Metabolic Characteristics of Frail Older People with Diabetes Mellitus-A Systematic Search for Phenotypes

Frailty in older people with diabetes is viewed as one homogeneous category. We previously suggested that frailty is not homogeneous and spans across a metabolic spectrum that starts with an anorexic malnourished (AM) frail phenotype and ends with a sarcopenic obese (SO) phenotype. We aimed to investigate the metabolic characteristics of frail older people with diabetes reported in the current literature to explore whether they fit into two distinctive metabolic phenotypes. We performed systematic review of studies published over the last 10 years and reported characteristics of frail older people with diabetes mellitus. A total of 25 studies were included in this systematic review. Fifteen studies reported frail patients' characteristics that could fit into an AM phenotype. This phenotype is characterised by low body weight, increased prevalence of malnutrition markers such as low serum albumin, low serum cholesterol, low Hb, low HbA1c, and increased risk of hypoglycaemia. Ten studies reported frail patients' characteristics that describe a SO phenotype. This phenotype is characterised by increased body weight, increased serum cholesterol, high HbA1c, and increased blood glucose levels. Due to significant weight loss in the AM phenotype, insulin resistance decreases, leading to a decelerated diabetes trajectory and reduced hypoglycaemic agent use or deintensification of therapy. On the other hand, in the SO phenotype, insulin resistance increases leading to accelerated diabetes trajectory and increased hypoglycaemic agent use or intensification of therapy. Current literature suggests that frailty is a metabolically heterogeneous condition that includes AM and SO phenotypes. Both phenotypes have metabolically distinctive features, which will have a different effect on diabetes trajectory. Therefore, clinical decision-making and future clinical studies should consider the metabolic heterogeneity of frailty.