Glucose-Dependent Insulinotropic Polypeptide Is Involved in Postprandial Regulation of Splanchnic Blood Supply
Administration of the gut hormone glucose-dependent insulinotropic polypeptide (GIP) increases splanchnic blood flow. Researchers identified a novel physiological aspect of vascular biology related to the GIP receptor in humans. Treatments targeting the GIP receptors are likely to affect splanchnic blood flow.
KEY FINDINGS: Infusion of GIPR-An during oral glucose ingestion resulted in lower insulin secretion and higher levels of carboxy-terminal collagen crosslinks (bone resorption biomarker) compared with saline infusion, whereas glucagon levels were unaffected by both the injection of GIP and the GIPR-An infusions. Authors conclude that endogenous GIP increases splanchnic blood flow and contributes to postprandial intestinal hyperemia in healthy men.
BACKGROUND: Gastrointestinal hormones are essential for nutrient handling and regulation of glucose metabolism and may affect postprandial blood redistribution.
DETAILS: In a randomized cross-over design in 10 healthy men, the involvement of glucose-dependent insulinotropic polypeptide (GIP) in splanchnic blood flow regulation was investigated using an infusion of GIP receptor antagonist (GIPR-An) GIP(3-30)NH2 during ingestion of oral glucose (75 g). In five separate sessions, authors investigated GIP(1-42), GIPR-An with and without oral glucose, oral glucose alone, and a control saline infusion. Blood flow was assessed by phase contrast MRI, hepatic oxygen consumption by T2*, and plasma glucose, insulin, C-peptide, glucagon, GIP, GIPR-An, glucagon-like peptide 2, and bone metabolism markers by frequent blood sampling during all sessions. Authors found GIP(1-42) to stimulate blood flow in the superior mesenteric artery by ~10% in the fasting state. Oral glucose alone increased mean blood flow in the superior mesenteric artery by ~70% and portal vein by ~40% of baseline. During oral glucose ingestion with concurrent infusion of GIPR-An, blood flow in the superior mesenteric artery was ~22% lower. The hormone infusions did not affect blood flow in the hepatic artery and the celiac artery.
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Source: Rasmussen, R. S., Langberg, L. S., Østergaard, F., et al. Glucose-Dependent Insulinotropic Polypeptide Is Involved in Postprandial Regulation of Splanchnic Blood Supply. Diabetes. 2025; 74(8): 1355-1366. Published: August, 2025. DOI: 10.2337/db25-0149.
Neovascular Glaucoma Associated With Increased Long-Term Mortality and Systemic Morbidity
A large TriNetX cohort study found that neovascular glaucoma was associated with increased long-term risks of mortality and systemic complications beyond underlying retinal vascular disease. At 10 years, NVG in patients with proliferative diabetic retinopathy was associated with higher mortality and end-stage renal disease, while NVG in patients with central retinal vein occlusion was associated with higher mortality and stroke risk. The findings highlight the potential value of coordinated ophthalmic and systemic care when NVG develops.
KEY FINDINGS: The development of NVG was associated with additional long-term systemic morbidity and mortality beyond the underlying PDR or CRVO in this large retrospective cohort. The strongest associations included mortality and ESRD among patients with PDR and mortality and stroke among those with CRVO. The findings suggest that development of NVG may identify patients with substantial systemic vascular risk and support closer coordination between ophthalmic and other medical specialties. Because the study was retrospective and based on electronic health records, the observed associations should not be interpreted as evidence that NVG itself directly causes these systemic outcomes.
BACKGROUND: Neovascular glaucoma (NVG) is a serious ocular complication of retinal vascular disease, including proliferative diabetic retinopathy (PDR) and central retinal vein occlusion (CRVO). Although NVG is primarily recognized for its effects on vision and intraocular pressure, less is known about whether its development is associated with additional long-term systemic health risks. This multicenter retrospective cohort study evaluated mortality and major systemic outcomes among adults with PDR or CRVO who did or did not subsequently develop NVG.
