Potential association of metabolic and musculoskeletal disorders with lumbar intervertebral disc degeneration: Cross-sectional study using medical checkup data.

BACKGROUND: The pathogenesis of intervertebral disc (IVD) degeneration is complex and involves the interaction of multiple factors. However, few systemic studies have explored the associations of metabolic disorders and age-related musculoskeletal disorders with the development of IVD degeneration. METHODS: We analyzed clinical data obtained from healthy individuals who had undergone a musculoskeletal checkup. In total, 276 subjects comprising 142 males and 134 females were enrolled. The subjects were divided into two groups based on the degree of IVD degeneration according to Pfirrmann grading: those with grades 1-3, the group with non-degenerative discs; and grades 4 and 5, the group with degenerative discs. The subjects underwent examinations including abdominal circumference, blood pressure, bilateral hand grip strength, abdominal computed tomography, magnetic resonance imaging of the lumbar spine, and dual X-ray absorptiometry. To examine the independent association with IVD degeneration at L3/4, L4/5, and L5/S levels, we constructed a Poisson regression model and estimated relative risks (RRs) and 95% confidence intervals (CIs) of IVD degeneration. RESULTS: Multivariable analysis showed that advanced age was markedly associated with IVD degeneration at all levels and that men had an inverse association with the IVD degeneration, particularly at the L4/5 level (RR = 0.7, 95% CI = 0.6-0.9). In addition, metabolic syndrome was significantly associated with IVD degeneration at the L5/S level (RR = 1.4, 95% CI = 1.1-1.8). Meanwhile, sarcopenia showed no significant association with IVD degeneration at any level. Osteoporosis was inversely associated with IVD degeneration, particularly at the L4/5 level (RR = 0.7, 95% CI = 0.6-0.9). CONCLUSIONS: Our data suggest that advanced age, female sex, and metabolic syndrome are associated with IVD degeneration. In addition, osteoporosis showed an inverse association with IVD degeneration. Our data should promote understanding of the etiology of lumbar IVD degeneration.

A high BNP level predicts an improvement in exercise tolerance after a successful catheter ablation of persistent atrial fibrillation.

INTRODUCTION: Restoration of sinus rhythm (SR) by catheter ablation (CA) of atrial fibrillation (AF) improves exercise tolerance. However, it is still unclear what characteristics of patients are contributing to an improvement in exercise tolerance after CA of AF without heart failure. METHODS AND RESULTS: This study consisted of 51 consecutive patients with persistent or long-standing persistent AF without heart failure who were restored to SR for over 6 months by a successful CA. Exercise tolerance was evaluated by cardiopulmonary exercise testing before and 3 and 6 months after CA. The clinical characteristics contributing to an improvement in exercise tolerance was elucidated. The peak oxygen uptake (VO2 )% significantly increased from 101.4 ± 20.3% to 110.9 ± 19.9% 3 months after the CA (P < .001). The improvement rate in the peak VO2 % exhibited a positive correlation to the baseline brain natriuretic peptide (BNP; ρ = 0.39, P < .01), but not to the age, AF duration, left ventricular ejection fraction, or left atrial size. The linear regression analysis revealed that the baseline BNP was an independent predictor of an improvement in the peak VO2 % (coefficients = 0.32; 95% confidence interval = 0.08, 0.54; P = .01). The peak VO2 % improved significantly in the patients whose baseline BNP level was greater than 100 pg/mL, compared to the others (P < .01). These favorable findings were also observed 6 months after the CA. CONCLUSION: Elimination of persistent AF by CA was associated with an improvement in exercise tolerance. This was particularly true in patients with high BNP values at baseline.

Relationships of Muscle Echo Intensity with Walking Ability and Physical Activity in the Very Old Population.

This study investigated the relationships between muscle echo intensity (EI), physical activity (PA), and functional mobility in 108 Japanese (88-92 years). We measured EI and muscle thickness (MT) at the midpoint of the anterior superior iliac spine and patella using B-mode ultrasound. Light and moderate-to-vigorous PA (LPA and MVPA) were assessed with a triaxial accelerometer. The timed up and go (TUG) test was used to measure for functional mobility. EI, but not MT, was significantly associated with both TUG scores (ß = 0.17, p = .047) and MVPA (ß = -0.31, p = .01) when adjusted by potential confounders. However, association between EI and TUG disappeared after adjusted for MVPA. Meanwhile, MVPA was significantly associated with TUG scores independent of EI (ß = -0.35, p < .001). Although EI of anterior thigh muscles might be a weaker predictor of functional morbidity than MVPA, it is a noninvasive and practical approach for assessing muscle quality in the very old.

