Response rates and associated factors after a multicomponent intervention in frail older adults with diabetes.

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.

Overtreatment of older people with type 2 diabetes-a high impact frequent occurrence in need of a new definition.

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 overtreatment 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 HbA1c 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.

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

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.

Diabetes in COVID-19 pandemic-prevalence, patient characteristics and adverse outcomes.

BACKGROUND: Current literature on COVID-19 pandemic has identified diabetes as a common comorbidity in patients affected. However, the evidence that diabetes increases the risk of infection, effect of diabetes on outcomes and characteristics of patients at risk is not clear. OBJECTIVES: To explore the prevalence of diabetes in COVID-19 pandemic, effect of diabetes on clinical outcomes and to characterise the patients with diabetes affected by COVID-19. METHODS: A literature review of articles published in English language and reported outcomes on prevalence and effect of diabetes on outcomes and patients' characteristics. RESULTS: The prevalence of diabetes in COVID-19 patients appears similar to that in the general population. The evidence of diabetes increasing the risk of severe infection and adverse outcomes is substantial. The progression of the disease into acute respiratory distress syndrome, the requirement for intensive care admission or mechanical ventilation and mortality all have been increased by the presence of diabetes. Patients with diabetes at risk of COVID-19 appear to be obese, of older age, have uncontrolled glycaemia and have coexisting comorbidities especially cardiovascular disease and hypertension. Tight glycaemic control on admission to hospital using insulin infusion has shown some beneficial effects; however, the role of hypoglycaemic medications in the management of these patients is not yet clear. CONCLUSION: High risk group should be identified and prioritised in future vaccination programmes. Future research is required to optimise management of patients with diabetes and develop new ways to manage them via technological developments such as telecare.

Evaluating glucose-lowering treatment in older people with diabetes: Lessons from the IMPERIUM trial.

Understanding the benefits and risks of treatments to be used by older individuals (≥65 years old) is critical for informed therapeutic decisions. Glucose-lowering therapy for older patients with diabetes should be tailored to suit their clinical condition, comorbidities and impaired functional status, including varying degrees of frailty. However, despite the rapidly growing population of older adults with diabetes, there are few dedicated clinical trials evaluating glucose-lowering treatment in older people. Conducting clinical trials in the older population poses multiple significant challenges. Despite the general agreement that individualizing treatment goals and avoiding hypoglycaemia is paramount for the therapy of older people with diabetes, there are conflicting perspectives on specific glycaemic targets that should be adopted and on use of specific drugs and treatment strategies. Assessment of functional status, frailty and comorbidities is not routinely performed in diabetes trials, contributing to insufficient characterization of older study participants. Moreover, significant operational barriers and problems make successful enrolment and completion of such studies difficult. In this review paper, we summarize the current guidelines and literature on conducting such trials, as well as the learnings from our own clinical trial (IMPERIUM) that assessed different glucose-lowering strategies in older people with type 2 diabetes. We discuss the importance of strategies to improve study design, enrolment and attrition. Apart from summarizing some practical advice to facilitate the successful conduct of studies, we highlight key gaps and needs that warrant further research.

Challenges and Strategies for Diabetes Management in Community-Living Older Adults.

The prevalence of diabetes is increasing, especially in older people, mainly because of an increase in life expectancy. The number of comorbidities also increases with increasing age, leading to a unique diabetes phenotype in old age that includes vascular disease, physical and neuropathic complications, and mental dysfunction. These three categories of complications appear to have a synergistic effect that can lead to a vicious cycle of deterioration into disability. Early assessment and appropriate, timely interventions may delay adverse outcomes. However, this complex phenotype constitutes a great challenge for health care professionals. This article reviews the complex diabetes phenotype in old age and explores management strategies that are predominantly based on the overall functional status of patients within this heterogeneous age-group.

The "Sarcopenia and Physical fRailty IN older people: multi-componenT Treatment strategies" (SPRINTT) randomized controlled trial: design and methods.

