Factors related to trunk intramuscular adipose tissue content - A comparison of younger and older men.

The present study investigated factors related to trunk intramuscular adipose tissue (IntraMAT) content in younger and older men. Twenty-three healthy younger (20 to 29 years) and 20 healthy older men (63 to 79 years) participated in this study. The trunk IntraMAT content was measured using magnetic resonance imaging at the height of the 3rd lumbar vertebra. In addition to blood properties and physical performance, dietary intake was assessed by a self-administered diet history questionnaire. The dietary intake status was quantified using the nutrient adequacy score for the intake of 10 selected nutrients by summing the number of items that met the criteria of dietary reference intakes for Japanese individuals. The results obtained revealed that the trunk IntraMAT content was significantly higher in the older group than in the younger group (p < 0.05). In the younger group, the trunk IntraMAT content significantly correlated with systolic and diastolic blood pressure and HbA1c (rs = 0.443 to 0.464, p < 0.05). In the older group, significant and negative correlations were observed between the trunk IntraMAT content and 5-m usual walking speed, handgrip strength, and nutrient adequacy scores (rs = -0.485 to -0.713, p < 0.05). These results indicate that factors associated with the trunk IntraMAT content differed in an age dependent manner. In the younger group, the trunk IntraMAT content correlated with the metabolic status such as blood pressure and HbA1c. In the older group, physical performance and the dietary intake status negatively correlated with the trunk IntraMAT content.

Dietary intake and physical activity in Japanese patients with type 2 diabetes: the Japan Diabetes Complication and its Prevention prospective study (JDCP study 8).

Medical nutrition therapy and exercise therapy are the cornerstones of treatment for patients with type 2 diabetes; however, there has not been a nationwide study on the actual dietary intake and physical activity status of patients since the 2000s. We aimed to clarify this in Japanese patients with type 2 diabetes using data from the Japan Diabetes Complication and its Prevention prospective (JDCP), a nationwide study launched in 2007. A total of 1992 patients with type 2 diabetes, aged 40-75 years, completed either the Brief-type, self-administered Diet History Questionnaire (1643 patients) or International Physical Activity Questionnaire (1834 patients), and their data were analyzed in this study. Mean daily energy intake for all participants was 1686.8 kcal/day, and the mean proportions of carbohydrate, protein, and fat comprising total energy intake were 60.2, 16.2, and 23.6%, respectively. The patients in this study had similar energy and nutrient intake status to patients in the 1996 Japan Diabetes Complications Study; however, Japanese patients still had higher carbohydrate and lower fat consumption than patients with diabetes in Western countries. The physical activity questionnaire reported that 31.0% of patients did not have exercise habits; this was particularly noticeable in female patients and patients under the age of 65. BMI increased from 22.7 to 24.1 kg/m2 in men and 23.2 to 24.8 kg/m2 in women from 1996 to 2007, respectively. Further research is required to investigate how dietary intake and physical activity associates with the risk of developing complications in type 2 diabetes patients.

Relationship between adiponectin and intramuscular fat content determined by ultrasonography in older adults.

Age-associated intramuscular adipose tissue (IntraMAT) deposition induces the development of insulin resistance and metabolic syndrome. However, the relationship between IntraMAT and biochemical parameters in older adults remains unclear. The purpose of this study, therefore, was to elucidate the relationship between adiponectin and echo intensity-estimated IntraMAT using ultrasonography in normal-weight older adults (men 9, women 13) and examine biochemical parameters. Blood tests were performed to determine fasting levels of glucose, insulin, hemoglobin A1c, total cholesterol (Total-C), high-density-lipoprotein cholesterol, low-density-lipoprotein cholesterol (LDL-C), free fatty acid, triglycerides (TGs), adiponectin, leptin, high-sensitivity C-reactive protein, and high-sensitivity tumor necrosis factor, and homoeostasis model assessment index of insulin resistance (HOMA-IR). Mean gray-scale echo intensity was calculated as the IntraMAT index of the vastus lateralis. Waist circumference was measured at the level of the navel as the visceral adipose tissue (VAT) index. Echo intensity was significantly inversely correlated with adiponectin or LDL-C, and that was significantly positively correlated with TG. Adiponectin level was inversely correlated with waist circumference. Partial correlation analysis with waist circumference as the control variable revealed that adiponectin was inversely correlated with echo intensity, independent of waist circumference, whereas no such correlation was observed after controlling for LDL-C and TG levels. When biochemical parameters were grouped in the principal component analysis, among men, Total-C, insulin, and HOMA-IR or hemoglobin A1c, and high-sensitivity tumor necrosis factor-alpha were grouped with the same distribution for factors 1 and 2. Among women, glucose, insulin, HOMA-IR, and Total-C or TGs were grouped with the same distribution for factors 1 and 2. These data suggest that adiponectin level is related to IntraMAT content, independent of VAT in normal-weight older adults. The dynamics of adiponectin might not be similar to those of other circulating biochemical parameters in older men and women.