Rhabdomyolysis After Performing Blood Flow Restriction Training: A Case Report.

Tabata, S, Suzuki, Y, Azuma, K, and Matsumoto, H. Rhabdomyolysis after performing blood flow restriction training: a case report. J Strength Cond Res 30(7): 2064-2068, 2016-Rhabdomyolysis is a serious and potentially life-threatening condition related to resistance training. Despite numerous reports of low-intensity blood flow restriction (BFR) training inducing muscle hypertrophy and increasing strength, few reports of rhabdomyolysis related to BFR training have been published. Here, we report a 30-year-old obese Japanese man admitted to our hospital the day after his first BFR training session with complaints of severe muscle pain in his upper and lower extremities, high fever, and pharyngeal pain. He was diagnosed with acute rhabdomyolysis based on a serum creatine phosphokinase level of 56,475 U·L and a urine myoglobin level of >3,000 ng·ml, and with acute tonsillitis based on a white blood cell count of 17,390 and C-reactive protein level of 10.43 mg·dl. A number of factors are suspected to be related to the onset and exacerbation of rhabdomyolysis, including excessive muscular training with BFR, bacterial infection, and medication. After 10 days of hospitalization with intravenous fluids and antibacterial drugs, he recovered without complications. This case indicates that BFR training should be conducted with careful consideration of the physical condition and strength of the individual to prevent serious complications, such as rhabdomyolysis.

Breakfast Skipping is associated with More Deleterious Lifestyle Behaviors among Japanese Men: The TRF-Japan Study Using the Original "Taberhythm" Smartphone Application.

Background: Time-restricted eating has been increasingly recognized as a promising option to reduce food intake and combat obesity. Especially in Asian countries such as Japan, because of the wide variety of food choices available, a dietary approach that emphasizes meal timing can be more practical and easier to implement and adhere to, compared with approaches that focus on specific dietary content, such as low-fat or low-carbohydrate diets. Objectives: We aimed to identify eating patterns among Japanese men and women using a smartphone application (app) called "Taberhythm." In addition, we sought to evaluate the relationship of breakfast eating habits with lifestyle behaviors and body mass index, and determine whether sex differences were present. Methods: A total of 3369 smartphone users were eligible to participate in this observational study. Users recorded 1 mo of lifestyle logs using the app; 254 participants (178 women, 38 ± 12 y old, body mass index 23.3 ± 4.9 kg/m2) had sufficient records to calculate daily fasting duration and sleep duration, and were eligible for the analyses. Results: Fasting duration was ∼12.6 h and was longer in women than men, among participants who never skipped breakfast. Breakfast skipping was associated with longer screen time, and more frequent snacking, only in men. Men with irregular breakfast eating patterns had a longer duration of fasting after awakening that was associated with obesity. Conclusions: We investigated eating patterns among Japanese people using a smartphone app and revealed that skipping breakfast was more deleterious in men than in women.

Real-Time Estimation of Anaerobic Threshold during Exercise Using Electrocardiogram in Heart Failure Patients.

Exercise therapy at the aerobic level is highly recommended to improve clinical outcomes in patients with heart failure, in which cardiopulmonary exercise testing (CPX) is required to determine anaerobic thresholds (ATs) but is not available everywhere. This study aimed to validate a method to estimate the AT using heart rate variability (HRV) analysis from electrocardiography data in patients with heart failure. Between 2014 and 2019, 67 patients with symptomatic heart failure underwent CPXs in a single university hospital. During the CPX, RR intervals was measured continuously and the HRV threshold (HRVT), defined as the inflection point of <5 ms2 of a high-frequency component (HFC) using the power spectrum analysis, was determined. Patients were divided into two groups according to the mean HFC at rest (high-HFC group, n = 34 and low-HFC group, n = 33). The high-HFC group showed good correlation between the VO2 at AT and HRVT (r = 0.63, p < 0.001) and strong agreement (mean difference, -0.38 mL/kg, p = 0.571). The low-HFC group also showed modest correlation (r = 0.41, p = 0.017) but poor agreement (mean differences, 3.75 mL/kg, p < 0.001). In conclusion, the HRVT obtained from electrocardiography may be a useful indicator for estimating AT in patients with heart failure.

