The interplay between socio-psychological factors and biological systems is pivotal in defining human health and disease, particularly in chronic non-communicable diseases. Recent advancements in psychoneuroimmunology and mitochondrial psychobiology have emphasized the significance of psychological factors as critical determinants of disease onset, progression, recurrence, and severity. These insights align with evolutionary biology, psychology, and psychiatry, highlighting the inherent social nature of humans. This study proposes a theory that expands insulin’s role beyond traditional metabolic functions, incorporating it into the Mitochondrial Information Processing System (MIPS) and exploring it from an evolutionary medicine perspective to explore its function in processing psychological and social factors into biological responses. This narrative review comprises data from preclinical animal studies, longitudinal cohort studies, cross-sectional studies, machine learning analyses, and randomized controlled trials, and investigates the role of insulin in health and disease. The result is a proposal for a theoretical framework of insulin as a social substance within the socio-psycho-biological framework, emphasizing its extensive roles in health and disease. Type 2 Diabetes Mellitus (T2DM) with musculoskeletal disorders and neurodegeneration exemplifies this narrative. We suggest further research towards a comprehensive treatment protocol meeting evolutionary expectations, where incorporating psychosocial interventions plays an essential role. By supporting the concept of ‘insulin resilience’ and suggesting the use of heart rate variability to assess insulin resilience, we aim to provide an integrative approach to managing insulin levels and monitoring the effectiveness of interventions. This integrative strategy addresses broader socio-psychological factors, ultimately improving health outcomes for individuals with T2DM and musculoskeletal complications and neurodegeneration while providing new insights into the interplay between socio-psychological factors and biological systems in chronic diseases.
