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In the present super aged society that has limited financial resources for efficient health care for the elderly population, fall prevention is an urgent issue. The present study examined the relationship between exercise habit and fall risks among elderly people living in an urban area. A total of 1,014 elderly people (age: 65–89 years) living in Osaka City were enrolled in this study and assigned to 5 different age groups. The motor abilities of the participants were evaluated by the Functional Reach Test (FRT) and the Timed Up and Go (TUG) test, with the cutoff value for fall risk set at 25 cm and 13.5 s, respectively. Exercise habit (≤1 h, 1–2 h, or ≥2 h per week), history of recent falls, and anxiety about falling were also assessed using a questionnaire modified from the checklist by the Ministry of Health, Labour and Welfare of Japan. The results of the FRT and TUG tests were increasingly poorer in higher age groups. History of recent falls and anxiety about falling were also more frequent in higher age groups (all p < .05). The prevalence of exercise habits was similar among the age groups. In the age groups >75 years, there was an association between exercise habit and a decrease in fall risks, based on the FRT results (all p < .05). The mean FRT value of the participants with the greatest exercise habit was equivalent to that of the generation 10 years younger with the lowest exercise habit. There was an association between exercise habit and decreased anxiety about falling (p = .003), but not with a history of recent falls. Our results suggest that exercise should be promoted among elderly people living in urban areas to contribute to fall prevention.

Cerebral blood flow (CBF) would be impaired with dual stresses of heat and orthostatic changes, even if those stresses are mild, in the elderly with declined cardio- and cerebrovascular functions with aging. To test the hypothesis, we compared the response of blood flow in the internal carotid artery (ICA) and vertebral artery (VA) to dual stresses of heat and orthostatic changes between the elderly and young individuals. Nine elderly and eight young healthy men (71.3 ± 3.0 and 23.3 ± 3.1 years, mean ± SD, respectively) underwent measurements of blood flow in the ICA, VA and external carotid artery (ECA) via ultrasonography. The measurements were obtained in sitting and supine positions under normothermic (NT) and mildly hyperthermic (HT) conditions (ambient temperature 28 °C). Esophageal temperatures increased from NT (36.4 ± 0.2 °C, mean ± SE) to HT (37.4 ± 0.2 °C) with lower legs immersion in 42 °C water. With heat stress, ECA blood flow increased in both postures in both age groups (effect of heat, p

Fragrance inhalation of essential oils is widely used in aromatherapy, and it is known to affect blood pressure (BP) and heart rate (HR) via autonomic control of circulation. In this study, we aimed to test the hypothesis that the changes in hemodynamics with fragrance inhalation were observed along with changes in muscle sympathetic nerve activity (MSNA). In study 1, thirteen healthy men were exposed to fragrance stimulation of grapefruit essential oil for 10 min, and BP, HR, and MSNA were continuously measured. In study 2, another nine healthy men were exposed to the same fragrance stimulation; responses in BP and HR were continuously measured, and plasma noradrenaline and cortisol concentrations were determined. We found that diastolic BP increased significantly during fragrance inhalation, while the other variables remained unchanged in both studies. Although MSNA burst frequency, burst incidence, and total activity remained unchanged during fragrance inhalation, we found a significant linear correlation between changes in diastolic BP in the last 5 min of fragrance inhalation and changes in MSNA burst frequency. The plasma cortisol concentration decreased significantly at 10 min of fragrance inhalation, though the noradrenaline concentration remained unchanged. These results suggest, for the first time, that changes in BP with fragrance inhalation of essential oil are associated with changes in MSNA even with decreased stress hormone.

We assessed whether plasma lactate accumulation increased and the lactate threshold (LT) declined when the skin temperature was lowered by whole body skin surface cooling before exercise in cool, but not temperate, conditions, and whether the lowered LT was associated with sympathetic activation or lowered plasma volume (PV) by cold-induced diuresis. Ten healthy subjects performed a graded maximal cycling exercise after pre-conditioning under three different conditions for 60 min. Ambient temperature (using an artificial climatic chamber) and water temperature in a water-perfusion suit controlled at 25 and 34 °C in temperate–neutral (Temp–Neut); 25 and 10 °C in temperate–cool (Temp–Cool); and at 10 and 10 °C in cool–cool (Cool–Cool) conditions, respectively. Esophageal (Tes) and skin temperatures were measured; plasma lactate ([Lac]p) and noradrenaline concentrations ([Norad]p), and relative change in PV (%ΔPV) were determined before and after pre-conditioning and during exercise, and LT was determined. After pre-conditioning, Tes was not different among trials, whereas the mean skin temperature was lower in Cool–Cool and Temp–Cool than in Temp–Neut (P

