<p>Diabetes mellitus encompasses a spectrum of disorders unified by hyperglycaemia but diverse in aetiology, pathophysiology and clinical expression. Despite repeated efforts at refinement, current classification systems—most recently defined by the WHO—fail to fully capture the heterogeneity of diabetes, particularly in elderly. Recent cluster analyses reveal that diabetes is not a binary entity but a continuum of overlapping subtypes with distinct molecular and physiological signatures. Here, we propose SAGE-DM (Senescence-Associated Gluco-Endocrinopathy Diabetes Mellitus), a novel conceptual framework that extends the definition of so-called “type 4 diabetes.” SAGE-DM is characterised by insulin resistance and glucose dysregulation in lean or olders with sarcopenic obesity individuals, arising from endocrine senescence, chronic low-grade inflammation, and immune–metabolic crosstalk. Distinct from classical type 2 diabetes, SAGE-DM involves impaired beta-cells and alfa-cells function, altered insulin clearance, visceral fat redistribution, and immune alterations, such as adipose accumulation of regulatory T cells. Emerging data also implicate FGF-1 signalling and age-related hormonal declines—including adrenopause, andropause and somatopause—as contributors to its pathogenesis. Recognising SAGE-DM underscores the need for precision diagnosis in diabetes care, moving beyond the one-size-fits-all paradigm. Future research should focus on validating this construct, identifying specific biomarkers, and testing targeted interventions such as immune modulation and senotherapeutic strategies. By reframing diabetes through the lens of aging biology, SAGE-DM offers a new avenue for understanding and managing metabolic disease in the growing elderly population.</p>

错误:搜索内容不能为空,请输入英文关键词
错误:关键词超出字数限制,请精简
高级检索

SAGE-DM—Senescence-Associated Gluco-Endocrinopathy Diabetes Mellitus: comprehensive review

  • Michał Szklarz,
  • Katarzyna Wołos-Kłosowicz,
  • Julia Modzelewska,
  • Jan Górny,
  • Robert Modzelewski,
  • Wojciech Matuszewski

摘要

Diabetes mellitus encompasses a spectrum of disorders unified by hyperglycaemia but diverse in aetiology, pathophysiology and clinical expression. Despite repeated efforts at refinement, current classification systems—most recently defined by the WHO—fail to fully capture the heterogeneity of diabetes, particularly in elderly. Recent cluster analyses reveal that diabetes is not a binary entity but a continuum of overlapping subtypes with distinct molecular and physiological signatures. Here, we propose SAGE-DM (Senescence-Associated Gluco-Endocrinopathy Diabetes Mellitus), a novel conceptual framework that extends the definition of so-called “type 4 diabetes.” SAGE-DM is characterised by insulin resistance and glucose dysregulation in lean or olders with sarcopenic obesity individuals, arising from endocrine senescence, chronic low-grade inflammation, and immune–metabolic crosstalk. Distinct from classical type 2 diabetes, SAGE-DM involves impaired beta-cells and alfa-cells function, altered insulin clearance, visceral fat redistribution, and immune alterations, such as adipose accumulation of regulatory T cells. Emerging data also implicate FGF-1 signalling and age-related hormonal declines—including adrenopause, andropause and somatopause—as contributors to its pathogenesis. Recognising SAGE-DM underscores the need for precision diagnosis in diabetes care, moving beyond the one-size-fits-all paradigm. Future research should focus on validating this construct, identifying specific biomarkers, and testing targeted interventions such as immune modulation and senotherapeutic strategies. By reframing diabetes through the lens of aging biology, SAGE-DM offers a new avenue for understanding and managing metabolic disease in the growing elderly population.