Effect of Treatment With Sodium-Glucose Cotransporter 2 Inhibitor on the Initiation of Continuous Positive Airway Pressure Therapy in Type 2 Diabetic Patients With Obstructive Sleep Apnea Syndrome.

BACKGROUND: Obese patients with type 2 diabetes mellitus often develop obstructive sleep apnea syndrome (OSAS). In this study, continuous positive airway pressure (CPAP) was initiated in Japanese patients with type 2 diabetes mellitus who developed OSAS during treatment with a sodium-glucose cotransporter 2 (SGLT2) inhibitor, and the effect of the SGLT2 inhibitor therapy on the patients was investigated. METHODS: The study was conducted in outpatients with type 2 diabetes mellitus with serum hemoglobin A1c (HbA1c) values of ≥ 6.5% who developed OSAS. The patients were divided into two groups according to whether they were receiving treatment with an SGLT2 inhibitor or with other oral hypoglycemic agents: the SGLT2 inhibitor group (n = 9) and non-SGLT2 inhibitor group (n = 7). The patients in the former group were under treatment with one of the following three SGLT2 inhibitors: luseogliflozin (2.5 mg/day), dapagliflozin (5 mg/day) and empagliflozin (10 mg/day). The patients took the drugs once daily, before or after breakfast. The patients were initiated on CPAP therapy for OSAS, and their weight, body mass index (BMI), serum HbA1c level, lipid profile, liver function parameters, serum uric acid, and apnea-hypopnea index (AHI) measured before the initiation of CPAP therapy (baseline) were compared with the values measured 3 months after the start of CPAP therapy. RESULTS: The AHI decreased significantly after 3 months of CPAP therapy, as compared to that at the baseline, in both the SGLT2 inhibitor and non-SGLT2 inhibitor groups. There was no significant change in the serum HbA1c value after 3 months of CPAP therapy as compared to that at the baseline in either group. The body weight and BMI increased significantly after 3 months of CPAP therapy in the SGLT2 inhibitor group, but not in the non-SGLT2 inhibitor group. CONCLUSION: The body weight and BMI increased significantly after 3 months of CPAP therapy initiated for OSAS in the type 2 diabetic patients who were receiving SGLT2 inhibitor therapy. Thus, when CPAP therapy is adopted for an obese diabetic patient with OSAS, it should be borne in mind that the body weight may increase if the patient is receiving SGLT2 inhibitor treatment.

Relationship between physical activity time and intramuscular adipose tissue content of the thigh muscle groups of younger and older men.

We investigated the effect of physical activity on muscle tissue size and intramuscular adipose tissue (IntraMAT) content in the thigh muscle groups of younger and older men. Twenty younger and 20 older men participated in this study. The muscle tissue cross-sectional area (CSA) and the IntraMAT content in the quadriceps femoris (QF), hamstrings (HM), hip adductors (AD), and mid-thigh total were measured using magnetic resonance imaging. The physical activity time was measured using a triaxial accelerometer, and four levels of physical activity were determined depending on the metabolic equivalent of task (METs), including sedentary (≤ 1.5 METs), light intensity (≤ 2.9 METs), moderate intensity (3.0-5.9 METs), and vigorous intensity (≥ 6.0 METs). No significant correlation was observed between the physical activity parameters and muscle tissue CSA in both groups. The IntraMAT content of the three muscle groups (QF, AD, and HM) and the total thigh was inversely correlated with the time of moderate-intensity physical activity (rs = - 0.625 to - 0.489, P < 0.05, for all comparisons) in the young group, but not in the older group. These results indicate that IntraMAT accumulation was associated with the amount of moderate-physical activity in younger men.

