Metformin's disruption of gluconeogenesis in type 2 diabetes impairments of the cori and alanine cycles as hidden drivers of metabolic waste accumulation, NF-κBHIF-1α-mediated low-grade inflammation, and multisystem dysfunction

Abstract: Gluconeogenesis, a dual-purpose pathway in type 2 diabetes mellitus (T2DM), not only synthesizes glucose but also clears metabolic waste via the Cori cycle (lactate recycling through LDH, PC, PEPCK) and Alanine cycle (nitrogen disposal via ALT, GDH, urea cycle), preventing acidosis, ROS accumulation, and ammonia toxicity. Metformin, the cornerstone T2DM therapy, inhibits gluconeogenesis by targeting mitochondrial complex I, elevating AMP/ATP ratios, and activating AMPK-PKCι/λ signaling to repress CREB-CRTC2-driven PEPCK/G6Pase expression, disrupting these cycles. This leads to lactate, pyruvate, and ammonia buildup, triggering pro-inflammatory cascades: HIF-1α stabilization induces IL-6/VEGF, ROS from pyruvate excess activates NF-κB for TNF-α, and ammonia primes NLRP3 inflammasome for IL-1β/IL-18 release, fostering chronic inflammation. Multisystem consequences include musculoskeletal fatigue from ATP deficits, cognitive fog via neuroinflammation, atherosclerosis from endothelial dysfunction, hepatic fibrosis from urea cycle stress, and immune inflammaging impairing macrophage function. Clinical evidence reveals short-term anti-inflammatory benefits (reduced IL-6, CRP) via AMPK and microbiota effects, contrasted by long-term risks like lactic acidosis and neurodegeneration in renal-impaired or elderly patients. This review integrates physiological roles, molecular mechanisms, inflammatory pathways, systemic impacts, and clinical findings, highlighting metformin's dual-edged profile glycemic efficacy versus "inflammatory debt." Researchers are urged to explore precision interventions, such as antioxidants or biomarker-guided dosing, to optimize metformin's pleiotropic potential in T2DM and inflammaging-related disorders, redefining therapeutic paradigms.

Metformin
Humans
Diabetes Mellitus, Type 2
Inflammation
Gluconeogenesis
Hypoglycemic Agents
NF-kappa B
Animals
Alanine
Signal Transduction


Association of Functional Health Literacy Among Patients With Type-2 Diabetes in Bangladesh: A Cross-sectional Study

Abstract: Functional health literacy (FHL) plays a dynamic role in diabetes care, yet research on its implications is erratic in Bangladesh. The aim of this study was to ascertain the level of FHL among patients with type 2 diabetes (T2D) in Dhaka and its correlation with their glycemic level, lifestyle, sleep quality, and sociodemographic characteristics. A total of 401 patients with T2D were included by simple random sampling method in this cross-sectional study from three diabetes centers in Dhaka. A Bengali adaptation of the S-TOFHLA (Short Test of Functional Health Literacy) and a semi-structured questionnaire was used to collect data on FHL and other study information. Bivariate analysis, multi-nominal regression, Pearson's χ2 test, and Cramér's V coefficient was used to assess the correlations between variables, with a significance threshold of p < .05. Among the 401 participants, 59% were female and 34.9% lived in rural areas; among whom only 27.3% had adequate FHL. Sex, occupation, education, income, physical activity regularity, diabetes treatment regimen, family history, current fasting blood sugar (FBS), 3-month average FBS, 3-month average 2-hour after breakfast blood glucose, and hemoglobin A1c showed significant associations (p < .0001) with the level of FHL. Higher education level significantly increased the odds for adequate FHL (adjusted odds ratios (AOR) = 5.70 to 78.81). Adequate FHL was significantly associated with higher sleep metrics (AOR = 5.67 and 9.17). Longer sleep duration and higher quality sleep increased the likelihood of having adequate FHL (AOR = 9.17 and 5.67, respectively; p < .05) and higher glucose levels were linked to reduced FHL odds (AOR <1). Higher FHL was associated with better diabetes management. FHL interventions should be evaluated to determine if increasing a patient's health literacy will improve their diabetes management.

Islam MM
Hossain SB
Rahman KM
Sinthia MK
Chowdhury ABMA
Khan S

Humans
Female
Cross-Sectional Studies
Diabetes Mellitus, Type 2
Male
Bangladesh
Health Literacy
Middle Aged
Surveys and Questionnaires
Adult
Aged


Antiviral ribavirin binding to human serum albumin in diabetes and uraemia: A molecular docking study

Abstract: Human Serum Albumin (HSA) is abundant plasma protein in human blood. It plays a critical role in the transport and distribution of endogenous and exogenous compounds. Protein binding affects free fraction of a drug thus affecting pharmacokinetics and therapeutic efficacy. Glycation of HSA under diabetic conditions and the accumulation of uremic toxins in uraemia may alter drug-protein interactions. Therefore, the present study aimed to investigate the binding interactions of ribavirin and selected uremic toxins with binding interactions involving glycation-sensitive HSA residues using molecular docking analysis. Molecular docking results demonstrated that ribavirin bind to HSA with hydrogen bonding and hydrophobic interactions. Key glycation-prone residues, including ARG222, ARG218, and LYS195, were identified at the ribavirin binding site. Several of these residues were also involved in the binding of uremic toxins, indicating potential competition for ligand binding in diabetic and uremic conditions. The overlap of interaction sites suggests that glycation and toxin accumulation may influence the structural and biochemical properties of HSA, thereby affecting ribavirin binding affinity and distribution. In conclusion, this study highlights the important role of glycation-sensitive HSA residues in mediating ribavirin and uremic toxin interactions. These insights may support the future design and optimization of ribavirin-based therapeutics.

Cellular and molecular biology (Noisy-le-Grand, France)

Hydrophobic and Hydrophilic Interactions


Diabetic and ER-stressed pancreatic islet β cells are in need of some JNK removal

Abstract: Pancreatic β cells regulate glucose homeostasis through insulin secretion, but nutrient overload and genetic defects can trigger ER stress and apoptosis, contributing to type 2 diabetes. Within β cells, the kinases PERK, IRE1α, and ATF6 initiate the unfolded protein response (UPR) as a result of ER stress, a process that is constitutively suppressed under nonstress conditions by GRP78 binding to these proteins. To gain insight into the mechanisms of β cell death upon dysregulated ER stress, Sharma et al. used β cell-specific GRP78 knockout models, revealing that hyperactivation of the UPR promoted β cell death primarily through the IRE1α/JNK/p53 signaling pathway. Pharmacological inhibition of JNK improved β cell survival, increased insulin levels, and lowered blood glucose in multiple diabetic mouse models. These findings highlight JNK signaling as a promising therapeutic target for preserving β cell function.

Animals
Insulin-Secreting Cells
Endoplasmic Reticulum Chaperone BiP
Humans
Mice
Diabetes Mellitus, Type 2
Unfolded Protein Response
Protein Serine-Threonine Kinases
Endoplasmic Reticulum Stress
Heat-Shock Proteins
JNK Mitogen-Activated Protein Kinases
Apoptosis
Endoribonucleases
eIF-2 Kinase
MAP Kinase Signaling System
Activating Transcription Factor 6
Endoplasmic Reticulum
Signal Transduction
Mice, Knockout
Insulin


JNK and p53 cause human and mouse β cell death during excessive unfolded protein response

Abstract: Endoplasmic reticulum (ER) stress contributes to β cell death in both Type 1 and Type 2 diabetes (T1D and T2D). However, the molecular mechanisms driving β cell death during ER stress remain insufficiently defined, limiting development of protective therapies. GRP78, an ER chaperone, is the master regulator of unfolded protein response (UPR), suppressing UPR initiators during the unstressed state and releasing them to allow UPR activation during stress. To dissect the pathways leading to ER-stress response related β cell decompensation, we engineered mice genetically lacking GRP78 in pancreatic β cells. GRP78 deletion caused acute insulin-deficient diabetes in pups before weaning, with reduced β cell mass due to increased apoptosis. Molecular studies identified deregulated UPR, specifically IRE1 activity, as driving cell death. Unbiased and targeted analyses identified a JNK-p53 axis downstream of IRE1 kinase as a key mediator of β cell death during UPR activation. In vivo JNK inhibition protected against β cell death in 2 distinct ER stress diabetes models. In human β cells, pharmacological inhibition of both JNK and p53 improved β cell survival during GRP78 knockdown-induced UPR. These findings provide insight into mechanisms causing β cell death during ER stress and outline possible therapeutic targets to preserve insulin secretory capacity in diabetes.

Sharma RB
Darko C
Wang Y
Castro TA
Lama TD
Gablaski B
Rappa A
Redmond D
Kim JK
Lee AS
Alonso LC

Animals
Endoplasmic Reticulum Chaperone BiP
Unfolded Protein Response
Insulin-Secreting Cells
Humans
Tumor Suppressor Protein p53
Mice
Heat-Shock Proteins
Protein Serine-Threonine Kinases
Endoplasmic Reticulum Stress
Mice, Knockout
Endoribonucleases
Apoptosis
JNK Mitogen-Activated Protein Kinases
Diabetes Mellitus, Type 2
MAP Kinase Signaling System


Adverse Events Associated with Incretin-Based Therapies: A Narrative Review on Mechanisms, Clinical Management, and Risk Mitigation

Abstract: Incretin-based therapies, including glucagon-like peptide-1 receptor agonists (GLP-1RAs), are established therapies for obesity and type 2 diabetes mellitus, providing sustained weight reduction, improved glycaemic control, cardiovascular and renal benefits. Despite these established benefits, safety concerns remain an important clinical issue because adverse events may affect treatment persistence, patient acceptability, and clinical decision-making. This review evaluates a number of safety profiles of GLP-1RAs using clinical, mechanistic, and pharmacovigilance evidence, with attention to both common adverse events and emerging safety signals. A narrative review was conducted to evaluate the safety profile of GLP-1RAs in obesity and type 2 diabetes mellitus. PubMed/MEDLINE, Embase, and Web of Science were searched for studies published between January 2005 and April 2026. Evidence from randomised controlled trials, observational studies, meta-analyses, pharmacovigilance investigations, and regulatory safety reports was synthesised qualitatively. Findings from 60 studies and safety reports were included. Common adverse events were predominantly gastrointestinal, particularly nausea, vomiting, diarrhoea, and constipation, and represented the most consistently reported adverse effects and the principal cause of treatment discontinuation. Uncommon safety concerns included renal adverse events, which were reported infrequently and often occurred in clinical contexts involving gastrointestinal intolerance, volume depletion, or other predisposing factors. Gallbladder and biliary complications were also infrequent and appeared to be influenced by rapid weight loss and baseline patient risk factors. Acute pancreatitis remained rare in clinical trials, although severe cases have been reported in postmarketing settings. Human evidence did not demonstrate an increased risk of thyroid malignancy. Emerging safety signals, including early worsening of diabetic retinopathy, muscle mass reduction, psychiatric symptoms, and alopecia, were identified mainly through observational and pharmacovigilance evidence. GLP-1RA adverse events predominantly reflect predictable pharmacological and physiological effects rather than off-target toxicity. Safety profiles appear agent-specific, dose-dependent, and influenced by underlying mechanisms and patient characteristics. Risk-stratified prescribing should therefore align agent selection, dose escalation, and monitoring intensity with patient-specific vulnerabilities, particularly gastrointestinal tolerability, risk of renal dehydration, gallbladder history, retinopathy risk during rapid glycaemic improvement, and frailty or sarcopenia risk. Continued long-term surveillance and further evidence generation are needed to better define rare, delayed, and emerging safety signals and to optimise safe use across diverse clinical populations.