PET imaging reveals distinctive roles for different regional adipose tissue depots in systemic glucose metabolism in nonobese humans.

Excess amounts of abdominal subcutaneous (SAT) and visceral (VAT) adipose tissue (AT) are associated with insulin resistance, even in normal-weight subjects. In contrast, gluteal-femoral AT (GFAT) is hypothesized to offer protection against insulin resistance. Dynamic PET imaging studies were undertaken to examine the contributions of both metabolic activity and size (volume) of these depots in systemic glucose metabolism. Nonobese, healthy volunteers (n = 15) underwent dynamic PET imaging uptake of [¹8F]FDG at a steady-state (20 mU·m⁻²·min⁻¹) insulin infusion. PET images of tissue [¹8F]FDG activity were coregistered with MRI to derive K values for insulin-stimulated rates of fractional glucose uptake within tissue. Adipose tissue volume was calculated from DEXA and MRI. VAT had significantly higher rates of fractional glucose uptake per volume than SAT (P < 0.05) or GFAT (P < 0.01). K(GFAT) correlated positively (r = 0.67, P < 0.01) with systemic insulin sensitivity [glucose disappearance rate (R(d))] and negatively with insulin-suppressed FFA (r = -0.71, P < 0.01). SAT (r = -0.70, P < 0.01) and VAT mass (r = -0.55, P < 0.05) correlated negatively with R(d), but GFAT mass did not. We conclude that rates of fractional glucose uptake within GFAT and VAT are significantly and positively associated with systemic insulin sensitivity in nonobese subjects. Furthermore, whereas SAT and VAT amounts are confirmed to relate to systemic insulin resistance, GFAT amount is not associated with insulin resistance. These dynamic PET imaging studies indicate that both quantity and quality of specific AT depots have distinct roles in systemic insulin resistance and may help explain the metabolically obese but normal-weight phenotype.

Retrospective study of factors associated with progression and remission/regression of diabetic kidney disease-hypomagnesemia was associated with progression and elevated serum alanine aminotransferase levels were associated with remission or regression.

AIM: This study was aimed at retrospectively investigating some common clinical factors, including the serum level of magnesium (Mg), associated with progression and remission/regression of diabetic kidney disease (DKD). METHODS: The subjects were 690 Japanese patients with type 2 diabetes mellitus who were receiving treatment with oral antidiabetic drugs other than SGLT2 inhibitors. Routine clinical data were collected on the first and last day of the observation period. The prognosis of DKD is categorized into four stages according to the Kidney Disease Improving Global Outcomes classification. Progression was defined as transition from any of the lower three risk categories (LR, MIR, HR) at the start of the observation period, to the VHR stage/category at the end of the observation period. Remission/regression was defined as improvement of the risk category by at least one stage from the start to the end of the observation period. Factors associated with progression and regression/remission were investigated using Cox proportional hazards analysis. Furthermore, the factors associated with the annual decrease in eGFR of 5 ml/min/1.73 m2 or more were examined by logistic regression analysis. Factors associated with transition of urinary protein negative to trace or positive, or transition of negative or trace to positive, were investigated by Cox proportional hazard analysis. RESULTS: The observation period was 2251 ± 1614 days. Age (Exp [B] = 1.10, 95% CI; 1.06-1.14; P < 0.01; 1 year old), serum Mg (Exp [B] = 0.82, 95% CI; 0.71-0.95; P < 0.01); 0.1 mg/dl), and serum HbA1c (Exp [B] = 1.03, 95% CI; 1.01-1.05; P < 0.01: 0.1%) were associated with progression of DKD; on the other hand, serum ALT was associated with the likelihood of remission/regression of DKD (Exp [B] = 1.01, 95% CI; 1.002-1.018; P < 0.05; 1 IU/L). The decline in eGFR was associated with higher HbA1c levels, hypomagnesemia, and lower ALT. The new appearance of trace or overt proteinuria was correlated with higher HbA1c levels, advancing age, hypomagnesemia and hypertriglycemia. CONCLUSION: Our findings confirmed previous reports that advancing age and serum HbA1c levels were associated with an increased risk of progression of DKD. Lower serum Mg concentrations were also found to be associated with a high risk of progression of DKD, and interventional studies are needed to confirm a causal relationship. Elevated HbA1c levels and hypomagnesemia were common factors in the decline in eGFR and the appearance of trace or overt proteinuria. Lower serum ALT levels were associated with the decline in eGFR. Since serum ALT is known to decrease as the renal function deteriorates, serum ALT is considered to be a marker of renal function. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13340-020-00483-1.