Investigation of d-allulose effects on high-sucrose diet-induced insulin resistance via hyperinsulinemic-euglycemic clamps in rats.

d-Allulose, a C-3 epimer of d-fructose, is a rare sugar that has no calories. Although d-allulose has been reported to have several health benefits, such as anti-obesity and anti-diabetic effects, there have been no reports evaluating the effects of d-allulose on insulin resistance using a hyperinsulinemic-euglycemic clamp (HE-clamp). Therefore, we investigated the effects of d-allulose on a high-sucrose diet (HSD)-induced insulin resistance model. Wistar rats were randomly divided into three dietary groups: HSD containing 5% cellulose (HSC), 5% d-allulose (HSA), and a commercial diet. The insulin tolerance test (ITT) and HE-clamp were performed after administration of the diets for 4 and 7 weeks. After 7 weeks, the muscle and adipose tissues of rats were obtained to analyze Akt signaling via western blotting, and plasma adipocytokine levels were measured. ITT revealed that d-allulose ameliorated systemic insulin resistance. Furthermore, the results of the 2-step HE-clamp procedure indicated that d-allulose reversed systemic and muscular insulin resistance. d-Allulose reversed the insulin-induced suppression of Akt phosphorylation in the soleus muscle and epididymal fat tissues and reduced plasma TNF-α levels. This study is the first to show that d-allulose improves systemic and muscle insulin sensitivity in conscious rats.

Effect of electromyostimulation on intramyocellular lipids of the vastus lateralis in older adults: a randomized controlled trial.

BACKGROUND: Excessive intramyocellular lipid (IMCL) accumulation is a primary cause of skeletal muscle insulin resistance, especially in older adults, and interventions that reduce IMCL contents are important to improve insulin sensitivity. Electromyostimulation (EMS)-induced changes in IMCL content in older adults remain unknown. The purpose of this study was to clarify the effects of a single bout of EMS on the IMCL content of the vastus lateralis muscle in older adults. METHODS: Twenty-two physically active, non-obese older men and women were randomly assigned to an EMS intervention group (69.0 ± 5.2 years, n = 12) or a control group (68.4 ± 3.5 years, n = 10). EMS was applied to the vastus lateralis (7 s on and 7 s off) for 30 min; control participants sat quietly for 30 min. IMCL content within the vastus lateralis was quantified with 1H-magnetic resonance spectroscopy (n = 7 per group). Fasting plasma glucose and insulin values were determined from blood samples collected before and after the EMS intervention. RESULTS: EMS induced a significant reduction in plasma glucose (93.1 ± 9.6 to 89.5 ± 9.1 mg/dL, p < 0.01), but not IMCL content (15.7 ± 15.7 to 15.8 ± 13.1 mmol/kg wet weight, p = 0.49) or insulin (5.4 ± 2.4 to 4.7 ± 2.7 µIU/mL, p = 0.18). In the control group, no changes in IMCL content in the vastus lateralis was observed after prolonged quiet sitting. CONCLUSION: EMS intervention for 30 min induces changes in plasma glucose, but no changes in IMCL content in older adults. TRIAL REGISTRATION: University hospital Medical Information Network (UMIN) Center ID: UMIN000020126 . Retrospectively registered on December 222,015. https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000023242.

Effects of Aerobic, Resistance, or Combined Exercise Training Among Older Adults with Subjective Memory Complaints: A Randomized Controlled Trial.

