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Background: Type 2 diabetes mellitus (T2DM) and frailty are associated with functional decline in older population. Objective: To explore the individual response to a multimodal intervention on functional performance. Design: A cluster-randomised multicentre clinical trial. Setting: Outpatients in hospital or primary care. Subjects: 843 (77.83 years, 50.65% men) prefrail and frail individuals ≥70 years with T2DM. Methods: Participants were allocated to usual care group (UCG) or a multicomponent intervention group (IG): 16-week progressive resistance training, seven nutritional and diabetological educational sessions and achievement of glycated haemoglobin (7-8%) and blood pressure (<150 mmHg) targets. Functional performance was assessed with the Short Physical Performance Battery (SPPB) at 1 year. We used multivariate binomial and multinomial logistic regression models to explore the effect of the IG, and adherence on the outcomes studied, in several adjusted models. Results: 53.7% in the IG versus 38.0% in the UCG improved by at least 1 point in their SPPB score [OR (95% CI): 2.07 (1.43, 2.98), P value <0.001]. Age, SPPB score and number of frailty criteria met decreased the probability of improving the SPPB score. Factors associated with worsening were pertaining to IG (decreased), age, SPPB score and the number of frailty criteria (increased). An adherence ≥84% was needed to achieve benefits, reaching the peak in the probability of improving SPPB when this was ≥85% [OR(95%CI): 2.38 (1.29, 4.79), P value 0.014]. Conclusions: Factors predicting the likelihood of improvement in a multimodal programme in pre-frail and frail older adults with diabetes are age, basal SPPB score, the number of frailty criteria and adherence.

An altered amino acid metabolism has been described in frail older adults which may contribute to muscle loss and functional decline associated with frailty. In the present investigation, we compared circulating amino acid profiles of older adults with physical frailty and sarcopenia (PF&S, n = 94), frail/pre-frail older adults with type 2 diabetes mellitus (F-T2DM, n = 66), and robust non-diabetic controls (n = 40). Partial least squares discriminant analysis (PLS-DA) models were built to define the amino acid signatures associated with the different frailty phenotypes. PLS-DA allowed correct classification of participants with 78.2 ± 1.9% accuracy. Older adults with F-T2DM showed an amino acid profile characterized by higher levels of 3-methylhistidine, alanine, arginine, ethanolamine, and glutamic acid. PF&S and control participants were discriminated based on serum concentrations of aminoadipic acid, aspartate, citrulline, cystine, taurine, and tryptophan. These findings suggest that different types of frailty may be characterized by distinct metabolic perturbations. Amino acid profiling may therefore serve as a valuable tool for frailty biomarker discovery.

Background: Diabetes overtreatment is a frequent and major issue in older people with type 2 diabetes but its definition is often inconsistent and may be misleading. This critical review has aimed at examining the definitions of diabetes overtreatment in older people used in research studies. Methods: Studies addressing diabetes overtreatment in people aged 65 or older were identified by searching the PubMed database according to an extensive search equation. Results: Twenty-two research studies providing a definition of diabetes over-treatment in people aged were found. Overall, 12 different definitions of diabetes overtreatment were used. All studies defined overtreatment according to a HbA1c threshold (varying from <42 mmol/mol [<6.0%] to <64 mmol/mol [<8%]). Amongst them, 2 definitions had no consideration about glucose-lowering (GL)treatment, 6 required the prescribing of ≥1 GL agent(s), and 4 the prescribing of ≥1 GL agent(s) inducing the high risk of hypoglycaemia (i.e., sulfonylurea(s) or insulin(s)). Only 4 definitions (four studies) were individualised, using varying HbA 1c thresholds according to patients' age or health status. Conclusions: Definitions of diabetes overtreatment are heterogeneous across research studies, which is confusing. A standardised definition, based on the individual risk of hypoglycaemia and/or its complications must be promoted in order to bring clarity and greater insight into this field, as well as to improve the quality of management of diabetes in older patients