Possible favorable lifestyle changes owing to the coronavirus disease 2019 (COVID-19) pandemic among middle-aged Japanese women: An ancillary survey of the TRF-Japan study using the original "Taberhythm" smartphone app.

Coronavirus disease 2019 (COVID-19) has had a global effect on people's lifestyles. Many people have become physically inactive and developed irregular eating patterns, which leads to unhealthier lifestyles and aggravation of lifestyle-related diseases; these in turn increase the severity of COVID-19. Prior to the COVID-19 pandemic, we developed a smartphone application called "Taberhythm" to investigate eating patterns, physical activity, and subjective feelings of happiness. We aimed to compare lifestyle data before and during the first phase of the COVID-19 pandemic to objectively assess lifestyle changes during quarantine. A total of 464 smartphone users (346 women, 35 ± 12 years old, body mass index [BMI] 23.4 ± 4.5) participated in Period A (January 7 to April 28, 2019) and 622 smartphone users (533 women, 32 ± 11 years old, BMI 23.3 ± 4.0) participated in Period B (January 6 to April 26, 2020). Compared with Period A, there was a sharp decline in physical activity during Period B (4642 ± 3513 vs. 3814 ± 3529 steps/day, p<0.001), especially during the final 9 weeks in both periods (4907 ± 3908 vs. 3528 ± 3397 steps/day, p<0.001); however, there were large variations in physical activity among participants. We found a surprising trend during Period B toward increased happiness among women aged 30-50 years, the group most affected by stay-at-home policies that led to working from home and school closure. Moreover, daily eating duration declined in this population. Additionally, there was a positive association of happiness with steps per day in Period B (ρ = 0.38, p = 0.02). Despite the many negative effects of the COVID-19 pandemic, subjective feelings of happiness among middle-aged Japanese women tended to increase, which indicates that some favorable lifestyle changes that could be adopted during quarantine in the ongoing COVID-19 pandemic.

Metabolic Syndrome is a Predisposing Factor for Diffuse Idiopathic Skeletal Hyperostosis.

OBJECTIVE: Diffuse idiopathic skeletal hyperostosis (DISH) causes spinal ankylosis, which can result in patients suffering specific spinal fractures that lead to a reduction in the activities of daily life in older patients. Currently, DISH is associated with diabetes mellitus and cardiovascular disease; however, the association between DISH and metabolic syndrome has not been established. The purpose of this study was to investigate a potential association between DISH and metabolic syndrome. METHODS: We retrospectively reviewed clinical data from consecutive subjects undergoing the musculoskeletal health medical checkups, and enrolled 327 subjects (174 men and 153 women; mean, 63.4 ± 13.7-years). Subjects who had spinal ankylosis at least 4 contiguous vertebral bodies were classified as the DISH group (n = 39) while the others were part of the non-DISH group (n = 288). The definition of the metabolic syndrome comes from diagnostic criteria used by the Japanese Society for Internal Medicine. Age, sex, body max index (BMI), hematological evaluation, blood pressure, presence of metabolic syndrome, the visceral fat area on abdominal computed tomography, and spinal epidural lipomatosis (SEL) on magnetic resonance imaging were evaluated. RESULTS: Compared to the non-DISH group, in the DISH group, mean age (DISH group, 74.3 years; non-DISH group, 1.9 years; p < 0.001), male prevalence were higher (DISH group, 82.1%; non-DISH group, 49.3%; p < 0.001), and BMI was greater (DISH group, 24.8; non-DISH group, 23.0; p = 0.006). the metabolic syndrome was more frequently observed in DISH group (28.9%) than in the non-DISH group (16.0%) (p = 0.045). The visceral fat area was significantly larger in the DISH group than in the non-DISH group (DISH group, 130.7 ± 58.2 cm2; Non-DISH group, 89.0 ± 48.1 cm2; p < 0.001). The prevalence of SEL was similar between the 2 groups (10.3% in the DISH group vs. 8.7% in the nonDISH group; p = 0.464). Poisson regression analysis revealed that the metabolic syndrome was significantly associated with DISH with odds ratio of 2.0 (95% confidence interval, 1.0-3.7; p = 0.004). CONCLUSION: Metabolic syndrome was significantly associated with DISH. Our data showed metabolic syndrome is potentially related to DISH.