BACKGROUND: Physical exercise is suggested to be effective for preventing cognitive decline in older adults, but the relative efficacy of different types of exercise have yet to be clarified. OBJECTIVE: This single-blinded randomized controlled trial was designed to investigate the differential effects of aerobic exercise training (AT), resistance exercise training (RT), and combined exercise training (CT) on cognition in older adults with subjective memory complaints (SMC). METHODS: Community-dwelling older adults with SMC (n = 415; mean age = 72.3 years old) were randomly assigned to one of the four groups: AT, RT, CT, or control group. The study consisted of two phases: a 26-week intervention and a 26-week follow-up. The participants were evaluated at baseline, 26 weeks (postintervention), and 52 weeks (follow-up). The primary outcome of this study was memory function, which was assessed using the Logical Memory II subtest of the Wechsler Memory Scale-Revised (WMS-R) score. The secondary outcomes included global cognitive function, verbal fluency, working memory, processing speed, and executive functions. RESULTS: Intention-to-treat analysis by a mixed-effect model repeated measure showed that the AT group had significantly improved performance on the WMS-R Logical Memory II test (2.74 [1.82-3.66] points) than the control group (1.36 [0.44-2.28] points) at the postintervention assessment (p = 0.037). The effect was more pronounced in those without amnesia than those with amnesia. No significant improvement was observed in the RT and CT groups. CONCLUSION: This study suggests that AT intervention can improve delayed memory in community-dwelling older adults, particularly in individuals without objective memory decline.

The Effects of Pemafibrate in Japanese Patients with Type 2 Diabetes Receiving HMG-CoA Reductase Inhibitors.

OBJECTIVE: The combination therapy of HMG-CoA reductase inhibitors (statins), which are anti-hyperlipidemic agents, and fibrates may increase the risk of hepatic dysfunction and myopathy, therefore, this combination required careful administration for patients. In the present study, the effects of combination therapy of pemafibrate, a novel fibrate, and statins, was evaluated. METHODS: Pemafibrate was administered for 6 months as an add-on to statin therapy in 27 type 2 diabetes patients with dyslipidemia already receiving statins for 6 months (combination group), and the efficacy and safety of the combination therapy in comparison with a pemafibrate monotherapy group was examined. RESULTS: In the combination group, a decrease in serum total cholesterol levels was observed after 6 months of pemafibrate treatment compared to baseline, along with an increase in HDL-cholesterol. While serum triglyceride level was reduced, HbA1c level was elevated in both the groups. Serum creatinine kinase level, which is an indicator of myopathy, was lowered in the combination group. In addition, a decrease in γ-glutamyl transpeptidase, a parameter of hepatic dysfunction, was observed in the combination group. CONCLUSION: The statin-pemafibrate combination therapy in type 2 diabetes patients with dyslipidemia improved lipid metabolism safely without increasing the risk of hepatic dysfunction and myopathy.

Comparing intramuscular adipose tissue on T1-weighted and two-point Dixon images.

PURPOSE: The purpose of this study was to compare intramuscular adipose tissue content determined by two-point Dixon imaging and T1-weighted imaging, calculated using thresholding techniques. METHODS: In total, 19 nonobese younger adults (26.2 ± 4.9 years) and 13 older adults (72.2 ± 6.0 years) were recruited. Axial images of the mid-thigh were taken using T1-weighted and two-point Dixon sequences with a 3.0 T whole-body magnetic resonance device and used to measure intramuscular adipose tissue content of the vastus lateralis, adductor magnus, and long head of the biceps femoris. RESULTS: There was no significant difference in intramuscular adipose tissue content between T1-weighted and two-point Dixon imaging for the vastus lateralis (11.0 ± 4.4% and 12.2 ± 2.4%); however, intramuscular adipose tissue content determined by T1-weighted imaging was significantly higher than that of two-point Dixon imaging for the other muscles. Bland-Altman analysis showed a proportional bias for intramuscular adipose tissue calculations in all three muscles. CONCLUSION: The validity of intramuscular adipose tissue content measurements between T1-weighted and two-point Dixon imaging is muscle-specific. This study showed discrepancies of intramuscular adipose tissue content between T1-weighted and two-point Dixon imaging. ADVANCES IN KNOWLEDGE: This study's results suggest that care should be taken when selecting an imaging modality for intramuscular adipose tissue, especially for patients who would be suspected to have higher intramuscular adipose tissue values.

