Gestational diabetes mellitus (GDM) is characterized by an inadequate pancreatic β-cell response to pregnancy-induced insulin resistance, resulting in hyperglycemia. The pathophysiology involves reduced incretin hormone secretion and signaling, specifically decreased glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), impairing insulinotropic effects. Pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), impair insulin receptor substrate-1 (IRS-1) phosphorylation, disrupting insulin-mediated glucose uptake. β-cell dysfunction in GDM is associated with decreased pancreatic duodenal homeobox 1 (PDX1) expression, increased endoplasmic reticulum stress markers (CHOP, GRP78), and mitochondrial dysfunction leading to impaired ATP production and reduced glucose-stimulated insulin secretion. Excessive gestational weight gain exacerbates insulin resistance through hyperleptinemia, which downregulates insulin receptor expression via JAK/STAT signaling. Additionally, hypoadiponectinemia decreases AMP-activated protein kinase (AMPK) activation in skeletal muscle, impairing GLUT4 translocation. Placental hormones such as human placental lactogen (hPL) induce lipolysis, increasing circulating free fatty acids which activate protein kinase C, inhibiting insulin signaling. Placental 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) overactivity elevates cortisol levels, which activate glucocorticoid receptors to further reduce insulin sensitivity. GDM diagnostic thresholds (≥92 mg/dL fasting, ≥153 mg/dL post-load) are lower than type 2 diabetes to prevent fetal hyperinsulinemia and macrosomia. Management strategies focus on lifestyle modifications, including dietary carbohydrate restriction and exercise. Pharmacological interventions, such as insulin or metformin, aim to restore AMPK signaling and reduce hepatic glucose output. Emerging therapies, such as glucagon-like peptide-1 receptor (GLP-1R) agonists, show potential in improving glycemic control and reducing inflammation. A mechanistic understanding of GDM pathophysiology is essential for developing targeted therapeutic strategies to prevent both adverse pregnancy outcomes and the progression to overt diabetes in affected women.

Atypical eating disorder presentations challenge traditional diagnostic frameworks, leading to underdiagnosis and diagnostic delay, as each patient had prior clinical contacts in which eating disorder pathology went unrecognized. This study examines four cases highlighting unique risk factors, including high-performance athletics, trauma history, substance use, gender dysphoria, and environmental stressors. These patients were not identified as having eating disorders at initial clinical contact, as presenting complaints, including anxiety, alcohol use disorder, attention-deficit/hyperactivity disorder, and environmental stressors, obscured the underlying eating pathology. Athletes, particularly those in weight-class sports, may engage in restrictive eating while maintaining higher body weight, as seen in Case 1. Trauma history increases vulnerability, yet routine screening remains inadequate. Case 2 demonstrates the interplay between alcohol use disorder and binge-purge cycles, where substance use masked eating pathology. Gender dysphoria in Case 3 contributed to restrictive behaviors as a means of body modification, underscoring the importance of integrating gender-affirming care. Case 4 illustrates how environmental instability can drive disordered eating independent of body image concerns. These cases emphasize the necessity of broadening screening criteria and provider education to recognize atypical presentations. Addressing coexisting psychiatric conditions and social determinants of health is critical for early intervention and improved outcomes in patients with eating disorders.