The Effects of Switching from Dipeptidyl Peptidase-4 Inhibitors to Glucagon-Like Peptide-1 Receptor Agonists on Bone Mineral Density in Diabetic Patients.

Purpose: Diabetes increases the risk of fragility fractures. As a result, when choosing a diabetes treatment, whether the drug affects bone density should be taken into account. The goal of this study was to determine how switching from dipeptidyl peptidase-4 inhibitors (DPP-4i) to glucagon-like peptide-1 receptor agonists (GLP-1RA) influenced bone mineral density (BMD) in diabetic patients. Patients and Methods: In this retrospective cohort study, diabetic patients with osteoporosis or osteopenia who used DPP-4i but not anti-osteoporosis medications were divided into two groups: those who switched to GLP-1RA (n = 132) and those who did not (control group, n = 133). We compared changes in glycemic control and BMD with and without conversion from DPP-4i to GLP-1RA. Results: Prior to switching, there was no difference between the groups in terms of age, gender, glycosylated hemoglobin (HbA1c), or BMD. HbA1c was 8.7% in the participants (mean age 62.7 years, 17.4% female). Despite the fact that there was no difference in femoral neck BMD, the GLP-1RA group had a greater decrease in lumbar spine BMD (-0.028 g/cm2 versus -0.019 g/cm2, p = 0.041) than the control group. Furthermore, HbA1c levels in the GLP-1RA-treated group were considerably lower than in the control group (7.5% versus 8.0%, p = 0.027). Conclusion: While switching to GLP-1RA improves glycemic control, it appears to have a less favorable effect on bone density than continuing DPP-4i. More research is needed, however, to determine whether diabetic patients with low bone density should be switched from DPP-4i to GLP-1RA.

Effects of Vibration Resistance Exercises on EMG and Skeletal Muscle Hemodynamics.

Objectives: Past studies show that vibration can stimulate muscle activity and improve muscle performance. However, further verification is needed on the effects of different vibration frequencies combined with different muscle strength exercise intensities on EMG activity and skeletal muscle hemodynamics. Methods: We recruited 27 male college athletes for 40%, 60%, and 80% maximum voluntary contraction (MVC) tests at the vibration frequencies of 0 Hz, 10 Hz, 20 Hz, and 30 Hz. We collected EMG activity signals using wireless EMGs and skeletal muscle hemodynamic parameters using a near-infrared spectrometer. Results: At an 80% MVC intensity of the rectus femoris, the mean, peak, and area of EMG at 30 Hz were significantly increased, compared with those at 0 Hz. At a 40% MVC intensity with vibration frequencies of 10 Hz, 20 Hz, and 30 Hz, the HHb of skeletal muscles was significantly increased, while the O2Hb and TSI were significantly decreased, compared with those at 0 Hz. Conclusions: We conclude that high frequency and strongly vibrated muscle strength exercise can improve EMG activity, while vibration and low-intensity muscle strength exercise could increase the oxygen consumption of skeletal muscles.

Retrospective Analysis of the Effects of Non-Compliance with Denosumab on Changes in Bone Mineral Density During the COVID-19 Pandemic.

PURPOSE: Although denosumab is a safe and effective treatment for osteoporosis in various clinical trials, few studies have investigated its efficacy in specific clinical situations. The effect of non-compliance with the standard six-month dosing regimen for denosumab on bone mineral density (BMD) was assessed in a retrospective study of patients prescribed denosumab during the COVID-19 pandemic. PATIENTS AND METHODS: Between February 2019 and September 2020, 638 patient records were reviewed, with 236 patients meeting the eligibility criteria. Patients were divided into three groups: those who received denosumab injections between five and seven months after their initial subcutaneous injection, those who received denosumab injections between seven and nine months after their initial subcutaneous injection, and those who received denosumab injections more than nine months after their initial subcutaneous injection. A multivariate regression study was conducted to compare the BMD shift (at least one year apart) before and after two denosumab injections between the three pre-specified groups in both the lumbar spine (LS) and the femoral neck (FN). RESULTS: The difference between LS BMD indicates that there is a statistical difference between subjects who received denosumab injections between 5 and 7 months (near-standard dosing interval) and more than 9 months (P=0.03), but not in FN BMD, and no clinically significant association was identified. CONCLUSION: The results of this study show that in special clinical situations, such as the COVID-19 pandemic, clinicians may have some flexibility to prescribe denosumab, but the interval between injections should not exceed 9 months.

A Novel Game-Based Intelligent Test for Detecting Elderly Cognitive Function Impairment.