研究グループは、パラアスリートの栄養に関する知識や理想とする食事の実現ができているか等の食行動上の課題を明らかにするため、国際大会および国体出場レベルかつ肢体不自由を伴うパラアスリート32名に、栄養知識や食行動、ボディイメージ(自分自身が無意識に持っている「自分の身体」についてのイメージ)等をアンケート形式で調査しました。その結果、対象の約4割が食材の調達や調理に介助を必要としており、自力ではパラアスリート自身が理想としている食事の実現が難しいことがわかりました。また、良いボディイメージを持っているパラアスリートほど自身の食習慣を健康的であると評価していましたが、実際には栄養知識について問う設問の正答率は低く、「体調が良い」「身体に異常がない」といった主観的感覚をもとに自分の食事量を「適切」と判断していることがわかりました。さらに、パラアスリートが栄養に関する知識を得る手段として、栄養士を挙げた例は極めて少なく、スポーツ栄養の正しい知識を持っている栄養士との接点がほとんどないのが実態であると思われました。本研究によってパラアスリートに対する栄養知識の教育や、食行動におけるサポート体制の必要性が明らかになりました。今後、このような対処に関わる研究の蓄積によって、より効果的な栄養サポート方法の開発に貢献することが期待されます。, Limited information exists on dietary practices in para-athletes. The aim of this study was to clarify the actual situation of para-athletes' dietary practice and to sort out the factors (i.e., eating perception, nutrition knowledge, and body image), that may hinder their dietary practices, and explored the practical challenges in nutritional support and improving nutrition knowledge for para-athletes. Thirty-two Japanese para-athletes (22 men) and 45 collegiate student athletes without disabilities (27 men) participated in the online survey. The questionnaire included demographic characteristics, eating perception, dietary practices, and nutrition knowledge. The Japanese version of the body appreciation scale was used to determine their body image. Para-athletes who answered that they knew their ideal amount and way of eating showed significantly higher body image scores (r = 0.604, p < 0.001). However, mean score for nutrition knowledge of para-athletes were significantly lower than collegiate student athletes (19.4 ± 6.8 vs. 24.2 ± 6.1 points, p = 0.001). Both groups did not identify a dietitian as the source of nutrition information or receiving their nutrition advice. The results indicate para-athletes have unique eating perceptions and inadequate nutrition knowledge. Future interventions are needed to examine nutritional supports and education in relation to the role of dietitians.

This study examined the effect of an exercise intervention on the composition of the intestinal microbiota in healthy elderly women. Thirty-two sedentary women that were aged 65 years and older participated in a 12-week, non-randomized comparative trial. The subjects were allocated to two groups receiving different exercise interventions, trunk muscle training (TM), or aerobic exercise training (AE). AE included brisk walking, i.e., at an intensity of &ge, 3 metabolic equivalents (METs). The composition of the intestinal microbiota in fecal samples was determined before and after the training period. We also assessed the daily physical activity using an accelerometer, trunk muscle strength by the modified Kraus&ndash, Weber (K-W) test, and cardiorespiratory fitness by a 6-min. walk test (6MWT). K-W test scores and distance achieved during the 6MWT (6MWD) improved in both groups. The relative abundance of intestinal Bacteroides only significantly increased in the AE group, particularly in subjects showing increases in the time spent in brisk walking. Overall, the increases in intestinal Bacteroides following the exercise intervention were associated with increases in 6MWD. In conclusion, aerobic exercise training that targets an increase of the time spent in brisk walking may increase intestinal Bacteroides in association with improved cardiorespiratory fitness in healthy elderly women.

