The effects of single and a combination of determinants of anaemia in the very old: results from the TULIPS consortium.

BACKGROUND AND OBJECTIVES: Nutritional deficiencies, renal impairment and chronic inflammation are commonly mentioned determinants of anaemia. The aim of this study was to investigate the effects of these determinants, singly and in combination, on anaemia in the very old. METHOD: The TULIPS Consortium consists of four population-based studies in oldest-old individuals: Leiden 85-plus Study, LiLACS NZ, Newcastle 85+ study, and TOOTH. Five selected determinants (iron, vitamin B12, and folate deficiency; low estimated glomerular filtration rate (eGFR); and high C-reactive protein (CRP)) were summed. This sum score was used to investigate the association with the presence and onset of anaemia (WHO definition). The individual study results were pooled using random-effects models. RESULTS: In the 2216 participants (59% female, 30% anaemia) at baseline, iron deficiency, low eGFR and high CRP were individually associated with the presence of anaemia. Low eGFR and high CRP were individually associated with the onset of anaemia. In the cross-sectional analyses, an increase per additional determinant (adjusted OR 2.10 (95% CI 1.85-2.38)) and a combination of ≥2 determinants (OR 3.44 (95% CI 2.70-4.38)) were associated with the presence of anaemia. In the prospective analyses, an increase per additional determinant (adjusted HR 1.46 (95% CI 1.24-1.71)) and the presence of ≥2 determinants (HR 1.95 (95% CI 1.40-2.71)) were associated with the onset of anaemia. CONCLUSION: Very old adults with a combination of determinants of anaemia have a higher risk of having, and of developing, anaemia. Further research is recommended to explore causality and clinical relevance.

The impact of aging and reaching movements on grip stability control during manual precision tasks.

BACKGROUND: Operating an object by generating stable hand-grip force during static or dynamic posture control of the upper extremities simultaneously is an important daily activity. Older adults require different attentional resources during grip strength control and arm movements. However, the impact of aging and reaching movements on precise grip strength and stability control among older adults is not well understood. This study investigated the impact of aging and reaching movements on grip strength and stability control in both hands of the upper extremities. METHODS: Fifty healthy young adults (age: 28.8 ± 14.0 years) and 54 healthy older adults (73.6 ± 6.3 years) were recruited to perform isometric grip strength test at 20% maximal voluntary contraction as the target force during three manual precision tasks simultaneously: stationary task (without arm movements), forward-reach task, and backward-reach task. The average grip force (in kg) and coefficient of variation values (expressed as a percentage) during manual precision tasks were calculated to determine the quality of participants' grip strength. The deviation error, absolute error, and force-stability index values were calculated to determine the strength control relative to the target force. RESULTS: For both the young and older groups, the force-stability index values in both hands were significantly higher during forward- and backward-reaching movements than in the stationary condition (p < 0.05). The older group exhibited a significantly lower hand-grip strength and stability of strength control in both hands than the young group (p < 0.05). CONCLUSIONS: Aging and reaching task performance reduced the grip strength of participants and increased the variations in strength control of both hands relative to the target force, indicating that older adults exhibit poor grip strength and stability control when performing arm-reaching movements. These findings may help clinical therapists in establishing objective indexes for poor grip-stability control screening and developing appropriate rehabilitation programs or health-promotion exercises that can improve grip strength and stability control in older people.

Association Between Specificity of Sulfonylureas to Cardiac Mitochondrial KATP Channels and the Risk of Major Adverse Cardiovascular Events in Type 2 Diabetes.

OBJECTIVE: Previous studies have revealed an intraclass difference in major adverse cardiovascular events (MACE) among sulfonylureas. In vitro and ex vivo studies reported several sulfonylureas to exhibit high-affinity blockage of cardiac mitochondrial ATP-sensitive potassium (mitoKATP) channels and could interfere with ischemic preconditioning, the most important mechanism of self-cardiac protection. However, no studies have examined whether these varying binding affinities of sulfonylureas could account for their intraclass difference in MACE. We compared mitoKATP channel high-affinity versus low-affinity sulfonylureas regarding the MACE risk in real-world settings. RESEARCH DESIGN AND METHODS: Using the Taiwan nationwide health care claims database, patients with type 2 diabetes initiating sulfonylurea monotherapy between 2007 and 2016 were included in the cohort study. A total of 33,727 new mitoKATP channel high-affinity (glyburide and glipizide) and low-affinity (gliclazide and glimepiride) sulfonylurea users, respectively, were identified after 1:1 propensity score matching. Cox proportional hazard models were used to estimate adjusted hazard ratios (aHRs) and 95% CI. RESULTS: MitoKATP channel high-affinity sulfonylureas were associated with a significantly increased risk of three-point MACE (aHR 1.21 [95% CI 1.03-1.44]), ischemic stroke (aHR 1.23 [95% CI 1.02-1.50]), and cardiovascular death (aHR 2.61 [95% CI 1.31-5.20]), but not with that of myocardial infarction (aHR 1.04 [95% CI 0.75-1.46]). The duration-response analyses revealed the highest MACE risk to be within 90 days of therapy (aHR 4.67 [95% CI 3.61-6.06]). CONCLUSIONS: Cardiac mitoKATP channel high-affinity sulfonylureas were associated with an increased MACE risk compared with low-affinity sulfonylureas in a nationwide population with diabetes.

