To evaluate postpartum type 2 diabetes testing and classification using the revised 2022 American Diabetes Association (ADA) diagnostic criteria, in comparison with the American College of Obstetricians & Gynecologists' (ACOG) criteria, in women with gestational diabetes mellitus (GDM) across inpatient and outpatient testing settings. Secondarily, we aimed to evaluate whether the timing of administration of the screening test was associated with differences in results. This was a retrospective cohort study of patients with GDM who delivered at a single institution between 2023 and 2025. The traditional cohort (January-December 2023) was recommended an outpatient 75-g, 2-hour oral glucose tolerance test (OGTT). The hybrid cohort (June 2024-June 2025) was given the option of inpatient screening during the delivery hospitalization or outpatient testing. The primary outcome was OGTT completion. Secondary outcomes were diagnoses of glucose intolerance or diabetes. In January 2022, the ADA revised postpartum diagnostic criteria so that a diabetes diagnosis would require two abnormal values instead of a single abnormal OGTT value. The ACOG and 2022 ADA criteria were applied to OGTT results retrospectively to estimate their effect on postpartum diabetes classification. In a subgroup analysis, we examined whether the timing of postpartum OGTTs influenced the results. In the traditional cohort, 6,689 deliveries occurred; of these, 309 patients (4.6%) had GDM and met inclusion criteria. In the hybrid cohort, 6,312 deliveries occurred; of these, 276 (4.4%) patients met inclusion criteria. Rates of OGTT completion were higher in the hybrid cohort than in the traditional cohort (73.9% vs 31.7%, P <.001). Inpatient testing yielded higher rates of glucose intolerance (48.0%) and diabetes (15.4%) than outpatient testing in either cohort (traditional: 19.4% glucose intolerance and 4.1% diabetes; hybrid: 20.7% glucose intolerance and 3.4% diabetes). Application of the 2022 ADA criteria resulted in the reclassification of most ACOG-defined diabetes results as glucose intolerant (Bowker χ 2 =24, P <.001). In an adjusted multinomial regression that used ACOG criteria, inpatient testing was associated with glucose intolerance (adjusted odds ratio [aOR] 3.06; 95% CI, 1.57-5.97) and overt diabetes (aOR 4.65; 95% CI, 1.14-18.9) when compared with outpatient testing. Testing on postpartum day 1 relative to outpatient testing was associated with glucose intolerance (aOR 2.20; 95% CI, 1.36-3.57) and overt diabetes (aOR 3.92; 95% CI, 1.69-9.06), whereas testing on or after postpartum day 2 did not show a statistically significant association. Inpatient screening improves the rate of postpartum testing, but diagnostic classification varies widely by the criteria used (ACOG vs ADA) and test timing (postpartum day 1 vs 2), which underscores the need for national guidance on optimal timing and interpretation of postpartum OGTTs.

Latex-enhanced immunoturbidimetric assay of human HbA1c using a highly specific mouse anti-human monoclonal antibody (HbA1c-6C2).

Corticotropin-releasing hormone (CRH) induces an increase in growth hormone (GH) secretion in a subset of patients with acromegaly; however, the characteristics of these CRH responders remain poorly defined. 22 CRH responders were retrospectively compared with 43 nonresponders. CRH responders exhibited significantly larger tumors and more frequent visual field impairment than nonresponders, despite comparable baseline GH and insulin-like growth factor 1 (IGF-1) levels, and disease duration. Tumor volume and diameter were positively correlated with the GH increase ratio in CRH test, whereas GH and IGF-1 per tumor volume or diameter were significantly lower in CRH responders, indicating reduced GH secretory capacity relative to tumor size. Immunohistochemical analyses revealed higher corticotropin-releasing hormone receptor 1 (CRHR1) and lower CRHR2 expression in CRH responders. In addition, T-box transcription factor (TPIT) and adrenocorticotropic hormone (ACTH) expression were significantly more frequent in adenomas from CRH responders, suggesting a corticotroph-like phenotype. GH responses to CRH were significantly correlated with those to luteinizing hormone-releasing hormone but not thyrotropin-releasing hormone or oral glucose tolerance testing. GH responses to CRH tended to be inversely correlated with somatostatin receptor subtype 2 expression as a predictor of first-generation somatostatin receptor ligand efficacy but not with octreotide response or MRI signal intensity. These findings support that GH responsiveness to CRH identifies a biologically distinct subset of somatotroph adenomas characterized by corticotroph-like features, larger tumor size, and reduced GH secretory capacity. GH responsiveness to CRH may serve as a noninvasive indicator of intrinsic tumor biology and behavior.