Trehalose (TRE), a disaccharide, is absorbed slowly and gradually increases the blood glucose (GLU) level along with reducing insulin secretion. The aim of this study was twofold. First, we examined exercise performance following ingestions of either GLU, TRE, or water (WAT). The second purpose was to investigate the effects of TRE energy metabolism during prolonged exercise. We examined exercise performance using the Wingate test, with 30-min constant load exercise at 40% VO2peak after exercising for 60 min at 40% VO2peak, by using an electromagnetic brake-type bicycle ergometer (Part 1). The power values, blood glucose and lactate, and respiratory exchange ratio (RER) were measured. In addition, we investigated the energy metabolism after a single ingestion of TRE, by measuring the RER and estimating the lipid oxidation for 60 min at 40% VO2peak (Part 2). Healthy college male students performed three trials&mdash, (1) placebo (WAT), (2) GLU, and (3) TRE. Repeated two-way analysis of variance (ANOVA) was used for a comparison of the data among the three trial groups. A multiple comparison test was performed using post hoc Bonferroni correction. The TRE ingestion significantly increased the average and maximum power values (p &lt, 0.01). The TRE ingestion showed significantly higher lipid utilization than the GLU lipid oxidation values the in TRE, 12.5 &plusmn, 6.1 g/h, GLU, 9.3 &plusmn, 4.7 g/h, and WAT, 15.0 &plusmn, 4.4 g/h, (p &lt, 0.01). In conclusion, we provide novel data that a single TRE ingestion was effective in improving prolonged exercise performance by effective use of glucose and lipids.

Thermal sensation represents the primary stimulus for behavioral and autonomic thermoregulation. We assessed whether the sensation of skin and core temperatures for the driving force of behavioral thermoregulation was modified by postural change from the supine (Sup) to sitting (Sit) during mild hyperthermia. Seventeen healthy young men underwent measurements of noticeable increase and decrease (±0.1 °C/s) of skin temperature (thresholds of warm and cold sensation on the skin, 6.25 cm2 of area) at the forearm and chest and of the whole-body warm sensation in the Sup and Sit during normothermia (NT; esophageal temperature (Tes), ∼36.6 °C) and mild hyperthermia (HT; Tes, ∼37.2 °C; lower legs immersion in 42 °C of water). The threshold for cold sensation on the skin at chest was lower during HT than NT in the Sit (P

The purpose of the present study was to investigate the effect of walking in water on respiratory muscle fatigue compared with that of walking on land at the same exercise intensity. Ten healthy males participated in 40-min treadmill walking trials on land and in water at an intensity of 60 % of peak oxygen consumption. Respiratory function and respiratory muscle strength were evaluated before and after walking trials. Inspiratory muscle strength and forced expiratory volume in 1 s were significantly decreased immediately after walking in water, and expiratory muscle strength was significantly decreased immediately and 5 min after walking in water compared with the baseline. The decreases of inspiratory and expiratory muscle strength were significantly greater compared with that after walking on land. In conclusion, greater inspiratory and expiratory muscle fatigue was induced by walking in water than by walking on land at the same exercise intensity in healthy young men.

[Purpose] The purpose of the present study was to evaluate the effect of water immersion at different water depths on respiratory function and the effect of inspiratory load breathing (ILB) during water immersion at different water depths on respiratory muscle strength evaluated by maximum inspiratory and expiratory pressures (PImax and PEmax, respectively). [Subjects] Eight healthy men participated randomly in three trials. [Methods] All sessions were conducted with the participants in a sitting position immersed in a water bath. We evaluated respiratory function, PImax and PEmax during submersion at three different levels of water depth (umbilicus; 4th-rib; or clavicle, CL) and after subsequent 15-min ILB. [Results] Decreases in vital capacity and expiratory reserve volume from baseline by water immersion were significantly greater in the CL trial than those in the other trials. In the CL trial, PImax was immediately reduced after ILB compared to that at baseline, and the reduction was significantly greater than those in the other trials. PEmax was not affected by ILB in any of the trials. [Conclusion] Forced respiration during deeper water immersion caused greater inspiratory muscle fatigue in healthy young men.