Effects of Additional Administration of a Selective Inhibitor of Sodium Glucose co-transporter-2 Inhibitor on the Glycemic Control in Japanese Type 2 Diabetes Mellitus Patients Receiving Treatment with a Dipeptidyl Peptidase-4 Inhibitor.

We conducted this study to determine whether additional administration sodium-glucose co-transporter 2 (SGLT2) inhibitor might provide further improvement of glycemic control and also to explore any advantages in Japanese type 2 diabetes patients showing relatively good glycemic control under treatment dipeptidyl peptidase-4 (DPP-4) inhibitors. We divided the patients in two groups, MT group and CT group. The MT group were continued on the DPP-4 inhibitor treatment for 6-months, and CT group were additionally administered an SGLT2 inhibitor treatment for 6-months. The MT group showed a significant decrease of hemoglobin A1c (HbA1c), but a significant increase of body weight, body mass index and serum uric acid, compared to the baseline values, while the CT group showed a significant decrease of HbA1c, body weight, BMI, and serum uric acid, and also a significant increase of serum HDL-cholesterol and decrease of serum triglyceride levels. Furthermore, this group showed a significant decrease of serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma-glutamyl transpeptidase (γ-GTP), which are markers of liver function. These results suggest that the combination therapy is useful, in particular, for the treatment of type 2 diabetes mellitus patients with hyperlipidemia and liver dysfunction. Among the SGLT2 inhibitors added to the DPP-4 inhibitor treatment, the decreases of serum levels of AST, ALT and γ-GTP were particularly significant in the group receiving luseogliflozin, suggesting that the combination of a DPP-4 inhibitor with luseogliflozin is particularly effective for the treatment of type 2 diabetes mellitus patients with liver dysfunction.

Muscle deoxygenation and neuromuscular activation in synergistic muscles during intermittent exercise under hypoxic conditions.

The purpose of this study was to elucidate the effects of hypoxia on deoxygenation and neuromuscular activation in synergistic quadriceps femoris (QF) muscles (i.e., the rectus femoris, vastus medialis, vastus intermedius, and vastus lateralis) during submaximal intermittent knee extension. Ten healthy men performed isometric intermittent knee extension exercises with the right leg at 50% of maximal voluntary contraction for 3 min while inhaling a normoxic [inspired oxygen (O2) fraction = 0.21] or hypoxic (inspired O2 fraction = 0.10-0.12) gas mixture. Muscle deoxygenation was measured by tissue O2 saturation (StO2), and neuromuscular activation by root mean square (RMS) of the surface electromyographic signals, from individual muscles of the QF using near-infrared spectroscopy and surface electromyography. StO2 was decreased more in hypoxia than normoxia during the exercises, and there was a greater increase in RMS during intermittent knee extension in hypoxia than normoxia in individual muscles of the QF. There were no differences in the ratios of StO2 and RMS in hypoxia compared with normoxia between individual muscles of the QF. These findings suggest that submaximal, isometric, and intermittent exercises in hypoxic conditions enhanced muscle oxygen consumption and muscle activity similarly for synergistic muscles.

Age-related changes in muscle volume and intramuscular fat content in quadriceps femoris and hamstrings.

