What are the consequences of over and undertreatment of type 2 diabetes mellitus in a frail population? A systematic review

Diabetes mellitus and dementia are common chronic diseases affecting older people in the community and in hospitals. Even though both diseases have been independently well-characterized, comorbid diabetes and dementia/cognitive impairment are much less understood. In particular, cognitive impairment can make glucose monitoring much more challenging and can more readily lead to diabetes-related emergencies such as hypoglycemia, hyperosmolar hyperglycemic state, or diabetic ketoacidosis. Based on this, improving diabetes management in the community and in the hospital settings via glucose monitoring is essential in older people with T2DM and particularly those with comorbid diabetes and dementia. The use of continuous glucose monitoring (CGM) holds promise for greater glycemic management in older patients with diabetes and those at high risk for dementia. In this brief review, we will review the few existing studies for CGM use in the community and the hospital in this population, as well as the link between hospital admissions. Existing studies show high feasibility and good adherence with using CGM among older people. In addition, diabetes technologies can improve risk factors associated with hospitalization, leading to decreased hospitalization rates. We illustrate how the current studies highlight the need for studies in the hospital in this frail population, who potentially will benefit most from CGM systems. Although existing feasibility studies show high promise in this frail population, more data are needed on CGM for older people living with diabetes and memory problems in the hospital setting.

Role of Oral Agents in Improving Cardiovascular Prognosis in Diabetes Mellitus–Reply–I

APOL1 renal risk variants are strongly associated with chronic kidney disease in Black adults, but reported associations with cardiovascular disease (CVD) have been conflicting. We examined associations of APOL1 with incident coronary heart disease (n=323), ischemic stroke (n=331), and the composite CVD outcome (n=500) in 10 605 Black participants of the REGARDS study (Reasons for Geographic and Racial Differences in Stroke). Primary analyses compared individuals with APOL1 high-risk genotypes to APOL1 low-risk genotypes in Cox proportional hazards models adjusted for CVD risk factors and African ancestry. APOL1 high-risk participants were younger and more likely to have albuminuria at baseline than APOL1 low-risk participants. The risk of incident stroke, coronary heart disease, or composite CVD end point did not significantly differ by APOL1 genotype status in multivariable models. The association of APOL1 genotype with incident composite CVD differed by diabetes mellitus status (Pinteraction=0.004). In those without diabetes mellitus, APOL1 high-risk genotypes associated with greater risk of incident composite CVD (hazard ratio, 1.67; 95% confidence interval, 1.12-2.47) compared with those with APOL1 low-risk genotypes in multivariable adjusted models. This latter association was driven by ischemic strokes (hazard ratio, 2.32; 95% confidence interval, 1.33-4.07), in particular, those related to small vessel disease (hazard ratio, 5.10; 95% confidence interval, 1.55-16.56). There was no statistically significant association of APOL1 genotypes with incident CVD in subjects with diabetes mellitus. The APOL1 high-risk genotype was associated with higher stroke risk in individuals without but not those with chronic kidney disease in fully adjusted models. APOL1 high-risk status is associated with CVD events in community-dwelling Black adults without diabetes mellitus.

Microvascular complications of diabetes: the role of angiotensin converting enzyme inhibitors Proceedings of a Round Table Meeting, June 1999, San Diego, USA

T he cardiovascular disease (CVD) risk associated with diabetes mellitus (DM) has become increasingly evident, accounting for Ϸ80% of deaths among patients with this disease 1 and making CVD risk modification a key therapeutic objective in diabetic patients.2][3][4] The rapidly increasing global burden of DM, 5 coupled with the associated CVD risk, underscores the imperative for continued generation and application of evidence-based therapies to reduce CVD risk in this high-risk cohort.In this 2-part series, we first review the CVD effects of the thiazolidinedione medications, the most broadly investigated class of antihyperglycemic drugs evaluated in the context of CVD risk.In the second part, we review the modulators of the incretin axis that have most recently achieved US Food and Drug Administration approval, with a focus on CVD considerations; introduce selected drugs in advanced development; summarize glucose control strategies for cardiovascular patients; and discuss the regulatory review of glucose-lowering medications.

