XI. STRATEGIES FOR IMPROVING DIABETES CARE D iabetes is a chronic illness that requires continuing medical care and patient self-management education to prevent acute complications and to reduce the risk of long-term complications. Diabetes care is complex and requires that many issues, beyond glycemic control, be addressed. A large body of evidence exists that supports a range of interventions to improve diabetes outcomes. These standards of care are intended to provide clinicians, patients, researchers, payors, and other interested individuals with the components of diabetes care, treatment goals, and tools to evaluate the quality of care. While individual preferences, comorbidities, and other patient factors may require modification of goals, targets that are desirable for most patients with diabetes are provided. These standards are not intended to preclude more extensive evaluation and management of the patient by other specialists as needed. For more detailed information, refer to Bode (Ed.): Medical Management of Type 1 Diabetes (1), Burant (Ed): Medical Management of Type 2 Diabetes (2), and Klingensmith (Ed): Intensive Diabetes Management (3). The recommendations included are diagnostic and therapeutic actions that are known or believed to favorably affect health outcomes of patients with diabetes. A grading system (Table 1), developed by the American Diabetes Association (ADA) and modeled after existing methods, was utilized to clarify and codify the evidence that forms the basis for the recommendations. The level of evidence that supports each recommendation is listed after each recommendation using the letters A, B, C, or E.

Standards of Medical Care in Diabetes

Mini Mental State

Cytokine dysregulation is believed to play a key role in the remodeling of the immune system at older age, with evidence pointing to an inability to fine-control systemic inflammation, which seems to be a marker of unsuccessful aging. This reshaping of cytokine expression pattern, with a progressive tendency toward a pro-inflammatory phenotype has been called "inflamm-aging." Despite research there is no clear understanding about the causes of "inflamm-aging" that underpin most major age-related diseases, including atherosclerosis, diabetes, Alzheimer's disease, rheumatoid arthritis, cancer, and aging itself. While inflammation is part of the normal repair response for healing, and essential in keeping us safe from bacterial and viral infections and noxious environmental agents, not all inflammation is good. When inflammation becomes prolonged and persists, it can become damaging and destructive. Several common molecular pathways have been identified that are associated with both aging and low-grade inflammation. The age-related change in redox balance, the increase in age-related senescent cells, the senescence-associated secretory phenotype (SASP) and the decline in effective autophagy that can trigger the inflammasome, suggest that it may be possible to delay age-related diseases and aging itself by suppressing pro-inflammatory molecular mechanisms or improving the timely resolution of inflammation. Conversely there may be learning from molecular or genetic pathways from long-lived cohorts who exemplify good quality aging. Here, we will discuss some of the current ideas and highlight molecular pathways that appear to contribute to the immune imbalance and the cytokine dysregulation, which is associated with "inflammageing" or parainflammation. Evidence of these findings will be drawn from research in cardiovascular disease, cancer, neurological inflammation and rheumatoid arthritis.

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Age and Age-Related Diseases: Role of Inflammation Triggers and Cytokines.

Inflammation and frailty in the elderly: A systematic review and meta-analysis.

Longevity and aging are two sides of the same coin, as they both derive from the interaction between genetic and environmental factors. Aging is a complex, dynamic biological process characterized by continuous remodeling. One of the most recent theories on aging focuses on immune response, and takes into consideration the activation of subclinical, chronic low-grade inflammation which occurs with aging, named "inflammaging". Long-lived people, especially centenarians, seem to cope with chronic subclinical inflammation through an anti-inflammatory response, called therefore "anti-inflammaging". In the present review, we have focused our attention on the contrast between inflammaging and anti-inflammaging systems, by evaluating the role of cytokines and their impact on extreme longevity. Cytokines are the expression of a network involving genes, polymorphisms and environment, and are involved both in inflammation and anti-inflammation. We have described the role of IL-1, IL-2, IL-6, IL-12, IL-15, IL-18, IL-22, IL-23, TNF-α, IFN-γ as pro-inflammatory cytokines, of IL-1Ra, IL-4, IL-10, TGF-β1 as anti-inflammatory cytokines, and of lipoxin A4 and heat shock proteins as mediators of cytokines. We believe that if inflammaging is a key to understand aging, anti-inflammaging may be one of the secrets of longevity.