Socioeconomic position and type 2 diabetes: The mediating role of physical work environment - the Maastricht study.

MRI-derived hepatic fat and its clinical correlates in non-transfusion-dependent thalassemia: a cross-sectional study.

To establish the rates of and variables associated with glycaemic disturbances in people with type 1 diabetes with a functioning pancreas transplant, and to quantify the association with graft failure. An observational study on routinely collected data from pancreas transplant recipients at University Hospital Wales from January 2013 to April 2019 with glucose tolerance test (GTT) data. Their variables were analysed to assess rates and risk factors for glycaemic disturbance. Of the 96 participants in this study, 30% developed glycaemic disturbance. Hyperglycaemia was twice as common as hypoglycaemia (22% vs. 10%). Recipients who developed hypoglycaemia were predominantly women (90% vs. 26% for those who developed hyperglycaemia, p = 0.001), had a lower mean BMI (23.7 vs. 27.6 kg/m2 for hyperglycaemic individuals, difference: 3.89, CI: 0.77-7.0, p = 0.017). There was no increase in graft failure rates for recipients with glycaemic disturbances (normoglycaemia: 12%, hypoglycaemia: 10%, hyperglycaemia: 4.8%, p = 0.70). Recipients with post-transplantation hypoglycaemia were more likely to be women and of low body weight, which may be due to disordered eating with restricted calorie or carbohydrate intake. Recipients with post-transplantation hyperglycaemia had features of insulin resistance and type 2 diabetes with increased weight and men predominance. Glycaemic disturbance was not associated with graft failure, suggesting it relates to insulin-glucose mismatch rather than rejection. Further follow-up is required to identify the long-term sequelae of glycaemic disturbance after pancreas transplants and if relevant dietary counselling has the potential to attenuate these disturbances.

This study evaluates whether continuous glucose monitoring (CGM) metrics predict adverse neonatal outcomes among individuals undergoing gestational diabetes screening. Building on findings by Fishel Bartal et al, who reported an association between ≥10% time above 140 mg/dL and a composite neonatal outcome, this analysis examines 13 additional CGM-derived measures reflecting glycemic variability (GV) and glycemic extremes. Eighty-four pregnant individuals wore CGM devices for 10 days following a 1-hour 50 g glucose challenge test. Generalized estimating equation logistic regression models assessed associations between CGM metrics and a composite neonatal outcome consisting of large-for-gestational-age birth, need for intravenous glucose treatment, or shoulder dystocia. Model discrimination was quantified using the area under the receiver operating characteristic curve (AUROC). Several CGM measures-including mean glucose, standard deviation (SD), maximum glucose, %Time >140 mg/dL, %Time >120 mg/dL, glucose management indicator (GMI), mean of daily differences (MODD), mean amplitude of glycemic excursions (MAGE), area under the CGM curve (AUC-CGM), and high blood glucose index (HBGI)-were significantly associated with adverse neonatal outcomes (P < .05). Metrics demonstrating higher discrimination than the original ≥10% time-above-range measure (AUROC = 0.643) included SD (0.656), MAGE (0.665), mean glucose (0.676), GMI (0.676), maximum glucose (0.683), %Time >120 mg/dL (0.683), AUC-CGM (0.692), HBGI (0.701), and %Time >140 mg/dL (0.703). Continuous glucose monitoring metrics reflecting sustained or high-level hyperglycemia, rather than GV-focused metrics, more strongly predicted adverse neonatal outcomes. These findings suggest that persistent or extreme maternal glucose elevations, rather than variability alone, may drive neonatal risk and support refining CGM-based screening approaches in pregnancy.

