise as first-line management, with metformin the most commonly chosen oral agent (77.45%), followed by voglibose (20.6%) and sitagliptin (1.9%); no doctor chose an oral drug alone. A 2021 study of diabetic mothers with severe fetopathy identified serological protein changes, including a 7% depletion of DFP3 in central nervous system defects and elevated transthyretin, but this concerns diabetic pregnancy complications, not prediabetes treatment.
A 2022 manuscript describes prediabetes as a link between normoglycaemia and diabetes and argues it is often inadequately addressed in clinical practice, but it presents no efficacy data. Across all abstracts, there is no randomised trial, no survival or remission endpoint, and no evidence that any drug alters the course of prediabetes. What is missing is a prospective trial with hard clinical outcomes, a validated biomarker to stratify which prediabetic patients progress, and funding for long-term follow-up in youth-onset disease, where the decline in β-cell function is described as precipitous.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Diabetes · 1967 · 174 citations
“What Is Inherited – What Is Added” Hypothesis for the Pathogenesis of Diabetes Mellitus
AbstractA working hypothesis for the pathogenesis of diabetes mellitus has been drawn up which has found partial support in experimental data in human subjects. An impaired insulin response, common to all types of diabetes including prediabetes, has been brought to attention as a major possible inherited pathogenetic component. Other factors besides the impaired insulin production have been suggested as significant in the subsequent development of manifest diabetes.
Archives of Internal Medicine · 1977 · 46 citations
Genetic, Acquired, and Related Factors in the Etiology of Diabetes Mellitus
AbstractDiabetes mellitus is not a single disease entity, but a heterogenous group of disorders with a striking diversity of etiopathogenetic mechanisms as well as clinical manifestations. Lack of a known genetic marker for the disease(s) and variable influences of environmental factors on the expression of a putative diabetic genome have resulted in considerable debate over its etiology. Over the past few years, systematic epidemiologic studies, along with knowledge gained from a close association of certain human-leukocyte-antigens with the diabetic diathesis and possible role of host-immune factors, and gene-virus interaction have led to considerable advancement in the understanding of the disease-complex. Pending the availability of definite genetic marker(s), we propose a new, tentative classification based on the etiologic mechanisms. We also suggest that the term "prediabetes" be abandoned as a prospective entity, since as presently employed, this connotation carries a risk probability no different than the terms like prehypertension or precoronary thrombosis.
Pathophysiology and Treatment of Prediabetes and Type 2 Diabetes in Youth
AbstractYouth-onset type 2 diabetes is a heterogeneous disease with increasing prevalence in relation to increased rates of obesity in children. It has genetic, epigenetic, social, and environmental determinants. Youth-onset type 2 diabetes is alarming given a rapidly progressive course compared with the course of adult-onset disease, early-onset vascular complications, and long-term exposure to hyperglycemia and associated complications. It is often preceded by prediabetes, a disease phase where defects in β-cell function relative to insulin sensitivity emerge. Herein, we review the current understanding of the pathophysiology of prediabetes and type 2 diabetes in youth. We describe the mechanisms underlying insulin resistance, the precipitous decline of β-cell function, and the role of other hormonal abnormalities in the pathogenesis of the disease. We discuss the critical importance of social determinants of health in the predisposition and progression of these conditions and present current management strategies and the advances in therapeutic approaches. These must adapt to meet the unique needs of the individual patient and family. Significant knowledge gaps remain that need to be addressed in future research.
