Baroreflex function and postprandial hypotension in older adults.

PURPOSE: Postprandial hypotension (PPH) is a common but poorly understood etiology for fainting in older adults. One potential mechanism is age-related baroreflex dysfunction. We examined baroreflex function in older adults with PPH and without PPH (noPPH) during a standardized meal test. METHODS: 57 adults (age ≥ 65; 24 PPH, 33 noPPH, mean age 77.9 ± 0.9 years, 54% female) were recruited and had meal tests performed. The baroreflex effectiveness index (BEI, %) and baroreflex sensitivity (BRS, ms/mm Hg) were calculated using the sequence method. RESULTS: Baseline BEI (22 ± 2 versus 23 ± 2 percent, t = - 0.411, p = 0.682) and BRS (14.1 ± 2.4 versus 13.8 ± 2.5 ms/mm of Hg, t = - 0.084, p = 0.933) were similar in PPH and noPPH subjects. During the meal test PPH subjects showed significantly lower BEI as compared to noPPH subjects (time × PPH, F = 2.791, p = 0.042), while there was no difference in the postprandial change in BRS (time, F = 0.618, p = 0.605). CONCLUSION: Patients with PPH demonstrated an acute postprandial decrease in baroreflex effectiveness during meal testing as compared with normal subjects, suggesting a potential contributing mechanism for this condition.

A rapid point-of-care ultrasound marker for muscle mass and muscle strength in older adults.

BACKGROUND/OBJECTIVES: Sarcopenia is defined as the gradual age-associated loss of both muscle quantity and strength in older adults, and is associated with increased mortality, falls, fractures and hospitalisations. Current sarcopenia criteria use dual-energy X-ray absorptiometry (DXA) measures of muscle mass, a test that cannot be performed at the bedside, unlike point-of-care ultrasound (PoCUS). We examined the association between ultrasonic measures of muscle thickness (MT, vastus medialis muscle thickness) and measures of muscle quantity and strength in older adults. METHODS: A total of 150 older adults (age ≥ 65; mean age 80.0 ± 0.5 years, 66 women, 84 men) were recruited sequentially from geriatric medicine clinics. Each subject had lean body mass (LBM, by bioimpedance assay), grip strength, mid-arm biceps circumference (MABC), gait speed and MT measured. All initial models were adjusted for biological sex. RESULTS: In our final parsimonious models, MT showed a strong significant correlation with all measures of muscle mass, including LBM (Standardised ß = 0.204 ± 0.058, R2 = 0.577, P < 0.001) and MABC (Standardised ß = 0.141 ± 0.067, R2 = 0.417, P = 0.038). With respect to measures of muscle quality, there was a strong significant correlation with grip strength (Standardised ß = 0.118 ± 0.115, R2 = 0.511, P < 0.001) but not with subject performance (gait speed). CONCLUSIONS: MT showed strong correlations with both measures of muscle mass (LBM and MABC) and with muscle strength (grip strength). Although more work needs to be done, PoCUS shows potential as a screening tool for sarcopenia in older adults.

Point-of-care ultrasound measures of muscle and frailty measures.

PURPOSE: Frailty is defined as a syndrome of increased vulnerability due to both age and disease that leads to an inability to cope with acute stressors. There has been growing interest in the surgical and emergency medicine literature in the potential use of Point-of-Care ultrasonic (PoCUS) measures of muscle mass to assess frailty in older adults. Our study examined the association between a simple ultrasonic measure of muscle thickness (MT, vastus medialis muscle thickness) and commonly used frailty measures (Cardiovascular Health Study, CHS; Rockwood Clinical Frailty Scale, RCFS) in older adults. METHODS: Participants were recruited sequentially from ambulatory geriatric medicine clinics in an academic medical centre (Vancouver General Hospital, Vancouver, Canada). Each subject had MT measured by PoCUS, as well as the CHS index and Rockwood Clinical Frailty Scale. RESULTS: 150 older adults (age ≥ 65; mean age 80.0 ± 0.5 years, 66 women, 84 men) were recruited. In our final parsimonious models, MT showed a weak inverse association with the CHS index (Standardized ß = - 0.180 ± 0.080, R2 = 0.06, p = 0.027) and no association with the RCFS (p = 0.776). Within the CHS index, most of the association was due to grip strength in men (Standardized ß = - 0.326 ± 0.099, R2 = 0.26, p = 0.001). CONCLUSION: Frailty is a multifactorial syndrome, and caution must be used in trying to screen for this condition with a single ultrasonic measure. Further work might indicate associations with a more restricted syndrome, such as sarcopenia.