The impact of maternal gestational diabetes mellitus (GDM) and its glycemic subtypes on the early visual development of infants remains unclear. Based on the Jiangsu Birth Cohort, we included 2139 infants born to 2041 mothers recruited from 2014 to 2018. Maternal GDM was categorized into three categories based on oral glucose tolerance test results: impaired fasting glucose, impaired glucose tolerance, and comorbid impaired fasting glucose and impaired glucose tolerance. Infants' grating visual acuity was measured at 1 year of age using Teller Acuity Cards II. We used generalized estimating equation models to examine the association between maternal GDM and infant visual acuity, accounting for the dependence of twin observations. We then conducted a metabolomics analysis to explore the metabolic profiles associated with GDM and infant visual acuity. Prenatal GDM exposure was associated with a 70% increase in risk of abnormal visual acuity in infants (relative risks [RR] = 1.7; 95% confidence interval [CI] = 1.2, 2.3). The increased risks were more pronounced among infants in the comorbid impaired fasting glucose and impaired glucose tolerance group (RR = 3.2; 95% CI = 1.4, 7.7), followed by the impaired glucose tolerance group (RR = 1.8; 95% CI = 1.1, 3.0) and the impaired fasting glucose group (RR = 1.6; 95% CI = 0.7, 3.6), compared with unexposed infants. The metabolomics analysis suggested glycine, serine, and threonine metabolism as an enriched pathway and identified creatine as a metabolite of interest. Maternal GDM is associated with an increased risk of abnormal grating visual acuity in infants at 1 year of age. Glycine, serine, and threonine metabolism pathways may contribute to this association.

The appendicular skeletal muscle mass to visceral fat area ratio (SVR) reflects the interplay between muscle mass and fat distribution and is increasingly recognized as an indicator of metabolic health. However, its association with prediabetes remains unclear. Therefore, this study aimed to investigate the relationship between SVR and prediabetes. Data from 4195 participants in the 2011-2018 National Health and Nutrition Examination Survey (NHANES) were analysed using a cross-sectional design. Weighted logistic regression and restricted cubic splines (RCS) were applied to assess the association between SVR and prediabetes. The diagnostic performance of SVR versus body mass index (BMI) and muscle-to-fat ratio (MFR) was compared using weighted receiver operating characteristic curves. Mediation analysis was performed to explore potential indirect associations. Higher SVR was significantly associated with reduced risk of prediabetes (adjusted OR 0.24; 95% CI: 0.19-0.31). SVR exhibited a nonlinear relationship with prediabetes, with the inflection point of 0.334 kg/cm2 for males and 0.199 kg/cm2 for females. Notably, SVR demonstrated superior diagnostic performance compared to BMI and MFR, with an area under the curve of 0.653, 0.614 and 0.605 in males and 0.689, 0.651 and 0.619 in females, respectively. Moreover, SVR appeared to be more strongly associated with isolated impaired glucose tolerance than with isolated impaired fasting glucose, consistent with its stronger inverse association with 2-h oral glucose tolerance test glucose (β = -0.44, 95% CI: -0.52 to -0.36) than with fasting glucose (β = -0.12, 95% CI: -0.14 to -0.10). Mediation analysis indicated that homeostatic model assessment for insulin resistance explained 51.08% of the total association. SVR showed a significant nonlinear association with prediabetes, with gender-specific diagnostic thresholds. Moreover, it demonstrated superior diagnostic capability compared to BMI and MFR for identifying prediabetes.