Endurance training at a level (FATmax) that raises the maximal fat oxidation rate (max FOR) may contribute to body weight loss in obese individuals. However, max FOR and FATmax are reduced in subjects with obesity and/or with insulin resistance compared with those without. On the other hand, in humans, intranasal insulin administration increases the concentration of insulin in cerebrospinal fluid when peripheral effects are absent, resulting in reduced food intake and body weight. However, it remains unclear whether insulin delivery to the brain affects fat oxidation during exercise. In this study, we examined the effects of nasal insulin administration on max FOR during exercise in 11 normal-weight (N group) and seven overweight (O group) young individuals. On two separate days, either 40 IU regular insulin (INS) or normal saline, as placebo (PL), was randomly administered intranasally after overnight fasting, and then each participant underwent a graded exercise test. Indirect calorimetry was used to assess max FOR during exercise and FATmax. Blood insulin and glucose levels did not change after insulin administration. In the N group, max FOR tended to decrease in the INS trial (p = 0.050); FATmax and the total amount of fat oxidation during exercise were significantly smaller in the INS trial than in the PL trial. Max FOR was significantly smaller in the O group than in the N group (p = 0.021) and was not influenced by insulin administration. Blood adrenaline levels increased by exercise tended to be reduced by insulin administration in the N group only. In conclusion, intranasal insulin administration reduces fat oxidation during exercise without increasing peripheral insulin levels, possibly via the suppression of sympathetic nerve activity. The inhibitory effects of intranasal insulin administration on fat oxidation during exercise are diminished in overweight subjects, suggesting cerebral insulin effects are attenuated in this population. Disclosure H. Yokoyama: None. R. Takeda: None. E. Kawai: None. A. Ota: None. E. Morita: None. D. Imai: None. Y. Suzuki: None. T. Morioka: Consultant; Self; Ono Pharmaceutical Co., Ltd.. Research Support; Self; Novartis Pharma K.K., MSD K.K., Eli Lilly and Company, Sanofi K.K., Mitsubishi Tanabe Pharma Corporation. Speaker's Bureau; Self; Takeda Pharmaceuticals U.S.A., Inc., Novo Nordisk Inc., Kowa Pharmaceuticals America, Inc., Astellas Pharma US, Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Sumitomo Dainippon Pharma Co., Ltd. M. Emoto: Speaker's Bureau; Self; Eli Lilly and Company, Boehringer Ingelheim Pharmaceuticals, Inc., Sumitomo Dainippon Pharma Co., Ltd.. Research Support; Self; Astellas Pharma Inc, Ono Pharmaceutical Co., Ltd., Kissei Pharmaceutical Co., Ltd., Kowa Pharmaceutical Company Ltd., Taisho Toyama Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation. M. Inaba: None. K. Okazaki: None.

We aimed to examine the effect of 2-year cognitive–motor dual-task (DT) training on cognitive functions and motor ability of healthy elderly people without marked cognitive impairment. From the 25 participants of our 12-week DT trial conducted in 2014, we recruited 8 subjects who voluntarily participated in a new DT training program once a week for 2 years (exercise (EX) group). Their cognitive functions were evaluated by the Modified Mini-Mental State (3MS) examination and the Trail Making Test, and results were compared with those of the 11 subjects who discontinued the training and did not perform any types of exercise for 2 years (non-exercise (NO) group). Subjects in the NO group showed deterioration in the 3MS examination results, especially in the cognitive domain of attention. Meanwhile, participation in DT training maintained the scores in almost all domains of cognitive function, as well as the total 3MS scores. However, both groups had impaired quadriceps muscle strength and motor ability after the 2-year observation period. These results suggest that participating in exercise program comprising DT training for 2 years may be beneficial for maintaining the broad domains of cognitive function in healthy elderly people, although further verification is needed.

A small number of patients with chronic kidney disease (CKD), particularly those on maintenance hemodialysis, are in the habit of exercise, and this sedentary lifestyle and poor physical fitness is associated with a high prevalence of fall-associated fracture and an increased mortality risk. However, exercise training has various therapeutic benefits in these patients. It delays the progression of microalbuminuria or CKD, increases physical fitness and strength, improves mental health, enhances dialysis efficacy, results in a better glycemic control, and reduces both cardiovascular and mortality risks.