Diabetes in ageing: pathways for developing the evidence base for clinical guidance.

Older adults with diabetes are heterogeneous in their medical, functional, and cognitive status, and require careful individualisation of their treatment regimens. However, in the absence of detailed information from clinical trials involving older people with varying characteristics, there is little evidence-based guidance, which is a notable limitation of current approaches to care. It is important to recognise that older people with diabetes might vary in their profiles according to age category, functional health, presence of frailty, and comorbidity profiles. In addition, all older adults with diabetes require an individualised approach to care, ranging from robust individuals to those residing in care homes with a short life expectancy, those requiring palliative care, or those requiring end-of-life management. In this Review, our multidisciplinary team of experts describes the current evidence in several important areas in geriatric diabetes, and outlines key research gaps and research questions in each of these areas with the aim to develop evidence-based recommendations to improve the outcomes of interest in older adults.

Correction to: Combining GLP-1 Receptor Agonists and Basal Insulin in Older Adults with Type 2 Diabetes: Focus on Lixisenatide and Insulin Glargine.

There are some corrections in the original article, Page 11, "/LYXUMIA" word has to be removed from the section RATIONALE FOR COMBINATION THERAPY COMPRISING GLP-1 RAs AND BASAL INSULIN.

Combining GLP-1 Receptor Agonists and Basal Insulin in Older Adults with Type 2 Diabetes: Focus on Lixisenatide and Insulin Glargine.

Estimates suggest that there are currently 122.8 million adults 65-99 years of age living with diabetes, of whom 90-95% are diagnosed with type 2 diabetes (T2D). Over the past two decades, a greater understanding of the complex and multifactorial pathogenesis of T2D has resulted in the development and introduction of new-generation classes of glucose-lowering therapies, which are now extensively endorsed by prevailing guidelines and are increasingly being used worldwide. These newer agents may further assist in the effective pharmacological management of T2D through the provision of patient-centered care that acknowledges multimorbidity and is respectful of and responsive to individual patient preferences and barriers. Given these considerations, the therapeutic approach in older patients with T2D is complex, particularly in those who have functional dependence, frailty, dementia, or who are at end-of-life. It is currently too early to draw conclusions on the long-term use of newer glucose-lowering agents in this population, as their efficacy and safety in older adults remains largely unknown. In this review, we will discuss considerations for the use of glucose-lowering treatments in older adults, with particular focus on the use of basal insulin and glucagon-like peptide-1 receptor agonists, and the rationale for the use of combination therapy comprising these agents. Finally, we will review clinical data from studies of the fixed-ratio combination of insulin glargine and lixisenatide in older patients with T2D. FUNDING: Sanofi US, Inc.

Efficacy and safety of lixisenatide as add-on therapy to basal insulin in older adults with type 2 diabetes in the GetGoal-O Study.

BACKGROUND: This study compared the efficacy and safety of lixisenatide with placebo as add-on therapy to basal insulin (BI) in adults aged ≥70 years with type 2 diabetes (T2D), with or without moderate renal insufficiency. METHODS: This post hoc analysis evaluated data from non-frail patients with T2D inadequately controlled on BI with or without oral antidiabetic drugs (n = 108), randomized to once-daily lixisenatide 20 µg or placebo for 24 weeks (GetGoal-O Study). The primary endpoint was the change in HbA1c from baseline to Week 24. Secondary endpoints included changes from baseline in fasting plasma glucose, 2-hour postprandial plasma glucose (PPG), average seven-point self-monitored plasma glucose (SMPG), area under the curve for SMPG, daily BI dose, body weight, proportion of patients achieving HbA1c > 0.5%, and composite endpoints. Safety outcomes included the incidence of documented symptomatic hypoglycemia (plasma glucose <60 mg/dL) and gastrointestinal treatment-emergent adverse events (TEAEs). Outcomes were also analyzed by the occurrence of moderate renal insufficiency. RESULTS: Compared with placebo, lixisenatide-treated patients had significantly greater reductions in HbA1c, 2-hour PPG, average seven-point SMPG, and body weight. Documented symptomatic hypoglycemia was approximately two-fold higher in patients treated with placebo than lixisenatide (12.7% vs 5.7%). GI TEAEs occurred more frequently in the lixisenatide- than placebo-treated group (34% vs 9.1%). Moderate renal insufficiency (estimated glomerular filtration rate between ≥30 and <60 mL/min/1.73 m2 ) did not negatively affect lixisenatide efficacy or safety. A greater proportion of patients treated with lixisenatide than placebo achieved composite endpoints. CONCLUSIONS: Add-on therapy with lixisenatide in non-frail patients aged ≥70 years with T2D uncontrolled with BI is effective, safe, and well tolerated and should be considered in this population.