Sleeve gastrectomy (SG) leads to substantial weight loss and improvement in type 2 diabetes, but the underlying mechanisms remain incompletely understood. Given that circulating ghrelin concentrations are reduced after SG, we hypothesized that lower ghrelin levels may contribute to enhanced insulin sensitivity and β-cell function after SG. This was a human, placebo-controlled, randomized, crossover study. We investigated the effect of elevating ghrelin by an intravenous ghrelin infusion on β-cell function and insulin sensitivity using the "Botnia-clamp" (intravenous glucose tolerance test combined with hyperinsulinemic-euglycemic clamp), compared with saline coinfusion. Twelve SG-operated [aged 51 ± 10.9 yr, BMI 32.1 ± 4.6 kg/m2 (means ± SD)], and 10 sex-, age-, and body mass index (BMI)-matched unoperated controls without diabetes were included. Outcomes were peripheral insulin sensitivity (M/I) and β-cell function, assessed as the disposition index (DI), calculated as first phase insulin secretion × M/I. Ghrelin infusion significantly reduced peripheral insulin sensitivity (M/I) by 25% following SG and 29% in controls compared with saline infusion. Beta-cell function was significantly impaired with a 37% and 29% reduced first phase insulin secretion, and a 49% and 48% reduction in DI, respectively. No group differences were observed. Ghrelin infusion impairs insulin sensitivity and β-cell function in individuals who have undergone SG as well as in matched control. However, the present findings do not provide evidence that the lower circulating ghrelin concentrations following SG are directly responsible for improvements, as it remains unclear whether this relationship reflects a simple and reversible mechanism.NEW & NOTEWORTHY In a randomized, placebo-controlled crossover study, intravenous ghrelin infusion impaired insulin sensitivity and β-cell function in individuals with previous sleeve gastrectomy as well as in matched controls. Ghrelin reduced peripheral insulin sensitivity by 25%-29% and decreased β-cell function (disposition index) by 48%-49%. These findings suggest that the postoperative reduction in circulating ghrelin following sleeve gastrectomy may contribute to improved glucose metabolism, while underscoring the complex role of ghrelin in human glucose homeostasis.

The 1-hour plasma glucose as a specific marker for early-phase insulin secretory defects in young adults with obesity.

Gestational diabetes mellitus (GDM) affects over 10% of pregnancies worldwide, leading to various maternal and neonatal complications. The American College of Obstetricians and Gynecologists (ACOG) recommends a two-step diagnostic approach using the Glucose Challenge Test (GCT) and the oral glucose tolerance test (OGTT), which can yield between 0 and 4 abnormal values (AbVs). The primary objective of this study was to evaluate the association between the number of AbVs in the OGTT and the risk of GDMA2 - gestational diabetes mellitus requiring pharmacological treatment (insulin or oral glucose-lowering agents) - compared with GDMA1, which is diet-controlled. Secondary outcomes included assessing the relationship between the number of AbVs and adverse maternal and neonatal outcomes, considering its impact on the course of pregnancy, delivery, maternal health, and neonatal outcomes. This retrospective cohort study included all pregnant women who underwent OGTT between the years 2015 and 2022, and diagnosed with GDM, at our department. The study cohort was divided into four groups based on the number of AbVs in the OGTT: one AbV, two AbVs, three AbVs and four AbVs group. Maternal characteristics and pregnancy outcomes were compared between these groups. A total of 1821 women diagnosed with GDM following the diagnostic OGTT were included in the analysis. The distribution of abnormal OGTT AbVs was as follows: one AbV (36.95%), two AbVs (43.71%), three AbVs (16.09%), and four AbVs (3.24%). Presence of GDMA2 varied significantly among groups (p < 0.001), with higher occurrence correlating with increased AbVs. Maternal outcomes differed across the AbV groups in induction of labor (p < 0.001), episiotomy (p = 0.006), and maternal composite outcomes (p = 0.011). Neonatal outcomes also differed across the AbV groups, with differences in gestational age at delivery (p = 0.007) and Apgar score < 7 (p = 0.021). Logistic regression adjusted for confounders revealed that the number of AbVs (aOR 1.2, 95% CI 1.01-1.42) and maternal BMI (aOR 1.07, 95% CI 1.05-1.1) were significantly associated with GDMA2. An elevated number AbVs indicates challenges in glycemic control through dietary measures alone, necessitating potential medical interventions. An increased number of AbVs in OGTT was associated with GDMA2 and induction of labor. Differences were also observed across groups in episiotomy rates and Apgar < 7, although Apgar < 7 did not show a consistent positive correlation with the number of AbVs. From the study results we can infer that OGTT serves not only as a diagnostic tool for GDM but also enables healthcare practitioners to enhance their awareness of potential adverse outcomes for both the mother and neonate through meticulous analysis of AbVs.