Glucagon-Like Peptide-1 Receptor Agonists


Imeglimin in Type 2 Diabetes Mellitus: Expert Opinions and Consensus in Indian Context

Abstract: Dear Editor, We read with interest the expert consensus by Seshadri et al. on imeglimin for the management of type 2 diabetes mellitus (T2DM). The article is timely and informative, particularly in view of the increasing complexity of diabetes management in India. The debate around the novel mechanism of imeglimin, which addresses both insulin resistance and mitochondrial dysfunction through mitochondrial routes, is well summarized and is in line with the increasing emphasis on preserving the function of the beta cell.1.

The Journal of the Association of Physicians of India

Duraiswamy J
Gawari NC
Naik T
Deshpande TA

Humans
Diabetes Mellitus, Type 2
India
Hypoglycemic Agents
Insulin Resistance
Consensus


Continuous Glucose Monitoring-Purposes, Benefits, and Problems: A Review of the Indian Scenario

Abstract: One of the global epicenters of the diabetes mellitus pandemic is India. Over the past 40 years, there has been a sharp rise in the prevalence of diabetes mellitus in India due to rapid socioeconomic development, demographic shifts, and increasing susceptibility in the Indian population. Diabetes affects 74.2 million individuals in India, which places a significant strain on the country's economy and healthcare system. A patient's diet, lifestyle, medication, and glucose monitoring must all be customized for optimal diabetes control. The rates of glucose monitoring in India are abysmal. Most of the monitoring methods currently in use are based on single-point-in-time readings, which may not be totally indicative of the state of diabetes control. This presents problems. With advancements in technology, the new monitoring tool-continuous glucose monitoring (CGM)-provides visibility into the glycemic profile 24 × 7 with user-friendly reports that provide information much beyond glycated hemoglobin (HbA1c) and self-monitoring of blood glucose. This device also detects the time spent in range by the individual with diabetes. This review article discusses CGM in terms of its purposes, technologies, accuracy, clinical indications, benefits, and problems associated with it.

Kushwaha A
Kodirekkala AN
Saharawat A
Jaiswal R

Humans
Continuous Glucose Monitoring
India
Blood Glucose Self-Monitoring
Diabetes Mellitus
Blood Glucose
Glycated Hemoglobin


From Clinic to Community: A Public Health Framework for Metabolic Dysfunction-associated Steatotic Liver Disease Prevention in India

Abstract: India is witnessing a rapid rise in metabolic dysfunction-associated steatotic liver disease (MASLD), driven by the country's expanding population with obesity, type 2 diabetes (T2D), and other metabolic comorbidities. Despite this growing burden, structured liver disease screening is absent from routine noncommunicable disease (NCD) services at the primary care level. A majority of MASLD diagnoses in India occur only after progression to advanced fibrosis or cirrhosis, even among individuals regularly engaged with healthcare systems for diabetes or hypertension. Primary health centers (PHCs) and community health centers (CHCs) currently lack standardized protocols for liver risk stratification, leading to critical missed opportunities for early intervention. This article outlines a scalable, systems-integrated model for community-based liver care, piloted at the All India Institute of Medical Sciences (AIIMS), Rishikesh. The model incorporates noninvasive fibrosis scoring tools (FIB-4, APRI), selective deployment of nurse-led FibroScan services, maternal hepatitis B virus screening, lifestyle modification strategies, and digital follow-up systems-seamlessly embedded within existing maternal health and NCD platforms. Insights: A real-world vignette from an urban diabetes outreach program in Kolkata illustrates the diagnostic gap: a high-risk patient remained undiagnosed for MASLD despite multiple healthcare encounters. International experiences, such as the Gwent model in Wales, further reinforce the feasibility of decentralized hepatology through community triage, nurse-led services, and simplified biochemical tools. India stands at a pivotal moment in redefining hepatology as a preventive, public health-oriented discipline. By embedding liver screening within existing NCD frameworks, leveraging task-sharing, and mobilizing digital infrastructure and public-private partnerships, India can develop a replicable model for early MASLD detection and intervention. This community hepatology framework-if scaled nationally-has the potential to position India as a global leader in MASLD prevention for low- and middle-income countries.

Humans
India
Fatty Liver
Public Health
Primary Health Care
Community Health Services
Diabetes Mellitus, Type 2
Non-alcoholic Fatty Liver Disease


Association of Hemoglobin-Albumin-Lymphocyte-Platelet Count (HALP) Score and Type 2 Diabetes Retinopathy

Abstract: Diabetic retinopathy (DR) represents a frequent microvascular consequence of type 2 diabetes mellitus (T2DM). Both inflammatory activity and nutritional status influence its development. The hemoglobin-albumin-lymphocyte-platelet (HALP) index is a composite marker that reflects these factors and has been explored in several diseases. This study assessed its association with the occurrence and severity of DR. We carried out a cross-sectional analysis of 150 individuals with T2DM (equal male-female distribution, mean age 58.9 ± 10.9 years). Retinal changes were graded through fundus examination. Laboratory values for calculating the HALP index were obtained. Statistical analysis included t-tests, Mann-Whitney U tests, and receiver operating characteristic (ROC) curves. DR was found in 43.4% of patients, predominantly in the moderate stage. The mean HALP index was 34.3 ± 36.6. Differences in HALP values between the DR and non-DR groups were not statistically significant (p = 0.249), although lower scores tended to appear in DR. ROC analysis showed modest discriminatory power (AUC 0.555 for DR; 0.599 for moderate-severe DR). Hemoglobin was significantly higher among those with moderate-severe DR (p = 0.006). Although the HALP index did not independently predict DR, its downward trend in advanced stages suggests potential as part of a multifactorial risk assessment. Owing to its affordability and simplicity, the HALP index may complement existing tools for identifying patients at higher risk of vision-threatening DR.

Kumar V
Gururaj K
Modi P
Kumar S
Balivada A
Raj A

Humans
Diabetic Retinopathy
Female
Male
Diabetes Mellitus, Type 2
Middle Aged
Cross-Sectional Studies
Platelet Count
Hemoglobins
Severity of Illness Index
ROC Curve
Aged
Lymphocyte Count
Biomarkers
Serum Albumin


The Darwinization of Diabetes

Abstract: Diabetes is a dynamic disease, an ever-evolving entity. In existence for centuries, the prevalence of diabetes has increased manifold over the past few decades.1 This evolution is associated with a change in classification, clinical features, comorbidities, complications, and clinical management strategies. These changes are what we describe as the Darwinization of diabetes. Charles Darwin was one of the most important scientists in human history. His research forms the basis of evolutionary biology. His hypothesis on natural selection, created along with Alfred Wallace, is accepted as the most important mechanism of evolution.2 A similar situation occurs with diabetes.

Kalra S
Vora A
Tiwaskar M
Raizada N
Verma M
Kapoor N

Humans
Diabetes Mellitus
History, 19th Century
Biological Evolution
Selection, Genetic
History, 20th Century


Index Presentation of Diabetes Mellitus as a Hyperkinetic Movement Disorder: A Thin-veiled Entity Colloquially called Diabetic Striatopathy

Abstract: Often referred to as the diabetes capital of the world, new-wave urbanization and westernization of lifestyle have rendered India vulnerable to the so-called lifestyle diseases, especially diabetes mellitus. Arguably the most characterized of diseases, diabetes somehow still has a few tricks up its sleeve. Diabetic striatopathy (DS), also known as hyperglycemic nonketotic hemichorea/hemiballism, chorea/hemichorea associated with nonketotic hyperglycemia, diabetic hemiballism/hemichorea, or chorea-hyperglycemia-basal ganglia syndrome, is a long-known disease of many names but sparse characterization. With an estimated prevalence of 1 in 100,000 (Ondo, 2011), DS is, in our opinion, greatly underestimated and is often misdiagnosed as intracerebral hemorrhage (ICH), which is a travesty given the excellent prognosis DS carries, even with just the control of blood sugar levels. Here, we describe the case of a 73-year-old male, previously undiagnosed diabetic, who presented with an acute-onset movement disorder, initially thought to have had a stroke, but was later diagnosed as DS. We also discuss in brief the pathophysiology and treatment options.

Agrawal BK
Singhal K
Sharma NK
Sharma AA

Humans
Male
Aged
Hyperkinesis
Diabetes Mellitus, Type 2
Diagnosis, Differential
Chorea
Diabetes Complications
Movement Disorders


Consensus Guidance for the Diagnosis and Management of Diabetic Kidney Disease: Executive Summary

Abstract: Diabetic kidney disease (DKD) is becoming an increasingly common consequence of diabetes in India, where the number of affected individuals is rising at an alarming pace. The illness is often silent in its early stages, and many patients are diagnosed only when kidney damage is advanced, leading to high rates of kidney failure and cardiovascular complications. This consensus document was developed by a broad group of experts to provide practical, evidence-based recommendations tailored for Indian healthcare settings. It stresses the importance of timely screening using the urine albumin-to-creatinine ratio and estimated glomerular filtration rate, along with routine evaluation of cardiovascular risks. The guidance covers key management areas such as blood pressure and glycemic control, the use of renin-angiotensin system blockers, newer agents such as sodium-glucose cotransporter 2 inhibitors (SGLT2) inhibitors and finerenone, as well as lifestyle and dietary measures. Equal attention is given to affordability, patient education, and integrating care into national health programs. By adapting international standards to local realities, this document aims to improve early detection, reduce inequalities in treatment, and support better long-term outcomes for people living with DKD in India.