Characteristics Associated with the Postprandial Hypotensive Response in Falling Older Adults.

Il a été démontré que l'intensité de la réponse hypotensive postprandiale (RHP) peut constituer un facteur de risque pour les chutes, les fractures et le décès. Bien que ce risque ait été bien établi, les cliniques de chutes font rarement des analyses liées aux repas, en raison de contraintes logistiques. Afin de mieux cibler les patients à risque de RHP parmi les personnes âgées affectées par des chutes, cette étude a examiné les caractéristiques individuelles associées à des RHP plus intenses. Cinquante-deux patients (âge moyen : 77,8 ± 0,9 ans, 29 femmes, 23 hommes) référés par des cliniques de prévention des chutes ont été recrutés pour un repas-test de 90 minutes. Les variables significatives ont ensuite été insérées dans un modèle linéaire multivarié incluant l'âge, le sexe, la présence de diabète, la présence d'hypertension, la pression systolique de base (PSB) et la chute de la PSB orthostatique. Bien que de plus amples recherches soient nécessaires, notre étude suggère que les hommes, les patients présentant une tension artérielle élevée et ceux avec une chute orthostatique pourraient être plus à risque de réponses hémodynamiques postprandiales plus intenses.The magnitude of the postprandial hypotensive (PPH) response has been shown to be an independent risk factor for falls, fractures, and death. Despite this well-established risk, meal tests are rarely done in the falls clinic setting because of logistical issues. In order to better target potential PPH patients among older falling adults, this study examines which subject characteristics are associated with larger PPH responses. A total of 52 falls clinic patients (mean age 77.8 ± 0.9 years, 29 women, 23 men) were recruited for a 90 minute meal test. Significant variables were then entered into a stepwise multivariate linear model containing age, sex, presence of diabetes, presence of hypertension, baseline systolic blood pressure (SBP), and the orthostatic drop in SBP. Although further work is required, our study suggests that men, patients with higher blood pressure, and patients with an orthostatic drop might be more likely to have higher postprandial hemodynamic responses.

Blood pressure measurement and the prevalence of postprandial hypotension.

BACKGROUND: Postprandial hypotension (PPH) is a serious condition that has been shown to be an independent risk factor for falls, fractures and death. PURPOSE: The prevalence of this problem in older adults with a past history of falls has shown a wide variability in the literature; the present study seeks to examine how the frequency with which blood pressure is measured impacts the prevalence and severity of PPH. METHODS: Older adults were recruited sequentially from a geriatric medicine falls clinic for meal testing (n=95). All subjects (mean age 77.5±0.7 years, 61±5% female) were fasting prior to each 90 min standardized meal test. A Finometer (Finapres Medical Systems BV) was used to monitor blood pressure. Beat-by-beat systolic (SBP) measures were averaged for 0.5, 1, 2, 3, 5, 6, 9, 10, 15, 18, 30, 45 and 90 min respectively during the meal test. RESULTS: Using the original diagnostic method of checking mean blood pressure every 10 min resulted in a PPH prevalence of 42.1±5.1% in our population, with an overall range from 81.1±4.0% to 11.6±3.3% depending on the frequency of calculating SBP. The maximal observed postprandial decrease in SBP also showed a significant difference with blood pressure measurement frequency (p.

Insights Into the Current Management of Older Adults With Type 2 Diabetes in the Ontario Primary Care Setting.

OBJECTIVE: The Goal Oriented controL of Diabetes in the Elderly populatioN (GOLDEN) Program assessed the management of older persons with type 2 diabetes in Canadian primary care. METHODS: Data were extracted from the records of 833 consecutively identified persons 65 years of age or older who had type 2 diabetes and were taking 1 antihyperglycemic agent or more; they were managed by 64 physicians from 36 Ontario clinics. RESULTS: More than half (53%) had glycated hemoglobin (A1C) levels of 7.0% or lower, 41% had blood pressure levels below 130/80 mm Hg, and 73% had low-density lipoprotein levels of 2.0 mmol/L or lower; 19% met all 3 criteria. Over the past year, 11% had been assessed for frailty, 16% for cognitive dysfunction and 19% for depression; 88% were referred for eye checkups, and 83% had undergone foot examinations. One-tenth were taking 4 or more antihyperglycemic agents, 87% statins and 52% an angiotensin-converting enzyme inhibitor. More than half of those with high clinical complexity had A1C levels of 7.0% or lower; of these, one-third were taking a sulfonylurea, and one-fifth were taking insulin. In the patients with A1C levels of 7.0% or above and low clinical complexity, there was often no up-titration or initiation of additional antihyperglycemic agents. CONCLUSIONS: Older persons with type 2 diabetes often have multiple comorbidities. Unlike eye and foot examinations, there was less emphasis on evaluating for frailty, cognitive dysfunction and depression. The GOLDEN patients had generally well-controlled glycemic, blood pressure and cholesterol profiles, but whether these would be reflected in a "sicker" population is not known. Personalized strategies are necessary to avoid undertreatment of "healthy" older patients and overtreatment of the frail elderly.