Deficiency of electron transport chain in human skeletal muscle mitochondria in type 2 diabetes mellitus and obesity.

Insulin resistance in skeletal muscle in obesity and T2DM is associated with reduced muscle oxidative capacity, reduced expression in nuclear genes responsible for oxidative metabolism, and reduced activity of mitochondrial electron transport chain. The presented study was undertaken to analyze mitochondrial content and mitochondrial enzyme profile in skeletal muscle of sedentary lean individuals and to compare that with our previous data on obese or obese T2DM group. Frozen skeletal muscle biopsies obtained from lean volunteers were used to estimate cardiolipin content, mtDNA (markers of mitochondrial mass), NADH oxidase activity of mitochondrial electron transport chain (ETC), and activity of citrate synthase and beta-hydroxyacyl-CoA dehydrogenase (beta-HAD), key enzymes of TCA cycle and beta-oxidation pathway, respectively. Frozen biopsies collected from obese or T2DM individuals in our previous studies were used to estimate activity of beta-HAD. The obtained data were complemented by data from our previous studies and statistically analyzed to compare mitochondrial content and mitochondrial enzyme profile in lean, obese, or T2DM cohort. The total activity of NADH oxidase was reduced significantly in obese or T2DM subjects. The cardiolipin content for lean or obese group was similar, and although for T2DM group cardiolipin showed a tendency to decline, it was statistically insignificant. The total activity of citrate synthase for lean and T2DM group was similar; however, it was increased significantly in the obese group. Activity of beta-HAD and mtDNA content was similar for all three groups. We conclude that the total activity of NADH oxidase in biopsy for lean group is significantly higher than corresponding activity for obese or T2DM cohort. The specific activity of NADH oxidase (per mg cardiolipin) and NADH oxidase/citrate synthase and NADH oxidase/beta-HAD ratios are reduced two- to threefold in both T2DM and obesity.

Body Motion and Rowing Performance: Association between Hip Angle and Rowing Performance: A Pilot Study.

The importance of aerobic fitness in rowing has been widely studied, and it is accepted that aerobic fitness is a key factor in rowing performance. In contrast, the impact of rowing efficacy, especially rowing form, on rowing performance has not yet been fully elucidated. The present study aimed to investigate this subject via the analysis of hip kinematics and the association of this variable with 2000 m ergometer rowing test performance. Eleven adult male rowers underwent a 2000 m rowing test on an ergometer and the exhaled gas was analyzed. The hip joint angle, the pelvic rotation, and the knee joint angle were measured at the catch position throughout the test. Peak VO2 was strongly associated with the time taken to complete the test (ρ=-0.96, P<0.01), thereby confirming the importance of aerobic capacity in rowing performance. The variance of the hip joint angle of each rower was associated with peak VO2, lean mass, and test time (ρ=-0.72, -0.84, and 0.66, respectively, all P<0.05). Greater knee flexion was accompanied by larger posterior rotation of the pelvis (ρ=0.74, P<0.05), and was negatively associated with hip flexion (ρ=-0.76, P<0.05). Although we cannot confirm whether the consistency of the hip joint angle actually leads to better rowing performance, our results suggest that there are associations between the consistency of the hip joint angle, aerobic capacity, lean mass, and the time taken to complete the 2000 m ergometer rowing test.

Physical activity levels in American and Japanese men from the ERA-JUMP Study and associations with metabolic syndrome.