Yadav K
Jha V
Abraham G
Almeida AF
Bansal S
Bansal SB
Bhowmik D
Ghosh S
Gopalakrishnan N
Gulati S
Joshi SR
Kalra S
Kesavadev J
Kher V
Khullar D
Mahajan AU
Mohan V
Oomman A
Parameswaran S
Phadke U
Ponde CK
Prakash SR
Prasad N
Raju SB
Ramachandran A
Sahay M
Sahay RK
Sawhney J
Sethi BK
Sethi DS
Shah P
Sharma RK
Singh S
Sreedhara R
Tiwaskar M
Wangnoo SK

Humans
Diabetic Nephropathies
India
Sodium-Glucose Transporter 2 Inhibitors


Expert Consensus and Physician Perspectives on a Low-dose Triple Fixed-dose Combination for Type 2 Diabetes in India

Abstract: Fixed-dose combinations (FDCs), particularly sulfonylurea-based triple therapies, play a central role in managing type 2 diabetes in India. With growing focus on safety and personalization, lower-dose alternatives are gaining attention, especially for early-stage and vulnerable patients. To obtain expert consensus from Indian physicians on the clinical relevance, preferred patient profiles, and prescribing intent for a low-dose triple FDC comprising glimepiride 0.5 mg, metformin 500 mg sustained-release (SR), and voglibose 0.2 mg. A structured cross-sectional survey was conducted among 112 physicians from metro and nonmetro regions of India. The survey used close- and open-ended questions to explore the need, clinical positioning, and use scenarios for this low-dose triple combination. Responses were analyzed and synthesized into expert consensus per the Oxford Centre for Evidence-Based Medicine (OCEBM) framework (Level V evidence). Most physicians (86.6%) supported the need for this combination. Common use cases included early-stage diabetes, elderly patients, and those with postprandial hyperglycemia or hypoglycemia risk. It was also preferred for step-up therapy and deintensification with agents, such as SGLT2 inhibitors or insulin (77.7%). Advantages cited included improved safety, simplified dosing, and affordability. Expert consensus affirms this FDC's clinical relevance across multiple diabetes stages. Further real-world evidence and outcome-driven studies are warranted to support broader clinical integration and guideline inclusion.

Kesavadev J
Unnikrishnan AG
Saboo B
George J
Kalra S
Sen SS
Gadia S
Anthuvan T

Humans
Diabetes Mellitus, Type 2
India
Hypoglycemic Agents
Sulfonylurea Compounds
Cross-Sectional Studies
Metformin
Drug Combinations
Consensus
Practice Patterns, Physicians'
Male


Beyond Time in Range: Targeting Glucose Oscillations to Transform Vascular Outcomes in Diabetes

Abstract: Time in range (TIR) is now widely adopted as a metric in diabetes management, offering a dynamic improvement over HbA1c alone. However, TIR does not capture the clinically relevant burden of glucose oscillations-rhythmic, intrarange fluctuations that independently drive oxidative stress, endothelial dysfunction, and inflammation, even when mean glucose remains well-controlled. We propose oscillatory burden as a measurable, actionable dimension of glycemic risk. This review synthesizes mechanistic and clinical evidence linking oscillations to vascular complications and outlines a conceptual oscillatory burden index (OBI) that combines amplitude and frequency metrics using continuous glucose monitoring (CGM) data. We reviewed studies published from 2002 to 2024 examining postprandial and intraday glucose dynamics, oxidative and inflammatory biomarkers, endothelial dysfunction, and real-world CGM applications. Intermittent glucose swings increase mitochondrial ROS generation, activate NF-κB, and impair nitric oxide availability-mechanisms confirmed by translational studies. Patients with comparable TIR (70-80%) but high oscillatory burden showed 2-3 times higher CRP and ICAM-1 levels compared to low-burden peers (p < 0.05). Practical strategies-precision meal timing, low-GI diets, gut microbiota modulation, and advanced CGM-driven insulin titration-can reduce oscillatory burden by up to 30%. Achieving TIR must not mask hidden glucose instability. Integrating oscillatory metrics into routine practice, supported by modern CGM analytics and patient-specific coaching, offers a new frontier for protecting vascular health in diabetes.

Humans
Continuous Glucose Monitoring
Blood Glucose
Oxidative Stress
Diabetes Mellitus
Diabetic Angiopathies
Postprandial Period


Diabetes Distress: Identifying Prevalence and Associated Factors in Type 2 Diabetes Mellitus Patients in Western India

Abstract: Type 2 diabetes mellitus (T2DM) poses a significant health burden globally, with India accounting for a large proportion of cases. Beyond physical complications, diabetes distress (DD)-the emotional and psychological strain associated with diabetes management-is increasingly recognized as a critical factor affecting patient outcomes. However, data on the prevalence and determinants of DD in Western India remain limited. A cross-sectional study was conducted among 158 adult T2DM patients attending an outpatient clinic in Vadodara, Gujarat. DD was assessed using the validated Diabetes Distress Scale-17 (DDS-17). Demographic, clinical, and psychosocial variables were collected and analyzed using descriptive statistics, Chi-squared tests, t-tests, and logistic regression to identify factors associated with DD. The prevalence of DD was 70.2%, with 31.6% experiencing moderate distress and 38.6% experiencing high distress. Emotional burden was the most prevalent distress domain, followed by regimen-related, interpersonal, and physician-related distress. Factors significantly associated with lower DD included higher education, good family support, regular physical activity, and diabetes duration over 10 years. Conversely, poor glycemic control, insulin therapy, hypoglycemic episodes, and the presence of diabetic complications were linked to higher DD. DD is highly prevalent among T2DM patients in Western India and is influenced by both clinical and psychosocial factors. Incorporating routine psychosocial screening and patient-centered interventions into diabetes care is essential to address this underrecognized burden and improve overall disease management.

Mitra S
Patel P
Muley A
Patel R
Kella M
Patel K

Humans
Diabetes Mellitus, Type 2
India
Female
Male
Cross-Sectional Studies
Prevalence
Middle Aged
Adult
Stress, Psychological
Aged
Risk Factors


Glucagon Agonist Therapies and Vision Loss: Balancing Promise with Prudence in India

Abstract: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual incretin therapies such as tirzepatide have transformed the management of type 2 diabetes mellitus and obesity, with expanding cardiometabolic indications and rapid market growth globally and in India. However, emerging postmarketing evidence has raised concerns regarding ocular safety. Pharmacovigilance analyses, cohort studies, and case reports suggest an association between GLP-1-based therapies and ophthalmic adverse events, including early worsening of diabetic retinopathy and, more concerningly, nonarteritic anterior ischemic optic neuropathy (NAION)-a potentially irreversible cause of sudden vision loss in adults over 50 years. Although the absolute risk appears very low, regulatory agencies, including the WHO and European Medicines Agency, now recognize NAION as a very rare adverse effect of semaglutide, and similar signals are being explored for other agents, suggesting a possible class effect. Proposed mechanisms include altered optic nerve head perfusion, sympathetic-mediated vasoconstriction, and rapid glycemic shifts affecting vascular autoregulation; however, causality remains unproven. In India, where over 100 million adults live with diabetes and obesity rates are rising, even rare adverse events may translate into substantial public health impact, particularly given limited access to ophthalmic care and increasing unsupervised drug use. We advocate a balanced approach: baseline ophthalmic evaluation in high-risk individuals, informed consent regarding visual symptoms, early referral for visual complaints, strengthened pharmacovigilance, and coordinated endocrinology-ophthalmology surveillance systems. As newer triple agonists approach clinical use, integrating ocular safety into prescribing frameworks is imperative. Metabolic gains must not come at the cost of preventable vision loss.


Type 2 Diabetes and Cognitive Dysfunction: Cardiorespiratory Fitness and Physical Activity Matters

Abstract: Diabetes is associated with an increased risk of cognitive dysfunction. We are aimed at examining cognitive performance in people with Type 2 diabetes mellitus (T2DM) and their correlation with physical activity (PA)/fitness level and mood. A cross-sectional study involving 47 individuals with T2DM, 30 diabetes-free individuals (controls): ages of 40-65 years and without dementia. Subjects were evaluated using a neuropsychological test battery that included Stroop, VLMT, CORSI, TMT and neuropsychiatric scales. The Global Physical Activity Questionnaire (GPAQ) was assessed. Physical fitness was evaluated using a maximal cardiopulmonary exercise testing (CPX). Compared with controls, people with T2DM had lower cardiorespiratory fitness (CRF) and more frequent cognitive performance below 1 SD of the normative value. Those individuals with T2DM, who displayed low fitness, showed significantly poorer cognitive inhibition (Stroop, p < 0.001), processing speed (TMT-A, p < 0.001), cognitive flexibility (TMT-B, p < 0.001), visuospatial memory (CORSI, p < 0.001) and memory consolidation (VLMT, p < 0.001). Higher ventilatory and metabolic CRF markers and higher PA levels correlated significantly with higher cognitive performance. None of the neuropsychological or psychiatric background variables correlated significantly with any of the cognitive scales. Individual CRF markers and PA levels correlated positively with cognitive performance in people with T2DM and in nondiabetic individuals. However, individuals with T2DM showed at least two to three times more frequent cognitive performances more than 1 SD below norm as compared with controls. Among people with T2DM, those with low aerobic fitness/PA levels showed significantly lower cognitive performance, especially in the attention-concentration, executive functioning, episodic memory and visuospatial processing domains.

Rojas Vega S
Solera-Herrera A
Vafa R
Acero-Moreno D
Wahrmann V
Scheef L

Humans
Diabetes Mellitus, Type 2
Cardiorespiratory Fitness
Middle Aged
Cross-Sectional Studies
Male
Female
Exercise
Neuropsychological Tests
Adult
Aged
Cognitive Dysfunction
Cognition
Exercise Test
Processing Speed


Bayesian Workflow for Minimal PBPK Models: Case Study of Dapagliflozin

Abstract: Numerous clinical trials (CTs) and population pharmacokinetic (PK) models have been published on dapagliflozin, an approved SGLT2 inhibitor used to treat type 2 diabetes, heart failure, and chronic kidney disease. This study proposes a Bayesian workflow for the development of minimal physiologically-based PK models (mPBPK) that integrates all available PK information, to support uncertainty quantification and informed drug development. First, a systematic collection of published dapagliflozin PK data and models was performed. A mPBPK model was then developed, and posterior parameter distributions were obtained based on data from parallel-design CTs. Three Bayesian modeling packages: NIMBLE (v1.1.0), MCSim (v6.2.0), and Torsten (v0.89.0), and three alternative prior specifications were evaluated. Model validation was performed using PK data from crossover CTs and urinary recovery data, followed by sensitivity analysis. 18 studies reporting PK data and 10 reporting PK models were identified. Posterior distributions were comparable across programs: 95% credible intervals overlapped. Torsten showed superior sampling efficiency, as compared to NIMBLE and MCSim (5.7 and 10.0 times higher in tails and central posterior regions, respectively); however, the average effective sample size per hour was comparable for Torsten and MCSim. The predicted urinary recovery was 2.2%-4.4% (mean 3.2%), while the observed values were in the 0.8%-4.0% range (mean 2.0%). Glomerular filtration rate and fraction unbound were the main contributors to inter-trial variability in urinary recovery, while volume of distribution and clearance had the highest influence on maximum concentration and area-under-the-concentration curve, respectively. The proposed Bayesian workflow is flexible and transferable to other mechanistic model types.