Comparing Physical Examination With Sonographic Versions of the Same Examination Techniques for Splenomegaly.

OBJECTIVES: To determine whether sonographic versions of physical examination techniques can accurately identify splenomegaly, Castell's method (Ann Intern Med 1967; 67:1265-1267), the sonographic Castell's method, spleen tip palpation, and the sonographic spleen tip technique were compared with reference measurements. METHODS: Two clinicians trained in bedside sonography patients recruited from an urban hematology clinic. Each patient was examined for splenomegaly using conventional percussion and palpation techniques (Castell's method and spleen tip palpation, respectively), as well as the sonographic versions of these maneuvers (sonographic Castell's method and sonographic spleen tip technique). Results were compared with a reference standard based on professional sonographer measurements. RESULTS: The sonographic Castell's method had greater sensitivity (91.7% [95% confidence interval, 61.5% to 99.8%]) than the traditional Castell's method (83.3% [95% confidence interval, 51.6% to 97.9%]) but took longer to perform [mean ± SD, 28.8 ± 18.6 versus 18.8 ± 8.1 seconds; P = .01). Palpable and positive sonographic spleen tip results were both 100% specific, but the sonographic spleen tip method was more sensitive (58.3% [95% confidence interval, 27.7% to 84.8%] versus 33.3% [95% confidence interval, 9.9% to 65.1%]). CONCLUSIONS: Sonographic versions of traditional physical examination maneuvers have greater diagnostic accuracy than the physical examination maneuvers from which they are derived but may take longer to perform. We recommend a combination of traditional physical examination and sonographic techniques when evaluating for splenomegaly at the bedside.

Lixisenatide Therapy in Older Patients With Type 2 Diabetes Inadequately Controlled on Their Current Antidiabetic Treatment: The GetGoal-O Randomized Trial.

OBJECTIVE: To evaluate the efficacy and safety of lixisenatide versus placebo on glycemic control in older patients with type 2 diabetes uncontrolled on their current antidiabetic treatment. RESEARCH DESIGN AND METHODS: In this phase III, double-blind, randomized, placebo-controlled, two-arm, parallel-group, multicenter trial, patients aged ≥70 years were randomized to receive once-daily lixisenatide 20 µg or placebo before breakfast concomitantly with their existing antidiabetic therapy (including insulin) for 24 weeks. Patients at risk for malnutrition or with moderate to severe cognitive impairment were excluded. The primary end point was absolute change in HbA1c from baseline to week 24. Secondary end points included change from baseline to week 24 in 2-h postprandial plasma glucose (PPG) and body weight. RESULTS: A total of 350 patients were randomized. HbA1c decreased substantially with lixisenatide (-0.57% [6.2 mmol/mol]) compared with placebo (+0.06% [0.7 mmol/mol]) from baseline to week 24 (P < 0.0001). Mean reduction in 2-h PPG was significantly greater with lixisenatide (-5.12 mmol/L) than with placebo (-0.07 mmol/L; P < 0.0001). A greater decrease in body weight was observed with lixisenatide (-1.47 kg) versus placebo (-0.16 kg; P < 0.0001). The safety profile of lixisenatide in this older population, including rates of nausea and vomiting, was consistent with that observed in other lixisenatide studies. Hypoglycemia was reported in 17.6% of patients with lixisenatide versus 10.3% with placebo. CONCLUSIONS: In nonfrail older patients uncontrolled on their current antidiabetic treatment, lixisenatide was superior to placebo in HbA1c reduction and in targeting postprandial hyperglycemia, with no unexpected safety findings.

Cytomegalovirus Seropositivity Predicts a Decline in the T Cell But Not the Antibody Response to Influenza in Vaccinated Older Adults Independent of Type 2 Diabetes Status.