Inflammaging and Anti-Inflammaging: The Role of Cytokines in Extreme Longevity

Context Sarcopenia is a progressive and generalized skeletal muscle disorder associated with an increased risk of adverse outcomes such as falls, disability, and death. The Belgian Society of Gerontology and Geriatrics has developed evidence-based guidelines for the prevention and treatment of sarcopenia. This umbrella review presents the results of the Working Group on Nutritional Interventions. Objective The aim of this umbrella review was to provide an evidence-based overview of nutritional interventions targeting sarcopenia or at least 1 of the 3 sarcopenia criteria (ie, muscle mass, muscle strength, or physical performance) in persons aged ≥ 65 years. Data sources Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, the PubMed and Web of Science databases were searched for systematic reviews and meta-analyses reporting the effect of nutritional supplementation on sarcopenia or muscle mass, strength, or physical performance. Data extraction Two authors extracted data on the key characteristics of the reviews, including participants, treatment, and outcomes. Methodological quality of the reviews was assessed using the product A Measurement Tool to Assess Systematic Reviews. Three authors synthesized the extracted data and generated recommendations on the basis of an overall synthesis of the effects of each intervention. Quality of evidence was rated with the Grading of Recommendations Assessment, Development and Evaluation approach. Data analysis A total of 15 systematic reviews were included. The following supplements were examined: proteins, essential amino acids, leucine, β-hydroxy-β-methylbutyrate, creatine, and multinutrient supplementation (with or without physical exercise). Because of both the low amount and the low to moderate quality of the reviews, the level of evidence supporting most recommendations was low to moderate. Conclusions Best evidence is available to recommend leucine, because it has a significant effect on muscle mass in elderly people with sarcopenia. Protein supplementation on top of resistance training is recommended to increase muscle mass and strength, in particular for obese persons and for ≥ 24 weeks. Effects on sarcopenia as a construct were not reported in the included reviews.

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Nutritional interventions to improve muscle mass, muscle strength, and physical performance in older people: an umbrella review of systematic reviews and meta-analyses.

Could geriatric characteristics explain the under-prescription of anticoagulation therapy for old patients admitted with atrial fibrillation

Background Anticoagulation therapy with anti-vitamin K (AVK; vitamin K antagonist) for the prevention of thromboembolism in patients with atrial fibrillation (AF) is based on information derived from numerous well constructed, randomized controlled trials. Despite this conclusive evidence of efficacy, several studies have shown that ‘real world’ use of AVK in patients with AF is suboptimal. Our hypothesis was that geriatric characteristics (functional impairment, cognitive disorders, malnutrition, risk for falls, depression) could be an explanation for the underprescription of AVK in older patients with AF. Objective To analyse the barriers to the prescription of AVK therapy, with special attention on geriatric characteristics. Methods This was a retrospective study of 768 consecutive geriatric patients admitted to an acute geriatric unit of an academic hospital between April 2006 and November 2008. Data from comprehensive geriatric assessments were collected from computerized medical charts. Results Analysis of data from the 768 medical charts showed that 111 patients (14%) presented with AF. Among the 111 patients (72% women), 45% were living in an institution before admission. These patients presented a high prevalence of geriatric syndromes: cognitive disorders 59%, malnutrition risk 59%, incontinence 35%, depression 37%, and falls 61%. Ninety percent of the patients had an Identification of Seniors At Risk (ISAR) questionnaire score ≥2, which indicates an increased risk of frailty and functional decline during hospitalization. The prevalence of conditions measured by the CHADS2 (congestive heart failure, hypertension, age >75 years, diabetes mellitus and previous stroke or transient ischaemic attack [TIA]) clinical prediction scale was as follows: heart failure 19%, hypertension 79%, age >75 years 95%, diabetes 15% and stroke 24%. The mean ± SD number of daily classes of drugs received at admission was 7.1±3.3 (median 7, range 0–20). Forty-nine percent of patients had not received any AVK treatment before admission. The level of functional dependence for basic and instrumental activities of daily living did not differ between patients receiving AVK before admission and those not receiving AVK. Similarly, the proportion of geriatric problems (cognitive, malnutrition, depression and falls) did not differ between these two groups. To determine whether the decision to administer AVK therapy before admission was influenced by the risk of an embolic stroke, determined by the presence of CHADS2 conditions, we compared the proportions of patients who fulfilled those conditions in each group: again, no difference was found. Conclusions Almost half of the patients presenting with AF did not receive any AVK therapy before admission. In this population, in which most patients had multiple impairments, no single impairment or geriatric characteristic was identified as a barrier to AVK use. It is possible that combinations of impairments and geriatric characteristics were barriers to the prescription of AVK therapy across the whole of this population. More research is needed to identify and clarify the relative importance of patient-, physician- and healthcare system-related barriers to the prescription of AVK therapy in older patients with AF.

