老年糖尿病的诊疗进展

糖尿病呈流行之势,65岁以上的老年糖尿病患者亦呈逐年增加趋势.老年糖尿病患者的身体状况各有不同,而针对老年糖尿病患者的临床试验相对缺乏,这些问题对于管理老年糖尿病患者提出了挑战.临床医师应该根据共患病的情况、认知和功能状态确定不同的血糖控制目标.每一种药物在老年糖尿病患者中的应用有其特殊之处.了解不同降糖药物的优缺点有利于个体化治疗.与非糖尿病老年人相比,老年糖尿病患者更易发生影响生活质量的老年综合征,如认知功能障碍、抑郁、跌倒、营养不良、尿失禁等,及时发现并处理老年综合征有助于更好的管理老年糖尿病患者.     

Management of diabetes in older adults

Type 2 diabetes prevalence is high in older adults and is expected to rise in the next decades. Diabetes in the population of frail older adults is accompanied by functional disability, several comorbidities, and premature mortality. A comprehensive geriatric assessment, including functional, cognitive, mental and social status, is advisable for identifying the glycemic targets and glucose-lowering therapies, focused on patient preferences, needs, and risks. The therapeutic options for older adults with diabetes are like those for the adult population. However, the pharmacological treatments must be carefully prescribed and monitored, taking into consideration the patient cognitive capacities, the potentially life-threatening drug–drug interactions, the cardiovascular risk, and with the main goal of avoiding hypoglycemia. Also, a careful nutritional evaluation with appropriate tools, as well as a balanced and periodically monitored physical activity, contribute to an effective tailored care plan, as needed by older adults with diabetes. This review evaluates the currently available hypoglycemic drugs and the current indications to the Italian diabetology community, specifically with regard to the treatment of adults aged 75 years or older with diabetes, including the unmet needs by the guidelines.     

Type 2 diabetes mellitus in older people: a brief statement of key principles of modern day management including the assessment of frailty. A national collaborative stakeholder initiative

Rates of population ageing are unprecedented and this, combined with the progressive urbanization of lifestyles, has led to a dramatic shift in the epidemiology of diabetes towards old age, particularly to those aged 60–79 years. Both ageing and diabetes are recognized as important risk factors for the development of functional decline and disability. In addition, diabetes is associated with a high economic, social and health burden. Traditional macrovascular and microvascular complications of diabetes appear to account for less than half of the diabetes‐related disability observed in older people. Despite this, older adults are under‐represented in clinical trials. Guidelines from organizations such as the National Institute for Health and Care Excellence (NICE), the European Association for the Study of Diabetes, and the American Diabetes Association acknowledge the need for individualized care, but the glycaemic targets that are suggested to constitute good control [HbA_1c 53–59 mmol/mol (7–7.5%)] are too tight for frail older individuals. We present a framework for the assessment of older adults and guidelines for the management of this population according to their frailty status, with the intention of reducing complications and improving quality of life for these people.     

Therapie mit oralen Antidiabetika und/oder Insulin im höheren Alter?

Type 2 diabetes mellitus affects more and more of the world adult population with older people being disproportionately affected. Treatment of older people, especially geriatric people with type 2 diabetes who are usually older than 65 years with disabilities affecting the daily routine and quality of life, differs in many ways from that of younger adults. Differences can be found in the choice of diabetes medication as well as in respect to the practical choice of the treatment. However, there are still no outcome data on long-term effects of diabetes therapy or therapeutic strategies specifically for older people but considering the recent outcome trials it is known that HbA1c targets should be individualized, which is highly relevant for the group of older patients. The HbA1c targets for these patients are usually less stringent compared to most other patients but despite good therapy options, insulin therapy in particular is often too late or insufficiently initiated mainly because of concerns about adverse reactions. The present review discusses available therapy options specifically for the older patient with type 2 diabetes.     

Therapeutic Interventions for Frail Elderly Patients: Part I. Published Randomized Trials

The body of literature for frailty as a prognostic marker continues to grow, yet the evidence for frailty as a therapeutic target is less well defined. In the setting of cardiovascular disease, the prevalence of frailty is elevated and its impact on mortality and major morbidity is substantial. Therapeutic interventions aimed at improving frailty may impart gains in functional status and survival. Randomized clinical trials that tested one or more therapeutic interventions in a population of frail older adults were reviewed. The interventions studied were exercise training in 13 trials, nutritional supplementation in 4 trials, combined exercise plus nutritional supplementation in 7 trials, pharmaceutical agents in 8 trials, multi-dimensional programs in 5 trials, and home-based services in 1 trial. The main findings of these trials are explored along with a discussion of their relative merits and limitations.     

