Mothers with diabetes using insulin may nurse their infants. Exogenous insulin is excreted into breastmilk, including newer biosynthetic insulins (e.g., aspart, deglutec, detemir, glargine glulisine, lispro). Even direct administration of recombinant insulin orally to preterm infants is safe.[1] Insulin is a normal component of breastmilk and may decrease the risk of type 1 diabetes in breastfed infants.[2-5] Women taking insulin for type 2 diabetes have higher milk insulin levels than those controlled with diet alone.[6] Insulin requirements are reduced postpartum in women with type 1 diabetes,[7,8] although postpartum insulin requirements do not significantly differ between breastfeeding and non-breastfeeding women.[9] In general, insulin requirements are 30% to 50% lower than prepregnancy dosages immediately postpartum. Then the insulin requirements during breastfeeding average 21% lower than prepregnancy dosages, but there is wide variation.[8,10] In one study, insulin requirements were lower than prepregnancy dosage only during the first week postpartum: 54% of prepregnancy dosage on day 2 and 73% on day 3 postpartum. On day 7 postpartum, insulin dosage returned to prepregnancy requirements.[11] Another study found that dosage requirements did not return to normal for up to 6 weeks in some mothers.[12] A third study found that at 4 months postpartum, patients with type 1 diabetes who exclusively breastfed had an average of 13% lower (range -52% to +40%) insulin requirement than their prepregnancy requirement.[13] A retrospective case-control study found a 34% decrease in postpartum insulin requirement compare to preconception values. There was a nonsignificant trend towards lower requirements in exclusively breastfeeding mothers compared to partial or full formula feeding.[6] A small study found that mothers on insulin pumps were found to have an average basal insulin rates 14% lower and carbohydrate-to-insulin ratios were 10% higher than pre-pregnancy settings.[14] Breastfeeding appears to improve glucose postpartum glucose tolerance in mothers with gestational diabetes mellitus and in normal women.[15-17] A small, well-controlled study of women with type 1 diabetes mellitus using continuous subcutaneous insulin found that the average basal insulin requirement in women with type 1 diabetes who breastfed was 0.21 units/kg daily and the total insulin requirement was 0.56 units/kg daily. In similar women who did not breastfeed, the basal insulin requirement was 0.33 units/kg daily and the total insulin requirement was 0.75 units/kg daily. The 36% lower basal insulin requirement was thought to be caused by glucose use for milk production.[18] Lactation onset occurs later in patients with type 1 diabetes than in women without diabetes, with a greater delay in mothers with poor glucose control.[11,19] Mothers with type 1 diabetes also discontinue nursing at a higher rate during the first week postpartum.[20-22] Women with any form of diabetes during pregnancy had more problems with low milk supply than women without diabetes.[23] Once established, lactation persists as long in mothers with diabetes as in mothers without diabetes.[19,24] However, as in women without diabetes, smoking has a strong negative impact on lactation among mothers with type 1 diabetes.[13,25] Other factors that have been identified as causes of shorter duration of breastfeeding among type 1 diabetic patients are more frequent caesarean sections and earlier delivery.[26] Among patients with gestational diabetes, those treated with insulin have a delayed onset of lactogenesis II and lower exclusive breastfeeding rates compared to those not treated with insulin.[27,28]

Background: Fasting-mimicking diets (FMDs) induce metabolic changes associated with immunomodulation in preclinical studies, yet little is known about the effects of FMD on the human circulating immune system. Methods: In the single-arm FIND pilot study (NCT04833439), six of nine healthy participants completed two cycles of a 4-day FMD separated by 3 weeks of regular diet in a repeated-measures design. Blood samples were collected at baseline, after an overnight fast, and the morning after completion of the second FMD cycle. Peripheral blood mononuclear cells (PBMCs) were analyzed by transcriptomic profiling and spectral flow cytometry. Results: FMD was associated with reduced plasma glucose and insulin-like growth factor-1 and increased ketone levels. Transcriptomic analysis showed increased expression of genes involved in the TNFα, IFNγ and IFNα signaling pathway after two FMD cycles. Fifteen of the 39 leading-edge genes of the TNFα signature that have previously been associated with myeloid activity and rapid stress responses corresponded with the increased frequencies of circulating CD14-CD11b-CD11c+ dendritic cells (DCs), CD123+ plasmacytoid DCs, and CD14+ CD16+ intermediate monocytes. Moreover, the frequencies of HLA-DR-expressing CD4+ and CD8+ T-cells increased (p < 0.05) after two FMD cycles. Conclusions: In healthy volunteers, two cycles of FMD were associated with metabolic changes and alterations in circulating myeloid and T-cell populations consistent with activation of selected inflammatory pathways. These exploratory findings warrant larger validation studies in healthy volunteers in combination with functional analyses.

