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Category From the literature

An Evaluation of Multimodal Interventions for Co-morbid Frailty and Type 2 Diabetes Mellitus

It is estimated that 1 in 5 adults aged over 65 present with type 2 diabetes mellitus (T2DM), a statistic which is projected to double over the next 20 years. Importantly, the pathological interplay between T2DM and frailty exacerbates functional decline in older populations. While lifestyle interventions centred on physical activity and nutrition have shown promise in managing both conditions, preliminary findings in older T2DM patients highlight a significant non-response rate. Behavioural interventions’ ability to enhance physical function among frail older adults with T2DM, however, remains inadequately investigated. This study aims to assess individual responses to a structured multimodal intervention on functional performance through a cluster-randomised multicentre clinical trial enrolling 843 prefrail and frail individuals aged ≥70 years with T2DM. Participants were randomised into usual care control or multimodal intervention groups, which included 16-week progressive resistance training, seven nutritional and diabetological educational sessions, and achieving glycated haemoglobin (7–8%) and blood pressure (<150 mmHg) targets.

Assessing the Clinical Relevance of the C-Reactive Protein-Triglyceride-Glucose Index in Cancer Cachexia

Cancer cachexia (CC) is a multifaceted syndrome characterised by declines in appetite, weight, and skeletal muscle which induce fatigue, increased treatment-related toxicity, reduced quality of life, and poor survival rates. CC’s progression involves metabolic disturbances, e.g. alterations in carbohydrate, lipid, and protein metabolism, combined with increased anorexia, insulin resistance (IR), and muscle protein breakdown. The C-reactive protein (CRP)-triglyceride-glucose (TyG) index (CTI), reflecting inflammation and IR levels, is associated with poor cancer prognosis and tumour recurrence. Despite the close association between systemic inflammation, IR, and CC, the CTI remains to be clinically validated in CC patients.

Cancer Cachexia: Molecular Mechanisms and Therapeutic Strategies

Cancer cachexia (CC) is a feature of cancer-related muscle wasting characterised by reduced energy intake and heightened activation of skeletal muscle catabolic pathways. CC is particularly prevalent amongst older individuals and significantly contributes to increased morbidity and mortality, with approximately 20-30% of cancer patient deaths attributed to this condition. Effectively addressing cancer-associated wasting, which includes interconnected pathologies such as anorexia, cachexia, and sarcopenia, in affected older patients is thus paramount to preserving their independence, improving their quality of life, and enhancing their ability to endure and respond to cancer treatments. This review aims to investigate the molecular mechanisms underlying CC as well as the pharmacological and non-pharmacological strategies to alleviate it, with a particular focus on the unique needs of older demographics.

The Path to Holistic Multimodal Care for Cancer Cachexia Patients

Cancer cachexia (CC) is a pathophysiologically complex and multifactorial wasting disorder prevalent in cancer patients. Physical symptoms include fever, hyperalgesia, nausea, and oral mucositis. Patients often also present with exhaustion, anxiety, depression, and disorientation. Despite its high prevalence and detrimental impact on the quality of life of affected patients and family caregivers, no established standard care for CC management yet exists. In response to this unmet need, emerging research has highlighted the potential of holistic multimodal care - a comprehensive approach integrating medical, pharmacological, nutritional, and rehabilitative interventions as well as psychological, emotional, and social well-being issues in line with the specific needs of patients and family caregivers. This review aims to provide an overview of existing knowledge on holistic multimodal care for CC.

Sarcopenia Metrics and Quality of Life Components: What Is the Link?

Sarcopenia is known to be negatively associated with quality of life in affected patients. However, the individual impacts of its metrics, i.e. muscle mass, strength, and physical performance, on patients’ overall quality of life remain to be thoroughly investigated. This pre-printed study aimed to characterise the associations between sarcopenia metrics and quality of life outcomes in community-dwelling older adults from the SOMMA (Study of Muscle, Mobility and Aging) study. Health-related quality of life was ascertained using the EQ-5D questionnaire, which measures 5 subcomponents: mobility, self-care, usual activities, pain and discomfort, as well as anxiety and depression.