DETAILS: The investigators used the TriNetX Research Network, a deidentified electronic health record database containing information from more than 177 million patients across more than 150 healthcare organizations worldwide. Adults older than 40 years with PDR or CRVO were identified and compared according to whether NVG subsequently developed. Patients were propensity-score matched 1:1 based on demographic characteristics and comorbidities. Outcomes were assessed at 1, 5, and 10 years and included all-cause mortality, stroke, myocardial infarction (MI), end-stage renal disease (ESRD), and deep-vein thrombosis (DVT). A total of 1,278 patients with PDR and NVG were matched with 1,278 patients with PDR without NVG. The study also evaluated patients with CRVO and NVG compared with matched CRVO patients without NVG, as well as an NVG cohort compared with a cataract control cohort.
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Among patients with PDR, development of NVG was associated with higher 10-year mortality (HR, 1.34; 95% CI, 1.14-1.57) and ESRD (HR, 1.43; 95% CI, 1.23-1.67) compared with PDR without NVG. Ten-year survival was 60.4% in the PDR + NVG group compared with 68.4% in the PDR without NVG group. Among patients with CRVO, those who developed NVG had higher 10-year mortality (HR, 1.61; 95% CI, 1.17-2.20) and stroke risk (HR, 1.86; 95% CI, 1.19-2.90). Differences in MI and ESRD were not statistically significant in this comparison, and DVT risk was also not significantly different. When PDR + NVG was compared directly with CRVO + NVG, the PDR + NVG group had higher 10-year risks of mortality (HR, 1.56; 95% CI, 1.17-2.07), MI (HR, 1.94; 95% CI, 1.13-3.32), and ESRD (HR, 4.04; 95% CI, 2.43-6.73). Compared with the cataract control cohort, NVG was associated at 10 years with higher risks of mortality (HR, 2.66; 95% CI, 2.40-2.94), stroke (HR, 2.17; 95% CI, 1.85-2.54), MI (HR, 1.89; 95% CI, 1.60-2.23), and ESRD (HR, 3.34; 95% CI, 2.89-3.88).
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Source: Margolis, R., Vasu, P., and Dorairaj, S. K. Long-Term Risk of Mortality and Systemic Morbidity in Neovascular Glaucoma: A Multicenter Retrospective Cohort Study. Ophthalmology Glaucoma. 2026; 9(5): 517-526. Published: September-October, 2026. DOI: 10.1016/j.ogla.2026.01.017.
Biochemical Effects of Oral Contraceptives in Young Women With Classic Congenital Adrenal Hyperplasia
A prospective study found that ethinylestradiol/levonorgestrel reduced key adrenal androgens while increasing cortisol levels. Nearly half of participants had a reduction in hydrocortisone dose following biochemical changes. Larger randomized studies are needed to confirm these findings.
KEY FINDINGS: In adolescent and young women with classic 21OHD, combined OC containing 0.03 mg ethinylestradiol and 0.15 mg levonorgestrel was associated with broad reductions in circulating and urinary androgen-related steroids and an increase in cortisol levels. Nearly half of the participants who completed the study required a reduction in hydrocortisone dosage during the six-OC-cycle observation period. These findings suggest that combined OCs may provide an adjunctive approach for managing persistent androgen excess in females with classic CAH when conventional glucocorticoid treatment does not provide satisfactory biochemical control. However, the study was small and observational, so the findings do not establish a causal relationship, and randomized studies are needed to determine the longer-term clinical and metabolic effects of OC therapy in this population.
BACKGROUND: Androgen excess remains a therapeutic challenge in adolescent and young women with classic 21-hydroxylase deficiency (21OHD), the most common form of congenital adrenal hyperplasia (CAH). Combined oral contraceptives (OCs) containing ethinylestradiol and a progestin can influence ovarian and adrenal steroidogenesis, but their effects on the broader steroid profile in women with classic 21OHD have not been systematically characterized. This prospective observational study evaluated changes in circulating and urinary steroid metabolites following initiation of a combined OC in adolescent and young women with classic 21OHD.