Insulin edema syndrome is a rare and underrecognized complication of insulin initiation or intensification, characterized by peripheral or generalized edema. Its pathophysiology is multifactorial, involving renal salt retention, increased capillary permeability, and vasodilation, and it is often a diagnosis of exclusion. We report the case of a 41-year-old man with newly diagnosed type 2 diabetes mellitus presenting with hyperglycemia (772 mg/dL) and marked weight loss. After initiation of insulin glargine and lispro, he developed rapid-onset generalized edema, including scrotal and lower extremity swelling, weight gain of 32 pounds, dyspnea, and pleural effusions. An extensive workup excluded cardiac, renal, hepatic, infectious, autoimmune, and protein-losing enteropathy etiologies. The edema worsened with higher insulin doses despite treatment with diuretics and corticosteroids. Transition to NPH (neutral protamine Hagedorn) and regular insulin, with adjunct dapagliflozin, resulted in rapid resolution of the edema, allowing discontinuation of the diuretics. Risk factors for insulin edema include newly diagnosed diabetes, rapid glycemic correction, low body weight, and high insulin doses. While generally self-limiting, severe or refractory cases may require diuretics or modification of the insulin regimen. Recognition is critical to avoid unnecessary interventions and to manage symptoms effectively. Insulin edema syndrome should be considered in patients presenting with unexplained edema after insulin initiation. Dose adjustment or switching insulin analogs, combined with supportive management, can lead to rapid improvement. Awareness of this condition may help prevent misdiagnosis and unnecessary invasive procedures.

Islet amyloid deposition derived from human islet amyloid polypeptide (hIAPP, amylin) is a hallmark of type 2 diabetes (T2D) and is tightly linked to progressive β-cell dysfunction and loss. It is now well established that the "toxic oligomer" hypothesis, in which soluble or intracellular hIAPP assemblies contribute to β-cell proteotoxicity and to the amplification of inflammatory stress, coexists with fibril associated and inflammation-driven mechanisms of toxicity. Regular physical activity (PA) is a cornerstone of T2D management and improves insulin sensitivity, glycemic control, ectopic lipid handling, and systemic inflammation, all of which could reduce β-cell secretory burden and the cellular milieu that favors hIAPP misfolding. However, direct demonstrations that PA delays or reduces islet amyloid formation remain scarce. This gap largely reflects methodological constrains in quantifying amyloid dynamics in humans and the absence of exercise studies with amyloid-specific endpoints. Herein, we synthesize mechanistic links by which exercise could influence hIAPP aggregation propensity (β-cell workload, glucolipotoxicity, endoplasmic reticulum stress, mitochondrial function, and inflammatory signaling) and highlight proteostasis pathways, particularly autophagy/lysosomal clearance, which are experimentally shown to defend β-cells against hIAPP oligomer toxicity. Overall, while direct evidence remains sparse, substantial mechanistic plausibility supports a link between PA and hIAPP amyloid biology. Future studies incorporating amyloid-specific outcomes are needed to determine whether exercise directly modifies amyloid formation, reduces oligomer burden, or primarily enhances β-cell resilience to proteotoxic stress.

This retrospective real-world cohort study evaluated the effectiveness and safety of recombinant human growth hormone therapy in Chinese children with Noonan syndrome, with a predefined comparison between short-acting growth hormone and long-acting growth hormone during the first 2 years of treatment. Twenty children with Noonan syndrome were included; 16 were boys, and the median age at recombinant human growth hormone initiation was 5.55 years. The baseline height standard deviation score was-3.01. During the first 2 years, 10 patients received short-acting growth hormone and 10 patients received long-acting growth hormone. The median height standard deviation score increased to-2.20 after 1 year and-1.84 after 2 years, with significant longitudinal improvement over time. The cumulative change in height standard deviation score did not differ significantly between short-acting growth hormone and long-acting growth hormone at year 1 (0.58 vs. 0.71) or year 2 (1.01 vs. 1.30). First-year growth velocity was comparable between groups, whereas the apparent second-year difference was no longer significant after excluding short-acting growth hormone-treated patients who entered puberty and received adjunctive therapy. Among 16 patients with PTPN11 variants, the median cumulative change in height standard deviation score was 1.20 and 56.3% achieved an HtSDS of above-2 standard deviation score at the last follow-up. No diabetes mellitus, malignancy, new cardiovascular events, intracranial hypertension, or slipped capital femoral epiphysis occurred. Insulin-like growth factor-1 standard deviation score elevations were transient. Recombinant human growth hormone therapy was associated with sustained linear growth in children with Noonan syndrome, and short-acting growth hormone and long-acting growth hormone showed broadly comparable short-term efficacy under regular safety monitoring.

