Frailty in Older Adults with Obesity and the Effect of Lifestyle Interventions

The prevalence of diabetes is increasing specially in older people due to increased life expectancy. In old age, frailty is an emerging new complication of diabetes. Diabetes and frailty appear to have a reciprocal relationship and may share a common pathogenic pathway. Frailty associated with diabetes is likely due to diabetes-related complications, diabetes-associated comorbidities and persistent dysglycaemia. The development of frailty will have significant consequences on diabetes. Frailty will accelerate the adverse outcomes associated with diabetes such as increased risk of cardiovascular events, hospitalisations and mortality. Furthermore, the development of frailty will have a metabolic effect on diabetes. Frail older people with diabetes will have a heterogenous metabolic spectrum, which starts from a sarcopenic obese (SO) phenotype at one end and an anorexic malnourished (AM) phenotype at the other end. The SO phenotype is associated with unfavourable metabolic profile, increased insulin resistance and accelerated diabetes trajectory. The AM phenotype is associated with significant weight loss, reduced insulin resistance and decelerated diabetes trajectory. As a result, metabolic phenotypes should be taken into consideration in the management of frail older people with diabetes. For example, in the SO phenotype early use of sodium glucose transporter-2 (SGLT-2) inhibitors and glucagon like peptide-1 receptor agonists (GLP-1RA) should be considered because of their weight losing properties and their favourable effect on the metabolic profile with a main focus on cardiovascular risk reduction. In the AM phenotype, early use of long-acting insulin analogues should be considered due to its weight gaining and anabolic properties with a main focus on quality of life. Adequate nutrition with high protein intake and exercise training is recommended in both phenotypes. Future research is needed to investigate the effect of glycaemic control on the risk of frailty and to explore novel hypoglycaemic agents with anti-frailty effect independent of glycaemic control