DETAILS: The multicenter study enrolled 20 young women with genetically confirmed classic 21OHD between March 2021 and March 2024. Participants were 13-25 years old at baseline sampling, although the recruited cohort had a median age of 16 years and a range of 11-24 years. The participants initiated a combined OC containing 0.03 mg ethinylestradiol and 0.15 mg levonorgestrel. The study included three assessments: before OC initiation, during the third OC cycle, and during the sixth OC cycle. Blood samples and 24-hour urine collections were obtained at each visit, with plasma steroids measured using liquid chromatography-mass spectrometry and urinary metabolites assessed using gas chromatography-mass spectrometry. Seventeen of the 20 participants completed the study, with a median age of 16.8 years (range, 11-24). The reasons for OC initiation included irregular menses, contraception, amenorrhea, dysmenorrhea, and hyperandrogenemia. Most participants were receiving hydrocortisone and fludrocortisone for CAH management. The prospective design and combined assessment of plasma and urinary steroid profiles allowed detailed characterization of biochemical changes during OC treatment.
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Combined OC therapy was associated with significant reductions in several circulating androgens and androgen precursors. Compared with baseline, plasma concentrations of 17α-hydroxyprogesterone, androstenedione, dehydroepiandrosterone, and testosterone decreased significantly, with all P values <0.005. Plasma cortisol concentrations increased significantly (P<0.001), while urinary 24-hour excretion of androgen metabolites, including the 11-oxygenated androgen metabolite 11-oxo-etiocholanolone, also declined.
The broader steroid analysis showed reductions in multiple androgen-related metabolites, including androsterone, etiocholanolone, DHEA, testosterone, dihydrotestosterone, 11-oxo-etiocholanolone, and 11β-hydroxyandrosterone. Cortisol concentrations and urinary cortisol excretion increased during OC treatment. These biochemical changes had implications for glucocorticoid management: 8 of 17 participants (47%) who completed the study had at least one reduction in hydrocortisone dose during follow-up in response to laboratory changes.
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Source: Kouri, C., Sommer, G., Cavalieri Costa, F., et al. Biochemical Control in Young Women With Congenital Adrenal Hyperplasia Taking Oral Contraceptives: A Prospective Observational Study. v. 2026; 195(3): 385-395. Published: September, 2026. DOI: 10.1093/ejendo/lvag160.
Irregularly Shaped Microplastics May Compromise the Kidney’s Glomerular Filtration Barrier
In a mouse study, irregularly shaped microplastic particles persisted in circulation, accumulated in the kidneys, and were detected in urine despite more than 99% of administered particles being excreted in feces. Irregular particles caused renal vascular and tubular lesions, capillary flow disturbances, and changes suggesting disruption of the glomerular filtration barrier. They also produced glomerular albumin hyperfiltration and increased proximal tubular albumin uptake. These effects were not observed with spherical microplastic particles, highlighting particle shape as a potentially important determinant of renal toxicity.
KEY FINDINGS: In this experimental mouse study, irregularly shaped microplastic particles demonstrated a different biological distribution and renal effect profile from spherical particles. Despite >99% of administered particles being excreted in feces, irregular fragments persisted in the circulation, accumulated in the kidneys, and were detected in urine. Renal exposure was associated with vascular and tubular lesions, capillary flow disturbances, and changes suggesting disruption of the glomerular filtration barrier. The findings indicate that microplastic morphology may be an important determinant of biological effects, although the clinical relevance to human kidney health remains to be established.
BACKGROUND: Human exposure to microplastics is widespread, but the biological effects of particle shape remain incompletely understood. Most experimental studies have used spherical particles, despite environmental microplastics commonly occurring as irregular fragments. This study compared spherical and irregularly shaped microplastic particles to determine whether particle morphology influences their distribution in the body and their effects on renal function.
DETAILS: Investigators administered labeled spherical and irregular microplastic particles to mice by oral gavage, either as a single dose or daily for 7 days. Microplastic distribution was evaluated in multiple organs, while renal effects were assessed using histochemistry and intravital multiphoton microscopy. Additional functional experiments were performed using isolated perfused mouse kidneys. Overall intestinal absorption was limited, with >99% of administered microplastic particles being eliminated in feces. However, irregular fragments remained detectable in the circulation for several days and accumulated in multiple organs following oral exposure.
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Irregular microplastic particles were detected in the urine as well as within renal blood vessels, glomeruli, and tubules. Their presence in the urine suggested that these particles could cross the glomerular filtration barrier. Within the kidney, irregular particles were associated with phagocytic cells. Functional studies demonstrated that irregular microplastics caused disturbances in capillary flow and produced lesions involving renal blood vessels and the tubular system. They also resulted in glomerular albumin hyperfiltration and increased proximal tubular albumin uptake, findings consistent with impairment of the glomerular filtration barrier. These effects were not observed following ingestion of spherical microplastic particles.
