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Clinical implications While there is no clearly defined subtype of metabolic frailty, the observation that lean older adults are especially vulnerable to aging-related illness has several clinical implications Assessment of in vivo endogenous insulin reserve (eg fasting or stimulated C-peptide) to assess the functional reserve of the pancreatic -cell, disproportionately decreased by insulin resistance Screen regularly for sarcopenia and frailty, both of which directly influence glucose disposal and metabolic resilience Attempt to avoid hypoglycaemia and overtreatment due to limited physiological reserve and counterregulation Focus on resistance exercise, protein intake, maintenance of muscle mass and functional status These considerations are consistent with principles of geriatric guidelines for diabetes but hold even greater mechanistic importance in the context of age-related decline in insulin secretory reserve and metabolic flexibility These considerations are of particular relevance to older adults with diabetes aged 65 years or older but should be interpreted with caution as biological heterogeneity is further increased beyond age 80 years A summary of the diagnostic and therapeutic procedure in SAGE-DM is presented in Fig

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Impaired methylation can lead to imbalanced levels of estrogen or buildup of estrogen metabolites [1].* Eliminating Heavy Metals and Toxins Methylation supports the transsulfuration pathway