It remains unknown whether the high insulin (INS) levels in the brain affect fat oxidation during exercise. We examined the effects of the intranasal administration of INS, which increases the INS concentration in the cerebrospinal fluid when peripheral effects are lacking, on the maximum fat oxidation rate (maxFOR) and its intensity (FATmax) during exercise in 15 young normal-weight (N group) and eight young overweight (O group) individuals. On two separate days, either INS or placebo (PL) was randomly administered intranasally before a graded exercise test. Indirect calorimetry was used to assess maxFOR and FATmax during exercise. Blood INS and glucose levels did not change after INS administration. In the N group, maxFOR and FATmax were significantly smaller in the INS trial than in the PL trial. MaxFOR was significantly smaller in the O group than in the N group and was not influenced by INS administration. Exercise-induced elevation in blood epinephrine levels tended to be reduced by INS administration only in the N group. Intranasal INS administration reduces fat oxidation during exercise without any peripheral effects, possibly by suppressing sympathetic nerve activity. This inhibitory effect is diminished in overweight subjects, suggesting that cerebral insulin effects are attenuated in this population.

Whole-body glucose utilization consists of mitochondrial glucose oxidation and non-oxidative glycogen synthesis. We examined whether reduction of both non-oxidative glucose disposal and glucose oxidation contributes to insulin resistance in type 2 diabetes. We also examined the effects of exercise on these two components. Whole-body glucose disposal rate (GDR, mg/kg/min) was evaluated in 37 type 2 diabetic (T2DM) and 17 non-diabetic (non-DM) subjects as the mean of glucose infusion rate during steady state in the euglycaemic-hyperinsulinaemic clamp study. Glucose oxidation rates were assessed by indirect calorimetry, and non-oxidative GDR was calculated by subtracting glucose oxidation rate from GDR. Intramyocellular lipid (IMCL) content of the soleus muscle was measured using (1)H-magnetic resonance spectroscopy. In 10 T2DM subjects, the changes in oxidative and non-oxidative glucose disposal during clamp were examined after 3-month exercise intervention. GDR (2.93 +/- 1.55 vs. 4.55 +/- 1.83, p = 0.001) and non-oxidative GDR (1.45 +/- 1.52 vs. 3.01 +/- 1.87, p = 0.002) were significantly lower in T2DM than in non-DM subjects. Glucose oxidation rate was comparable in the two groups, and inversely correlated with IMCL (n = 15, r =-0.565, p = 0.028). GDR (2.28 +/- 1.67 to 4.63 +/- 2.42, p = 0.021) and non-oxidative GDR (0.72 +/- 1.27 to 2.26 +/- 1.91, p = 0.047) were increased after exercise intervention, although the change in glucose oxidation rate was not significant. In summary, reduction of non-oxidative glucose disposal may contribute to decreased whole-body glucose utilization. In addition, exercise improves insulin resistance mainly by increasing non-oxidative glucose disposal in type 2 diabetes.

Summary Objective Fetuin-A is a circulating glycoprotein which is well characterized as an inhibitor of ectopic calcification. Vascular calcification commonly found in chronic kidney disease (CKD) patients is a predictor of cardiovascular death. Recently, several groups have demonstrated that low fetuin-A levels are associated with mortality in uraemic patients, possibly through regulation of vascular calcification. However, the physiological significance of fetuin-A in atherosclerosis remains unknown, except in specific conditions, such as vascular calcification in CKD patients. The objective of this study was to investigate the association between serum fetuin-A levels and arterial stiffness, a functional property of atherosclerosis, in healthy subjects. Patients and measurements The study subjects comprised 141 healthy subjects. We measured serum fetuin-A levels and stiffness parameter β for the common carotid artery, which was assessed by ultrasound using a phase-locked echo-tracking system. Results Simple regression analyses indicated that serum fetuin-A levels were significantly correlated with stiffness parameter β (r = 0·200, P = 0·018). Multiple regression analyses showed that, besides age, fetuin-A (β = 0·166, P = 0·033) independently contribute to the stiffness parameter β (R2 = 0·310, P