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Source: Triebel, H., De Luca, F., Baumann, S. J., et al. Irregularly Shaped Microplastic Particles Compromise the Integrity of the Glomerular Filtration Barrier of the Kidney. Kidney360. 2026; 7(8): 1750-1762. Published: May 12, 2026. DOI: 10.34067/KID.0000001215.
Somatic Diseases May Affect the Brain Primarily Through Vascular Injury and Neuronal Loss
A narrative review found that common age-related somatic diseases were consistently associated with brain atrophy, neuronal loss, and cerebrovascular lesions. Evidence linking these diseases to amyloid and tau pathology was limited and inconsistent. The findings suggest that systemic diseases may contribute to dementia primarily through non-Alzheimer's mechanisms, particularly vascular injury and neuronal loss. The review underscores the importance of recognizing mixed dementia and considering systemic health in the assessment of cognitive decline.
KEY FINDINGS: Common age-related somatic diseases appear to be more consistently associated with cerebrovascular injury, brain atrophy, and neuronal loss than with amyloid or tau pathology. These findings suggest that the relationship between systemic disease and dementia may involve multiple non-AD pathways rather than a direct effect on classical AD pathology. The review highlights the importance of recognizing mixed dementia and considering systemic health when evaluating brain aging and cognitive decline.
BACKGROUND: Several common age-related somatic diseases are associated with an increased risk of dementia, but the neuropathological pathways underlying these associations remain incompletely understood. This narrative review examined evidence linking heart disease, type 2 diabetes, kidney disease, liver disease, lung disease, and anemia with brain pathology, including Alzheimer's disease (AD)-related amyloid and tau pathology and non-AD changes such as neuronal loss, brain atrophy, cerebrovascular lesions, neuroinflammation, and non-AD proteinopathies.
DETAILS: The authors conducted a PubMed search for human studies investigating associations between somatic diseases and brain pathology using postmortem examinations, brain imaging, or cerebrospinal fluid biomarkers. The available evidence was qualitatively synthesized and graded according to its strength. The review specifically evaluated whether common systemic diseases were associated with AD-related pathology or with other forms of brain injury that may contribute to cognitive impairment and dementia.
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Across the conditions examined, the strongest and most consistent associations were between somatic diseases and global neuronal loss or brain atrophy, as well as cerebrovascular lesions. In contrast, associations between somatic diseases and amyloid or tau deposition were limited and inconsistent. The review found no systematic studies examining neuroinflammation or non-AD proteinopathies in relation to somatic diseases.
Overall, the available evidence suggests that systemic diseases may contribute to brain damage predominantly through non-AD mechanisms, particularly cerebrovascular injury and diffuse neuronal loss, rather than by directly driving the characteristic amyloid and tau pathology of AD. The authors emphasize that these processes may contribute to the complex combination of pathologies frequently underlying dementia in older adults.
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Source: Grande, G., Valletta, M., Gasparini, F., et al. Brain pathology in relation to somatic diseases: Exploring the body–brain crosstalk. Journal of Internal Medicine. 2026; 300(3): 223–237. Published: June 2, 2026. DOI: 10.1111/joim.70119.
Hypertension at 5 Months Postpartum in Women With Gestational Diabetes
Among 678 women with recent gestational diabetes mellitus, 26.4% developed hypertension by 5 months postpartum. Higher early-pregnancy weight and blood pressure, Black or mixed ethnicity, and gestational hypertension or pre-eclampsia were associated with increased risk. Postpartum hypertension was also associated with greater adiposity and dyslipidemia. The findings support structured postpartum screening for blood pressure and broader cardiometabolic risk after GDM.