Significance of frailty for predicting adverse clinical outcomes in different patient groups with specific medical conditions

Frailty is a major health burden in an aging society. It constitutes a clinical state of reduced physiological reserves that is associated with a diminished ability to withstand internal and external stressors. Frail patients have an increased risk for adverse clinical outcomes, such as mortality, readmission to hospital, institutionalization and falls. Of further clinical interest, frailty might be at least in part reversible in some patients and subject to preventive strategies. In daily clinical practice older patients with a complex health status, who are mostly frail or at least at risk of developing frailty, are frequently cared for by geriatricians. Recently, clinicians and scientists from other medical disciplines, such as cardiology, pulmonology, gastroenterology, nephrology, endocrinology, rheumatology, surgery and critical care medicine also discovered frailty to be an interesting instrument for risk stratification of patients, including younger patients. In this review we highlight the results of recent studies that demonstrated the significance of frailty to predict adverse clinical outcomes in patients with specific medical conditions, such as cardiac, lung, liver and kidney diseases as well as diabetes mellitus, osteoarthritis, trauma patients, patients undergoing surgery and critically ill patients. Multiple studies in patients with the aforementioned specific medical conditions could be identified demonstrating a predictive role of frailty for several adverse clinical outcomes. The association between frailty and adverse clinical outcomes reported in these studies was in part independent of several major potential confounder factors, such as age, sex, race, comorbidities and disabilities and were also detected in younger patients.     

Frailty in older Mexican Americans

OBJECTIVES: To identify sociodemographic characteristics and health performance variables associated with frailty in older Mexican Americans. DESIGN: A prospective population-based survey. SETTING: Homes of older adults living in the southwest. PARTICIPANTS: Six hundred twenty-one noninstitutionalized Mexican-American men and women aged 70 and older included in the Hispanic Established Populations for Epidemiologic Study of the Elderly participated in a home-based interview. MEASUREMENTS: Interviews included information on sociodemographics, self-reports of medical conditions (arthritis, diabetes mellitus, heart attack, hip fracture, cancer, and stroke) and functional status. Weight and measures of lower and upper extremity muscle strength were obtained along with information on activities of daily living and instrumental activities of daily living. A summary measure of frailty was created based on weight loss, exhaustion, grip strength, and walking speed. Multivariable linear regression identified variables associated with frailty at baseline. Logistic regression examined variables predicting frailty at 1-year follow-up. RESULTS: Sex was associated with frailty at baseline (F=4.28, P=.03). Predictors of frailty in men included upper extremity strength, disability (activities of daily living), comorbidities, and mental status scores (Nagelkerke coefficient of determination (R(2))=0.37). Predictors for women included lower extremity strength, disability (activities of daily living), and body mass index (Nagelkerke R(2)=0.29). At 1-year follow-up, 83% of men and 79% of women were correctly classified as frail. CONCLUSION: Different variables were identified as statistically significant predictors of frailty in Mexican-American men and women aged 70 and older. The prevention, development, and treatment of frailty in older Mexican Americans may require consideration of the unique characteristics of this population.     

Hypothalamic regulatory pathways and potential obesity treatment targets

With an ever-growing population of obese people as well as comorbidities associated with obesity, finding effective weight loss strategies is more imperative than ever. One of the challenges in curbing the obesity crisis is designing successful strategies for long-term weight loss and weight-loss maintenance. Currently, weight-loss strategies include promotion of therapeutic lifestyle changes (diet and exercise), pharmacological therapy, and bariatric surgery. This review focuses on several pharmacological targets that activate central nervous system pathways that normally limit food intake and body weight. Though it is likely that no single therapy will prove effective for everyone, this review considers several recent pre-clinical targets, and several compounds that have been in human clinical trials.     