It is important to know how thermal sensation is affected by normal aging under conditions that elevate core body temperature for the prevention of heat-related illness in older people. We assessed whether thermal sensation under conditions of normothermia (NT) and mild hyperthermia (HT) is lowered in older adults. Seventeen younger (23 ± 3 years) and 12 older (71 ± 3 years) healthy men underwent measurements of the cold and warmth detection thresholds ( ± 0.1 °C/s) of their chest and forearm skin, and whole body warmth perception under NT (esophageal temperature, T es, ~36.5 °C) and HT (T es, ~37.3 °C; lower legs immersed in 42 °C water) conditions. Warmth detection threshold at the forearm was increased in older compared with younger participants under both NT (P = 0.006) and HT (P = 0.004) conditions. In contrast, cold detection threshold at the forearm was decreased in older compared with younger participants under NT (P = 0.001) but not HT (P = 0.16). Mild hyperthermia decreased cold detection threshold at forearm in younger participants (P = 0.001) only. There were no effects of age and condition on warmth and cold detection thresholds at chest. Whole body warmth perception increased during HT compared with NT in both groups (both, P

Background Physical activity reduces the incidence and progression of cognitive impairment. Cognitive-motor dual-task training, which requires dividing attention between cognitive tasks and exercise, may improve various cognitive domains; therefore, we examined the effect of dual-task training on the executive functions and on plasma amyloid β peptide (Aβ) 42/40 ratio, a potent biomarker of Alzheimer’s disease, in healthy elderly people. Methods Twenty-seven sedentary elderly people participated in a 12-week randomized, controlled trial. The subjects assigned to the dual-task training (DT) group underwent a specific cognitive-motor dual-task training, and then the clinical outcomes, including cognitive functions by the Modified Mini-Mental State (3MS) examination and the Trail-Making Test (TMT), and the plasma Aβ 42/40 ratio following the intervention were compared with those of the control single-task training (ST) group by unpaired t-test. Results Among 27 participants, 25 completed the study. The total scores in the 3MS examination as well as the muscular strength of quadriceps were equally improved in both groups after the training. The specific cognitive domains, “registration & recall”, “attention”, “verbal fluency & understanding”, and “visuospatial skills” were significantly improved only in the DT group. Higher scores in “attention”, “verbal fluency & understanding”, and “similarities” were found in the DT group than in the ST group at post-intervention. The absolute changes in the total (8.5 ± 1.6 vs 2.4 ± 0.9, p = 0.004, 95 % confidence interval (CI) 0.75―3.39) and in the scores of “attention” (1.9 ± 0.5 vs −0.2 ± 0.4, p = 0.004, 95 % CI 2.25―9.98) were greater in the DT group than in the ST group. We found no changes in the TMT results in either group. Plasma Aβ 42/40 ratio decreased in both groups following the training (ST group: 0.63 ± 0.13 to 0.16 ± 0.03, p = 0.001; DT group: 0.60 ± 0.12 to 0.25 ± 0.06, p = 0.044), although the pre- and post-intervention values were not different between the groups for either measure. Conclusions Cognitive-motor dual-task training was more beneficial than single-task training alone in improving broader domains of cognitive functions of elderly persons, and the improvement was not directly due to modulating Aβ metabolism.

Adiponectin, an adipocyte-specific plasma protein, has been reported to exhibit protective effects against atherosclerosis as well as an insulin-sensitizing effect. This study was designed to investigate the effect of adiponectin on carotid arterial stiffness in type 2 diabetic patients treated with pioglitazone and metformin. Twenty type 2 diabetic patients were enrolled and divided into 2 groups, a pioglitazone-treated group (n = 10) and a metformin-treated group (n = 10). Before and after intervention, plasma adiponectin levels were measured by enzyme-linked immunosorbent assay and carotid arterial stiffness was evaluated by the stiffness parameter beta, measured by ultrasound equipped with a phase-locked echo-tracking system. In the pioglitazone group, plasma adiponectin level significantly increased and stiffness parameter beta significantly decreased, whereas in the metformin group neither of these parameters changed significantly. The changes in stiffness parameter beta were significantly and inversely correlated with change in plasma adiponectin level after treatment with pioglitazone or metformin in the group of all subjects (r = -0.472, P = .036). In conclusion, the present study is the first to demonstrate that increase in adiponectin level after treatment with the insulin sensitizers pioglitazone and metformin may improve arterial stiffness in patients with type 2 diabetes mellitus.