CPT: pharmacometrics & systems pharmacology

Mikhailova A
Peskov K
Helmlinger G
Sokolov V

Benzhydryl Compounds
Bayes Theorem
Glucosides
Humans
Models, Biological
Sodium-Glucose Transporter 2 Inhibitors
Workflow
Diabetes Mellitus, Type 2


[Distribution patterns and clinical characteristics of traditional Chinese medicine syndromes in diabetic peripheral neuropathy]

Abstract: Using multiple statistical methods, this study investigated the core diagnostic information from the four diagnostic methods, the distribution patterns of syndrome elements, and their relationship with laboratory biochemical indicators in diabetic peripheral neuropathy(DPN). The aim is to deepen the understanding of the disease-symptom-syndrome relationship in DPN. A retrospective study was conducted on 1 420 inpatients diagnosed with DPN patients at the Department of Endocrinology, the First Affiliated Hospital of Anhui University of Chinese Medicine, from June 2014 and June 2023. Data mining techniques, including frequency statistics, association rule analysis, factor analysis, cluster analysis, and Bayesian network analysis, were applied to examine general patient information, TCM diagnostic data from the four diagnostic methods, and laboratory biochemical indicators. The core clinical manifestations in DPN patients were dry mouth, limb numbness, blurred vision, fatigue, thirst, and a thready pulse. Association rule analysis indicated Yin deficiency leading to blood stasis is the core pathogenesis. Factor analysis indicated that the disease location primarily involved the spleen, kidney, and liver, while main disease nature elements were Yin deficiency, Qi deficiency, and blood stasis, often complicated by concomitant phlegm turbidity, Yang deficiency, and essence depletion. Cluster analysis identified five syndrome patterns: Yin deficiency with blood stasis syndrome, Qi deficiency with blood stasis syndrome, Yang deficiency with cold aggregation syndrome, phlegm stasis obstructing collateral syndrome, and liver-kidney deficiency syndrome. Among these, Yin deficiency with blood stasis syndrome and Qi deficiency with blood stasis syndrome were the most prevalent. Bayesian network analysis revealed associations between abnormal fasting blood glucose(FBG) and symptoms such as chest tightness, palpitations, dizziness, insomnia, and constipation. Abnormal glycosylated hemoglobin(HbA1c) was associated with frequent urination, polyphagia, polydipsia, thirst and dry mouth. Abnormal total cholesterol(TC) was linked to emaciation, fear of cold and cold limbs, and a weak pulse. Abnormal serum creatinine(SCr) was associated with slow reaction, a wiry pulse, and limb pain. The distribution of TCM syndromes in DPN primarily involves Yin deficiency with blood stasis syndrome and Qi deficiency with blood stasis syndrome. The core pathogenesis is Yin deficiency leading to blood stasis, with the disease location in the spleen, kidney, and liver. The identified associations between FBG, HbA1c, TC, SCr and specific TCM syndromes provide an objective basis for the microscopic syndrome differentiation of DPN and its integrated diagnosis and treatment combining Chinese and western medicine.

Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica

Li JJ
Liu JX
Guo JC
Jiang AJ
Fang ZH
Shen GM
Wen WB

Humans
Female
Diabetic Neuropathies
Male
Medicine, Chinese Traditional
Middle Aged
Retrospective Studies
Aged
Adult
Yin Deficiency
Diagnosis, Differential
Bayes Theorem
Cluster Analysis


[Roles of vascular smooth muscle cells phenotype transformation in mediating progression of diabetic macroangiopathy and current status of traditional Chinese medicine treatment]

Abstract: Diabetic macroangiopathy, a major chronic complication of diabetes, is characterized by atherosclerosis. Its pathological core involves the phenotype transformation of vascular smooth muscle cells(VSMCs) towards synthesis, aging, calcification, macrophage-like and fibroblast-like phenotypes. These phenotypic transformations jointly drive atherosclerotic plaque formation, vascular remodeling and calcification, leading to high-risk events such as myocardial infarction and stroke, which are important causes of disability and mortality in diabetic patients. Current conventional treatment provides insufficient long-term protection against macroangiopathy. In contrast, traditional Chinese medicine(TCM), through its holistic regulation via multi-component and multi-target mechanisms, has shown unique advantages in regulating VSMCs phenotype transformation. The progression of diabetic macroangiopathy mediated by VSMCs phenotypic transformation is characterized by deficiency in origin and excess in superficiality in TCM theory. Conceptualizing this phenotypic switching as "phlegm turbidity and blood stasis obstructing the collaterals", therapeutic strategies should focus on resolving phlegm and turbidity, transforming stasis and unblocking collaterals, while simultaneously reinforcing healthy Qi and tonifying deficiencies. A growing body of research indicates that monomers such as matrine, baicalein, and tanshinone Ⅱ_A, as well as sour Chinese herbal medicines and compound formulas such as Huoluo Xiaoling Dan, can inhibit pathological VSMCs phenotype transformations, including abnormal proliferation, migration, aging, and calcification. These interventions align with the pathogenesis and therapeutic principles, thereby delaying the progression of vascular lesions. This review briefly outlined the pathological progression of diabetic macroangiopathy, elaborated on how VSMCs phenotype transformation mediated diabetic macroangiopathy, and summarized key studies on the intervention of TCM active compounds, monomers and formulas in diabetic macroangiopathy by regulating VSMCs phenotype transformation. It aims to provide new strategies for the prevention and treatment of diabetic macroangiopathy and ultimately enhance clinical diagnosis and treatment.

Liu HY
Zhang ZH
Zhu YJ
Li XL
Wang XR
Yang C
Xie CG

Humans
Muscle, Smooth, Vascular
Animals
Drugs, Chinese Herbal
Phenotype
Diabetic Angiopathies
Medicine, Chinese Traditional
Myocytes, Smooth Muscle
Disease Progression


[Therapeutic effect and mechanism of Qingxin Lianzi Decoction in ameliorating diabetic kidney disease based on renal metabolomics]

Abstract: Renal metabolomics and molecular biology techniques were employed to investigate the interventional effect and underlying mechanism of Qingxin Lianzi Decoction(QXLZ) in rats with diabetic kidney disease(DKD). Sprague-Dawley rats were randomly assigned to the following groups: a blank group, a model group, a metformin(0.2 g·kg~(-1)) group, and QXLZ low-, medium-, and high-dose groups(10, 20, and 40 g·kg~(-1), respectively). The DKD model was established in all groups except the blank group by feeding with a high-fat diet combined with intraperitoneal injection of streptozotocin(STZ, 30 mg·kg~(-1)). After successful modeling, the rats received the corresponding treatments by oral gavage for six consecutive weeks. Upon completion of the intervention, random blood glucose levels were measured to assess the glucose-regulating capacity of QXLZ in DKD rats. Renal histopathological changes and fibrosis degree were evaluated by hematoxylin-eosin, Masson's trichrome, and periodic acid-Schiff staining. Renal function indicators(24-hour urinary total protein [24h-UTP], blood urea nitrogen [BUN], creatinine [Cr]) were measured by biochemical assays. The levels of blood glucose(glycated hemoglobin [GHb]), inflammatory markers(tumor necrosis factor-α [TNF-α], interleukin-1β [IL-1β]), and fibrosis markers(collagen type Ⅳ [Col Ⅳ], α-smooth muscle actin [α-SMA]) were detected by enzyme-linked immunosorbent assay. Immunofluorescence was used to determine the expression of TNF-α, IL-1β, α-SMA, and Col Ⅳ in renal tissues. Metabolomics was applied to identify differentially expressed metabolites in renal tissues. The results showed that compared with the blank group, the model group showed significant increases in several key indicators, including random blood glucose and GHb reflecting glucose metabolism, 24h-UTP, BUN, and Cr assessing renal function, as well as the inflammatory cytokines TNF-α and IL-1β and the fibrosis markers Col Ⅳ and α-SMA(P<0.05). The renal histology also exhibited typical features of DKD. Compared with the model group, all intervention groups showed significant reductions in these indicators, along with decreased collagen deposition and inflammatory resolution. Metabolomic analysis revealed that the intervention of QXLZ in DKD was closely associated with the arachidonic acid metabolism pathway. In conclusion, QXLZ effectively regulates blood glucose, improves renal function, and ameliorates renal inflammation and fibrotic injury in DKD rats, and its mechanism may be related to the arachidonic acid metabolic pathway.

Animals
Drugs, Chinese Herbal
Diabetic Nephropathies
Rats
Rats, Sprague-Dawley
Male
Kidney
Metabolomics
Humans
Tumor Necrosis Factor-alpha
Blood Glucose


[Study on mechanism of ultrafiltration membrane extract of Angelicae Sinensis Radix and Hedysari Radix regulates mitochondrial function to ameliorate diabetic kidney disease]

Abstract: This study aims to investigate the action mechanism and target molecules of the ultrafiltration membrane extract of Angelicae Sinensis Radix and Hedysari Radix in improving renal tissue injury in rats with diabetic kidney disease(DKD) from the perspective of mitochondrial function. Ten SPF-grade male Wistar rats were selected as the control group, while 40 rats were fed a high-fat and high-sugar diet for four weeks followed by a single intraperitoneal injection of streptozotocin(STZ) 35 mg·kg~(-1) to establish the DKD model. The successfully modeled rats were then randomly divided into four groups: the model group, the canagliflozin group, the Angelicae Sinensis Radix and Hedysari Radix aqueous decoction group, and the ultrafiltration membrane extract of Angelicae Sinensis Radix and Hedysari Radix group, with ten rats per group. All groups were administered via gavage for eight weeks. Renal function was assessed through 24 h urinary total protein(24-UTP) and biochemical parameters. HE staining, TUNEL staining, and transmission electron microscope were used to observe pathological morphological changes, apoptosis, and the status of intracellular organelles in cells. ELISA and Western blot were employed to measure adenosine triphosphate(ATP) content and the expression of mitochondrial function-related proteins, including optic atrophy 1(OPA1), mitofusin 2(Mfn2), dynamin-related protein 1(Drp1), ubiquitin-binding protein P62(P62), B-cell lymphoma/leukemia-2(Bcl-2), Bcl-2 interacting protein1(Beclin-1), and Bcl-2-associated X protein(Bax) in renal tissue. The results show that, compared to those in the control group, the rats in the model group exhibit a significant decrease in body weight(P<0.01), along with elevated levels of blood glucose, 24-UTP, blood urea nitrogen(BUN), and serum creatinine(Scr)(P<0.01). Renal tubular dilation, vacuolar changes in renal tissue cells, and a significant increase in apoptosis rate(P<0.01) are observed, accompanied by mitochondrial swelling, cristae disappearance, and rupture. ATP levels in renal tissue are significantly reduced(P<0.01), while the protein expressions of OPA1, Mfn2, Drp1, Beclin-1, and Bax are significantly increased(P<0.05, P<0.01). The expression levels of P62 and Bcl-2 are significantly decreased(P<0.01). Compared to those in the model group, the rats in the ultrafiltration membrane extract group show an upward trend in body weight, with reductions in 24-UTP, BUN, and Scr levels(P<0.01). Renal tubular dilation and glomerular cell vacuolation are alleviated, and the apoptosis rate of renal tissue cells is significantly reduced(P<0.01). Mitochondria exhibit mild swelling but remain largely intact. ATP levels in renal tissue are significantly increased(P<0.01), while the expressions of OPA1, Mfn2, Drp1, Beclin-1, and Bax are significantly decreased(P<0.01). The expression of Bcl-2 is significantly increased(P<0.01). In conclusion, ultrafiltration membrane extract of Angelicae Sinensis Radix and Hedysari Radix may attenuate renal tissue injury and delay disease progression in DKD rats by restoring mitochondrial dynamics, controlling mitochondrial fission-fusion balance, and improving mitochondrial function.