Whether age-related changes in muscle components differ between the quadriceps femoris and hamstrings has remained unclear. This study aimed to compare the muscle volume and echo intensity-estimated intramuscular adipose tissue content of the vastus lateralis (VL) and long head of biceps femoris (BF) muscles between young and older adults. Thirty young adults (n = 15; mean age, 21 years) and older adults (n = 15; mean age, 71 years) participated in this study. Magnetic resonance imaging was performed to determine muscle volumes of the VL and BF, and muscle volume normalized to body weight (muscle volume/weight). Mean gray-scale echo intensity was calculated as the intramuscular adipose tissue index. Muscle volume/weight and echo intensity were normalized using Z-scores in young and older adults. Muscle volume/weight was lower in older adults than in young adults, and lower in overall women than in men for VL (both p < 0.001) and BF (p < 0.01 and p < 0.05). Echo intensity was higher in older adults than in young adults for VL and BF (both p < 0.001), but did not differ between men and women. Z-score of muscle volume/weight was lower in older adults than in young adults for VL (-2.41 ± 1.22; p < 0.05), and Z-score of echo intensity was higher in older adults than in young adults for BF (2.00 ± 0.68; p < 0.05). These results suggest that muscle volume of quadriceps femoris was lower in older adults than in young adults, whereas intramuscular adipose tissue content of hamstrings was greater in older adults than in young adults.

Higher and Lower Muscle Echo Intensity in Elderly Individuals Is Distinguished by Muscle Size, Physical Performance and Daily Physical Activity.

This study was performed to identify factors that discriminate muscle echo intensity (EI) among parameters of body composition, physical function and daily physical activity in elderly individuals. A total of 209 men and women (73.7 ± 2.8 y) were evaluated. EI was measured on ultrasonographic axial thigh muscle images. The participants were categorized into the low, mid and high EI groups. We measured the skeletal muscle mass index (SMI) and physical functions. The high EI group exhibited a significantly lower SMI, slower 5-m walking time and shorter 6-min walking distance than the low EI group and had a shorter moderate-intensity activity time than the mid EI group. As a result of the discriminant analysis, elderly individuals were categorized into EI groups by SMI, daily activity and physical function. The data indicate that morphologic and functional parameters and the daily activity level help to discriminate higher and lower muscle EI.

Relationship between physical activity and intramyocellular lipid content is different between young and older adults.

PURPOSE: Intramyocellular lipid (IMCL) is influenced by physical exercise; however, whether the habitual level of physical activity affects resting IMCL content remains unclear. The purpose of this study was to determine the relationship between physical activity levels and resting IMCL content in young and older adults. METHODS: In total, 15 nonobese young adults (21.0 ± 0.0 years) and 15 older adults (70.7 ± 3.8 years) were recruited. Time spent performing physical activities for 10 days was assessed using a three-dimensional ambulatory accelerometer, and intensity was categorized as light [< 3.0 metabolic equivalents (METs)], moderate (3.0-6.0 METs), or vigorous (> 6.0 METs). Physical activity level was calculated as the product of METs and time spent performing physical activities (MET h) at each intensity level. The IMCL content in the vastus lateralis was determined using 1H-magnetic resonance spectroscopy after overnight fasting. RESULTS: No significant differences in IMCL content were observed between young and older adults. Vigorous intensity physical activity (time and MET h) was significantly lower in older than young adults (p < 0.01); this difference was not observed for light and moderate intensity physical activity. Light intensity physical activity (time and MET h) was significantly and inversely correlated with IMCL content in young adults (r = - 0.59 and r = - 0.58; both p < 0.05), but not in older adults. CONCLUSIONS: These results suggest that daily light intensity physical activity reduces resting IMCL content in young adults, whereas no significant relationship was seen between daily physical activity and resting IMCL content in older adults.

Effects of 10-week walking and walking with home-based resistance training on muscle quality, muscle size, and physical functional tests in healthy older individuals.