住院共病老年人衰弱状态分布及其影响因素

目的明确住院共病老年人衰弱状态分布特点,进一步探讨其影响因素。方法横断面调查选取2015年11月至2017年7月成都市第五人民医院老年科收治的≥60岁住院共病患者440例。根据衰弱状态将患者分为衰弱组150例及非衰弱组290例,比较2组患者一般人口学资料、共病、衰弱状态及老年综合征情况。采用SPSS 23.0进行统计分析。根据数据类型,组间比较采用独立样本t检验、Mann-Whitney U检验或χ~2检验。采用Mantel-Haenszel χ~2检验分析衰弱分布趋势。危险因素分析采用向后逐步法二元logistic回归。结果 440例患者总体存在5(4,7)种慢性疾病,Charlson合并症指数(CCI)为(5.59±1.82)分。入选患者衰弱患病率为34.1%(150/440),衰弱前期占60.0%(264/440)。趋势性检验结果显示,随年龄和CCI评分升高,衰弱患病率显著增加,差异有统计学意义(P0.05);衰弱五要素中,体质量下降发生率随年龄和CCI评分增加而增加,握力下降和疲乏发生率随年龄增加而增加,差异亦有统计学意义(P0.05)。与非衰弱患者比较,衰弱组患者年龄增大,学历较低,合并慢性心力衰竭、慢性阻塞性肺疾病、抑郁、认知功能障碍、尿失禁、高跌倒风险、功能依赖的比例显著升高,但多重用药比例显著降低,差异有统计学意义(P0.05)。经校正混杂因素后,二元logistic回归分析表明,抑郁(OR=2.178,95%CI 1.252～3.790)和功能依赖(OR=1.942,95%CI 1.029～3.668)是衰弱的独立危险因素。结论住院共病老人中普遍存在衰弱,且衰弱的患病率与年龄和共病严重程度呈趋势性增加,抑郁和功能依赖与衰弱状态密切相关。     

The importance of frailty assessment in multiple myeloma: a position statement from the Myeloma Scientific Advisory Group to Myeloma Australia

Multiple myeloma (MM) is a disease of older people, yet factors relating to comorbidity and frailty may threaten treatment tolerability for many of this heterogenous group. There has been increasing interest in defining specific and clinically relevant frailty assessment tools within the MM population, with the goal of using these frailty scores, not just as a prognostic instrument, but also as a predictive tool to allow for a frailty-adapted treatment approach. This paper reviews the various frailty assessment frameworks used in the evaluation of patients with MM, including the International Myeloma Working Group Frailty Index (IMWG-FI), the Mayo Frailty Index and the simplified frailty scale. While the IMWG-FI remains the most widely accepted tool, the simplified frailty scale is the most user-friendly in busy day-to-day clinics based on its ease of use. This paper summarises the recommendations from the Myeloma Scientific Advisory Group (MSAG) of Myeloma Australia, on the use of frailty assessment tools in clinical practice and proposes a frailty-stratified treatment algorithm to aid clinicians in tailoring therapy for this highly heterogeneous patient population.     

Cronicidad,envejecimiento y multimorbilidadChronicity,ageing and multimorbidity

Thanks to highly active antiretroviral therapy (HAART), HIV-related mortality has been drastically reduced and HIV infection has become a chronic disease. The HIV-infected population is ageing prematurely. Despite good immunovirological control, HIV causes chronic inflammation and accelerated immunosenes-cence. This clinically manifests as an increased prevalence of age-related comorbidity and frailty occurring earlier than in the general population. The heterogeneity of older HIV-infected adults highlights the rele-vance of identifying those who are at risk of poor health, and frailty may be an effective indicator. The rela-tionship between ageing, HIV infection, antiretroviral treatment, comorbidities and frailty still needs to be clarified. Elderly HIV-infected adults are complex patients who require a specific, global and multidisci-plinary approach.     

Metformin revisited: A critical review of the benefit–risk balance in at-risk patients with type 2 diabetes

Metformin is unanimously considered a first-line glucose-lowering agent. Theoretically, however, it cannot be prescribed in a large proportion of patients with type 2 diabetes because of numerous contraindications that could lead to an increased risk of lactic acidosis. Various observational data from real-life have shown that many diabetic patients considered to be at risk still receive metformin and often without appropriate dose adjustment, yet apparently with no harm done and particularly no increased risk of lactic acidosis. More interestingly, recent data have suggested that type 2 diabetes patients considered at risk because of the presence of traditional contraindications may still derive benefit from metformin therapy with reductions in morbidity and mortality compared with other glucose-lowering agents, especially sulphonylureas. The present review analyzes the benefit–risk balance of metformin therapy in special populations, namely, patients with stable coronary artery disease, acute coronary syndrome or myocardial infarction, congestive heart failure, renal impairment or chronic kidney disease, hepatic dysfunction and chronic respiratory insufficiency, all conditions that could in theory increase the risk of lactic acidosis. Special attention is also paid to elderly patients with type 2 diabetes, a population that is growing rapidly, as older patients can accumulate several comorbidities classically considered contraindications to the use of metformin. A review of the recent scientific literature suggests that reassessment of the contraindications of metformin is now urgently needed to prevent physicians from prescribing the most popular glucose-lowering therapy in everyday clinical practice outside of the official recommendations.     

Treatment of cancer in old age, shortcomings and challenges.