Adiponectin plays important roles in protecting against both insulin resistance and the development of atherosclerosis. The aim of the present study was to investigate the clinical impact of plasma adiponectin on arterial stiffness, a functional property of atherosclerosis, in type 2 diabetic and nondiabetic subjects. We evaluated plasma adiponectin levels and stiffness index β for the common carotid artery assessed by ultrasound using a phase-locked echo-tracking system for 98 type 2 diabetic subjects and 116 nondiabetic subjects as controls. Plasma adiponectin levels were significantly lower in the diabetic than in the nondiabetic group. The stiffness index β was significantly higher in the diabetic than in the nondiabetic group. Plasma adiponectin level was significantly correlated with stiffness index β in the group of all subjects ( r = −0.189, P = .006) and the nondiabetic group ( r = −0.187, P = .045), but not in the diabetic group ( r = 0.045, P = .665). On multiple regression analysis, plasma adiponectin level was found to be a significant independent contributor to stiffness index β in the group of all subjects ( β = −0.232, P = .020) and the nondiabetic group ( β = −0.337, P = .016), but not in the diabetic group. In conclusion, adiponectin is significantly but weakly associated with carotid arterial stiffness independently of known atherogenic factors in the nondiabetic group and that of all subjects, although no significant association between these variables was found in the group of diabetic subjects.

Impaired nonoxidative glucose disposal and decrease in mitochondrial glucose oxidation both contribute to insulin resistance in diabetic subjects.In the present study, we investigated whether plasma adiponectin is associated with glucose oxidation and nonoxidative glucose disposal in subjects with and without type 2 diabetes.Euglycemic-hyperinsulinemic clamp was performed in 42 type 2 diabetic (T2DM) and 13 nondiabetic (non-DM) subjects. The whole-body glucose disposal rate (GDR) was evaluated as the mean of the glucose infusion rate during steady state of the clamp. Glucose and fat oxidation rates were assessed by indirect calorimetry, and nonoxidative glucose disposal rate was calculated by subtracting glucose oxidation rate from GDR.Plasma adiponectin level was significantly lower in T2DM than non-DM (2.87 +/- 1.40 vs. 3.96 +/- 2.39 microg/ml, P = 0.045). GDR (3.39 +/- 1.53 vs. 4.83 +/- 1.70 mg/kg x min, P = 0.006) and nonoxidative glucose disposal rate (1.89 +/- 1.39 vs. 3.11 +/- 1.76 mg/kg x min, P = 0.012) were significantly lower in T2DM, compared with non-DM, although no difference was found in glucose oxidation rate between the two groups. In all subjects, plasma adiponectin level was positively correlated with GDR (r = 0.351, P = 0.009) and nonoxidative glucose disposal rate (r = 0.324, P = 0.016) but not glucose oxidation rate. There was no significant correlation between plasma adiponectin level and fat oxidation, either before or during the clamp.In conclusion, plasma adiponectin level is associated with nonoxidative glucose disposal, which is reduced in type 2 diabetic subjects. Our results suggest that adiponectin controls insulin sensitivity by modulating the glycogen synthetic process in human skeletal muscle.

Objectives— Advanced glycation endproducts, AGEs, and its specific receptor, RAGE, are involved in diabetic vascular complications. Endogenous secretory RAGE, esRAGE, has been identified as an alternatively spliced form of RAGE, and shown to act as a decoy receptor for AGE. Here, we measured plasma esRAGE level with a recently developed enzyme-linked immunosorbent assay (ELISA) and examined its association with atherosclerosis in age- and gender-matched 203 type 2 diabetic and 134 nondiabetic subjects. Methods and Results— Plasma esRAGE was inversely associated with carotid or femoral atherosclerosis, as quantitatively measured as intimal-medial thickness (IMT) by arterial ultrasound. Stepwise regression analyses revealed that plasma esRAGE was the third strongest and independent factor associated with carotid IMT, following age and systolic blood pressure. Plasma esRAGE was significantly lower in diabetic patients (0.176±0.092 ng/mL) than nondiabetic controls (0.253±0.111). Of note, in all, diabetic or nondiabetic group, plasma esRAGE was significantly and inversely correlated with components of the metabolic syndrome including body mass index, blood pressure, triglyceride, HbA1c, or an insulin resistance index. Stepwise regression analyses showed that body mass index or insulin resistance index was the major factor determining plasma esRAGE in all, nondiabetic or diabetic population. Conclusions— esRAGE is a novel and potential protective factor for the metabolic syndrome and atherosclerosis.

