Diabetes is a highly prevalent, chronic condition requiring complex treatment strategies and close monitoring. Achievement of optimal glucose management reduces vascular complications of diabetes and the long-term burden of the disease. Attenuation of postprandial rise in glucose is a critical component of overall glycemic management and often the most difficult for people with insulin-treated diabetes to achieve. While postprandial glucose (PPG) elevations are a consequence of insufficient endogenous insulin secretion or exogenous insulin dose to cover ingested carbohydrates, a mismatch between the absorption of nutrients and peak insulin concentration is also a key factor in managing PPG. Type 2 diabetes is characterized by loss of first-phase insulin secretion, resulting in elevations in PPG and prolongation of hyperglycemia after eating. In type 1 diabetes and other forms of insulin-requiring diabetes, insulin administration must match carbohydrate and other nutrient intake in both quantity and timing. Continuous glucose monitoring (CGM) has provided insights into glucose patterns and the effectiveness of diabetes therapies in managing glucose levels at all times of the day. When CGM is used with an automated insulin delivery pump or connected insulin pen, prandial insulin dosing can be analyzed for more effective coaching and education. Based on the 2026 American Diabetes Association Standards of Care guidelines, delivery devices and method of insulin administration should be assessed regularly and individualized based on the needs of each person, considering options such as automated insulin delivery, inhaled insulin, or multiple daily injections. This manuscript reviews the causes and contributors of postprandial hyperglycemia and strategies for its management. In particular, use of lifestyle management, insulin dose adjustments, timing of premeal insulin doses, and insulin kinetics will be reviewed for precision management of postprandial hyperglycemia.
Diabetic kidney disease (DKD) remains the leading cause of end-stage renal disease worldwide. Current diagnostic approaches rely mainly on albuminuria and eGFR, but these are insufficiently sensitive for detecting early lesions, and treatment options remain limited. Metabolites are not merely byproducts of metabolism but serve as central signaling hubs that orchestrate DKD progression. These metabolites can act as receptor ligands, substrates for epigenetic modifications, and cargoes of extracellular vesicles. Together, they form a complex metabolic signaling network that links systemic metabolic disturbances to local kidney injury. Adopting this metabolite-centric new perspective transforms DKD from a collection of isolated pathways into a systemic, network-level disease. Recent advances in multidimensional metabolomics technologies—including static profiling, spatial metabolomics, metabolic flux analysis, and multi-omics approaches—enable us to dissect the metabolic network of DKD with unprecedented resolution. This review synthesizes current knowledge on metabolite-driven mechanisms, including the AGEs–RAGE pathway, lipotoxicity, amino acid reprogramming, and EV-mediated crosstalk. It systematically categorizes metabolite biomarkers according to their clinical functions, covering early detection, progression prediction, and pathogenic drivers. In addition, emerging therapeutic strategies targeting specific metabolic nodes are discussed. Finally, building on these established findings, we propose a hypothetical roadmap toward metabolic precision medicine. This framework hypothesizes the stratification of patients into distinct metabolic phenotypes, such as the high-TMAO, high-BCAAs, and high-AGEs subtypes. It suggests that treatment regimens could be selected based on the underlying metabolic mechanisms and that therapeutic responses could be assessed by dynamic monitoring of circulating metabolites. If validated, this conceptual strategy holds promise for overcoming current diagnostic and therapeutic bottlenecks and improving outcomes for patients with DKD.
IntroductionHypothalamic dysfunction (HD) after treatment for a pediatric (supra)sellar tumor severely affects quality of life of patients, as well as their parents and families. Patients may develop signs of fatigue as a result of persistent disturbances in thermoregulation, sleep-wake rhythm, or hormonal insufficiencies. The management of HD requires around-the-clock care by the parent or caregiver. To support patients with HD and their parents/caregivers, we co-created a smart wearable device for continuous monitoring (EndoWatch) to detect early signs of hypothalamic dysregulation. We aimed to evaluate adherence to and user experiences of the first EndoWatch design.MethodsIn co-creation with clinicians, patient representatives, and design researchers and engineers, an existing smart device (wearable sensor and mobile application (app)) was adapted to a first design tailored for this purpose. In a prospective, observational study, 10 pediatric brain tumor survivors with HD (8 children; 2 adults) tested the first design of the device for 14 days. The primary outcome was adherence to wearing the EndoWatch. Secondary outcomes included usability, learnability, and desirability (through questionnaires), and barriers and facilitators (through semi-structured interviews).ResultsTen patients participated (8 children, mean age 10.8 (SD 3.5); 2 adults, aged 18.9 and 31.0 years). Median overall adherence was 99.4% (IQR 22.8); two patients discontinued early due to wristband-related discomfort. Key facilitators were ease of use of the device and reliable technical performance. Main barriers included the absence of a separate caregiver app and limitations of the patient diary. These findings informed design modifications for future improvements of the device.DiscussionThe concept of the first EndoWatch design was considered acceptable and usable by patients with HD and their caregivers. This study identified key barriers and the modifications required for improvement, which were incorporated into a second EndoWatch design, to be evaluated in a larger prospective study.
Immune checkpoint inhibitors (ICIs) have revolutionized oncologic therapy by substantially improving survival outcomes in various malignancies. These agents—such as ipilimumab, nivolumab, pembrolizumab, atezolizumab, and durvalumab—modulate the immune system by inhibiting key checkpoint receptors, including cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed cell death protein 1 (PD-1), and programmed cell death ligand 1 (PDL-1), thereby facilitating tumor regression. However, immune modulation frequently triggers immune-related adverse events, which can affect any organ system, particularly the skin, liver, gastrointestinal tract, lung, and endocrine glands. Among the most common endocrine disorders induced by ICIs are thyroid, pituitary, adrenal, and beta-cell dysfunctions. Pituitary dysfunction is most commonly associated with combined CTLA-4 and PD-1/PDL-1 inhibitor regimens. This case report discusses a rare instance of presumed arginine vasopressin deficiency (AVP-D) secondary to pembrolizumab-monotherapy-induced hypophysitis, which was unmasked following glucocorticoid therapy. A 59-year-old male with metastatic lung adenocarcinoma treated with pembrolizumab developed gastrointestinal symptoms and was subsequently diagnosed with toxic colitis. Following the initiation of glucocorticoid therapy, he developed hypernatremia, polyuria, and polydipsia. Further evaluation suggested AVP-D, with rapid symptom resolution under desmopressin. This report underscores the complexity of endocrine disturbances associated with ICIs and the diagnostic challenges associated with glucocorticoid therapy in patients with ICI-related hypophysitis. The occurrence of arginine vasopressin deficiency in the context of pembrolizumab-induced hypophysitis is rare and not well investigated, highlighting the need for further research into the underlying mechanisms and optimal clinical management of these immune-mediated endocrine disorders.