Pakistan Journal of Medical Sciences · 2013 · 13 citations · open access
Carotid artery intima media thickness and HsCRP: Predictors for atherosclerosis in prediabetic patients
AbstractOBJECTIVE: We aimed to assess carotid intima media thickness (CIMT) and serum high-sensitivity C-reactive protein (hs-CRP) levels as estimated markers of subclinical atherosclerosis and inflammation in prediabetic patients. METHODOLOGY: One hundred and ten patients were defined as prediabetic and seventy-six subjects (age and sex matched) were assigned as control group in our cross sectional study. Bilateral CIMT measurements and hs-CRP levels were evaluated. RESULTS: The prevalance of hypertension, hyperlipidemia, angiotensin receptor blockers and antihyperlipidemic medication use were statistically higher in the prediabetic group. Serum hs-CRP levels, left, right and maximum CIMT were statistically higher among prediabetics compared to control group. There was a positive, significant correlation between left, right, maximum CIMT and fasting blood glucose, HbA1c, hs-CRP levels and BMI. CONCLUSION: Recognising and focusing on the intervention of prediabetic state as early as possible and identifying the susceptible patients who may benefit from more aggressive preventive therapy is an important issue of primary prevention of diabetes and cardiovascular diseases.
Severe types of fetopathy are associated with changes in the serological proteome of diabetic mothers
AbstractABSTRACT: Pregestational or gestational diabetes are the main risk factors for diabetic fetopathy. There are no generalized signs of fetopathy before the late gestational age due to insufficient sensitivity of currently employed instrumental methods. In this cross-sectional observational study, we investigated several types of severe diabetic fetopathy (cardiomyopathy, central nervous system defects, and hepatomegaly) established in type 2 diabetic mothers during 30 to 35 gestational weeks and confirmed upon delivery. We examined peripheral blood plasma and determined a small proportion of proteins strongly associated with a specific type of fetopathy or anatomical malfunction. Most of the examined markers participate in critical processes at different stages of embryogenesis and regulate various phases of morphogenesis. Alterations in CDCL5 had a significant impact on mRNA splicing and DNA repair. Patients with central nervous system defects were characterized by the greatest depletion (ca. 7% of the basal level) of DFP3, a neurotrophic factor needed for the proper specialization of oligodendrocytes. Dysregulation of noncanonical wingless-related integration site signaling pathway (Wnt) signaling guided by pigment epithelium-derived factor (PEDF) and disheveled-associated activator of morphogenesis 2 (DAAM2) was also profound. In addition, deficiency in retinoic acid and thyroxine transport was exhibited by the dramatic increase of transthyretin (TTHY). The molecular interplay between the identified serological markers leads to pathologies in fetal development on the background of a diabetic condition. These warning serological markers can be quantitatively examined, and their profile may reflect different severe types of diabetic fetopathy, producing a beneficial effect on the current standard care for pregnant women and infants.
JOURNAL OF CLINICAL AND DIAGNOSTIC RESEARCH · 2015 · 5 citations · open access
Prediabetes Awareness and Practice Among Indian Doctors– A Cross-sectional Study
AbstractINTRODUCTION: Prediabetes is an intermediate state between diabetes and normoglycaemia, where the glucose levels are higher than normal but not significant to be diagnosed as diabetes mellitus. Guidelines from various associations suggest different types of management in this situation. OBJECTIVE: To assess knowledge and attitude of the doctors regarding prediabetes using questionnaire. MATERIALS AND METHODS: A cross-sectional questionnaire based study was conducted to assess the knowledge, attitude and practice among doctors regarding prediabetes treatment. One hundred twenty two (of 150) filled questionnaires were received from general practitioners, post graduates (PGs), physicians and super specialists in and around Kolar and Bangalore. Data was analysed using descriptive statistics and expressed as percentage. RESULTS: A total of 81.3% responded to the questionnaire, of which 14 were general practitioners (MBBS), 48 PGs in General Medicine, 46 physicians (MD General Medicine), and 14 super specialists (DM). Knowledge response was 85.7% (definition - 100%, prevalence - 50.8%, approved drug- 45.2%, progression- 86.2%). Screening for prediabetes was done by 71% of the general practitioners and physicians, but specialists would screen all. 100% general practitioners, 97.9% post graduates, 91.3% of physicians and 64.2 % specialist preferred diet and exercise and rest of them opted for oral antidiabetic drug (OAD) along with diet and exercise, but none of the doctors considered OAD alone for prediabetes. Among OADs metformin (77.45%) was the most preferred followed by voglibose (20.6%) and sitagliptin (1.9%). CONCLUSION: All doctors had awareness of prediabetes and most of them would regularly screen and treat prediabetes. Majority considered diet and exercise as first modality of treatment. The OAD opted commonly was metformin.
