Metabolic phenotypes explain the relationship between dysglycaemia and frailty in older people with type 2 diabetes

Dysglycaemia (hyperglycaemia and hypoglycaemia) increase the risk of frailty in older people with diabetes, which appears contradictory. However, the characteristics of patients included in these studies are different and may reflect different metabolic phenotypes of frailty that may explain this apparent contradiction.

To review the characteristics of frail patients included in clinical studies that reported an association between dysglycaemia and frailty in order to explore whether there is any metabolic differences in the profile of these patients.

A systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. Key words around older people, type 2 diabetes mellitus, frailty, hyperglycaemia and low glycaemia were used in the literature search.

Only 8 studies met the inclusion criteria. Four studies investigated the risk of frailty associated with low glycaemia. Two studies showed that hypoglycaemia increased the risk of frailty by 44% (HR 1.60, 95% CI 1.14 to 2.42) and predicted greater level of dependency (p < 0.001), respectively. The other two studies reported that HbA1c inversely correlated with clinical frailty scale (r = -0.31, p < 0.01) and HbA1c < 6.0% was associated with increased risk of disability (3.45, 1.02 to 11.6), respectively. Compared with non-frail patients, those with frailty tended to have lower body weight or body mass index (BMI), have features of malnutrition such as low serum albumin or low total cholesterol and suffer from more comorbidities including dementia. Four studies explored the association of high glycaemia with frailty. Higher HbA1c predicted frailty (OR 1.43, 95% CI 1.045 to 1.97) and positively correlated with Edmonton frail score (r = 0.44, p < 0.001), respectively in two studies. The other two studies found that subjects with HbA1c ≥ 6.5% had the greatest prevalence of frailty (70.3%) and subjects with higher HbA1c at baseline to have a higher frailty level throughout later life, respectively. Compared with non-frail patients, those with frailty tended to have higher body weight, waist circumference and BMI. They also have less physical activity, higher cholesterol level and have more comorbidities.

Dysglycaemia increases the risk of frailty but the characteristics of patients in these studies suggest different metabolic phenotypes of frailty. Therefore, these metabolic differences in frailty should be taken into consideration in the management of older people with diabetes.