MicroRNAs (miRNAs) are key components in the interaction between lifestyle-related risk factors and cancer development. In particular, miR-1303 expression is deregulated in breast cancer tissues, with elevated levels associated with poor prognosis. We have previously shown that regular exercise reduces the expression of this miRNA in skeletal muscle. The present pilot study aimed to evaluate the impact of lifelong football training on circulating miR-1303 expression and miR-1303 modulation on proliferation, migration, and invasion pathways in human breast cancer MCF-7 cells.

Background: Growth hormone deficiency (GHD) may result from structural abnormalities or space-occupying lesions of the pituitary gland; therefore, pituitary magnetic resonance imaging (MRI) is routinely performed as part of the etiological assessment. The reported prevalence of incidentally detected pituitary neuroendocrine tumors (PitNETs) in pediatric patients with GHD ranges from 0.5% to 20.3% across studies. PitNETs are rare in childhood and account for approximately 2.7% of supratentorial pediatric tumors and 3.6-6% of surgically treated PitNETs. Insulin-like growth factor-1 (IGF-I), a mitogenic agent elevated during recombinant human growth hormone (rhGH) therapy, has raised theoretical concerns regarding tumor growth stimulation. Objective: To evaluate longitudinal changes in tumor size of nonfunctional PiNETs, in patients with pre-existing PitNETs receiving rhGH therapy compared with untreated controls. Methods: This single-center retrospective cohort study included 15 GHD patients with PitNETs detected before rhGH initiation and 30 control patients with nonfunctional incidental PitNETs who did not receive rhGH therapy. Radiological follow-up was performed at baseline and at 6, 12, 18, 24, and 36 months. Results: No significant longitudinal changes in PitNETs width or length were observed in either group. One rhGH-treated patient underwent PitNET excision. Indications for pituitary imaging in the control group were predominantly central precocious puberty, headache, central hypothyroidism, and short stature. Conclusion: RhGH therapy was not associated with significant progression of nonfunctional PitNETs during a 36-month follow-up, supporting its safety when accompanied by regular radiological surveillance.

U-500 regular insulin use in automated insulin delivery systems (AIDs) is off-label and minimally studied. In this four-individual cohort, HbA1c remained stable, time below range stayed low, and no diabetic ketoacidosis or severe hypoglycemia occurred, despite lower TIR. These findings provide early clinical experience to inform cautious, individualized off-label use.

Male infertility refers to the inability of a male partner to contribute to pregnancy after 12 months or more of regular unprotected intercourse. It is frequently associated with impaired spermatogenesis, and many cases cannot be completely explained by genetic, inflammatory, endocrine, or environmental factors. Trimethylamine N-oxide (TMAO) is generated when gut bacteria convert dietary choline, L-carnitine, and betaine into trimethylamine (TMA), which is oxidized in the liver mainly by flavin-containing monooxygenase 3 (FMO3). This focused review evaluates current evidence on TMAO and impaired spermatogenesis within the gut-testis axis. The rationale is biologically plausible because sperm motility depends on coordinated glycolytic and mitochondrial energy metabolism, whereas Leydig cell steroidogenesis depends on mitochondrial cholesterol transport and redox balance. Human observational studies associate TMAO with asthenozoospermia and Leydig cell-related markers, particularly insulin-like peptide 3 (INSL3), while mouse studies suggest testicular injury and reduced spermatogenesis after TMAO-related exposure. The Hippo/Yes-associated protein (YAP)-mitochondria-steroidogenic acute regulatory protein (StAR) axis has been proposed as one possible mechanism, but direct reproductive tract exposure, blood-testis barrier kinetics, and human validation remain unresolved. Overall, TMAO should be considered as a candidate metabolic mediator and not a proven causal factor or therapeutic target in male infertility.