PURPOSES: This research explores the game-based intelligent test (GBIT), predicts the possibilities of Mini-Mental State Examination (MMSE) scores and the risk of cognitive impairment, and then verifies GBIT as one of the reliable and valid cognitive assessment tools. METHODS: This study recruited 117 elderly subjects in Taiwan (average age is 79.92 ± 8.68, average height is 156.91 ± 8.01, average weight is 59.14 ± 9.67, and average MMSE score is 23.33 ± 6.16). A multiple regression model was used to analyze the GBIT parameters of the elderly's reaction, attention, coordination, and memory to predict their MMSE performance. The binary logistic regression was then utilized to predict their risk of cognitive impairment. The statistical significance level was set as α = 0.05. RESULTS: Multiple regression analysis showed that gender, the correct number of reactions, and the correct number of memory have a significantly positive predictive power on MMSE of the elderly (F = 37.60, R 2 = 0.69, and p < 0.05). Binary logistic regression analysis noted that the correct average number of reactions falls by one question, and the ratio of cognitive dysfunction risk increases 1.09 times (p < 0.05); the correct average number of memory drops by one question, the ratio of cognitive dysfunction risk increases 3.76 times (p < 0.05), and the overall model predictive power is 88.20% (sensitivity: 84.00%; specificity: 92.30%). CONCLUSIONS: This study verifies that GBIT is reliable and can effectively predict the cognitive function and risk of cognitive impairment in the elderly. Therefore, GBIT can be used as one of the feasible tools for evaluating older people's cognitive function.

Retrospective Study of the Effects of Zoledronic Acid on Muscle Mass in Osteoporosis Patients.

PURPOSE: Several osteoporosis drugs can continuously improve bone mass, but the impact on muscle mass is still unknown. This study aims to investigate how zoledronic acid monotherapy affected muscle mass in osteoporosis patients. PATIENTS AND METHODS: Patients from an osteoporosis database were divided into two groups in this retrospective cohort, case-control study: zoledronic acid-treated patients (n = 113) and a control group without osteoporosis treatment (n = 118). At four years, appendicular skeletal muscle mass (ASM) and appendicular skeletal muscle mass index (ASMI) were calculated using dual-energy X-ray absorptiometry. The differences in muscle mass between the groups were compared. RESULTS: At baseline, there was no difference in sex, ASM, ASMI, and bone mineral density between the zoledronic acid treatment group and the control group. The treatment group's skeletal muscle mass increased by 841 g in ASM and 0.35 kg/m2 in ASMI after three years, while decreased in the control group. CONCLUSION: This study for the first time demonstrated that that zoledronic acid is beneficial not only to the bone but also to muscle.

A metabolomics approach to investigate the proceedings of mitochondrial dysfunction in rats from prediabetes to diabetes.

Diabetes mellitus (DM) is a leading cause of preventable cardiovascular disease, but the metabolic changes from prediabetes to diabetes have not been fully clarified. This study implemented a metabolomics profiling platform to investigate the variations of metabolites and to elucidate their global profiling from metabolic syndrome to DM. METHODS: Male Sprague-Dawley rats (n = 44) were divided into four groups. Three groups were separately fed with a normal diet, a high-fructose diet (HF), or a high-fat (HL) diet while one group was treated with streptozotocin. The HF and HL diet were meant to induce insulin resistance, obesity, and dyslipidemia, which known to induce DM. RESULTS: The most significant metabolic variations in the DM group's urine samples were the reduced release of citric acid cycle intermediates, the increase in acylcarnitines, and the decrease in urea excretion, all of which indicated energy metabolism abnormalities and mitochondrial dysfunction. Overall, the metabolic analysis revealed tryptophan metabolic pathway variations in the prediabetic phase, even though the mitochondrial function remains unaffected. CONCLUSION: This study show that widespread methylations and impaired tryptophan metabolism occur in metabolic syndrome and are then followed by a decline in citric acid cycle intermediates, indicating mitochondrial dysfunction in diabetes.

Detection of ventilatory thresholds using near-infrared spectroscopy with a polynomial regression model.

Whether near-infrared spectroscopy (NIRS) is a convenient and accurate method of determining first and second ventilatory thresholds (VT1 and VT2) using raw data remains unknown. This study investigated the reliability and validity of VT1 and VT2 determined by NIRS skeletal muscle hemodynamic raw data via a polynomial regression model. A total of 100 male students were recruited and performed maximal cycling exercises while their cardiopulmonary and NIRS muscle hemodynamic data were measured. The criterion validity of VT1VET and VT2VET were determined using a traditional V-slope and ventilatory efficiency. Statistical significance was set at α = . 05. There was high reproducibility of VT1NIRS and VT2NIRS determined by a NIRS polynomial regression model during exercise (VT1NIRS, r = 0.94; VT2NIRS, r = 0.93). There were high correlations of VT1VET vs VT1NIRS (r = 0.93, p < .05) and VT2VET vs VT2NIRS (r = 0.94, p < .05). The oxygen consumption (VO2) between VT1VET and VT1NIRS or VT2VET and VT2NIRS was not significantly different. NIRS raw data are reliable and valid for determining VT1 and VT2 in healthy males using a polynomial regression model. Skeletal muscle raw oxygenation and deoxygenation status reflects more realistic causes and timing of VT1 and VT2.

