DeCure for Diabetes mellitus, transient neonatal, 2
DeCure's autonomous Metabolic AI scientist is researching a drug-repurposing hypothesis for diabetes mellitus, transient neonatal, 2 — screening already-approved drugs against its 2-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleDiabetes mellitus, transient neonatal, 2 maps to a 2-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
Structures already discussed alongside diabetes mellitus, transient neonatal, 2 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 AKR1C3 — Glimepiride has a real, experimentally solved structure in complex with this target (PDB 4YVX, 2.3 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 gmrdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4YVX · 2.3 Å · ligand Glimepiride (GMR). Experimental structure, not a prediction.
What the evidence adds up to
Neonatal diabetes mellitus is defined by hyperglycaemia within the first month of life requiring insulin, and is divided into transient and permanent forms. A 2007 overview states that diabetes developing before six months of age is rarely, if ever, caused by classic type 1 autoimmune processes. Over ten distinct genetic anomalies have been identified. Transient neonatal diabetes can be caused by defects in the normal methylation pattern of an imprinted gene on chromosome 6q24 and by mutations in the two genes encoding the beta-cell ATP-sensitive potassium channel. A genetic cause can be identified in over 90% of transient cases. About 30% of cases of permanent diabetes still have no identified genetic cause.
A 2001 case report describes a female infant with birth weight 1590 g treated with intravenous insulin from 48 hours, but achieving good glycaemic control was difficult and physical growth was poor. Continuous subcutaneous insulin infusion (CSII) was started at 86 days. Insulin requirement began to decrease after one year, and therapy was terminated at 14 months. At four years, intrinsic insulin secretion had improved, but post-meal hyperglycaemia sometimes occurred and glycosylated haemoglobin had risen to 6.0%. A 2005 report presents three cases, the first treated with conventional insulin and the latter two successfully treated with subcutaneous insulin pump therapy, and suggests guidelines for this approach.
A 2010 update notes that activating mutations in the two protein subunits of the ATP-sensitive potassium channel are responsible for about half of all cases of permanent neonatal diabetes and some cases of transient neonatal diabetes. Identification of these mutations allows patients treated with insulin to be transferred to sulfonylureas. Abnormalities of chromosome 6q24 remain the most common cause of transient neonatal diabetes. A 2016 Chinese report states that sulfonylureas can improve insulin secretion in most patients with transient neonatal diabetes mellitus and provide effective glycaemic control, and that genetic analysis helps select treatment and predict disease recurrence. A 2025 review notes that neonatal and syndromic diabetes often result in severe insulin deficiency or insulin resistance, and that many other organ systems are affected beyond diabetes.
What is still missing are large, prospective trials comparing insulin pump therapy versus sulfonylureas specifically in transient neonatal diabetes, standardised protocols for timing of genetic testing and treatment switching, and long-term follow-up data on neurological and metabolic outcomes beyond early childhood. The rarity of the condition makes recruitment and funding for such trials difficult, and patient stratification by precise genetic aetiology remains incomplete for the 30% of permanent cases without a known cause.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Journal of Paediatrics and Child Health · 2005 · 46 citations
Neonatal diabetes mellitus: Insulin pump as an alternative management strategy
AbstractNeonatal diabetes mellitus (hyperglycaemia within the first month of life, with an insulin requirement) may be transient or permanent. Management is complex, due to lack of subcutaneous fat and the need for small doses of insulin, and may be complicated by additional medical problems. Three cases are presented, the first of which was treated with conventional insulin therapy. The latter two were successfully treated with subcutaneous insulin pump therapy. We present suggested guidelines for treatment of neonatal diabetes, using this novel approach to management.