Background: Metabolic syndrome (MetS) is a global health problem. Physical activity (PA) is a known modifiable risk factor for MetS and individual MetS components. However, the role of PA could differ between sub-populations due to differences in the variability of PA and other MetS risk factors. To examine these differences, multi-country studies with standardized outcome measurement methods across cohorts are needed. Methods: Cross-sectional PA levels (total and domain specific) in healthy middle-aged (44-56 years) men in the Risk Factor Assessment among Japanese and U.S. Men in the Post-World War II Birth Cohort (ERA-JUMP) Study (n = 730; American: n = 417; Japanese: n = 313; from population-representative samples in Pittsburgh, Pennsylvania, USA, and Kusatsu, Shiga, Japan) were compared. The relationships between PA levels and MetS (overall and specific components) in/across the American and Japanese sub-cohorts (adjusting for age, smoking, and alcohol consumption) were also assessed using the same instruments (pedometer and validated questionnaire) to measure PA in both cohorts. Results: A total of 510 individuals provided complete data on PA (American: n = 265; Japanese: n = 245). The American cohort had significantly lower mean ± SD steps/day (7878 ± 3399 steps/day) vs. the Japanese cohort (9055 ± 3797 steps/day) (p < 0.001) but had significantly higher self-reported moderate-vigorous leisure PA (American: 15.9 (7.4-30.3) metabolic task equivalent hours per week (MET-h/week) vs. Japanese: 4.0 (0-11.3) MET-h/week, p < 0.0001). In both sub-cohorts, each 1000 steps/day increase was associated with lower odds of having MetS (American: OR = 0.90, 95%CI: 0.83-0.98; Japanese: OR = 0.87, 95%CI: 0.79-0.95) and the individual MetS component of high waist circumference (American: OR = 0.86, 95%CI: 0.79-0.94; Japanese: OR = 0.87, 95%CI: 0.80-0.95). In the American cohort only, higher self-reported leisure PA (Met-h/week) was associated with lower odds of MetS and high waist circumference (OR = 0.98, 95%CI: 0.97-0.99 for MetS and waist circumference, respectively). Conclusion: Higher total step counts/day had an important protective effect on MetS prevalence in both the Japanese and American cohorts, despite differences in PA levels and other MetS risk factors. The effect of steps/day (across all intensity levels) was much greater than domain-specific moderate-vigorous PA captured by questionnaire, suggesting the need for measurement tools that can best capture total movement when examining the effects of PA on MetS development.

Spinal epidural lipomatosis is a previously unrecognized manifestation of metabolic syndrome.

BACKGROUND CONTEXT: Spinal epidural lipomatosis (SEL) is a condition in which excess lumbar epidural fat (EF) deposition often leads to compression of the cauda equina or nerve root. Although SEL is often observed in obese adults, no systematic research investigating the potential association between SEL and metabolic syndrome has been conducted. PURPOSE: To elucidate potential association between SEL and metabolic syndrome. STUDY DESIGN: An observational study used data of a medical checkup. PATIENT SAMPLE: We retrospectively reviewed data from consecutive subjects undergoing medical checkups. A total of 324 subjects (174 men and 150 women) were enrolled in this study. OUTCOME MEASURES: The correlation of EF accumulation with demographic data and metabolic-related factors was evaluated. METHODS: The degree of EF accumulation was evaluated based on the axial views of lumbar magnetic resonance imaging. Visceral and subcutaneous fat areas were measured at the navel level using abdominal computed tomography. Metabolic syndrome was diagnosed according to the criteria of the Japanese Society of Internal Medicine. The correlation of SEL with metabolic syndrome and metabolic-related conditions was statistically evaluated. RESULTS: The degree of EF accumulation demonstrated a significant correlation to body mass index, abdominal circumference, and visceral fat area. However, age, body fat percentage, and subcutaneous fat area showed no correlation with the degree of EF accumulation. Logistic regression analysis revealed that metabolic syndrome (odds ratio [OR]=3.8, 95% confidence interval [CI]=1.5-9.6) was significantly associated with SEL. Among the diagnostic criteria for metabolic syndrome, visceral fat area ≥100 cm2 (OR=4.8, 95% CI=1.5-15.3) and hypertension (OR=3.5, 95% CI=1.1-11.8) were observed to be independently associated with SEL. CONCLUSION: This is the first study to demonstrate that metabolic syndrome is associated with SEL in a relatively large, unbiased population. Our data suggest that metabolic-related conditions are potentially related to EF deposition and that SEL could be a previously unrecognized manifestation of metabolic syndrome.

Measurements of islet function and glucose metabolism with the dipeptidyl peptidase 4 inhibitor vildagliptin in patients with type 2 diabetes.