Animals
Male
Rats
Mitochondria
Diabetic Nephropathies
Drugs, Chinese Herbal
Rats, Wistar
Angelica sinensis
Ultrafiltration
Humans
Kidney
Apoptosis


[Unveiling efficacy targets and differentiated mechanisms of Colquhounia Root Tablets in "homotherapy for heteropathy" of rheumatoid arthritis and diabetic kidney disease: a analysis based on topological feature identification and path priority assessment]

Abstract: Based on a strategy integrating topological feature identification and path priority assessment, this study systematically explored the efficacy targets and differentiated mechanisms of Colquhounia Root Tablets(CRT) in the "homotherapy for heteropathy" of rheumatoid arthritis(RA) and diabetic kidney disease(DKD). Firstly, candidate targets of CRT and disease-specific genes were retrieved by integrating multi-source databases and transcriptomic data. Protein-protein interaction(PPI) networks were constructed to identify key targets shared by or specific to RA and DKD via topological feature identification. Subsequently, a path priority assessment was introduced to calculate the average shortest path(ASP) values from drug targets to various pathological segments, thereby quantifying intervention efficacy to lock onto "dominant pharmacodynamic links". The predicted key functional axes were validated through animal experiments. The results indicated that the core targets of CRT for both diseases involved shared pathways such as phosphatidylinositol 3-kinase(PI3K)-protein kinase B(Akt), tumor necrosis factor(TNF), and glycolysis/gluconeogenesis. Notably, path priority assessment revealed distinct dominant intervention links: for RA, CRT preferentially targeted "fibroblast-like synoviocyte(FLS) activation and invasion"(ASP=2.361), which mapped to the TNF-p38 mitogen-activated protein kinase(p38)-LIM domain kinase 1(LIMK1)-Cofilin1 axis to regulate cytoskeleton remodeling; for DKD, the dominant link was "filtration barrier injury and interstitial fibrosis"(ASP=2.295), converging on the TNF-poly(ADP-ribose) polymerase 1(PARP1)-signal transducer and activator of transcription 1(STAT1)-matrix metallopeptidase 9(MMP9) axis to mediate cellular senescence and senescence-associated secretory phenotype(SASP) secretion. Animal experiments confirmed that CRT significantly alleviated RA synovial invasion and DKD renal fibrosis by inhibiting these two differentiated signaling axes, respectively. By employing topological feature identification and path priority assessment, this study elucidates the scientific connotation of "homotherapy for heteropathy" of RA and DKD with CRT through both shared network regulation and intervention in disease-specific differential signaling axes associated with pharmacodynamic links.

Cai BB
Mao X
Ma ZC
Xu MZ
Lin Y
Lin N
Zhang YQ

Animals
Arthritis, Rheumatoid
Diabetic Nephropathies
Plant Roots
Drugs, Chinese Herbal
Humans
Protein Interaction Maps
Tablets


Glycemic control and its associated factors among children and adolescents with type 1 diabetes in Ethiopia: a narrative review

Abstract: Glycemic control is a critical component in the management of diabetes mellitus among children and adolescents. This narrative review synthesizes existing evidence on the status of glycemic control-both good and poor-and its associated factors among Ethiopian children and adolescents living with diabetes. The objective of the review was to assess the pattern of glycemic control and identify factors associated with both good and poor glycemic outcomes among children and adolescents with diabetes in Ethiopia. Relevant studies reporting on glycemic control and associated factors were identified through searches conducted in Google Scholar, PubMed/MEDLINE, African Journals Online, and the Ethiopian Medical Journal. Additional grey literature sources were also reviewed. Eligible studies were screened and narratively synthesized. The prevalence of poor glycemic control among Ethiopian children and adolescents ranged from 39.3% to 89.3%. Conversely, good glycemic control was reported in 16.4% to 60.7% of participants. Factors associated with glycemic control included socio-demographic characteristics, treatment-related variables, health system constraints, and dietary habits. Poor glycemic control is widespread among Ethiopian children and adolescents with diabetes, underscoring the urgent need for improved management strategies and targeted interventions. Strengthening diabetes education, promoting self-monitoring of blood glucose, and improving access to essential medical supplies and insulin may help enhance glycemic outcomes.

Humans
Ethiopia
Adolescent
Glycemic Control
Diabetes Mellitus, Type 1
Blood Glucose
Child
Hypoglycemic Agents
Insulin
Blood Glucose Self-Monitoring
Prevalence


Under-recognition of autoimmune polyendocrine syndromes in T1DM: results from an extended screening workup

Abstract: Type 1 diabetes mellitus (T1DM) is frequently associated with other autoimmune disorders, particularly autoimmune thyroid disease (AITD) and celiac disease. Guidelines recommend screening for thyroid and celiac disease in T1DM patients. Nevertheless, in case of their positivity, indicating the presence of an autoimmune polyendocrine syndrome (APS), there is a lack of guidance on how to proceed. Should we screen these patients for other autoimmune diseases? This study's aim was to evaluate the prevalence of additional autoimmune conditions in a cohort of T1DM patients with AITD and/or celiac disease. This cross-sectional study includes adult T1DM patients identified through electronic medical records. Patients with concomitant AITD or celiac disease were invited to undergo an extended screening workup for autoimmune disorders. 639 T1DM patients were identified, and 198 (31%) met the clinical criteria for APS (T1DM plus AITD and/or celiac disease), but only 17 (8.6%) had a formal APS diagnosis in their records. After the extended screening in 139/198 patients, 39% exhibited previously unknown autoantibody positivity, and 11.5% had new autoimmune diseases. Overall, among the patients who underwent the extended screening, 32% (44/139) were diagnosed with at least three autoimmune diseases. Our study shows that APS is often under-recognized and rarely formally documented in patients with T1DM. In addition, 32% of T1DM patients with AITD or celiac disease have at least a third autoimmune disease. These findings highlight that the identification of AITD or celiac disease in T1DM marks only one stage of the diagnostic journey. APS recognition should lead to a formal diagnosis and ensure heightened clinical vigilance with tailored evaluation of further autoimmune comorbidities during lifelong patient follow-up.

Velardi V
Sanson L
Toffoli B
Favaro F
Fischetti F
Fabris B
Candido R
Bernardi S

Humans
Polyendocrinopathies, Autoimmune
Female
Diabetes Mellitus, Type 1
Cross-Sectional Studies
Male
Adult
Celiac Disease
Middle Aged
Thyroiditis, Autoimmune
Mass Screening
Prevalence
Autoantibodies
Young Adult


Integrated UPLC-MS/MS profiling and network pharmacology-based analysis of the anti-hyperglycemic potential of Baihu Jia Renshen Decoction combined with Sanghuangporus vaninii extract in mice

Abstract: Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder requiring multi-target therapeutic strategies. Traditional Chinese medicine offers potential multi-component interventions, yet the material basis and molecular mechanisms of novel formulations often remain incompletely defined. This study developed an integrated formula (FSV) combining a modified Baihu Jia Renshen Decoction with Sanghuangporus vaninii extract and explored its anti-hyperglycemic potential using chemical profiling, network pharmacology, in vitro α-glucosidase inhibition, and an STZ/HSHFD-induced hyperglycemic mouse model. A total of 2,413 database-matched features were annotated, most of which should be regarded as putative rather than standard-confirmed identifications. Mangiferin and several flavonoids were retained as plant/fungus-compatible candidate constituents, whereas implausible xenobiotic matches were excluded from biological interpretation. Network pharmacology predicted the involvement of inflammation- and insulin-resistance-related targets, including TNF, AKT1, IL6, NFKB1, and MAPK3 (also known as ERK1), whereas ALB was treated as a high-connectivity carrier protein rather than a direct druggable mediator. FSV inhibited α-glucosidase in vitro and was associated with improvements in hyperglycemia, insulin-sensitivity indices, dyslipidemia, and tissue morphology in the mouse model. These phenotypic findings are presented as experimental support accompanying the pathway predictions, while direct pathway validation is left for future mechanistic studies. Overall, the results provide a preliminary basis for further chemical validation and mechanistic investigation of FSV in diabetes-related metabolic dysfunction.

Zhang J
Chen Y
Lin Y
Huang Z
Ge X
Liu B
Huang Z

Animals
Mice
Network Pharmacology
Drugs, Chinese Herbal
Hypoglycemic Agents
Tandem Mass Spectrometry
Male
Chromatography, High Pressure Liquid
Diabetes Mellitus, Experimental
Plant Extracts
Blood Glucose
Glycoside Hydrolase Inhibitors
alpha-Glucosidases


Using Linked Administrative Health Data to Examine Maternal Preconception Diabetes and Hypertension and Child Growth in Ontario, Canada: A Longitudinal Cohort Study

Abstract: Research on whether maternal diabetes and hypertension prior to conception influence their children's health is limited. In Ontario, Canada, ICES is an independent research institute that securely houses population-based administrative health data, including diagnostic information, for individuals covered under the province's universal health insurance program. To determine whether maternal preconception diabetes and hypertension were associated with child age- and sex- standardized body mass index (zBMI). This longitudinal cohort study included children 0 to 12 years enrolled in the TARGet Kids! primary care practice-based cohort (www.targetkids.ca) in Ontario, Canada (2008-2021). Maternal diagnoses of diabetes and hypertension prior to conception were identified through provincial administrative datasets held at ICES, deterministically linked to TARGet Kids! data using individual health insurance numbers. Child zBMI was derived from directly measured height and weight and electronic medical records. Linear mixed effects models were used to assess associations adjusting for confounders. Among 7,351 mothers (mean age at delivery 33 years), 308 (4.6%) had preconception diabetes (2.1%) or hypertension (2.9%). Children (n = 9,087; mean age 4.6 years; 48.4%female) contributed to 28,861 zBMI measures. Maternal preconception hypertension was associated with higher mean child zBMI. The adjusted estimated difference for children of mothers with preconception hypertension with the average duration of hypertension prior to conception was 0.29 units higher in zBMI (95%CI: 0.03;0.55) compared with children of mothers without hypertension. The association between preconception hypertension and higher child zBMI may indicate a potential maternal health target for the prevention of child overweight and obesity.