Current Opinion in Endocrinology Diabetes and Obesity · 2010 · 43 citations
Update in neonatal diabetes
AbstractPURPOSE OF REVIEW: Here we give context to new data on neonatal diabetes mellitus, a rare group of insulin-requiring monogenic forms of diabetes presenting at birth or shortly thereafter. Genetic studies are critical in the diagnosis and treatment of these patients. The most common causes of neonatal diabetes are activating mutations in the two protein subunits of the ATP-sensitive potassium channel. These are responsible for about half of all cases of permanent neonatal diabetes and some cases of transient neonatal diabetes. Identification of these mutations allows patients treated with insulin to be transferred to sulfonylureas, but associated conditions and other causes must be considered. RECENT FINDINGS: Recent data suggest that neonatal diabetes is more common than previously thought, with variable presentations. Continued studies provide further evidence for amelioration of developmental and neurological dysfunction exhibited by a significant proportion of patients. Abnormalities of chromosome 6q24 remain the most common cause of transient neonatal diabetes. Other causes of neonatal diabetes being studied include mutations in proinsulin, FOXP3 mutations in immunodysregulation, polyendocrinopathy, enteropathy, X-linked syndrome, homozygous glucokinase mutations, and Wolcott-Rallinson/EIF2AK3 diabetes. SUMMARY: We still have much to learn about the different forms of neonatal diabetes, their associated clinical features, and the optimization of therapy using a growing number of available therapeutic agents.
Hormone and Metabolic Research · 1996 · 32 citations
An Overview of the Safety and Tolerance of Glimepiride
AbstractThe objective of this paper is to obtain an overview of the safety and tolerance of glimepiride by presenting results from the clinical trials in patients with non-insulin-dependent diabetes mellitus that were conducted during the development of this new product. A total of 21 clinical studies with a minimum duration of two weeks were conducted during the clinical development of glimepiride in the United States and Europe. This included four placebo-controlled, four active-controlled (with glyburide and glipizide), and three noncomparative trials conducted in the United States and 10 European studies (eight active controlled and two non-comparative). All of the patients provided an extensive medial history which included information on concomitant medications, underlying diseases, and ongoing adverse events. During the clinical studies, the patients were monitored for treatment-emergent signs and symptoms (TESS), clinical laboratory abnormalities, discontinuations, deaths, and serious adverse events. Over 6,500 patients were included in the worldwide clinical trials with more than 4,200 of these patients treated with glimepiride; 1,500 of these patients were treated for at least 1 year. In controlled clinical trials in the United States, 2,013 subjects received glimepiride, 294 placebo, 322 glyburide, and 258 glipizide. In European studies, the duration of therapy ranged from 14 days to 2.8 years in the 1,489 patients who received glimepiride and the 1,247 control patients who were treated with either glyburide or gliclazide. In the japanese studies, a total of 983 patients were treated, 718 on glimepiride. In the US trials, similar types of adverse events were reported in subjects who received glimepiride, glyburide, or glipizide. The most commonly reported TESS were upper respiratory infection, headache, accidental injury, flu-like syndrome, and sinusitis. None of the TESS that were considered possibly or probably treatment related occurred in more than 2% of the patients. Those which occurred in ≥1% of glimepiride patients include dizziness, headache, asthenia, and nausea. The incidence of laboratory-confirmed hypoglycemia (blood glucose <60 mg/dl) ranged from 0.9% to 1.7% for glimepiride recipients in the US studies. Discontinuation from the study was most commonly a result of hyperglycemia in placebo recipients. Among the more than 6,500 patients in the clinical program, 52 deaths occurred, the majority of which were attributable to cardiovascular events. Glimepiride did not interact with any disease condition, concomitantly used medication, or concomitant disease in a medically meaningful manner. European data supported the findings of the US trials as did the Japanese data. A number of placebo-controlled, active-controlled, and non-comparative studies involving more than 6,500 patients (>4,200 patients treated with glimepiride) who were treated for up to three years have demonstrated that glimepiride has a superior safety profile. The incidence of laboratory confirmed hypoglycemia was consistently < 1.7%. The risk of cardiovascular events during treatment with glimepiride was equivalent to that seen with other sulfonylureas. No medically important interactions were found between glimepiride and any demographic variable, disease, or concomitant drug use. No pattern of laboratory abnormalities could be attributed to the use of glimepiride. The safety profile of glimepiride in controlled clinical trials was excellent and was as good as, or better than, that of the marketed sulfonylureas (glyburide, glipizide, and gliclazide) that were used as comparative agents in this clinical development program.