The sustainability of health and social care systems is threatened by a growing population of older persons with heterogeneous needs related to multimorbidity, frailty, and increased risk of functional impairment. Since disability is difficult to reverse in old age and is extremely burdensome for individuals and society, novel strategies should be devised to preserve adequate levels of function and independence in late life. The development of mobility disability, an early event in the disablement process, precedes and predicts more severe forms of inability. Its prevention is, therefore, critical to impede the transition to overt disability. For this reason, the Sarcopenia and Physical fRailty IN older people: multi-componenT Treatment strategies (SPRINTT) project is conducting a randomized controlled trial (RCT) to test a multicomponent intervention (MCI) specifically designed to prevent mobility disability in high-risk older persons. SPRINTT is a phase III, multicenter RCT aimed at comparing the efficacy of a MCI, based on long-term structured physical activity, nutritional counseling/dietary intervention, and an information and communication technology intervention, versus a healthy aging lifestyle education program designed to prevent mobility disability in 1500 older persons with physical frailty and sarcopenia who will be followed for up to 36 months. The primary outcome of the SPRINTT trial is mobility disability, operationalized as the inability to walk for 400 m within 15 min, without sitting, help of another person, or the use of a walker. Secondary outcomes include changes in muscle mass and strength, persistent mobility disability, falls and injurious falls, disability in activities of daily living, nutritional status, cognition, mood, the use of healthcare resources, cost-effectiveness analysis, quality of life, and mortality rate. SPRINTT results are expected to promote significant advancements in the management of frail older persons at high risk of disability from both clinical and regulatory perspectives. The findings are also projected to pave the way for major investments in the field of disability prevention in old age.

In Search of 'Omics'-Based Biomarkers to Predict Risk of Frailty and Its Consequences in Older Individuals: The FRAILOMIC Initiative.

An increase in the number of older people experiencing disability and dependence is a critical aspect of the demographic change that will emerge within Europe due to the rise in life expectancy. In this scenario, prevention of these conditions is crucial for the well-being of older citizens and for the sustainability of our healthcare systems. Thus, the diagnosis and management of conditions like frailty, which identifies the people at the highest risk for developing those adverse outcomes, is of critical relevance. Currently, assessment of frailty relies primarily on measuring functional parameters, which have limited clinical utility. In this viewpoint article, we describe the FRAILOMIC Initiative, an international, large-scale, multi-endpoint, community- and clinic-based research study funded by the European Commission. The aim of the study is to develop validated measures, comprising both classic and 'omics-based' laboratory biomarkers, which can predict the risk of frailty, improve the accuracy of its diagnosis in clinical practice and provide a prognostic forecast on the evolution from frailty to disability. The initiative includes eight established cohorts of older adults, encompassing >75,000 subjects, most of whom (∼70%) are aged >65 years. Data on function, nutritional status and exercise habits have been collected, and cardiovascular health has been evaluated at baseline. Subjects will be stratified as 'non-frail' or 'frail' using Fried's definition, all adverse outcomes of interest will be recorded and differentially expressed biomarkers associated with the risk of frailty will be identified. Genomic, proteomic and transcriptomic investigations will be carried out using array-based systems. As circulating microRNAs in plasma have been identified in the context of senescence, ageing and age-associated diseases, a miRNome-wide analysis will also be undertaken to identify a miRNA-based signature of frailty. Blood concentrations of secreted proteins known to be upregulated significantly in senescent endothelial cells and other hypothesis-driven biomarkers will be measured using ELISAs. The FRAILOMIC Initiative aims to issue a series of interim scientific reports as key results emerge. Ultimately, it is hoped that this study will contribute to the development of new clinical tools, which may help individuals to enjoy an old age that is healthier and free from disability.

Associations of mutually exclusive categories of physical activity and sedentary time with markers of cardiometabolic health in English adults: a cross-sectional analysis of the Health Survey for England.