This study examined how insulin resistance and impaired insulin secretion are associated with hyperglucagonemia during oral glucose tolerance tests (OGTT) in type 2 diabetes mellitus (T2DM). A retrospective analysis included 247 patients with T2DM treated at Tianjin Medical University General Hospital from October 2022 to March 2025. All underwent a 75 g OGTT, with blood samples collected at 0, 0.5, 1, 2, and 3 hours for glucose, insulin, C-peptide, and glucagon measurement. Insulin resistance was assessed via homeostasis model assessment of insulin resistance (HomaIR) and C-peptide immunoreactivity insulin resistance (CPRIR), while insulin secretion was evaluated using C-peptide area under the curve (AUCcp), homeostasis model assessment of beta cell function (HomaB), first-phase and second-phase insulin secretion during OGTT (first PH and second PH). Generalized linear models and mediation analyses examined associations between glucagon levels and above indices. Model fitness and robustness were evaluated via residual diagnostics, Cook's distance, and bootstrapped CIs. Glucagon levels during the OGTT were significantly elevated in patients with severe insulin resistance (HomaIR Q3 and CPRIR Q1), even after adjusting for confounders. In contrast, groups with the poorest insulin secretion (AUCcp Q1, HomaB Q1, first PH Q1, and second PH Q1) did not show elevated glucagon levels compared with those with better secretion. Mediation analysis confirmed that neither AUCcp nor HomaB mediated the relationship between insulin resistance and glucagon levels. Residual diagnostics demonstrated a satisfactory model fit. Furthermore, sensitivity analyses, both by excluding influential points identified via Cook's distance and by applying bootstrapped CIs, yielded consistent results, thereby affirming the robustness of the model. In T2DM, impaired glucagon suppression during OGTT is associated with insulin resistance closely, highlighting insulin resistance as a key factor in alpha-cell dysfunction.

Diabetes mellitus is a progressive metabolic disorder broadly classified into insulin-deficient (type 1) and insulin-resistant (type 2) forms. Both forms ultimately lead to chronic hyperglycemia and pancreatic dysfunction, posing a major global health burden. Limitations associated with the long-term use of conventional antidiabetic drugs have encouraged investigation of plant-based treatments that may offer safer therapeutic benefits. Although Cinnamon species have traditionally been used to manage metabolic disorders, evidence from solvent-fraction studies demonstrating their antidiabetic efficacy remains limited. This study evaluated the antidiabetic activity of ethyl acetate fractions obtained from Cinnamomum tamala (Buch.-Ham.) T. Nees & C. H. Eberm. (CT) leaves and Cinnamomum verum J. Presl (CV) bark in streptozotocin (STZ)-induced diabetic Wistar rats. Acute oral toxicity was assessed according to OECD guideline 423. Diabetic rats were treated with the ethyl acetate fractions at doses of 150 and 200 mg/kg body weight for 28 days, with metformin (100 mg/kg) used as the standard drug. Body weight and fasting blood glucose levels were recorded, and the oral glucose tolerance test (OGTT) and pancreatic histopathology were used to assess antihyperglycemic efficacy and tissue-protective effects. Both fractions were safe up to 2,000 mg/kg. STZ-induced diabetic rats showed weight loss, hyperglycemia, impaired glucose metabolism, and pancreatic β-cell damage. Treatment with both fractions dose-dependently lowered fasting blood glucose and improved glucose tolerance. Cinnamomum verum at 200 mg/kg showed significant antihyperglycemic activity, although its effect remained lower than that of metformin. Histopathological findings suggested that high-dose ethyl acetate fractions preserved pancreatic structure and β-cell integrity. The ethyl acetate fractions of Cinnamomum tamala and Cinnamomum verum demonstrated notable antidiabetic effects by improving glycemic control and protecting pancreatic islets in STZ-induced diabetic rats, supporting their traditional use and potential as plant-based therapies.