AbstractDiabetes developing within the first 6 months of life is rarely, if ever, caused by a classic type 1 diabetes-related autoimmune process. Currently, patients developing diabetes before 6 months of age are defined as having neonatal diabetes although this terminology possibly needs amending. Neonatal diabetes has a transient and permanent form and over 10 distinct genetic anomalies or mutations have been identified causing the disease. Transient neonatal diabetes can be caused by defects in the normal methylation pattern of an imprinted gene on chromosome 6 and by mutations in the 2 genes encoding the beta-cell ATP-sensitive potassium channel which is vital to normal glucose-stimulated insulin secretion. A genetic cause can be identified in over 90% of transient cases. Permanent neonatal diabetes can be caused by mutations in beta-cell transcription factors leading to abnormal pancreatic development often with other significant developmental anomalies, by defects in the glucose sensing, insulin secretory network and by accelerated Beta-cell destruction. About 30% of cases of permanent diabetes have yet to have a genetic cause identified.
Current Diabetes Reports · 2025 · 3 citations · open access
Neonatal and Syndromic Forms of Diabetes
AbstractPURPOSE OF REVIEW: Neonatal and syndromic diabetes are rare but important conditions. These conditions often result in severe insulin deficiency or insulin resistance. In this review, we aim to discuss the clinical characteristics and genetics of neonatal and syndromic forms of diabetes. RECENT FINDINGS: Beyond the development of diabetes mellitus, many other organ systems are affected. Understanding the pathophysiology of these conditions have improved our collective understanding of the genetics and developmental biology related to glucose metabolism and beyond. This review will provide new information for researchers and provide a helpful resource for clinicians when evaluating a patient for neonatal and syndromic forms of diabetes.
A Therapeutic Approach in A Patient with Neonatal Diabetes.
AbstractWe describe a case of neonatal diabetes mellitus treated with insulin. The patient was a female with a birth weight of 1590 g, which was small for her gestational age. Although intravenous insulin infusion was started at 48 hours after birth, it was difficult to achieve a good glycemic control, which resulted in poor physical growth in spite of insulin infusion. Continuous subcutaneous insulin infusion (CSII) was started at 86 days after birth. Insulin requirement began to decrease after she reached 1 year of age, and insulin therapy was terminated at 14 months of age. When a VSD patch closure operation was performed at 2 years of age, insulin treatment by CSII was needed for only 10 days. Intrinsic insulin secretion provoked by glucagon was poor at 4 months, but had improved to some extent at 4 years. The patient's physical and neurological development has been normal until now without any diabetic complications. Recently hyperglycemia sometimes has occurred after meals, and her glycosylated hemoglobin has risen to 6.0%. Neonatal diabetes is very rare and most cases are reported to be of a transient type. Careful follow up of the clinical course for a long time and appropriate treatment, including CSII, will be necessary for individual cases.
Approach to the patients with transient neonatal diabetes mellitus
AbstractTransient neonatal diabetes mellitus is a kind of rare special types of diabetes. It should be distinguished from type 1 diabetes. Genetic analysis can be used to define the subtype of neonatal diabetes mellitus, which helps us to select the most appropriate treatment and to predict the disease recurrence. Sulfonylureas is able to improve insulin secretion in most patients with transient neonatal diabetes mellitus and provide effective glycemic control. A case of transient neonatal diabetes mellitus is reported in order to call attention to the diagnosis and treatment of this disease. (Chin J Endocrinol Metab, 2016, 32: 510-513)
Key words:
Transient neonatal diabetes mellitus; Gene; Sulfonylureas
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.