Type 2 diabetes mellitus (T2DM) and persistent cytomegalovirus (CMV) infection are postulated contributors to inflammatory processes that impact on the age-related decline in T-cell responses to influenza vaccination. Older subjects with T2DM (n = 30) and healthy aged controls (n = 40) were enrolled and received influenza vaccination in this study. Serum inflammatory markers and CMV serostatus were measured. Pre- to post-vaccination changes in serum antibody titers to the A/H3N2 strain, and levels of granzyme B (GrB, cytotoxic T lymphocytes) in lysates and cytokines in supernatants from influenza A/H3N2-challenged peripheral blood mononuclear cells were measured. We found no difference between the T2DM and healthy groups in the immune responses measured. However, CMV serostatus was a key determinant of the GrB response to influenza challenge; CMV+ subjects had low levels of inducible GrB (iGrB) activity in response to influenza challenge. In contrast, the serum antibody response to the A/H3N2 vaccine strain did not differ with CMV serostatus, and serum levels of the inflammatory marker, ß2-microglobulin, were positively correlated with age, T2DM, and serum IL-10 levels. In conclusion, CMV seropositivity associated with a decline in GrB responses to influenza may predict increased susceptibility to influenza in older adults.

Influence of Blood Pressure and Other Clinical Variables on Long-Term Mortality in a Cohort of Elderly Subjects with Type 2 Diabetes.

BACKGROUND: Diabetes mellitus and high blood pressure (HBP) are commonly associated conditions in the elderly population. An effect of treatments, biologic and anthropometric variables on long-term mortality is unknown in this population. OBJECTIVES: To determine the prevalence of HBP control in a sample of elderly patients with type 2 diabetes with office blood pressure (BP) readings and ambulatory blood pressure monitoring (ABPM) and evaluate the influence of BP, anthropometric and laboratory variables on long term mortality. METHODS: Cohort study in patients living at home in the area of Sherbrooke, ≥65 years old, receiving reimbursement for antidiabetic medication. The study included medical history, 2 sets of BP measurements, 2 24-hour urinary collections for microalbuminuria, 1 24-hour ABPM, blood level of creatinine and glycosylated hemoglobin. Charts were reanalyzed 8 years later for analysis of cardiovascular and total mortality cases. RESULTS: 198 patients were initially recruited. By history, 83% of the subjects had diagnoses and treatments for high blood pressure. In multivariate analysis, factors associated with an 8-year increased risk for cardiovascular mortality were creatinine ≥84 µmol/L, office seated systolic blood pressure ≤130 and diastolic BP ≤67.6 over 24 hours. Factors associated with total mortality were lower waist circumference, serum creatinine ≥84 and diastolic BP ≤67.6 over 24 hours. CONCLUSIONS: Lower systolic and diastolic BP (office and ABPM), lower waist circumference and higher creatinine values are associated with an increased mortality risk. This suggests that a lower BP, declining kidney function and frailty are factors associated with this observation.

Diabetes, Dementia and Hypoglycemia.

We are experiencing an epidemic of both diabetes and dementia among older adults in this country. The risk for dementia appears to be increased in patients with diabetes, and patients with dementia and diabetes appear to be at greater risk for severe hypoglycemia. In addition, there may be an increased risk for developing dementia by older patients with diabetes who have had episodes of severe hypoglycemia, although this issue is controversial. In this article, we review the factors that contribute to the increased risk for dementia in older adults with diabetes and outline the complex relationships between hypoglycemia and dementia.

Does GLP-1 suppress its own basal secretion?

PURPOSE/AIM: Negative feedback controls in endocrine regulatory systems are well recognized. The incretins and their role in glucose regulation have been of major interest recently. Whether the same negative control system applies to the regulation of incretin secretion is not clear. We sought to examine the hypothesis that exogenous administration of glucagon like peptide-1, GLP-1(7-36) amide or its metabolite GLP-1(9-36) amide, reduces the endogenous basal release of this incretin. MATERIALS AND METHODS: We evaluated the endogenous basal release of GLP-1 using two separate study designs. In protocol A we examined the GLP-1(7-36) amide levels during the infusion of GLP-1(9-36) amide. In protocol B, we used PYY and GLP-2 as biomarkers for the endogenous basal release of GLP-1(7-36) amide and assessed the endogenous basal release of these two hormones during the GLP-1(7-36) infusion. Twelve lean and 12 obese subjects were enrolled in protocol A and 10 obese volunteers in protocol B. RESULTS: The plasma levels of GLP-1(7-36) amide in protocol A and PYY and GLP-2 in protocol B remained unchanged during the exogenous infusion of GLP-1(9-36) and GLP-1(7-36) amide, respectively. CONCLUSIONS: The negative feedback control system as described by inhibition of the release of endogenous hormone while infusing it exogenously was not observed for the basal secretion of GLP-1(7-36) amide.