Background : It is difficult to predict the hypoglycemic effect of pioglitazone (a thiazolidinedione) as an insulin sensitizer. The purpose of the present study was to investigate whether insulin resistance index, homeostasis model assessment index (HOMA-IR) is a useful predictor of hypoglycemic effect of pioglitazone in comparison with body mass index (BMI). / Methods : Thirty-four type 2 diabetic patients (14 men and 20 women, mean age 60±14 years) were treated with pioglitazone, 15 mg per day for 3 months. Eighteen subjects showed a decrease of 0.5% or more in HbA1C after treatment and were considered responders while 16 subjects were non-responders. A receiver operating characteristic (ROC) analysis was performed to determine HOMA-IR and BMI sensitivity and the false positive rate (1-specificity) for discriminating responders from non-responders....

Intercellular adhesion molecule-1 (ICAM-1) is involved in inflammation and development of atherosclerotic change of vascular endothelium. The aim of the present study is to investigate whether K469E polymorphism of the ICAM-1 gene is associated with various clinical factors including plasma fibrinogen in patients with type 2 diabetes. ICAM-1 gene polymorphism was examined using polymerase chain reaction and restriction enzyme analysis in 360 type 2 diabetic patients. Plasma fibrinogen levels and other clinical variables were measured as well as circulating soluble ICAM-1 (sICAM-1) levels by enzyme-linked immunosorbent assay. The distribution of ICAM-1 genotypes, EE, EK, and KK, was not significantly different between type 2 diabetes and 152 healthy control subjects. Among 3 groups according to ICAM-1 genotypes in type 2 diabetes, no difference was found in adiposity, glycemic control, lipid profile, insulin sensitivity evaluated by homeostasis model assessment, or sICAM-1. Regarding fibrinogen, the patients with E allele showed significantly lower plasma fibrinogen levels in a dose-dependent manner (P = .033). Spearman rank correlation analyses revealed that ICAM-1 genotype showed significant correlation with plasma fibrinogen level (P < .001). In multiple regression analysis, ICAM-1 genotype was independent contribution factor of plasma fibrinogen level as well as high-density lipoprotein-cholesterol and urinary albumin excretion (R2 = 0.148, P < .001). In conclusion, K469E polymorphism of the ICAM-1 gene had impact on plasma fibrinogen level independently of other clinical factors in 360 type 2 diabetic patients, suggesting that fibrinogen is a candidate which links the ICAM-1 gene polymorphism to atherosclerosis.

Objective: To investigate whether: (1) aerobic exercise decreases arterial stiffness and (2) reduction in arterial stiffness is associated with improvement in insulin resistance in type 2 diabetes. Methods: Common carotid and femoral arterial stiffness was ultrasonographically evaluated using stiffness index β in 23 type 2 diabetic subjects before and after a 3-week exercise protocol including ergometer and walking. Insulin sensitivity (Clamp-IR) was assessed using euglycemic-hyperinsulinemic clamp before and after the protocol. Arterial stiffness was also examined in steady hyperinsulinemic state during clamp. Results: Anthropometrical factors did not change following exercise. Clamp-IR tended to increase after exercise protocol (P=0.061). Stiffness index β decreased following exercise in both common carotid and femoral arteries (P=0.020 and P

The insulin analogues, aspart and lispro, have been considered safe alternatives for patients with insulin allergy, because of their decreased immunogenicity. However, recent several reports showed that neither of them was completely free from allergic reactions. We also experienced a patient with insulin allergy not only to human regular insulin but also to both of the insulin analogues. Interestingly, the insulin analogues, which readily dissociate from polymer to monomer, induced the most severe allergic reaction among several types of human insulin reagents in the present case. Allergy to crystalline zinc-insulin, the three-dimensional structure of which results in delayed dissociation and absorption, was negative on intradermal tests. However, its large subcutaneous injection caused local allergic reaction. These results suggested that the allergic reaction might depend on the rapidity of insulin monomerization and absorption, and thus that the immunogenic residue of insulin is concealed when insulin is polymerized. Based on the intradermal tests, we speculated that the antigenic epitope might be B30-Thr in the present case. We also report here the modified method of insulin desensitization using crystalline zinc-insulin with prednisolone tapering. This might be a simple and useful treatment for insulin allergy.