BACKGROUND: Both physical activity and sedentary behaviour have been individually associated with health, however, the extent to which the combination of these behaviours influence health is less well-known. The aim of this study was to examine the associations of four mutually exclusive categories of objectively measured physical activity and sedentary time on markers of cardiometabolic health in a nationally representative sample of English adults. METHODS: Using the 2008 Health Survey for England dataset, 2131 participants aged ≥ 18 years, who provided valid accelerometry data, were included for analysis and grouped into one of four behavioural categories: (1) 'Busy Bees': physically active & low sedentary, (2) 'Sedentary Exercisers': physically active & high sedentary, (3) 'Light Movers': physically inactive & low sedentary, and (4) 'Couch Potatoes': physically inactive & high sedentary. 'Physically active' was defined as accumulating at least 150 min of moderate-to-vigorous physical activity (MVPA) per week. 'Low sedentary' was defined as residing in the lowest quartile of the ratio between the average sedentary time and the average light-intensity physical activity time. Weighted multiple linear regression models, adjusting for measured confounders, investigated the differences in markers of health across the derived behavioural categories. The associations between continuous measures of physical activity and sedentary levels with markers of health were also explored, as well as a number of sensitivity analyses. RESULTS: In comparison to 'Couch Potatoes', 'Busy Bees' [body mass index: -1.67 kg/m(2) (p < 0.001); waist circumference: -1.17 cm (p = 0.007); glycated haemoglobin: -0.12% (p = 0.003); HDL-cholesterol: 0.09 mmol/L (p = 0.001)], 'Sedentary Exercisers' [body mass index: -1.64 kg/m(2) (p < 0.001); glycated haemoglobin: -0.11 % (p = 0.009); HDL-cholesterol: 0.07 mmol/L (p < 0.001)] and 'Light Movers' [HDL-cholesterol: 0.11 mmol/L (p = 0.004)] had more favourable health markers. The continuous analyses showed consistency with the categorical analyses and the sensitivity analyses indicated robustness and stability. CONCLUSIONS: In this national sample of English adults, being physically active was associated with a better health profile, even in those with concomitant high sedentary time. Low sedentary time independent of physical activity had a positive association with HDL-cholesterol.

Tailor treatment in the older patient with type 2 diabetes.

Around 50% of older people with diabetes are asymptomatic. When symptoms are present they are often nonspecific, patients may feel generally unwell, tired or lethargic. Classic osmotic symptoms are usually less prominent in older age because of an increased renal threshold for glucose, resulting in reduced polyuria, and impairment of thirst sensation, resulting in reduced polydipsia. Because of the complexity of diabetes in old age a comprehensive assessment is important at initial diagnosis, with the aim of preventing loss of autonomy and preserving independence. Diabetes should be diagnosed if fasting plasma glucose is > or = 7 mmol/L or 2 hour postprandial glucose > or = 11.1 mmol/L. In addition to traditional micro- and macrovascular complications seen in younger people, older people with diabetes are at risk of developing atypical complications or geriatric syndromes such as cognitive dysfunction, depression, disability, falls, persistent pain and urinary incontinence. Glycaemic targets should be individualised taking into consideration the patient's overall health and life expectancy. Older people may tolerate higher levels of blood glucose before they develop osmotic symptoms because of a higher renal threshold for glucose with increasing age. On the other hand, they may appear to tolerate lower levels of blood glucose because of diminished autonomic symptoms of hypoglycaemia. Older people with diabetes are twice as likely to develop Alzheimer's disease or vascular dementia as age-matched controls without diabetes.

Metabolic Impact of Frailty Changes Diabetes Trajectory.

Diabetes mellitus prevalence increases with increasing age. In older people with diabetes, frailty is a newly emerging and significant complication. Frailty induces body composition changes that influence the metabolic state and affect diabetes trajectory. Frailty appears to have a wide metabolic spectrum, which can present with an anorexic malnourished phenotype and a sarcopenic obese phenotype. The sarcopenic obese phenotype individuals have significant loss of muscle mass and increased visceral fat. This phenotype is characterised by increased insulin resistance and a synergistic increase in the cardiovascular risk more than that induced by obesity or sarcopenia alone. Therefore, in this phenotype, the trajectory of diabetes is accelerated, which needs further intensification of hypoglycaemic therapy and a focus on cardiovascular risk reduction. Anorexic malnourished individuals have significant weight loss and reduced insulin resistance. In this phenotype, the trajectory of diabetes is decelerated, which needs deintensification of hypoglycaemic therapy and a focus on symptom control and quality of life. In the sarcopenic obese phenotype, the early use of sodium-glucose transporter-2 inhibitors and glucagon-like peptide-1 receptor agonists is reasonable due to their weight loss and cardio-renal protection properties. In the malnourished anorexic phenotype, the early use of long-acting insulin analogues is reasonable due to their weight gain and anabolic properties, regimen simplicity and the convenience of once-daily administration.

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.