Journal of the Pakistan Medical Association · 2022 · 4 citations · open access
Prediabetes: A Pragmatic approach to counselling and coaching
AbstractPrediabetes is often considered as the link between normoglycaemia and diabetes. Though a lot of emphasis is given to an individual after the development of diabetes, pre-diabetes is often not adequately addressed in clinical practice. Given a distinct diagnostic criterion, its association with metabolic complications, an opportunity to prevent further progression to diabetes and the large number of people affected with it, makes it a subject of great importance and opportunity. In this brief manuscript we compare and contrast prediabetes with diabetes mellitus. We also describe a pragmatic approach to address a patient with prediabetes.
AbstractEditorials1 July 1963Pregnancy and DiabetesELSIE R. CARRINTON, M.D.ELSIE R. CARRINTON, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-59-1-120 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe combination of diabetes mellitus and pregnancy poses more controversial and provocative problems than almost any other problem appearing in gravid women. Although adverse effects of each upon the other are recognized clinically, these are poorly understood. The wide differences of opinion referable to practically every aspect of diabetic pregnancies illustrate the magnitude of the perplexities and the extensive fields for medical research.Current studies exploring various genetic aspects of diabetes offer new concepts and the promise of solving some of the mysteries now harassing internist, obstetrician, and pediatrican alike. Causes for the frequent first appearance of diabetes during the...References1. CONNFAJANS JWSS: The prediabetic state. A concept of dynamic resistance to a genetic diabetogenic influence. Amer. J. Med. 31: 839, 1961. CrossrefMedlineGoogle Scholar2. O'SULLIVAN JB: Gestational Diabetes. Unsuspected asymptomatic diabetes in pregnancy. New Eng. J. Med. 264: 1082, 1961. CrossrefMedlineGoogle Scholar3. FREINKELGOODNER NCJ: Carbohydrate metabolism in pregnancy. I. The metabolism of insulin by human placental tissue. J. Clin. Invest. 39: 116, 1960. CrossrefMedlineGoogle Scholar4. CARRINGTONMESSICK ERRR: Diabetogenic effects of pregnancy. A 10-year survey. Amer. J. Obstet. Gynec. 85: 669, 1963. CrossrefMedlineGoogle Scholar5. JACKSON WP: The cortisone glucose tolerance test with special reference to the prediction of diabetes. Diabetes 10: 33, 1961. CrossrefMedlineGoogle Scholar6. REMEIN QR: A current estimate of the prevalence of diabetes mellitus in the U. S. Ann. NY Acad. Sci. 82: 229, 1959. CrossrefMedlineGoogle Scholar7. HAGBARD L: Pregnancy and diabetes mellitus. Acta Obstet. Gynec. Scand. 35 (supp. 1): 1, 1956. MedlineGoogle Scholar8. GREENETOUCHSTONE JWJC: Urinary estriol as an Index of placental function. Amer. J. Obstet. Gynec. 85: 1, 1963. CrossrefMedlineGoogle Scholar9. VALLANCE-OWENLILLEY JM: Insulin antagonism in the plasma of obese diabetics and prediabetics. Lancet 1: 806, 1961. CrossrefMedlineGoogle Scholar10. LOWYBLANSHARDPHEAR CGD: Antagonism of insulin by albumin. Lancet 1: 802, 1961. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Department of Obsetrics and Gynecology Woman's Medical College of Pennsylvania Philadelphia 29, Pennsylvania PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByComparative validity of oral and intravenous glucose tolerance tests in pregnancy 1 July 1963Volume 59, Issue 1_Part_1Page: 120-124KeywordsDiabetes mellitusGeneticsGestational diabetesPregnancy Issue Published: 1 July 1963 PDF DownloadLoading ...
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works using Disease Ontology synonyms, resolved on OpenAlex.
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