Objective: To explore the predictive value of early-and mid-trimester glycolipid metabolic indicators for adverse pregnancy outcomes in pregnant women with normal glucose levels. Methods: A total of 12 457 pregnant women admitted to Yantai Yantaishan Hospital from January 2020 to December 2024 were retrospectively included. According to the occurrence of adverse pregnancy outcomes, they were divided into an adverse pregnancy outcome group (n=852) and a normal pregnancy outcome group (n=11 605). General data, pregnancy-related information, lipid profile, and fasting plasma glucose (FPG) in early pregnancy (gestational age≤14 weeks; T1), and oral glucose tolerance test (OGTT) results in the second trimester (24-28 weeks; T2) were compared between the two groups. The participants were randomly assigned to a training set (n=8 712) and a validation set (n=3 745) in a 7∶3 ratio. Multivariable logistic regression was applied in the training set to identify independent risk factors for adverse pregnancy outcomes, and a nomogram prediction model was constructed. The area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve were used to evaluate the discrimination, calibration, and clinical applicability of the model, respectively. Results: The overall age was (30.9±3.8) years, BMI was (22.77±2.12) kg/m², T1 FPG was (4.43±0.29) mmol/L, T2 FPG was (4.51±0.27) mmol/L, the second-trimester 1 h glucose was (8.54±0.43) mmol/L, and the second-trimester 2 h glucose was (7.10±0.54) mmol/L. Multivariable logistic regression analysis showed that age (OR=1.126, 95%CI: 1.080-1.175), history of adverse pregnancy outcomes (OR=2.080, 95%CI 1.023-4.232), ΔMAP (the change in mean arterial pressure from the first to the second trimester) (OR=1.162, 95%CI 1.124-1.202), the TG/HDL-C ratio (OR=18.849, 95%CI: 11.512-30.862), T1 FPG (OR=3.191, 95%CI 2.120-4.803), ΔFPG (T2 FPG-T1 FPG) (OR=1.154, 95%CI: 1.036-1.285), ΔT2(1 h-FPG) (T2 1 h glucose-FPG) (OR=3.427, 95%CI: 2.674-4.391), and ΔT2(2 h-FPG) (T2 2 h glucose-FPG) (OR=4.155, 95%CI: 3.306-5.221) were risk factors for adverse pregnancy outcomes (all P<0.05). The AUC of the nomogram was 0.902 (95%CI: 0.884-0.919) in the training set and 0.895 (95%CI: 0.877-0.913) in the validation set. The calibration curve showed good agreement between predicted and observed probabilities (Hosmer-Lemeshow test: training set, P=0.708; validation set, P=0.102), and decision curve analysis indicated a net clinical benefit over a threshold probability range of 0.05 to 0.95. Conclusions: Age, history of adverse pregnancy outcomes, ΔMAP, the TG/HDL-C ratio, and dglycemic dynamic indicators during early and mid-trimester are independent predictors of adverse pregnancy outcomes in pregnant women with normal perinatal glucose levels. The nomogram constructed based on these factors demonstrates good discrimination, calibration, and clinical utility, and can serve as a quantitative tool for early risk identification in this population.