Impact of deintensifying hypoglycaemic drugs in older adults with type 2 diabetes: protocol for an emulation of a target trial.

INTRODUCTION: In older adults with type 2 diabetes (T2D), overtreatment with hypoglycaemic drugs (HDs: sulfonylureas, glinides and/or insulins) is frequent and associated with increased 1-year mortality. Deintensification of HD is thus a key issue, for which evidence is though limited. The primary objective of this study will be to estimate the effect of deintensifying HD on clinical outcomes (hospital admission or death) within 3 months in older adults (≥75 years) with T2D. METHODS: We will emulate with real-world data a target trial, within The Health Improvement Network cohort, a large-scale database of data collected from electronic medical records of 2000 general practitioners in France. From 1 January 2010 to 28 February 2019, we will include eligible patients ≥75 years who will have T2D, a stable dose of HDs, glycated haemoglobin A1c (HbA1c) value <75 mmol/mol (9.0%) and no deintensification in the past year. The target trial will be sequentially emulated (ie, eligibility assessed) every month in the database. Patients will be classified at baseline of each sequential trial in the intervention arm (deintensification of HDs: decrease of ≥50% in the total dose of HDs, including complete cessation) or control arm (no deintensification of HDs). The pooled dataset for all sequential emulated trials will be analysed. The primary outcome will be time to first occurrence of hospital admission or death, within 3 months. Secondary outcomes will be hospitalisation, death, appropriateness of glycaemic control and occurrence of HbA1c >75 mmol/mol within 1 year. Participants will be followed from baseline to 12 months after randomisation, administrative censoring, or death, whichever occurs first. A pooled logistic regression will be used to estimate the treatment effect on the incidence of the outcomes. DISSEMINATION AND ETHICS: No ethical approval is needed for using retrospectively this fully anonymised database. The results will be disseminated during conferences and through publications in scientific journals.

Amino Acid Profiles in Older Adults with Frailty: Secondary Analysis from MetaboFrail and BIOSPHERE Studies.

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.

Factors associated with initiation of antihyperglycaemic medication in UK patients with newly diagnosed type 2 diabetes.

AIM: To assess the factors associated with antihyperglycaemic medication initiation in UK patients with newly diagnosed type 2 diabetes. METHODS: In a retrospective cohort study, patients with newly diagnosed type 2 diabetes were identified during the index period of 2003-2005. Eligible patients were ≥ 30 years old at the date of the first observed diabetes diagnosis (referred to as index date) and had at least 2 years of follow-up medical history (N = 9,158). Initiation of antihyperglycaemic medication (i.e., treatment) was assessed in the 2-year period following the index date. Adjusted Cox regression models were used to examine the association between time to medication initiation and patient age and other factors. RESULTS: Mean (SD) HbA1c at diagnosis was 8.1% (2.3). Overall, 51% of patients initiated antihyperglycaemic medication within 2 years (65%, 55%, 46% and 40% for patients in the 30- < 45, 45- < 65, 65- < 75, 75+ age groups, respectively). Among the treated patients, median (25th, 75th percentile) time to treatment initiation was 63 (8, 257) days. Of the patients with HbA1c ≥ 7.5% at diagnosis, 87% initiated treatment within 2 years. These patients with a higher HbA1c also had shorter time to treatment initiation (adjusted hazard ratio (HR) = 2.44 [95% confidence interval (CI): 1.61, 3.70]; p < 0.0001). Increasing age (in years) was negatively associated with time to treatment initiation (HR = 0.98 [95% CI: 0.97, 0.99]; p < 0.001). Factors significantly associated with shorter time to treatment initiation included female gender and use of cardiovascular medications at baseline or initiated during follow up. CONCLUSIONS: In this UK cohort of patients with newly diagnosed type 2 diabetes, only 51% had antihyperglycaemic medication initiated over a 2-year period following diagnosis. Older patients were significantly less likely to have been prescribed antihyperglycaemic medications. Elevated HbA1c was the strongest factor associated with initiating antihyperglycaemic medication in these patients.

Multimorbidity, Frailty and Diabetes in Older People-Identifying Interrelationships and Outcomes.