International journal of population data science

Li X
Chomka L
Keown-Stoneman C
Allen C
Anderson L
Ara Begum E
D'Annunzio D
Thadani S
Maguire J
Birken C

Humans
Female
Longitudinal Studies
Ontario
Child
Hypertension
Child, Preschool
Pregnancy
Body Mass Index
Adult
Infant
Child Development
Male
Infant, Newborn
Diabetes Mellitus
Pregnancy in Diabetics


New-onset diabetes following SARS-CoV-2 Omicron infection: a matched cohort study

Abstract: Understanding the longer-term health impacts of SARS-CoV-2 infection is essential for informing public health policy. While earlier studies suggested increased diabetes risk after infection, evidence for the Omicron period and the modifying effect of vaccination remains limited and inconsistent. A matched cohort study was conducted using a large-scale linked asset covering over 90% of the Australian population, integrating COVID-19 notifications with demographic information and administrative health records. Individuals aged ≥16 years diagnosed with COVID-19 between 15 December 2021 and 31 December 2022 were matched 1:1 to those without COVID-19 by age, sex, and COVID-19 vaccine recency. Cox-models were used to estimate the association between COVID-19 and initiation of diabetes treatment, adjusting for relevant demographic and health-related factors. Negative control outcomes were assessed. Among 5,736,501 matched pairs followed for a median of 200 days, 45,816 initiated diabetes treatment. Compared to those without COVID-19, individuals with COVID-19 had a 14% higher risk of subsequently initiating diabetes treatment (aHR 1.14 [95%CI 1.12; 1.17]), with the highest risk observed among those hospitalised due to COVID-19 (aHR 2.52 [95%CI 2.23; 2.84]). The risk was also higher for individuals with ≤2 COVID-19 vaccine doses compared to those boosted within the last 90 days (aHR of 1.22 [95%CI 1.18; 1.25] vs 1.08 [95%CI 1.04; 1.12]). We found an increased risk of diabetes following SARS-CoV-2 infection during the Omicron dominant period and a protective effect of COVID-19 vaccination. However, the findings should be interpreted with caution considering the potential for unmeasured confounding.

Qian J
Stepien S
Cheng A
Newall A
Wood J
Rowe S
Thompson K
O'Donnell B
Dore G
Macartney K

Humans
COVID-19
Female
Adult
Diabetes Mellitus
Cohort Studies
Male
Australia
Middle Aged
Aged
SARS-CoV-2
Risk Factors
Adolescent
Young Adult
COVID-19 Vaccines
Proportional Hazards Models


Temporal Signals of Disease: A Transformer Approach for Predicting Diabetes from Longitudinal EHRs

Abstract: To develop and evaluate a Transformer-based temporal representation learning framework for predicting incident diabetes using longitudinal laboratory data, and to compare its performance with state-of-the-art pretrained models and traditional machine-learning baselines. We deterministically linked a cardiac registry cohort (2015-2019) in Alberta, Canada, and retrieved three years of laboratory tests preceding each patient's diabetes diagnosis. Each laboratory event was modelled as a triplet consisting of test type, test value, and time gap with the previous test, to preserve temporal structure. Our Transformer architecture learned contextual embeddings that capture both intra-test dynamics and inter-test interactions, indicating the onset of diabetes. Performance was benchmarked against two pretrained Transformer models (Moment, PatchTST) and an XGBoost baseline trained on aggregated test summaries (mean, standard deviation, minimum, maximum). The final cohort included 30,462 patients and 19 laboratory test types relevant to diabetes. The proposed method achieved the highest predictive accuracy (AUC = 0.92), outperforming Moment (0.80), PatchTST (0.74), and XGBoost (0.88). It also demonstrated superior sensitivity (0.70) and positive predictive value (0.777) while maintaining high specificity (0.938) and negative predictive value (0.911). Conclusion: Modelling raw laboratory trajectories with a dedicated temporal Transformer substantially improves diabetes prediction compared with both pretrained sequence models and aggregation-based baselines. This framework provides a generalizable pathway for leveraging routine laboratory data in early disease detection. It highlights the clinical value of sequence-level modelling and supports the integration of temporal representation learning into population-level surveillance and decision-support systems.

Pan J
Lee S
Virani A
Riazi K
Martin E
Leung A
Quan H
Li N

Humans
Diabetes Mellitus
Electronic Health Records
Longitudinal Studies
Predictive Learning Models
Alberta
Boosting Machine Learning Algorithms
Registries
Prediction Algorithms


Exposure to diabetes and own diabetes status using a whole population network of the Netherlands

Abstract: Diabetes is one of the most common chronic diseases in the Netherlands: approximately 1.2 million people have diabetes, of which 1.1 million have type 2 diabetes. Type 2 diabetes is strongly related to lifestyle factors (e.g. unhealthy eating habits, being overweight and smoking), but also to ageing and it has a genetic component. An individual's social environment may influence their lifestyle (choices), and subsequently their chance of having diabetes. This study examines the relationship between an individual's social environment and diabetes with administrative data from the Person Network of Statistics Netherlands. The Person Network includes five types of relationships (so-called network layers) of each inhabitant of the Netherlands in 2022: household members, (extended) family members, colleagues, neighbours and classmates. Individuals' diabetes status was based on whether they were prescribed diabetes medication in 2022. An "exposure score" was calculated for each individual indicating to what extent diabetes was present in their (local) network. The exposure score was decomposed to assess the distinct contribution of each network layer to the overall score. The population was limited to individuals aged 40+ years as the prevalence of type 2 diabetes increases rapidly after age 40. Exposure to diabetes was higher for individuals with diabetes than those without. Both before and after adjusting for individual background factors (e.g. age, gender, origin, income, social economic category, household composition, urbanity of the neighbourhood), individuals who had relatively more network members with diabetes were more likely to have diabetes themselves than those with fewer network members with diabetes.

van Hedel K
de Jonge E
van der Laan J
Das M

Humans
Netherlands
Diabetes Mellitus, Type 2
Female
Middle Aged
Adult
Male
Life Style
Aged
Social Environment
Socioeconomic Factors


Dermatological lesions in diabetes

Abstract: Diabetes is a chronic metabolic disease characterised by high glucose levels and altered carbohydrate and lipid metabolism, affecting an increasing number of people worldwide. Spain ranks fifth among European countries with the highest incidence of diabetes. Hyperglycaemia causes damage to numerous cell types, including keratinocytes and fibroblasts in the skin. Dermatological manifestations appear in more than 30% of cases of diabetes at the onset of the disease and in up to 100% during the course of the disease. This makes skin examination of patients particularly important, as early treatment of diabetes can slow the progression of the disease and improve its prognosis. In addition, some dermatological changes may alert us to suboptimal metabolic control of previously known diabetes. Some lesions are associated with insulin resistance, others are due to fungal or bacterial infections, there are also alterations due to diabetes itself or to chronic complications of diabetes; finally, there are lesions due to pharmacological treatment of the disease and to devices such as insulin infusion pumps and sensors for interstitial glucose measurement. Knowing and recognising dermatological changes is therefore essential in our daily work, because they guide us towards a better management of the disease and its causes.

Revista espanola de sanidad penitenciaria

Casado-Hoces SV
González-Tejedor D
Martín-Velasco R

Humans
Diabetes Complications
Skin Diseases
Diabetes Mellitus
Insulin Resistance


Immune checkpoint inhibitor-induced diabetes mellitus in metastatic NSCLC: a case report with extended follow-up and management considerations

Abstract: Immune checkpoint inhibitors-induced diabetes mellitus (ICI-DM) is a rare but potentially life-threatening endocrine immune-related adverse event, often characterized by abrupt onset of insulin deficiency and frequent presentation with diabetic ketoacidosis and difficulty with daily management with the available therapies. Lung cancer patients represent a substantial proportion of reported cases, reflecting the widespread use of PD-1/PD-L1 inhibitors in thoracic oncology. We report on the case of an elderly patient with metastatic lung adenocarcinoma treated with pembrolizumab who developed severe DM requiring permanent insulin therapy and leading to treatment discontinuation. The patient was subsequently followed over a prolonged period, during which oncological disease remained under sustained control despite immunotherapy interruption. We describe the clinical course, diagnostic workup, and multidisciplinary management, and review current guideline recommendations addressing acute metabolic management, diabetic treatment, and decision-making regarding continuation of immunotherapy. This case highlights the complexity of managing ICI-DM in real-world clinical practice. The current guidelines may help in broad terms. Although guidelines have been published, they remain cursory. Nevertheless, therapeutic decisions should ultimately be individualized through close multidisciplinary collaboration.

Nova D
Pagliari GG
Mambrito S
Cortinovis DL
Canova S

Humans
Immune Checkpoint Inhibitors
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Antibodies, Monoclonal, Humanized
Diabetes Mellitus
Male
Insulin
Neoplasm Metastasis
Aged


Improving Pain Literacy Among Future Educators: Contemporary Pain Neuroscience Education in Teacher Preparation

Abstract: Persistent pain affects approximately one in five children and adolescents globally and is associated with school absenteeism, reduced academic engagement, psychosocial distress, and long-term health consequences. Schools are important settings for developing health beliefs and self-management behaviors, yet educators receive little formal preparation about pain. This Practitioner's Perspective describes integration of a brief contemporary pain neuroscience education (CPNE) module into an undergraduate teacher preparation course. Two interactive sessions delivered by a physical therapist introduced pain as a protective nervous system output influenced by biological, psychological, and social factors. Participants demonstrated improved pain knowledge and beliefs, increased confidence discussing pain-related concepts, and greater appreciation for the relevance of pain literacy to educational practice. Pain literacy may improve educator responses to student pain, reduce stigma, support appropriate participation, and promote equitable school environments. Physical therapists may be well positioned to collaborate with teachers, school nurses, counselors, coaches, and other school-based professionals. Teacher preparation programs may represent an upstream opportunity to improve pain literacy, support student health and learning, and contribute to the prevention of persistent pain.

Curfman SE
Best WJ
Harrison DA
Austin GP
Finch DC

Humans
Neurosciences
Health Literacy
School Teachers
Health Knowledge, Attitudes, Practice
Teacher Training
Chronic Pain
Pain Management
Curriculum
School Health Services


From trade-offs to translation: An interdisciplinary roadmap for neurotechnology

Abstract: Neurotechnologies are transforming how we measure, interpret, and modulate brain-body interactions, integrating real-time sensing, computation, and stimulation to enable precise physiological control. They hold transformative potential across clinical and nonclinical domains, from treating disorders to enhancing cognition and performance. Realizing this potential requires navigating complex, interdisciplinary challenges spanning neuroscience, materials science, engineering, signal processing, and regulatory and ethical frameworks. This Perspective presents a strategic roadmap for neurotechnology development, created by early-career researchers at the intersection of disciplines. We identify five cross-cutting trade-offs that shape the development and translation of neurotechnology: material functionality versus long-term stability, innovative development versus scalable manufacturing, spatiotemporal resolution versus real-time capability, multiscale multimodal integration versus system adaptability, and technological complexity versus clinical or commercial translatability. Rather than a domain-specific review, we focus on shared challenges and strategic opportunities that transcend disciplines, propose a unified framework for collaborative innovation and education, highlight ethical and regulatory priorities, and outline a timeline for overcoming key bottlenecks.

Serrano RR
Troughton JG
Mirkhani N
Martínez N
Mariello M
Tsigarides J
Williamson S
Sapriza J
Susnoschi Luca I
Dominguez-Alfaro A
Cuttaz E
Thompson N
Swedick S
Almulla L
Güemes A

Humans
Neurosciences
Translational Research, Biomedical


Transitions in development - an interview with Helen Willsey

Abstract: Helen Willsey is an Associate Professor at the Weill Institute for Neuroscience at the University of California, San Francisco (UCSF), USA. Helen's group uses frog models to dissect how risk genes contribute to psychiatric disorders. We spoke to Helen to learn more about her career trajectory, the importance of mentorship and the value of maintaining a full life both in and out of the lab.