OBJECTIVE: Pharmacological inhibition with the dipeptidyl peptidase 4 (DPP-4) inhibitor vildagliptin prolongs the action of endogenously secreted incretin hormones leading to improved glycemic control in patients with type 2 diabetes mellitus (T2DM). We undertook a double-blinded, randomized-order, crossover study to examine the vildagliptin mechanisms of action on islet function and glucose utilization. RESEARCH DESIGN AND METHODS: Participants with T2DM (n = 16) who had a baseline hemoglobin A(1c) of 7.1 +/- 0.2% completed a crossover study with 6 wk of treatment with vildagliptin and 6 wk with placebo. At the completion of each arm, participants had a study of postprandial metabolism and a two-step glucose clamp performed at 20 and 80 mU/min x m(2) insulin infusions. RESULTS: Vildagliptin increased postprandial glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide by 3- and 2-fold, respectively, reduced fasting plasma glucose and postprandial plasma glucose by 1.3 +/- 0.3 mmol/liter and 1.6 +/- 0.3 mmol/liter (both P <0.01), and improved glucose responsiveness of insulin secretion by 50% (P < 0.01). Vildagliptin lowered postprandial glucagon by 16% (P <0.01). Examined by glucose clamp, insulin sensitivity and glucose clearance improved after vildagliptin (P < 0.01). CONCLUSIONS: Vildagliptin improves islet function in T2DM and improves glucose metabolism in peripheral tissues.

Practical guidance for treatment of patients with diabetes using flash glucose monitoring: a pilot study.

BACKGROUND: Flash glucose monitoring (FGM) is a factory-calibrated, blood glucose measuring sensor system for patients with diabetes. We aimed to investigate the correlation between the sensor glucose (SG) value obtained using an FGM device and the traditional self-monitoring of blood glucose (SMBG) value. METHODS: In 30 patients with diabetes under insulin treatment, SG and SMBG values were measured for 2 weeks, and the correlation between the values was analyzed. RESULTS: The mean number of accumulated measurements of SG values was 1223.2 ± 193.0, whereas that of the SMBG values was 49.2 ± 21.3. Although SG and SMBG values showed a favorable correlation (R2 = 0.8413), SG values were lower than SMBG values by an average of 7.9 ± 29.8 mg/dL. The correlation patterns fell into four types: low type (SG values lower than SMBG values; n = 12), high type (SG values higher than SMBG values; n = 3), cross type (the slope of the two regression lines crossed at a certain measurement value; n = 14), and matching type (the values overlapped; n = 1). CONCLUSIONS: Recognition of the characteristic correlation patterns between SG and SMBG values is indispensable for certified diabetes educators to provide appropriate treatment guidance to patients with diabetes.

Real-Time Analysis of the Heart Rate Variability During Incremental Exercise for the Detection of the Ventilatory Threshold.

BACKGROUND: It has never been possible to immediately evaluate heart rate variability (HRV) during exercise. We aimed to visualize the real-time changes in the power spectrum of HRV during exercise and to investigate its relationship to the ventilatory threshold (VT). METHODS AND RESULTS: Thirty healthy subjects (29.1±5.7 years of age) and 35 consecutive patients (59.0±13.2 years of age) with myocardial infarctions underwent cardiopulmonary exercise tests with an RAMP protocol ergometer. The HRV was continuously assessed with power spectral analyses using the maximum entropy method and projected on a screen without delay. During exercise, a significant decrease in the high frequency (HF) was followed by a drastic shift in the power spectrum of the HRV with a periodic augmentation in the low frequency/HF (L/H) and steady low HF. When the HRV threshold (HRVT) was defined as conversion from a predominant high frequency (HF) to a predominant low frequency/HF (L/H), the VO2 at the HRVT (HRVT-VO2) was substantially correlated with the VO2 at the lactate threshold and VT) in the healthy subjects (r=0.853 and 0.921, respectively). The mean difference between each threshold (0.65 mL/kg per minute for lactate threshold and HRVT, 0.53 mL/kg per minute for VT and HRVT) was nonsignificant (P>0.05). Furthermore, the HRVT-VO2 was also correlated with the VT-VO2 in these myocardial infarction patients (r=0.867), and the mean difference was -0.72 mL/kg per minute and was nonsignificant (P>0.05). CONCLUSIONS: A HRV analysis with our method enabled real-time visualization of the changes in the power spectrum during exercise. This can provide additional information for detecting the VT.