BACKGROUND: Older individuals have been shown to present muscle atrophy in conjunction with increased fat fraction in some muscles. The proportion of fat and connective tissue within the skeletal muscle can be estimated from axial B-mode ultrasound images using echo intensity (EI). EI was used to calculate the index of muscle quality. Walking, home-based weight-bearing resistance training, and its combinations are considered simple, easy, and practical exercise interventions for older adults. The purpose of this study was to quantify the effects of walking and walking with home-based resistance training on muscle quality of older individuals. METHODS: Thirty-one participants performed walking training only (W-group; 72 ± 5 years) and 33 participants performed walking and home-based resistance training (WR-group; 73 ± 6 years). This study was a non-randomized controlled trial with no control group. All participants were instructed to walk 2 or 3 sets per week for 10 weeks (one set: 30-min continuous walking). In addition, the WR-group performed home-based weight-bearing resistance training. EI was measured as a muscle quality index using axial B-mode ultrasound images of the rectus femoris and vastus lateralis of the mid-thigh. We further averaged these parameters to obtain the EI of the quadriceps femoris (QF). Participants further performed five functional tests: sit-ups, supine up, sit-to-stand, 5-m maximal walk, and 6-min walk. RESULTS: QF EI was significantly decreased in both groups after training (W-group 69.9 ± 7.4 a.u. to 61.7 ± 7.0 a.u., WR-group 64.0 ± 9.5 a.u. to 51.1 ± 10.0 a.u.; P < 0.05), suggesting improved muscle quality. QF EI was further decreased in the WR-group compared with the W-group. The sit-up test in both groups and the sit-to-stand and 5-m maximal walk tests in the W-group were significantly improved after training. CONCLUSION: These results suggest that training-induced stimulation is associated with a decrease in EI in some thigh regions. Furthermore, the addition of home-based resistance training to walking would be effective for a greater reduction of EI.

Effects of Concomitant Administration of a Dipeptidyl Peptidase-4 Inhibitor in Japanese Patients with Type 2 Diabetes Showing Relatively Good Glycemic Control Under Treatment with a Sodium Glucose Co-Transporter 2 Inhibitor.

We conducted this study to determine whether additional administration of a dipeptidyl peptidase-4 (DPP-4) inhibitor might provide further improvement of the glycemic control in Japanese type 2 diabetes patients showing relatively good glycemic control under treatment with a sodium glucose co-transporter 2 (SGLT2) inhibitor. Five SGLT2 inhibitor (luseogliflozin, dapagliflozin, tofogliflozin, empagliflozin and canagliflozin) preparations and five DPP-4 inhibitor (sitagliptin, vildagliptin, alogliptin, anagliptin and linagliptin) preparations were used. The results showed that monotherapy with SGLT2 inhibitor produced significant decreases of the body weight and BMI, hemoglobin A1c (HbA1c) also decreased, but not to a significant extent. However, decreases of the serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), γ-glutamyltransferase (γ-GTP) and uric acid were observed in this group. On the other hand, in type 2 diabetes patients treated concomitantly with a DPP-4 inhibitor and SGLT2 inhibitor, significant decrease of the HbA1c was observed, indicating the favorable effect of the concomitant therapy. The body weight and BMI decreased. As for the serum lipid profile, elevation of the serum HDL-cholesterol (HDL-C) was observed. Furthermore, AST, ALT, γ-GTP and uric acid decreased in the combined treatment group. Then, the therapeutic responses to concurrent administration with SGLT2 inhibitor of each of the 5 individual DPP-4 inhibitors used in this study were analyzed. The results showed that concomitant administration of sitagliptin, a DPP-4 inhibitor, with the SGLT2 inhibitor yielded the best results in terms of the lowering of the HbA1c and improvement of the serum lipid profile.

Effects of Concomitant Administration of Sodium Glucose Co-transporter 2 Inhibitor with Insulin on Hemoglobin A1c, Body Mass Index and Serum Lipid Profile in Japanese Type 2 Diabetic Patients.

In patients with type 2 diabetes mellitus who show suboptimal blood glucose control under insulin therapy alone, concomitant treatment with an additional hypoglycemic agent that differs in its mechanism of action from insulin may be considered. We conducted this clinical trial to explore whether further control of increased blood glucose level can be achieved with concomitant use of sodium glucose co-transporter 2 (SGLT2) inhibitor as concomitant with other hypoglycemic therapy, as compared to SGLT2 inhibitor monotherapy, in patients with type 2 diabetes mellitus showing decrease in blood glucose level but less than the effect of insulin monotherapy and there was no significant differences. In the SGLT2 inhibitor monotherapy group, decreases of the serum hemoglobin A1c (HbA1c) level, body weight, body mass index (BMI) and serum triglyceride, and elevation of the serum high density lipoprotein cholesterol concentration were observed as compared to the baseline values. In the type 2 diabetic patients under insulin therapy who received combined insulin plus SGLT2 inhibitor therapy, however decreases in the body weight and BMI, with only a tendency towards decrease of the serum HbA1c value, not reaching statistical significance, were observed. The combined therapy group also showed no appreciable changes of the serum triglyceride level, while the serum adiponectin level increased. The present study data indicate that combined insulin plus SGLT2 inhibitor treatment failed to afford any further improvement of the blood glucose control, as compared to SGLT2 monotherapy, in Japanese type 2 diabetic patients.