Interplay Between Multidimensional Frailty and Chronic Diseases: A Review

Despite the clinical emphasis placed on its physical characteristics, frailty remains a multidimensional, biopsychosocial disease which is directly associated with multimorbidity in community-dwelling older adults. Multimorbidity is further linked with increased mortality, declines in physical functioning, and polypharmacy amongst this patient population. In this vein, individual and pathophysiologically interconnected chronic diseases may drive multidimensional frailty. Studies exploring these associations, however, have primarily focused on frailty’s physical operationalisation. This study investigated the associations between multidimensional frailty and six chronic diseases: diabetes mellitus, cancer, hypertension, arthrosis, urinary incontinence, and severe back disorder. To do so, it diffused the Tilburg Frailty Indicator (TFI), a user-friendly self-report questionnaire assessing biopsychosocial frailty, to a large cohort of Dutch older adults.

Sarcopenia and Type 2 Diabetes: A Bidirectional Relationship

Sarcopenia is characterised by age-related reductions in skeletal muscle strength, mass, and functional ability. Importantly, sarcopenia is a multifactorial condition associated with metabolic alterations, including poor glucose disposal, insulin resistance, decreased metabolic rate and, thus, type 2 diabetes (T2D). Developing non-pharmaceutical guidelines for the prevention and treatment of both diseases when they coexist is essential to optimise patient health and reduce premature mortality within this patient population. This review aimed to examine 1) the pathophysiological link between sarcopenia and T2D, and 2) lifestyle interventions with the potential to mitigate both sarcopenia and T2D.

Leucine-enriched Protein Supplementation for the Pre-frail: What Are the Benefits?

It is known that one in five adults with pre-frailty progresses to frailty over a 3-year period. Low protein and energy intake, increased prevalence of multimorbidity, and a sedentary lifestyle are well-characterised drivers of sarcopenia. Consequently, they act as catalysts of older adults’ transition to frailty. In this vein, stimulating increased muscle protein synthesis through regular physical exercise and protein-enriched diet consumption is pivotal for pre-frail older adults. Current U.S. Food and Nutrition Board guidelines recommend a dietary allowance of 0.8 g/kg of protein per day for older adults. However, this amount may be insufficient for those with pre-frailty due to their low-grade inflammation, multimorbidity, and increased susceptibility to anabolic resistance. This study aimed to examine the impact of leucine-enriched protein supplementation with or without exercise on 1) physical function, 2) body composition, and 3) systemic inflammation in pre-frail older adults with a daily protein consumption of ≤1 g/kg.

Evaluating health-related quality of life in patients with sarcopenia

The normal ageing process is accompanied by progressive declines in muscle mass and strength. Abnormal and excessive losses of skeletal muscle mass and quality emerge as a consequence of age-related musculoskeletal disorders, e.g. sarcopenia. The latter confers affected patients with increased risks of adverse outcomes, including falls, fractures, and mortality. Moreover, sarcopenic patients often exhibit higher levels of dependency and disability, both of which impact their health-related quality of life (HRQoL). HRQoL measures are well-characterised predictors of hard clinical outcomes, including hospitalisation and mortality. Accordingly, the use of sarcopenia-specific HRQoL tools in clinical practice and interventional trials is recommended by recent European Working Group on Sarcopenia in Older People (EWGSOP2) guidelines. This meta-analysis aimed to characterise the relationship between sarcopenia and patient-reported HRQoL.

GDF-15: a mediator of exercise’s link with late-life weight loss?

Ageing is often associated with appetite reduction and ensuing weight loss. Although it is known that physical activity (PA) can prevent these ageing-related processes, the exact molecular mechanisms underpinning this ability remain unknown. Recent research has highlighted the role of exerkines, i.e. proteins released during and after PA, in controlling energy metabolism. Growth differentiation factor 15 (GDF-15), a stress-signalling cytokine secreted during PA and involved in ageing, exercise, and appetite control, has emerged as a potential mediator of late-life, ageing-related weight loss. This study aimed to explore the associations between PA, GDF-15, and body weight changes in older adults enrolled in the Multidomain Alzheimer Preventive Trial over a 3-year period.

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