Interactions between delivery, transport, and phosphorylation of glucose in governing uptake into human skeletal muscle.

Skeletal muscle accounts for a large proportion of insulin-stimulated glucose utilization. It is generally regarded that much of the control over rates of uptake is posited within the proximal steps of delivery, transport, and phosphorylation of glucose, with glucose transport as the main locus of control. Whether insulin modulates the distribution of control across these steps and in what manner remains uncertain. The current study addressed this in vivo using dynamic positron emission tomography (PET) imaging of human muscle with sequential injections of three tracers ([(15)O]H(2)O, [(11)C]3-O-methyl glucose [3-OMG], and [(18)F]fluoro-deoxy glucose [FDG]) that enabled quantitative determinations of glucose delivery, transport, and its phosphorylation, respectively. Lean, healthy, research volunteers were studied during fasting conditions (n = 8) or during a euglycemic insulin infusion at 30 mU/min per m(2) (n = 8). PET images were coregistered with magnetic resonance imaging to contrast glucose kinetics in soleus, a highly oxidative muscle, with tibialis anterior, a less oxidative muscle. During fasting conditions, uptake of [(11)C]3-OMG was similar in soleus and tibialis anterior muscles, despite higher delivery to soleus (by 35%; P < 0.01). Uptake of [(18)F]FDG was also similar between muscle during fasting, and glucose transport was found to be the dominant locus of control (90%) for glucose uptake under this condition. Insulin increased uptake of [(11)C]3-OMG substantially and strongly stimulated the kinetics of bidirectional glucose transport. Uptake of [(11)C]3-OMG was higher in soleus than tibialis anterior muscle (by 22%; P < 0.01), a difference partially due to higher delivery, which was again found to be 35% higher to soleus (P < 0.01). The uptake of [(18)F]FDG was 65% greater in soleus compared with tibialis anterior muscle, a larger difference than for [(11)C]3-OMG (P < 0.01), indicating an added importance of glucose phosphorylation in defining insulin sensitivity. Analysis of the distribution of control during insulin-stimulated conditions revealed that most of the control was posited at delivery and transport and was equally divided between these steps. Thus, insulin evokes a broader distribution of control than during fasting conditions in governing glucose uptake into skeletal muscle. This redistribution of control is triggered by the robust stimulation of glucose transport, which in turn unmasks a greater dependence upon delivery and glucose phosphorylation.

Characteristics of skeletal muscle mitochondrial biogenesis induced by moderate-intensity exercise and weight loss in obesity.

There are fewer mitochondria and a reduced oxidative capacity in skeletal muscle in obesity. Moderate-intensity physical activity combined with weight loss increase oxidative enzyme activity in obese sedentary adults; however, this adaptation occurs without a significant increase in mitochondrial DNA (mtDNA), which is unlike the classic pattern of mitochondrial biogenesis induced by vigorous activity. The objective of this study was to examine the hypothesis that the mitochondrial adaptation to moderate-intensity exercise and weight loss in obesity induces increased mitochondrial cristae despite a lack of mtDNA proliferation. Content of cardiolipin and mtDNA and enzymatic activities of the electron transport chain (ETC) and tricarboxylic acid cycle were measured in biopsy samples of vastus lateralis muscle obtained from sedentary obese men and women before and following a 4-mo walking intervention combined with weight loss. Cardiolipin increased by 60% from 47 +/- 4 to 74 +/- 8 microg/mU CK (P < 0.01), but skeletal muscle mtDNA content did not change significantly (1,901 +/- 363 to 2,169 +/- 317 Rc, where Rc is relative copy number of mtDNA per diploid nuclear genome). Enzyme activity of the ETC increased (P < 0.01); that for rotenone-sensitive NADH-oxidase (96 +/- 1%) increased more than for ubiquinol-oxidase (48 +/- 6%). Activities for citrate synthase and succinate dehydrogenase increased by 29 +/- 9% and 40 +/- 6%, respectively. In conclusion, moderate-intensity physical activity combined with weight loss induces skeletal muscle mitochondrial biogenesis in previously sedentary obese men and women, but this response occurs without mtDNA proliferation and may be characterized by an increase in mitochondrial cristae.