KEY FINDINGS: Approximately one in four women with recent GDM developed hypertension by 5 months postpartum. Higher maternal weight and blood pressure early in pregnancy, as well as Black or mixed ethnicity, were associated with increased risk, while gestational hypertension or pre-eclampsia was also associated with postpartum hypertension. Women with postpartum hypertension had greater adiposity and more frequent dyslipidemia, highlighting the broader cardiometabolic abnormalities present after GDM. Because early-pregnancy characteristics provided only modest prediction, the findings support structured postpartum assessment that includes blood pressure and broader cardiometabolic risk evaluation rather than focusing solely on dysglycemia.
BACKGROUND: Gestational diabetes mellitus (GDM) is associated with an increased risk of later cardiometabolic disease, including hypertension. However, the occurrence and determinants of hypertension soon after pregnancy complicated by GDM have not been well defined. This prospective study evaluated the incidence and predictors of hypertension at 5 months postpartum and examined its relationship with other cardiometabolic abnormalities in women with recent GDM.
DETAILS: This single-center observational prospective cohort study was conducted at King's College Hospital, London, between September 2023 and January 2025. Women with GDM who received routine prenatal care at 12 weeks' gestation were invited for a postpartum assessment at approximately 5 months after delivery; women with chronic hypertension were excluded. The assessment included blood pressure, BMI, waist circumference, glucose status, lipid profile, and renal function. Hypertension was defined as systolic BP ≥ 130 mmHg, diastolic BP ≥ 80 mmHg, or receipt of antihypertensive treatment. Of 912 women with GDM invited for postpartum review, 696 (76.3%) attended. After excluding 18 women with chronic hypertension, 678 women constituted the study cohort. Follow-up occurred at a median of 5.1 (IQR, 4.4-6.7) months after birth.
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Among the 678 women with previous GDM, 179 (26.4%) developed hypertension at a median of 5.1 (IQR, 4.4-6.7) months postpartum. Women who subsequently developed hypertension had higher early-pregnancy weight and blood pressure. At 12 weeks' gestation, median weight was 79.3 kg versus 69.3 kg among women who remained normotensive, while median systolic BP was 121.8 versus 115.5 mmHg and median diastolic BP was 74.5 versus 70.3 mmHg, respectively. Obesity at this stage was also more frequent among women who later developed hypertension (50.3% vs 28.5%). Pregnancy hypertensive disorders were more common among women who developed postpartum hypertension. Gestational hypertension occurred in 8.4% versus 3.8%, and pre-eclampsia in 9.5% versus 1.8%, among women who developed postpartum hypertension compared with those who remained normotensive.
Multivariable analysis identified higher maternal age, Black or mixed ethnicity, higher weight, and higher systolic and diastolic BP at 12 weeks as predictors of postpartum hypertension. Black ethnicity was associated with an adjusted OR of 1.88 (95% CI, 1.19-3.00), mixed ethnicity with an adjusted OR of 2.75 (95% CI, 1.21-6.24), and weight ≥ 73 kg with an adjusted OR of 1.57 (95% CI, 1.04-2.38). Each 1-mmHg increase in systolic BP was associated with an adjusted OR of 1.04 (95% CI, 1.02-1.07), and each 1-mmHg increase in diastolic BP with an adjusted OR of 1.04 (95% CI, 1.00-1.07). Development of gestational hypertension or pre-eclampsia was associated with an adjusted OR of 3.00 (95% CI, 1.69-5.34).
At the postpartum assessment, women with hypertension had a median BMI of 30.1 (IQR, 26.7-36.8) kg/m² compared with 27.0 (IQR, 23.5-30.6) kg/m² among normotensive women. A waist-to-height ratio > 0.5 was present in 87.7% versus 69.1%, and dyslipidemia in 35.8% versus 24.4%, respectively. Dysglycemia and renal dysfunction did not differ significantly between the groups.
The prenatal prediction model had only modest discriminatory ability. The AUC was 0.723 (95% CI, 0.680-0.766) using characteristics available at 12 weeks and 0.739 (95% CI, 0.697-0.782) after adding gestational hypertension or pre-eclampsia. At a 20% false-positive rate, detection rates were 49.5% and 53.7%, respectively.
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Source: Gomez Fernández, C., Charakida, M., Moser, M., et al. Hypertension at 5 months postpartum in women with gestational diabetes. Ultrasound in Obstetrics & Gynecology. 2026; 68(2): 202-210. Published: July 17, 2026. DOI: 10.1002/uog.70291.
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