Ambient PM2.5 exposure and gestational diabetes mellitus: Evidence from an instrumental variable analysis in a prospective birth cohort study in China.

One-hour postload plasma glucose (1h-PG) is an early marker of dysglycemia in adults, but its utility in children and adolescents is uncertain because insulin sensitivity changes during growth and puberty. We aimed to establish age- and pubertal stage-specific 1h-PG thresholds for identifying prediabetes and Type 2 diabetes (T2D) in children with overweight or obesity. In this cross-sectional study, 4344 children and adolescents with overweight or obesity underwent an oral glucose tolerance test. Participants were classified into four groups: normal glucose tolerance (NGT) with normal 1 h-PG, NGT with elevated 1 h-PG, prediabetes and T2D. Insulin resistance and β-cell function indices were assessed. Participants were stratified by chronological age and pubertal stage. The optimal 1h-PG cut-offs were obtained via receiver operating characteristic (ROC) and age- and pubertal stage-based thresholds were compared for diagnostic performance. These thresholds were then validated in two independent cohorts. Among individuals with NGT, those with elevated 1h-PG exhibited greater insulin resistance, impaired β-cell function and a higher insulin area under the curve (29 916 vs. 23 524, p < 0.001). 1 h-PG levels increased with pubertal progression. Pubertal stage-specific thresholds showed superior discrimination compared with age-based stratification and adult cut-offs. Compared with adult thresholds (8.6 mmol/L for prediabetes and 11.6 mmol/L for T2D), a prepubertal cut-off of 7.78 mmol/L improved sensitivity for prediabetes (75.40% vs. 56.68%) and a pubertal cut-off of 10.48 mmol/L improved sensitivity for T2D (89.47% vs. 73.68%). Elevated 1h-PG proved to be a practical marker for identifying early metabolic dysfunction in children and adolescents with euglycemia. Given that widely used adult-derived cut-offs (8.6 and 11.6 mmol/L) are suboptimal for pediatric populations, we established pubertal stage-specific thresholds that outperformed both age-specific and adult-derived cut-offs. These stage-specific thresholds may serve as an effective screening tool for diabetes risk in children and adolescents with overweight or obesity.

Insulinoma is a functional pancreatic neuroendocrine tumor that usually causes fasting hypoglycemia through inappropriate autonomous insulin secretion. However, some insulinomas show postprandial or stimulus-induced hypoglycemia, suggesting that some tumors retain the ability to respond to physiological stimuli. We examined four patients with confirmed insulinoma who showed different clinical patterns of hypoglycemia and integrated clinical stimulation tests with DNA microarray analysis. Insulin secretory dynamics were assessed using an oral glucose tolerance test, meal tolerance test, and glucagon stimulation test, as clinically indicated. Among the four cases, Case 1 showed no clear fasting hypoglycemia but developed hypoglycemia after meals and oral glucose loading, accompanied by marked insulin secretion. In this case, insulin or C-peptide increased markedly after glucose, meal, and glucagon stimulation. In contrast, the other three cases showed relatively weak insulin secretory responses to stimulation. During the fasting test, Cases 3 and 4 developed hypoglycemia early, whereas Case 2 showed a prolonged time to hypoglycemia. Transcriptomic analysis showed that, by hierarchical clustering, Case 1 was clearly separated from Cases 3 and 4, whereas Case 2 was relatively close to Case 1. Case 1 showed relatively preserved expression of genes involved in glucose sensing, ATP-sensitive potassium channel function, incretin/cAMP signaling, exocytosis, and β-cell differentiation. In contrast, cases with predominant fasting hypoglycemia showed higher expression of hexokinase 1 and stress-response genes. These findings suggest that clinical heterogeneity in insulinoma may reflect differences in β-cell-like stimulus-response mechanisms, glucose sensing, stress responses, and differentiation status.