Comparison of Mitochondrial Adenosine Triphosphate-Sensitive Potassium Channel High- vs Low-Affinity Sulfonylureas and Cardiovascular Outcomes in Patients With Type 2 Diabetes Treated With Metformin.

Importance: Sulfonylureas are frequently used as add-on to metformin in type 2 diabetes (T2D), and individual sulfonylurea agents carry different risks of cardiovascular disease. Sulfonylureas' different affinities to cardiac mitochondrial adenosine triphosphate-sensitive potassium (mitoKATP) channels have been speculated to account for the intraclass difference in cardiovascular risk from in vitro and ex vivo studies; however, this hypothesis has not been assessed in a general population with diabetes receiving sulfonylureas added to metformin. Objective: To compare the risk of myocardial infarction (MI), ischemic stroke, or cardiovascular death in patients with T2D treated with mitoKATP channel high-affinity sulfonylureas and low-affinity sulfonylureas as add-on to metformin. Design, Setting, and Participants: This is a new-user, active-comparator, and propensity score-matched cohort study with analysis of the Taiwanese Diabetes Mellitus Health Database from 2006, to 2017. Data analysis was performed from August 2020 to July 2021. Exposures: Cardiac mitoKATP channel high-affinity (glyburide and glipizide) and low-affinity (gliclazide and glimepiride) sulfonylureas combined with metformin. Main Outcomes and Measures: Primary outcome was major adverse cardiovascular events (MACEs), a composite of cardiovascular death or hospitalization for either MI or ischemic stroke. Secondary outcomes included individual MACE components, heart failure, arrhythmia, all-cause mortality, and severe hypoglycemia. Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs). Results: Each sulfonylurea group comprised 53 714 patients (mean [SD] age, 54.7 [12.1] years; 31 962 men [59.5%]). MitoKATP channel high-affinity sulfonylureas vs low-affinity sulfonylureas when combined with metformin were associated with an increased risk of MACE (aHR, 1.18; 95% CI, 1.03-1.34), MI (aHR, 1.34; 95% CI, 1.04-1.73), all-cause mortality (aHR, 1.27; 95% CI, 1.03-1.57), and severe hypoglycemia (aHR, 1.82; 95% CI, 1.58-2.10), but not with increased risks of ischemic stroke, cardiovascular death, arrhythmia, and heart failure. The duration analyses revealed the highest MACE risk during 1 to 90 days after initiation of mitoKATP channel high-affinity sulfonylureas (aHR, 6.06; 95% CI, 4.86-7.55). Conclusions and Relevance: Use of mitoKATP channel high-affinity sulfonylureas vs low-affinity sulfonylureas was associated with an increased MACE risk in patients with T2D concomitantly receiving metformin, suggesting that high-affinity blockage of the mitoKATP channels could account for sulfonylurea-associated MACEs.

Influence of aging and visual feedback on the stability of hand grip control in elderly adults.

Aging causes a gradual decrease in maximal grip strength and leads many elderly people to have to rely on visual feedback to compensate for poorer muscle strength in performing daily activities and preventing accidents. Previous studies have investigated age and visual feedback-related changes in grip strength. However, little is known about methods of determining the quality and stability of hand grip strength control in the elderly, which is important for understanding their ability to generate grip force when handling objects with and without visual feedback in daily living. Therefore, the purpose of this study was to investigate the influence of aging and visual feedback on the stability of hand grip control in both hands in elderly adults. Forty-four healthy elderly persons (age 80.5 ±â€¯4.53 years) and 36 young adults (age 32.69 ±â€¯16.48 years) were recruited to execute grip force stability tasks using both hands at a 2 kg target force level. To perform the grip force stability task, the participants were asked to hold the dynamometer tightly in an attempt to achieve the target force level under visual and non-visual feedback conditions. Strength performances (grip force and coefficient of variation values) and stability of strength control (deviation error, variation error and force stability index values) for hand grip force stability tasks were calculated and analyzed. Compared with the visual feedback condition, the stability of grip force control in the hands of the young and elderly groups were significantly reduced in the non-visual feedback condition by 23.5%-57.1% (p < .05). The elderly group also showed significantly worse hand grip strength performances and stability of hand strength control than the young adult group (p < .05). Aging and non-visual feedback reduced the hand grip force output and stability of grip strength control of the hands. This may reveal the difficulty with manipulating hand-held objects in the absence of visual feedback while performing activities of daily living among the elderly.