Effects of post-fracture non-weight-bearing immobilization on muscle atrophy, intramuscular and intermuscular adipose tissues in the thigh and calf.

OBJECTIVE: Disuse and/or a non-weight-bearing condition changes muscle composition, with decreased skeletal muscle tissue and increased fat within (intramuscular adipose tissue, IntraMAT) and between (intermuscular adipose tissue, InterMAT) given muscles. Excessive adipose tissue contributes to dysfunctional and metabolically impaired muscle. How these adipose tissues change during orthopedic treatment (e.g., cast immobilization, daily use of crutches) is not well documented. This study aimed to quantify changes in IntraMAT, InterMAT, and thigh and calf muscle tissue during orthopedic treatment. MATERIALS AND METHODS: We studied 8 patients with fifth metatarsal bone or fibular fractures. The ankle joint involved underwent plaster casting for approximately 4 weeks, with crutches used during that time. Axial T1-weighted MRI at the mid-thigh and a 30% proximal site at the calf were obtained to measure IntraMAT and InterMAT cross-sectional areas (CSAs) and skeletal muscle tissue CSA before treatment and 4 weeks afterward. RESULTS: Thigh and calf muscle tissue CSAs were significantly decreased from before to after treatment: thigh, 85.8 ± 7.6 to 77.1 ± 7.3 cm2; calf, 53.3 ± 5.5 to 48.9 ± 5.0 cm2 (p < 0.05). None of the IntraMAT or InterMAT changes was statistically significant. There was a relation between the percentage change of thigh IntraMAT CSA and muscle tissue CSA (rs = -0.86, p < 0.01). CONCLUSIONS: The 4 weeks of treatment primarily induced skeletal muscle atrophy with less of an effect on IntraMAT or InterMAT. There is a risk of increasing IntraMAT relatively by decreasing skeletal muscle tissue size during orthopedic treatment.

Muscle quality characteristics of muscles in the thigh, upper arm and lower back in elderly men and women.

PURPOSE: The ratio of fat within skeletal muscle is an important parameter that is indicative of muscle quality, and can be assessed using ultrasonography to measure echo intensity (EI). Muscle EI indicates muscle strength and risk of physical dysfunction; however, this observation was determined following examinations of only selected muscle. The purpose of this study was to investigate the EI characteristics of muscles in several regions in elderly men and women, using physical function tests and serum cholesterol levels. METHODS: Twenty-two men and women (age 78 ± 8 years) participated in this study. The EIs were calculated from rectus femoris (RF), biceps femoris (BF) triceps brachii (TB) and multifidus (MF) using B-mode transverse ultrasound images. Seven functional tests (isometric knee-extension peak torque, functional reach, sit-to-stand, 5-m normal/maximal speed walking, handgrip strength and timed up-and-go) and blood lipid components including adipocytokines were measured in all participants. RESULTS: A statistically significant correlation between EI of the RF, TB and BF was observed (r = 0.46-0.50, P < 0.05), but not between EI of the MF and that of other muscles. EI of muscles of the limbs, which was averaged EI for RF, TB and BF, was negatively correlated with leptin levels (adjusted R2 = 0.27, P < 0.01), and EI of the MF was correlated with muscle mass and performance in the timed up-and-go test (adjusted R2 = 0.61, P < 0.01). CONCLUSION: These results suggest that EI might be influenced by specific parameters depending on the location of the muscle.