The burden of cancer in old age is increasing as a result from both the expanding number of older persons in the population and the high and still increasing cancer incidence in this group. The goal of this article is to outline the shortcomings and challenges of the management of cancer in the elderly. Several factors contribute to the complexity of this management, such as the enormous heterogeneity in this population, increased co-morbidity, reduced functional status, increased frailty and different treatment goals from those in younger patients. Other problems include the lack of data on the efficacy and toxicity of cancer treatment in this age group, the lack of awareness of life-expectancy and the lack of an easy applicable and validated frailty scale. Improvement of the quality of oncological care in this age group could be achieved by initiation of clinical trials specifically directed at the elderly, in which a frailty scale is implemented. The results of these trials may lead to more evidence-based decision making in cancer treatment in the elderly.     

Diabetes in the older patient: heterogeneity requires individualisation of therapeutic strategies

Owing to the worldwide increase in life expectancy, the high incidence of diabetes in older individuals and the improved survival of people with diabetes, about one-third of all individuals with diabetes are now older than 65 years. Evidence is accumulating that type 2 diabetes is associated with cognitive impairment, dementia and frailty. Older people with diabetes have significantly more comorbidities, such as myocardial infarction, stroke, peripheral arterial disease and renal impairment, compared with those without diabetes. However, as a consequence of the increased use of multifactorial risk factor intervention, a considerable number of older individuals can now survive for many years without any vascular complications. Given the heterogeneity of older individuals with type 2 diabetes, an individualised approach is warranted, which must take into account the health status, presence or absence of complications, and life expectancy. In doing so, undertreatment of otherwise healthy older individuals and overtreatment of those who are frail may be avoided. Specifically, overtreatment of hyperglycaemia in older patients is potentially harmful; in particular, insulin and sulfonylureas should be avoided or, if necessary, used with caution. Instead, glucose-dependent drugs that do not induce hypoglycaemia are preferable since older patients with diabetes and impaired kidney function are especially vulnerable to this adverse event.     

Musculoskeletal health,frailty and functional decline

Frailty in older people is associated with a vulnerability to adverse events. While ageing is associated with a loss of physiological reserves, identifying those with the syndrome of frailty has the potential to assist clinicians to tailor treatments to those at the risk of future decline into disability with an increased risk of complications, morbidity and mortality. Sarcopenia is a key component of the frailty syndrome and on its own puts older people at risk of fragility fractures; however, the clinical syndrome of frailty affects the musculoskeletal and non-musculoskeletal systems. Hip fractures are becoming a prototype condition in the study of frailty. Following a hip fracture, many of the interventions are focused on limiting mobility disability and restoring independence with activities of daily living, but there are multiple factors to be addressed including osteoporosis, sarcopenia, delirium and weight loss. Established techniques of geriatric evaluation and management allow systematic assessment and intervention on multiple components by multidisciplinary teams and deliver the best outcomes. Using the concept of frailty to identify older people with musculoskeletal problems as being at the risk of a poor outcome assists in treatment planning and is likely to become more important as effective pharmacological treatments for sarcopenia emerge.This review will focus on the concept of frailty and its relationship with functional decline, as well as describing its causes, prevalence, risk factors, potential clinical applications and treatment strategies.     

Innovative biomarkers for predicting type 2 diabetes mellitus: relevance to dietary management of frailty in older adults

Type 2 diabetes mellitus (T2DM) increases in prevalence in the elderly. There is evidence for significant muscle loss and accelerated cognitive impairment in older adults with T2DM; these comorbidities are critical features of frailty. In the early stages of T2DM, insulin sensitivity can be improved by a “healthy” diet. Management of insulin resistance by diet in people over 65 years of age should be carefully re-evaluated because of the risk for falling due to hypoglycaemia. To date, an optimal dietary programme for older adults with insulin resistance and T2DM has not been described. The use of biomarkers to identify those at risk for T2DM will enable clinicians to offer early dietary advice that will delay onset of disease and of frailty. Here we have used an in silico literature search for putative novel biomarkers of T2DM risk and frailty. We suggest that plasma bilirubin, plasma, urinary DPP4-positive microparticles and plasma pigment epithelium-derived factor merit further investigation as predictive biomarkers for T2DM and frailty risk in older adults. Bilirubin is screened routinely in clinical practice. Measurement of specific microparticle frequency in urine is less invasive than a blood sample so is a good choice for biomonitoring. Future studies should investigate whether early dietary changes, such as increased intake of whey protein and micronutrients that improve muscle function and insulin sensitivity, affect biomarkers and can reduce the longer term complication of frailty in people at risk for T2DM.     

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

BackgroundDysglycaemia (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.AimsTo 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.MethodsA 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.ResultsOnly 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.ConclusionsDysglycaemia 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.