Animals
History, 21st Century
History, 20th Century
Humans
Neurosciences
Developmental Biology
Mentors


Cancer neuroscience: Mechanisms to medicine

Abstract: The nervous system is now recognized as an enabling hallmark of cancer biology. Neural inputs drive tumor growth in both central nervous system tumors and extracranial tumors through different mechanisms, including synaptic signaling, adrenergic regulation, perineural invasion, neuropeptides, immune remodeling, and bioelectric mechanisms. These insights have facilitated repurposing of neuroactive agents that are now in clinical trials as adjuncts to standard cancer therapy. The central translational challenge now is how to match the right neural circuit to the right patient and to pair appropriate neuromodulators with immunotherapy in combinations designed to restore, rather than merely supplement, antitumor immunity.

Pasvolsky L
Jones GH
Vu Y
Winkler F
Amit M


The neuroscience of childhood brain cancers

Abstract: Nervous system activity drives both normal neurodevelopment and childhood brain cancers through paracrine and synaptic signaling. In childhood gliomas, cancer cells integrate structurally and electrically into neural networks, and neuron-cancer interactions are strongly growth-promoting. Understanding the neuroscience mechanisms regulating childhood brain cancers opens a previously unexplored avenue for much-needed therapeutic interventions.

Humans
Brain Neoplasms
Neurosciences
Child
Animals
Neurodevelopment
Glioma
Neurons


Comparative Neuroanatomy of Hydrothermal Vent Shrimps: Ecological Differentiation Among Four Alvinocaridid Species

Abstract: Alvinocaridid shrimps colonize hydrothermal vent fields along the Mid-Atlantic Ridge (MAR), where they experience extreme environmental conditions including high hydrostatic pressure, steep thermal and chemical gradients, and dim light. While various aspects of the biology of the dominant vent shrimp Rimicaris exoculata, such as general anatomy, microhabitat, symbiotic relationships, or trophic networks, have been extensively studied, little is known about how brain organization varies among alvinocaridid species occupying different ecological niches. Here, we investigated whether vent shrimps share common neuroanatomical features and whether differences in brain and vascular organization reflect ecological diversification among species. Using histology, immunohistochemistry, µCT scans, and 3D reconstruction, we compared the brain and the neurovascular system (cor frontale) in four MAR species with distinct ecologies (R. exoculata, Rimicaris chacei, Mirocaris fortunata, Alvinocaris markensis) and in the coastal relative Palaemon elegans. Our results reveal strong commonalities in brain organization among vent shrimps. All MAR species display a compact brain architecture with hypertrophied mushroom bodies (MBs), suggesting enhanced multisensory integration and memory capacities. Corresponding to the low-light environment, the visual neuropils (lamina, medulla, lobula) are smaller than those of the coastal species P. elegans. In all species living near hydrothermal vents, the retina exhibits modifications; it extends along the dorsal part of the cephalothorax, and its length varies according to the species, being the longest in the genus Rimicaris. The lobula satellite neuropil is absent in all alvinocaridids, suggesting a limited capacity to track moving visual signals. The olfactory lobes exhibit a common glomerular organization but differ among species in quantitative parameters, such as volume and number of glomeruli. The neurovascular system shows marked interspecific variation; the cor frontale differs in size and volume among hydrothermal vent species but retains a conserved subdivision of central arteries surrounding a longitudinal muscle bundle. We conclude that the observed variations in the volume of neuropils and arrangement of the vascular system likely reflect the ecological divergence related to microhabitat conditions and trophic strategies near hydrothermal emissions.

Mathou A
Machon J
Meth R
Zbinden M
Ravaux J
Harzsch S

Animals
Brain
Decapoda
Species Specificity
Hydrothermal Vents
Ecosystem
Neuroanatomy


Improvement in Pain Neuroscience Knowledge and Patient Perceptions Following a One-Day Multidisciplinary Pain Education Program

Abstract: Pain neuroscience education is recognized as a core component of multidisciplinary chronic pain management. Although meta-analyses report small to medium clinical benefits across a range of chronic pain conditions and delivery settings, further evidence is needed to support implementation. To evaluate changes in knowledge of pain neurophysiology and patient perceptions following participation in a single-session, multidisciplinary "Introduction to Pain Management" (IPM) program delivered within a tertiary pain service. This quality improvement study examined outcomes from patients attending one of 16 IPM sessions delivered between February and December 2025. Participants completed the Revised Neurophysiology of Pain Questionnaire (R-NPQ) immediately before and after the program. Rasch analysis was conducted to generate person estimates, and pre-post changes were analyzed using the paired-sample t-test. A post-program survey assessed perceived relevance, clarity, and intended use of self-management strategies. Of the 172 patients who attended the program, paired Rasch person estimates were available for 158 patients following exclusion of those with extreme Rasch scores. Participation in the IPM program was associated with a statistically significant increase in knowledge of pain neurophysiology (p < 0.001), with a moderate-to-large effect size (d = 0.73). Post-program survey responses indicated high levels of perceived relevance, clarity, and intended use of self-management strategies. Participation in a single-session, multidisciplinary pain education program was associated with immediate improvements in pain neurophysiology knowledge and positive patient perceptions. These findings support the role of brief, structured pain education as a foundational component of multidisciplinary tertiary chronic pain services. Further research is needed to determine whether improvements in pain neurophysiology knowledge are maintained over time and associated with longer-term clinical outcomes.

Journal of evaluation in clinical practice

Humans
Pain Management
Female
Patient Education as Topic
Health Knowledge, Attitudes, Practice
Male
Neurosciences
Middle Aged
Adult
Chronic Pain
Quality Improvement
Surveys and Questionnaires
Aged


Neuropathology in a diverse cohort of oldest-old: The LifeAfter90 study

Abstract: Studies of the oldest-old show great neuropathologic heterogeneity; little is known in diverse populations after age 90. LifeAfter90 is a lifecourse cohort study of individuals aged ≥ 90 years evaluated every 6 months with optional brain donation; this study presents initial neuropathological findings. A total of 124 decedents (mean age 96, 49.2% White, 12.1% Black, 16.9% Asian, 18.5% Latino individuals) came to autopsy. At last evaluation, 35% had dementia, 23% cognitive impairment, and 41% normal cognition. 35.5% had intermediate AD, 8.1% had high AD neuropathologic changes, 73% had moderate/severe arteriolosclerosis, 23% one or more microinfarcts, 32% Lewy bodies, 24% TDP-43 deposits, and 4% hippocampal sclerosis. There was a high degree of mixed neuropathology, with 69% having three or more pathologies. Cognitive impairment was most strongly associated with AD pathology. Multiple pathologies were common, and many individuals maintained normal cognition indicating substantial neuropathologic burden may be present in the absence of overt cognitive impairment, especially in the oldest-old.

Alzheimer's & dementia : the journal of the Alzheimer's Association

Dugger BN
Luu MN
Patel V
DeCarli C
Jin LW
Gilsanz P
Mungas D
Kawas C
Corrada MM
Whitmer RA

Humans
Aged, 80 and over
Female
Male
Brain
Cohort Studies
Alzheimer Disease
Hippocampal Sclerosis
Cognitive Dysfunction
Neuropathology


SACS: A Reproducible, Configuration-Driven Software Framework for Schematic Multi-Region Circuit Simulation and Integrated Analytics

Abstract: Computational neuroscience projects often combine simulation code, configuration files, analysis scripts, plotting utilities, and provenance records through loosely coupled and difficult-to-replay workflows. SACS is presented as a configuration-driven research-software framework for reproducible schematic multi-region circuit simulation with integrated analytics, validation checks, deterministic execution, deterministic replay, artifact replay, and graphical inspection. Implemented as the Python package brain_sim, the framework converts declarative model and scenario specifications into standardized run directories containing numerical outputs, machine-readable summaries, figure-generation recipes, validation reports, and provenance metadata. The contribution is methodological and neuroinformatics-oriented. SACS is not presented as a biologically validated model of anxiety, brain function, or treatment response, and its built-in circuit materials are used as configurable demonstration components rather than as evidence of clinical or biological validity. Instead, the framework is evaluated as software for reproducible computational experimentation: hypotheses are encoded as explicit configurations, executed under recorded seeds, inspected through analytics and validation layers, and then used to inform subsequent configurations in an iterative workflow. The manuscript describes the software architecture, configuration and execution model, artifact structure, replay mechanisms, and graphical/programmatic interfaces that support this workflow. The central claim is that SACS improves transparency, inspectability, and reuse for schematic circuit experiments by binding configuration, execution, analytics, provenance, and replay within a single software environment.

Software
Computer Simulation
Humans
Animals
Brain
Models, Neurological
Reproducibility of Results
Neurosciences


My Fifty Years Thinking about Emotional Consciousness in the Brain

Abstract: This piece provides an overview of my fifty-year career as a neuroscientist. I spent much of this time trying to understand what emotions are and how they relate to human behavior and consciousness. I am pleased that my work on the amygdala helped bring emotion into the field. But late in the game I changed my views about the amygdala and emotions, causing some unrest in the field. Note that this is a personal, not an encyclopedic, overview of the neuroscience of emotion. In other words, this is my story about emotions and the brain, especially in relation to emotional consciousness.

The Journal of neuroscience : the official journal of the Society for Neuroscience

Humans
Consciousness
Emotions
Brain
History, 21st Century
History, 20th Century
Neurosciences
Animals


Active Ingredients in Digital Cognitive Interventions: Integrating Dismantling Designs With Mechanistic Neuroscience

Abstract: Digital cognitive interventions (DCIs) have emerged as scalable approaches for treating cognitive dysfunction across psychiatric, neurological, and aging populations. Despite growing evidence of efficacy, little is known about which intervention components drive therapeutic effects or through which neurocognitive mechanisms they operate. As a result, null findings are often difficult to interpret, making it unclear whether interventions failed to engage their intended targets, or whether the targets themselves are not causally related to meaningful outcomes. This limits intervention refinement, comparative evaluation, and precision personalization. Here, we argue that DCI research should shift from broad efficacy testing toward mechanistic trials designed to identify active ingredients-the intervention components responsible for engaging prespecified neurocognitive targets and producing clinically meaningful benefits. We propose adapting dismantling design methodology from psychotherapy research in order to integrate Research Domain Criteria constructs, mechanistic neuroscience, and high-resolution digital behavioral data to identify factors driving cognitive and functional outcomes. This approach aligns with the National Institute of Mental Health experimental therapeutics framework by explicitly linking target specification and target engagement with downstream clinical and functional outcomes. Mechanistic dismantling trials can determine whether specific DCI features, including adaptive difficulty, reward schedules, feedback contingencies, task variability, cognitive targets, and human support, are necessary, sufficient, or synergistic for engaging neural circuitry and producing durable and clinically meaningful transfer. Beyond optimizing intervention design, such studies may transform null or negative trials into mechanistically interpretable findings, while clarifying disease mechanisms and supporting the development of personalized, optimized, and usable DCIs.