The metabolic syndrome is a construct that has come into common usage over the last few decades. In 1956, Jean Vague1 first demonstrated that upper-body obesity determined predisposition to diabetes mellitus, atherosclerosis, gout, and renal calculi; however, it was the presentation of this concept by Gerald Reaven in his Banting Lecture in 19882 that initiated the current focus on this entity as a clinical and pathological construct. Dr Reaven suggested that 3 major conditions—non–insulin-dependent diabetes mellitus (type 2 diabetes mellitus), hypertension, and coronary artery disease—had an causal commonality (resistance to insulin-stimulated glucose uptake and hyperinsulinemia) and referred to this constellation of abnormalities as “syndrome X.” He did not include abdominal obesity in the original description, nor did he comment significantly on a potential clinical role for his observations. In fact, his concluding sentences stated, “What remains to be seen is the magnitude of the role that resistance to insulin-stimulated glucose uptake plays in the etiology of human disease. I can only hope that this presentation has outlined the possibilities for future efforts to answer this question.” Response by Kahn p 1818 Since that time, this construct has evolved conceptually and functionally into an entity that many refer to as a “syndrome.” More recently, there have been many questions about the legitimacy of this designation, summarized by Kahn et al3 in a September 2005 position statement for the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Their comments called into question many of the assumptions that underlay the designation of “syndrome,” and they posed the following key questions: How clear is the existing definition of the metabolic syndrome for diagnostic purposes? How useful is the syndrome definition in predicting cardiovascular disease (CVD) risk? Do the individual components of the syndrome convey “risk” …

BackgroundFrailty is associated with increased mortality risk among middle-aged and older adults. Selenium, a trace element with antioxidant properties, may play a role in reducing mortality by modulating inflammatory processes. This study aimed to investigate the association between serum selenium and mortality in individuals with prefrailty or frailty, with a specific focus on potential mediators.MethodsData of participants of National Health and Nutrition Examination Survey (1988–1994 and 2011–2016) of the US, aged 40–79 years with serum selenium measurements and frailty-related assessments were analyzed. All-cause and cardiovascular disease (CVD) mortality were confirmed by the National Death Index death certificate data. Systematic inflammation status was surrogated by the systemic immune inflammation index. Multivariable Cox proportional hazards models, restricted cubic spline (RCS) analysis, and mediation analysis were used to assess the associations.ResultsAmong 1,454 participants, those in the second, third, and fourth quartiles of serum selenium had significantly lower risks of all-cause mortality compared to the lowest quartile. The highest selenium quartile also showed a reduced risk of cardiovascular disease (CVD) mortality. Non-linear analysis indicated a significant relationship between selenium levels and all-cause mortality. Mediation analysis did not reveal that the protective effects of selenium were mediated by, CVD, chronic kidney disease, diabetes mellitus, or systemic inflammation status [as surrogated by the systemic immune-inflammation index (SII)].ConclusionHigher serum selenium levels are linked to a lower risk of all-cause and CVD mortality in individuals with prefrailty or frailty. These findings highlight the need for future studies to clarify the pathways through which selenium may reduce mortality in prefrail and frail populations, and to determine whether selenium supplementation could offer therapeutic benefits.

Background: This thesis explores the concept of frailty, as a latent vulnerability in older people, with the aim of refining its measurement by generating a new measure of frailty - the British Frailty Index (FI). This index was developed and validated in a cohort of community-dwelling older women, the British Women's Heart and Health Study (BWHHS), in 23 towns in Britain. Findings were replicated in another large Medical Research Council (MRC) Assessment of Older People study Methods: A systematic literature review examined the evolution of the concept and definitions of frailty. A meta-analysis on the prognostic value of current frailty measures confirmed extensive heterogeneity in the prediction of all-cause mortality despite consideration of age, sex, type of measure and duration of follow up. A 'General Specific' model of frailty was derived from factor analysis in the BWHHS population and replicated in the MRC cohort. Construct, external criterion and predictive validity of the British FI were assessed and its performance compared to another widely used index - the Canadian Frailty Index - with single indicators of frailty. Results: Frailty was explained by seven factors; physical ability, cardiovascular and respiratory disease and symptoms, visual impairments, other comorbidities, psychological problems and physiological measures. Associations with frailty included increased age, female sex, smoking, living alone, not living in own home, poor social contact and low socioeconomic position. Frailty was an independent predictor of all-cause mortality in both cohorts and predicted hospitalization and institutionalization in the MRC study, performing better than the Canadian Index. Conclusion: This thesis provides better understanding of the multi-dimensional domains of frailty in older people. The British FI demonstrates validity in relation to adverse outcomes, provides a more reliable measurement tool and its application offers further opportunities for the prevention, detection and treatment of frailty at a clinical level.

