Potential Triggers of Primary Hyperinsulinemia: Dietary Factors Excess refined carbs/protein, and overactive incretin hormones (GLP-1, GIP) overstimulate -cells -Cell Hyperactivity Some individuals inherently secrete more insulin due to genetics or nutrient-driven -cell expansion Lipid Overload Insulin drives fat storage, leading to increased intrahepatic and visceral fat, worsening insulin resistance Cortisol & Chronic Stress High cortisol raises blood sugar, triggering compensatory insulin secretion Gut Dysbiosis Increased endotoxins (LPS) from an imbalanced microbiome promote systemic inflammation and insulin resistance 3 The Likely Reality: A Bidirectional Cycle Rather than one causing the other, hyperinsulinemia and insulin resistance likely reinforce each other in a vicious cycle: 1 Primary Hyperinsulinemia (from genetics, diet, or other factors) Drives fat accumulation and insulin receptor downregulation Leads to insulin resistance 2 Insulin Resistance Forces -cells to produce more insulin Further exacerbates hyperinsulinemia 3 Chronic Metabolic Stress Worsens both insulin resistance and hyperinsulinemia over time This cycle explains why hyperinsulinemia often precedes obesity and diabetes in some individuals, while in others, it develops as a consequence of insulin resistance
Finally, the FlowJo software (Version 10.4, BD Biosciences, USA) was used to analyze the result with a gating strategy shown in Supplementary Fig
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The method of embodiment 83, wherein the internal radiation therapy is high dose rate internal radiation therapy
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