Hypoglycaemic therapy in frail older people with type 2 diabetes mellitus—a choice determined by metabolic phenotype

Abstract

Frailty is a newly emerging complication of diabetes in older people and increasingly recognised in national and international clinical guidelines. However, frailty remains less clearly defined and frail older people with diabetes are rarely characterised. The general recommendation of clinical guidelines is to aim for a relaxed glycaemic control, mainly to avoid hypoglycaemia, in this often-vulnerable group of patients. With increasing age and development of frailty, body composition changes are characterised by an increase in visceral adipose tissue and a decrease in body muscle mass. Depending on the overall body weight, differential loss of muscle fibre types and body adipose/muscle tissue ratio, the presence of any associated frailty can be seen as a spectrum of metabolic phenotypes that vary in insulin resistance of which we have defined two specific phenotypes. The sarcopenic obese (SO) frail phenotype with increased visceral fat and increased insulin resistance on one side of spectrum and the anorexic malnourished (AM) frail phenotype with significant muscle loss and reduced insulin resistance on the other. In view of these varying metabolic phenotypes, the choice of hypoglycaemic therapy, glycaemic targets and overall goals of therapy are likely to be different. In the SO phenotype, weight-limiting hypoglycaemic agents, especially the new agents of GLP-1RA and SGLT-2 inhibitors, should be considered early on in therapy due to their benefits on weight reduction and ability to achieve tight glycaemic control where the focus will be on the reduction of cardiovascular risk. In the AM phenotype, weight-neutral agents or insulin therapy should be considered early on due to their benefits of limiting further weight loss and the possible anabolic effects of insulin. Here, the goals of therapy will be a combination of relaxed glycaemic control and avoidance of hypoglycaemia; and the focus will be on maintenance of a good quality of life. Future research is still required to develop novel hypoglycaemic agents with a positive effect on body composition in frailty and improvements in clinical outcomes.

Metabolic Impact of Frailty Changes Diabetes Trajectory

“…Clinical guidelines are focused on function and recommend tighter targets in functionally independent and relaxed goals in those with poor function [ 107 , 108 , 109 ]. However, SO frail phenotype patients are likely to benefit from the new therapy based on their metabolic profile rather than their function [ 110 ]. In addition, the cardio–renal protective effects occur early in treatment and are not related to HbA1c levels, suggesting that this frail phenotype will still benefit, even if they do not have a long life expectancy [ 105 ].…”

Vascular frailty, a proposal for new frailty type: A narrative review

“…With our understanding of physical frailty becoming deeper, reclassification of the frailty construct can help researchers and clinicians identify and manage relevant degenerative syndromes on time. For example, researchers recently proposed to divide frailty into two subtypes: the sarcopenic obese phenotype and the anorexic malnourished phenotype 55 . This reclassification guides the use of different hypoglycemic treatments and therapeutic goals.…”

“…For example, researchers recently proposed to divide frailty into two subtypes: the sarcopenic obese phenotype and the anorexic malnourished phenotype. 55 This reclassification guides the use of different hypoglycemic treatments and therapeutic goals. Along the same line, an organ and vital function-directed phenotype also exists.…”

Various clinical efficacy of sodium-glucose co-transporter-2 inhibitor (SGLT2i) to sarcopenia, muscle mass and function

“…On the other hand, the problems of aging and sarcopenia related to diabetes are now attracting attention. 6 . Various debates have been found about the relationship between SGLT2i and sarcopenia.…”