Hypoxic exercise training causes erythrocyte senescence and rheological dysfunction by depressed Gardos channel activity.

Despite enhancing cardiopulmonary and muscular fitness, the effect of hypoxic exercise training (HE) on hemorheological regulation remains unclear. This study investigates how HE modulates erythrocyte rheological properties and further explores the underlying mechanisms in the hemorheological alterations. Twenty-four sedentary males were randomly divided into hypoxic (HE; n = 12) and normoxic (NE; n = 12) exercise training groups. The subjects were trained on 60% of maximum work rate under 15% (HE) or 21% (NE) O(2) condition for 30 min daily, 5 days weekly for 5 wk. The results demonstrated that HE 1) downregulated CD47 and CD147 expressions on erythrocytes, 2) decreased actin and spectrin contents in erythrocytes, 3) reduced erythrocyte deformability under shear flow, and 4) diminished erythrocyte volume changed by hypotonic stress. Treatment of erythrocytes with H(2)O(2) that mimicked in vivo prooxidative status resulted in the cell shrinkage, rigidity, and phosphatidylserine exposure, whereas HE enhanced the eryptotic responses to H(2)O(2). However, HE decreased the degrees of clotrimazole to blunt ionomycin-induced shrinkage, rigidity, and cytoskeleton breakdown of erythrocytes, referred to as Gardos effects. Reduced erythrocyte deformability by H(2)O(2) was inversely related to the erythrocyte Gardos effect on the rheological function. Conversely, NE intervention did not significantly change resting and exercise erythrocyte rheological properties. Therefore, we conclude that HE rather than NE reduces erythrocyte deformability and volume regulation, accompanied by an increase in the eryptotic response to oxidative stress. Simultaneously, this intervention depresses Gardos channel-modulated erythrocyte rheological functions. Results of this study provide further insight into erythrocyte senescence induced by HE.

Effects of normoxic and hypoxic exercise regimens on cardiac, muscular, and cerebral hemodynamics suppressed by severe hypoxia in humans.

Hypoxic preconditioning prevents cerebrovascular/cardiovascular disorders by increasing resistance to acute ischemic stress, but severe hypoxic exposure disturbs vascular hemodynamics. This study compared how various exercise regimens with/without hypoxia affect hemodynamics and oxygenation in cardiac, muscle, and cerebral tissues during severe hypoxic exposure. Sixty sedentary males were randomly divided into five groups. Each group (n = 12) received one of five interventions: 1) normoxic (21% O(2)) resting control, 2) hypoxic (15% O(2)) resting control, 3) normoxic exercise (50% maximum work rate under 21% O(2); N-E group), 4) hypoxic-relative exercise (50% maximal heart rate reserve under 15% O(2); H-RE group), or 5) hypoxic-absolute exercise (50% maximum work rate under 15% O(2); H-AE group) for 30 min/day, 5 days/wk, for 4 wk. A recently developed noninvasive bioreactance device was used to measure cardiac hemodynamics, and near-infrared spectroscopy was used to assess perfusion and oxygenation in the vastus lateralis (VL)/gastrocnemius (GN) muscles and frontal cerebral lobe (FC). Our results demonstrated that the H-AE group had a larger improvement in aerobic capacity compared with the N-E group. Both H-RE and H-AE ameliorated the suppression of cardiac stroke volume and the GN hyperemic response (Delta total Hb/min) and reoxygenation rate by acute 12% O(2) exposure. Simultaneously, the two hypoxic interventions enhanced perfusion (Delta total Hb) and O(2) extraction [Delta deoxyHb] of the VL muscle during the 12% O(2) exercise. Although acute 12% O(2) exercise decreased oxygenation (Delta O(2)Hb) of the FC, none of the 4-wk interventions influenced the cerebral perfusion and oxygenation during normoxic/hypoxic exercise tests. Therefore, we conclude that moderate hypoxic exercise training improves cardiopulmonary fitness and increases resistance to disturbance of cardiac hemodynamics by severe hypoxia, concurrence with enhancing O(2) delivery/utilization in skeletal muscles but not cerebral tissues.