A dvances in our understanding of vascular cognitive impairment (VCI) have springboarded from further elucidation of the role of vascular risk factors, surgical procedures, medications, and neuroimaging studies that are related to this condition. The main focus of this VCI review will highlight the relation of diabetes mellitus and hippocampal dysfunction in VCI; coronary artery bypass surgery and cognitive decline; the role of cerebral amyloid angiopathy (CAA) in vascular dysfunction; and a discussion of other cardiovascular risk factors, treatment, and neuroimaging findings related to disease progression; and histopathologic and genetic correlates.

Current management of malnutrition can include prescribed oral nutritional supplements (ONS); however, there is uncertainty whether these supplements are effective in people who are older (≥65 years) and frail. We assessed the effectiveness, cost-effectiveness, and adherence and acceptability of ONS in frail older people who are malnourished or at risk of malnutrition. In this systematic review and meta-analysis, five bibliographic databases (MEDLINE, EMBASE, Cochrane Library, Scopus, and CINAHL) and grey literature sources were searched from inception to Sept 13, 2021, to identify studies assessing the effectiveness and cost-effectiveness of ONS (with or without other dietary interventions) in frail older people who are malnourished or at risk of malnutrition. Multiple reviewers independently did study screening, data extraction, and risk of bias assessment. Quality was assessed using version 1.0 of the Cochrane risk of bias tool for randomised controlled trials (RCTs), and the BMJ Drummond checklist was used to assess the quality of the included cost-effectiveness study. A meta-analysis was done for the effectiveness review; for the other reviews, a narrative synthesis approach was used. This systematic review and meta-analysis was registered on PROSPERO, CRD42020170906. Of 8492 records retrieved and screened, we included 11 RCTs involving 822 participants, six of which were fully or partly funded by industry. For the majority of the outcomes for which meta-analyses were possible (11/12), Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) assessments suggested that the evidence was of very low certainty. Results suggested that ONS might have a slightly positive effect on energy (kcal) intake (standardised mean difference 1·02 [95% CI 0·15 to 1·88]; I2=87%; four studies), protein intake (standardised mean difference 1·67 [-0·03 to 3·37; I2=97%; four studies), and mobility (mean difference 0·03 [0·02 to 0·04]; I2=0%; four studies), compared with standard care. Narrative syntheses suggested that the effect of ONS on quality of life, compared with standard care, was mixed. In the identified studies, there was very little information related to active components, determinants, or acceptability of interventions. One economic evaluation, done in a care home setting, showed that ONS could be cost-effective. We found little evidence of ONS reducing malnutrition or its associated adverse outcomes in older people who are frail. High-quality, non-industry-funded, adequately powered studies reporting on short-term and long-term health outcomes, determinants, and participant characteristics are needed. UK National Institute of Health and Care Research (NIHR) Health Technology Assessment (NIHR128729).

The Interactions Between Physicians and Dentists in Managing the Care of Patients With Diabetes Mellitus

Cardiovascular Disease Risk Factors and Cognitive Impairment

Cardiovascular disease (CVD) and type 2 diabetes are two major public health challenges. There is strong evidence that both conditions are predictable and preventable. Accurate identification of individuals at higher risk of CVD and type 2 diabetes is critical for the most effective and efficient prevention of these conditions, as it ensures preventive resources are focused on those who are most likely to benefit. Firstly, using baseline data from the nation-wide, population-based Australian Diabetes, Obesity and Lifestyle (AusDiab) study, this thesis examined how well the current Australian Pharmaceutical Benefits Scheme eligibility criteria for subsidy of lipid-lowering drugs identified individuals who were at high risk of developing CVD events according to the current national guidelines; and whether an anthropometric index can be used as an ancillary measure to help identify individuals with a high absolute cardiovascular risk estimate. Secondly, a validated risk prediction tool for future CVD mortality was developed based on recalibration of the SCORE (Systematic COronary Risk Evaluation) risk chart using Australian national mortality data and the major CVD risk factor profiles from eight Australian population-based surveys. Since diabetes is a major and independent risk factor for CVD, this thesis was expanded to include the prediction of risk of diabetes by analysing data from the two waves of the AusDiab study. Relevant work entailed development and validation of a self-completed, non-invasive Australian Type 2 Diabetes Risk Assessment Tool (AUSDRISK); and investigation of four different screening strategies to maximise efficiency of screening for people with a high risk of future diabetes and those with prevalent undiagnosed diabetes. The study found that: i) 11.0% of all Australian men and 3.6% of women aged 30-74 years old with neither CVD nor diabetes were found to be at high absolute CVD risk, and less than 20% of these high-risk individuals were being treated with lipid-lowering agents. Conversely many individuals eligible for statins subsidy were estimated to be at relatively low risk; ii) measurement of waist-to-hip ratio could be used as an ancillary measure to help identify individuals who are likely to have an increased absolute cardiovascular risk estimate; iii) an Australian risk prediction chart for CVD mortality was generated and validated, and offers an easy and simple approach to assessing 10-year risk of CVD death; iv) the AUSDRISK provides a valid and reliable method to estimate the 5-year risk of developing type 2 diabetes and is also able to identify asymptomatic individuals who are likely to have prevalent undiagnosed diabetes in cross-sectional settings; v) a sequential risk stratification strategy, using AUSDRISK then a second score incorporating fasting glucose, would maximise efficiency of type 2 diabetes screening and inform appropriate intervention. In conclusion, this work provides two validated tools for predicting risk of CVD mortality and incident type 2 diabetes, respectively. These tools will help improve strategies for detection of individuals at high risk of CVD or diabetes to ensure they might receive adequate prevention and treatment. The overall findings will help inform national health strategies and clinical practice related to the prevention and management of CVD and type 2 diabetes in Australia.