Multimorbidity and frailty are highly prevalent in older people with diabetes. This high prevalence is likely due to a combination of ageing and diabetes-related complications and other diabetes-associated comorbidities. Both multimorbidity and frailty are associated with a wide range of adverse outcomes in older people with diabetes, which are proportionally related to the number of morbidities and to the severity of frailty. Although, the multimorbidity pattern or cluster of morbidities that have the most adverse effect are not yet well defined, it appears that mental health disorders enhance the multimorbidity-related adverse outcomes. Therefore, comprehensive diabetes guidelines that incorporate a holistic approach that includes screening and management of mental health disorders such as depression is required. The adverse outcomes predicted by multimorbidity and frailty appear to be similar and include an increased risk of health care utilisation, disability and mortality. The differential effect of one condition on outcomes, independent of the other, still needs future exploration. In addition, prospective clinical trials are required to investigate whether interventions to reduce multimorbidity and frailty both separately and in combination would improve clinical outcomes.

Dual effects of insulin resistance on mortality and function in non-diabetic older adults: findings from the Toledo Study of Healthy Aging.

Insulin signalling declines with increasing age and impacts skeletal muscle function and longevity in animal models. Our aim was to assess the relationships between insulin resistance (IR) and frailty and mortality in a unique community-dwelling cohort of older people. 991 non-diabetic subjects from the Toledo Study of Healthy Ageing (TSHA) cohort were included. IR was estimated by the homeostasis model assessment index (HOMA-IR) at baseline while frailty was determined by frailty phenotype (FP) and Frailty Trait Scale (FTS) at baseline and after 5-year follow-up. Deaths were also determined. Multivariate regression models were used to analyze the effects of HOMA-IR on outcomes. Age, gender, BMI, education level, cardio- and cerebro-vascular disease, glomerular filtration rate, and disability were included as potential confounding variables in progressive adjustment models. IR determined as increasing log HOMA-IR was inversely associated with risk of mortality. The association remained significant for all adjustment models (HR: 0.64-0.69). When we analyzed survival curves, the higher the HOMA-IR tertile, the lower the mortality rate (highest vs lowest tertile, p = 0.0082). In contrast, IR increased the risk of incident frailty determined by FP (OR 1.81 [1.14-2.87]) as well as deterioration of frailty status determined by worsening in FTS score (OR 1.28 [1.01-1.63]) at 5-year follow-up. In non-diabetic older subjects, IR significantly increases the risk for frailty and functional decline but decreased the risk of death at 5-year follow-up. This finding raises the need of assessing the effect of biomarkers on different outcomes before establishing their role as biomarkers of aging.

A Therapeutic Vibrating Insole Device for Postural Instability in Older People with Type 2 Diabetes: A Randomized Control Study.

INTRODUCTION: Frail older people with diabetes often present with or develop walking impairments, in part due to lower-limb sensory-motor neuropathy. Several studies suggest a possible improvement of balance control using somatosensory stimulation. We undertook a novel randomized control trial, the aim of which was to observe whether use of this device for 1 month improves walking speed as measured in the 10-m fast walking speed test standardized to body size at month 1 (M1) (FWS). Secondary outcomes were the differences between intervention (VS) and control (C) in the 10-m normal walking speed test, step length, short physical performance battery, timed up and go test, and posturographic measures. METHODS: Subjects were aged ≥ 70 years and had had type 2 diabetes for at least 2 years. The intervention (VS) at home consisted of 22-min daily vibrating sequences with noise intensity set at 90% of the tactile threshold for each foot. The same device was used in group C but noise was set to 0. Compliance was retrieved from the device. RESULTS: Among 56 subjects, 27 were in the VS group and 29 in the C group; 35 subjects were frail, 15 were prefrail ,and 6 were non-frail. Bilateral neuropathy was present in 17 subjects. More than half of sessions were done in 36 subjects with no discernible difference according to intervention. At M1 there were no discernible differences in FWS between the groups [VS: 0.96 (0.53) cm s-1 cm-1, C: 0.94 (0.47) cm s-1 cm-1]. There were also no discernible differences in other outcomes, irrespective of the presence of bilateral neuropathy. CONCLUSION: In a cohort of frail, prefrail, or non-frail older subjects with diabetes, a 1-month intervention using a vibrating insole device did not alter measures of walking speed and related measures. Larger studies with longer term and different stimulation protocols are required to test this hypothesis more fully.