Morimoto SS
Lindbergh CA
Conley A
Jones DR
Steffens DC

Humans
Digital Media
Research Design
Cognitive Dysfunction
Neurosciences
Cognitive Behavioral Therapy


Divergent philosophical commitments in neuroscience: Evidence from a global survey

Abstract: The mind-brain relationship is a foundational yet underexplored dimension of contemporary neuroscience, shaping research framing, data interpretation, and public communication. We conducted a large-scale international survey of 2,657 neuroscientists to assess their views on the mind-brain problem, free will, and the future of the discipline. Our results reveal a complex and sometimes paradoxical worldview. While 64% of participants endorse reductive physicalism-the view that mental activity is fully reducible to brain function-only 17.5% reject free will. Despite estimating that current knowledge covers only a limited portion of brain structure and function (30%), respondents express marked optimism about the future of neuroscience, including the prospect of fully understanding the human being and mental disorders through neuroscience, and even achieving mind reading and mental uploading. A principal component analysis identified five latent dimensions, some of which vary systematically across sociodemographic and disciplinary factors. These findings indicate that neuroscientists hold diverse philosophical commitments that diverge from common narratives of hard determinism. The prevalence of neuroessentialist views further highlights the need for sustained interdisciplinary dialogue to address the conceptual, ethical, and societal implications of neuroscientific progress.

Proceedings of the National Academy of Sciences of the United States of America

Navarro-Peña F
Arrondo G
Barrett NF
Güell F
Madirolas G
Murillo JI
Sánchez-Cañizares J
Bernacer J


The Importance of Studying the Cognitive Neuroscience of Aging Across Cultures

Abstract: It is now widely appreciated that culture can shape cognition and neural engagement. However, research investigating the effects of culture across the adult lifespan, with a focus on cognitive aging, is lacking. In this article, we consider why this integration of topics is useful and discuss the ways in which culture has been proposed to affect cognition and the cognitive neuroscience of aging. The literature thus far is reviewed from the perspectives of long-term memory and decision-making, which broadly encompass information processing in the brain and reflect a person's worldview and resulting actions. We argue for the importance of integrating aging into the study of cultural neuroscience, making the case from two different perspectives: the importance of studying cultural influences over the trajectory of the adult lifespan and the importance of understanding the cognitive neuroscience of aging across cultural groups. We discuss challenges and opportunities for future research, concluding that studying the cognitive neuroscience of aging across cultures has the potential to broaden understanding of the factors that contribute to successful cognitive aging as well as age-related decline and pathology.

Annals of the New York Academy of Sciences

Humans
Cognitive Neuroscience
Aging
Cognition
Culture
Decision Making
Cognitive Aging
Brain
Memory, Long-Term
Neurosciences


The steady-state visual evoked potential (SSVEP): A review of applications in cognitive and clinical neuroscience and neural engineering

Abstract: The steady-state visual evoked potential (SSVEP), the brain's oscillatory response to repetitive visual stimulation (RVS), has emerged as a powerful tool in neuroscience with wide-ranging applications in multiple disciplines. This review provides a scoping, narrative roadmap of SSVEP applications organized into three primary domains: fundamental research in vision and cognition, clinical neuroscience, and neural engineering. Although these fields differ in focus, they often converge in their use of similar research questions, stimulation paradigms, analysis techniques, and application scenarios. At the same time, specialization may have created knowledge silos that limit cross-disciplinary transfer of methods and insights. By bridging findings from seemingly disparate domains, this review highlights the versatility of SSVEPs in investigating neural mechanisms, supporting diagnosis and treatment of neurological and psychiatric conditions, and advancing brain-computer interface technology. We conclude with cross-field insights on how stimulus and analysis choices affect interpretation and usability, and we outline directions for improving the comparability and transferability of SSVEP research and applications.

Tsoneva T
Desain P
Garcia-Molina G
Thielen J

Humans
Evoked Potentials, Visual
Cognitive Neuroscience
Electroencephalography
Brain
Brain-Computer Interfaces


Altered EEG in Creutzfeldt-Jakob Disease: Improving Diagnostic Accuracy Using American Clinical Neurophysiology Society 2021 Criteria

Abstract: Creutzfeldt-Jakob disease (CJD) is a rapidly progressive neurodegenerative disease characterized by significant changes in EEG and structural alterations on MRI. Both are integrated in the current World Health Organization (WHO) surveillance criteria of CJD. We aimed to re-evaluate the EEG recordings, along with clinical and MRI data, in patients with different subtypes of definite CJD by applying the adapted American Clinical Neurophysiology Society (ACNS) criteria, 2021. Fifty-one routine EEG recordings in 16 patients with sporadic CJD were reanalyzed. Generalized slowing, according to standard terminology, was present in 94% of patients. Generalized periodic discharges (GPDs) and generalized rhythmic delta activity (GRDA), as defined by the 2021 ACNS criteria, occurred frequently (31% and 38%, respectively). The differentiation from ictal activity may be challenging because 25% (4/16) of the patients fulfilled the criteria of the recently proposed ictal-interictal continuum (IIC) in at least 1 EEG. By contrast, no status epilepticus (SE) was observed. The EEG alterations varied among the different CJD molecular subgroups: more cortical involvement in MM/MV1 and mixed MM/MV1 + 2C histotypes was associated with periodic discharges (PDs) (57% and 80%) and also IIC (43% and 20%). We could not detect any PD or IIC in patients with the VV1 or MV2K (predominant subcortical pathology) histotype. Assessing the EEGs according to the 2021 ACNS criteria may help prevent misdiagnosis of nonconvulsive status epilepticus, and repetitive recordings may help in earlier diagnosis of CJD.

Berger-Sieczkowski E
Zulehner G
Klotz S
Regelsberger G
Haider L
Bonelli-Nauer S
Trimmel K
Gelpi E

Creutzfeldt-Jakob Syndrome
Humans
Electroencephalography
Female
Male
Aged
Middle Aged
Societies, Medical
Magnetic Resonance Imaging
Neurophysiology


Diagnostic Agreement and 1-Year Outcomes in Functional Neurological Disorder Following Neuroscience-Informed Assessment, Education, and Counseling: A Retrospective Cohort Study

Abstract: We sought to explore outcomes at 1 year in functional neurological disorder (FND) following a neuroscience-informed education and counseling assessment. Patients with FND were assessed at a quaternary neuropsychiatry clinic in Toronto, Canada, and provided education and counseling to build insight into their FND diagnosis. Patient-determined diagnostic agreement at follow-up was categorized as a binary variable: (i) symptoms attributable primarily to FND or (ii) attributable to another cause (neurological disease or unknown). One-year symptom status was patient-reported on a 7-point scale (-3 to +3), with scores ≥2 defined as meaningful improvement. Return to work/school was assessed as an indicator of global improvement of functional status. Univariate tests screened variables for inclusion in multivariate logistic regression models, which evaluated associations between diagnostic agreement and other outcomes. A total of 282 patients with FND were assessed (mean age 38.9 ± 12.0 years; 80.3% female), and of these, 127 had 1-year follow-up data. FND subtypes included functional movement disorder (functional weakness [26.8%], hyperkinetic movement [15.7%]), seizure (15.0%), sensory (16.5%), functional cognitive disorder (7.9%), persistent postural perceptual dizziness (14.2%), and speech/swallowing (3.9%). Diagnostic agreement was significantly associated with symptom improvement (odds ratio [OR] = 3.81, 95% CI: 1.33-11.71, p = 0.015) and global improvement (OR = 5.74, 95% CI: 1.11-37.54, p = 0.047). Psychiatric comorbidity (p = 0.026), childhood trauma (p = 0.015), and psychological triggers (p = 0.013) were associated with diagnostic agreement, while ongoing medical/neurological workup was linked to disagreement (p < 0.001). Diagnostic agreement was associated with symptom improvement and return-to-work/school status in FND patients who received a neuroscience-informed education and counseling assessment. However, given the observational design and lack of baseline measurement of diagnostic agreement, the directionality of this relationship cannot be determined.

Mollica A
Ng E
Nannapaneni S
Bhayat U
Feinstein A
Perez DL
Burke MJ

Humans
Female
Male
Adult
Retrospective Studies
Nervous System Diseases
Middle Aged
Counseling
Patient Education as Topic
Neurosciences
Follow-Up Studies
Conversion Disorder


The ontological status of behaviour: lessons from experimental neurosis (1900-1950)

Abstract: This article examines how early twentieth-century comparative psychology treated behaviour as a primary site for studying regulation, dysfunction, and adaptation, using experimental neurosis as a historical case study. Beginning with Pavlov's observation that dogs exposed to irresolvable conflict developed persistent behavioural and autonomic disturbances, the paradigm expanded through mid-century work by Liddell, Gantt, and Masserman, who introduced new species, longitudinal designs, and ecologically grounded conditions revealing dysregulation as a multilevel, temporally extended phenomenon. In this tradition, behaviour was not construed as mechanistic output but as an autonomous level of organisation whose structured patterns, i.e., variability, context-sensitivity, stability, and breakdown, made internal regulatory dynamics experimentally accessible in ways physiology alone could not. Hybrid methodologies integrating laboratory control with naturalistic observation showed that pathological breakdown provides access to organisational features obscured during normal function. By mid-century, however, this behaviourally rich framework was displaced by reductionist approaches based on standardised assays and physiological endpoints. Recent historiography documents this shift as an epistemological transformation in which behaviour was redefined from interface to index, from organised system to dependent variable. These tensions persist in contemporary neuroscience and translational research, where behaviour is routinely subordinated to mechanism despite gaps between circuit-level manipulation and behavioural explanation. This historical analysis supports the claim that mechanistic approaches which bypass behaviour incur explanatory loss, eliminating the domain in which neurophysiological processes acquire functional meaning. Progress in understanding psychopathology requires restoring behaviour to ontological and epistemological centrality as the irreducible interface through which adaptive and pathological regulation become scientifically accessible.

History and philosophy of the life sciences

Animals
Dogs
Behavior, Animal
History, 20th Century
Neurosciences
Psychology, Comparative
History, 19th Century

Journal Article
Historical Article
Review


Learning Under Uncertainty: Predictive Processing as an Integrative Framework for Educational Research

Abstract: Research at the intersection of neuroscience and education has generated substantial empirical findings but has often lacked a unifying theoretical framework capable of explaining why those findings belong together. Predictive processing, a family of accounts characterizing the brain as a hierarchical system that continuously generates expectations and updates internal models in response to prediction errors, has been proposed as a candidate umbrella framework for the cognitive sciences, though it remains actively debated. We examine whether its core concepts transfer meaningfully to educational contexts. Rather than deriving concrete instructional prescriptions, we propose four constraints that are especially relevant when instruction aims to produce conceptual model revision under uncertainty. We further suggest that developmental differences between children and adults can be interpreted as systematic variations in these inferential parameters. The contribution of this paper is primarily integrative: findings from educational research have largely been articulated within separate paradigms, and we argue that predictive processing may offer a common inferential vocabulary for describing them. Future work may derive empirically testable predictions from this framework, though the limitations of these accounts must be kept carefully in view.

Integrative psychological & behavioral science

Humans Learning Neurosciences Research Uncertainty