ABSTRACTObjective:Diabetes mellitus (DM) is a chronic disease of increasing importance in public health, associated with chronic complications including retinopathy, neuropathy, and kidney, cardiovascular and cerebrovascular disease. This study assessed the impact of strategic DM education actions on glycemic control and prevalence of chronic complications in patients with DM.Subjects and methods:Retrospective, quantitative, cohort study at a diabetes patients association comprised of a multidisciplinary team. In all, 533 individuals with DM were included. Sociodemographic and clinical data were collected using questionnaire and medical records. Of these, 333 patients evaluated for 12 to 24 months, with type 2 DM (T2DM, n = 317) and other types of DM (n = 16), were selected to collect data on retinopathy and diabetes kidney disease (DKD).Results:There was a predominance of elderly individuals, low education level, women, high rate of overweight and obesity, physical inactivity, dietary errors, dyslipidemia, and T2DM. More patients with T2DM versus type 1 DM had optimal glycemic control (46.3% vs. 12.2%, respectively; p < 0.001). The impact of the educational processes was demonstrated by the analysis of the initial and final glycated hemoglobin (HBA1c) levels. There was an increased prevalence of individuals with well-controlled DM during follow-up (prevalence ratio [PR] 2.76, 95%, p = 0.001), along with a significant reduction in retinopathy (PR: 0.679, p = 0.001) and albuminuria (PR: 0.637, 95%, p = 0.002) when these variables were evaluated in well-controlled versus uncontrolled HbA1c groups.Conclusions:A multidisciplinary approach with integration and quality was associated with improvements in DM control and reduced occurrence of chronic DM complications.

Many factors contribute to the development of clinical atherosclerotic disease in adults. Observational studies conducted from the late 1940s onward have helped us to identify cigarette smoking, cholesterol levels, diabetes, blood pressure, and other factors as important determinants of cardiovascular disease (CVD) outcomes.1,2 The effects are multiplicative. For example, smoking, hypertension, and diabetes each double the risk of a heart attack, and having all 3 factors can lead to a risk that was ≈8 times that of an adult of similar age and sex who did not have any of the factors.3 A major focus in the earlier population and clinical studies was identification of persons at increased risk before the clinical atherosclerotic event. Less attention has been directed toward other types of events, such as occurrence of a myocardial infarction in persons presenting with chest pain, recurrent CVD events, and long-term vascular disease complications such as cardiac failure. The determinants of these vascular events are likely to include some of the classical risk factors, but new factors will no doubt be important as well. Improvements in outpatient and inpatient care, diagnosis, and biomarker discovery have reshaped the landscape. It is possible to visualize subclinical CVD with modern atherosclerotic imaging techniques such as carotid intima-media thickness and arterial calcification assessments. Clinical chemists and geneticists identify new biomarkers that promise to help refine assessments of CVD risk, but it is not clear how such tests should be used for research or for clinical care. This article addresses several of the questions posed above and takes the perspective of research and care for clinical atherosclerotic disease, emphasizing the progress we have made from traditional risk factor assessment to the present time that includes newer assessment methods such as genomics, metabolomics, and predictive medicine. ### Traditional Risk Factors for Cardiovascular Disease The traditional risk factors include cholesterol, blood …