Introduction Carney complex (CNC) is a rare autosomal dominant syndrome characterized by multiple endocrine and non-endocrine tumors. In childhood, Cushing’s syndrome due to primary pigmented nodular adrenocortical disease (PPNAD) may occur, while growth hormone (GH) hypersecretion before puberty is exceptionally rare. Case presentation A 5-year-old girl presented with rapid weight gain, facial changes, hypertension, hypokalemic alkalosis, and kidney stones. Biochemical evaluation confirmed ACTH-independent Cushing’s syndrome, and abdominal magnetic resonance imaging (MRI) revealed bilateral adrenal nodules consistent with PPNAD. Family history of endocrine tumors and cardiac myxomas suggested CNC, subsequently confirmed by genetic testing showing a mutation of the PRKAR1A gene in both the patient and her father. Bilateral adrenalectomy resolved hypercortisolism. At 8.6 years, the patient showed an accelerated growth velocity (+2.48 SDS) with elevated IGF-1 levels and lack of GH suppression during an oral glucose tolerance testing, despite a normal pituitary MRI. She remained asymptomatic apart from growth acceleration, which was carefully monitored during follow-up. Over 18 months accelerated growth persisted with pubertal progression, but IGF-1 levels eventually normalized and brain MRI remained stable; therefore, treatment for GH excess was deferred. Conclusions This case highlights the importance of considering CNC in pediatric ACTH-independent Cushing’s syndrome and underlines the role of genetic testing. It also demonstrates that GH hypersecretion may emerge earlier than current screening recommendations, underscoring the need for surveillance starting at the onset of puberty.

Polycystic ovary syndrome (PCOS) has been associated with adverse pregnancy outcomes, although reported risks vary across studies. Metabolic heterogeneity within PCOS may contribute to this variability. Dysglycemia during pregnancy may identify a subgroup at increased obstetric risk. The study aims to evaluate whether dysglycemia is associated with preeclampsia and other adverse pregnancy outcomes among individuals with PCOS. We performed a secondary analysis of the prospective Fatty Liver in Pregnancy (FLIP) cohort (n = 1,321). PCOS was defined by chart review of the electronic health record. Dysglycemia was defined as current or prior gestational diabetes, abnormal glucose tolerance testing, hemoglobin A1c > 5.7% during pregnancy, or pregestational diabetes. Participants were categorized as PCOS with dysglycemia (n = 36), PCOS without dysglycemia (n = 44), or non-PCOS controls (n = 1,238). The primary outcome was preeclampsia. Secondary outcomes included gestational hypertension, preterm birth, abnormal neonatal weight, and neonatal hypoglycemia. Multivariable logistic regression adjusted for maternal age and body mass index. Among 80 individuals with PCOS, 45% had evidence of dysglycemia. Preeclampsia occurred in 33% of those with PCOS and dysglycemia, 7% of those with PCOS without dysglycemia, and 12% of controls (p = 0.005 for PCOS with dysglycemia versus controls). In adjusted analyses, PCOS with dysglycemia was associated with preeclampsia (odds ratio [OR] 2.9; 95% confidence interval [CI]: 1.4-6.1), whereas PCOS without dysglycemia was not (adjusted odds ratio [aOR] 0.53; 95% CI: 0.16-1.73). PCOS with dysglycemia was also associated with increased preterm birth (OR: 2.3; 95% CI: 1.04-5.14), abnormal neonatal weight (OR: 2.87; 95% CI: 1.36-6.10), neonatal hypoglycemia (OR: 2.8; 95% CI: 1.38-5.77), and any adverse pregnancy outcome (aOR: 4.49; 95% CI: 1.94-10.40). In this prospective cohort, dysglycemia was associated with higher rates of hypertensive and metabolic pregnancy complications among individuals with PCOS. These findings suggest that coexisting dysglycemia may contribute to heterogeneity in obstetric risk among individuals with PCOS and warrant confirmation in larger studies.