Metabolic Impact of Frailty Changes Diabetes Trajectory

Diabetes mellitus prevalence increases with increasing age. In older people with diabetes, frailty is a newly emerging and significant complication. Frailty induces body composition changes that influence the metabolic state and affect diabetes trajectory. Frailty appears to have a wide metabolic spectrum, which can present with an anorexic malnourished phenotype and a sarcopenic obese phenotype. The sarcopenic obese phenotype individuals have significant loss of muscle mass and increased visceral fat. This phenotype is characterised by increased insulin resistance and a synergistic increase in the cardiovascular risk more than that induced by obesity or sarcopenia alone. Therefore, in this phenotype, the trajectory of diabetes is accelerated, which needs further intensification of hypoglycaemic therapy and a focus on cardiovascular risk reduction. Anorexic malnourished individuals have significant weight loss and reduced insulin resistance. In this phenotype, the trajectory of diabetes is decelerated, which needs deintensification of hypoglycaemic therapy and a focus on symptom control and quality of life. In the sarcopenic obese phenotype, the early use of sodium-glucose transporter-2 inhibitors and glucagon-like peptide-1 receptor agonists is reasonable due to their weight loss and cardio-renal protection properties. In the malnourished anorexic phenotype, the early use of long-acting insulin analogues is reasonable due to their weight gain and anabolic properties, regimen simplicity and the convenience of once-daily administration.