Could geriatric characteristics explain the under-prescription of anticoagulation therapy for older patients admitted with atrial fibrillation? A retrospective observational study.

Aging is associated with progressive alterations of immune functions, leading to higher susceptibility to bacterial and viral infections and reduced vaccine responses. Data concerning cytokine production in response to Toll-like receptor (TLR) ligands are highly variable in old people, reflecting the heterogeneity of the geriatric population. The aim of our study was to define the relative contribution of age and clinical status on TLR-induced interleukin (IL)-12p70 and IL-23 production as these cytokines play an important role in the protection against intracellular and extracellular pathogens, respectively. For this purpose, we recruited 100 subjects (aged 23-96 years) in the general population or hospitalized for chronic diseases. We collected information on clinical status (medical history, ongoing comorbidities, treatments and geriatric scales), biological parameters (biochemical and hematological tests, telomere length determination, cytomegalovirus serology). Whole blood samples were stimulated with a combination of TLR4 and TLR7/8 ligands. We performed univariate and stepwise backward multivariate analyses regression to define which set of clinical variables could be predictive for IL-12p70 and IL-23 production in these conditions. Our results indicated that age was not correlated with TLR-mediated IL-12p70 and IL-23 production. In contrast, poor nutritional status and frailty in subjects >75 years were associated with decreased IL-12p70 and IL-23 production. By intracytoplasmic staining, we confirmed that production of IL-12/23p40 by conventional dendritic cells (DCs) upon TLR ligation was decreased in frail patients. However, proportion of DCs and monocytes subsets, phenotypic maturation and proximal signaling events were found to be comparable in frail and healthy old subjects. These results suggest the importance of age-associated clinical parameters and not age by itself in the alteration of innate immune responses in old individuals and emphasis the importance of innate immune responses in the susceptibility of frail geriatric patients to infections.

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Frailty in Old Age Is Associated with Decreased Interleukin-12/23 Production in Response to Toll-Like Receptor Ligation

Objectives: The comprehensive geriatric assessment (CGA) can detect geriatric problems and potentially improve survival, physical, and cognitive state of patients, as well as increase an older person’s chances of staying at home longer In older people, the number and severity of comorbidity increase with age and are an important determinant of survival The aim of the study was to assess to which extent CGA and comorbidities could be seen as determinants of survivalMaterials and methods: This study analyzed data from two hospitals that included geriatric assessments of patients aged 70 years and more with cancer linked to mortality Logistic regression was used to model survival predictorsResults: Two hundred and five various cancer patients (47% females) with a median age of 79 were included They presented with a lot of undiagnosed geriatric problems Screening scales (G8, SEGA), cognitive, and psychological disorders, and low albumin levels appeared to be independent survival factors A frailty prof

Sandra De Breucker

Papers

Nutritional interventions to improve muscle mass, muscle strength, and physical performance in older people: an umbrella review of systematic reviews and meta-analyses.

Could geriatric characteristics explain the under-prescription of anticoagulation therapy for old patients admitted with atrial fibrillation

Could geriatric characteristics explain the under-prescription of anticoagulation therapy for older patients admitted with atrial fibrillation? A retrospective observational study.

Frailty in Old Age Is Associated with Decreased Interleukin-12/23 Production in Response to Toll-Like Receptor Ligation

Comprehensive geriatric assessment and comorbidities predict survival in geriatric oncology